Professional Documents
Culture Documents
Lifestyle Medicine - 2019
Lifestyle Medicine - 2019
me/MBS_MedicalBooksStore
Lifestyle Medicine
Lifestyle Medicine
Third Edition
Edited by
James M. Rippe, MD
CRC Press
Taylor & Francis Group
6000 Broken Sound Parkway NW, Suite 300
Boca Raton, FL 33487-2742
This book contains information obtained from authentic and highly regarded sources. Reasonable efforts have been made to publish reliable data and
information, but the author and publisher cannot assume responsibility for the validity of all materials or the consequences of their use. The authors
and publishers have attempted to trace the copyright holders of all material reproduced in this publication and apologize to copyright holders if per-
mission to publish in this form has not been obtained. If any copyright material has not been acknowledged please write and let us know so we may
rectify in any future reprint.
Except as permitted under U.S. Copyright Law, no part of this book may be reprinted, reproduced, transmitted, or utilized in any form by any elec-
tronic, mechanical, or other means, now known or hereafter invented, including photocopying, microfilming, and recording, or in any information
storage or retrieval system, without written permission from the publishers.
For permission to photocopy or use material electronically from this work, please access www.copyright.com (http://www.copyright.com/) or contact
the Copyright Clearance Center, Inc. (CCC), 222 Rosewood Drive, Danvers, MA 01923, 978-750-8400. CCC is a not-for-profit organization that
provides licenses and registration for a variety of users. For organizations that have been granted a photocopy license by the CCC, a separate system
of payment has been arranged.
Trademark Notice: Product or corporate names may be trademarks or registered trademarks, and are used only for identification and explanation
without intent to infringe.
Chapter 3: Physical Activity and Fitness in the Chapter 14: Exercise Prescription for Apparently
Prevention of Cardiovascular Disease............................... 37 Healthy Individuals and for Special Populations............. 177
Robert F. Zoeller Jr., PhD Paul G. Davis, PhD, ACSM-CEP
Chapter 9: Optimal Nutrition Guidance for Older Adults...... 125 Chapter 20: The Intention–Behavior Gap........................ 241
Alice H. Lichtenstein, DSc Mark D. Faries, PhD and Wesley C. Kephart, PhD
vii
viii Contents
Chapter 21: Cognitive and Behavioral Approaches Chapter 31: Implementing Nutritional Lifestyle
to Enhancing Physical Activity Participation and Treatment Programs in Type 2 Diabetes......................... 393
Decreasing Sedentary Behavior...................................... 253 George Guthrie, MD, MPH, CDE, CNS, FAAFP, FACLM
Barbara A. Stetson, PhD and Patricia M. Dubbert, PhD
Chapter 22: Enhancing the Nutrition Prescription Part VII Lifestyle Issues in the Prevention
Using Behavioral Approaches......................................... 269 and Treatment of Cancer
Jonas Sokolof, DO, Margaret Loeper Vasquez, MS, Cindy D. Davis, PhD and
RD, LDN, Jenny Sunghyun Lee, PhD, MPH, CHES, Sharon Ross, PhD, MPH
CWP, CHWC, BCLM, Daniel B. Clarke, MBA, and
P. Michael Stone, MD, MS, IFMCP Chapter 32: Diet and Cancer Prevention......................... 409
Cindy D. Davis, PhD and Sharon Ross, PhD, MPH
Chapter 23: Behavioral Approaches to Manage
Stress............................................................................... 281 Chapter 33: Lifestyle Approaches Targeting Obesity to
Elise Loiselle, RN, MSN, FNP-C, Darshan Mehta, MD, Reduce Cancer Risk, Progression, and Recurrence..........419
and Jacqueline Proszynski, BS Debora S. Bruno, MD, MS and Nathan A. Berger, MD
Chapter 24: Health Coaching and Behavior Change...... 299 Chapter 34: Physical Activity and the Prevention and
Karen L. Lawson, MD, ABIHM, NBC-HWC, Treatment of Cancer........................................................ 431
Margaret Moore, MBA, ACC, Matthew M. Clark, PhD, Case H. Keltner, MPH and Heather R. Bowles, PhD
Sara Link, MS, NBC-HWC, and Ruth Wolever, PhD
Chapter 35: Nutrition Therapy for the Cancer Patient.......441
Chapter 25: Digital Health Technology for Behavior Sandeep (Anu) Kaur, MS, RDN, RYT-500 and Elaine
Change............................................................................. 311 Trujillo, MS, RDN
Jeffrey Krauss, MD, DipABLM, Patricia Zheng, MD,
Courtenay Stewart, DO, and Mark Berman, MD, FACLM
Part VIII Obesity and Weight Management
John P. Foreyt, PhD
Part V Women’ s Health Chapter 36: Epidemiology of Adult Obesity.................... 455
Paulette Chandler, MD, MPH R. Sue Day, MS, PhD, Nattinee Jitnarin, PhD,
Michelle L. Vidoni, MPH, PhD, Christopher M.
Chapter 26: Breast Health: Lifestyle Modification for Kaipust, MPH, and Austin L. Brown, MPH, PhD
Risk Reduction................................................................. 331
Beth Baughman DuPree, MD, FACS, ABOIM and Chapter 37: Exercise Management for the Obese
Jodi Hutchinson, PA-C Patient.............................................................................. 473
John M. Jakicic, PhD, Renee J. Rogers, PhD, and
Chapter 27: Sports and Physical Activity for Women Katherine A. Collins, MS, CBDT
and Girls........................................................................... 341
Elizabeth A. Joy, MD, MPH, FACSM Chapter 38: Dietary Management of Overweight and
Obesity............................................................................. 483
Nina Crowley, PhD, RDN, LD, Katherine R.
Arlinghaus, MS, RD, LD, and Eileen Stellefson Myers,
Part VI Endocrinology and Metabolism MPH, RDN, LDN, CEDRD, FADA, FAND
Jeffrey I. Mechanick, MD, FACP, FACE,
FACN, ECNU Chapter 39: Pharmacological Management of the
Patient with Obesity......................................................... 491
Chapter 28: Impact of Lifestyle Medicine on Magdalena Pasarica, MD, PhD and Nikhil V.
Dysglycemia-Based Chronic Disease............................. 355 Dhurandhar, PhD
Michael A. Via, MD and Jeffrey I. Mechanick, MD,
FACP, FACE, FACN, ECNU Chapter 40: Surgery for Severe Obesity......................... 505
Robert F. Kushner, MD and Lisa A. Neff, PhD
Chapter 29: Lifestyle Medicine and the Management
of Prediabetes.................................................................. 367 Chapter 41: Adiposity-based Chronic Disease a New
Karla I. Galaviz, PhD, MSc, Lisa Staimez, PhD, MPH, Diagnostic Term............................................................... 517
Lawrence S. Phillips, MD, and Mary Beth Weber, PhD, Michael A. Via, MD and Jeffrey I. Mechanick, MD,
MPH FACP, FACE, FACN, ECNU
Chapter 30: Lifestyle Therapies for the Management Chapter 42: Future Directions in Obesity and Weight
of Diabetes....................................................................... 383 Management.................................................................... 529
Marion J. Franz, MS, RD, CDE Theodore K. Kyle, RPh, MBA
Contents ix
Part IX Immunology and Infectious Disease Chapter 56: Contraception.............................................. 687
Gregory A. Hand, PhD, MPH, FACSM, FESPM Karen Carlson, MD and Sadia Haider, MD, MPH
Chapter 43: Exercise, Inflammation, and Respiratory Chapter 57: Prevention, Screening, and Treatment of
Infection........................................................................... 539 Sexually Transmitted Infections....................................... 697
Wesley D. Dudgeon, PhD, David C. Nieman, DrPH, Karen Carlson, MD
FACSM, and Elizabeth Kelley, MS, ACSM-RCEP
Chapter 58: Menstrual Disorders and Menopause......... 707
Chapter 44: Chronic Exercise and Immunity................... 547 Amanda McKinney, MD, FACLM, FACOG, CPE
Melissa M. Markofski, PhD, Paul M. Coen, PhD, and
Michael G. Flynn, PhD Chapter 59: Risk Reduction and Screening for
Women’s Cancers............................................................ 715
Chapter 45: HIV and Exercise.......................................... 555 Amanda McKinney, MD, FACLM, FACOG, CPE and
Jason R. Jaggers, PhD and Gregory A. Hand, PhD, Jo Marie Tran Janco, MD
MPH, FACSM, FESPM
Chapter 54: Exercise in Pregnancy................................. 663 Chapter 66: Counseling Cardiac Patients to Facilitate
Kristin Bixel, MD and Christie Mitchell Cobb, MD Behavior Change............................................................. 781
Lola A. Coke, PhD, ACNS-BC, CVRN-BC, FAHA,
Chapter 55: Breast-Feeding............................................ 673 FPCNA, FAAN, Nancy Houston Miller, RN, BSN,
Julia Head, MD, Stephanie-Marie L. Jones, MD, Marcie FAHA, FPCNA, FAACVPR, and Kathy Berra, MSN,
K. Richardson, MD, and Angela Grone, MD, FACOG NP-BC, FAANP, FPCNA, FAHA, FAAN
x Contents
Chapter 67: Extreme Exercise and High Intensity Chapter 79: Identification and Management of
Interval Training in Cardiac Rehabilitation....................... 787 Children with Dyslipidemia.............................................. 921
Kathy Berra, MSN, NP-BC, FAANP, FPCNA, FAHA, Julie A. Brothers, MD and Stephen R. Daniels, MD, PhD
FAAN and Barry A. Franklin, PhD
Chapter 80: Diagnosis, Management, and Treatment
Chapter 68: Counseling Coronary Patients About of Systemic Hypertension in Youth, Updates from
Their Body Weight: Implications Regarding the the 2017 American Academy of Pediatrics Clinical
Obesity Paradox.............................................................. 801 Practice Guideline............................................................ 937
Sergey Kachur, MD, Carl J. Lavie, MD, FACC, FACP, Carissa M. Baker-Smith, MD, MS, MPH, FAAP, FAHA
FCCP, FESPM, and Richard V. Milani, MD and Samuel Gidding, MD
Chapter 69: Vitamins and Supplements: Evidence Chapter 81: Prevention of Osteoporosis in Children
in the Prevention and Treatment of Cardiovascular and Adolescents.............................................................. 951
Disease............................................................................. 811 Heidi J. Kalkwarf, PhD
Jenna M. Holzhausen, PharmD, BCPS and Aaron D.
Berman, MD, FACC
Part XIV The Practice of Lifestyle Medicine
Chapter 70: Intensive Cardiac Rehabilitation: George Guthrie, MD, MPH, CDE, CNS,
Evolution, Preliminary Outcomes, Considerations, FAAFP, FACLM
and Future Directions...................................................... 825
Jenna Brinks, MS, FAACVPR and Amy Fowler, BS Chapter 82: Definition of Lifestyle Medicine.................... 961
George Guthrie, MD, MPH, CDE, CNS, FAAFP, FACLM
Chapter 71: Alternative Models to Improve the
Delivery and Impact of Cardiac Rehabilitation................ 833 Chapter 83: Health Provider Core Competencies in
Randal J. Thomas, MD, MS, Robert Scales, PhD, and Lifestyle Medicine............................................................ 969
Regis Fernandes, MD, FACC, FASE Liana Lianov, MD, MPH, FACPM, FACLM
Chapter 72: Primordial/Primary Prevention: Chapter 84: Lifestyle Medicine Clinical Processes......... 977
Implications and Challenges for Families and Children..... 841 Ingrid Edshteyn, DO, MPH
Laura L. Hayman, PhD, MSN, FAAN, FAHA, FPCNA
and James M. Muchira, MSN, PhD candidate Chapter 85: Sleep as Medicine and Lifestyle
Medicine for Optimal Sleep............................................. 995
Virginia F. Gurley, MD, MPH
Part XIII Lifestyle Components of Pediatric Medicine
Stephen R. Daniels, MD, PhD Chapter 86: Emotional Health and Stress
Management.................................................................. 1003
Chapter 73: Pediatric Lifestyle Medicine......................... 851 Neil Nedley, MD and Francisco E. Ramirez, MD, BS, SC
Jonathan R. Miller, PhD, Richard Boles, PhD, and
Stephen R. Daniels, MD, PhD Chapter 87: High-intensity Therapeutic Lifestyle
Change........................................................................... 1019
Chapter 74: Life Course Approach to Prevention of John Kelly, MD, MPH
Chronic Disease............................................................... 861
Katherine A. Sauder, PhD and Dana Dabelea, MD, PhD Chapter 88: Physician Health Practices and Lifestyle
Medicine......................................................................... 1033
Chapter 75: Cardiovascular Risk and Physical Erica Frank, MD, MPH, FACPM and Debora Holmes,
Activity in Children........................................................... 873 MES
Lars Bo Andersen, Dr Sc and Robert G. Murray, PhD
Chapter 76: Cardiovascular Risk and Diet in Children....... 887 Part XV Substance Abuse and Addiction
Jessica L. Hildebrandt, MS, RD and Sarah C. Couch, Elizabeth Pegg Frates,
PhD, RD MD and Joji Suzuki, MD
Chapter 77: Sleep and Obesity Prevention in Chapter 89: Introduction to Addiction Section.............. 1047
Children and Adolescents............................................... 901 Joji Suzuki, MD, Elizabeth Pegg Frates, MD, and Irena
Jill Landsbaugh Kaar, PhD and Stacey L. Simon, PhD Matanovic
Chapter 78: Childhood Obesity....................................... 909 Chapter 90: History of Alcohol and Opioid Use and
Jaime M. Moore, MD and Matthew Allen Haemer, MD, Treatment in the United States...................................... 1051
MPH Sanchit Maruti, MD, MS and Steven A. Adelman, MD
Contents xi
Chapter 91: Behavioral Approaches to Enhancing Chapter 104: The Employer’s Role in Lifestyle
Smoking Cessation........................................................ 1057 Medicine..........................................................................1175
Joseph T. Ciccolo, PhD, CSCS, Nicholas J. Dexter Shurney, MD, MBA, MPH
SantaBarbara, MS, and Andrew M. Busch, PhD
Chapter 105: Why, How, and What in Leveraging the
Chapter 92: Alcohol Use Disorders: Diagnosis and Value of Health................................................................1181
Treatment....................................................................... 1069 Ron Loeppke, MD, MPH, FACOEM, FACPM
Chwen-Yuen Angie Chen, MD, FACP, FASAM and Sara
C. Slatkin, MD
Chapter 106: International Health & Lifestyle.................1191
Wayne N. Burton, MD, FACP, FACOEM
Chapter 93: Diagnosis and Treatment of Opioid Use
Disorders........................................................................ 1083
Joseph R. Volpicelli, MD Chapter 107: The Community as a Catalyst for
Healthier Behaviors........................................................ 1199
Chapter 94: Cannabis Use Disorder and Treatment....... 1093 Jane Ellery, PhD and Peter Ellery, PhD, MLA
Christina Aivadyan, MS and Deborah Hasin, PhD
Chapter 108: Motivation as Medicine............................ 1209
Chapter 95: Smartphone-Based Technologies in Jennifer S. Pitts, PhD
Addiction Treatment....................................................... 1105
Emily Wu, MD and John Torous, MD Chapter 109: Future Directions of Health Promotion:
Role of the Physician......................................................1217
Chapter 96: Psychosocial Interventions for Alyssa B. Schultz, PhD
Treatment of Substance Use Disorders.........................1113
Saria El Haddad, MD
Part XVIII Exercise Psychology
Part XVI Lifestyle Medicine in Geriatrics Steven J. Petruzzello, PhD
Arthur S. Leon, MS, MD, FACSM
Chapter 110: My, How Those Seedlings Have Grown:
Chapter 97: Lifestyle Medicine and the Older An Update on Mind/Body Interactions
Population: Introductory Framework..............................1123 in the Exercise Domain.................................................. 1225
Arthur S. Leon, MS, MD, FACSM and Charlotte A. Steven J. Petruzzello, PhD, Allyson G. Box, BS, and
Tate, PhD Dakota G. Morales, MS
Chapter 98: Reducing Aging-associated Risk of Chapter 111: Genetic Influences on Regular Exercise
Sarcopenia......................................................................1127 Behavior......................................................................... 1235
Arthur S. Leon, MS, MD, FACSM Matthijs D. van der Zee, MSc, Nienke Schutte, PhD,
and Marleen H.M. de Moor, PhD
Chapter 99: Aging-Associated Cognitive Decline and
its Attenuation by Lifestyle..............................................1141 Chapter 112: The Influence of Physical Activity
Arthur S. Leon, MS, MD, FACSM on Brain Aging and Cognition: The Role of
Cognitive Reserve, Thresholds for Decline,
Chapter 100: Aging Successfully: Predictors and Genetic Influence, and the Investment
Pathways.........................................................................1147 Hypothesis..................................................................... 1251
Debra J. Rose, PhD Maureen K. Kayes, MS and Bradley D. Hatfield, PhD,
FACSM, FNAK
Chapter 101: Role of Physical Activity in the Health
and Wellbeing of Older Adults........................................1157
Chapter 113: Physical Activity and Anxiety................... 1271
Andiara Schwingel, PhD and Wojtek J. Chodzko-Zajko,
Katharina Gaudlitz, MSc, Brigitt-Leila von
PhD
Lindenberger, MSc, and Andreas Ströhle, MD
Part XVII Health Promotion Chapter 114: Physical Activity and Depression............. 1281
Kayla N. Fair, DrPH and Chad D. Rethorst, PhD
Dee W. Edington, PhD
Chapter 116: Traffic Injury Prevention: Strategies Part XX Public Policy and Environmental
That Work....................................................................... 1303 Supports for Lifestyle Medicine
Ann M. Dellinger, PhD, MPH, David A. Sleet, PhD, Gregory W. Heath, DHSc, MPH FAHA, FACSM
FAAHB, and Merissa A. Yellman, MPH
Chapter 122: Lifestyle Medicine in an Era of
Chapter 117: Review and Implementation of the CDC Healthcare Reform— Seven Years of Healthcare
Guideline for Prescribing Opioids for Chronic Pain.......1315 Disruption: 2010– 2017................................................... 1357
LeShaundra Cordier, MPH, CHES and Helen Kingery, Aaron F. Hajart, MS, ATC, FACNA, Sandra Weisser,
MPH MSEd, ATC, Gary B. Wilkerson, EdD, ATC, and
Gregory W. Heath, DHSc, MPH, FAHA, FACSM
Chapter 118: Improving the Care of Young Patients
with Mild Traumatic Brain Injury: CDC’s Evidence-
Chapter 123: Policy and Environmental Supports for
Based Pediatric Mild TBI Guideline............................... 1319
Physical Activity and Active Living................................ 1365
Kelly Sarmiento, MPH, Angela Lumba-Brown, MD,
Elizabeth A. Dodson, PhD, MPH and Gregory W.
Matthew J. Breiding, PhD, CDR, US,
Heath, DHSc, MPH, FAHA, FACSM
Wayne Gordon, PhD, ABPP/Cn, David Paulk, PA-C,
EdD, DFAAPA, Kenneth Vitale, MD FAAPMR, and
Chapter 124: Policy and Environmental Supports for
David A. Sleet, PhD, FAAHB
Healthy Eating................................................................ 1375
Charlene Schmidt, PhD, MS, RDN, Emily Maddux, MS,
Chapter 119: Older Adult Falls: Epidemiology and
MPH, RD, LDN, and Elizabeth Hathaway, PhD, MPH
Effective Injury Prevention Strategies............................ 1327
Ann M. Dellinger, PhD, MPH, David A. Sleet, PhD,
FAAHB, and Jeanne Nichols, PhD, FACSM Chapter 125: Building Strategic Alliances to Promote
Healthy Eating and Active Living................................... 1383
Chapter 120: Prevention of Suicidal Behavior............... 1337 Risa Wilkerson, MA, Elizabeth A. Baker, PhD, MPH, Matt
Alex E. Crosby, MD, MPH, Deborah M. Stone, ScD, M. Longjohn, MD MPH, Shewanee D. Howard-Baptiste,
MSW, MPH, and Kristin Holland, PhD, MPH PhD, Kara C. Hamilton, PhD, and Kori Hahn, BS, MS
Chapter 121: Unintentional Injuries to Disabled Chapter 126: Obesity and Health.................................. 1391
Persons: An Unrecognized Yet Preventable Problem...... 1349 James M. Rippe, MD and Theodore J. Angelopoulos,
Louis Hugo Francescutti, MD, PhD, MPH, David A. PhD, MPH
Sleet, PhD, FAAHB, Linda Hill, MD, and Henry Xiang,
MD, MPH, PhD Index������������������������������������������������������������������������������ 1405
Preface
There is no longer any serious doubt that daily habits • American Heart Association Nutrition
and actions profoundly impact both short- and long-term Implementation Guidelines
health and quality of life. The scientific and medical lit- • Guidelines from the American Academy of Pediatrics
erature that supports this concept is now overwhelming. for the Prevention and Treatment of Childhood
Thousands of studies provide evidence that regular physi- Obesity
cal activity, maintenance of a healthy body weight, not • Guidelines from the American Academy of Pediatrics
smoking cigarettes, as well as following sound nutrition, for the Treatment of Pediatric Blood Pressure
stress reduction, and other health promoting practices all • Guidelines from the American Academy of Pediatrics
profoundly impact health. Conversely, an inactive life- for the Treatment of Lipids
style, obesity, high levels of stress, and cigarette smoking • Guidelines from the American Heart Association
or exposure to cigarette smoke and other pollutants all and the American Academy of Pediatrics for
significantly and negatively impact health. the Prevention and Treatment of the Metabolic
Since the publication of the second edition of Lifestyle Syndrome
Medicine (CRC Press, 2013), this literature has continued • American Heart Association Strategic Plan for 2020
to grow stronger and even more robust. The field of life- • Joint Statement from the American Heart
style medicine has continued to expand around the globe, Association and American Cancer Society for the
and multiple new initiatives in the area of lifestyle medi- Prevention of Heart Disease and Cancer
cine have sprung up in the last few years. • Presidential Advisory from the AHA and American
Because the field of lifestyle medicine has grown and Stroke Association
expanded, it is necessary for our Lifestyle Medicine text • AHA/ACC/TOS Guideline for the Management of
to continue to grow and expand in order to serve the needs Overweight and Obesity in Adults
of an increasing number of individuals who are incorpo- • ACC/ADA/AHA Scientific Statement on Preventing
rating lifestyle medicine practices in various components Cancer, Cardiovascular Disease and Diabetes
of health care. The text also serves other physicians and • Physical Activity Guidelines Advisory Committee
other health care professionals in their practices. Serving Report of 2018
all these providers is the goal of the third edition of
Lifestyle Medicine. Unfortunately, despite the widespread recognition in these
This edition has been thoroughly rewritten and evidence-based guidelines and consensus statements about
updated, and incorporates a number of new sections the important role of lifestyle measures and practices in
which address the needs and concerns of lifestyle medicine the prevention and treatment of metabolic diseases, lit-
practitioners and other physicians throughout the world. tle progress has been made in improving the habits and
The evidence-base for lifestyle medicine procedures practices of the American population. In fact, in some
and practices is based on the enormous strength of the instances, risk factors for chronic diseases have actually
literature and underscored by its incorporation into vir- continued to increase in the past decade. For example,
tually every evidence-based clinical guideline addressing consider the following:
the prevention and treatment of metabolic diseases. For
example, the following guidelines and consensus state- • Cardiovascular disease, which remains the leading
ments from various prestigious medical organizations all killer of both men and women in the United States,
provide significant emphasis on lifestyle medicine prin- resulting in over 37% of all mortality each year, has
ciples and practices as key components of the prevention multiple lifestyle factors as underlying risk factors.
and treatment of disease: • Over 80% of the adult population in the United
States does not get enough physical activity to result
• JNC VIII Guidelines for Hypertension, Prevention in health benefits.
and Treatment • Over two-thirds of the adult population in the
• ACC/AHA Guidelines for the Prevention, Detection, United States is either overweight or obese
Evaluation and Treatment of High Blood Pressure • The prevalence of pediatric obesity has tripled in the
• NCEP (ATP IV) Guidelines for Blood Cholesterol past 20 years.
• Institute of Medicine Guidelines for Obesity • Less than one-third of the adult population con-
Treatment sumes adequate levels of fruits and vegetables and
• ACC/AHA Scientific Consensus Statement on the follows other simple evidenced-based nutritional
Treatment for Blood Cholesterol practices related to good health.
• Guidelines from the American Diabetes Association • Over 15% of individuals still smoke cigarettes.
for the Management of Diabetes • Over 40% of the adult population in the United
• Dietary Guidelines for Americans 2015–2020 States has high blood pressure.
xiii
xiv Preface
• The choice of an inactive lifestyle increases the risk late 1990s. Following the publication of the first edition
of an individual developing heart disease by as much of Lifestyle Medicine, a number of initiatives took place,
as smoking a pack of cigarettes a day does. including the launch of a peer-reviewed academic journal
• Obesity is the leading cause of osteoarthritis in in lifestyle medicine (the American Journal of Lifestyle
women and the second leading cause in men. Medicine; SAGE Publications). A consensus statement
• Cigarette smoking is the leading cause of cancer in on the core principles of lifestyle medicine was published
the United States and obesity is the second leading in the Journal of the American Medicine Association
cause. based on recommendations from representatives from
major medical groups, including the American Medical
There is now a wide body of scientific evidence that posi- Association, the American College of Physicians, the
tive lifestyle factors dramatically lower risk factors for American Academy of Pediatrics, the American College
chronic disease and promote good health. For example, of Sports Medicine, the American College of Preventive
in the Nurses’ Health Study, 80% of all heart disease and Medicine, and others.
over 91% of all diabetes in women could be eliminated if In addition, an academic medical society in lifestyle
they would adopt a cluster of positive lifestyle practices, medicine, the American College of Lifestyle Medicine,
including maintenance of a healthy body weight (BMI of has been established for physicians and other health
19–25 kg/m 2), regular physical activity (30 minutes or care workers. This organization has more than doubled
more on most days), not smoking cigarettes, and follow- its membership each year for the past five years and has
ing a few simple nutritional practices such as increasing launched a number of important initiatives in the educa-
whole grains and consuming more fruits and vegetables. tion and practice of lifestyle medicine. Other professional
The U.S. Health Professionals Study showed similar dra- groups have increasingly embraced the concept of lifestyle
matic reductions of risk in men from these same positive medicine. These include the American Heart Association,
lifestyle factors. Importantly, if individuals adopted only which now has a council entitled the “Council on Lifestyle
one of these positive factors, their risk of developing coro- and Cardiometabolic Health.” The American Academy of
nary artery disease would be cut in half. Unfortunately, Family Practice and the American College of Preventive
numerous studies have shown that less than 5% of adults Medicine now offer education tracks for individuals inter-
in the United States follow most or all of these health- ested in adding lifestyle medicine as a key component of
promoting practices. their medical practices.
The power of daily lifestyle practices and habits has All of these advances are welcome and will enhance
also been shown in multiple large, randomized controlled the likelihood of formal adoption of lifestyle medicine
trials. For example, in the Diabetes Prevention Program, practices within the medical community. Unfortunately,
individuals with baseline glucose intolerance who however, at the current time, less than 30% of physicians
increased physical activity and lost 5–7% of their body routinely counsel their patients on weight management,
weight also reduced their risk of developing diabetes by physical activity, and proper nutrition. This is a squan-
58%. dered opportunity, since more than 75% of the adult
In the LOOK AHEAD Trial, individuals who lost 7% population sees a primary care physician at least once
of their body weight significantly reduced risk factors for per year. This gap between evidence and application rep-
heart disease and diabetes. Importantly, in both of these resents an enormous mandate and opportunity to under-
studies, over 90% of initial weight loss was maintained score the links between lifestyle habits and practices and
over four years for individuals who continued to follow health outcome.
the program and received periodic follow-up from health So what is “lifestyle medicine?” In the first edition of
professionals. Levels of physical activity remained high in our textbook we defined it as “the integration of lifestyle
both of these studies in follow-up periods of up to four practices into the modern practice of medicine both to
years. lower the risk factors for chronic disease and/or, if dis-
Because the literature to relating lifestyle practices and ease is already present, serve as an adjunct in its therapy.
habits has continued to grow deeper and more complex, Lifestyle medicine brings together sound, scientific evi-
the challenge for physicians and other health care profes- dence in diverse health-related fields to assist the clinician
sionals to keep abreast of this ever-expanding field and in the process of not only treating disease but also promot-
incorporate these findings into modern medical practice ing good health.” While this definition was put forth over
has become even more daunting. To further complicate almost two decades ago, it has largely stood the test of
the challenge, the literature relating lifestyle and health time. Other organizations have offered very similar defi-
is spread over a wide variety of disciplines, journals, and nitions of lifestyle medicine, and these definitions serve as
textbooks. The need to provide comprehensive evidence- the defining principle behind the third edition of Lifestyle
based summaries concerning lifestyle and health in a text- Medicine.
book that spans the field of lifestyle medicine has clearly The third edition of Lifestyle Medicine is divided into
become even more evident in the five years since the pub- 20 parts related to lifestyle medicine; each part’s chapters
lication of the second edition of our textbook. Another have been edited by a leader of that particular discipline.
goal for the third edition of Lifestyle Medicine has been to All chapters have been fundamentally rewritten or sub-
address this need. stantially revised and brought up-to-date with current
With the first edition of Lifestyle Medicine in 1999 understandings and practices. There are also many new
we coined the term “lifestyle medicine” and summarized chapters and several new parts added to reflect modern
key findings across multiple disciplines that existed in the understandings and particular areas which have emerged
Preface xv
as critically important in lifestyle medicine over the past Part V focuses on specific issues related to Women’s
five years. Health and includes chapters on breast health and physi-
The third edition of Lifestyle Medicine opens cal activity. Part VI, Endocrinology and Metabolism, is a
with Part I, Lifestyle Management and Prevention of thoroughly updated and expanded section which focuses
Cardiovascular Disease. I chose to have this as the initial on lifestyle factors particularly in the area of the preven-
part for a number of reasons. First, I am a cardiologist, tion and management of diabetes and the metabolic syn-
and my initial interest in lifestyle medicine came through drome. Part VII, Lifestyle Issues in the Prevention and
issues related to lowering the risk of cardiovascular dis- Treatment of Cancer, represents an important area which
ease. Secondly, the area of cardiovascular medicine has has been underestimated in many clinicians’ practices.
been one of the leaders in adopting lifestyle habits and The chapters are written by leading world experts not only
practices to reduce the risk of disease. These concepts are from the Centers from Disease Control but from various
further articulated in the AHA Strategic Goals for the Year universities. These chapters are particularly important
2020. In addition, the council that I sit on within the AHA since many physicians are unaware of the multiple links
has changed its name from the “Council on Nutrition, between lifestyle practices and a wide variety of cancers.
Physical Activity and Metabolism” to the “Council on Part VIII, Obesity and Weight Management, has been
Lifestyle and Cardiometabolic Health,” a welcome recog- thoroughly rewritten with state-of-the-art chapters on epi-
nition of the key role that lifestyle plays in the prevention demiology, exercise management, dietary management,
and treatment of heart disease. Within this opening part pharmacologic management, and surgery for obesity. Also
are state-of-the-art chapters on various aspects of risk included is a new chapter entitled “Impact of Lifestyle
reduction incorporating the most recent guidelines pro- Medicine on Dysglycemia-Based Chronic Disease,” which
mulgated by the American College of Cardiology (ACC) focuses on recently released statements from the American
and the American Heart Association (AHA). College of Endocrinology and provides an intriguing new
Part II, is Nutritional Aspects of Lifestyle Medicine. framework for considering obesity-related conditions.
Of course, nutrition plays a very prominent role in healthy The Immunology and Infectious Disease and
lifestyle habits and actions. This section has been entirely Pulmonary Medicine sections have both been entirely
updated and includes such new chapters as the one on the rewritten and updated. The section on Obstetrics and
Dietary Guidelines for Americans 2015 and one on hydra- Gynecology contains a number of new chapters and revi-
tion, which is an important area that is often overlooked sions of other chapters related to how lifestyle impacts on
in nutrition. pregnancy and other key issues in obstetrics and gynecol-
Part III is a greatly expanded section on Physical ogy, such as breastfeeding, contraception, sexually trans-
Activity. This Part contains state-of-the- art chapters on mitted diseases, menstrual disorders, and risk reduction
exercise prescription in various populations and what phy- of cancers. Part XII is an entirely rewritten and expanded
sicians should know about prescribing exercise and physi- section on Cardiovascular Rehabilitation and Secondary
cal activity. Levels of physical activity remain extremely Prevention, which provides contemporary information on
low in the American population, and I hope that this sec- the intersection between traditional cardiac rehabilitation
tion will encourage physicians to play a more active role and emerging areas of secondary prevention in cardiovas-
in this area. Physical activity is one of the most powerful cular medicine.
tools we have to lower the risk of chronic disease. These Part XIII, Lifestyle Components of Pediatric Medicine,
chapters further elucidate the findings of the Physical contains state-of-the-art chapters by world leaders in the
Activity Guidelines for 2018 Advisory Committee report, application of lifestyle practices to the treatment of the
which documents the expanding list of health benefits of pediatric population. We have increasingly come to under-
physical activity for both adults and children. stand that many diseases which are manifested in adults
Part IV is also a greatly expanded section on have their roots in childhood. Key issues related to cardio-
Behavioral Medicine. Understandings of how to change vascular risk, obesity, diabetes, lipids, blood pressure, and
behaviors are fundamental to virtually every other aspect osteoporosis in children are all highlights of this impor-
of lifestyle medicine. This Part includes not only chap- tant section.
ters on theoretical frameworks for how to apply psycho- Increasingly individuals are opting to make lifestyle
logical theories to promote healthy lifestyles but also medicine the cornerstone of their medical practice. For
important new chapters on Motivational Interviewing, this reason we have included an entirely new section, The
the Transtheoretical Model of Change, and Positive Practice of Lifestyle Medicine, which contains chapters
Psychology. An important new chapter delves into how by leading practitioners within the American College of
to address the gap between what people intend to do and Lifestyle Medicine (ACLM). Many of these chapters relate
what they actually do. This “Intention-Behavior Gap” specifically to educational efforts by the ACLM to engage
has not received enough attention in the past, but the physicians in this area and provide the core competencies
state-of-the-art chapter on this topic provides practical needed to practice lifestyle medicine.
advice in this important area. Three chapters focus on Part XV is an entirely new section in the area of
how to use behavioral approaches in the areas of physical Substance Abuse and Addiction. It will come as no sur-
activity, nutrition, and stress management. The section prise to members of the medical community that the
concludes with a state-of-the-art chapter on the emerg- United States is in the midst of an opioid epidemic, but
ing field of health coaching and a chapter on the latest there are also a variety of other addictions such as alcohol,
technologies and devices which hold great promise for tobacco, marijuana, and so on which should be part of
facilitating behavioral change. the knowledge base for every physician. There is also an
xvi Preface
important chapter in this section on emerging technolo- measures. The final section of the book, Public Policy and
gies and apps for treating addiction. Environmental Supports for Lifestyle Medicine, deals
Individuals over the age of 65 represent the fastest with this important aspect of lifestyle medicine in consid-
growing portion of the United States population. The erable detail.
expanded section on Lifestyle Medicine in Geriatrics The work of generating this comprehensive and up-to-
deals with a number of issues that are highly relevant to date volume in lifestyle medicine involved the hard work
this segment of the population. In particular, age-related and talent of 21 section editors who have devoted enor-
declines in skeletal muscle and cognitive function which mous energy and talent to the difficult task of organizing
are increasingly prevalent in this population have both and editing parts and ensuring that they are both scien-
been demonstrated to be significantly ameliorated by life- tifically accurate and clinically useful. What has resulted
style practices and habits. There are two new chapters on from their efforts and those of over 250 distinguished
these topics. In addition, a separate chapter on physical contributors is a textbook which I hope and believe will
activity in individuals over the age of 65 is presented as be clinically useful in guiding health care professionals
well as a general overview on the concept of “success- and providing state-of-the-art summaries and practical
ful aging.” This latter concept has changed the way we applications of modern science and medical understand-
approach lifestyle measures in people over the age of 65. ings related to the interaction between lifestyle practice,
Rather than focusing on declining physiological and emo- medicine, and good health.
tional characteristics in this population, there are now We have further emphasized clinical utility in the
data and programs that show how individuals in this third edition of Lifestyle Medicine by asking each author
phase of life can maintain a healthy lifestyle and benefit to list “Key Points” at the beginning of each chapter and
from their wealth of experience while slowing down the “Clinical Applications” at the end of each chapter. These
normal physical and mental declines often experienced additions, we hope, will respectively be a helpful introduc-
with aging. tion to each chapter and guidance for applying the infor-
Part XVII, Health Promotion, is an important concept mation in the chapter to the daily practice of medicine.
in lifestyle medicine, and this section contains a substan- As in previous editions, we hope this work will help our
tial increase in the number of chapters devoted to this patients lead happier, healthier, and more productive lives
very important topic. This Part focuses largely on differ- while lowering their risk of chronic diseases and enhanc-
ent venues where health promotion can be delivered and ing their quality of life.
offers practical, evidence-based advice about successful Over the two decades since the publication of the first
health promotion programs. The psychological benefits of edition of Lifestyle Medicine, important and extensive
exercise represent an area of increasing research, interest, new information has emerged to provide scientific links
and application. The expanded and updated section on between daily habits and actions and their ever-expanding
Exercise Psychology (Part XVIII) deals with the science impact on short- and long-term health and quality of life.
that is known about how exercise impacts psychological A key consideration remains for those of us in the health
well-being. New chapters on the role of physical activity care community with respect to applying these under-
to ameliorate anxiety and depression as well as improve standings to the modern practice of medicine. Lifestyle
or maintain cognitive function are important chapters in medicine is, in my view, the single greatest opportunity
this area. that we have to improve health outcomes and lower cost.
Often injuries are not considered in the area of life- This is crucial to underscoring and advancing the value
style medicine. However, injuries have a direct impact on proposition in the practice of medicine. This is both the
lifestyle for many individuals. These topics are handled challenge and the enormous opportunity in front of all
in detail in the expanded Part XIX, Injury Prevention. of us who are blessed as gatekeepers to the health of our
These chapters are largely written by experts from the patients in our country. I hope that this edition of Lifestyle
National Center for Injury Prevention and Control at the Medicine will continue to support the magnificent efforts
Centers for Disease Control. of all of those who strive to enhance the health of all their
Of course, lifestyle changes do not occur in isola- patients.
tion. Public policy issues play a very important role in
how the environment either supports or undercuts indi- James M. Rippe, MD
viduals’ ability to improve their health through lifestyle Boston, Massachusetts
Acknowledgments
Textbook writing and editing are collaborative efforts and travel plans to free up the time necessary for such large
that involve the hard work and passion of numer- writing and publishing projects. Our Office Assistant,
ous contributors. Individuals who have stimulated Deb Adamonis, assists all of us in the multiple daily tasks
my thinking about the interaction between lifestyle required to expedite diverse projects in our office, while
and health over many years are too numerous to our Chief Financial Officer, Connie Martell, makes sure
acknowledge all by name. However, I would like to that the financial processes are in place for all or our
particularly thank a few individuals who have made projects to move forward smoothly. The research team at
substantial contributions to the third edition of Rippe Lifestyle Institute has always contributed enormous
Lifestyle Medicine. insights to clarify my thinking about a number of aspects
First, my longtime Editorial Director, Beth Grady, of lifestyle medicine, while our Director of Marketing and
who plays a critically important role in all of the major Client Services, Amy Continelli, coordinates the day-to-
writing and editing projects that emerge from my research day interactions with multiple research sponsors.
organization, deserves special thanks. The third edition of I would also like to thank the outstanding editorial
Lifestyle Medicine is one of over 50 books that Beth has team at Taylor & Francis Group/CRC Press. Included in
managed which have been generated through our organi- this group are Randy Brehm, Senior Editor, who has been
zation. In addition to the current textbook, she provides an early key supporter of our textbooks, Jay Margolis, the
editorial direction to two academic journals which I edit Project Editor who managed every step of the production
as well as a major intensive-care textbook (Irwin and process with expertise, patience, and knowledge, Laura
Rippe’s Intensive Care Medicine, 8th Edition, Wolters Piedrahita, Editorial Assistant, who prepared and orga-
Kluwer, 2018). She also helps to coordinate other academic nized our files for production while managing communi-
endeavors. Beth possesses superb editorial skills and puts cation with hundreds of authors, as well as Rachel Cook,
in enormous efforts with unfailing good humor to make Senior Project Manager at Deanta, who managed the edit-
all of these complex and difficult projects possible. ing, design, and typesetting of the book with great skill.
I would also like to thank 21 section editors who con- Finally, I am grateful to my family, including my lov-
tributed hard work and exceptional editorial skills to ing wife, Stephanie Hart Rippe, and our four beautiful
ensure scientific accuracy and clinical relevance for each daughters, Hart, Jaelin, Devon, and Jamie, who continue
of the sections of this book. I am deeply grateful to all of to love and support me through the arduous process of
these individuals. A special thanks goes out to the more many major textbooks and journals and the other diverse
than 250 scientists and clinicians who have contributed professional responsibilities that I juggle along with my
chapters to this textbook. These individuals, who are family life.
internationally renowned experts in the key fields related If there are errors or omissions in Lifestyle Medicine,
to lifestyle medicine, have made invaluable contributions the responsibility is mine. If there is credit due for this
to assemble and explain enormous amounts of data in this project, it belongs to the numerous people who have made
rapidly emerging discipline. substantial contributions along the way.
I would also like to express my appreciation to my
office support staff, including my Executive Assistant, James M. Rippe, MD
Carol Moreau, who seamlessly coordinates my schedule Boston, Massachusetts
xvii
About the Editor
James M. Rippe, MD , is a graduate of Harvard College of lifestyle medicine and high-performance health. RLI
and Harvard Medical School. His postgraduate training also conducts numerous studies every year on physical
was at Massachusetts General Hospital. He is currently activity, nutrition, and healthy weight management.
the founder and director of the Rippe Lifestyle Institute. A lifelong and avid athlete, Dr. Rippe maintains his
Over the past 25 years, Dr. Rippe has established and personal fitness with a regular walk, jog, swimming, and
run the largest research organization in the world that weight training program. He holds a black belt in karate
explores how daily habits and actions impact short- and and is an avid wind surfer, skier, and tennis player. He
long-term health and quality of life. This organization, lives outside of Boston with his wife, television news
the Rippe Lifestyle Institute (RLI), has published hun- anchor Stephanie Hart and their four children, Hart,
dreds of papers that form the scientific basis for the fields Jaelin, Devon, and Jamie.
xix
Contributors
Nathan A. Berger, MD
Christina Aivadyan, MS
Distinguished University Professor
School of Social Work
Hanna-Payne Professor of Experimental Medicine
Columbia University
Professor of Medicine, Biochemistry, Oncology, Genetics
New York, New York
and Genome Sciences
Director, Center for Science, Health and Society
Jean M. Altman, MS Case Comprehensive Cancer Center
Nutritionist Case Western Reserve University School of Medicine
Office of Nutrition Guidance and Analysis Cleveland, Ohio
Center for Nutrition Policy and Promotion
U.S. Department of Agriculture Aaron D. Berman, MD, FACC
Alexandria, Virginia Clinical Chief, Department of Cardiovascular Medicine
Beaumont Hospital
Lars Bo Andersen, Dr Sc Royal Oak, Michigan
Professor and
Faculty of Teacher Education and Sport Associate Professor, Oakland University William
Western Norwegian University of Applied Sciences Beaumont School of Medicine
Oslo, Norway Rochester, Michigan
xxi
xxii Contributors
Division of General Internal Medicine Department of Psychology
Department of Medicine University of California Santa Cruz
University of Pennsylvania Perelman School of Medicine Santa Cruz, California
Philadelphia
LeShaundra Cordier, MPH, CHES
Wojtek J. Chodzko-Zajko, PhD
Communications Team Lead
Dean
Division of Unintentional Injury Prevention (DUIP)
Graduate College
National Center for Injury Prevention and Control
Shahid and Ann Carlson Khan Professor in Applied
(NCIPC)
Health Sciences
Centers for Disease Control and Prevention (CDC)
University of Illinois at Urbana-Champaign
Atlanta, Georgia
Urbana, Illinois
School of Architecture & Built Environment Professor
Deakin University—Geelong Waterfront Campus Department of Medicine
Geelong, Victoria, Australia and
Director
James E. Eubanks, Jr., DC, MS Behavioral Medicine Research Center
Research Scholar Baylor College of Medicine
MD Candidate, Class of 2018 Houston, Texas
Brody School of Medicine at East Carolina University
Amy Fowler, BS
Department of Physical Medicine and Rehabilitation
Senior Exercise Physiologist
Greenville, North Carolina
Preventive Cardiology & Rehabilitation
Beaumont Health
Gethin H. Evans, BSc, PhD Royal Oak, Michigan
Principle Lecturer in Healthcare Science
School of Healthcare Science Louis Hugo Francescutti, MD, PhD, MPH
Manchester Metropolitan University Professor
Manchester, UK School of Public Health
Department of Emergency Medicine Faculty of Medicine
Kayla N. Fair, DrPH University of Alberta
Postdoctoral Researcher Edmonton, AB, Canada
Center for Depression Research and Clinical Care
Department of Psychiatry Erica Frank, MD, MPH, FACPM
University of Texas Southwestern Medical Center Professor and Canada Research Chair
Dallas, Texas University of British Columbia
Founder and President, www.NextGenU.org
and
Mark D. Faries, PhD Principal Investigator
Texas A&M AgriLife Extension Service Healthy Doc = Healthy Patient
Texas A&M School of Public Health Vancouver, BC, Canada
Texas A&M University College of Medicine
College Station, Texas Barry A. Franklin, PhD
Director, Preventive Cardiology and
Regis Fernandes, MD, FACC, FASE Cardiac Rehabilitation
Medical Director, Cardiac Rehabilitation Program Beaumont Health
Mayo Clinic Beaumont Health & Wellness Center
Scottsdale, Arizona Royal Oak, Michigan
Assistant Professor of Medicine
Mayo Clinic School of Medicine Marion J. Franz, MS, RD, CDE
Scottsdale, Arizona Nutrition/Health Consultant
Nutrition Concepts by Franz, Inc.
Minneapolis, Minnesota
Antonio B. Fernandez, MD
Director
Cardiac Intensive Care Unit Elizabeth Pegg Frates, MD
The Heart and Vascular Institute Lifestyle Medicine Specialist
Hartford Hospital Health and Wellness Coach
Hartford, Connecticut Wellness Synergy, LLC
and
Assistant Professor, Part Time
Peter Fifield, EdD, LCMHC, MLADC Harvard Medical School
Adjunct Faculty Harvard Extension School
Department of Education Boston, Massachusetts
University of New England
Biddeford, Maine Karla I. Galaviz, PhD, MSc
Assistant Professor
Michael G. Flynn, PhD Hubert Department of Global Health
Division Director of Research Rollins School of Public Health
HCA South Atlantic Emory University
Charleston, South Carolina Atlanta, Georgia
xxvi Contributors
Professor Clinical Dietitian
Department of Psychiatry Lifestyle Medicine Program
College of Physicians and Surgeons, Children’s Hospital Colorado
Department of Epidemiology, Mailman School of Public Aurora, Colorado
Health
Columbia University Linda Hill, MD
New York, New York Director
Center for Human and Urban Mobility
and
Bradley D. Hatfield, PhD, FACSM, FNAK
Director
President National Academy of Kinesiology
Preventive Medicine Residency
Professor and Chair
and
Department of Kinesiology
Professor
and
Department of Family Medicine and Public Health
Associate Dean for Faculty Affairs
School of Medicine
School of Public Health
University of California, San Diego
Affiliate – Neuroscience and Cognitive Science Program
San Diego, California
University of Maryland
College Park, Maryland
Kristin Holland, PhD, MPH
Lead Behavioral Scientist
Elizabeth Hathaway, PhD, MPH Division of Violence Prevention (DVP)
Assistant Professor Centers for Disease Control and Prevention (CDC)
Exercise Science National Center for Injury Prevention and Control
Department of Health and Human Performance (NCIPC)
University of Tennessee at Chattanooga Atlanta, Georgia
Chattanooga, Tennessee
Debora Holmes, MES
Laura L. Hayman, PhD, MSN, FAAN, FAHA, FPCNA Chief Editor
Professor NextGenU.org
Department of Nursing Clear Lake, Washington
College of Nursing and Health Sciences
Jenna M. Holzhausen, PharmD, BCPS
University of Massachusetts Boston
Clinical Pharmacy Specialist, Critical Care
Adjunct Professor of Medicine
Cardiac Intensive Care Unit
Department of Medicine
Beaumont Hospital
Division of Preventive and Behavioral Medicine
Royal Oak, Michigan
University of Massachusetts Medical School
Boston, Massachusetts
Shewanee D. Howard-Baptiste, PhD
Associate Professor
Julia Head, MD Department of Health and Human Performance
Clinical Fellow University of Tennessee at Chattanooga
Department of Obstetrics and Chattanooga, Tennessee
Gynecology, and Reproductive Biology
Beth Israel Deaconess Medical Center Joel W. Hughes, PhD, FAACVPR
Harvard Medical School Professor
Boston, Massachusetts Department of Psychological Sciences
Kent State University
Gregory W. Heath, DHSc, MPH FAHA, FACSM Kent, Ohio
Guerry Professor, Public Health Program
Jodi Hutchinson, PA-C
Department of Health and Human Performance
Director of Integrative Medicine
University of Tennessee at Chattanooga
Holy Redeemer Health System
Chattanooga, Tennessee
Meadowbrook, Pennsylvania
Assistant Professor University of Minnesota
University of Wisconsin Whitewater Assistant Professor
Health, Physical Education, Recreation and Coaching Family Medicine and Community Health
Whitewater, Wisconsin Director of Integrative Health Coaching
Earl E. Bakken Center for Spirituality and Healing
Helen Kingery, MPH Minneapolis, Minnesota
Division of Unintentional Injury Prevention (DUIP)
National Center for Injury Prevention and Control Jenny Sunghyun Lee, PhD, MPH, CHES, CWP,
(NCIPC) CHWC, BCLM
Centers for Disease Control and Prevention (CDC) Assistant Professor of Family Medicine
Atlanta, Georgia Founder & Director, GoodNEWS Lifestyle Medicine and
Holistic Wellness Program
Peter Kokkinos, PhD Director, Community Engagement in PRECISION Pain
Professor Research, Osteopathic Research Center
Veterans Affairs Medical Center Texas College of Osteopathic Medicine
Cardiology Department University of North Texas Health Science Center
Washington, DC Fort Worth, Texas
Georgetown University School of Medicine
Washington, DC Arthur S. Leon, MS, MD, FACSM
Rutgers University, Department of Kinesiology and Henry L. Taylor Professor
Health Laboratory of Physiological Hygiene and Exercise
New Brunswick, NJ Science
University of South Carolina, Department of Exercise School of Kinesiology
Science University of Minnesota
Columbia, SC Minneapolis, Minnesota
Jeffrey Krauss, MD, DipABLM
Liana Lianov, MD, MPH, FACPM, FACLM
Veterans Affairs Palo Alto Health Care System
Founder and Principal
and
HealthType LLC
Department of Orthopaedic Surgery
and
Stanford University School of Medicine
Chair
Palo Alto, California
Happiness Science and Positive Health Committee
American College of Lifestyle Medicine
Robert F. Kushner, MD
and
Professor
Vice-Chair
Department of Medicine
American Board of Lifestyle Medicine
Division of General Endocrinology
Fair Oaks, California
Northwestern Medicine
Chicago Illinois
Alice H. Lichtenstein, DSc
Theodore K. Kyle, RPh, MBA Gershoff Professor of Nutrition Science and Policy
Principal and Founder Director and Senior Scientist, Cardiovascular Nutrition
ConscienHealth Laboratory
Pittsburgh, Pennsylvania Tufts University
JM USDA Human Nutrition Research Center on Aging
Boston, Massachusetts
Carl “Chip” J. Lavie, MD, FACC, FACP, FCCP,
FESPM
Medical Director, Cardiac Rehabilitation and Preventive Sara Link, MS, NBC-HWC
Cardiology Department of Family Medicine and Public Health
Director, Exercise Laboratories University of California, San Diego
John Ochsner Heart and Vascular Institute La Jolla, California
and
Editor-in-Chief Progress in Cardiovascular Diseases Sarah Linke, PhD, MPH
Associate Editor and Cardiovascular Section Editor, Assistant Clinical Professor
Mayo Clinic Proceedings Department of Family Medicine and Public Health
Professor of Medicine University of California, San Diego
Ochsner Clinical School-the University of Queensland and
School of Medicine Family Medicine and Public Health
New Orleans, Louisiana La Jolla, California
xxx Contributors
Assistant Professor President
Department of Psychiatry Weimar Institute
University of Colorado School of Medicine Adjunct Professor of Clinical Medicine
Aurora, Colorado Loma Linda University
and
Nancy Houston Miller, RN, BSN, FAHA, FPCNA, Owner
FAACVPR Nedley Clinic, Depression and Anxiety Recovery Programs
Co-Director Weimar, California
The LifeCare Company
Lisa A. Neff, PhD
Stanford University School of Medicine (Ret)
Associate Professor
Los Altos, California
Department of Medicine
Division of Endocrinology
Samantha Minski, PhD Northwestern University
Behavioral Health Fellow Feinberg School of Medicine
Department of Family Medicine and Community Health Chicago, Illinois
University of Massachusetts Medical School
Worcester, Massachusetts Jeanne Nichols, PhD, FACSM
Research Director
Jaime M. Moore, MD Exercise and Physical Activity Resource Center (EPARC)
Postdoctoral Fellow Department of Family Medicine and Public Health
University of Colorado School of Medicine University of California, San Diego
Department of Pediatrics, Section of Nutrition San Diego, California
Children’s Hospital Colorado
David C. Nieman, DrPH, FACSM
Aurora, Colorado
Professor and Director
Appalachian State University
Margaret Moore, MBA, ACC Human Performance Lab
Founder/CEO North Carolina Research Campus
Wellcoaches Corporation Kannapolis, North Carolina
Wellesley, Massachusetts
Michael Parkinson, MD, MPH, FACPM
Dakota G. Morales, MS Senior Medical Director
Department of Kinesiology and Community Health Health and Productivity
University of Illinois Urbana-Champaign UPMC Health Plan and Work Partners
Urbana, Illinois Pittsburgh, Parkinson
Jacqueline Proszynski, BS
Edward M. Phillips, MD Clinical Research Program Coordinator
Assistant Professor The Benson-Henry Institute for Mind Body Medicine
Physical Medicine & Rehabilitation Massachusetts General Hospital
Harvard Medical School Boston, Massachusetts
and
Director Elizabeth B. Rahavi, RDN
Institute of Lifestyle Medicine Nutritionist
Spaulding Rehabilitation Hospital Center for Nutrition Policy and Promotion
Boston, Massachusetts United States Department of Agriculture
Alexandria, Virginia
Lawrence S. Phillips, MD
Medical Director Francisco E. Ramirez, MD, BS, SC
Clinical Studies Center Director of Research
Atlanta VA Medical Center Nedley Clinic
Decatur, Georgia Weimar Institute
and Colfax, California
Professor of Medicine
Chad D. Rethorst, PhD
Division of Endocrinology and Metabolism
Associate Professor
Department of Medicine
Department of Psychiatry
Emory University School of Medicine
University of Texas Southwestern Medical Center
Atlanta, Georgia
Dallas, Texas
Founder and Director Program Director
Rippe Lifestyle Institute Cardiac Rehabilitation & Wellness
Shrewsbury, Massachusetts Department of Cardiovascular Diseases
Mayo Clinic
Renee J. Rogers, PhD Scottsdale, Arizona
Assistant Professor and
University of Pittsburgh Clinical Professor
Department of Health and Physical Activity College of Health Solutions
Healthy Lifestyle Institute Arizona State University
Physical Activity and Weight Management Research Phoenix, Arizona
Center
Pittsburgh, Pennsylvania
Sandra Scheinbaum, PhD
Founder and CEO
Debbie Rose, PhD, FNAK
Functional Medicine Coaching Academy
President, National Academy of Kinesiology
Chicago, Illinois
Professor
Director
Center for Successful Aging Charlene Schmidt, PhD, MS, RDN
Co-Director Associate Professor, Nutrition/Dietetics,
Fall Prevention Center of Excellence Department of Health and Human Performance
California State University, Fullerton. University of Tennessee at Chattanooga
Fullerton, California Chattanooga, Tennessee
Former Director of Nutrition and Food Services
Dean, College of Applied Health Spaulding Rehabilitation Hospital
Sciences and
University of Illinois at Chicago Clinical Associate
Chicago, Illinois Boston University
Clinical Associate
Randal J. Thomas, MD, MS Framingham State University
Medical Director Boston, Massachusetts
Cardiac Rehabilitation Program
Mayo Clinic Michael A. Via, MD
Rochester, MN Assistant Professor
and Department of Medicine
Professor of Medicine Fellowship Director
Mayo Clinic School of Medicine Division of Endocrinology, Diabetes and Bone Disease
Rochester, Minnesota Mount Sinai Beth Israel Medical Center
Icahn School of Medicine
New York, New York
Paul D. Thompson, MD
Co-Chair Heart and Vascular Institute
Chief of Cardiology Michelle L. Vidoni, MPH, PhD
Hartford Hospital Senior Statistician
Hartford, Connecticut Department of Medical School
Center for Clinical and Translational Sciences
The University of Texas Health Science Center at
Emil Tigas, MD Houston (UTHealth)
Assistant Professor of Medicine Houston, Texas
Division of Pulmonary, Allergy & Critical Care Medicine
University of Massachusetts Medical School
Kenneth Vitale, MD FAAPMR
Worcester, Massachusetts
Physical Medicine and Rehabilitation
Subspecialty Certification in Sports Medicine
John Torous, MD Associate Professor
Psychiatrist and Director of Digital Psychiatry Department of Orthopaedic Surgery
Department of Psychiatry University of California, San Diego
Beth Israel Deaconess Medical Center La Jolla, California
Harvard Medical School
Boston, Massachusetts
Joseph R. Volpicelli, MD
Executive Director
Sunkaru Touray, MBChB, MSc Institute of Addiction Medicine, Inc.
Clinical Fellow in Pulmonary Diseases & Critical Care Plymouth Meeting, Pennsylvania
Medicine
Division of Pulmonary, Allergy & Critical Care Medicine Brigitt-Leila von Lindenberger, MSc
University of Massachusetts Medical School Department of Psychiatry and Psychotherapy
Worcester, Massachusetts Charite-Universitatsmedizin Berlin
Berlin, Germany
Elaine B. Trujillo, MS, RDN
Nutritionist Mary Beth Weber, PhD, MPH
Nutritional Science Research Group Assistant Professor
Division of Cancer Prevention Emory University
National Cancer Institute Hubert Department of Global Health
National Institutes of Health Rollins School of Public Health,
Rockville, Maryland Atlanta, Georgia
1
1
CHAPTER
3
4 Chapter 1 The Rationale for Intervention to Reduce the Risk of Cardiovascular Disease
comes from cardiovascular disease.1 Although knowledge an estimated decrease of 341,745 deaths.3 About half of
of many factors contributing to CVD is incomplete, it is this decline resulted from improvements and advances in
clear that many risk factors contribute in significant ways treatment, while approximately 44% related to risk factor
to the ongoing epidemic of cardiovascular disease. reduction. An estimated 149,635 fewer deaths from CVD
Cardiovascular disease is truly a pandemic and represents came from improved treatment3 of some of its risk factors,
the most important cause of death worldwide. In 2010, car- while an estimated 59,370 increase in deaths occurred
diovascular disease resulted in an estimated 16 million deaths from the higher rates of obesity and diabetes. 3 The increas-
and 293 million disability-adjusted life years (DALYs) lost. ing prevalence of obesity and diabetes has the potential to
These represent approximately 30% of all deaths worldwide completely wipe out the advances in the reduction of other
and 11% of all DALYs lost that year. This disease not only risk factors if the trends of these two lifestyle risk factors
impacts high-income countries but has become increasingly are not reversed.
prevalent in both low- and middle-income countries, which Despite advances in reducing certain lifestyle-related
have seen an alarming increase in CVD rates. risk factors for CVD, these risk factors remain extremely
So prominent has been the role of certain lifestyle fac- common. For example, the prevalence of hypertension in
tors that it has been argued that the world is entering into the United States has continued to increase, with recent
a new epidemiologic transition. In the past four epidemio- data suggesting that more than one-third of American
logic transitions, the predominant causes of death have been adults have high blood pressure,7,8 The Surgeon General’s
identified starting with pestilence and famine, then receding Report on Physical Activity and Health documented that
pandemics, followed by degenerative and man-made dis- over 70% of the adult population in the United States fail
eases, and finally delayed degenerative diseases. It has been to get enough regular physical activity to lower their risk
argued that the modern world maybe entering a fifth epide- of CVD,9 despite the fact that the 2008 Physical Activity
miologic phase highlighted by inactivity and obesity/diabe- Guidelines for Americans demonstrate multiple health
tes, both of which contribute in significant ways to CVD.2 benefits for virtually every population group.10 Overweight
Lifestyle habits and practices constitute a significant and obesity has continued to rise in the United States, with
contributor to this ongoing epidemic. While progress has over 68% of the population showing one of these two
been made in some of these areas (e.g., hypertension, total conditions.11
cholesterol, smoking cessation, physical activity), unfortu- The epidemic of diabetes in the United States continues
nately, regression has occurred in such areas as obesity and to rise, with approximately 9% of the adult population
diabetes. 3 The increasing prevalence of these latter two currently suffering from this chronic condition—almost
conditions has the potential to wipe out progress made on double the rate of 20 years ago.12 After several decades
all the other lifestyle-related risk factors for CVD.3 of encouraging declines in cigarette smoking, progress
In addition to its human cost, CVD also represents an unfortunately appears to have leveled off in this area, with
enormous financial drain in the United States. It has been esti- about 20% of the overall population in the United States
mated that over $150 billion per year is spent on direct medi- still smoking.13 Thus, some progress in reducing risk fac-
cal expenses and other associated costs related to CVD.4,5 tors has occurred, but enormous challenges and oppor-
Lifestyle factors play a particularly prominent role in tunities remain for applying lifestyle measures often, in
the development and pathogenesis of CVD. Indeed, five conjunction with pharmaceutical therapy, to reduce the
of the major risk factors for developing CVD relate to risk of CVD.
lifestyle practices, including the following: the choice of
whether or not to use tobacco products, level of physical
activity, control of lipids, diabetes, and obesity.6 1.1.1 The Pathophysiology of
In this chapter we focus on the rationale for interven-
ing to reduce risk factors for CVD. The next chapter,
Atherosclerosis
“Lifestyle Strategies for Risk Factor Reduction, Prevention, As knowledge of the pathophysiology of atherosclerosis
and Treatment of Cardiovascular Disease,” will discuss has advanced, new understandings have provided crucial
applications of lifestyle interventions in clinical practice linkages to the role of various lifestyle interventions in the
to reduce the risk of CVD. reduction of risk of CVD. For example, the role of poor
Deaths from CVD and stroke have been declining in diet (e.g., elevated consumption of saturated fats) and
the United States for the past four decades. For example, diminished physical activity have been known for years
between 1963 and 1990 the mortality of coronary heart to contribute to atherogenesis.14,15 However, only in the
disease fell by more than 50%.7 Nonetheless, CVD and past decade has the significant role of inflammation as an
stroke remain the leading causes of morbidity and mortal- initiating event in the process of atherosclerosis begun to
ity in the United States and in most other industrialized be elucidated. Since multiple related conditions such as
countries. The decline in CVD and stroke is a result of not CHD, obesity, diabetes, glucose intolerance and the meta-
only reduced prevalence of risk factors but also advances bolic syndrome have significant overlap; it may indeed be
in treatment and therapies. However, the increased prev- a component of systemic inflammation that unites all of
alence of diabetes and obesity, and an aging population, these processes.
work against reductions in CVD and stroke prevalence and Fundamental to the understanding of the interplay
require expanded efforts to reduce lifestyle-related risk fac- between lifestyle and atherosclerosis is the evolving con-
tors in order to continue reducing the burden of CVD. cept of the role of various structures and the interaction
Between 1980 and 2000, the decline in the age of components of both normal and diseased arteries (e.g.,
related death from coronary heart disease (CHD) led to endothelium, smooth muscle, and intima) as well as how
1.3 Primordial Prevention and “Ideal” Cardiovascular Health 5
various cells in these structures function both in health young individual with abnormal lipids would be treated
1
and disease.16–18 differently than an older individual with a similar lipid
The evolving understanding of the biology of athero- profile, all other things being equal, since while their
sclerosis is beyond the scope of the current chapter. The increased relative risk may be the same, their absolute risk
reader is referred to several recent excellent reviews that may be quite different.45–47
discuss current understandings of the atherosclerotic pro- One way of viewing relative risk may be that it provides
cess in detail.18,19 an indication of how rapidly an individual may move to
absolute risk. Thus, a young individual with high relative
risk would be at greater risk of ultimately developing high
1.2 UNDERSTANDING RISK FACTORS absolute risk and that fact might motivate the clinician
to devise strategies for lowering risk as a means of slow-
1.2.1 The Concept of Risk Factors ing the early stages of developing CVD. Such interventions
as lifestyle measures, which carry multiple benefits and
The concept of risk factors is relatively new in the his- relatively little risk and expense, are attractive means for
tory of medicine. In fact, until the initial findings from lowering both relative and absolute risk of CVD.
the Framingham Study were published in the 1960s, the
concept of risk factors for CVD did not formally exist.20
Framingham data showed that factors such as diabe-
tes,21–24 dyslipidemia,25–29 high blood pressure,30–33 and
1.2.3 Primary versus Secondary
cigarette smoking34–37 each independently and signifi- Prevention
cantly increased the risk of CVD. The concept of CVD It is also important to distinguish between “primary”
risk factors has been expanded to include physical inac- and “secondary” prevention when approaching risk fac-
tivity38 and obesity.39 Other emerging risk factors where tor reduction. Primary prevention is based on the goal of
lifestyle habits and practices may play a role are under preventing or delaying the development of CVD, while
active investigation. secondary prevention focuses on interventions designed to
Framingham data also demonstrated that risk factors reduce the likelihood of repeat cardiovascular events and/
act synergistically and tend to cluster with each other.40 or mortality in individuals who already have established
Thus, in the presence of two risk factors, an individual CVD. More aggressive measures for risk factor reduction
quadruples their chance of developing CVD compared are typically indicated in individuals when they are used
to individuals with no risk factors. Individuals with three in secondary prevention (see Chapters 64 and 70).
risk factors increase their risk of developing CHC between Guidelines for risk factor reduction in primary pre-
eight- and twenty-fold compared to individuals with no vention are available from a variety of sources. Perhaps
risk factors.41 the most widely used is the Framingham Risk Scoring
In addition to the lifestyle-related risk factors identi- system.48 Guidelines for interventions for secondary pre-
fied by the Framingham Study and other observational vention have also been published by the American Heart
and interventional studies, other risk factors have been Association (AHA) and are discussed in detail in Chapter
determined, including age, gender, family history of CVD, 64 and 70 later in this book.
elevated C-reactive protein (CRP), hemostatic factors,
excessive alcohol consumption, hypertriglyceridemia, ele-
vated homocysteine levels, and perhaps stress and other 1.3 PRIMORDIAL PREVENTION AND
psychological factors such as depression.
Numerous studies have demonstrated that reducing “IDEAL” CARDIOVASCULAR
risk factors for CVD can significantly decrease its likeli-
hood.42–44 Lifestyle measures are a particularly powerful
HEALTH
and effective way of lowering risk factors, since these mea- In 2010 the American Heart Association issued a stra-
sures are low-risk and many of them simultaneously affect tegic plan through the year 2020 and beyond.49 New to
multiple risk factors. this plan was a concept of “primordial” prevention. The
goal of primordial prevention as articulated by the AHA
is “that by 2020 to improve the cardiovascular health of
1.2.2 Relative Risk versus Absolute Risk Americans by 20% while reducing deaths from cardio-
It is important to differentiate between “relative” and vascular and stroke by 20%.” In issuing this statement,
“absolute” risk, since this distinction underlies treatment the AHA recognized and declared: “Health is a broader,
strategies for risk factor reduction in CVD. Relative risk is more positive construct than just the absence of clinically
a comparison between different risk levels. It compares the evident disease.” It defined “primordial” prevention as a
likelihood that an individual who possesses a specific risk process to avoid adverse levels of risk factors in the first
factor will develop CVD in comparison to an individual place rather than trying to reduce risk factors when they
without that risk factor. Absolute risk represents the likeli- are already present or treating already established disease.
hood of developing CVD over a specified period of time. This broader risk factor reduction strategy is completely
Framingham risk scores, for example, typically assess the consistent with the goals and vision of lifestyle medicine
absolute risk of developing CVD over a ten-year period. and will require careful attention to daily lifestyle habits
The difference between relative and absolute risk is a and actions and their impact on risk factors and overall
critical factor in clinical decision making. For example, a health.
6 Chapter 1 The Rationale for Intervention to Reduce the Risk of Cardiovascular Disease
The AHA Strategic Plan49 also defined a construct of evidence rather than epidemiologic evidence. 56,57 This
“ideal” cardiovascular health, which was defined as the has been particularly useful when thinking about when
following: to use statin medications for prevention of cardiovascu-
lar disease. Preventive cardiologists in the United States,
The simultaneous presence of four favorable health Canada, and Europe have combined a list of recommenda-
behaviors: absence of smoking within the last year, tions on clinical trial data concerning when to use statins
physical activity at goal, consumption of a “heart in prevention of cardiovascular disease.58,59 This strategy
healthy” dietary pattern and an ideal body mass has been summarized as “what works” and “in whom.”
index (BMI). These recommendations will be handled in more detail in
Simultaneous presence of four favorable health Chapter 2.
factors: absence of smoking for at least one year,
untreated cholesterol less than 200 mg/dL, untreated
blood pressure less than < 120/<80 mm Hg, and the 1.7 MODIFIABLE RISK FACTORS
abstinence of diabetes mellitus, absence of clini-
cal cardiovascular disease (including CVD, stroke, This section will focus on risk factor reduction for those
heart failure, etc.) risk factors which can be modified, while the next section
will focus on those risk factors which cannot be modi-
Clearly this very welcome framework will result in an fied. The modifiable risk factors represent a particularly
increased emphasis on physicians treating, and patients important area for clinical intervention. Numerous stud-
following, positive lifestyle behaviors to improve their ies have demonstrated that lifestyle measures for reducing
cardiovascular health. modifiable risk factors is an effective strategy for reducing
the risk of developing CVD.
slightly more than half of smokers who had at least one NCEP Adult Treatment Panel (ATP III) Guidelines sup-
1
physician visit in the previous year were advised to quit port an HDL level of > 60 mg/dL as a negative risk factor
smoking cigarettes.68 The impact of spouse, friends, and for CVD.81 It should be noted that several recent trials of
families on cigarette smoking cessation is also significant. novel pharmaceutical agents designed to raise HDL have
Recent studies suggest that smoking cessation by a spouse been somewhat disappointing and have resulted in untow-
decreases an individual’s chance of smoking by 67%, ard side effects such as hypertension. Trials such as the
while smoking cessation by a co-worker, sibling, or friend “AIM-HIGH” study, which randomly allocated high-risk
contributes to a person’s decrease in likelihood of smoking patients to niacin supplementation, increased HDL cho-
by 25–36%.69 lesterol and reduced triglycerides yet did not yield reduc-
tions in clinical events.82 Furthermore, the investigation of
lipid-level management to understand its impact on ath-
1.7.2 Dyslipidemias erosclerotic events (ILLUMINATE), individuals at higher
vascular risks who were given a Cholesterylester Transfer
Numerous trials have demonstrated that a variety of dys- Protein (CETP) inhibitor torcetrapib actually showed an
lipidemias or combination of dyslipidemias increase the unanticipated increase in all-cause mortality.83 Despite
risk of CVD.43,70–80 these negative results, HDL cholesterol levels as “nega-
tive risk factors” for CVD are strongly supported both by
1.7.2.1 Elevated Low Density Lipoprotein cross-sectional and prospective studies which support the
continued use in guidelines worldwide.
Cholesterol and Hyperlipidemia
Hypercholesterolemia has been clearly associated with
increased risk of CVD. In particular, increased plasma 1.7.2.3 Hypertriglyceridemia
levels of low-density lipoprotein (LDL) have been asso- An association between elevated triglyceride levels
ciated with increased incidence of CVD. Based on these and cardiovascular disease has been known for many
data, the Nutrition Cholesterol Education Program Adult years.84,85 However, the evidence supporting a direct
Treatment Panel Guidelines (ATP III) established LDL as linkage is less robust than that for elevated LDL or low
the primary target for intervention.74 Numerous observa- HDL and CVD. Recent attention has been focused on
tional trials, including the Framingham Study, MRFIT, elevated triglycerides as a risk for heart disease, given its
the Nurses’ Health Study and the U.S. Male Health association with obesity, insulin resistance and diabe-
Professional follow-up study have all demonstrated tes. Statements from the American Heart Association on
an association between elevated blood cholesterol and Childhood and Adolescent Obesity and on Triglycerides
increased risk of CVD. Numerous interventional studies and Cardiovascular Health emphasize the importance
have also established that elevated blood cholesterol and, of lowering triglycerides through lifestyle measures as a
in particular, elevated LDL, is associated with increased means of lowering risk of CVD.86 Current designations
incidence of CVD.70–80 Several lines of evidence have sug- for triglyceride levels are as follows: 150–199 mg/dL,
gested that what are regarded as “normal” cholesterol borderline high; 200–499 mg/dL, high; and > 500 mg/
levels in Western society are higher than necessary for dL, very high. Overall, 31% of the adult population in
good health. Furthermore, cholesterol levels measured in the United States has a triglyceride level > to 150 mg/dL.43
early in life influence long-term cardiovascular risk, sug-
gesting that cholesterol should be routinely measured in
children. These studies have become particularly robust 1.7.3 Hypertension
since the development of hydroxymethylglutaryl-coen- High blood pressure constitutes a significant increased
zyme A (HMG-CoA) reductase inhibitors (statins). These risk of CVD. The prevalence of hypertension has increased
agents lower LDL cholesterol much more efficiently than steadily in the United States over the past ten years.87
previously available drugs. Numerous large clinical trials, According to the report of the most recent Joint National
where statins have been utilized to lower LDH cholesterol Committee on Prevention, Evaluation and Treatment of
by 20–60%, reduced coronary events by up to one-third High Blood Pressure (JNC VII), more than one out of
over a five-year period without evidence of increased non- every three adults suffers from high blood pressure.87 This
vascular mortality.42 means that more than 50 million individuals have high
blood pressure.87 A subsequent report based on data from
the most recent National Health and Nutrition Evaluation
1.7.2.2 Low Levels of HDL Cholesterol Survey (NHANES III) places the number even higher at
A number of prospective cohort studies have also demon- 38% of the population (65 million individuals).88 Even
strated an inverse relationship between high-density lipo- individuals who have normal blood pressure at the age
protein (HDL) cholesterol and risk of CVD. Conversely, of 55 have a 90% lifetime risk of developing hyperten-
low HDL increases the risk of CVD.42 Each increase in sion during their lifetime according to data from the
HDL cholesterol by 1 mg/dL is associated with a 2–3% Framingham Heart Study.89
decrease in risk of total cardiovascular disease.42 Low The relationship between blood pressure and the risk
HDL cholesterol has been defined as an HDL lower than of CVD events is independent of other risk factors for
40 mg/dL. Levels lower than this are defined as an inde- CVD. For every 10 mm Hg rise in diastolic blood pressure
pendent risk factor for CVD in the most recent National or 20 mmHg rise in systolic blood pressure above 115/75
Cholesterol Education Program Guidelines. Moreover, the mm Hg, the increase in risk of CVD doubles.87
8 Chapter 1 The Rationale for Intervention to Reduce the Risk of Cardiovascular Disease
The JNC VII guidelines create a guideline lower than VIII recommend lifestyle interventions such as regular
previously established for normal blood pressure (below aerobic exercise, eliminating salt intake, maintenance of
120/80 mmHg) and create a new category of “prehyper- proper healthy weight, and not smoking cigarettes as the
tension” to replace the old category of “high normal.” cornerstone of any antihypertensive regimen.
The JNC VII classification for blood pressure in adults is
found in Table 1.1.87
High blood pressure is also frequently found coexisting
1.7.4 Diabetes and Glucose Intolerance
with other risk factors for CVD. For example, individuals The incidence of type 2 diabetes, which represents a major
with high blood pressure have a greater than 40% chance of risk factor for CVD, has increased dramatically in both
having elevated blood cholesterol.90–92 This is particularly men and women in the United States over the past 20
important since over half of heart disease occurs in indi- years. Diabetes now affects over 9% of adults.12 Perhaps
viduals with two or more risk factors. JNC VII guidelines of even greater importance is that an estimated 35–40% of
recommend a six month trial of lifestyle related measures adults have impaired glucose tolerance or impaired fasting
such as weight loss, smoking cessation, regular exercise, glucose levels.90 Diabetes is also one of the most common
and improved nutrition for individuals with Stage1 hyper- chronic diseases in the world, affecting an estimated 285
tension before starting pharmacologic therapy.87 million adults in 2010 (6.4% of the global adult popula-
It should be noted that a commission was established tion).93 It is estimated that the prevalence of diabetes will
to formulate JNC VIII guidelines and made somewhat dif- grow to more than 430 million individuals (7.7% of the
ferent recommendations.93 The JNC VIII Guidelines con- global adult population) by the year 2030.93 Diabetes rep-
tain the following statement: “There is strong evidence to resents a significant risk factor for CVD. Individuals with
support treating hypertensive individuals aged 60 or older diabetes have between two and eight times higher rates of
to a BP goal of less than 150/90 mmHg and hypertensive cardiovascular events, compared to nondiabetic controls.91
patients 30–59 years of age to a diastolic goal of less than This risk factor is particularly potent in women with dia-
90 mmHg; however there is insufficient evidence in hyper- betes who increase their risk of developing CVD 3–7 times
tensive persons younger than 60 years for a systolic goal compared to an increased risk in men of 2–3 times. The
or in those younger than 30 years for a diastolic goal. So increase in diabetes parallels the increase of obesity in
the panel recommends a BP of less than 140/90 mmHg for the United States.92 It has been estimated that individuals
those groups based on expert opinion.” born in the United States in the year 2000 will have a 36%
The goal of the JNC VIII guidelines was to make the chance of developing diabetes in their lifetime.94
blood pressure control recommendations based on evi- For all of these reasons, prevention, early detection,
dence from randomized controlled trials. However, these and treatment of diabetes assumes great importance as
recommendations have not been widely adopted. The JNC a modality for reducing risk of CVD. Typical treatment
VIII guidelines emphasize that while these targets have involves multiple components of lifestyle measures such
been articulated, people’s judgment should still prevail in as weight loss for individuals who are overweight or obese
hypertensive therapy.93 Of note, both JNC VII and JNC and regular physical activity.
TABLE 1.1 Classification and management of blood pressure for adults aged 18 years or older
Management*
Initial drug therapy
BP Systolic BP, Diastolic Lifestyle Without compelling With compelling
classification mm Hg* BP, mm Hg* modification indication indications
Normal < 120 and < 80 Encourage
Prehypertension 120– 139 or 80– 89 Yes No antihypertensive drug Drug(s) for the compelling
indicated indications†
Stage 1 140– 159 or 90– 99 Yes Thiazide-type diuretics for Drug(s) for the compelling
hypertension most; may consider ACE indications; other
inhibitor, ARB, β -blocker, antihypertensive drugs
CCB, or combination (diuretics, ACE inhibitor, ARB,
β -blocker, CCB) as needed
Stage 2 ≥ 160 or ≥ 100 Yes 2-Drug combination for Drug(s) for the compelling
hypertension most (usually thiazide-type indications; other
diuretic and ACE inhibitor antihypertensive drugs
or ARB or β -blocker or (diuretics, ACE inhibitor, ARB,
CCB)‡ β -blocker, CCB) as needed
Abbreviations: ACE, angiotensin-converting enzyme; ARB, angiotensin-receptor blocker; BP, blood pressure; CCB, calcium channel blocker.
*Treatment determined by highest BP category.
† Treat patients with chronic kidney disease or diabetes to BP goal of less than 130/80 mm Hg.
‡ Initial combined therapy should be used cautiously in those at risk for orthostatic hypotension.
1.7 Modifiable Risk Factors 9
1
dently associated with CVD over and above increased
The prevalence of overweight and obesity has increased body weight. In particular, increased abdominal obesity
significantly in the United States and other developed has been demonstrated to increase risk of CVD.103,104
countries over the past 30 years. It is estimated that over A practical way of estimating abdominal obesity is to
two-thirds of the adult population in the United States is measure waist circumference. A waist circumference
now overweight or obese.11 Increases have been particu- of > 40 inches in men and > 35 inches in women confers
larly prominent in the area of Stage 1 obesity and severe a significantly increased risk of CVD compared to lower
obesity. Between 1980–2004, the prevalence of obesity levels of abdominal fat.
among adults in the United States doubled. In 2006, it was Adult weight gain also confers additional risk of CVD.
estimated that 35% women and 33% of men in the United According to the Nurses’ Health Study105 and U.S. Men’s
States were obese.95 Numerous studies have demonstrated Health Professional Study,106 individuals who gained 20
that obesity constitutes a strong and independent risk fac- lbs or more during their adult life significantly increased
tor for CVD in addition to its association with other risk their risk of type 2 diabetes and CVD.
factors such as dyslipidemia, diabetes, and hypertension.
The American Heart Association classifies obesity as a
major risk factor for CVD because of these associations.
The most practical and recognized way of assessing 1.7.6 Inactive Lifestyle
obesity in clinical practice is to determine an individual’s Physical activity carries multiple health benefits. 51
body mass index (BMI). BMI has also been shown in Unfortunately, the population in the United States (both
numerous studies to correlate with health risk. BMI clas- children and adults) has become increasingly inactive.
sifications, according to the Institute of Medicine,96 are Numerous studies have demonstrated that an inactive
listed in Table 1.2. lifestyle significantly increases the risk of CVD. In one
The linkages between obesity and CVD are not com- study, fitness level was more strongly associated with
pletely understood, although they are probably not only heart disease than any other risk factor, including ciga-
mediated by direct effects on the cardiovascular system rette smoking and hypertension.107 The Physical Activity
(a hyperdynamic state and increased blood flow) but Guidelines for Americans 2008 lists multiple significant
also by systemic inflammation. Adipocytes used to be benefits for increased physical activity as demonstrated
considered relatively inactive storage depots, but recent in Table 1.3.
studies have shown that, in fact, adipocytes are very There is strong evidence that regular physical activ-
metabolically active and generate a variety of inflamma- ity lowers the risk of high blood pressure, adverse lipid
tory markers such as interleukin-6 (IL-6), tumor necrosis profiles, type 2 diabetes, the metabolic syndrome, and
factor alpha (TNF- a), and C-reactive protein (CRP)97–100 weight gain. In addition, regular physical activity also
Excess weight is also associated with a variety of novel reduces overall risk for CVD, risk for stroke and all-cause
risk factors, including an atherogenic dyslipidemia (low mortality.
HDL-C, elevated triglycerides, elevated apoprotein B, and The Healthy People 2010 Initiative108 recommended the
elevated low-density lipoprotein). In addition, obesity is goal that at least 30% of the population over the age of six
associated with elevations in thrombotic factors such as should engage in light-to-moderate physical activity of at
Plasminogen Activator Inhibitor I and increased levels of least 30 minutes per day. This goal has been repeated in the
fibrinogen.101,102 Healthy People 2020 guidelines.109 Clearly, we are falling
TABLE 1.2 Classification of overweight and obesity as recommended by the National Heart, Lung, and Blood Institute
guidelines
Disease riska relative to normal weight and waist circumference
Waist circumference
<102 cm (men) >102 cm (men)
BMI (kg/m2) Obesity class <88 cm (women) >88 cm (women)
Underweight <18.5 _ _
Normalb 18.5–24.9 _ _
Overweight 25.0–29.9 Increased High
Obesity 30.0–34.9 1 High Very high
35.0–39.9 2 Very high Very high
Extreme obesity ≥40.0 3 Extremely high Extremely high
Source: National Heart, Lung, and Blood Institute; National Institutes of Health; U.S. Department of Health and Human Services. Bethesda, MD.
Disease risk for type 2 diabetes, hypertension, and cardiovascular disease.
a
b Increased waist can also be a marker for increased risk in normal weight individuals.
BMI, body mass index.
10 Chapter 1 The Rationale for Intervention to Reduce the Risk of Cardiovascular Disease
far short of these goals. The Surgeon General’s Report on Numerous guidelines, including those from the
Physical Activity documented that 24% of individuals American Heart Association, the American College of
report no recent physical activity, 54% are active but fall Sports Medicine,110 the Centers for Disease Control, and
short of the recommendations from Healthy People 2010, the Physical Activity Guidelines for Americans 2008,10 all
while only 22% of adults achieve this level of activity.9 consistently recommend that adults accumulate at least
30 minutes of moderate-intensity physical activity on
most, if not all, days. The Physical Activity Guidelines for
TABLE 1.3 Health benefits of regular physical activity Americans 2008 provides an alternative of 75 minutes per
Health Benefits Associated with Regular Physical Activity week of vigorous intensity physical activity.10 Definitions
Children and Adolescents of low, medium, and high physical activity are found in
Table 1.4.
Strong evidence
• Improved cardiorespiratory and muscular fitness Recently a corollary to the physical activity issue has
• Improved bone health been raised by studies suggesting that time spent sitting,
• Improved cardiovascular and metabolic health biomarkers particularly watching television or screen time, correlates
• Favorable body composition with increased risk of CVD. A meta-analysis of prospec-
• Moderate evidence tive cohort studies estimated that if every adult in the
• Reduced symptoms of depression United States decreased sitting time to less than three
Adults and Older Adults hours per day, life expectancy of the population would
increase by 2.0 years. In addition, if every adult reduced
Strong evidence
• Lower risk of early death
television viewing time to less than two hours a day, life
• Lower risk of coronary heart disease expectancy would increase by 1.4 years.111
• Lower risk of stroke Numerous studies have shown that physician recom-
• Lower risk of high blood pressure mendation is a powerful motivator to change lifestyle hab-
• Lower risk of adverse blood lipid profile its, including level of physical activity. Moreover, several
• Lower risk of type 2 diabetes studies support the finding that if the physician him- or
• Lower risk of metabolic syndrome
• Lower risk of colon cancer
herself is physically active, they are more likely to recom-
• Lower risk of breast cancer mended physical activity to their patients.112,113 The most
• Prevention of weight gain common form of physical activity recommended by physi-
• Weight loss, particularly when combined with reduced cians (first choice of over 90% of physicians) is walking.114
calorie intake
• Improved cardiorespiratory and muscular fitness
• Prevention of falls
• Reduced depression 1.7.7 Poor Nutritional Habits
• Better cognitive function (for older adults) A large body of research supports a linkage between
Moderate to strong evidence
• Better functional health (for older adults)
nutritional habits and risk of CVD. The American
• Reduced abdominal obesity Heart Association Guidelines for Pediatric and Adult
Moderate evidence Nutrition,115 the Dietary Guidelines for Americans
• Lower risk of hip fracture 2010,49 and the American Heart Association’s Strategic
• Lower risk of lung cancer Impact Goal Plan through 2020 and Beyond all recom-
• Lower risk of endometrial cancer mend nutrition intervention to lower the risk of CVD.
• Weight maintenance after weight loss
These guidelines are consistent in recommending lower
• Increased bone density
• Improved sleep quality fat, higher fiber, increased consumption of fruits and veg-
etables, and control of calories to maintain a healthy body
Source: 2008 Physical Activity Guidelines for Americans. weight.116
The AHA Strategic Plan for 202049 establishes the fol- than in women.120 Framingham Study data demonstrate
1
lowing metric for nutrition goals to lower the risk of CVD that men typically display the onset of symptoms of CVD
and states that “in the context of diet that is appropriate ten years younger than women.120 It is important to note
in energy balance, pursuing an overall dietary pattern that that symptoms of CVD may present differently in women
is consistent with a DASH (Dietary Approaches to Systolic than in men. The American Heart Association “Wear
Hypertension] type eating plan, including, but not limited to: Red” program has provided an important emphasis on
reducing risk factors for heart disease in women.121
• Fruits and vegetables: ≥5 cups per day
• Fish: ≥ two 3.5 servings per week (preferably oily
fish) 1.8.3 Family History
• Fiber-rich whole grains: ≥1.1 g of fiber per 10 g of
A positive family history CVD before the age of 65 in a
carbohydrate (≥ three one oz equivalent servings per
first-degree relative constitutes an independent risk factor
day)
for CVD.119 Why CVD tends to aggregate in some families
• Sodium: <1,500 mg per day
is not completely understood, although it may be medi-
• Sugar sweetened beverages: < 450 kcal (36 oz) per
ated through genetics or through risk factors that relate
week.”
to lifestyle components, such as levels of physical activity,
nutritional habits, dyslipidemias, or weight.
While these recommendations do not cover all aspects
of a heart-healthy diet, they represent a good starting
point for physicians counseling patients about improved
nutritional practices to lower the risk of CVD. These 1.9 THE METABOLIC SYNDROME
recommendations have been expanded upon in recent
reviews.117,118 Some recent evidence has suggested that
AND THE CONCEPT OF
diets adhering to the principles of a Mediterranean-style MULTIPLE RISK FACTORS
diet supplemented with extra virgin olive oil or nuts
reduced the incidence of major cardiovascular events in Framingham data clearly support that clustering of risk
the individuals with high cardiovascular risk.118 Evidence- factors is common.40 One type of clustering of risk fac-
based guidelines for overall dietary health are summa- tors has been referred to as “metabolic syndrome.” While
rized in the Dietary Guidelines for 2015 report. 50 there is ongoing debate about the criteria for the metabolic
syndrome,122 and numerous different definitions exist, the
one most commonly employed (such as in the National
1.8 NONMODIFIABLE RISK FACTORS Cholesterol Education Program ATP III Guidelines),81
includes the following criteria:
The risk factors described in the previous section can all
be reduced through appropriate lifestyle practices and • Waist circumference > 40 inches
habits in patients’ daily lives. There are also a number of • Blood pressure > 135/85 mm Hg
non-modifiable risk factors for CVD which will be dis- • Fasting blood glucose > 110 mg/dL
cussed in this section. • HDL cholesterol < 40 mg/dL
Although this second group of risk factors cannot • Fasting triglycerides > than 150 mg/dL
be altered through lifestyle habits, they play an impor-
tant role as part of the overall patient risk factor profile. According to the ATP III Guidelines, if an individual
Specifically, individuals who have significant non-modifi- has three or more of these five criteria, he or she is consid-
able risk factors should be even more strongly counseled ered to have the metabolic syndrome.
to make appropriate lifestyle changes to alter those risk Individuals with metabolic syndrome are at signifi-
factors which are modifiable. cantly higher risk for both coronary heart disease and dia-
betes than the general population. The ATP III Guidelines
recommend that an individual with the metabolic syn-
1.8.1 Age drome should be treated as though they already have
CVD. Data from the Framingham Study demonstrate that
Strong and consistent evidence associates increased age
60% of CVD is found in individuals who possess two or
with increased risk of CVD. Approximately 80% of all
more risk factors.
fatal myocardial infarctions occur in individuals over the
Debate is ongoing about the exact mechanism through
age of 65.119 Thus, in the elderly population, control of
which metabolic syndrome increases the risk of CVD.
modifiable risk factors assumes increasing importance.
Some investigators maintain that the mechanism is
Regular physical activity, weight management, control
through insulin resistance.123 Others have emphasized
of lipids, and control of blood pressure are all important
underlying inflammatory processes as part of the meta-
areas for physicians to counsel patients over the age of 65.
bolic syndrome which link to increased risk of CVD.124
While the metabolic syndrome and obesity are not synony-
mous, they are strongly linked to each other. According to
1.8.2 Gender Framingham Study data, obese individuals have approxi-
More women die each year than men of heart disease, mately a 50% chance of having at least two other risk
although CVD typically occurs at a younger age in men factors for coronary heart disease.41
12 Chapter 1 The Rationale for Intervention to Reduce the Risk of Cardiovascular Disease
The increased prevalence of obesity in children has inflammation in addition to CRP have emerged as poten-
drawn attention to its linkage to the increasing prevalence tial risk factors for CVD. Most prominently TNF-α and
of both diabetes and the metabolic syndrome in children.125 Interleukin-6 (IL-6) have been associated with increased
While considerable controversy exists about the criteria for risk of CVD, but the data supporting these relationships
the metabolic syndrome in children, the American Heart are not as advanced as with CRP.42
Association has recommended careful exploration for
other risk factors for CVD in children who are obese.
It should also be noted that recent data support that 1.10.3 Hemostatic Factors
metabolic syndrome also results in a pro-inflammatory Factors that may contribute to thrombogenesis have also
state. This is recognized by the most recent definition of been associated with increased risk of CVD. Factors cur-
the metabolic syndrome by the National Heart, Lung, and rently under investigation that may contribute to thrombo-
Blood Institute.126 This observation is important since a genesis include Plasminogen Activator Inhibitor I (PAI-1),
pro-inflammatory state also occurs in diabetes, hyperten- fibrinogen,140,141 and coagulation Factor VII.
sion, and obesity.
1.10.4 Homocysteine
1.10 EMERGING RISK FACTORS Elevated levels of homocysteine, an amino acid derived
Recent research has identified a variety of other risk fac- from the degradation of methionine, have been associ-
tors which are associated to a greater or lesser degree with ated with increased risk of CVD. Although the epidemi-
CVD. These risk factors are discussed in this section. ologic evidence is somewhat diverse, on average a 25%
lower homocysteine level appears to be associated with
approximately 11% lower risk of coronary heart disease
1.10.1 High Sensitivity C-Reactive in the general population. Homocysteine elevations are
typically found in diets that are low in folate. In countries
Protein (hs-CRP) such as the United States, where folate supplementation
Inflammation has been identified as a key component of occurs, prevalence of elevated homocysteine is signifi-
arthrosclerothrombosis and provides an important link cantly reduced. While laboratory tests are available to
between plaque formation and acute rupture.127 CRP, assess homocysteine, studies attempting to reduce the risk
which is a marker of inflammation, has been identified as a of CVD by reducing homocysteine levels have not yielded
significant cardiovascular CVD risk marker.128 Numerous promising results.142,143 Thus, homocysteine is not cur-
prospective studies have demonstrated that hs-CRP inde- rently included as part of a risk factor profile.
pendently predicts the risk of CVD.129–134 These data also
apply not only to individuals with existing CVD but also
to healthy individuals, including both men and women at 1.10.5 LDL Subclasses and Particle Size
all age levels. Elevated hs-CRP is not only associated with
Laboratory tests are available to determine the amount
obesity and diabetes but also found in increased prevalence
of cholesterol carried by individual lipoprotein particles
in individuals who lead sedentary lifestyles or are cigarette
which are characterized by their particle size. Some stud-
smokers.128 These findings carry significant practical impli-
ies have suggested that small, dense LDL particles may be
cations for counseling individuals concerning a variety of
more atherogenic than larger LDL particles.144,145 Of note,
lifestyle measures. Comprehensive meta-analyses of the
small, dense LDL particles have been associated more fre-
hazard associated with CVD associated with hs-CRP dem-
quently in obese individuals and individuals with abdomi-
onstrated that it may exceed the risks associated with either
nal obesity than normal weight individuals. The data have
elevated blood pressure or cholesterol.135 The Emerging
not established the association between LDL particle size
Risk Factor Collaboration study showed that hs-CRP is as
and CVD risk at a level that is useful for risk factor reduc-
accurate in predicting future coronary heart disease events
tion strategies.
as is total HDL cholesterol.136 Individuals with elevated hs-
CRP and low levels of LDL cholesterol have higher abso-
lute risk of vascular disease than those with low levels of 1.10.6 Lipoprotein (a)
hs-CRP and elevated levels of LDL. For all these reasons, it
appears clinically wise to include hs-CRP along with lipid Lipoprotein (a) is an LDL particle linked to a protein by
evaluation as a strategy for lowering the risk of CVD.137 a disulfide bridge. A number of studies have supported
Several of the statin medications have been dem- the role for LP(a) as a determinant of vascular risk.146
onstrated to lower CRP in addition to lowering LDL However, it remains uncertain whether LP(a) contributes
cholesterol, which carries significant implications for further sensitivity or specificity to standard risk factor
combining pharmaceutical therapies along with lifestyle reduction strategies.147
measures.138,139
1.11 OTHER RISK FACTORS
1.10.2 Other Markers of Inflammation A variety of other risk factors for CVD have either been
The relationship between CVD and inflammation is an identified or postulated to potentially influence the likeli-
area of active research. A variety of other markers of hood of its development.
1.12 Future Trends in Risk Factor Assessment 13
1.11.1 Levels of Antioxidants patients with heart failure and one out of five patients
1
with coronary heart disease. Whether therapy for depres-
Initial observational studies, including the Health sion lowers risk for CVD is uncertain.
Professional Follow-up Study148 and the Nurses Health
Study149 showed an association between high levels of
vitamin E and other antioxidants and reduced risk of
CVD. Subsequent interventional trials, however, have 1.12 FUTURE TRENDS IN RISK
not corroborated these findings.150 The American Heart
Association does not currently advocate antioxidant sup-
FACTOR ASSESSMENT
plementation as a means of reducing CVD risk. Some technologic enhancements, both in imaging tech-
niques and genomics, have provided opportunities which
may yield more precise and individualized characteriza-
1.11.2 Alcohol tions of atherosclerotic plaque and risk of CVD.
Alcohol consumption exerts a variety of effects on the
overall cardiovascular system. A number of studies
have demonstrated that moderate alcohol consumption 1.12.1 Direct Plaque Imaging
reduces the overall risk of CVD.151 “Moderate” alcohol High-speed computed tomography (CT Scanning) of the
consumption is typically defined as no more than one coronary arteries has been demonstrated in several stud-
to two beers, one to two glasses of wine, or one to two ies to detect pre-clinical atherosclerosis.159 Advances such
“shots” of distilled spirits daily. Men are typically able as volume CT scanning (VCT) may further enhance the
to drink higher amounts of alcohol within the moder- precision and predictive value of these technologies. At
ate range than women because of higher levels of alco- the current time, these technologies remain investiga-
hol dehydrogenase—the enzyme in the liver that breaks tional. Concern has also been raised about the potential
down alcohol. The mechanism by which moderate alco- to overinterpret predictive values from imaging tech-
hol consumption may reduce the risk of coronary heart niques such as coronary calcium scoring. In one study,
disease is attributed either to increasing HDL or decreas- 41% of all future vascular events occurred in individuals
ing platelet aggregation.152 In contrast, alcohol consump- with a coronary calcium score lower than 100, and 17%
tion of three alcoholic drinks per day or more has been occurred with a coronary calcium score of zero.160 In this
associated with increased risk of hypertension, overall study, individuals with high risk scores by Framingham
risk of heart disease, congestive heart failure, a variety criteria but low coronary calcium scores still remained at
of gastrointestinal cancers, and motor vehicle accidents. high risk of CVD. Another imaging test which has been
Thus, a U-Shaped Curve153 relationship exists related to employed to attempt to assess risk of CVD is ultrasound
risk of CVD and alcohol consumption. Any individual measurement of the common carotid intima-media thick-
or population-wide recommendation for levels of alco- ness (CIMT). With regard to CIMT, a meta-analysis of 14
hol consumption must consider the complexity of this population-based cohorts reported a consistent and stati-
relationship.154 cally significant 9% increase of future vascular risk for
each 0.1 mm increase in CIMT thickness.161 This same
analysis, however, found that CIMT measurement did not
1.11.3 Stress and Type A Personality improve clinical accuracy once risk estimates and re clas-
Some studies have supported the concept that personality sification were utilized to adjust for usual risk factors.162
type may contribute to the risk of CVD, but these data In addition, Framingham investigators have reported lim-
remain controversial and inconclusive.155,156 In particular, ited usefulness for CIMT in this prediction.163
the anger element of Type A personality (a Type A person-
ality is often found in individuals who are highly competi-
tive and ambitious, and perceive a constant struggle with 1.12.2 Genomic Approaches
their environment) may increase the risk of CVD. The
Advances continue to be made in genetic determinants
mechanism by which stress may lead to increased risk of
of atherothrombosis. Although this field remains in its
vascular disease is not completely understood but is pos-
early stages of development, progress continues to be
sibly related to platelet and endothelial dysfunction as well
made.164–166 Challenges exist because of multiple gene-
as the induction of ventricular arrhythmias.
environment interactions. Although this remains an area
of active research, no genetic markers for atherothrombo-
sis have yet achieved clinical utility. A recent study involv-
1.11.4 Depression ing over 55,000 individuals, including 7,814 participants
Depression has been demonstrated in a number of studies in the Atherosclerosis Risk in Community (ARIC) study,
to predict CVD.157,158 This association appears to be an 21,222 in the Women’s Genome Health Study (WGHS),
independent one, although depression is also associated and 22,389 in the Malmö Diet and Cancer Study (MDCS)
with lack of physical activity, hypertension, and smok- and 4,260 participants in the cross-sectional BioImage
ing.157,158 The mechanism through which depression may assessed thus the risk of pulmonary events in individu-
increase the risk of CVD includes elevated levels of hs- als who had high genetic risk (top quintile of polygenic
CRP, increased platelet activation, and decreased heart scores) compared to low risks (bottom quintile of poly-
rate variability. Depression occurs in one out of three genic scores). Coronary events were 91% higher in the high
14 Chapter 1 The Rationale for Intervention to Reduce the Risk of Cardiovascular Disease
genetic risk group. Importantly, among participants in the 1.12.4 Implementation of Risk Factor
high genetic risk profile, a favorable lifestyle (defined by
no current smoking, no obesity, regular physical activity,
Reduction Strategies
and a healthy diet) resulted in a 46% lower relative risk of One encouraging trend in risk factor reduction is an
coronary events than those who had an unfavorable life- increased emphasis on more sophisticated and comprehen-
style. While this type of research167 is in its infancy, it sug- sive approaches to implementation of currently existing
gests that healthy lifestyle practices interact with playing risk factor reduction guidelines.50,52,115 Both the Dietary
an important role in individuals who are at high genetic Guidelines for Americans 201550 and the Nutrition
risk of CVD. Guidelines from the American Heart Association52 make
a substantial effort to focus on strategies for implementing
existing guidelines.
1.12.3 New Risk Factor Scoring Systems
The Framingham Risk Scoring System has contributed in 1.13 CONCLUSIONS
substantial ways to the ability to predict the risk of CVD,
but it is limited by not incorporating such risk factors as The identification of risk factors for coronary heart dis-
level of physical activity and obesity. One particularly ease continues to evolve and is an area of great practical
attractive system has emerged from the New Zealand relevance to clinicians. Particularly given the high level of
Guidelines Group, which provides useful information on modifiable risk factors for CVD, an enormous opportu-
five- and ten-year risk of atherosclerosis. This area remains nity exists for physicians and other healthcare workers to
one of active research. Another attractive scoring system counsel patients on lifestyle medicine concepts to lower
is the Reynolds Risk Score (www.reynoldsriskscore.com) their risk of CVD. Specific concepts for how to integrate
which has the advantage of including both hs-CRP and lifestyle measures into clinical practice will be the topic of
family history as part of global risk assessment.168 the next chapter.
CLINICAL APPLICATIONS
Action Available Tools Comment
Determine risk of CVD in Multiple risk factor scoring systems are available See Chapter 2 for more details
all patients
Determine “vital signs” of Include body mass index (BMI), level of physical These are key determinants of lifestyle CVD risk
positive lifestyle activity, nutritional practices, and smoking status in
all initial assessments
Discuss smoking cessation Multiple tools available from many sources Over one-third of smokers are never counseled
with all smokers about cigarette smoking
Counsel all patients on Obtain weight and BMI on all patients Forty percent of overweight and obese patients are
weight management never counseled on weight management
Counsel all patients on U.S. Physical Activity Guidelines Become familiar with these guidelines and utilize
physical activity them in counseling
Counsel all patients on Dietary Guidelines for Americans 2015, also multiple Improved nutrition is a key in reducing the CVD risk
nutrition materials from the American Heart Association
REFERENCES
1. Mozaffarian D, Benjamin EJ, Go AS, 5. American Heart Association. Heart American Heart Association. Circulation
et al. Heart disease and stroke statis- Disease and Stroke Statistics—2004 2013;127(1):e6–e245. Epub 2012/12/15.
tics—2016 update. A report from the Update. Dallas, TX: American Heart 9. Surgeon General’s Report on Physical
American Heart Association. Circulation Association, 2003. Activity and Health. Washington, DC:
2016 Jan 26;133(4):e38–e360. Epub 6. Gaziano TA, Prabhakaran D, and US Department of Health and Human
2015/12/16. Gaziano JM. Global burden of cardio- Services, Centers for Disease Control,
2. Olshansky SJ and Ault AB. The fourth stage vascular disease. In: Braunwald’s Heart 1999.
of the epidemiologic transition: The age of Disease, 10th ed., Volume 1, Chapter 1, 10. 2008 Physical Activity Guidelines
delayed degenerative diseases. Milbank Q. 2014. p. 1–20. for Americans. Washington, DC: US
1986;64(3):355–391. Epub 1986/01/01. 7. The Seventh Report of the Joint National Department of Health and Humans
3. Ford ES, Ajani UA, Croft JB, et al. Committee on Prevention, Detection, Services. www.health.gov/paguidelines.
Explaining the decrease in US deaths Evaluation, and Treatment of High Accessed March 22, 2017.
from coronary disease, 1980–2000. N. Blood Pressure (JNC 7). Washington, 1. Flegal KM, Carroll MD, Ogden CL, and
1
Engl. J. Med. 2007;256:2388–2398. DC: National Heart Lung and Blood Curtin LR. Prevalence and trends in obe-
4. National Institutes of Health, National Institute, 2004. sity among US adults, 1999–2008. JAMA
Heart, Lung and Blood Institute. Fact 8. Go AS, Mozaffarian D, Roger VL, 2010;303(3):235–241.
Book Fiscal Year 2003. Bethesda, MD: et al. Heart disease and stroke statis- 12. American Diabetes Association.
National Institutes of Health, 2004. tics – 2013 update: A report from the Diagnosis and classification of diabetes
References 15
mellitus. Diabetes Care 2010;33(Suppl 29. Gordon DL, Probstfield JL, Garrison RJ, subsequent cardiovascular disease. N.
1):S62–S69. et al. High-density lipoprotein cholesterol Engl. J. Med. 1993;308:363–366.
13. Centers for Disease Control and
Prevention (CDC). Cigarette smoking
among adults—United States. JAMA
and cardiovascular disease: Four pro-
spective American studies. Circulation
1989;79:8–15.
46. Law MR, Wald NJ, Wu T, Hackshaw
A, and Bailey A. Systematic underesti-
mation of association between serum
1
2009;301:373. 30. Shea S, Cook EF, Kannel WB, and cholesterol concentration and ischemic
14. Bhatt DL, Steg PG, Ohman EM, et al. Goldman L. Treatment of hypertension heart disease in observational studies:
International prevalence, recognition, and and its effect on cardiovascular risk fac- Data from the BUPA study. Br. Med. J.
treatment of cardiovascular risk factors tors: Data from the Framingham Heart 1994;308:363–366.
in outpatients with atherothrombosis. Study. Circulation 1985;71:22–30. 47. Law MR, Wald NJ, and Thompson SG.
JAMA 2006;95:180. 31. Kannel WB, Danneberg AL, and Abbott By how much and how quickly does
15. Mozaffarian D. Nutrition and cardiovas- RD. Unrecognized myocardial infarc- reduction in serum cholesterol concentra-
cular and metabolic diseases. In: Mann tion and hypertension: The Framingham tion lower risk of ischemic heart disease?
DL, Zipes DP, Libby P, and Bonow RO, Study. Am. Heart J. 1985;109:581–585. Br. Med. J. 1994;308:367–373.
editors. Braunwald’s Heart Disease: A 32. Harris T, Cook EF, Kannel W, Schatzkin 48. Framingham Risk Scoring System. http://
Textbook of Cardiovascular Medicine, A, and Goldman L. Blood pressure www.heart.org/HEARTORG/Conditions/
10th ed. Philadelphia, PA: Elsevier, 2014. experience and risk of cardiovascular HeartAttack/HeartAttackToolsResources/
p. 1001–1028. disease in the elderly. Hypertension Heart-Attack-Risk-Assessment_UCM_303
16. Moutlon KS. Angiogenesis in atheroscle- 1985;7:118–124. 944_Article.jsp. Accessed March 22, 2017.
rosis: Gathering evidence beyond specula- 33. Castelli WP and Anderson K. A popula- 49. Lloyd-Jones DM, Hong Y, Labarthe D,
tion. Curr. Opin. Lipdol. 2006;17:548. tion at risk: Prevalence of high choles- et al. Defining and setting national goals
17. Libby P. Molecular and cellular terol levels in hypertensive patients in for cardiovascular health promotion
mechanisms of the thrombotic compli- the Framingham Study. Am. J. Med. and disease reduction: The American
cation of atherosclerosis. J. Lipid Res. 1986;80:23–32. Heart Association’s strategic impact goal
2009;50:S352. 34. Kannel WB. Cigarette smoking and coro- through 2020 and beyond. Circulation
18. Libby P. The vascular biology of nary heart disease. Ann. Intern. Med. 2010;121(4):586–613.
atherosclerosis. In: Mann DL, Zipes 1964;60:1103–1106. 50. U.S. Department of Health and
DP, Libby P, and Bonow RO, editors. 35. Wilson PW, Garrison RJ, and Castell WP. Human Services and U.S. Department
Braunwald’s Heart Disease: A Textbook Postmenopausal estrogen use, cigarette of Agriculture. 2015–2020 Dietary
of Cardiovascular Medicine, 10th ed., smoking, and cardiovascular morbidity in Guidelines for Americans, 8th ed.,
Elsevier, Philadelphia, PA, 2014. p. women over 50: The Framingham Study. 2015. Available at http://health.gov/di
873–890. N. Engl. J. Med. 1985;313:1038–1043. etaryg uidelines/ 2015/guidelines /. Epub
19. Libby P and Theroux P. Pathophysiology 36. Kannel WB, McGee DL, and Castelli December 2015.
of coronary artery disease. Circulation WP. Latest perspectives on cigarette 51. Pate RR, Yancey AK, and Kraus WE.
2005;111:3481. smoking and cardiovascular disease: The The 2008 physical activity guidelines for
20. Wilson PWF, D’Agostino R, Levy D, Framingham Study. J. Card. Rehabil. Americans: Implications for clinical and
Belanger A, Silbershatz H, and Kannel 1984;4:267–277. public health practice. Am. J. Lifestyle
W. Prediction of coronary heart disease 37. Kannel WB, D’Agostino RB, and Med. 2010;4:209–217
using risk factor categories. Circulation Belanger AJ. Fibrinogen, cigarette smok- 52. Gidding SS, Lichtenstein AH, Faith MS,
1998;97:1837–1847. ing and risk of cardiovascular disease: et al. Implementing American Heart
21. Garcia MJ, McNamara P, Gordon T, and Insights from the Framingham Study. Association pediatric and adult nutrition
Kannel WB. Morbidity and mortality in Am. Heart J. 1987;113:1006–1010. guidelines: A scientific statement from
diabetics in the Framingham popula- 38. Fletcher G, Blair S, Blumenthal J, et the American Heart Association nutrition
tion 16-year follow-up study. Diabetes al. AHA medical/scientific statement. committee of the council on nutrition,
1974;23:105–111. Statement of exercise. Benefits and physical activity and metabolism, council
22. Kannel WB and McGee DL. Diabetes recommendations for physical activity on cardiovascular disease in the young,
and cardiovascular risk factors: The programs for all Americans. Circulation council on arteriosclerosis, thrombosis
Framingham Study. Circulation 1992;86:340–344. and vascular biology, council on cardio-
1979;59:8–13. 39. Anderson KM, Wilson PWF, Odell PM, vascular nursing, council on epidemiol-
23. Abbott RD, Donahue RP, Kannel WB, and Kannel WB. An updated coronary ogy and prevention, and council for high
and Wilson PW. The impact of diabetes risk profile: A statement for health profes- blood pressure research. Circulation
on survival following myocardial infarc- sional. Circulation 1991;83:356. 2009;119;1161–1175.
tion in men vs women: The Framingham 40. Kannel WB. Contributions of the 53. Garrison RJ and Castelli WP. Weight
Study. JAMA 1988;260:3456–3460. Framingham Study to the conquest of and thirty year mortality of men in the
24. Kannel WB, D’Agostino RB, Wilson PW, coronary artery disease. Am. J. Cardiol. Framingham Study. Ann. Int. Med.
Belanger AJ, and Gagnon DR. Diabetes, 1988;62:1109–1112. 1985;103:1006–1009.
fibrinogen, and risk of cardiovascular 41. Wilson P. Clustering of risk factors, obe- 54. Manson JE, Willett WC, Stampler
disease: The Framingham experience. sity, and syndrome X. Nutr. Clin. Care JM, et al. Body weight and mortal-
Am. Heart J. 1990;120:672–676. 1998;1(Suppl):44–50. ity among women. N. Engl. J. Med.
25. Kannel WB, Castell WP, Gordon T, and 42. Ridker M, Libby P, and Buring J. Risk 1995;141:1117–1127.
McNamara PM. Serum cholesterol, lipo- markers for and the primary prevention 55. Rimm EB, Stampler MJ, Giovannucci
proteins, and the risk of coronary heart of cardiovascular disease. In: Bonow B, et al. Body size and fat distribution
disease: The Framingham Study. Ann. RO, Mann DL, Zipes DP, and Libby P, as predictors of coronary heart disease
Intern. Med. 1971;74:1–12. editors. Braunwald’s Heart Disease, 10th among middle-aged and older US men.
26. Wilson PW, Garrison RJ, Castelli WP, ed., Elesvier, Philadelphia, PA, Chapter Am. J. Epidemiol. 1995;141:1117–1127.
Feinleib M, McNamara PM, and Kannel 42, 2014. p. 891–931. 56. Ridker PM, Pradhan A, MacFadyen JG,
WB. Prevalence of coronary heart disease 43. Grundy SM, Balady GJ, Criqui MH, et Libby P, and Glynn RJ. Cardiovascular
in the Framingham Offspring Study: al. Primary prevention of coronary heart benefits and diabetes risks of statin
Role of lipoprotein cholesterols. Am. J. disease: Guidance from Framingham. A therapy in primary prevention: An
Cardiol. 1980;46:649–654. statement for healthcare professionals analysis from the JUPITER trial. Lancet
27. Castelli WP, Abbott RD, and McNamara from the AHA task force on risk reduc- 2012;380(9841):565–571. Epub
PM. Summary estimates of cholesterol tion. Circulation 1998;97:1876–1887. 2012/08/14.
used to predict coronary heart disease. 44. Stamler J. Epidemiology established major 57. Cholesterol Treatment Trialists’
Circulation 1983;67:730–734. risk factors and the primary prevention Collaborators, Mihaylova B, Emberson J,
28. McNamara JR, Cohn JS, Wilson PW, of coronary heart disease. In: Chatterjee et al. The effects of lowering LDL choles-
and Schaefer EJ. Calculated values for K, Cheitlin MP, Karlines J, et al., editors. terol with statin therapy in people at low
low density lipoprotein cholesterol in Cardiology: An Illustrated Text Reference, risk of vascular disease: Meta-analysis
the assessment of lipid abnormalities Volume 2. Philadelphia: JB Lippincott, 1991. of individual data from 27 randomised
and coronary disease risk. Clin. Chem. 45. Klag MJ, Ford DE, Mead LA, et al. trials. Lancet 2012;380(9841):581–590.
1990;36:36–42. Serum cholesterol in young men and Epub 2012/05/23.
16 Chapter 1 The Rationale for Intervention to Reduce the Risk of Cardiovascular Disease
58. Ridker PM, Kastelein JJ, Genest J, Group of a randomized trial in healthy prevention, and treatment. Circulation
and Koenig W. C-reactive protein and men. Lancet 1991;2:1303. 2005;111:1999–2012.
cholesterol are equally strong predic- 73. Committee of Principal Investigators. A 87. Chobanian AV, Bakris G, Black H, et al.
tors of cardiovascular risk and both are cooperative trial in the primary preven- The seventh report of the Joint National
important for quality clinical care. Eur. tion of ischemic heart disease using Committee on prevention, detection,
Heart J. 2013;34(17):1258–1261. Epub clofibrate. Br. Heart J. 1978;40:1069. evaluation, and treatment of high blood
2013/02/05. 74. Shepherd J, Cobbe SM, Ford I, et al. pressure. JAMA 2003;289:2560–2571.
59. Ridker PM and Wilson PW. A trial- Prevention of coronary heart disease with 88. Hajjar I and Kotchen TA. Trends in prev-
based approach to statin guidelines. provastatin in men with hypercholesterol- alence, awareness, treatment, and control
JAMA 2013;310(11):1123–1124. Epub emia. N. Engl. J. Med. 1995;333:1301. of hypertension in the United States,
2013/08/15. 75. Brensike JF, Levy RI, Kelsy SF, et al. Effects 1988–2000. JAMA 2003;290:199–206.
60. Centers for Disease Control and of therapy with cholestryamine on progres- 89. Kannel WB. Fifty years of Framingham
Prevention (CDC). Smoking-attributable sion of coronary ateriosclerosis: Results Study contributions to understand-
mortality, years of potential life lost, of NHLBI Type II Coronary Intervention ing hypertension. J. Hum. Hypertens.
and productivity losses—United States. Study. Circulation 1984;69:313. 2000;14:83–90.
JAMA 2009;301:593. 76. Brown G, Albers J, Fisher L, et al. 90. Centers for disease control and preven-
61. Centers for Disease Control and Regression of coronary artery disease as a tion, prevalence of diabetes and impaired
Prevention (US), National Center for result of intensive lipid-lowering therapy fasting glucose in adults—United States,
Chronic Disease Prevention and Health in men with high levels of apoliporotein 1999–2000. MMWR Morb. Mortal.
Promotion (US), and Office on Smoking B. N. Engl. J. Med. 1990;323:1289. Wkly. Rep. 2003;52:833–837.
and Health (US). How Tobacco Smoke 77. Watts GF, Lewis B, Brunt JNH, et al. 91. Hu FB, Stampfer MJ, Haffner SM, et al.
Causes Disease: The Biology and Effects on coronary artery disease of Elevated risk of cardiovascular disease
Behavioral Basis for Smoking-Attributable lipid-lowering diet or diet plus cholestyr- prior to clinical diagnosis of type 2 diabe-
Disease: A Report of the Surgeon General. amine in the St. Thomas’ Atherosclerosis tes. Diabetes Care 2002;25:1129.
Atlanta, GA: Centers for Disease Control Regress Study (STARS). Lancet 92. Bassuk SS and Manson JE. Lifestyle and
and Prevention (US), 2010. Available at 1992;339:563. risk of cardiovascular disease and type 2
https://www.ncbi.nlm.nih.gov/books/ 78. Buchwald H, Varco RL, Matts JP, et diabetes in women: A review of the epide-
NBK53017/ al. Effect of partial ileal bypass surgery miologic evidence. Am. J. Lifestyle Med.
62. Centers for Disease Control and on mortality and morbidity from 2008;2:191–213.
Prevention (CDC). Smoking-attributable coronary heart disease in patients with 93. James PA, Oparil S, Carter BL, et al.
mortality, years of potential life lost, hypercholeterolemia: Report of the 2014 evidence-based guideline for
and productivity losses – United States, Program on the Surgical Control of the the management of high blood pres-
2000–2004. MMWR Morb. Mortal. Hyperlipidemias (POSCH). N. Engl. J. sure in adults: Report from the panel
Wkly. Rep. 2008;57(45):1226–1228. Med. 1990;323:946. members appointed to the Eighth Joint
63. Jha P, Ramasundarahettige C, Landsman 79. Wiviott SD, deLemos JA, Cannon CP, National Committee (JNC 8). JAMA
V, et al. 21 st-century hazards of et al. A tale of two trials: A com- 2014;311(5):507–520. Epub 2013/12/20.
smoking and benefits of cessation in parison of the post-acute coronary 94. Eyre H, Kahn R, and Robertson R. ACS/
the United States. N. Engl. J. Med. syndrome lipid-lowering trials A to Z ADA/AHA scientific statement: Preventing
2013;368(4):341–350. Epub 2013/01/25. and PROVE IT TIMI 22. Circulation cancer, cardiovascular disease and diabetes.
64. Centers for Disease Control and 2006;113:1406–1414. Circulation 2004;109:3244–3255.
Prevention. 2011 National Health 80. Gordon T, Castelli WP, Hjortland MC, et 95. Ogden CL, Carroll MD, McDowell MA,
Interview Survey (NHIS) Public Use al. High-density lipoprotein as a protec- and Flegal KM. Obesity Among Adults
Data Release Division of Health tive factor against coronary heart disease: in the United States—NO Change Since
Interview Statistics. Atlanta, GA: The Framingham Study. Am. J. Med. 2003–2004. NCHS Data Brief No. 1.
National Center for Health Statistics, 1977;62:707. Hyattsville, MD: National Center for
2012. 81. US Department of Health and Human Health Statistics, 2007.
65. Kannel WB and Higgins M. Smoking and Service National Heart Lung and Blood 96. Institute of Medicine. In: Thomas P, edi-
hypertension as predictors of cardio- Institute. Third Report of the Expert tor. Weighing the Options. Washington,
vascular risk in population studies. J. Panel on Detection, Evaluation, and DC: National Academy Press, 1995.
Hypertens. 1990;8:S3. Treatment of High Blood Cholesterol 97. Grundy SM. What is the contribution
66. Dobvson AJ, Alexander HM, Heller FR, in Adults (Adult Treatment Panel III). of obesity to the metabolic syndrome?
and Lloyd DM. How soon after quitting Washington, DC: National Institutes of Endocrinol. Metab. Clin. North Am.
smoking does risk of heart attack decline? Health, 2004. 2004;33:267–282.
Clin. Epidemiol. 1991;44:1247–1253. 82. AIM-HIGH Investigators, Boden WE, 98. Rajala MW and Scherer PE. Minireview:
67. Centers for Disease Control Prevention. Probstfield JL, et al. Niacin in patients The adiopocyte—At the crossroads of
Quitting smoking among adults – United with low HDL cholesterol levels receiv- energy, homeostasis, inflammation,
States, 2001–2010. MMWR Morb. ing intensive statin therapy. N. Engl. J. and atherosclerosis. Endocrinology
Mortal. Wkly. Rep. 2011;60(44):1513– Med. 2011;365(24):2255–2267. Epub 2003;144:3765–3773.
1519. Epub 2011/11/11. 2011/11/17. 99. Graham TE, Yang Q, Bluher M, et
68. Physician and other health-care profes- 83. Voight BF, Peloso GM, Orho-Melander al. Retinol-binding protein 4 and
sional counseling of smokers to quit M, et al. Plasma HDL cholesterol insulin resistance in lean, obese, and
– United States, 1991. MMWR Morb. and risk of myocardial infarction: diabetic subjects. N. Engl. J. Med.
Mortal. Wkly. Rep. 1993;42:854. A mendelian randomisation study. 2006;354:2552–2563.
69. Christakis NA and Fowler JH. The Lancet 2012;380(9841):572–580. Epub 100. Hotamisligil GS, Arner P, Caro JF,
collective dynamics of smoking in a 2012/05/23. Atkinson RL, and Spiegelman BM.
large social network. N. Engl. J. Med. 84. Sarwar N, Danesh J, Eiriksdottir G, et Increased adipose tissue expression of
2008;358:2249. al. Triglycerides and the risk of coronary tumor necrosis factor-alpha in human
70. Lipid Research Clinics Program. The heart disease: 10,158 incident cases obesity and insulin resistance. J. Clin.
lipid research clinics coronary primary among 262,525 participants in 29 Invest. 1995;95:2409–2415.
prevention trial results I. Reduction in western prospective studies. Circulation 101. Lundgren CH, Brown SL, Nordt TK,
incidence of coronary heart disease. 2007;115:450–458. Sobel BE, and Fujii S. Elaboration of
JAMA 1984;251:351. 85. Miller M, Stone NJ, Ballantyne C, et type-1 plasminogen activator inhibitor
71. Huttunen JK, Manninen V, Manttair M, al. Triglycerides and cardiovascular from adipocytes: A potential patho-
et al. The Helsinki Heart Study: Central disease: A scientific statement from the genetic link between obesity and
findings and clinical implications. Ann. American Heart Association. Circulation cardiovascular disease. Circulation
Med. 1991;23:155. 2011;123:2292–2333. 1996;93:106–110.
72. Hjermann I, Velve Byre K, Holme I, 86. Daniels SR, Arnett DK, Eckel RH, et 102. Cigolini M, Targher G, Bergamo AI,
and Leren P. Effect of diet and smoking al. AHA scientific statement, over- Tonoli M, Agostino G, and De Sandre G.
intervention on the incidence of coronary weight in children and adolescents: Visceral fat accumulation and its relation
heart disease: Report from the Oslo Study Pathophysiology, consequences, to plasma hemostatic factors in healthy
References 17
men. Arterioscler. Thromb. Vasc. Biol. and Rexrode KM, editors. Women and cardiovascular risk in the Framingham
1996;16:368–374. Health, 2nd ed. San Diego, CA: Academic Heart Study. Circ. Cardiovasc. Qual.
103. Despres JP. Abdominal obesity as impor-
tant component of insulin-resistance
syndrome. Nutrition 1993;4:452–459.
Press, 2013. p. 949–964.
121. 2011 American Heart Association,
Inc. Go Red for Women. http://www.
Outcomes 2008;1:92.
135. Emerging Risk Factors Collaboration,
Kaptoge S, Di Angelantonio E, et al.
1
104. Despres JP. Dyslipidaemia and obesity. goredforwomen.org/. Accessed January 4, C-reactive protein concentration and risk
Bailliere Clin. Endocrinol. Metab. 2017. of coronary heart disease, stroke, and
1994;8:629–660. 122. Kahn R, Buse J, Ferrannini E, and Stern mortality: An individual participant meta-
105. Willett W, Manson J, Stampfer M, et M. The metabolic syndrome: Time for a analysis. Lancet 2010;375(9709):132–140.
al. Weight, weight change, and coro- critical appraisal: Joint statement from Epub 2009/12/25.
nary heart disease in women. JAMA the American Diabetes Association and 136. Emerging Risk Factors Collaboration,
1995;273:461–465. the European Association for the Study of Kaptoge S, Di Angelantonio E, et al.
106. Chan JM, Rimm EB, Colditz GA, Diabetes. Diabetes Care 2005;28:2289. C-reactive protein, fibrinogen, and car-
Stampfer MJ, and Willett WC. Obesity, 123. Mathieu P, Lemieux I, and Despres JP. diovascular disease prediction. N. Engl.
fat distribution, and weight gain as risk Obesity, inflammation, and cardio- J. Med. 2012;367(14):1310–1320. Epub
factors for clinical diabetes in men. vascular risk. Clin. Pharmacol. Ther. 2012/10/05.
Diabetes Care 1994;17:961–969. 2010;87:407. 137. Ridker PM, Rifai N, Rose L, Buring JE,
107. Gu K, Cowie CC, and Harris MI. 124. Jeppesen J, Hansen TW, Rasmussen S, and Cook NR. Comparison of C-reactive
Mortality in adults with and without et al. Insulin resistance, the metabolic protein and low-density lipoprotein
diabetes in a national cohort of the US syndrome, and risk of incident cardiovas- cholesterol levels in the prediction of
population, 1971–1993. Diabetes Care cular disease: A population-based study. first cardiovascular events. N. Engl. J.
1998;21:1138. J. Am. Coll. Cardiol. 2007;49:2112. Med. 2002;347(20):1557–1565. Epub
108. Healthy People 2010. Washington, DC, 125. Steinberger J, Daniels SR, Eckel RH, et 2002/11/15.
www.healthypeople.gov. Accessed: al. Progress and challenges in metabolic 138. Ridker PM, Danielson E, Fonseca FA,
February 6, 2019. syndrome in children and adolescents: A et al. Rosuvastatin to prevent vascular
109. Healthy People 2020 Guidelines. https:// scientific statement from the American events in men and women with elevated
www.healthypeople.gov/. Accessed Heart Association atherosclerosis, C-reactive protein. N. Engl. J. Med.
January 4, 2017. hypertension, and obesity in the young. 2008;359:2195.
110. ACSM Physical Activity Guidelines. Committee of the council on cardiovas- 139. Glynn RJ, Danielson E, Fonseca FA, et al.
http: //www.acsm.org/public-informat cular disease in the young; council on A randomized trial of rosuvastatin in the
ion/acsm-journals/guidelines. Accessed cardiovascular nursing; and council on prevention of venous thromboembolism.
January 4, 2017. nutrition, physical activity, and metabo- N. Engl. J. Med. 2009;360:1851.
111. Katzmarzyk PT and Lee I-M. Sedentary lism. Circulation 2009;119:628–647. 140. Kerlin B, Cooley BC, Isermann BH, et al.
behaviour and life expectancy in the 126. Grundy SM, Brewer Jr HB, Cleeman JI, Cause-effect relation between hyperfi-
USA: A cause-deleted life table analysis. et al. Definition of metabolic syndrome: brinogenemia and vascular disease. Blood
BMJ Open 2012;2(4). doi: 10.1136/ Report of the National Heart, Lung, 2004;103:1728.
bmjopen-2012-000828. and Blood Institute/American Heart 141. Fibrinogen Studies Collaboration, Danesh
112. Frank E, Wright E, Serdule M, Elon L, Association conference on scientific J, Lewington S, et al. Plasma fibrinogen
and Baldwin G. Personal and profes- issues related to definition. Circulation level and the risk of major cardiovascular
sional nutrition-related practices of US 2004;109:433. diseases and nonvascular mortality: An
female physicians. Am. J. Clin. Nutr. 127. Libby P, Ridker PM, and Hansson GK. individual participant meta-analysis.
2002;75:326–332. Inflammation in atherosclerosis: From JAMA 2005;294:1799.
113. Abramson S, Stein J, Schaufele M, Frates pathophysiology to practice. J. Am. Coll. 142. Bonaa KH, Njolstad I, Ueland PM, et al.
E, and Rogan S. Personal exercise habits Cardiol. 2009;54:2129. Homocysteine lowering and cardiovascu-
and counseling practices of primary care 128. Ridker PM. C-reactive protein: Eighty lar events after acute myocardial infarc-
physicians: A national survey. Clin. J. years from discovery to emergence as tion. N. Engl. J. Med. 2006;354:1578.
Sport Med. 2000;10:40–48. a major risk marker for cardiovascular 143. The Heart Outcomes Prevention
114. Goldfine H, Ward A, Taylor P, Carlucci disease. Clin. Chem. 2009;55:209. Evaluation (HOPE) 2 Investigators.
D, and Rippe JM. Exercising to health: 129. Ridker PM. C-reactive protein and the Homocysteine lowering with folic acid
What’s really in it for your patients? Part prediction of cardiovascular events among and B vitamins in vascular disease. N.
I: The health benefits of exercise. Phys. those at intermediate risk: Moving an Engl. J. Med. 2006;354:1567–1577.
Sports Med. 1991;19:81. inflammatory hypothesis toward consen- 144. Lamarche B, Tchernof A, Moorjani S, et
115. Lichtenstein AH, Appel LJ, Brands M, et sus. J. Am. Coll. Cardiol. 2007;49:2129. al. Small, dense low-density lipoprotein
al. Diet and lifestyle recommendations 130. Kaptoge S, Di Angelantonio E, Lowe G, as a predictor of the risk of ischemic
revision 2006: A scientific statement et al. C-reactive protein concentration heart disease in men. Prospective trial
from the American Heart Association and risk of coronary heart disease, stroke, from the Quebec Cardiovascular Study.
Nutrition Committee. Circulation and mortality: An individual participant Circulation 1977;95:69.
2006;114(1):82–96. meta-analysis. Lancet 2010;375:132. 145. Rosenson RS, Otvos JD, and Freedman
116. Krebs-Smith SM and Kris-Etherton P. 131. Boekholdt SM, Hack CE, Sandhu MS, et DS. Relations of lipoproteins subclass
How does MyPyramid compare to other al. C-reactive protein levels and coronary levels and low density lipoprotein size to
population-based recommendations artery disease incidence and mortality progression of coronary artery disease in
for controlling chronic disease? JADA in apparently healthy men and women: the pravastatin limitation of arthrosclero-
2007;107(5):830–837. The EPIC-Norfolk prospective popula- sis in the coronary arteries (PLAC I) trial.
117. Mozaffarian D, Appel LJ, and Van tion study 1993–2003. Atherosclerosis Am. J. Cardiol. 2002;90:89.
Horn L. Components of a cardiopro- 2006;187:415. 146. The Emerging Risk Factors
tective diet: New insights. Circulation 132. Danesh J, Wheeler JG, Hirschfield GM, Collaboration. Lipoprotein(a) concentra-
2011;123(24):2870–2891. et al. C-reactive protein and other cir- tion and the risk of coronary heart dis-
118. Estruch R, Ros E, Salas-Salvado J, et al. culating markers of inflammation in the ease, stroke, and nonvascular mortality.
Primary prevention of cardiovascular prediction of coronary heart disease. N. JAMA 2009;302(4):412–423.
disease with a Mediterranean diet. N. Engl. J. Med. 2004;350:1387. 147. Marcovina SM, Koschinsky ML,
Engl. J. Med. 2013;368(14):1279–1290. 133. Pearson TA, Mensah GA, Alexander Albers JJ, and Skarlatos S. Report of
Epub 2013/02/26. RW, et al. Markers of inflammation and the National Heart, Lung, and Blood
119. Colditz GA, Rimm EB, Giovannucci E, et cardiovascular disease: Application to Institute Workshop on Lipoprotein(a) and
al. A prospective study of parental history clinical and public health practice: A Cardiovascular Disease: Recent advances
of myocardial infarction and coronary statement for healthcare professionals and future directions. Clin. Chem.
artery disease in men. Am. J. Cardiol. from the Centers for Disease Control 2003;49:1785.
1991;67:993. and Prevention and the American Heart 148. Rimm EB, Stampfer MJ, Ascherio A, et
120. Rillamus-Sun E, Beasley JM, and Lacroix Association. Circulation 2003;107:499. al. Vitamin E consumption and the risk of
A. Overview of risk factors for cardiovas- 134. Wilson PWF, Pencina M, Jacques P, et al. coronary heart disease in men. N. Engl.
cular disease. In: Goldman MB, Troisi R, C-reactive protein and reclassification of J. Med. 1993;328:1450.
18 Chapter 1 The Rationale for Intervention to Reduce the Risk of Cardiovascular Disease
149. Stampfer MJ, Hennekens CH, Manson 157. Rosengren A, Hawken S, Ounpuu S, et al. 163. Yeboah J, McClelland RL, Polonsky TS,
JE, et al. Vitamin E consumption and the Association of psychosocial risk factors et al. Comparison of novel risk markers
risk of coronary heart disease in women. with risk of acute myocardial infarc- for improvement in cardiovascular risk
N. Engl. J. Med. 1993;328:1444. tion in 11119 cases and 13648 controls assessment in intermediate-risk individu-
150. Alpha-Tocopheral, Beta Carotene Cancer from 52 countries (the INTERHEART als. JAMA 2012;308(8):788–795.
Prevention Study Group. The effect of vita- study): Case-control study. Lancet 164. Ioannidis JPA. Prediction of cardiovascu-
min E and beta carotenes on the incidence 2004;17:364(9438):953–962. lar disease outcomes and established car-
of lung cancer and other cancers in male 158. Whooley MA. Depression and cardiovas- diovascular risk factors by genome-wide
smokers. N. Engl. J. Med. 1994;330:1029. cular disease: Health the broken hearted. association markers. Circ. Cardiovasc.
151. Pohorecky LA. Interaction of alcohol and JAMA 2006;295:2874. Genet. 2009;2:7.
stress at the cardiovascular level. Alcohol 159. Detrano R, Guerci AD, Carr JJ, et 165. Ridker PM, Pare G, Parker A, et al.
1990;7:537–546. al. Coronary calcium as a predic- Loci related to metabolic-syndrome
152. Gaziano JM, Buring JE, Breslow JL, et tor of coronary events in four racial pathways including LEPR, HNF1A,
al. Moderate alcohol intake, increased or ethnic groups. N. Engl. J. Med. IL6R, and GCKR associate with plasma
levels of high-density lipoprotein and 2008;358:1336–1345. C-reactive protein: The Women’s Genome
its subfractions, and decreased risk of 160. Greenland P, LaBree L, Azen SP, et al. Health Study. Am. J. Hum. Genet.
myocardial infarction. N. Engl. J. Med. Coronary artery calcium score combined 2008;82:1185.
1993;329(25):1829–1834. with Framingham score for risk predic- 166. Paynter NP, Chasman DI, Pare G,
153. Chiuve S, Albert C, and Conen D. tion in asymptomatic individuals. JAMA Buring JE, Miletihc JP, and Ridker PM.
Arrhythmias in women: Atrial fibrillation 2004;291:210. Association between a literature-based
and sudden cardiac death. In: Goldman 161. Den Ruijter HM, Peters SA, Anderson genetic risk score and cardiovascular
MD, Troisi R, and RExrode KM, editors. TJ, et al. Common carotid intima-media events in women. JAMA 2010 Feb
Women and Health, 2nd ed. San Diego, thickness measurements in cardiovas- 17;303(7):631–637.
CA: Academic Press, 2013. p. 1039–1053. cular risk prediction: A meta-analysis. 167. Khera AV, Emdin CA, Drake I, et al.
154. Mozaffarian D, Appel LJ, and Van JAMA 2012;308(8):796–803. Epub Genetic risk, adherence to a healthy
Horn L. Components of a cardiopro- 2012/08/23. lifestyle, and coronary disease. N. Engl.
tective diet: New insights. Circulation 162. Erbel R, Mohlenkamp S, Moebus S, et al. J. Med. 2016;375(24):2349–2358.
2011;123(24):2870–2891. Coronary risk stratification, discrimina- 168. Ridker PM, Paynter NP, Rifai N,
155. Lachar BL. Coronary-prone behavior: tion, and reclassification improvement Gaziano JM, and Cook NR. C-reactive
Type A behavior revisited. Tex. Heart based on quantification of subclinical protein and parental history improve
Inst. J. 1993;20:143. coronary atherosclerosis: The Heinz global cardiovascular risk prediction: The
156. Littman AB. Review of psychosomatic Nixdorf Recall study. J. Am. Coll. Reynolds Risk Score for men. Circulation
aspects of cardiovascular disease. Cardiol. 2010;56(17):1397–1406. Epub 2008;118(22):2243–2251.
Psychotera. Psychosom. 1993;60:148. 2010/10/16.
2
CHAPTER
19
20 Chapter 2 Lifestyle Strategies for Risk Factor Reduction, Prevention and Treatment of Cardiovascular Disease
reimbursement models currently provide disincentives for It should also be noted that the majority of patients
using these strategies, since lifestyle interventions are typi- who make lifestyle behavior changes do this without for-
cally not covered by health insurance plans. Aspects of the mal participation in an organized program. For example,
Affordable Care Act of 2010,16 particularly the Accountable over 90% of individuals who have stopped smoking have
Care Organizations provision, provide financial models to done this without formal smoking cessation programs. 27
encourage these low-cost, potentially high-yield lifestyle Furthermore, the majority of patients who lose weight
measures. The challenge for health care professionals will also do this on their own. Nonetheless, health care profes-
be to understand and utilize these models to aggressively sional recommendations and support can be very valuable
incorporate lifestyle measures into the prevention and in motivating patients to start and to maintain the process
treatment of CVD and other lifestyle-related diseases. of behavioral change.
In addition to the financial disincentives, lack of time It is particularly important that physicians play a pro-
may also represent another hurdle. Delivery of those mea- active role in this area. At the current time, physician office
sures related to prevention of CVD recommended by the visits represent a missed opportunity to promote behav-
U.S. Preventive Services Task Force (USPSTF) has been ioral changes. It is hoped that the advent of such organi-
estimated to take the typical clinician a minimum of 1.5 zations as the American College of Lifestyle Medicine, 28
hours per day in non-reimbursable time.17 Thus, it will and the lifestyle medicine track in the American College
be important in clinical practice to find ways to deliver of Preventive Medicine29 will help physicians build the
proven lifestyle interventions with efficient strategies that knowledge, basic skills, and confidence needed to make
are time sensitive. these recommendations. A “blue ribbon” panel of physi-
A representative listing of national guidelines that cians representing most major medical organizations has
incorporate lifestyle medicine emphasis in the treatment of urged physicians to become involved in lifestyle medicine
CVD or as a strategy for lowering risk factors for related and outlined a series of competencies in this area. 30 The
metabolic conditions is presented in Table 2.1. American College of Lifestyle Medicine, a professional
Health care professionals can be enormously influen- organization dedicated to advancing the field of lifestyle
tial in helping patients take positive lifestyle actions to medicine, has doubled its membership each year for the
lower their risk of CVD. Health care providers’ recom- past two years. In 2016, this organization outlined a series
mendations to make changes in behavior such as cigarette of topics and offered certification for those interested in
smoking cessation, weight loss, or improved nutrition deepening their knowledge of lifestyle medicine and incor-
have all been demonstrated to play important roles in porating it into their clinical practices.31
lowering risk factors for CVD. Numerous studies have Increasingly, medical organizations in various sub-
shown that the public perceives medical professionals as specialties are understanding the power of daily lifestyle
a reliable and credible source of information concerning habits and practices in both the prevention and treat-
health-related behaviors.18–24 Often, however, health care ment of various diseases, including CVD. For example, in
workers underestimate how powerful their role as health 2013, the AHA and the American College of Cardiology
counselors can be. For example, less than 50% of smok- (ACC)32 jointly issued guidelines for lifestyle management
ers report receiving advice to quit from their physician, 25 to reduce cardiovascular risk. In conjunction with this ini-
and less than 40% of obese individuals report receiv- tiative, the study group within the AHA, which had pre-
ing advice about weight loss. This is unfortunate, since viously been called “The Council on Nutrition, Physical
the average adult in the United States visits a physician’s Activity and Metabolism,” changed its name to “The
office more than five times per year, and it has been esti- Council on Lifestyle and Cardiometabolic Health.”33
mated that physicians come in contact with over 75% of Along with these changes, a number of articles in a series
adults in the United States in any given year. 26 In addition entitled “Recent Advances in Preventive Cardiology and
to physicians, nutritionists, nurses with an interest and Lifestyle Medicine”34 were published by the AHA in the
background in preventive cardiology or diabetes educa- journal Circulation.
tion, and other health care professionals can play critically Furthermore, the Affordable Care Act,16 including the
important roles in counseling patients on positive lifestyle Accountable Care Organizations provision, mandated
behaviors to lower their risk of CVD. that physicians become more active in this area.
TABLE 2.1 Evidence-based guidelines which employ lifestyle measures to reduce the risk of CHD and other metabolic
conditions
• National Cholesterol Education Program
• JNC VII Guidelines for Prevention and Management of Hypertension
• Institute of Medicine Guidelines for Management of Obesity
• Guidelines for the American Heart Association for the Prevention and Management of Coronary Artery Disease
• Guidelines from the American Diabetes Association for the Management of Diabetes
• Dietary Guidelines for Americans
• American Heart Association Nutrition Implementation Guidelines
• Guidelines from the American Academy of Pediatrics for the Prevention and Treatment of Childhood Obesity
• Guidelines from the American Academy of Pediatrics for Heart Disease Risk Factor Reduction in Children
• Guidelines from the American Heart Association and American Academy of Pediatrics for the Prevention and Treatment of Metabolic
Syndrome
• Joint statement from the American Heart Association and American Cancer Society on the prevention of heart disease and cancer
2.4 Class 1 Interventions 21
The case for aggressive employment of lifestyle more recent set of guidelines was developed by the New
2
measures in clinical medicine has continued to grow. Zealand Guidelines Committee which assesses absolute
Multifactorial risk factor reduction programs have been cardiovascular risk during five years instead of ten.41
clearly demonstrated to reduce each of these risk factors
individually and in groups of risk factors treated together.
Epidemiologic studies have shown that positive lifestyle 2.3 CLASSIFYING INTERVENTIONS
measures, such as not smoking; engaging in at least 30
minutes of physical activity per day; consuming a diet FOR MODIFIABLE RISK FACTORS
of more fruits, whole grains, fish and vegetables; and
maintaining a healthy weight can reduce the incidence As outlined in Chapter 1, “The Rationale for Intervention
of CVD, 35,36 by over 80% and diabetes by over 90%. Of to Reduce the Risk of Cardiovascular Disease,” risk fac-
note is the fact that incorporating just one of these health- tors for CVD can be conveniently divided into “modifi-
promoting practices reduces the risk of developing CVD able” and “non-modifiable.” This framework also carries
and diabetes by over 50%.35,36 practical implications and is a commonly employed clas-
sification strategy.42 In addition, classifications employed
by the American College of Cardiology and the American
2.1 PREDICTING RISK Heart Association divide intervention to reduce risk fac-
tors into four categories based on the level of evidence that
A key first step prior to using lifestyle measures to lower modifying a particular risk factor will result in lower risk
risk factors for CVD involves predicting risk. Risk pre- of CVD. The following four classifications are typically
diction involves understanding the type and strength of employed:
evidence underlying risk factor assessment strategies as
well as clearly understanding the difference between rela- • Class 1 Interventions: These interventions involve
tive risk and absolute risk (see Chapter 1, “The Rationale risk factor reduction strategies that have been
for Intervention to Reduce the Risk of Cardiovascular proven to reduce risk when used.
Disease”). • Class 2 Interventions: This classification includes
Most currently employed, evidence-based frameworks risk factors where interventions are likely to lower
for lowering risk factors for CVD involve assessing abso- the incidence of events but proof is less strong than
lute risk. For example, lowering absolute risk underlies Class 1 interventions.
the strategies for the National Cholesterol Education • Class 3 Interventions: This classification includes
Program (NCEP) ATP-III Guidelines, 3 the American risk factors that have been clearly associated with
Diabetes Association Guide of Managing Diabetes,9 and increased risk of CVD which, if modified, might
The Seventh Report of the Joint National Committee on lower the likelihood of a coronary event.
Prevention, Detection, Evaluation, and Treatment of High • Class 4 Interventions: This classification includes
Blood Pressure (JNC 7).4 risk factors which have been associated with
increased risk of CVD which, if modified, are not
likely to decrease the risk of CVD or cannot be
2.2 ASSESSING RISK modified.
Multiple frameworks are available for assessing risk of This framework for classifications is summarized in
CVD. The most widely used and the one recommended by Table 2.2.
the AHA is the framework developed by the Framingham
Heart Study investigators.37 This framework is found in
Figure 2.1 and Figure 2.2. Figure 2.1 is used to assess risk 2.4 CLASS 1 INTERVENTIONS
for men, and Figure 2.2 is used to assess risk for women.
The Framingham framework is based on estimating an 2.4.1 Lifestyle Approach to Cigarette
individual’s ten-year risk of developing CVD. The higher
the ten-year risk, the more intensity of intervention is
Smoking Cessation
warranted. Cigarette smoking is the leading cause of preventable
It should be noted that there are alternatives to the death in the United States each year, resulting in an esti-
Framingham score. For example, the Reynolds Risk mated 443,000 deaths.43 More than 40% of deaths from
Score provides a variation to the Framingham score by cigarette smoking result from cardiovascular disease.38,44
incorporating whether a parent suffered an MI before the It has been estimated that over 49,000 of the smoking
age of 60 years as well as high-sensitivity CRP (hs-CRP) related deaths are the result of secondhand smoke expo-
level.38,39 The Reynolds score appears to be a better pre- sure. Smoking also has an enormous economic impact on
dictor of individuals in the middle risk category and is the U.S. economy.45 It has been estimated that the United
comparable to the Framingham risk score for individuals States incurs $96 billion in direct medical expenses and
with low or high risk. $97 billion in lost productivity annually as a result of
Other available risk scores include the Systematic cigarette smoking. 2 Smokers lose at least one decade of
Coronary Risk Evaluation Project (SCORE), developed life expectancy compared to never-smokers. The risk of
by the European Joint Task Force, utilizing studies in 12 death from cigarette smoking has continued to increase
European countries involving 250,000 individuals.40 A among women,46 and the increased risks are now identical
22 Chapter 2 Lifestyle Strategies for Risk Factor Reduction, Prevention and Treatment of Cardiovascular Disease
Figure 2.1 Coronary heart disease (CHD) score sheet for calculating 10-year CHD risk according to age, total cholesterol
(TC) (or low- density lipoprotein cholesterol [LDL-C]), high-density lipoprotein cholesterol (HDL-C), blood pressure, dia-
betes, and smoking. Score sheet for men based on the Framingham experience in men 30 to 74 years at baseline. Average risk
estimates are based on typical Framingham subjects, and estimates of idealized risk are based on optimal blood pressure, TC of
160 to 199 (or LDL- C of 100 to 129 mg/dL), no diabetes, and no smoking.
2.4 Class 1 Interventions 23
Figure 2.2 Score sheet for women based on Framingharri experience in women 20 to 74 years of age at baseline. Average
risk estimates are based on typical Framingham subjects, and estimates of Idealized risk are based on optimal blood pressure,
total cholesterol (TC) of 160 to 199 mg/dL (or low-density lipoprotein cholesterol [LDL-C of 100 to 129 mg/dL), high-density lipo-
protein cholesterol (HDL-C) of 55 mg.’ dL. no diabetes, and no smoking. Use of the LDL-C categories is appropriate when fast ng
LDL-C measurements are available. Pts. points.
From Wilson PW: D’ Agostino RD, Levy D, et al. Predication of coronary heart disease using risk factor categories. Circulation .
1998;97:1837– 1847.
24 Chapter 2 Lifestyle Strategies for Risk Factor Reduction, Prevention and Treatment of Cardiovascular Disease
It is important to understand that all of the above-refer- reduction to less than 100 mg/dL. Also in 2006, the AHA
2
enced guidelines advocate treatment based on assessment listed its nutritional and lifestyle recommendations. 59
of the patient’s overall risk. The NCEP ATP-III Guidelines A summary of these recommendations and their lifestyle
utilize not only LDL level but also recommend calcula- interventions is found in Table 2.3. Within a clinical set-
tions based on the Framingham risk score (see Figure 2.1 ting, it may be valuable for patients to receive the services
and Figure 2.2). A guideline algorithm presented by the of a registered dietitian to help them adhere to nutritional
ATP-III Guidelines is presented in Figure 2.3. guidelines recommended by the AHA and NCEP ATP-III.
A variety of lifestyle recommendations are incorporated In 2013, the ACC and AHA issued “Guidelines for the
as first-line treatment in the NCEP ATP-III Guidelines. Treatment of Blood Cholesterol to Reduce Atherosclerotic
Nutritional intervention is recommended, including main- Cardiovascular Disease in Adults.” These Guidelines rec-
taining calories from fat between 25–35%, saturated fat ommend increased use of statin medications to reduce
counting for less than 7%, and cholesterol level intake atherosclerotic cardiovascular disease (ASCVD) events
limited to less than 200 mg/day. Complex carbohydrates in secondary and primary prevention and also recom-
are recommended at 50–60% of calories and protein at mend discontinuation of use of specific LDL and HDL
15%. NCEP ATP-III Guidelines recommend consumption treatment targets.60 The four major statin benefit groups
of 20–30 grams of dietary fiber daily—an amount far more where the use of statin medicines, according to this
than the average American adult currently consumes.3 report, were indicated to reduce ACSVD risk were the
In 2006 American College of Cardiology and the following: Individuals1 with clinical ASCVD, 2 primary
American Heart Association updated their secondary pre- elevations of LDL-C>190 mg/dL, 3 diabetics aged 40 to
vention guidelines for lipid management, including most 75 years with LDL-C 70 to 189 mg/dL and without clini-
of the provisions of the NCEP guidelines but also strength- cal ASCVD, and4 without clinical ASCVD or diabetes
ening them for individuals with established coronary with LDL-C 70 to 189 mg/dL who had a ten-year ASCVD
heart disease (CHD). The ACC/AHA Guidelines extend risk >7.5%These Guidelines were immediately criticized
the option of levels of less than 70 mg/dL for LDL for all for recommending excessive use of statins, particularly in
patients with CHD, not just those at very high risk. 58 The individuals with risk of >7.5%.61,62 This controversy per-
guidelines also recommend that patients with triglyceride sists as of this writing.
levels of 200–499 mg/dL should have a non-HDL choles- A variety of pharmaceutical agents have been demon-
terol level of less than 130 mg/dL and potentially further strated to lower both total and LDL cholesterol as well as
Figure 2.3 Algorithm for lipid-lowering therapy based on findings from intervention trials. CHD, coronary heart disease;
HDL-C, high-density lipoprotein cholesterol; LDL-C, low-density lipoprotein cholesterol; TG, triglycerides.
From the Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment
of High Blood Cholesterol in Adults [Adult Treatment Panel III]: final report. Circulation . 2002;106:3143– 3421.
26 Chapter 2 Lifestyle Strategies for Risk Factor Reduction, Prevention and Treatment of Cardiovascular Disease
TABLE 2.3 AHA 2008 diet and lifestyle recommendations for cardiovascular disease risk reduction
. Balance caloric intake and physical activity to achieve or maintain a healthy body weight.
1
2. Eat a diet rich in vegetables and fruits.
3. Choose and prepare foods with little or no salt.
4. Minimize your intake of beverages and foods with added sugars.
5. Consume oily fish at least twice a week.
6. Limit your intake of saturated fat to < 7% of energy, trans fat to < 1% of energy, and cholesterol to < 300 mg per day by choosing lean
meats and vegetable alternatives; selecting fat free (skim), 1% fat, and low-fat dairy products; and minimizing intake of partially
hydrogenated fats.
7. Choose whole grain, high-fiber foods in your diet.
8. If you consume alcohol, consume in moderation.
9. When you eat food that is prepared outside of your home, follow the AHA Diet and Lifestyle Recommendations.
Adapted from: Lichtenstein AH, Appel LJ, Brands M, Carnethon M, et al. Diet and Lifestyle Recommendations Revision 2006. A Scientific Statement From the American Heart
Association Nutrition Committee. Circulation. 2006;114:82–96.
reduce morbidity and mortality from CVD. Most promi- most favorable outcome (see also Chapter 4, “Clinical
nent among these medicines are the statins. While statins Strategies for Managing Dyslipidemias” and Chapter 64
vary according to potency, they appear to be equally effi- “Lipid Management in Secondary Prevention”).
cacious. Adherence is the key issue.
A recent approach to the use of statins based on evi-
dence from clinical trials has been suggested by preven- 2.4.3 Lifestyle Management
tive cardiologists in the United States, Canada, and
Europe.61,62 It is based on the following five guidelines:
of Hypertension
According to the JNC 7 Report, one out of every three
• Statin therapy should be used as an adjunct to diet, American adults has high blood pressure, which represents
exercise, and smoking cessation for secondary pre- more than 50 million Americans.4 Another 25% fall into the
vention in patients with a previous history of MI, “pre-hypertensive” category, which represents another 45
stroke, or clinically apparent after sclerosis. million Americans. The JNC 7 blood pressure classification
• Statin therapy can be considered as an adjunct to is found is in Chapter 1, “The Rationale for Intervention to
diet, exercise, and smoking cessation as a compo- Reduce the Risk of Cardiovascular Disease.”
nent of primary prevention in those age 50 or over A commission was established to formulate JNC
with either diabetes, related lower HDL cholesterol, 8 Guidelines. However, the report of this commission
or elevated hs-CRP. was never issued as formal guidelines. The intent was to
• When prescribing statin therapy, physicians should change the approach to guidelines to a more evidence-
seek to maximize the intensities of therapies based rather than epidemiologic-based approach.63 The
and focus efforts on compliance and long-term commission issued a report that, as already indicated in
adherence. Chapter 1, contained the following statement:
• The use of non-statins as lowering agents for mono-
therapy or in combination with a statin should There is strong evidence to support treating hyperten-
be limited until evidence is available that such an sive patients age 60 or older to a BP goal of <150/90
approach further reduces cardiovascular event rates mmHg and hypertensive patients 30–59 years of age
in specific patient groups. to a diastolic goal of < 90 mmHg. However, there is
• A guideline based on prior evidence and on prior insufficient evidence in hypertensive persons under
entry criteria must be simple, practical, and con- the age of 60 years for a systolic goal or in those
sistent with evidence-based principles and should, under the age of 30 years for a diastolic goal, so
therefore, result in broad clinical acceptance. New the panel recommends a BP of < 140/90 mmHg for
advances in prevention should be incorporated into those groups based on expert opinion.63
these guidelines as quickly as possible.
As a practical matter, it should be noted that most orga-
It should be noted that these guidelines underscore the nizations, including the AHA in their Clinical Guidelines
importance of lifestyle medicine principles of incorporat- for Establishing Goals for 2020, continue to use the cut-
ing diet, exercise, and smoking cessation into the regimens offs articulated in the JNC 8 Guidelines.
that may also employ statin medicines. According to data from the Framingham Heart Study,
Other agents available include niacin, fibrates, bile individuals who have a normal blood pressure at the age
acid sequestrans, and cholesterol absorption inhibitors. of 55 still have a 90% chance of developing hyperten-
A complete review of pharmaceutical therapies for the sion in their lifetime.64 Control of high blood pressure in
management of dyslipidemia is beyond the scope of this the United States remains abysmally low, with over two-
chapter and has been well treated in a variety of other thirds of individuals with hypertension not adequately
publications. All the major cholesterol management guide- controlled.65
lines advocate that lifestyle measures be combined if phar- A number of lifestyle measures are recommended by
maceutical agents are employed in order to produce the JNC 7 and can play significant roles either in reducing the
2.4 Class 1 Interventions 27
likelihood of developing hypertension or treating it if it simultaneously appear to have additive benefits. The
2
currently exists. These lifestyle measures include weight PREMIER trial showed that a combination of weight loss,
management, regular physical activity, proper nutrition, sodium restriction, increased physical activity, and limited
cessation of cigarette smoking, and moderation of alco- alcohol consumption when practiced together resulted in
hol—all of which represent first-line lifestyle-related mea- substantial blood pressure reductions in individuals with
sures in the treatment of high blood pressure within the above optimal blood pressure, including Stage 1 hyperten-
JNC 7 framework.4 sion (140–159 mmHg systolic and 90–95 mmHg diastolic)
Increased body weight has clearly been associated and in individuals who were not taking antihypertensive
with increased risk of high blood pressure.66 Conversely, medications.78 Further benefits were achieved by individu-
weight reduction in overweight or obese individuals rep- als who implemented a DASH diet in addition to these
resents a highly reliable way of lowering blood pressure. other lifestyle modifications.
In most studies, individuals who are overweight or obese Some controversy has continued to exist related to
can anticipate losing one mm Hg both systolic and dia- whether or not lowering blood pressure to 140/90 mmHg
stolic blood pressure for every two lbs of weight loss.67 is the optimum recommendation. The recently completed
The mechanism of blood pressure lowering resulting from SPRINT (Systolic Blood Pressure Intervention Trial)79
weight loss is not completely understood. It may represent showed a benefit from reduced risk of kidney disease and
a decrease in blood volume, an initial diuresis, or a reduc- heart failure in individuals who were at elevated risk for
tion in systemic vascular resistance.68 these conditions from lowering systolic blood pressure
Proper nutrition can also play a significant role in to 120 mmHg as compared to 140 mmHg. One negative
blood pressure control. Both the JNC 7 Guidelines4 and aspect of this study is that it required an average of three
the AHA Nutrition Guidelines59 recommend that indi- pharmaceutical agents to obtain these further reductions.
viduals with hypertension should consume a diet with no This would argue for a combination of fewer pharmaceu-
more than 2,300 mg of sodium per day. Recently released tical agents plus lifestyle measures which are likely to be
Dietary Guidelines for Americans 201569 recommends an synergistic with pharmaceutical therapy.
even lower sodium consumption of 1,500 mg per day for In late 2017, the American College of Cardiology and
individuals at increased risk for cardiovascular disease the American Heart Association issued new guidelines
and all individuals over the age of 50. recommending more stringent control of blood pressure.
Practical ways to lower salt consumption, including These guidelines lowered the definition of high blood
removing the salt shaker from the table, reduction of salt pressure to any level higher than 120/80 mm Hg. These
in cooking, careful label reading of processed foods (a guidelines are intended to account for an increased risk of
significant and often under-recognized source of sodium), cardiovascular complications above these numbers.
and increased consumption of whole grains and fruits and As a practical matter, the new definition of high blood
vegetables. The Dietary Approaches to Stop Hypertension pressure resulted in nearly half of the U.S. population
(DASH) diet which emphasizes whole grains, fruits and (46%) being categorized as having high blood pressure.
vegetables, and low-fat dairy products has been shown to The greatest impact occurred in younger people. The
reliably lower high blood pressure.70 An addition of fur- prevalence of high blood pressure was expected to triple in
ther sodium restriction to the DASH diet results in further men under the age of 45 and double among women under
reduction in blood pressure.71 Unfortunately, less than the age of 45, according to the new guidelines.
20% of individuals with established high blood pressure The ACC/AHA guidelines also recommended that
are following a DASH-type diet.72 high blood pressure should be treated earlier with life-
Regular physical activity also helps prevent high blood style changes and in some instances with medication to
pressure and lowers blood pressure in individuals with reach levels of 130/80 mm Hg rather than 140/90 mm Hg
currently existing hypertension. Physically active indi- in young, asymptomatic individuals. Abundant research
viduals reduce their risk of hypertension between 20 and suggests that increased physical activity and proper nutri-
50%.73 Individuals with established hypertension who tion (including lower amounts of salt and fats in the diet
start a physical activity program (emphasizing aerobic and weight loss if necessary) can significantly lower blood
activities such as walking) may lower both systolic and pressure and act synergistically with each other and also
diastolic blood pressure by 5–10 mm Hg by participating with medications.
in such moderate-intensity physical activity.73 Categories in the new blood pressure guidelines are:
Excessive alcohol consumption is a risk factor for hyper-
tension.74 Moderation of this habit also can contribute • Normal: less than 120/80 mm Hg
significantly to controlling blood pressure. Cigarette smok- • Elevated: systolic between 120–129 and diastolic
ing and use of other tobacco products has been repeatedly less than 80 mm Hg
shown to raise blood pressure.75,76 Cessation of this deadly • Stage 1: Systolic between 130–139 OR diastolic
habit should be recommended for multiple reasons. between 80–89 mm Hg
Some evidence supports stress reduction as playing • Stage 2: Systolic at least 140 or diastolic at least 90
a role in lowering blood pressure, although this effect mm Hg
seems to be less prominent than the other lifestyle mea-
sures already discussed.77 A beneficial aspect of lifestyle Hypertensive crisis was defined as systolic over 180
measures in relationship to blood pressure control is that mm Hg and/or diastolic over 120 mm Hg. These patients
they often act synergistically with each other. It should need prompt changes in medication if there are no other
be noted that positive lifestyle measures when practiced indications of problems or hospitalization if there are signs
28 Chapter 2 Lifestyle Strategies for Risk Factor Reduction, Prevention and Treatment of Cardiovascular Disease
of organ damage. The guidelines also stressed the impor- Other potentially beneficial pharmaceutical agents
tance of using proper technique for measuring blood pres- include statins, beta adrenergic receptor blockers after
sure and use of home blood pressure monitoring using MI, and angiotensin-converting enzyme inhibitors in indi-
validated devices (79a) (see also Chapter 5). viduals at high risk for CVD events. Extensive reviews of
all these medications may be found elsewhere.
2.4.4 Pharmaceutical Measures
for Cardiac Protection 2.5 CLASS 2 INTERVENTIONS
A detailed review of pharmacologic interventions to lower
the risk of heart disease is beyond the scope of this chap-
2.5.1 Obesity Prevention and Management
ter. However, it is important to recognize that certain Obesity,66 adult weight gain,84 and increased abdominal
pharmacologic interventions have been demonstrated to fat85 are all independently associated with increased risk
be effective in either primary or secondary prevention of for coronary heart disease.86–89 Obesity also contributes
cardiovascular disease. to a variety of other risk factors for CVD including hyper-
Aspirin has been demonstrated to lower the risk of sub- tension, type 2 diabetes, and dyslipidemia. The American
sequent events in individuals with existing CVD, where Heart Association recognizes obesity as an independent
aspirin reduces the risk of subsequent events by 25%.80 risk factor over and above its association with other risk
The ACC/AHA lowered the recommended prophylactic factors for CVD.90
dose of aspirin in individuals with existing CVD from Over the last 40 years the percentage of the U.S. popu-
75 to 325 mg/day to 75 to 162 mg/day, since anti-platelet lation considered to be overweight (BMI ≥ 25 < 29.9) and
trials had showed no difference in the reduction benefit obese (BMI ≥ 30.0) has risen steadily and substantially.
and reduced risk of bleeding at this lower dosage range.80 As depicted in Figure 2.4, over two-thirds of the adult
Other anti-platelet agents do not offer significant benefit population in the United States are now considered over-
over aspirin. These agents, such as Clopidogrel, should be weight or obese.91,92 The prevalence of obesity has risen
limited to patients with aspirin allergy or intolerance.81 particularly sharply, with the most dramatic increases in
The picture of aspirin usage in primary prevention is less individuals who are extremely obese (BMI ≥ 40.0).
clear.82 The AHA guidelines issued in 2007 for women rec- The same trends have occurred in children93 as depicted
ommend aspirin for high-risk women whose 10th-year risk in Figure 2.5. The prevalence of overweight has more than
of a coronary event, based on Framingham criteria, exceeds tripled among children in the United States in the past 40
20% and for all women over the age of 65 in whom blood years. (“Overweight” in children is defined by CDC crite-
pressure is controlled and the potential benefit for prevent- ria as ≥ 95th percentile weight for height based on CDC
ing MI or ischemic stroke outweighs the risk of bleeding or 2000 tables).94,95 Some criteria, such as those from the
hemorrhagic stroke. The USPSTF recommends aspirin for American Medical Association, also include a description
men 45–79 years of age and women 55–79 years of age for of ≥ 85th percentile weight for height as “overweight” and
benefit in reduction of risk of MI in men and ischemic stroke > 95th percentile of weight for height as an appropriate
in women if these benefits outweigh the risk of gastrointes- definition for “obese” in children.85
tinal bleeding.83 It should be emphasized that most of the Obese individuals are particularly likely to demon-
data on the use of aspirin in primary prevention predates strate clustering of risk factors.86 Framingham data have
concomitant use of statin therapy. Thus, many cardiologists demonstrated that over two-thirds of CVD is found in
consider utilizing statins as an adjunct to diet, exercise, and individuals with two or more risk factors.96 Moreover,
smoking cessation rather than aspirin in primary prevention. obesity is the major driver of the metabolic syndrome,
70 70
60 60
50 Overweight or obese 50
40 40
Percent
Percent
30 30
Obese
20 20
10 10
0 0
1976–1980 1988–1994 1999–2000 2003–2004
2001–2002
20 20
15 15
2
6–11 years 12–19 years
Percent
Percent
10 10
2–5 years
5 5
0 0
1963–1965 1971–1974 1976–1980 1988–1994 1999–2000 2003–2004
1966–1970 2001–2002
which afflicts between 25–35% of the adult population Bupropion, and Liraglutide. A description of dosages and
in the United States and represents a potent risk factor for actions of these medications is beyond the scope of this
both CVD and diabetes.97 chapter and has been extensively reviewed elsewhere.103 It
Although the association between obesity and increased should be noted that all of these medicines should be uti-
risk of CVD is well established, no large-scale, random- lized in conjunction with positive lifestyle measures such
ized trials of weight reduction as an intervention to lower as proper nutrition and regular physical activity.
risk of CVD are available to estimate the benefits of weight It has been regularly shown that physician involvement
loss. A number of trials, however, have shown that weight in recommendations for weight loss represents an impor-
loss in obese individuals reduces risk factors for CHD and tant predictor of both initial weight loss and maintenance
a variety of other chronic conditions. For example, in the of weight loss. A detailed description of available pro-
Diabetes Prevention Program, individuals who were over- grams and therapies for weight loss is beyond the scope of
weight who lost 5–7% of their body weight and adopted the current chapter. The authors have, however, co-edited
a program of regular physical activity reduced their risk of a textbook on this topic and the reader is referred to this
developing diabetes by 58%.98 Nutritional strategies, with textbook for more detailed information in this area.104
a particular emphasis on matching calorie intake to calo-
rie output, have demonstrated effectiveness for weight loss.
The Dietary Guidelines for Americans 201569 list overcon-
2.5.2 Diabetes/Glucose Intolerance
sumption of calories and overweight/obesity as the leading The prevalence of diabetes in the United States has grown
nutritional problems in the United States. significantly over the past decade, which appears to reflect
In addition, regular physical activity in conjunction corresponding increases in the prevalence of overweight
with attention on caloric consumption has been found in and obesity.103 Currently, approximately 8% of the adult
numerous studies to help in the maintenance of long-term population in the United States—nearly 24 million peo-
weight loss.99,100 The preferred form of physical activity ple—has diabetes mellitus. The vast majority of these
for most overweight or obese individuals is walking. Some individuals (more than 90%) have type 2 diabetes.103
studies have recommended 30–60 minutes of moderate- Unfortunately, approximately one-quarter of individu-
intensity walking per day as a reasonable goal for indi- als with diabetes are not aware they have this condition.
viduals as a component of an effective and safe weight Another significant problem is the recent increase in type
loss program.100 The Dietary Guidelines for Americans 2 diabetes in children. It is now estimated that more new
2015 recommend 60 minutes or more of moderate physi- cases of type 2 diabetes are found in children each year
cal activity as a component of weight management.69 than type 1 diabetes.105
Behavioral strategies and social support are also impor- Diabetes represents a significant risk factor for CVD
tant as components of an overall strategy for long-term which is the leading cause of death for both men and
weight loss.101 Support from an individual’s family and women with diabetes resulting in 75% of all mortality.106,107
friends or from groups (e.g., from an organization such as A variety of lifestyle measures, such as weight loss in over-
Weight Watchers International) has been demonstrated to weight or obese individuals and regular physical activity,
be helpful in long-term maintenance of weight loss.102 play important roles in the management of diabetes.108,109
A number of pharmaceutical therapies are cur- These modalities are particularly important for blood
rently available to assist in weight loss. These include sugar control in individuals with type 2 diabetes.
Phentermine the combination of topiramate/phentermine Because patients with diabetes often have other risk
(Qsymia), Supreza (phentermine) Lorcaserin, Orlistat factors for CVD, aggressive treatment of these other
(prescription), Orlistat (over-the-counter), Naltrexone, risk factors is imperative. For example, guidelines from
30 Chapter 2 Lifestyle Strategies for Risk Factor Reduction, Prevention and Treatment of Cardiovascular Disease
the American Diabetes Association for treating high The Physical Activity Guidelines for Americans 2008
blood pressure in individuals with diabetes recommend provides a listing of known or anticipated health bene-
a target of BP at ≤ 130/80 mm Hg for individuals with fits from increased physical activity.117 A listing of these
diabetes.109,110 NCEP ATP III Guidelines treat diabetes known benefits and the strength of the evidence support-
as a CVD equivalent and recommend reduction of LDL ing these relationships are found in Table 2.4. As can be
cholesterol in diabetic individuals to a goal of less than seen from this table, many of the known benefits from
100 mg/dL.3 physical activity involve reduction of risk of CVD.
Impaired glucose tolerance often precedes overt diabe-
tes and is particularly common in obese individuals. CDC
data indicate that 35–40% of the adult population in the TABLE 2.4 Health benefits associated with regular
physical activity
United States have glucose intolerance.111 Recent studies
have shown that overweight individuals with impaired glu-
cose tolerance who lose weight, reduce total fat intake, and
increase physical activity significantly decrease their risk of
developing diabetes.98,112 Thus, lifestyle measures are highly
appropriate in both diabetic and pre-diabetic patients.
Few data are available to address appropriate strategies
for long-term reduction in CVD mortality among patients
with type 2 diabetes. To date, interventions to improve
fitness and achieve weight loss as methods to reduce CVD
morbidity and mortality have been disappointing. The
Look AHEAD Trial randomized patients either to inten-
sive lifestyle intervention, which promoted weight loss
through increased physical activity and decreased caloric
intake, or to a diabetes support and education program.
The intent of the lifestyle intervention focused on weight
loss but did not reduce the rate of cardiovascular events
in this group during a median follow-up period of almost
ten years, despite the fact that beneficial effects occurred
on levels of several biomarkers.113 Thus, while this trial
did not demonstrate a reduction in the risk of cardiovas-
cular morbidity and mortality, it is important to note
that patients in the intervention group had meaningful
clinical improvement in multiple areas, including hemo-
globin A1C, weight, physical fitness, and all other mea-
sured cardiovascular risk factors, except for lower density
lipoprotein (LDL) cholesterol levels. In addition, benefits
to individuals in the intervention group included reduc-
tion in urinary incontinence, sleep apnea, and depression,
and improvements in quality of life, physical functioning,
and mobility. All of these were accomplished with a high
level of acceptance in the intervention group and low side
effects. Thus, this trial suggests that the high-intensity
lifestyle intervention approach can be safely conducted
and result in significant weight loss in diabetic patients.
Application of these findings will depend on clinical judg-
ment and individual patient characteristics for those phy-
sicians treating diabetes.
2.5.3 Physical Inactivity
The U.S. population has become increasingly sedentary.
Both the U.S. Surgeon General’s Report on Physical
Activity and Health,114 and data from the Behavior Risk
Factor Surveillance System (BRFSS)115 have suggested
that more than 70% of the adult population in the United
States does not achieve 30 minutes of moderate-intensity
physical activity on most, if not all, days. Multiple stud-
ies have demonstrated that an active lifestyle substan-
tially decreases the risk of CVD. The American Heart
Association has listed the lack of physical activity as a
major risk factor for CVD.116 Source: 2008 Physical Activity Guidelines for Americans.
2.7 Post Menopausal Estrogen Therapy 31
The Physical Activity Guidelines for Americans 2008 Association defined dietary goals as “in the context of a diet
2
recommend that individuals try to accumulate 150 min- that is appropriate in energy balance, pursuing an overall
utes of moderate-intensity activity or 75 minutes of vig- dietary plan that is consistent with DASH (Dietary Approach
orous activity on a weekly basis. Moderate-intensity to Stop Hypertension), including but not limited to:
activities include such forms of physical activity as walk-
ing, jogging, cycling, or swimming at moderate inten- • Fruits and vegetables ≥ 4.5 cups per day,
sity. A listing of physical activity guidelines is beyond the • Fish ≥ 3.5 ounce servings per week (preferably oily
scope of this chapter. The reader is referred to the Physical fish),
Activity Guidelines for Americans 2008 for an excellent • Fiber rich whole grain (≥1.1 g of fiber per 10 g of
compendium of literature in this area.117 carbohydrate: 3 one ounce equivalent servings per
day),
• Sodium < 1500 milligrams per day,
2.5.4 Moderate Alcohol Consumption • Sugar sweetened beverages ≤ 450 kcals (36 ounce)
A number of studies have demonstrated that moderate per week.”
alcohol consumption decreases the risk of vascular diseases
such as heart attack, peripheral vascular disease, and sud- These recommendations seem reasonable and have
den cardiac death.74 It should be noted that these studies been expanded upon in recent reviews.129,130 Some recent
have also demonstrated that excessive alcohol consump- evidence has suggested that diets adhering to the principles
tion increases both all-cause mortality and cardiovascular of the Mediterranean-style diet, which has been supple-
disease mortality.118,119 Moderate alcohol consumption mented with extra-virgin olive oil or nuts, can reduce the
has been defined as one drink per day for women and up incidence of major cardiovascular effects among individu-
to two drinks per day for men. The high level allowed for als with high cardiovascular risk. The Dietary Guidelines
men is a result of enhanced ability to metabolize alcohol for Americans 2015 incorporate and expand upon these
due to more robust activity of the enzyme alcohol hydrog- principles.69
enase in the liver in men. These levels of alcohol consump-
tion have consistently corresponded to reduction of risk
for cardiovascular disease of approximately 20–40%. The 2.6.2 Psychological Risk
most reasonable course in a clinical setting is to assess Factors/Counseling
risks and benefits of alcohol consumption on a case-by-
case basis with each patient. A number of psychological factors, including depression,
chronic hostility, social isolation, and lack of social sup-
port, have been linked to increased risk of CVD.131 Some
2.6 CLASS 3 INTERVENTIONS studies have suggested that improved psychological sup-
port systems may improve outcomes following myocardial
infarction. For example, one meta-analysis of 37 smaller
2.6.1 Nutritional Counseling studies showed that stress management and health educa-
Numerous studies have demonstrated that diet has an tion in individuals with CVD reduced recurrent myocar-
impact on CVD risk.120–124 The USPSTF listed nutritional dial infarction by 29% and cardiac mortality by 34%.131
counseling as having “moderate” evidence supporting Office visits following myocardial infarction clearly rep-
its role in lowering the risk of CVD. Recent Scientific resent an excellent opportunity to assess levels of depres-
Statements from the American Heart Association52 as well sion and social isolation in individuals who have suffered
as the Dietary Guidelines for Americans 201569 emphasize recent cardiac events.
the important role of nutritional counseling in lowering
the risk of CVD. In particular, improved nutritional prac-
tices may help improve blood lipids, and strategies such as
the DASH diet70,71 have been demonstrated to help control
2.7 POST MENOPAUSAL
high blood pressure. ESTROGEN THERAPY
Numerous guidelines and resource materials are avail-
able in this area from the American Heart Association125 It is well established that the risk of CVD in women
as well as the American Dietetic Association126 and the increases significantly following menopause. Relatively
Preventive Cardiovascular Nurses Association127 to assist few women experience CVD at younger than 45 years of
patients in making nutritional choices to lower their risk age in the United States.132 However, by the age of 60,
of CVD. Additional guidelines providing key components CVD is the leading cause of death among women.
of overall health and nutritional patterns are available Multiple factors may explain the increased risk of CVD
from various professional societies. The guidelines are all after menopause. For many years the increase in CVD
very consistent with each other, so the individual health after menopause was attributed to the decline in endoge-
care professional is able to choose the one that fits most nous estrogen that accompanies menopause. However, the
conveniently into his/her practice.128 Women’s Health Initiative findings did not support this
The complexity of recommending an optimal diet for concept.133–135 For this reason, hormone therapy is no lon-
cardiovascular health risk reduction has been recognized ger recommended as an approach to prevention of CVD
in all of these guidelines. Most recently, with this caveat for the USPSTF, the American Heart Association, or other
in place, the 2020 Strategic Plan from the American Heart scientific organizations.134
32 Chapter 2 Lifestyle Strategies for Risk Factor Reduction, Prevention and Treatment of Cardiovascular Disease
CLINICAL APPLICATIONS
Actions Available Tools Comments
Assess risk of CVD in all Framingham Risk Scores or the equivalent are Other risk scores, including the Reynolds Risk Score,
patients. available for this purpose. are alternatives to the Framingham Risk Scores.
Assess and counsel all Multiple tools are available from the American Secondhand smoke also poses danger and should
patients who smoke on the Heart Association, American Lung Association, be discussed with all patients.
importance of smoking etc.
cessation.
Assess and counsel all patients Use the National Cholesterol Education Lifestyle strategies, including proper nutrition, weight
related to dyslipidemias Program (NCEP) criteria and tools or the management and physical activity, are a key
equivalent. component of managing dyslipidemias
Assess and counsel all Use JNC VII criteria to help individuals Lifestyle strategies are a key component for
patients related to blood understand not only high blood pressure but individuals to maintain healthy blood pressure or
pressure. also high normal and normal blood pressure lower blood pressure if they are in the pre-
and what can be done to treat them. hypertension or hypertension categories.
References 33
Assess and counsel all Obtain weight, body mass index (BMI), and Both BMI and waist circumference independently
patients on obesity prevention
and management.
waist circumference on all patients. predict the risk of CVD.
2
Assess and counsel all Utilize criteria from the U.S. Physical Activity These are very useful guidelines for all age groups,
patients on physical activity. Guidelines. children up to senior citizens.
REFERENCES
1. Mozaffarian D, Benjamin E, Go A, Association pediatric and adult nutrition 5A’s for smoking cessation counseling.
et al. Heart disease and stroke statis- guidelines. AHA scientific statement. Nicotine Tob. Res. 2007;9:1095.
tics: 2016 Update. Circulation 2015. Circulation 2009;119:1161–1175. 26. National Center for Health Statistics.
CIR.0000000000000350. https: //do 12. American Academy of Pediatrics. Health, United States 1987. Washington,
i.org/10.1161/CI R.000 00000 00000350. Guidelines on Childhood Obesity. DC: US Department of Health and
Originally published December 16, 2015. http://www.aap.org/obesity/index.html. Human Services, Public Health Service,
Accessed January 3, 2017. Accessed August 29, 2011. 1988. USDHHS Pub. No. 88-1232.
2. Centers for Disease Control and 13. Daniels SR, Greer FR, and Committee on 27. Fiore M, Novotny T, Lynn W, et al.
Prevention (CDC). Smoking-attributable Nutrition. Lipid screening and cardio- Methods used to quit smoking in the
mortality, years of potential life lost, vascular health in childhood. Pediatrics United States: Do cessation programs
and productivity losses – United States, 2008;122:198–208. help? JAMA 1990;263:2760–2765.
2000—2004. MMWR Morb. Mortal. 14. Steinberger J, Daniels SR, Eckel RH, et 28. American College of Lifestyle Medicine.
Wkly. Rep. 2008;57:1226. al. Progress and challenges in metabolic http://lifestylemedicine.org. Accessed
3. National Heart Lung and Blood Institute. syndrome in children and adolescents. January 5, 2017.
Third report of the expert panel on AHA scientific statement. Circulation 29. American College of Preventive Medicine
detection, evaluation and treatment 2009;119:628–647. Website. http://www.acpm.org/. Accessed
of high blood cholesterol in adults 15. Eyre H, Kahn R, Robertson R, and January 16, 2017.
(Adult Treatment Panel III). Circulation ACS/ADA/AHA Scientific Statement. 30. Lianov L and Johnson M. Physician
2002;106:3143–3421. http://www.nhlb Preventing cancer, cardiovascular competencies for prescribing lifestyle
i.nih.gov/g uidelines /cholesterol/index.h disease and diabetes. Circulation medicine. JAMA 2010;304(2):202–203.
tm. Accessed March 22, 2017. 2004;109:3244–3255. 31. American College of Lifestyle Medicine.
4. Chobanian AV, Bakris GI, and Black HR. 16. The Patient Protection and Affordable Lifestyle Medicine Core Competencies
The seventh report of the joint national Care Act (Affordable Care Act for all Program. http://lifestylemedicine.org/L
committee on prevention, detection, Americans). https: //www.govi nfo.gov/c ifestyle-Medicine-Core-Competencies
evaluation, and treatment of high blood ontent /pkg / PLAW-111publ148/pdf / PLAW -Prog ram
pressure: The JNC 7 report. JAMA -111publ148.pdf. Accessed February 11, 32. Eckel RH, Jakicic JM, Ard JD, et al.
2003;289:2560–2571. 2019. 2013 AHA/ACC guideline on lifestyle
5. Poirier P, Giles TD, Bray GA, et al. 17. Yarnell KS, Pollack KI, Östbye T, Krause management to reduce cardiovascular
Obesity and cardiovascular disease: KM, and Michener JL. Primary care: Is risk: A report of the American College of
Pathophysiology, evaluation, and effect there enough time for prevention? Am. J. Cardiology/American Heart Association
of weight loss: An update of the 1997 Public Health 2003;93:635–641. task force on practice guidelines.
American Heart Association scien- 18. Ockene JK, Quirk ME, Goldberg Circulation 2014;129:S76–S79.
tific statement on obesity and heart RJ, et al. A resident’s training pro- 33. American Heart Association. Council on
disease from the obesity committee gram for the development of smoking Lifestyle and Cardiometabolic Health.
of the Council on Nutrition, Physical intervention skills. Arch. Intern. Med. https: //professional.heart.org /professio
Activity, and Metabolism. Circulation 1988;148:1039–1045. nal/MembershipCouncils/ScientificCo
2006;113:898–918. 19. Mojonnier ML, Hall Y, Brkson DM, et uncils /UCM _ 322856_Cou ncil- on-Lifest
6. Lee IM, Shiroma EJ, Lobelo F, et al. Experience in changing food habits of yle-and-Cardiometabolic-Health.jsp.
al. Effect of physical inactivity on hyperlipidemic men and women. JADA Accessed January 3, 2017.
major non-communicable diseases 1988;77:140–148. 34. Franklin BA and Cushman M. Recent
worldwide: An analysis of burden of 20. Dunbar J. Assessment of medication advances in preventive cardiology and
disease and life expectancy. Lancet compliance: A review. In Haynes RB, lifestyle medicine: A themed series.
2012;380(9838):219–229. Mattson ME, and Engebretson TO, Circulation 2011;123:2274–2283.
7. Lloyd-Jones DM, Hong Y, Labarthe D, eds. Patient Compliance to Prescribed 35. Liu S, Stampfer MJ, Hu FB, et al.
et al. Defining and setting national goals Antihypertensive Medication Regimen. Whole-grain consumption and risk of
for cardiovascular health promotion Washington, DC: USDHHS, 1988. coronary heart disease: Results from the
and disease reduction: The American USDHHS Pub. No. (NIH) 81-2101. Nurses’ health study. Am. J. Clin. Nutr.
Heart Association’s strategic impact goal 21. Greenfield S, Kaplan SH, Ware JE, et al. 1999;70:3412–3419.
through 2020 and beyond. Circulation Patients’ participation in medical care: 36. Stampfer MJ, Hu FB, Manson JE, Rimm
2010 Feb 2;121(4):586–613. Effects on blood pressure sugar control EB, and Willett WC. Primary preven-
8. Eckel RH, Kahn R, Robertson RM, and quality of life in diabetes. J. Gen. tion of coronary heart disease in women
and Rizza RA. Preventing cardiovas- Intern. Med. 1988;3:448–457. through diet and lifestyle. N. Engl. J.
cular disease and diabetes. Circulation 22. Schulman BA. Active patient orienta- Med. 2000;343:16.
2006;113:2943–2946. tion and outcomes in hypertensive 37. Framingham Heart Study. http://www.
9. American DiabetesAssociation. Are You treatment: Application of a socio- framinghamheartstudy.org/. Accessed
at Risk? http://www.diabetes.org/are-yo organizational perspective. Med. Care March 22, 2017.
u-at-risk/. Accessed March 22, 2017. 1979;17:267–280. 38. Ridker PM, Buring JE, Rifai N, and
10. US Department of Health and Human 23. Glynn TJ, Manley MW, Cullen JW, and Cook NR. Development and validation
Services and US Department of Mayer JW. Cancer prevention through of improved algorithms for the assess-
Agriculture. Report of the Dietary physical interventions. Semin. Oncol. ment of global cardiovascular risk in
Guidelines Advisory Committee on 1990;17:391–401. women: The Reynolds risk score. JAMA
the Dietary Guidelines for Americans. 24. Ford AS and Ford WS. Health educa- 2007;297:611.
Washington, DC: US Department tion and the primary care physician: The 39. Ridker PM, Paynter NP, Rifai N, et al.
of Health and Human Services, US practitioner’s perspective. Soc. Sci. Med. C-reactive protein and parental history
Department of Agriculture, 2010. 1983;17:1505–1512. improve global cardiovascular risk pre-
11. Gidding SS, Lichtenstein AH, Faith MS, 25. Chase EC, McMenamin SB, and Halpin diction: The Reynolds risk score for men.
et al. Implementing American Heart HA. Medicaid provider delivery of the Circulation 2008;118:2243.
34 Chapter 2 Lifestyle Strategies for Risk Factor Reduction, Prevention and Treatment of Cardiovascular Disease
40. Conroy RM, Pyorala K, Fitzgerald AP, 56. Centers for Disease Control and 70. Appel LJ, Moore TJ, Obarzanke E, et al.
et al. Estimation of ten-year risk of Prevention. NHANES 2005–2006. http: A clinical trial of the effects of dietary
fatal cardiovascular disease in Europe: //www.cdc.gov/nchs/nhanes/nhanes200 patterns on blood pressure. DASH collab-
The SCORE project. Eur. Heart J. 5-2006/nhanes05_ 06.ht m orative research group. N. Engl. J. Med.
2003;24:987. 57. American College of Physicians. 1997;336:1117–1124.
41. New Zealand Guidelines Group. New Guidelines for using serum cholesterol, 71. Sacks FM, Svetkey LP, Vollmer WM, et
Zealand Cardiovascular Guidelines high density lipoprotein cholesterol, al. Effects of blood pressure of reduced
Handbook: A Summary Resource for and triglyceride levels as screening dietary sodium and Dietary Approaches
Primary Care Practitioners, 2nd ed. tests for preventing coronary heart to Stop Hypertension (DASH) diet.
Wellington, NZ, 2009. http://www.nzgg disease in adults. Ann. Intern. Med. DASH sodium collaborative research
.org.n z/guidelines/0154/CV D_Handboo 1996;124:515–517. group. N. Engl. J. Med. 2001;344:3–10.
k_June _2009_update.pd f 58. Smith Jr SC, Allen J, Blair SN, et al. 72. Philip B, Mellen PB, Gao SK, Vitolins
42. Ridker PM, Libby P, and Buring J. Risk AHA/ACC guidelines for secondary MZ, and Goff DC. Deteriorating dietary
markers and the primary prevention of prevention for patients with coronary and habits among adults with hypertension.
cardiovascular disease. In Braunwald E, other atherosclerotic vascular disease: DASH dietary accordance, NHANES
ed. Heart Disease, 10th ed. Philadelphia, 2006 update endorsed by the national 1988–1994 and 1999–2004. Arch.
PA: Elsevier, 2014. p. 891–934. heart, lung, and blood institute. J. Am. Intern. Med. 2008;168(3):308–314.
43. Annual smoking-attributable mortality, Coll. Cardiol. 2006;47:2130. 73. ACSM Physical Activity Guidelines.
years of potential life lost, and productiv- 59. Lichtenstein AH, Appel LJ, Brands M, et http: //www.acsm.org/public-informat
ity losses—United States, 1997–2001. al. Diet and lifestyle recommendations ion/acsm-journals/guidelines. Accessed
MMWR Morb. Mortal. Wkly. Rep. revision 2006. A scientific statement from January 4, 2017.
2005;54:625. the American heart association nutrition 74. Chiuve S, Albert C, and Conen D.
44. Annual smoking attributable mortality, committee. Circulation 2006;114:82–96. Arrhythmias in women: Atrial fibrillation
years of potential life lost, and eco- 60. Stone NJ, Robinson J, Lichtenstein and sudden cardiac death. In Goldman
nomic costs – United States, 1995–1999. AH, et al. 2013 ACC/AHA guideline MD, Troisi R, and Rexrode KM, eds.
MMWR Morb. Mortal. Wkly. Rep. on the treatment of blood cholesterol to Women and Health, 2nd ed. San Diego,
2004;51:300–302. reduce atherosclerotic cardiovascular CA: Academic Press, 2013. p. 1039–1053.
45. Reducing the Health Consequences of risk in adults: A report of the American 75. Kaplan NM. Systemic hypertension:
Smoking: 25 Years of Progress: A Report college of cardiology/American Heart Therapy. Braunwald’s Heart Disease: A
of the Surgeon General: 1989 Executive Association task force on practice Textbook of Cardiovascular Medicine,
Summary. http: //profi les.nlm.n ih.gov/ps/ guidelines. Circulation 2013. doi: 10th ed. Elsevier, 2014.
access/NN BBXS.pdf. 01.cir.0000437738.63853.7a 76. Giannattasio C, Mangoni AA, Stella
46. Jha P, Ramasundarahettige C, Landsman 61. Ridker PM, Kastelein JJ, Genest J, ML, et al. Acute effects of smoking on
V, et al. 21 st-century hazards of and Koenig W. C-reactive protein and radial artery compliances in humans. J.
smoking and benefits of cessation in cholesterol are equally strong predic- Hypertens. 1994;12:691.
the United States. N. Engl. J. Med. tors of cardiovascular risk and both are 77. Eisenberg DM, Delbanco TL, Berkey CS,
2013;368(4):341–350. Epub 2013/01/25. important for quality clinical care. Eur. et al. Cognitive behavioral techniques for
47. Thun MJ, Carter BD, Feskanich D, et al. Heart 2013;34(17):1258–1261. hypertension: Are they effective? Am. J.
50-year trends in smoking-related mortal- 62. Ridker PM and Wilson PW. A trial-based Hypertens. 1993;4:416.
ity in the United States. N. Engl. J. Med. approach to statin guidelines. JAMA 78. Effects of Comprehensive Lifestyle
2013;368:351–364. 2013 Sep 18;310(11):1123–1234. Modification on Blood Pressure Control.
48. Jha P, Chaloupka FJ, Moore J, et al., eds. 63. James PA, Oparil S, Carter BL, et al. Main results of the PREMIER clinical
Disease Control Priorities in Developing 2014 evidence-based guideline for trial. JAMA 2003;289:2083–2093.
Countries, 2nd ed. New York, NY: Oxford the management of high blood pres- 79. The SPRINT Research Group. A random-
University Press, 2006. p. 869–885. sure in adults. Report from the panel ized trial of intensive versus standard
49. Centers for Disease Control and members appointed to the Eighth Joint blood-pressure control. N. Engl. J. Med.
Prevention. 2011 National Health National Committee (JNC 8). JAMA 2015;373:2103–2116.
Interview Study (NHIS) Public Use Data 2014;311(5):507–520. 80. Whelton PK, Carey RM, Aronow WS, et
Release: Division of Health Interview 64. Vasan RS, Beisor A, Seahandri S, et al. al. 2018 ACC/AH A/AAPA/ABC /ACPM /
Statistics. Atlanta, GA: National Center Residual lifestyle risk for developing AGS/APHA/ASH/A SPC/N MA/PC NA
for Health Statistics, 2012. hypertension in middle aged women guideline for the prevention, detection,
50. Johnston LD, O’Malley PM, and Bachman and men. The Framingham heart study. evaluation, and management of high
JG. Monitoring the Future: National JAMA 2002;287:1003–1010. blood pressure in adults. A report of
Survey Results on Drug Use, 1975–2005. 65. Sawicki PT and McGauran N. Have the American College of Cardiology/
Vol. I: Secondary School Students. ALLHAT, ANBP2, ASCOT-BPLA, and American Heart Association task force on
Rockville, MD: National Institutes of so forth improved our knowledge about clinical practice guidelines. Hypertension
Health, National Institute on Drug Abuse, better hypertension care? Hypertension 2018;71(6):1269–1324.
2005. NIH publication no. 99-4660. 2006;48:1. 81. Antithrombotic Trialists’ Collaboration.
51. A clinical practice guideline for treat- 66. Rippe J and Angelopoulos T. Obesity Collaborative meta-analysis of ran-
ing tobacco use and dependence: A US and Heart Disease. In Rippe JM domised trials of antiplatelet therapy for
publication health service report. The and Angelopoulos TA, eds. Obesity: prevention of death, myocardial infarc-
tobacco use and dependence clinical Prevention and Treatment. Boca Raton, tion, and stroke in high risk patients.
practice guidelines panel, staff, and FL: CRC Press, 2012. BMJ 2002;324:71.
consortium representatives. JAMA 67. National Education Blood Pressure 82. Gaspoz JM, Coxson PG, Goldman PA, et
1997;278:1759–1766. Education Program Work Group. al. Cost effectiveness of aspirin, clopido-
52. US Preventive Services Task Force. Guide National high blood pressure education grel, or both for secondary prevention of
to Clinical Preventive Services, 3rd ed. program working group report on pri- coronary heart disease. N. Engl. J. Med.
Rockville, MD: Agency for Healthcare mary prevention of hypertension. Arch. 2002;346:1800.
Research and Quality, 2000–2003. Intern. Med. 1993;153:186–208. 83. Berger JS, Roncaglioni MC, Avanzini
53. Bolin K, Lindgren B, and Willers S. The 68. Stepniakowski K and Egan BM. Additive F, Pangrazzi I, Tognoni G, and Brown
cost utility of bupropion in smoking ces- effects of obesity and hypertension DL. Aspirin for the primary preven-
sation health programs: Simulation model to limit venous volume. Am. J. Phys. tion of cardiovascular events in women
results for Sweden. Chest 2006;129:651. 1995;268:R562–R568. and men: A sex-specific meta-analysis
54. Stead LF, Perera R, Bullen C, et al. 69. U.S. Department of Health and of randomized controlled trials. JAMA
Nicotine replacement therapy for smok- Human Services and U.S. Department 2006;295(3):306–313.
ing cessation. Cochrane Database Syst. of Agriculture. 2015–2020 Dietary 84. Wolff T, Miller T, and Ko S. Aspirin for
Rev. 2008;23(1). Guidelines for Americans, 8th ed., the primary prevention of cardiovascular
55. Koh HK and Sebelius KG. Ending 2015. Available at http://health.gov/di events: An update of the evidence for the
the tobacco epidemic. JAMA etaryg uidelines/ 2015/guidelines /. Epub U.S. preventive services task force. Ann.
2012;308(8):767–768. December 2015. Intern. Med. 2009;150:405.
References 35
85. Manson JE, Willett WC, Stampler Treatment. Boca Raton, FL: CRC Press, on epidemiology and prevention, and
JM, et al. Body weight and mortal- 2012. council on cardiovascular nursing of the
ity among women. N. Engl. J. Med.
1995;333:677–685.
86. Rimm EB, Stampler MJ, Giovannucci
103. Rippe JM. Weight Loss that Lasts:
Break Through the 10 Big Diet Myths.
Hoboken, NJ: John Wiley & Sons, 2004.
American Heart Association. Circulation
2001;103:472.
120. Lindberg ML and Amsterdam EA.
2
B, et al. Body size and fat distribution 104. Apovian CM, Aronne LJ, Bessesen DH, Alcohol, wine, and cardiovascular health.
as predictors of coronary heart disease et al. Pharmacological management of Clin. Cardiol. 2008;31:347.
among middle-aged and older US men. obesity: An endocrine society clinical 121. Mosca L, Benjamin EJ, Berra K, et al.
Am. J. Epidemiol. 1995;141:1117–1127. practice guideline. J. Clin. Endocrinol. Effectiveness-based guidelines for the
87. Garrison RJ and Castelli WP. Weight Metab. 2015;100(2):342–362. prevention of cardiovascular disease
and thirty year mortality of men in the 105. Rippe JM and Angelopoulos TJ. Obesity: in women—2011 update. A guideline
Framingham Study. Ann. Int. Med. Prevention and Treatment. Boca Raton, from the American Heart Association.
1985;103:1006–1009. FL: CRC Press, 2012. Circulation 2011;123:1243–1262.
88. World Health Organization. Prevention 106. Johnston CA and Moreno JP. Managing 122. Hu FB and Willett WC. Optimal diets
and Management of the Global Epidemic childhood obesity. In Rippe JM for prevention of coronary heart disease.
of Obesity. Report of the WHO and Angelopoulos TJ, eds. Obesity: JAMA 2002;288:2569.
Consultation on Obesity No. 10. Geneva, Prevention and Treatment. Boca Raton, 123. Howard BV, Van Horn L, Hsia J, et al.
Switzerland: WHO, 1997. FL: CRC Press, 2012. Low-fat dietary pattern and risk of car-
89. Chan JM, Rimm EB, Colditz GA, et al. 107. Natarajan S, Liao Y, Cao G, et al. Sex diovascular disease: The women’s health
Obesity, fat distribution, and weight gain differences in risk for coronary heart initiative randomized controlled dietary
as a risk factor for clinical diabetes in disease mortality associated with diabetes modification trial. JAMA 2006;295:655.
men. Diabetes Care 1994;17:961–969. and established coronary heart disease. 124. de Lorgeril M, Salen P, Martin JL, et
90. Pouliot MC, Despres JP, Lemieux S, et Arch. Intern. Med. 2003;163:1735. al. Mediterranean diet, traditional risk
al. Waist circumference and abdominal 108. Franco OH, Steyerberg EW, Hu FB, et factors, and the rate of cardiovascular
sagittal diameter: Best simple anthro- al. Associations of diabetes mellitus with complications after myocardial infarc-
pometric indexes of abdominal visceral total life expectancy and life expectancy tion: Final report of the Lyon diet heart
adipose tissue accumulation and related with and without cardiovascular disease. study. Circulation 1999;99:779.
cardiovascular risk in men. Am. J. Arch. Intern. Med. 2007;167:1145. 125. Lavie CJ, Milani RV, Mehra MR, and
Cardiol. 1994;73:460–468. 109. Thomas DE, Elliott EJ, and Naughton Ventura HO. Omega-3 polyunsaturated
91. Eckel RH. Obesity and heart disease. GA. Exercise for type 2 diabetes mel- fatty acids and cardiovascular diseases. J.
A statement for healthcare profession- litus. Cochrane Database Syst. Rev. Am. Coll. Cardiol. 2009;54:585.
als from the Nutrition Committee, Hoboken, NJ: John Wiley & Sons 126. Eilat-Adar S, Mete M, Fretts A, et al.
American Heart Association. Circulation 2006;3:CD002968. Dietary patterns and their association
1997;96:3248–3250. 110. Mozaffarian D, Kamineni A, Carnethon with cardiovascular risk factors in a
92. Flegal KM, Carroll MD and Ogden M, et al. Lifestyle risk factors and new- population undergoing lifestyle changes:
CL. Prevalence and trends in obesity onset diabetes mellitus in older adults: The strong heart study. Nutr. Meta.
among US adults, 1999–2008. JAMA The cardiovascular health study. Arch. Cardiovasc. Dis. 2013; 23(6).
2010;303(3):235–241. Intern. Med. 2009;169:798. 127. American Dietetic Association. http://
93. Centers for Disease Control and 111. Buse JB, Ginsberg HN, Bakris GL, et www.eatright.org/. Accessed September
Prevention. National Center for Health al. Primary prevention of cardiovascular 8, 2011.
Statistics. http://www.cdc.gov/nchs/. diseases in people with diabetes mellitus: 128. Preventive Cardiovascular Nurses
94. Dietz WH and Robinson TN. Overweight A scientific statement from the American Association. http://www.pcna.net/.
children and adolescents. N. Engl. J. Heart Association and the American Accessed September 8, 2011.
Med. 2005;352:2100–2109. Diabetes Association. Circulation 129. Krebs-Smith S and Kris-Etherton P.
95. Kuczmarski RJ, Ogden CL, Grummer- 2007;115:114. How does mypyramid compare to other
Strawn LM, et al. CDC growth charts: 112. Centers for Disease Control and population based recommendations
United States. Adv. Data 2000;314:1–27. Prevention. Prevalence of diabe- for controlling chronic disease? JADA
96. Barlow SE. Expert committee recom- tes and impaired fasting glucose in 107;5:830–837.
mendations regarding the prevention, adults—United States, 1999–2000. 130. Mozaffarian D, Appel LJ, and Van
assessment, and treatment of child and MMWR. Morb. Mortal. Wkly. Rep. Horn L. Components of a cardiopro-
adolescent overweight and obesity [sum- 2003;52:833–837. tective diet: New insights. Circulation
mary report]. Pediatrics 2007;120(Suppl 113. The Finnish Diabetes Prevention Study. 2011;123(24):2870–2891.
4):S164–S192. http: //care.diabetesjournals.org/content 131. Estruch R, Ros E, Salas-Salvado J, et al.
97. Wilson P. Clustering of risk factors, obe- /26/12 /3230.full Primary prevention of cardiovascular
sity and syndrome X. Nutr. Clin. Care 114. The Look AHEAD Research Group. disease with a Mediterranean diet. N.
1998;1(Suppl):44–55. Cardiovascular effects of intensive life- Engl. J. Med. 2013;368(14):1279–1290.
98. Ford ES, Giles WH, and Dietz WH. style intervention in type 2 diabetes. N. Epub 2013/02/26.
Prevalence of the metabolic syndrome Engl. J. Med. 2013;369:145–154. 132. Drusseldorp E, van Elderen T, Maes
among US adults: Findings from the third 115. A Report of the Surgeon General on S, et al. A meta-analysis of psycho
national health and nutrition examina- Physical Activity and Health. Rockville, educational programs for coronary
tion survey. JAMA 2002;287(3):356–359. MD: US Department of Health and heart disease patients. Health Psychol.
99. Tumoilehto J, Lindstrom J, Eriksson JG, Human Services, Centers for Disease 1999;18:506–519.
et al. Prevention of type 2 diabetes melli- Control, 1999. 133. Lloyd-Jones D, Adams RJ, Brown TM,
tus by changes in lifestyle among subjects 116. Physical activity trends – United States, et al. Heart disease and stroke statis-
with impaired glucose tolerance. N. Engl. 1990–1998. MMWR. Morb. Mortal. tics—2010 update: A report from the
J. Med. 2001;344:1343–1350. Wkly. Rep. 2001;50:166–169. American Heart Association. Circulation
100. Knowler WC, Barrett-Connor E, Fowler 117. Fletcher G, Blair S, Blumenthal J, et 2010;121:e46.
SE, et al. For the diabetes prevention al. AHA medical/scientific statement. 134. Magliano DJ, Rogers SL, Abramson MJ,
program research group. Reduction in the Statement of exercise. Benefits and and Tonkin AM. Hormone therapy and
incidence of type 2 diabetes with lifestyle recommendations for physical activity cardiovascular disease: A systematic review
intervention or metformin. N. Engl. J. programs for all Americans. Circulation and meta-analysis. BJOG 2006;113:5.
Med. 2002;346:393–403. 1992;86:340–344. 135. Mosca L, Banka CL, Benjamin EJ, et al.
101. Wadden TA, Butryn MI, and Ryme KJ. 118. 2008 Physical Activity Guidelines for Evidence-based guidelines for cardiovas-
Efficacy of lifestyle modification for Americans. Washington, DC. www. cular disease prevention in women: 2007
long-term weight control. Obes. Res. health.gov/paguidelines. update. Circulation 2007;115:1481.
2004;12(Suppl):151 S–162 S. 119. Goldberg IJ, Mosca L, Piano MR, 136. Hsia J, Langer RD, Manson JE, et
102. Johnston CA, Moreno JL, and Foreyt and Fisher EA. AHA science advi- al. Conjugated equine estrogens and
JP. Behavioral management of the obese sory: Wine and your heart: A science coronary heart disease: The women’s
patient. In Rippe JM and Angelopoulos advisory for healthcare professionals health initiative. Arch. Intern. Med.
TJ, eds. Obesity: Prevention and from the Nutrition Committee, council 2006;166:357.
36 Chapter 2 Lifestyle Strategies for Risk Factor Reduction, Prevention and Treatment of Cardiovascular Disease
137. Ockene IS and Ockene JK. Prevention of Lifestyle Medicine, 2nd ed. Boca Raton, 144. Morton DP, Kent L, Rankin P, et al.
Coronary Heart Disease. Boston: Little, FL: CRC Press, 2013;35–47. Optimizing the intensity of life-
Brown, 1992. 141. Dysinger W. LM practice: Exploring style medicine interventions: Similar
138. Prochaska JO. Changing for Good. New workable models. Am. J. Lifestyle Med. outcomes for half the sessions.
York, NY: Avon Books, 1994. 2017;12:345–347. Am. J. Lifestyle Med. 2015. doi:
139. Linke SE, Robinson CJ, and Pekmezi 142. Frates EP and Bonnet J. Collaboration 1559827615612420.
D. Psychological theories to promote and negotiation: The key to therapeutic 145. Rippe J (moderator), Boone R, Mechley
healthy lifestyles. Am. J. Lifestyle Med. lifestyle change. Am. J. Lifestyle Med. A, Parkinson M, Porter R, and Shurney
2013;8(1):4–14. 2016;10(5). D. American College of lifestyle
140. O’Neil CE and Nicklas TA. Nutrition 143. Berwick DM. Making good on ACO’s medicine expert panel discussion:
Interventions for Cardiovascular promise—The final rule for the medi- Lifestyle medicine continued growth
Disease: Behavioral and Educational care shared savings program. NEJM and evolution. Am. J. Lifestyle Med.
Considerations. In Rippe JM, ed. 2011;265:1753. 2016;10(5):290–301.
3
CHAPTER
3.1 Physical Fitness Vs. Physical Activity..................................... 38 3.9.2 Preventing Weight Gain............................................. 43
3.2 General Recommendations for Physical Activity.................... 38 3.9.3 Physical Activity and Sustained Weight Loss............. 43
3.2.1 Adults......................................................................... 39 3.9.4 How Much Physical Activity Is Required for
3.2.2 Children and Adolescents............................................ 39 Sustained Weight Loss?������������������������������������������� 44
3.2.3 Older Adults................................................................ 39 3.9.5 Resistance Training and Weight Loss........................ 44
3.3 Women and CHD................................................................... 39 3.10 Lipids................................................................................. 44
3.4 Stroke.................................................................................. 40 3.11 Metabolic Syndrome........................................................... 45
3.5 Hypertension........................................................................ 40 3.11.1 Different Medical Society Definitions of the
3.5.1 Resistance Exercise Training and Blood Pressure...........41 Metabolic Syndrome���������������������������������������������� 45
3.6 Heart Failure......................................................................... 41 3.11.2 Current Prevalence Estimates................................. 45
3.7 Diabetes............................................................................... 41 3.11.3 Physical Activity and Prevalence of the
3.7.1 The Metabolic Syndrome, CVD, and T2DM................... 41 Metabolic Syndrome���������������������������������������������� 45
3.7.2 Glycemic Control........................................................ 42 3.11.4 Cardiorespiratory Fitness and the Metabolic
3.7.3 Strength Training........................................................ 42 Syndrome�������������������������������������������������������������� 47
3.8 Obesity................................................................................. 42 3.11.5 Muscular Strength and the Metabolic Syndrome........47
3.9 Central Adiposity, Inflammation, and CVD.............................. 43 3.12 Conclusion.......................................................................... 47
3.9.1 The “Fitness vs. Fatness” debate................................ 43 References.................................................................................. 47
Cardiovascular disease (CVD), as defined by the Centers modest amounts of physical activity compared with the
for Disease Control and Prevention (CDC), encompasses most physically inactive, 3 even relatively small increases
coronary heart disease (CHD), stroke, hypertension, and in physical activity could result in a significant decrease
heart failure.1 CVD accounts for nearly one in three deaths in CHD for a large portion of the American population.
in the United States. Approximately 2,150 Americans die For example, epidemiological data suggest that the esti-
from some manifestation of CVD every day—roughly one mated 2.3% decline in physical inactivity between 1980
every 40 seconds.1 CVD has been the leading cause of and 2000 prevented or at least postponed 17,445 deaths
death since 1900 and remains so despite a decades-long due to CHD in the United States.4
decline in CVD mortality.1 In spite of the overwhelming evidence implicating
It’s predicted that some 635,000 Americans will physical inactivity as an important and significant risk
experience a first myocardial infarction this year, and factor for CHD, fewer than half of adults meet even the
approximately 300,000 will be victims of a reinfarc- minimum recommendation for aerobic exercise.5 Statistics
tion.1 It’s estimated that another 155,000 infarctions will for young people are even more alarming, with fewer than
be “silent,” with no symptoms or with symptoms other 20% of adolescents performing the recommended 60 min-
than angina which are missed or ignored.1 Collectively, utes or more of daily physical activity.6
this means that an American experiences a coronary event Despite the documented lack of physical activity in the
every 34 seconds. Compared to those who are very physi- United States, and the well-established benefits of regu-
cally active, the risk of CHD in sedentary individuals is lar exercise, many physicians are not encouraging their
150 to 240% higher.1 Unfortunately, only about a quarter patients to exercise and lose weight.7–9 Of equal impor-
of all Americans engage in enough exercise to meet the tance, they do not appear to be adequately prepared to
minimum standards of the Centers for Disease Control provide recommendations for exercise and physical activ-
and Prevention (CDC): at least 150 minutes per week of ity. For example, a survey of 175 primary care physicians
moderate-intensity aerobic exercise or at least 75 minutes revealed that only 12% were aware of the recommenda-
of vigorous exercise and muscle-strengthening activities at tions of the American College of Sports Medicine (ACSM)
least two days per week. 2 Given that the greatest reduction for physical activity.9 An evaluation of 51 internal medi-
in risk for CHD appears to be for those engaging in even cine residents reported that while 88% were confident in
37
38 Chapter 3 Physical Activity and Fitness in the Prevention of Cardiovascular Disease
Physical fitness, specifically cardiorespiratory fitness, is found that the risk of CHD or CVD decreased linearly
defined here as the ability to deliver and utilize oxygen with increasing percentiles of physical activity. He also
during sustained activity and typically quantified as maxi- found that the reduction in risk for CHD or CVD associ-
mal oxygen uptake (VO2max). When respiratory gases are ated with increasing percentiles of physical fitness dem-
measured with a metabolic cart during a maximal graded onstrated a precipitous decrease occurring just before
exercise test, VO2max is valid and reliable. However, sub- the 25th percentile of the physical fitness distribution.
maximal tests or those relying on indirect measures such Further, at all percentiles ≥ 25th, the reduction in risk for
as time to exhaustion are subject to considerable error. CHD and CVD was significantly greater for physical fit-
Measures of physical activity, on the other hand, usu- ness compared to physical activity (Figure 3.1).
ally rely on retrospective self-reported data (i.e., physical These findings are supported in a more recent com-
activity questionnaires). Non-vocational or leisure-time parison of fitness versus physical activity in predicting
physical activity (LTPA) is most commonly assessed. all-cause mortality in a cohort of 842 men referred for
Vocational physical activity, household chores, and bik- exercise testing.12 While both physical activity and fitness
ing or walking to work are also sometimes quantified but were strong predictors of all-cause mortality, physical fit-
less often. The definitions of physical activity vary greatly ness was a stronger predictor of mortality than activity
from study to study, and the components of physical activ- level. A 1000 kcal per week increase in physical activity
ity or exercise such as intensity, duration, and frequency was found to be similar to a one MET (metabolic equiva-
are often not reported or inadequately assessed. lent; oxygen uptake of 3.5 ml . kg−1 . min−1) improvement
The categorization of physical activity (i.e., low, mod- in fitness, with both conferring a 15–20% reduction in
erate, or high) also varies from study to study. Many mortality. Of equal, if not greater, interest is the fact that
studies use different criteria for moderate and vigorous- these data also demonstrated that 40% of the reduction in
intensity exercise or activity. ACSM defines moderate mortality occurred between the least active or fit and the
physical activity as any activity requiring 50–70% of next least fit or active groups, suggesting that even modest
VO2max or maximal heart rate.11 Vigorous physical activ- increases in physical activity or fitness, especially in those
ity is anything greater than 70% VO2max or maximal who are inactive, may result in a significant reduction in
heart rate.11 Walking or brisk walking is generally recom- mortality.
mended as the type of exercise that meets the criteria for
moderate physical activity. However, it is important to
understand that the intensity of walking, or any exercise
for that matter, is relative to an individual’s age, physi-
3.2 GENERAL RECOMMENDATIONS
cal condition, and fitness level. For example, based on the FOR PHYSICAL ACTIVITY
ACSM Guidelines for Exercise Testing and Prescription,11
even brisk walking may not be of sufficient intensity to In 1996, the Surgeon General’s Report on Physical Activity
meet the minimum criteria for moderate physical activity and Health recommended “people of all ages [should]
in a normal, healthy individual of college age. Conversely, include a minimum of 30 minutes of physical activity of
brisk walking might be considered vigorous activity for moderate intensity (such as brisk walking) on most, if
someone over the age of 65. As such, any exercise recom- not all, days of the week. It is also acknowledged that for
mendations should be applied relative to the individual’s most people, greater health benefits can be obtained by
capabilities and limitations. engaging in physical activity of more vigorous intensity
Surprisingly, physical fitness has been shown to be or of longer duration.”14 More recently, the 2008 Physical
only modestly correlated with physical activity, with cor- Activity Guidelines for Americans15 provide updated and
relations ranging from 0.0912 to 0.60.13 In a meta-analysis more specific recommendations for different age groups
of seven physical fitness and 16 physical activity cohorts and some clinical populations. Below is a very brief sum-
cited in the 1996 Surgeon General’s Report,14 Williams5 mary of their recommendations.
3.3 Women and CHD 39
3
more days per week. 5
• All adults should avoid inactivity. Some physical Although a greater exercise volume and/or intensity
activity is better than none, and adults who partici- appears to produce greater health benefits for most peo-
pate in any amount of physical activity gain some ple, the literature examining the relationship between
health benefits. exercise intensity and risk for CHD is not unequivocal. 3
• For substantial health benefits, adults should do A meta-analysis of 16 gender-specific physical activity
at least 150 minutes a week of moderate-intensity cohorts found that the risk for CHD decreased linearly
or 75 minutes a week of vigorous-intensity aerobic with increasing percentiles of physical activity, but exam-
physical activity, or an equivalent combination of ination of the individual cohorts revealed considerable
moderate- and vigorous-intensity aerobic activity. variation in the outcomes. 3 Specifically, there is evidence
• Adults should also do muscle-strengthening activi- to suggest that the dose-response relationship between
ties that are moderate or high intensity and involve exercise intensity and risk for CHD or mortality may dif-
all major muscle groups on two or more days a week, fer between men and women.16–20 For example, based on
as these activities provide additional health benefits. data from the Nurses’ Health Study, a cohort of 72,488
female nurses 40 to 65 years old, Manson et al.17 con-
cluded that “the reduction in risk for CHD for women
3.2.2 Children and Adolescents who walked at a brisk pace three or more hours per
• Children and adolescents should do 60 minutes (one week was similar to those women who engaged in regu-
hour) or more of physical activity daily. lar vigorous (≥6 MET) exercise.” In 2001, data from the
• Aerobic: Most of the 60 or more minutes a day Women’s Health Study16 showed that walking one to 1.5
should be either moderate- or vigorous-intensity aer- hours per week was associated with a 51% reduction in
obic physical activity, and should include vigorous- risk for CHD, but walking ≥ 2 hours per week conferred
intensity physical activity at least three days a week. no greater reduction in risk. More vigorous activity was
• It is important to encourage young people to par- not associated with a lower risk for CHD, (comparing
ticipate in physical activities that are appropriate for highest with lowest). Similarly, the relationship between
their age, that are enjoyable, and that offer variety. walking pace and risk for CHD did not demonstrate a
linear trend.
Other studies have not demonstrated an association
between physical activity/inactivity and CHD and/or
3.2.3 Older Adults mortality in women, with one review reporting no rela-
• When older adults cannot do 150 minutes of mod- tionship between physical inactivity and CHD in 10 of 14
erate-intensity aerobic activity a week because of studies.18 More recently, Blair et al.19 found that all-cause
chronic conditions, they should be as physically mortality rates in women did not differ across the range of
active as their abilities and conditions allow. physical activity levels. The Framingham Study also found
• Older adults should do exercises that maintain or no association between physical activity level and mor-
improve balance if they are at risk of falling. tality in women. 20 In contrast, a 2004 meta-analysis of
• Older adults should determine their level of effort 30 longitudinal studies examining the impact of physical
for physical activity relative to their level of fitness. activity on the risk for CVD in women showed a dose-
• Older adults with chronic conditions should under- response relationship with a 20–40% reduction in risk for
stand whether and how their conditions affect their CVD in the most active women, compared to those who
ability to do regular physical activity safely. were sedentary. 21
This inconsistency in findings has been observed
elsewhere17 and may be the result of real gender differ-
3.3 WOMEN AND CHD ences or may reflect differences in study participants and/
or design. For example, in the 16 studies he examined,
One in three women have some form of CVD; 6.6 million Williams3 found that the intervals (tertiles, quartiles, etc.)
have been diagnosed with CHD.1 In 2013 alone, 398,086 reported differed greatly, with nine studies using three
women died from CVD—about one death every 80 sec- levels, six using four levels and one study using six lev-
onds.1 Just over 40% of these deaths was attributable to els. In particular, the apparent gender differences in the
CHD, including 50,742 from MI.1 On average, new and response to physical activity may also be mediated by
recurrent MI as well as fatal CHD impact 405,000 women the physical activity levels of the study participants. As
each year.1 Because women typically have heart attacks at an example, in 2001, the most active 20% of women in
older ages than men do, they’re more likely to die from the Women’s Health Study expended ≥ 1500 kcal per week
them within a few weeks.1 in LTPA, whereas men in the highest quintile of physi-
Despite these overwhelming statistics, surveys indicate cal activity in the Harvard Alumni Health Study reported
that some 44% of women still do not know that CHD expending ≥ 3129 kcal per week in LTPA.3 Interestingly,
is by far the number one killer of women in the United very recent physical activity data acquired by accelerome-
States.1 And while regular physical activity has been ter from over 17,000 older women in the Women’s Health
demonstrated to significantly reduce the risk of CVD in Study showed a clear dose-response relationship between
women, they are on average less physically active than time engaged in “moderate to vigorous” physical activ-
men, with only 46.1% of women compared with 54.2% ity. 22 Those women who exercised just over an hour per
40 Chapter 3 Physical Activity and Fitness in the Prevention of Cardiovascular Disease
day at this intensity had mortality rates almost 65% lower intense aerobic physical activity for at least 30 minutes
than women who were sedentary. per day to reduce the risk of ischemic stroke. 27 While
The limited data on the relation between physical fit- there is evidence that greater muscular strength in youth
ness and risk for CVD and/or mortality in women suggests is associated with a modestly reduced risk (~ 5–10%) for
a greater similarity with studies of men, when compared stroke later in life, 28 the relationship between muscular
with studies of physical activity. A relatively recent review strength, strength training, and stroke risk remains virtu-
of the literature revealed that low exercise capacity and ally unexplored.
slow recovery heart rate predicted CVD and mortal-
ity in both men and women. 23 Data from the St. James
Women Take Heart Project demonstrated a 17% reduc- 3.5 HYPERTENSION
tion in mortality in women for every one MET increase in
exercise capacity. 24 As such, it would appear that women Based on data from the National Health and Nutrition
who engage in exercise vigorous enough to improve aero- Examination Survey (NHANES), it’s estimated that some
bic fitness gain health benefits comparable to their male 80 million adults or almost one in three American adults
counterparts. suffer from hypertension (systolic blood pressure (SBP)
≥140 mmHg and/or diastolic blood pressure (DBP) ≥90
mmHg).1 The prevalence in African-American adults is
3.4 STROKE among the highest in the world. Looking at all Americans
with hypertension, 82.7% were aware of it, 76.5% were
While the incidence of stroke and its associated mortal- being treated, and only 54.1% had it under control.
ity rate has been declining since at least 2001, it is esti- A meta-analysis of 61 studies involving more than one
mated that 795,000 people in the United States experience million individuals demonstrated that mortality associ-
a new (~ 610,000) or recurrent (~ 185,000) stroke each ated with both ischemic heart disease (IHD) and stroke
year.1 Of these, the large majority are ischemic (~ 87%), increases linearly from levels as low as 115 mmHg sys-
with the remainder being hemorrhagic in nature.1 The tolic and 75 mmHg diastolic blood pressure. 29 For every
risk of a stroke for African-Americans is nearly double 20 mmHg systolic or 10 mmHg diastolic increase in blood
that for Caucasians and tends to occur at a younger age.1 pressure, there is a doubling of mortality from both IHD
Hispanics, particularly Mexican-Americans, have signifi- and stroke. 29 Those with hypertension have a shorter life
cantly higher rates of ischemic stroke and at a younger expectancy, shorter life expectancy free of CVD, and can
age.1 Annually, 55,000 more women than men have a expect to live more years with CVD compared with those
stroke, with the incidence in women aged 45–54 years who are normotensive.1
especially high.1 Regular physical activity has been shown to be an
Some 200,000 to 500,000 transient ischemic attacks effective way to lower blood pressure in 75% of persons
(TIAs) are estimated to occur in the United States with hypertension.30,31 Compared with sedentary adults,
each year, and the incidence is higher in men, African- those who are physically active have a lower incidence
Americans, and Mexican-Americans.1 The occurrence of of hypertension, 32–34 with blood pressures that average
a TIA increases the risk of a stroke both in the short term five mmHg lower.35 Higher levels of occupational and/
and the long term.1 Approximately 15% of all strokes are or LTPA are associated with lower BP.30,34,35 These data
preceded by a TIA, and about 12–13% of individuals will have led to recommendations for regular physical activity
die within a year of a TIA.1 as lifestyle therapy for the prevention and management of
The most important risk factors for stroke include hypertension.
a history of TIA, preexisting CHD, age, hypertension, The Seventh Report of the Joint National Committee
diabetes mellitus, cigarette smoking, and atrial fibrilla- on Prevention, Detection, Evaluation, and Treatment of
tion.1 Physical inactivity has also been shown to increase High Blood Pressure (JNC VII)36 recommends regular
the risk of a stroke and stroke mortality, but its relation- aerobic physical activity such as brisk walking at least 30
ship to cerebral events is less well understood than that min per day most days of the week for the prevention and
for CHD.1 Meta-analyses have shown that the reduction management of hypertension. In a meta-analysis of 44 tri-
in risk for stroke associated with aerobic exercise/activ- als of at least four weeks duration and after controlling
ity ranges between 20 and 40% depending on the type for other factors, increased physical activity was associ-
of stroke and study design. 25,26 The benefit for women is ated with a small but significant decrease of 3/2 mmHg
less clear and may not be as great as that for men.25 It in normotensive subjects and 7/6 mmHg in hypertensive
remains unresolved as to whether or not a dose-response subjects.37 The training intensity in these studies averaged
relationship exists between level of physical activity and 65% of heart rate or VO2 reserve. However, the charac-
stroke risk. While those studies that looked at different teristics of the training programs (intensity, duration, and
levels of physical activity generally found a greater benefit frequency) explained less than 5% of variance in blood
for higher levels of physical activity, there was a real lack pressure response. Weekly energy expenditure was not
of consistency their findings. 25 In addition, the criteria significantly related to the changes in systolic or diastolic
for different levels of physical activity are not uniform, blood pressure. Vigorous exercise was not found to be
varying from study to study and often poorly quantified. different from moderate-intensity exercise in its ability
As such, an exercise prescription to optimize the reduc- to reduce blood pressure, with some studies showing that
tion in risk for stroke remains undetermined. Currently, exercise at 40% of VO2 reserve to produce a greater reduc-
the American Heart Association recommends moderately tion in systolic blood pressure than exercise at 65 to 75%
3.7 Diabetes 41
of VO2 reserve.38,39 As such, and per JNC VII, regular individuals whose LTPA exceeded 1,000 MET . min/week
3
moderate-intensity exercise is recommended for the pre- had a risk for heart failure that was 19% less than that of
vention and management of hypertension. their sedentary counterparts. 50
that 43% of new cases of diabetes could be prevented by • For long-term maintenance of major weight loss
watching TV less than 10 hours per week and engaging in (≥13.6 kg or 30 lb), larger volumes of exercise (seven
brisk walking for 30 minutes or more per day.71 Modest hours per week of moderate or vigorous aerobic
improvements in diet and exercise habits have been shown physical activity) may be helpful.
to reduce the incidence of T2DM even in those at highest • Unless contraindicated, people with type 2 diabetes
risk for developing it—those with IFG and/or IGT.74 –76 should be encouraged to perform resistance exercise
three times per week, targeting all major muscle
groups. This should progress to three sets of eight to
3.7.2 Glycemic Control ten repetitions at a weight that cannot be lifted more
than eight to ten times. Initial supervision and peri-
Studies of aerobic exercise training have shown signifi- odic reassessments by a qualified exercise specialist
cant but modest reductions in glycosylated hemoglobin are recommended to ensure that resistance exercises
(HbA1c, long-term index of glycemic control) of about 8% are performed correctly in order to maximize health
from baseline.77,78 The exercise intensity in these studies benefits and minimize the risk of injury.
accounted for almost 83% of the differences in post-inter-
vention HbA1c compared to 21% determined by exercise
volume. Those interventions with an intensity > 65% of
VO2max demonstrated the greatest improvement in HbA1c. 3.8 OBESITY
As such, exercise interventions for glycemic control should
Based on the most recent data from the National Health
include some vigorous exercise.79
and Nutrition Examination Survey (NHANES), and
using body mass index (BMI, body weight in kg/(height
in meters)2) as the criterion measure, the prevalence of
3.7.3 Strength Training overweight and obesity in the United States decreased
Resistance training, especially in combination with aer- among those of higher socioeconomic status but increased
obic exercise training, can significantly improve HbA1c among those of lower socioeconomic status.1 The over-
levels, fasting blood glucose, and insulin sensitivity.80 all prevalence of extreme obesity in U.S. youth continues
Additionally, other risk factors such as blood pressure to increase, especially among adolescent boys. In adults,
have been shown to be significantly reduced in diabetics overweight is defined as a BMI of 25–29.9 kg/m 2 . Obesity
with a program combining strength and aerobic train- is defined as a BMI ≥ 30; extreme (formerly morbid) obe-
ing compared with either aerobic or resistance training sity is defined as a BMI ≥ 40. Overall, 69% of U.S. adults
alone.80 As such, the American Diabetes Association were overweight or obese (73% of men compared to 65%
now recommends strength training, in addition to aero- of women).1 Among men, non-Hispanic blacks were less
bic exercise training, as part of a program to prevent or likely to be overweight or obese (69%) compared with
manage T2DM.81 Weight training has been found to be Hispanics (80%) and non-Hispanic whites (73%).1 In
safe in persons with CVD, ST depression, myocardial women, non-Hispanic blacks (82%) and Hispanics (76%)
ischemia, ventricular dysrhythmias, and other cardiovas- were much more likely to be overweight or obese com-
cular complications.81 The myocardial demands of high- pared with non-Hispanic whites (61%).1 Among all U.S.
intensity weight training are comparable to activities such adults, 35% were obese (34% of men vs. 36% of women).1
as stair-climbing, walking uphill, or carrying 20–30 lbs Hispanic and non-Hispanic black males (38%) were
of groceries.81 more likely to be obese than non-Hispanic white men
Below are some of the specific recommendations from (34%).1 Among women, non-Hispanic blacks (58%) and
the American Diabetes Association Consensus Statement Hispanics (43%) were more likely to be obese than non-
on Physical Activity/Exercise and Type II Diabetes:81 Hispanic whites (33%).1
Over the last two decades, it has become increasingly
• People with IGT should begin and continue a pro- apparent that abdominal adipose tissue has unique meta-
gram of weight control, including at least 150 min- bolic properties and may be more predictive of CVD, the
utes per week of moderate-to-vigorous physical metabolic syndrome, and diabetes than BMI or measures
activity and a healthful diet with modest energy of overall adiposity.82–86 Abdominal or central obesity
restriction. is most commonly assessed measuring by waist circum-
• To improve glycemic control, assist with weight ference or waist-to-hip ratio (WHR). From 1988–1994
maintenance, and reduce risk for cardiovascular dis- to 1999–2000 (most recent data available), mean waist
ease (CVD), the panel recommends 150 minutes per circumference of adult Americans increased from 95.3
week or more of moderate-intensity aerobic physical cm to 98.6 cm in males and from 88.7 cm to 92.2 cm in
activity and/or 90 minutes per week or more of vig- females.87
orous aerobic exercise. The physical activity should Despite these rather alarming trends, only 40.3% of
be distributed over at least three days per week, with obese patients were advised to lose weight by their fam-
no more than two consecutive days without physical ily physician in 2004, down from 42.3% in 1994.88 An
activity. evaluation of an academic pediatric hospital found that
• Compared with lower volumes of activity, perform- little more than half (53%) of the children who met the
ing at least four hours per week of moderate-to-vig- NHANES criteria for overweight (>95th percentile for
orous aerobic and/or resistance exercise is associated BMI) were identified as such by their primary care phy-
with greater CVD risk reduction. sician.89 Interestingly, while a majority (69%) of the
3.9 Central Adiposity,Inflammation, and CVD 43
children’s charts contained an “adequate” dietary history, these factors or how they interact. An extensive review of
3
only 15% included information regarding physical activ- the literature addressing the fitness vs. fatness debate as
ity and/or television watching. it pertains to CHD and/or CVD concluded that a “physi-
cally active lifestyle and/or a moderately high fitness level
(i.e., not in the bottom 20% of the population) reduces
3.9 CENTRAL ADIPOSITY, the risk of CVD/CHD in overweight or obese persons.”113
While they suggest that overweight or obese individuals
INFLAMMATION, AND CVD who are physically fit or active have levels of risk that
approach those associated with those of lean, unfit per-
Atherosclerosis has now come to be understood as an sons, they also concede that their risk is still greater
inflammatory disease.90 –93 A growing body of evidence fur- than those who are fit/active and of normal weight. The
ther demonstrates that greater adipose tissue mass, espe- authors further observed that the risk reduction associ-
cially visceral adipose tissue, directly contributes to systemic ated with increased fitness or activity is greater in those
inflammation.94–96 The pro-inflammatory state associated who are overweight or obese compared with those of nor-
with abdominal obesity has been proposed as a common mal weight. Finally, they recommend that physical activ-
underlying condition linking CVD, insulin resistance/type ity should be encouraged, regardless of whether or not
2 diabetes, and the metabolic syndrome.97–99 A complete that activity induces weight loss. This recommendation
discussion of the complex physiology and mechanisms of is supported by the majority of the studies reviewed that
adipose-related inflammation is beyond the scope of this found physical activity/fitness to be independent risk fac-
chapter. However, it can be stated that it is increasingly tors for CHD/CVD.
evident that visceral adipose tissue secretes a veritable host Addressing obesity begins with the understanding that
of pro-inflammatory cytokines. Greater levels of central weight gain is caused by a cumulative positive energy bal-
adiposity have been shown to be associated with higher ance where energy intake exceeds energy expenditure.
circulating levels of these pro-inflammatory proteins, such As such, weight loss can only occur in the presence of a
as interleukin-6 (IL-6), tumor necrosis factor–alpha (TNF- negative energy balance. Maintenance of body weight,
alpha), and C-reactive protein (CRP).100 –102 therefore, requires that energy intake matches energy
A published review of lifestyle interventions and sys- expenditure. While the concept of energy balance or
temic inflammation observed that 9 of 12 studies reviewed imbalance is conceptually simple, the respective roles of
demonstrated an inverse relationship between physical diet and exercise in weight loss and management is less
activity or fitness and markers of inflammation, after clear. Below is a brief summary of recent and relevant
controlling for BMI or other measures of adiposity.103 investigations of the role of physical activity in (1) prevent-
For example, in a 20-year follow-up of 4,252 elderly men ing weight gain, (2) causing weight loss, and (3) maintain-
(aged 40–59 at baseline), Wannamethee et al.104 found ing weight loss.
that physical activity level was inversely associated with
levels of CRP and other inflammatory markers, even after
adjusting for BMI and other covariates. In those men who 3.9.2 Preventing Weight Gain
went from “at least lightly active” to inactive, the levels
of these markers were similar to those men who had been In 2003, the International Association for the Study of
inactive throughout the follow-up period. Those who were Obesity (IASO) released the following statement regard-
inactive at baseline but increased their level of activity had ing physical activity and prevention of unhealthy weight
levels similar to those men who had remained continu- gain: “The current physical activity guideline for adults of
ously active. 30 minutes of moderate intensity activity daily, preferably
The HERITAGE Family Study examined the effects of all days of the week, is of importance for limiting health
20 weeks of exercise training on C-reactive protein (CRP) risks for a number of chronic diseases including coro-
levels in 652 sedentary, but healthy, adults.105 The training nary heart disease and diabetes. However for preventing
program was performed on cycle ergometers three days weight gain or regain this guideline is likely to be insuf-
per week progressing to 50 minutes at 75% of baseline ficient for many individuals in the current environment.
VO2max. This protocol resulted in a substantial (17.8%) There is compelling evidence that prevention of weight
increase in VO2max. However, reduction in CRP levels regain in formerly obese individuals requires 60–90 min-
occurred only in the individuals with high baseline levels utes of moderate intensity activity or lesser amounts of
of CRP. The positive relationship between baseline CRP vigorous intensity activity … For children, even more
levels and exercise-induced changes has been observed activity time is recommended. A good approach for many
elsewhere106 and may explain, at least in part, why some individuals to obtain the recommended level of physical
studies have not found that an exercise intervention activity is to reduce sedentary behavior by incorporating
reduces levels of inflammatory markers.107–112 more incidental and leisure-time activity into the daily
routine.”114
calorie restrictive diet, as an effective means to produce of calorie deficit, it does not appear to be able to prevent
short-term weight loss.115–117 However, physical activity the decrease in resting energy expenditure associated with
appears to play a major role in long-term maintenance of weight loss.120,122 In the absence of a dietary intervention,
weight loss.115–118 An extensive review of the role of exer- some studies have shown that high-intensity resistance
cise in promoting weight loss combined data sets and used training can significantly increase resting energy expendi-
weighted mean differences (WMD) to explore the efficacy ture for 16 hours or more.123–127 However, these findings
of exercise interventions.118 The randomized clinical trials are based on a very small number of subjects and are not
(RCTs) in this review only included studies that incorpo- supported by the results of other investigations.128–130 As
rated a follow-up of at least 12 months’ duration to assess such, in the absence of stronger evidence, resistance train-
long-term maintenance of weight loss. A summary of their ing is not recommended as the primary form of exercise
findings follows: to promote or enhance weight loss.120 However, weight
training may provide an advantage in maintaining fat-free
• Compared to diet alone, diet plus exercise pro- mass and enhancing body composition with a weight loss
duced significantly greater weight loss at 12 months intervention.120
(WMD = −1.95 kg),18 months (WMD = −7.83 kg),
and 36 months (WMD = −8.22 kg). In addition,
there were small but significantly greater differ-
ences/improvements in HDL and triglycerides at 12
3.10 LIPIDS
months. At 18 months, diet plus exercise demon- The role of blood lipids in the pathology of atheroscle-
strated large and significantly greater reductions in rosis is well established, and dyslipidemia is understood
systolic blood pressure (WMD = −8.90 mm Hg) and to be an important contributing factor for CHD.131
diastolic blood pressure (WMD = −12.10 mm Hg). Dyslipidemia includes elevations in total cholesterol (TC),
• A separate analysis in this review compared diet plus low-density lipoprotein cholesterol (LDL-C), and tri-
behavior therapy with diet plus behavior therapy glycerides (TG), and low levels of high-density lipopro-
and exercise. The addition of exercise produced sig- tein cholesterol (HDLC).131 In addition, newer lipid and
nificantly greater weight loss at 12 months (WMD lipoprotein measures such as lipoprotein particle size and
= −3.02 kg) and at 24 months (WMD = −2.16 kg). number, apolipoproteins, and triglyceride-rich lipopro-
There were no significant differences between teins (TRL) are emerging as risk factors that may also
groups for cholesterol, blood pressure, or glucose. increase CVD risk.132 The National Cholesterol Education
Program Adult Treatment Panel III has published guide-
These data suggest that regular physical activity is lines establishing lipid and lipoprotein modification goals
advantageous for sustained weight loss. for both primary and secondary prevention.131 However,
data from NHANES indicate that many Americans
have not achieved recommended levels for all lipids and
3.9.4 How Much Physical Activity Is lipoproteins.133
Required for Sustained Weight Loss? One of the proposed mechanisms by which regular
physical activity reduces the risk for CHD is its effect on
There is a general consensus that 2,500–2,800 kcal blood lipids, especially the increases in HDL-C and reduc-
per week (60–90 minutes per day of moderate-inten- tion in TG levels.134 –136 Cross-sectional studies have con-
sity physical activity) is required for long-term weight sistently shown a positive association between the volume
loss, as reflected in the recommendations and consen- and intensity of aerobic activities and HDL-C levels, and
sus statements of the U.S. Department of Health and a negative association with TG levels.137 However, reviews
Human Services,119 the ACSM,120 and the IASO.114 of the literature reveal a surprisingly inconsistent response
These recommendations are supported by data from the of other blood lipids to regular aerobic exercise.137,138
National Weight Control Registry (NWCR), a database These findings may be further confounded by concurrent
of approximately 5,000 individuals who have minimally changes in body weight or composition. In studies with-
lost 30 lbs for at least one year (average weight loss is out a dietary intervention, the most commonly reported
about 30 kg for an average of 5.5 years).121 Data col- change in lipids was an increase in HDL averaging 4.6%,
lected on these “successful losers” indicates that more ranging from a decrease of 5.8% to an increase of 25%.
than 90% of participants expend ~ 2,800 kcals per week Simultaneous reductions in TG (3.7%), LDL-C (5.0%), but
in physical activity. not TC, were also observed.137 Changes in TC and LDL-C
are much less frequently reported, are modest when they
do occur, and may be more attributable to weight loss than
3.9.5 Resistance Training and Weight Loss the exercise intervention per se. As such, regular exercise
Despite claims in the popular literature, strength train- alone cannot be recommended as an effective strategy to
ing is not recommended as the primary mode of exercise lower TC or LDL-C.136
for weight loss.120 While strength/resistance training has Relatively few studies have attempted to evaluate the
been shown to preserve fat-free mass when coupled with a effect of the exercise prescription (intensity, volume, etc.)
calorie- restrictive diet, it has not been shown to enhance on blood lipids and, as such, there is no consensus on the
weight loss either alone or in combination with a dietary optimal exercise regime for improving cholesterol profile.
intervention.115,117,118,120 Despite the apparent ability of In most of the studies reviewed, the exercise intervention
resistance training to maintain muscle mass in the presence was performed at moderate-to-high intensity three to five
3.11 Metabolic Syndrome 45
times per week for at least 30 minutes per session. Total Heart Association (AHA) and the National Heart, Lung,
3
caloric expenditure, as opposed to exercise intensity, has and Blood Institute (NHLBI) definition,174 which refers
been proposed to be of greatest importance for blood lip- to the updated National Cholesterol Education Program
ids, and a threshold of between 1,200 and 2,500 kcals per (NCEP) (2001) definition,175 (4) the American College of
week has been proposed.139 Endocrinology (ACE) and the American Association of
A meta-analysis of studies that explored the effect of Clinical Endocrinologists (AACE) consensus definition
strength training on blood lipids, dating back to 1955, for epidemiological research,173 and (5) the International
found that strength training resulted in modest but sig- Diabetes Federation (IDF).174
nificant improvements in blood lipid profiles (but not The majority of the recent research focusing on the
HDL-C).140 However, while earlier studies generally metabolic syndrome involved the use of the NCEP defi-
demonstrated an improvement in blood lipid profile with nition because of its clinical utility (see Table 3.1). The
resistance training, at least some suffered from design NCEP definition requires that three of the following five
flaws, including no or poor dietary control,140 –143 no con- criteria be present for a diagnosis of the metabolic syn-
trol group,140 –142 or no control for fat loss.141,142,144 Better drome: (1) impaired fasting glucose (IFG) represented by a
designed and/or more recent studies have not found an fasting blood sugar ≥ 110 milligrams per deciliter (mg/dL),
improvement in lipoprotein profiles with resistance/ including T2DM; (2) HDL-C < 40 mg/dL in men and < 50
strength training.145–150 mg/dL in women; (3) triglycerides ≥ 150 mg/dL; (4) an
augmented waist circumference (WC) of ≥ 102 centimeters
(cm) in men and ≥ 88 cm in women; (5) or a blood pressure
3.11 METABOLIC SYNDROME value of ≥ 130/85 millimeters of mercury (mmHg).
WC, waist circumference; W:H, waist hip; TG, triglycerides; OGTT, oral glucose tolerance test; Rx, medication; ACR, albumin: creatinine ratio; others designated in text. WHO = World Health Organization EGIR = European Group for the
study of Insulin Resistance AHA/NHLBI = American Heart Association/National Heart, Lung, and Blood Institute ACE/AACE = American College of Endocrinology/American Association of Clinical Endocrinologists IDF = International
46 Chapter 3 Physical Activity and Fitness in the Prevention of Cardiovascular Disease
Diabetes Federation.
a Family history of type 2 or gestational diabetes, known CVD, polycystic ovary syndrome, physically inactive lifestyle, >40 years of age, and ethnic populations at high risk for type 2 diabetes.
b In this analysis Mexican-American men were classified using a WC cut-off value of ≥ 90 cm and Mexican-American women ≥ 80 cm.9
References 47
REFERENCES
1. Mozaffarian D, Benjamin EJ, Go AS, health care professionals advising patients predicting mortality in men. Am. J. Med.
et al. Heart disease and stroke statis- with diabetes or at risk for developing 2004;117:912–918.
tics—2016 update a report from the diabetes to exercise more? Diabetes Care 13. Jacobs DR Jr, Ainsworth BE, Hartman
American Heart Association. Circulation 2006;29:543–548. TJ, and Leon AS. A simultaneous
2016:133:e38–360. 8. Abid A, Galuska D, Khan LK, Gillespie evaluation of 10 commonly used physical
2. Adult participation in aerobic and C, Ford CS, and Serdula MK. Are health- activity questionnaires. Med. Sci. Sports
muscle-strengthening physical activi- care professionals advising patients to Exerc. 1993;25:81–91.
ties – United States, 2011. MMWR lose weight? A trend analysis. Med. Gen. 14. U.S. Department of Health and Human
2013;62(17):326–330. Med. 2005;7(4):10. Services. Physical Activity and Health: A
3. Williams PT. Physical fitness and activity 9. Walsh JM, Swaganard DM, Davis T, Report of the Surgeon General. Atlanta,
as separate heart disease risk factors: A and McPhee SJ. Exercise counseling GA: U.S. Department of Health and
meta-analysis. Med. Sci. Sports Exerc. by primary care physicians in the era Human Services, Centers for Disease
2001;33:754–761. of managed care. Am. J. Prev. Med. Control and Prevention, July 11, 1996.
4. Ford ES, Ajani UA, Croft JB, et al. 1999;16:307–313. 15. Physical Activity Guidelines Advisory
Explaining the decrease in U.S. deaths 10. Rogers LQ, Gutin B, Humphries MC, Committee. Physical Activity
from coronary disease, 1980–2000. N. et al. Evaluation of internal medi- Guidelines Advisory Committee
Engl. J. Med. 2007;356:2388–2398. cine residents as exercise role models Report, 2008. Washington, DC: U.S.
5. Carlson SA, Fulton JE, Schoenborn CA, and associations with self-reported Department of Health and Human
and Loustalot F. Trend and prevalence counseling behavior, confidence, and Services, 2008.
estimates based on the 2008 Physical perceived success. Teach. Learn. Med. 16. Lee IM, Rexrode KM, Cook NR,
Activity Guidelines for Americans. Am. J. 2006;18:215–221. Manson JE, and Buring JE. Physical
Prev. Med. 2010;39:305–313. 11. American College of Sports Medicine. activity and coronary heart disease in
6. Youth Risk Behavior Surveillance System. ACSM’s Guidelines for Exercise Testing women: Is “no pain, no gain” passé?
Accessed online 10-30-17. https://www.cdc and Prescription. Philadelphia, PA: JAMA 2001;285:1447–1454.
.gov/healthyyouth/data/yrbs/index.htm. Lippincott, Williams and Wilkins, 2010. 17. Manson JE, Hu FB, Rich-Edwards JW,
7. Morrato EH, Hill OH, Wyatt HR, 12. Myers J, Kaykha A, George S, et al. et al. A prospective study of walking as
Ghushchyan V, and Sullivan PW. Are Fitness versus physical activity patterns in compared with vigorous exercise in the
48 Chapter 3 Physical Activity and Fitness in the Prevention of Cardiovascular Disease
prevention of coronary heart disease in 34. Tsai J, Yang H, Wang W, et al. The ben- of heart failure. J. Am. Coll. Cardiol.
women. NEJM 1999;341:650–658. eficial effect of regular endurance exercise 2017;69:1129–1142.
18. Powell KE, Thompson PD, Caspersen training on blood pressure and quality of 51. Hammoud T, Tanguay JF, and Bourassa
CJ, and Kendrick JS. Physical activ- life in patients with hypertension. Clin. MG. Management of coronary artery
ity and the incidence of coronary heart Exp. Hypertens. 2004;26:255–265. disease: Therapeutic options in patients
disease. Annu. Rev. Public Health 35. Halbert JA, Silagy CA, Finucane P, et with diabetes. J. Am. Coll. Cardiol.
1987;8:253–287. al. The effectiveness of exercise training 2000;36:355–365.
19. Blair SN, Kohl HW, and Barlow CE. in lowering blood pressure: A meta- 52. Van de Werf F, Ardissino D, Betriu A,
Physical activity, physical fitness, and analysis of randomised controlled trials et al. Management of acute myocardial
all-cause mortality in women: Do women of 4 weeks or longer. J. Hum. Hypertens. infarction in patients presenting with
need to be active? J. Am. Coll. Nutr. 1997;11:641–649. ST-segment elevation. Eur. Heart J.
1993;12:368–371. 36. Chobanian AV, Bakris GL, Black HR, 2003;24:28–66.
20. Sherman SE, D’Agostino RB, Cobb et al. The seventh report of the Joint 53. Steg PG, Dabbous OH, Feldman LJ,
JL, and Kannel WB. Physical activ- National Committee on prevention, et al. Determinants and prognostic
ity and mortality in women in the detection, evaluation, and treatment of impact of heart failure complicating
Framingham Heart Study. Am. Heart J. high blood pressure: The JNC 7 report. acute coronary syndromes observa-
1994;128:879–884. JAMA 2003;289:2560–2572. tions from the Global Registry of Acute
21. Oguma Y and Shinoda-Tagawa T. 37. Fagard RH. Exercise characteristics and Coronary Events (GRACE). Circulation
Physical activity decreases cardiovas- the blood pressure response to dynamic 2004;109:494–499.
cular disease risk in women: Review physical training. Med. Sci. Sports Exerc. 54. Vikman S, Niemela K, Ilva T, et al.
and meta-analysis. Am. J. Prev. Med. 2001;33(Suppl 6):S484–S492. Underuse of evidence-based treatment
2004;26:407–418. Review. 38. Kukkonen K, Rauramaa R, Voutilainen modalities in diabetic patients with non-
22. Lee IM, Shiroma EJ, Evenson KR, E, and Lansimies E. Physical training of ST elevation acute coronary syndrome. A
Kamada M, LaCroix AZ, and Buring JE. middle-aged men with borderline hyper- prospective nation-wide study on acute
Accelerometer-measured physical activity tension. Ann. Clin. Res. 1982;14(Suppl coronary syndromes (FINACS). Diabetes
and sedentary behavior in relation to 34):139–145. Res. Clin. Pract. 2003;61:39–48.
all-cause mortality: The Women’s Health 39. Leon AS, Casal D, and Jacobs D Jr. 55. Morrish NJ, Wang SL, Stevens LK, Fuller
Study. Circulation 2018;137:203–205. Effects of 2,000 kcal per week of walking JH, and Keen H. Mortality and causes of
23. D’Amore S and Mora S. Gender-specific and stair climbing on physical fitness and death in the WHO multinational study of
prediction of cardiac disease: Importance risk factors for coronary heart disease. J. vascular disease in diabetes. Diabetologia
of risk factors and exercise variables. Cardiopulm. Rehabil. 1996;16:183–192. 2001;44:S14–S21.
Cardiol. Rev. 2006;14:281–285. Review. 40. Manfredini F, Malagoni AM, Mandini 56. Smith SC. Multiple risk factors for car-
24. Gulati M, Pandey DK, Arnsdorf MF, S, et al. Sport therapy for hypertension: diovascular disease and diabetes mellitus.
et al. Exercise capacity and the risk Why, how, and how much? Angiology Am. J. Med. 2007;120:S3–S11.
of death in women: The St. James 2009;60:207–216. 57. Kahn BB and Flier JS. Obesity and
Women Take Heart Project. Circulation 41. Cornelissen VA and Fagard RH. Effect insulin resistance. J. Clin. Invest.
2003;108:1554–1559. of resistance training on resting blood 2000;106:473–481.
25. Reimers CD, Knapp G, and Reimers AK. pressure: A meta-analysis of random- 58. Wisse BE. The inflammatory syndrome:
Exercise as stroke prophylaxis. Dtsch. ized controlled trials. J. Hypertens. The role of adipose tissue cytokines in
Arztebl. Int. 2009;106:715–721. 2005;23:251–259. metabolic disorders linked to obesity. J.
26. Lee CD, Folsom AR, and Blair SN. 42. Kelley GA and Kelley KS. Progressive Am. Soc. Nephrol. 2004;15:2792–2800.
Physical activity and stroke risk: A meta- resistance exercise and resting blood 59. Poirier P, Giles TD, Bray GA, et al.
analysis. Stroke 2003;34:2475–2481. pressure: A meta-analysis of random- Obesity and cardiovascular disease:
27. Goldstein LB, Bushnell CD, Adams RJ, et ized controlled trials. Hypertension Pathophysiology, evaluation, and effect
al. Guidelines for the primary preven- 2000;35:838–843. of weight loss: An update of the 1997
tion of stroke: A guideline for health- 43. Wallace JP. Exercise in hyperten- American Heart Association scien-
care professionals from the American sion: A clinical review. Sports Med. tific statement on obesity and heart
Heart Association/American Stroke 2003;33:585–598. disease from the obesity committee
Association. Stroke 2011;42:517–584. 44. Pescatello LS. Exercise and hypertension: of the Council on Nutrition, Physical
28. Shrier I. Muscle strength and body size Recent advances in exercise prescription. Activity, and Metabolism. Circulation
and later cerebrovascular and coro- Curr. Hypertens. Rep. 2005;7:281–286. 2006;113:898–918.
nary heart disease. Clin. J. Sport Med. 45. Braith RW and Stewart KJ. Resistance 60. Alexander CM, Lansman PB, Teutsch
2010;20:131. exercise training: Its role in the pre- SM, and Haffner SM. NCEP-defined
29. Lewington S, Clarke R, Qizilbash N, vention of cardiovascular disease. metabolic syndrome, diabetes and
Peto R, and Collins R. Age-specific Circulation 2006;113:2642–2650. prevalence of coronary heart disease
relevance of usual blood pressure to 46. Rezk CC, Marrache RC, Tinucci T, et among NHANES III participants
vascular mortality: A meta-analysis of al. Post-resistance exercise hypotension, age 50 years and older. Diabetes
individual data for one million adults hemodynamics, and heart rate variability: 2003;52:1210–1214.
in 61 prospective studies. Prospective Influence of exercise intensity. Eur. J. 61. Lakka HM, Laaksonen DE, Lakka
Studies Collaboration. Lancet Appl. Physiol. 2006;98:105–112. TA, et al. The metabolic syndrome
2002;360:1903–1913. 47. Queiroz ACC, Gagliardi JFL, Forjaz and total and cardiovascular disease
30. Goodwin KA, Headley SA, and Pescatello CLM, et al. Clinic and ambulatory mortality in middle-aged men. JAMA
LS. Exercise prescription for the preven- blood pressure responses after resis- 2002;288:2709–2716.
tion and management of hypertension. tance exercise. J. Strength Cond. Res. 62. Wei M, Gibbons LW, Mitchell TL,
Am. J. Lifestyle Med. 2009;3:446–449. 2009;23:571–578. Kampert JB, Lee CD, and Blair SN. The
31. Hagberg JM, Park JJ, and Brown MD. 48. Kenchaiah S, Sesso HD, and Gaziano association between cardiorespiratory
The role of exercise training in the treat- JM. Body mass index and vigor- fitness and impaired fasting glucose and
ment of hypertension: An update. Sports ous physical activity and the risk of type 2 diabetes mellitus in men. Ann.
Med. 2000;30:193–206. heart failure among men. Circulation Intern. Med. 1999;130:89–96.
32. Chase NL, Sui X, Lee DC, et al. The 2009;119:44–52. 63. Sawada SS, Lee IM, Muto T, Matuszaki
association of cardiorespiratory fitness 49. Hu G, Jousilahti P, Antikainen R, K, and Blair SN. Cardiorespiratory fitness
and physical activity with incidence of Katzmarzyk PT, and Tuomilehto J. Joint and the incidence of type 2 diabetes:
hypertension in men. Am. J. Hypertens. effects of physical activity, body mass Prospective study of Japanese men.
2009;22:417–424. index, waist circumference, and waist- Diabetes Care 2003;26:2918–2922.
33. Pescatello LS, Franklin BA, Fagard R, et to-hip ratio on the risk of heart failure. 64. Helmrich SP, Ragland DR, Leung RW,
al. American College of Sports Medicine Circulation 2010;121:237–244. and Paffenbarger RF. Physical activity
position stand. Exercise and hyperten- 50. Pandey A, LaMonte M, Klein L, et and reduced occurrence of non-insulin
sion. Med. Sci. Sports Exerc. 2004 al. Relationship between physical dependent diabetes mellitus. N. Engl. J.
36:533–553. activity, body mass index, and risk Med. 1991;325:147–152.
References 49
65. Hu FB, Manson JE, Stampfer MJ, et al. 80. Snowling NJ and Hopkins WG. Effects 97. Lee YH and Pratley RE. Abdominal
Diet, lifestyle, and the risk of type 2 dia- of different modes of exercise train- obesity and cardiovascular disease risk:
betes mellitus in women. N. Engl. J. Med.
2001;345:790–797.
66. Hu FB, Sigal RJ, Rich-Edwards JW, et al.
ing on glucose control and risk factors
for complications in Type 2 diabetic
patients. A meta-analysis. Diabetes Care
The emerging role of the adipocyte. J.
Cardiopulm. Rehabil. 2007;27:2–10.
98. Wisse BE. The inflammatory syndrome:
3
Walking compared with vigorous physi- 2006;29:2518–2527. The role of adipose tissue cytokines in
cal activity and risk of type 2 diabetes 81. Sigal RJ, Kenny GP, Wasserman DH, metabolic disorders linked to obesity. J.
in women: A prospective study. JAMA Castaneda-Sceppa C, and White RD. Am. Soc. Nephrol. 2004;15:2792–2800.
1999;282:1433–1439. Physical activity/exercise and type 2 99. Fasshauer M and Paschke R. Regulation
67. Kriska AM, Saremi A, Hanson RL, et diabetes: A consensus statement from the of adipocytokines and insulin resistance.
al. Physical activity, obesity, and the American Diabetes Association. Diabetes Diabetologia 2003;46:1594–1603.
incidence of type 2 diabetes in a high- Care 2006 Jun;29(6):1433–1438. 100. Panagiotakos DB, Pitsavos C,
risk population. Am. J. Epideimiol. 82. National Heart, Lung and Blood Institute. Yannakoulia M, Chrysohoou C, and
2003;158:669–675. Obesity Education Initiative Expert Panel: Stefanadis C. The implication of obesity
68. Okada K, Hayashi T, Tsumura K, Clinical Guidelines on the Identification, and central fat on markers of chronic
Suematsu C, Endo G, and Fujii S. Evaluation, and Treatment of Overweight inflammation: The ATTICA study.
Leisure-time physical activity at week- and Obesity in Adults: The Evidence Atherosclerosis 2005;183:308–315.
ends and the risk of type 2 diabetes mel- Report. Bethesda, MD: National Institutes 101. Warnberg J, Nova E, Moreno LA, et al.
litus in Japanese men: The Osaka Health of Health, 1998 Sep. NIH publication no. Inflammatory proteins are related to total
Survey. Diabetes Med. 2000;17:53–58. 98-4083. pp. 1–228. and abdominal adiposity in a healthy
69. Wannamethee SG, Shaper AG, and 83. Abate N. Obesity and cardiovascular dis- adolescent population: The AVENA study.
Alberti KG. Physical activity, metabolic ease: Pathogenetic role of the metabolic Am. J. Clin. Nutr. 2006;84:505–512.
factors, and the incidence of coronary syndrome and therapeutic implications. J. 102. Park HS, Park JY, and Yu R. Relationship
heart disease and type 2 diabetes. Arch. Diabetes Complicat. 2000;14:154–174. of obesity and visceral adiposity with
Intern. Med. 2000;160:2108–2116. 84. Bonora E. Relationship between regional serum concentrations of CRP, TNF-
70. Hu FB, Leitzmann MF, Stamfer MJ, fat distribution and insulin resistance. alpha, and IL-6. Diabetes Res. Clin.
Colditz GA, Willett WC, and Rimm EB. Int. J. Obes. Relat. Metab. Disord. Pract. 2005;69:29–35.
Physical activity and television watch- 2000;24(Suppl 2):S32–S35. 103. Nicklas BJ, You T, and Pahor M.
ing in relation to risk for type 2 diabetes 85. Despres J-P and Marrette A. Obesity and Behavioural treatments for chronic
mellitus in men. Arch. Intern. Med. insulin resistance: Epidemiological, meta- systemic inflammation: Effects of dietary
2001;161:1542–1548. bolic and molecular aspects. In: Reaven weight loss and exercise training. CMAJ
71. Hu FB, Li TY, Colditz, GA, Willett WC, G and Laws A, editors. Contemporary 2005;172:1199–1209.
and Manson JE. Television watching Endocrinology. Insulin Resistance: The 104. Wannamethee SG, Lowe GO, Whincup
and other sedentary behaviors in relation Metabolic Syndrome X. Totowa, NJ: PH, Rumley A, Walker M, and Lennon
to risk of obesity and type 2 diabetes in Humana Press, Inc., 1999. L. Physical activity and hemostatic and
women. JAMA 289;1785–1791. 86. Sharma AM. Adipose tissue: A media- inflammatory variables in elderly men.
72. Weinstein AR, Sesso HD, Lee IM, et al. tor of cardiovascular risk. Int. J. Obes. Circulation 2002;105:1785–1790.
Relationship of physical activity vs. body 2002;26(Suppl 4):S5–S7. 105. Lakka TA, Lakka HM, Rankinen T, et
mass index with t diabetes in women. 87. Ford ES, Mokdad AH, and Giles al. Effect of exercise training on plasma
JAMA 2004;292:1148–1194. WH. Trends in waist circumfer- levels of C-reactive protein in healthy
73. Duncan GE, Perri MG, Theriaque DW, ence among U.S. adults. Obes. Res. adults: The Heritage Family Study. Eur.
Hutson AD, Eckel RH, and Stacpoole 2003;11:1223–1231. Heart J. 2005;26:2018–2025.
PW. Exercise training, without weight 88. Abid A, Galuska D, Khan LK, Gillespie 106. Milani RV, Lavie CJ, and Mehra
loss, increases insulin sensitivity and C, Ford CS, and Serdula MK. Are health- MR. Reduction in C-reactive protein
postheparin plasma lipase activity in pre- care professionals advising patients to through cardiac rehabilitation and
viously sedentary adults. Diabetes Care lose weight? A trend analysis. Med. Gen. exercise training. J. Am. Coll. Cardiol.
2003;26:557–562. Med. 2005;7:10. 2004;43:1056–1061.
74. Pan XR, Li GW, Hu YH, Wang JX, and 89. O’Brien SH, Holubkov R, and Reis 107. Barbeau P, Litaker RS, Woods KF, et al.
Yang WY. Effects of diet and exercise EC. Identification, evaluation, and Hemostatic and inflammatory markers
in preventing NIDDM in people with management of obesity in an aca- in obese youths: Effects of exercise and
impaired glucose tolerance. The Da Qing demic primary care center. Pediatrics adiposity. J. Pediatr. 2002;141:415–420.
IGT and Diabetes Study. Diabetes Care 2004;114:e154–e159. 108. Nassis GP, Papantakou K, Skenderi K,
1997;20:537–544. 90. Ross R. Atherosclerosis as an inflam- et al. Aerobic exercise training improves
75. Tuomilehto J, Lindstrom J, Eriksonn JG, matory disease. Am. Heart J. insulin sensitivity without changes in
et al. Prevention of type 2 diabetes melli- 1999;138:S419–S420. body weight, body fat, adiponectin,
tus by changes in lifestyle among subjects 91. Plutzky J. Inflammation in atherosclero- and inflammatory markers in over-
with impaired glucose tolerance. N. Engl. sis and diabetes mellitus. Rev. Endorc. weight and obese girls. Metabolism
J. Med. 2001;344:1343–1350. Metab. Disord. 2004;5:255–259. 2005;54:1472–1479.
76. Knowler WC, Barrett-Connor E, Fowler 92. Fan J and Watanabe T. Inflammatory 109. Huffman KM, Samsa GP, Slentz CA,
SE, et al. Reduction in the incidence of reactions in the pathogenesis of ath- et al. Response of high-sensitivity
type 2 diabetes with lifestyle interven- erosclerosis. J. Atheroscler. Thromb. C-reactive protein to exercise training
tion or metformin. N. Engl. J. Med. 2003;10:63–71. in an at-risk population. Am. Heart J.
2002;346:393–403. 93. Blake GJ and Ridker PM. Inflammatory 2006;152:793–800.
77. Boule NG, Haddad E, Kenny GP, Wells bio-markers and cardiovascular 110. Hammett CJ, Prapavessis H, Baldi JC,
GA, and Sigal RJ. Effects of exercise risk prediction. J. Intern. Med. et al. Effects of exercise training on
on glycemic control and body mass 2002;252:283–294. 5 inflammatory markers associated
in type 2 diabetes: A meta-analysis 94. Berg AH and Scherer PE. Adipose tis- with cardiovascular risk. Am. J. Heart
of controlled clinical trials. JAMA sue, inflammation, and cardiovascular 2006;151:367.e7–367.e16.
2001;286:1218–1227. disease. Circ. Res. 2005;96:939–949. 111. Marcell TJ, McAuley KA, Traustadottir
78. Boule NG, Haddad E, Kenny GP, Wells 95. Nanji AA and Freeman JB. Relationship T, and Reaven PD. Exercise training
GA, and Sigal RJ. Meta-analysis of the between body weight and total leukocyte is not associated with improved levels
effect of structured exercise train- count in morbid obesity. Am. J. Clin. of C-reactive protein or adiponectin.
ing on cardiorespiratory fitness in Pathol. 1985;84:346–347. Metabolism 2005;54:533–541.
type 2 diabetes mellitus. Diabetologia 96. Cottam DR, Mattar SG, Barinas-Mitchell 112. Rauramaa R, Halonen P, Vaisanen SB, et
2003;46:1071–1081. E, et al. The chronic inflammatory al. Effects of aerobic physical exercise on
79. Sigal RJ, Kenny GP, Wasserman DH, and hypothesis for the morbidity associ- inflammation and atherosclerosis in men:
Castaneda-Sceppa C. Physical activity/ ated with morbid obesity: Implications The DNASCO Study: A six-year random-
exercise and type 2 diabetes. Diabetes and effects of weight loss. Obes. Surg. ized, controlled trial. Ann. Intern. Med.
Care 2004;27:2518–2539. 2004;14:589–600. 2004;140:1007–1014.
50 Chapter 3 Physical Activity and Fitness in the Prevention of Cardiovascular Disease
113. Gill JM and Malkova D. Physical effect on excess post-exercise oxygen to aerobic exercise training. Med. Sci.
activity, fitness and cardiovascular consumption. Med. Sci. Sports Exerc. Sports Exerc. 1989;21:689–693.
disease risk in adults: Interactions with 1999;31:1613–1618. 147. Kokkinos PF, Hurley BF, Smutok MA,
insulin resistance and obesity. Clin. Sci. 129. Olds TS and Abernathy PJ. Postexercise et al. Strength training does not improve
2004;110:409–425. oxygen consumption following heavy lipoprotein-lipid profiles in men at risk
114. Sarris WH, Blair SN, van Baak MA, et al. and light resistance exercise. J. Strength for coronary heart disease (CHD). Med.
How much physical activity is enough to Cond. Res. 1993;7:147–152. Sci. Sports Exerc. 1991;23:1134–1139.
prevent unhealthy weight gain? Outcome 130. Elliot DL, Goldberg L, and Kuehl KS. 148. Smutok MA, Reece C, Kokkinos PF, et al.
of the IASO 1st Stock Conference Effects of resistance training on excess Aerobic versus strength training for risk
and consensus statement. Obes. Rev. post-exercise oxygen consumption. J. factor intervention in middle-aged men
2003;4:101–114. Appl. Sports Sci. Res. 1992;6:77–81. at high risk for coronary heart disease.
115. Hill JO and Wyatt HR. Role of physical 131. Grundy SM, Cleeman JI, Merz CN, et Metabolism 1993;42:177–184.
activity in preventing and treating obe- al. Implications of recent clinical trials 149. LeMura LM, von Duvillard SP,
sity. J. Appl. Physiol. 2005;99:765–770. for the National Cholesterol Education Andreacci J, Klebez JM, Chelland SA,
116. Wing RR. Physical activity in the Program Adult Treatment Panel III and Russo J. Lipid and lipoprotein
treatment of the adulthood overweight Guidelines. J. Am. Coll. Cardiol. profiles, cardiovascular fitness, body
and obesity: Current evidence and 2004;44:720–732. composition, and diet during and after
research issues. Med. Sci. Sports Exerc. 132. Fruchart JC, Nierman MC, Stroes resistance, aerobic, and combination
1999;31(Suppl):S547–S552. ES, Kastelein JJ, and Duriez P. New training in young women. Eur. J. Appl.
117. Catenacci VA and Wyatt HR. The role risk factors for atherosclerosis and Physiol. 2000;82:451–458.
of physical activity in producing and patient risk assessment. Circulation 150. Banz WJ, Maher MJ, Thompson
maintaining weight loss. Nat. Clin. Pract. 2004;109:315–319. WG, et al. Effects of resistance versus
Endocrinol. Metab. 2007;3:518–529. 133. Tóth PP, Potter D, and Ming EE. aerobic training on coronary artery
118. Avenell A, Broom J, Brown TJ, et al. Prevalence of lipid abnormalities in the disease risk factors. Exp. Biol. Med.
Systematic review of the long-term effects United States: The National Health and 2003;228:434–440.
and economic consequences of treatments Nutrition Examination Survey 2003– 151. Bonora E. The metabolic syndrome
for obesity and implications for health 2006. J. Clin. Lipidol. 2012;6:325–330. and cardiovascular disease. Ann. Med.
improvement. Health Technol. Assess. 134. O’Donovan G, McEneny J, Kearney EM, 2006;38:64–80.
2004;8(21):1–465. et al. LDL particle size in habitual exer- 152. Grundy SM, Brewer HB, Cleeman JI,
119. Department of Health and Human cisers, lean sedentary men and abdomi- Smith SC, and Lenfant C. Definition
Services. Dietary Guidelines, 2005. nally obese sedentary men. Int. J. Sports of metabolic syndrome: Report
[Online]. http://www.healt hierus.gov/die Med. 2007;28:644–649. of the National Heart, Lung, and
tarygu ideli nes 135. Kraus WE, Houmard JA, Duscha BD, et Blood Institute/American Heart
120. Donnelly JE, Blair SN, Jakicic JM, et al. al. Effects of the amount and intensity of Association conference on scientific
American College of Sports Medicine exercise on plasma lipoproteins. N. Engl. issues related to definition. Circulation
Position Stand. Appropriate physi- J. Med. 2002;347:1483–1492. 2004;109:433–438.
cal activity intervention strategies for 136. Mestek ML. Physical activity, blood 153. Haffner SM, Valdez RA, Hazuda HP,
weight loss and prevention of weight lipids, and lipoproteins. Am. J. Lifestyle Mitchell BD, Morales PA, and Stern MP.
regain for adults. Med. Sci. Sports Exerc. Med. 2009;3:279–283. Prospective analysis of the insulin-resis-
2009;41:459–471. 137. El Harchaoui K, Arsenault BJ, Franssen tance syndrome (syndrome X). Diabetes
121. Klem ML, Wing RR, McGuire MT, R, et al. High-density lipoprotein particle 1992;41:715–722.
Seagle HM, and Hill JO. A descrip- size and concentration and coronary risk. 154. Liese AD, Mayer-Davis EJ, and
tive study of individuals successful at Ann. Intern. Med. 2009;150:84–93. Haffner SM. Development of the mul-
long term maintenance of substan- 138. Kelley GA and Kelley KS. Aerobic tiple metabolic syndrome: An epide-
tial weight loss. Am. J. Clin. Nutr. exercise and lipids and lipoproteins in miologic perspective. Epidemiol. Rev.
1997;66:239–246. men: A meta-analysis of randomized 1998;20:157–172.
122. Wadden TA, Vogt RA, Andersen RE, et controlled trials. J. Mens. Health Gend. 155. Reaven GM. Banting lecture 1988. Role
al. Exercise in the treatment of obesity: 2006;3:61–70. of insulin resistance in human disease.
Effects of four interventions on body 139. Durstine JL, Grandjean PW, Cox CA, Diabetes 1988;37:1595–1607.
composition, resting energy expenditure, and Thompson PD. Lipids, lipoproteins, 156. Wilson PW, Kannel WB, Silbershatz H,
appetite, and mood. J. Consult. Clin. and exercise. J. Cardiopulm. Rehabil. and D’Agostino RB. Clustering of meta-
Psychol. 1997;65:269–277. 2002;22:385–398. bolic factors and coronary heart disease.
123. Jamurtas AZ, Koutedakis Y, Pachallis V, 140. Kelley GA and Kelley KS. Impact of pro- Arch. Intern. Med. 1999;159:1104–1109.
et al. The effects of a single bout of exer- gressive resistance training on lipids and 157. Kylin E. Studien uber das Hypertonie-
cise on resting energy expenditure and lipoproteins in adults: A meta-analysis of Hyperglyka ‘mie-Hyperurika’ mie-
respiratory exchange ratio. Eur. J. Appl. randomized controlled trials. Prev. Med. syndrom. Zentralbl. Inn. Med.
Phyiol. 2004;92:393–398. 2009;48:9–19. 1923;44:105–127.
124. Schuenke MD, Mikat RP, and McBride 141. Frippe RR and Hodgson JL. Effect of 158. Vague J. La differenciation sexuelle,
JM. Effect of an acute period of resis- resistance training on plasma lipid and facteur determinant des formes de
tance exercise on excess post-exercise lipoprotein levels in male adolescents. J. l’obesite. Presse Med. 1947;53:339–340.
oxygen consumption: Implications form Pediatr. 1987;111:926–931. 159. Avogaro P, Crepaldi G, Enzi G, and
body mass management. Eur. J. Appl. 142. Goldberg LE, Elliot DL, Schutz RW, and Tiengo A. Metabolic aspects of essential
Physiol. 2002;86:411–417. Kloster FE. Changes in lipid-lipoprotein obesity. Epatologia 1965;11:226–238.
125. Osterberg KL and Melby CL. Effect of levels after weight training. JAMA 160. Camus J. The deadly quintet. Rev. Rhum.
acute resistance exercise on postexercise 1984;252:504–506. Mal. Osteoartic. 1966;33:10–14.
oxygen consumption and resting meta- 143. Ulrich IH, Reid CM, and Yeater RA. 161. Jahnke K, Daweke H, Libermeister H,
bolic rate in young women. Int. J. Sport Increased HDL-cholesterol levels with a et al. Hormonal and metabolic aspects
Nutr. Exerc. Metab. 2000;10:71–81. weight training program. South. Med. J. of obesity in humans. In: Proceedings of
126. Gillette CA, Bullough RC, and Melby 1987;80:328–331. the Sixth Congress of the International
CL. Postexercise energy expenditure in 144. Weltman A, Janney C, Rians CB, Strand Diabetes Federation. Amsterdam:
response to acute aerobic or resistive exer- K, and Katch FI. The effects of hydraulic Excerpta Medica Foundation, 1969. pp.
cise. Int. J. Sport Nutr. 1994;4:347–360. resistance strength training on serum 533–539.
127. Melby C, Scholl C, Edwards G, and lipid levels in prepubertal boys. Am. J. 162. Haller H. Epidermiology and associated
Bullough R. Effect of acute resistance Dis. Child. 1987;141:777–780. risk factors of hyperlipoproteinemia. Z.
exercise on postexercise energy expendi- 145. Johnson CC, Stone MH, Lopez SA, Gesamte Inn. Med. 1977;32:124–128.
ture and resting metabolic rate. J. Appl. Herberg JA, Kilgore LT, and Byrd RJ. 163. Singer P. Diagnosis of primary hyperli-
Physiol. 1993;75:1847–1853. Diet and exercise in middle-aged men. J. poproteinemias. Z. Gesamte Inn. Med.
128. Haltom RW, Kraemer RR, Sloan RA, Diet. Assoc. 1982;81:695–701. 1977;32:129–133.
Herbert EP, Frank K, and Tryniecki 146. Hurley BF. Effects of resistive training on 164. American Diabetes Association. http://
JL. Circuit weight training and its lipoprotein-lipid profiles: A comparison www.diabetes.org/home.jsp
References 51
165. Zavaroni I, Bonini L, Fantuzzi M, on detection, evaluation, and treat- associated with lower risk of having
Dall’Aglio E, Passeri M, and Reaven ment of high blood cholesterol in adults the metabolic syndrome. Metabolism
GM. Hyperinsulinaemia, obesity,
and syndrome X. J. Intern. Med.
1994;235:51–56.
(Adult Treatment Panel III). JAMA
2001;285:2486–2497.
176. WHO. Definition Diagnosis and
2004;53:1503–1511.
185. Katzmarzyk PT, Leon AS, Wilmore JH,
et al. Targeting the metabolic syn-
3
166. Despres JP. Visceral obesity, insulin resis- Classification of Diabetes Mellitus and drome with exercise: Evidence from the
tance, and dyslipidemia: Contribution of Its Complications. Report of a WHO HERITAGE Family Study. Med. Sci.
endurance exercise training to the treat- Consultation, 1999. Sports Exerc. 2003;35:1703–1709.
ment of the plurimetabolic syndrome. 177. G rundy SM, Cleeman JI, Daniels 186. Farrell SW, Cheng YJ, and Blair SN.
Exerc. Sport Sci. Rev. 1997;25:271–300. SR, et al. Diagnosis and manage- Prevalence of the metabolic syndrome
167. Bonora E, Kiechl S, Willeit J, et al. ment of the metabolic syndrome: An across cardiorespiratory fitness levels in
Prevalence of insulin resistance in American Heart Association/National women. Obes. Res. 2004;12:824–830.
metabolic disorders: The Bruneck Study. Heart, Lung, and Blood Institute 187. Jurca R, Lamonte MJ, Barlow CE,
Diabetes 1998;47:1643–1649. Scientific Statement. Circulation Kampert JB, Church TS, and Blair
168. Isomaa B, Almgren P, Tuomi T, et al. 2005;112:2735–2752. SN. Association of muscular strength
Cardiovascular morbidity and mortality 178. Eckel RH, Grundy SM, and Zimmet with incidence of metabolic syndrome
associated with the metabolic syndrome. PZ. The metabolic syndrome. Lancet in men. Med. Sci. Sports Exerc.
Diabetes Care 2001;24:683–689. 2005;365:1415–1428. 2005;37:1849–1855.
169. Mota M, Panus C, Mota E, Lichiardopol 179. DuBose KD, Ainsworth BE, Hand 188. Castaneda C, Layne JE, Munoz-Orians
C, Vladu D, and Toma E. The metabolic GA, and Durstine JL. The relationship L, et al. A randomized controlled
syndrome – A multifaced disease. Rom. J. between leisure-time physical activity and trial of resistance exercise training to
Intern. Med. 2004;42:247–255. the metabolic syndrome: An examination improve glycemic control in older adults
170. Trevisan M, Liu J, Bahsas FB, and of NHANES III, 1988–1994. J. Phys. with type 2 diabetes. Diabetes Care
Menotti A. Syndrome X and mortality: A Act. Health 2005;2:470–487. 2002;25:2335–2341.
population-based study. Risk Factor and 180. Irwin ML, Ainsworth BE, Mayer-Davis 189. Dunstan DW, Daly RM, Owen N, et
Life Expectancy Research Group. Am. J. EJ, Addy CL, Pate RR, and Durstine JL. al. High-intensity resistance train-
Epidemiol. 1998;148:958–966. Physical activity and the metabolic syn- ing improves glycemic control in older
171. Churilla JR and Zoeller RF. Physical drome in a tri-ethnic sample of women. patients with type 2 diabetes. Diabetes
activity and the metabolic syndrome: A Obes. Res. 2002;10:1030–1037. Care 2000;25:1729–1736.
review of the evidence. Am. J. Lifestyle 181. Laaksonen DE, Lakka HM, Salonen 190. Harris KA and Holly RG. Physiological
Med. 2008;2:118–125. JT, Niskanen LK, Rauramaa R, and response to circuit weight training in
172. Balkau B and Charles MA. Comment on Lakka TA. Low levels of leisure-time borderline hypertensive subjects. Med.
the provisional report from the WHO physical activity and cardiorespira- Sci. Sports Exerc. 1987;19:246–252.
consultation. European Group for the tory fitness predict development of the 191. Honkola A, Forsen T, and Eriksson
Study of Insulin Resistance (EGIR). metabolic syndrome. Diabetes Care J. Resistance training improves the
Diabet. Med. 1999;16:442–443. 2002;25:1612–1618. metabolic profile in individuals with
173. Einhorn D, Reaven GM, Cobin RH, et 182. Park YW, Zhu S, Palaniappan L, Heshka type 2 diabetes. Acta Diabetol.
al. American College of Endocrinology S, Carnethon MR, and Heymsfield SB. 1997;34:245–248.
position statement on the insulin The metabolic syndrome: Prevalence 192. Hurley BF, Hagberg JM, Goldberg AP, et
resistance syndrome. Endocr. Pract. and associated risk factor findings in the al. Resistive training can reduce coronary
2003;9:237–252. US population from the Third National risk factors without altering VO2max or
174. IDF. International Diabetes Federation. Health and Nutrition Examination percent body fat. Med. Sci. Sports Exerc.
Worldwide Definition of the Metabolic Survey, 1988–1994. Arch. Intern. Med. 1988;20:150–154.
Syndrome, 2005. Available at: https: //ww 2003;163:427–436. 193. Bateman LA, Slentz CA, Willis LH, et al.
w.idf.org/our-ac tivities/advocacy-awaren 183. Ford ES, Kohl HW, Mokdad AH, and Comparison of aerobic versus resistance
ess/resources-and-tools/60 :idfconsensus- Ajani UA. Sedentary behavior, physi- exercise training effects on metabolic
worldw ide- definitionof-the -metabolic-syn cal activity, and the metabolic syn- syndrome (from the studies of a targeted
drome.html. Accessed December16, 2017. drome among U.S. adults. Obes. Res. risk reduction intervention through
175. NCEP. Executive summary of the third 2005;13:608–614. defined exercise – STRRIDE-AT/RT).
report of the National Cholesterol 184. Zhu S, St-Onge MP, Heshka S, and Am. J. Cardiol. 2011 Jul 7. [Epub ahead
Education Program (NCEP) expert panel Heymsfield SB. Lifestyle behaviors of print].
4
CHAPTER
The newer pharmacologic agents to reduce cholesterol Support for the protective role of HDL against CHD has
include ezetimibe and PCSK9 inhibitors. The role of ezeti- been shown by numerous randomized, controlled trials
mibe influencing LDL-C and CHD risk was highlighted by through several cardioprotective effects, including antioxi-
the IMPROVE-IT trial. This trial investigated ezetimibe plus dant effects, improved endothelial function, anti-inflam-
statin therapy compared to statin therapy alone in 18,000 matory effects, reduction in endothelial-derived adhesive
patients who had been hospitalized for acute coronary syn- proteins, antithrombotic and profibrinolytic effects, reverse
drome (ACS). The results indicated a statistically significant cholesterol transport from foam cells to the liver, and even
difference in LDL-C levels and improved cardiovascular regression of atherosclerotic plaques.13,24,26–28 Conversely, in
outcomes (absolute risk difference, 2.0).16 The SHARP trial a meta-analysis of over 100 trials, it was found that increas-
further showed that the addition of ezetimibe to simvastatin ing HDL alone does not reduce the risk of cardiovascular
reduced the incidence of atherosclerotic events (stroke, CHD, events.29 HDL functions in the body to remove cholesterol
revascularization procedures, MI) in patients with chronic from the cell membrane and transport it to the liver for dis-
kidney disease.17 Ezetimibe works by inhibiting Niemann- posal in the bile as cholesterol or as bile acids.30 Cholesterol
Pick C1 like 1 (NPC1L1) protein and by reducing cholesterol acyltransferase (LCAT), an enzyme carried by HDL and
absorption in the small intestine.18 Ezetimibe targets uptake activated by HDL’s apo A-I, acts by esterifying HDL’s newly
of cholesterol absorption at the jejunal enterocyte brush bor- acquired cholesterol, and the resulting cholesterol ester (CE)
der and can lower LDL-C and non-HDL-C.19 is drawn into the core of HDL. Cholesterol ester transfer
The PCSK9 (proprotein convertase subtilisin/kexin protein (CEPT) is another enzyme involved in reversed cho-
type 9) inhibitors are another newer class of medication lesterol transfer by catalyzing the transfer of CE from HDL
that have shown benefit when added to a statin regimen. to other lipoproteins in exchange for TG. If CEPT is inhib-
PCSK9 inhibitors are a human monoclonal antibody to ited via pharmacological measures or inherited, there is a
PCSK9, which binds to PCSK9 and increases LDL recep- resultant increase in HDL-C levels postulated to result in a
tors by increasing recycling of receptors to the cell surface, reduction in atherogenesis. However, it appears that more
which should decrease LDL-C.18,20 Three trials have sup- recently developed drugs that impair the function of CEPT
ported the use of PCSK9 inhibitors in decreasing CHD results in an increased level of HDL-C as designed, but in
risk. The FOURIER trial, a placebo-controlled trial of contrast to a hypothesized reduction in atherogenesis, this
over 27,000 patients, reported that the addition of evo- does not protect against CHD and may even promote pro-
locumab (PCSK9 inhibitor) to statin therapy lowered LDL gression of CHD and result in increased risk of morbidity
by 59% and reduced the risk of cardiovascular events. 21 and mortality.31–34 These studies suggest that very high levels
The ODYSSEY trial, utilizing the PCSK9 inhibitor ali- of large HDL particles laden with cholesterol may lose their
rocumab on over 2,000 patients, reported that, at 24 cardioprotective properties and may even be atherogenic.35
weeks, the difference in LDL-C between the placebo and Interestingly, individuals who have a specific genetic variant
alirocumab group was 62%, and this effect remained at of apo A-I (i.e., apo A-I Milano) have low levels of HDL-C
78 weeks. 22 The PCSK9 inhibitor, bococizumab was eval- and a very low risk of CHD, and vegetarians generally also
uated in the SPIRE-1 and SPIRE-2 trials, which found a have reduced levels of HDL-C (and LDL-C) and have a low
56% reduction in LDL-C, compared to the placebo group risk of CHD.36,37 Measurement of nascent or newly formed
that had a 2.9% increase in patients with high cardiovas- HDL particles, low in cholesterol and apo A-I levels, appar-
cular risk at 14 weeks. 23 Bococizumab further reduced risk ently better reflect the cardioprotective effects of HDL. It is
of cardiovascular events in the high-risk patients (HR.79, clear that additional research is needed to elucidate these
p = 0.02) but not the low-risk group (HR .99, p = 0.94). questions and to develop techniques to better reflect the
The trial was, however, stopped prematurely due to the antiatherogenic functions of HDL.
finding of high rates of antidrug antibodies. 23
4.4 TRIGLYCERIDES
4.3 HIGH DENSITY LIPOPROTEIN
Triglyceride (TG) levels in the blood are elevated for about
Low HDL-C also is associated with development and an hour following a meal, primarily as part of TG-rich
progression of atherosclerosis and is generally considered chylomicrons, and in the fasting state they are primar-
a secondary target for therapeutic intervention. A clear ily carried by Very Low Density Lipoprotein (VLDL).
inverse association of HDL-C to CHD has been shown by Apo C-II (carried by chylomicrons and VLDL) activates
a number of major prospective cohort studies. Gordon et Lipoprotein lipase (LPL) found in the capillaries of skele-
al. reported in 1989 (based on four prospective studies) tal and heart muscle, and in the adipose tissue. Associated
that a one mg/dl decrease in HDL-C was associated with LPL then acts on the TG of the lipoproteins to release free
a 2–3% increased CHD risk. Interestingly, for each one fatty acids and glycerol.30
mg/dl increase in HDL-C there appears to be a 6% lower Hypertriglyceridemia does not appear to as strong a
risk of fatal CHD events.24 It has similarly been found by risk factor for CHD as LDL-C. This may in part be due to
deGoma and colleagues in 2008 that HDL-C levels had an a greater biological and laboratory measurement variabil-
inverse relationship to myocardial infarction (MI) or hos- ity, as compared to the other dyslipidemia components and
pitalization for heart disease, even in the context of a low the other atherogenic risk factors that commonly accom-
LDL-C level. For every 10 mg/dL decrease in HDL-C, it was panies hypertriglyceremia.38 It should also be noted that
found in their sample of over 4,000 that there was a 10% triglyceride-rich VLDL is the precursor of circulating LDL
increased risk of MI or hospitalization for heart disease.25 via intermediate-density lipoprotein (IDL), which (together
4.6 Lipid Classification and Treatment Targets 55
with other apo B100-containing remnants of VLDL) appears fasting lipid panel within four to 12 weeks after initiation of
4
to be able to cross the arterial endothelium and contribute statin therapy or dose adjustment, and then every three to
to atherogenesis.39 Numerous epidemiological studies have 12 months thereafter.47 For patients started on other dyslip-
suggested that elevated TG is predictive of CHD, although idemia controlling agents, the 2013 ACC/AHA guidelines
this association appears to be lost (in some studies)40 fol- recommend additional monitoring. Prior to starting niacin,
lowing multivariate analysis that included HDL-C and baseline hepatic function, fasting glucose level, hemoglobin
other CHD risk factors.41 For example, a meta-analysis A1C, and uric acid should be checked.47 Prior to initiation
of six cohorts involving 46,000 men and 10,000 women of fibrates, renal baseline function should be established.47
indicated that each one mmol/L (88.5 mg/dl) increment in Additionally, before consideration of ezetimibe therapy,
TG level was associated with an increase in risk of CHD baseline hepatic transaminases should be evaluated.47
of 76% in women and 32% in men. However, after adjust- It is recommended that statin therapy is started if
ing for HDL-C, the increased risk was reduced to 37% a patient has any one of the following four conditions:
and 14% for women and men, respectively.41 It has fur- (1) known CHD, (2) LDL-C ≥ 190 mg/dL, (3) aged 40–75
ther been postulated that non-fasting TG may give a more years with concurrent diabetes and an LDL of 70–189 mg/
accurate assessment of risk of CHD, because postprandial dL, or (4) patients without CHD or DM between 40–75
TG-rich remnant lipoproteins can penetrate the endothe- yo with LDL-C 70–189 mg/dL and a ten-year CHD
lial cell layer and contribute in the subendothelial space to risk ≥ 7.5%.47 The guidelines advocate for the use of the
development of atherosclerosis. Although there have not Pooled Cohort Equation to estimate ten-year CHD risk.47
been any intervention trials specifically targeting TG and This risk calculation was developed by the Risk Assessment
few trials reporting the effect of triglyceride lowering on Work Group of the 2013 ACC/AHA guidelines to esti-
CHD risk, subgroup analysis of trials using fibrate or statin mate ten-year CHD risk, defined as the first nonfatal and
drugs indicated ~ 1% reduction in incidence of CHD asso- fatal occurrence of MI or stroke.47 In contrast to the 2004
ciated with each 1% reduction in TG level.42 ATP III Guidelines, the ACC/AHA guidelines do not rec-
ommend for or against specific LDL-C goals but instead
emphasize monitoring of the efficacy of statin therapy
4.5 NON-HDL CHOLESTEROL at lowering LDL-C to the desired intensity at four to 12
weeks after initiation.47 Intensity of statin treatment is
AND APO B outlined in the guidelines: high intensity treatment is con-
sidered a > 50% lowering of LDL-C, and moderate inten-
Reduction of the concentration of cholesterol within all apo
sity is considered lowering of LDL-C by 30–50%. The
B-containing lipoprotein particles (i.e., non-HDL-C, TC
intensity of statin treatment is initiated depending on the
minus HDL-C) was proposed by the National Cholesterol
degree of CHD risk according to the four conditions, or
Education Program (NCEP) Adult Treatment Panel III
“statin benefit groups,” outlined above47 (Table 4.1). The
(ATP III) as a secondary therapeutic goal in the presence
ACC/AHA guidelines do not strongly advocate for the use
of elevated TG following primary targeting of LDL-C.43 In
of pharmacotherapy other than statins, and the initiation
fact, non-HDL-C appears in observational studies to be an
of niacin, bile acid sequestrants, cholesterol-absorption
even better predictor of cardiovascular disease (CVD) than
inhibitors, fibrates, or omega-3 fatty acids have no higher
LDL-C or HDL-C alone.43 Since LDL and VLDL and its
than a level IIa recommendation,47 but these therapies can
remnants following TG lipolysis each contain one molecule
have further lipid lowering effects (Table 4.2).
of apo B, it is postulated that the plasma level of apo B rep-
The 2013 ACC/AHA guidelines do not recommend for
resents the total atherogenic particle number.44–46 A strong
or against specific LDL-C or non-HDL-C goal levels for
correlation (0.8–0.9) exists between non-HDL-C and apo
the prevention of CHD, either primary or secondary. The
B, but they are only modestly concordant.35
guidelines did not find evidence of therapies aimed at spe-
cific LDL-C or non-HDL-C improved CHD outcomes.47
4.6 LIPID CLASSIFICATION AND The 2013 ACC/AHA guidelines recommend evaluating
for secondary causes in individuals found to have triglyc-
TREATMENT TARGETS erides ≥ 500 mg/dL.47
The 2013 ACC/AHA guidelines advocate for the con-
The 2013 ACC/AHA Guideline on the Treatment of Blood sideration of non-statin therapies for the patients ≥ 21 yo
Cholesterol to Reduce Atherosclerotic Cardiovascular with untreated primary LDL-C ≥ 190 mg/dL after the
Risk in Adults emphasizes classification and treatment of maximum intensity of statin therapy has been achieved.47
hyperlipidemia (HLD) based on risk of CHD.47 The initial The use of non-statin medications were further outlined
screening for patients without CHD prior to the initiation in the 2017 Update to the 2016 ACC Expert Consensus
of pharmacotherapy is a fasting lipid panel, alanine ami- Decision Pathway on the Role of Non-Statin Therapies
notransferase (ALT, liver) level, hemoglobin A1C, CKD for LDL-Cholesterol Lowering in the Management of
level, and an evaluation of secondary causes of HLD.47 Atherosclerotic Cardiovascular Disease Risk. This expert
The screening battery for blood lipids consists of TC, LDL- consensus provides recommendations for the utilization
C, HDL-C, and TG. LDL is usually estimated using the of non-statin pharmacotherapy for the management of
Friedewald formula (LDL-C = TC minus TG/5).36 If TG HLD.18 As an update to the 2016 ACC consensus document
levels are > 400 mg/dl, isolation of the LDL fraction and on the use of non-statins, the 2017 update includes recom-
direct quantification of its cholesterol content is required. mendations integrated from recent RCTs on non-statin
The 2013 ACC/AHA guidelines recommend performing a lipid-lowering medications. The 2017 update supports the
56 Chapter 4 Clinical Strategies for Managing Dyslipidemias
TABLE 4.1 Risk category and recommended therapy intensity and expected response: 2013 ACC/AHA guidelines47
Expected response of statin Additional
Patient group Therapy intensity intensity considerations
≤75 yo with clinical CHD High intensity statin therapy Daily dose lowers LDL-C on
average by approximately 50%
≥75 yo with clinical CHD Moderate or high intensity statin* Daily dose lowers LDL-C on
average by approximately 30–50%
or 50%
≥21 yo with LDL-C ≥ 190 mg/dL High intensity statin therapy Daily dose lowers LDL-C on
average by approximately 50%
≥21yo with LDL-C ≥ 190 mg/dL on -Consider initiation
high- dose statin of non-statin drug*
40–75 yo with DM Moderate intensity statin therapy Daily dose lowers LDL-C on
average by approximately 30–50%
40–75 yo with DM with ≥ 7.5% High intensity statin therapy Daily dose lowers LDL-C on
estimated 10-year CHD risk average by approximately 50%
40–75 yo with LDL-C 70–189 without Moderate-to-high intensity Daily dose lowers LDL-C on
CHD, DM and with an estimated CHD statin* average by approximately 30–50%
risk ≥ 7.5%
40–75 yo with LDL-C 70–189 without Offer treatment with moderate Daily dose lowers LDL-C on
CHD, DM and an estimated CHD intensity statin therapy average by approximately 30–50%
risk ≤ 7.5%
* = Consider risk reduction, benefits vs. adverse effects, drug-drug interactions, and patient preferences.
TABLE 4.2 Percent changes in blood lipid/lipoprotein TABLE 4.3 Risk category and treatment goals: AACE/ACE
levels for each specific class of drugs guidelines48
Class/ LDL-C. HDL-C. TG. Treatment Treatment Treatment
Risk goal: LDL-C goal: non- goal: Apo-B
HMG-CoA reductase ↓20–63% ↑5–15% ↓10–37% category (mg/dL) HDL-C (mg/dL) (mg/dL)
inhibitors (statins, e.g.,
atorvastatin) Extreme Risk <55 <80 <70
Bile acid sequestrants ↓15–30% ↑5% ± Very High Risk <70 <100 <80
(e.g., cholestyramine)
High Risk <100 <130 <90
Fibric acid derivatives ↓10–15% ↑5–20% ↓20–50%
(e.g., gemfibrozil) Moderate Risk <100 <130 <90
scores and inflammatory marker assessment. It is prudent percent of energy from omega 6 PUFAs; and ΔZ is the
4
to use clinical judgment that includes informed patient square root of the dietary cholesterol expressed in mg per
input when prescribing medications to treat dyslipidemias. 1000 kcal of dietary energy). This equation shows that for
every 1% reduction in SFAs, serum TC is expected to be
reduced 2%. The relatively small impact of dietary cho-
4.7 ROLE OF LIFESTYLE IN THE lesterol on blood cholesterol levels is due to the limited
absorption of dietary cholesterol with about two-thirds
MANAGEMENT OF DYSLIPIDEMIA of circulating cholesterol synthesized de novo by the liver
from acetyl coenzyme A products of metabolism. 53 It
Lifestyle, particularly dietary habits, body weight, physi- should be noted that only three long-carbon chained SFAs
cal activity, alcohol consumption, and smoking, accounts have been shown experimentally to be responsible for
for the major differences in blood lipid levels in the popu- increasing TC (i.e., lauric (12:0), muristic (14:0), and pal-
lation (although heritability can make a substantial con- mitic (16:0) acid). These SFAs appear to markedly down-
tribution as well). These lifestyle habits are considered regulate hepatic synthesis of LDL apo B/E cell receptors,
major therapeutic lifestyle changes (TLC), targets for the which reduces the removal of circulating LDL, as well as
management of dyslipidemia, as supported by both the VLDL, IDL, and apo B-100-containing lipoprotein rem-
ATP III and the 2013 ACC/AHA Guidelines.47,48 nants and results in a significant increase in cholesterol
level. 53,54 Stearic acid (18:0) and SFAs with 1 0 or fewer
carbons have no effect on TC, and are not included in
4.7.1 Impact of Diet (see also chapter on the Keys equation. 52 Omega-6 PUFAs, in contrast, lower
cholesterol levels by upregulating hepatic LDL receptors
Nutrition and Cardiovascular Disease) and increasing the removal of lipoproteins and reduc-
The 2013 ACC/AHA Guideline on Lifestyle ing the rate of conversion of VLDL to LDL. The ATP-III
Management to Reduce Cardiovascular Risk advocates for recommendation is to keep intake of omega-6 PUFAs to
a diet the emphasizes intake of vegetables, fruits, and whole 10% or less of daily energy intake, since a higher intake
grains, while limiting intake of sweets, sugar-sweetened appears to lower HDL-C levels. Linoleic acid (18:2, n-6),
beverages, and red meats, in order to reduce LDL-C (level the parent compound for the omega-6 family of PUFAs,
IA).49 This guideline also supports that patients should is found in sunflower, corn, and soybean oils, seeds, and
reduce the percentage of their calories that comes from nuts. Linoleic acid form arachidonic acid (AA;20–4, n-6)
trans fat and saturated fat, with only 5–6% of total calories via enzymatic stepwise elongation of its carbon chain. AA
coming from saturated fat.49 The 2017 Update to the 2016 is the precursor of prostaglandins and eicosanoids via
ACC Expert Consensus Decision Pathway on the Role cyclooxygenase (COX) enzyme activity and is essential
of Non-Statin Therapies for LDL-Cholesterol Lowering for regulation of blood circulation, blood clotting, and
in the Management of Atherosclerotic Cardiovascular inflammatory responses.30
Disease Risk similarly advocates for the 2013 ACC/AHA Omega-3 PUFAs are a family of long-chained, essen-
perspective that lifestyle modification is needed both tial fatty acids required in the diet. They have an initial
before and after cholesterol-lowering medications are double bond/unsaturated carbon atom at the third rather
initiated.18 The primary dietary targets for a cholesterol- than the sixth position from the methyl end of the mol-
reducing program are to reduce intake of animal food ecule for omega-6 PUFA. There has been a steady increase
sources, specifically red meat, dairy products, butter, hard in the interest in omega-3-PUFA due to their apparent
margarines, and commercial baked goods25 that contain importance for eye and brain health through the life
saturated fatty acids (SFAs), since these are the principal cycle, and their postulated contribution to primary and
environmental/lifestyle contributors to elevated levels of secondary prevention of CHD. 54,55 The parent compound
blood lipid/lipoprotein levels. In addition, intake of trans- of this family is α-linolenic acid (ALA;18:3, n-3). Its car-
fatty acids should be minimized because they raise LDL-C bon chain is enzymatically converted to longer chained
and lower HDL-C. Observations from the seven countries and eventually become the more unsaturated fatty acids,
study indicated that 60–80% of the variance among the eicosapentaenoic acid (EPA; 20:5, n-3) and docahexae-
populations in mean TC levels could be accounted for by noic acid (DHA; 22:5, n-3). It should be noted that DHA
variation in mean percentage of energy from SFAs; specifi- competes with AA for conversion via COX enzyme to
cally, the cohorts which consumed 17–22% of their daily alternative eicosanoids and prostaglandins, which are
energy intake from foods high in SFAs had elevated mean believed to be cardioprotective. Because of the limited
TC levels, which was associated with a high incidence of conversion of ALA to EPA and DHA, all three are cur-
CHD. Those with a lower SFA intake (3% to 14% of daily rently considered essential dietary nutrients; however,
energy) displayed a lower CHD rate. This observation has DHA appears to be the most biologically active form of
been confirmed in the past two decades by both obser- the omega-3 PUFAs.56 ALA is primarily present in veg-
vational studies and controlled intervention trials.4,37,50,51 etable oils, particularly canola and soybean oils, whereas
Metabolic ward studies have shown that omega-6 PUFAs, fatty fish such as salmon, mackerel, herring, and sardines
particularly linoleic acid (18:1, n-6), has a cholesterol are rich sources of EPA and DHA. The apparent relation-
lowering effect, which is illustrated by the so-called Keys ship of omega-3 fatty acids to cardiovascular health was
equation:52 ΔTC = 1.3 (2ΔS – ΔP) + 1.5 ΔZ, (ΔTC is the first observed during studies of the unique dietary habits
change in total cholesterol; ΔS is the change in percent of the Greenland Inuits. 57 Despite a diet consisting pri-
of total calories provided by SFAs; ΔP is the change in marily of very fatty meat from sea mammals, they had a
58 Chapter 4 Clinical Strategies for Managing Dyslipidemias
surprisingly low rate of CVD. This was eventually attrib- 2.6% of usual daily energy intake of TFAs results from
uted to their high intake of EPA and DHA from these food intake of margarines and shortenings used in food prepa-
sources. Other epidemiological observational studies have ration. This is due to the formation of TFAs by the partial
consistently reported an inverse association between con- hydrogenation of the double bonds of unsaturated fatty
sumption of fish or fish oil supplements, with morbidity acids in liquid vegetable oils to solidify them, since this
and mortality from CVD. 58 The cardioprotective effects makes products more heat-stable and increases shelf life.66
of these fatty acids has further been confirmed in animal TFAs appear to promote an increase in cholesterol synthe-
models and by primary and secondary CHD prevention sis and a concomitant increase in LDL-C levels. But more
trials, indicating a 20–30% reduction in fatal and non- importantly, in contrast to SFAs, they increase LP(a) and
fatal CHD events.59,60 It appears that a modest intake of lower HDL-C levels.67
fatty fish, for example, two to three portions per week or A diet high in non-digestible fiber may have a mod-
a daily fish oil capsule can reduce risk of CHD, whereas est beneficial effect on TC and LDL-C levels.37,68 Soluble
consumption of ALA from vegetable oils does not appear fiber components, particularly β-glycans and pectin,
to be as cardioprotective (Table 4.4). contribute to blood cholesterol reduction. Soluble fibers
DHA and EPA fish oil-based supplements appear to are found in whole grains (especially oats), fruits and
result in a reduction in TG (6% to 10% per gm of EPA vegetables, and beans and legumes. Soluble fibers bind
and DHA), VLDL-C, VLDL-TG, and non-HDL-C, and and thus prevent reabsorption of bile salts in the small
an increase in HDL-C.62 Thus, large doses of EPA- and intestine, which results in upregulation of hepatic LDL
DHA-based fish oil supplements in combination with a receptors, thereby enhancing LDL removal and reduc-
statin drug appear to be an effective therapeutic approach ing LDL-C levels. An intake of 30 g/d of soluble fiber has
for treatment of mixed dyslipidemia, 39 and it appears that been reported to be associated with a 5 mg/dl reduction
intake of fatty acids in the form of fish or fish-oil supple- in total LDL-C levels and especially the smaller, dense,
ments reduces the rate of all-cause mortality, cardiac, and atherogenic LDL particles, thereby reducing fatal and
sudden death.63 nonfatal CHD events.37,69–72 It also should be noted that
Attention was first directed to the benign relationship dietary fiber slows gastric emptying and glucose absorp-
of monounsaturated fatty acids (MUFAs) in the diet to risk tion, which decreases insulin response and thus reduces
of CHD by the Seven Countries Study.4 Approximately hepatic lipogenesis and promotes satiety. The 2013 AHA/
80% of the fatty acids contained in olive oil are MUFAs, ACC Guideline on Lifestyle Management to Reduce
particularly oleic acid (18:1, n9). Oleic acid either has no Cardiovascular Risk states that more research is needed
effect on blood lipids or, as reported in some studies, it on the influence of fiber on lipids and CHD risk.49 Plant
reduces TC levels but appears to have no effect on HDL-C steroids and stanols (when esterified with a fatty acid, or
or TG levels.64 However, the presence of MUFAs in LDL when emulsified such as Benecol) are plentiful in vegetable
makes it less susceptible to oxidation. MUFAs are plenti- oils, seeds, and nuts.73 It appears that PUFA margarines
ful in olive oil, canola and peanut oil, avocados, nuts, and with or without the addition of 2 g/d of sterols/stanols to
fish. the diet may result in a reduction of 21 mg/dl in LDL-C
Trans fatty acids (TFAs) have attracted attention in (a 9–27% reduction) and non-HDL-C levels.73,74 LDL-C
recent years due to their adverse effects on blood lipids. removal is enhanced via an upregulation of LDL receptors
New York City and California have banned the use of in the liver, in part due to competitive inhibition of dietary
TFAs in restaurants for food preparation. In fact, the FDA and biliary cholesterol uptake in the small intestine.37 ATP
now mandates inclusion of quantities of TFAs on food III has endorsed the use of stanol-enriched margarines as
labels along with that of SFAs and PUSFs, and a recent an adjunct for lowering LDL, but neither the 2013 ACC/
FDA ruling deemed hydrogenated oils as not safe for use in AHA Guideline on the Treatment of Blood Cholesterol to
human food, with a mandate to remove partially hydroge- Reduce Atherosclerotic Cardiovascular Risk in Adults nor
nated oils from products by 2018.65 It should be noted that the 2013 AHA/ACC Guideline on Lifestyle Management
only a limited quantity of TFAs occurs naturally in meat to Reduce Cardiovascular Risk advocates for these
and dairy products, while essentially all of the reported products.47,49
Plant-derived antioxidants such as lipid-soluble vita-
min E and β and other carotenes, water-soluble vitamin
TABLE 4.4 Experimentally identified mechanisms C, and a large variety of non-nutrient phytochemicals are
postulated to contribute to the apparent cardioprotective
effects of Omega-3 PUFAs59–61
postulated to reduce the development and progression of
CHD by preventing oxidative stress and reducing LDL
• Reduced dyslipidemia (decreased TG and VLDL-C, and oxidation and endothelial dysfunction.68,75 Vitamin E,
increased HDL-C) found in vegetable oil, nuts, and seeds, is transported by
• A moderate reduction in elevated blood pressure LDL and has been associated with a reduction of CHD
• Improved endothelial function and endothelial-dependent
risk and reduction of oxidized LDL.68,75 However, it
and independent vasoreactivity
• Anti-inflammatory effects, inhibiting progression of should be noted that numerous large-scale randomized
atherosclerosis controlled clinical trials and meta-analyses have failed
• Antithrombotic effects to demonstrate any protective effect against CVD mor-
• Increased parasympathetic activity, as evidenced by tality by supplementation of antioxidant vitamins (vita-
increased heart rate variability min E, vitamin C, or beta carotene).68,75–77 Flavonoids are
• Improved myocardial electrical stability, reducing risk of a
another type of plant chemical (phytochemicals) of sig-
fatal ventricular arrhythmia
nificant health-promoting interest in recent years. They
4.8 Weight Management 59
are found in fruits, vegetables, tea, red wine (and grape Numerous dietary approaches have been promoted for
4
juice from which wine is derived), and cocoa bean prod- weight reduction. These diets often target a specific mac-
ucts. In vitro studies have shown these phytochemicals to ronutrient (i.e., fat, carbohydrates, or protein). However,
be potent inhibitors of LDL oxidation.68 In a prospective it should be noted that the greatest impact on the ini-
cohort study, flavonoid consumption was associated with tial amount of weight loss is the level of energy deficit
lower risk of death from CHD.78 However, overall there achieved, irrespective of the dietary approach. Current
have been inconsistent results from clinical trials, and cur- guidelines specify that daily energy intake should not be
rent evidence does not clearly support their use in a clini- lower than 1000 to 1500 kcal/d, to provide all essential
cal setting but suggests that more research is needed.68,79 nutrients while achieving an adequate negative energy
A moderate alcohol intake of one to two drinks per balance.69–76,80 –82,85 The 2013 AHA/ACC/TOS Guidelines
day has been associated with about a one-third lower risk for the Management of Overweight and Obesity in Adults
of mortality from CHD when compared to either no alco- recommends prescribing a calorie-restricted diet based
hol or heavy alcohol consumption, possibly due to both on patient preference and health status, since numerous
antithrombotic effects and ethanol-involved increased dietary approaches can lead to weight loss in obese adults
HDL-C levels (by ~12%).68,80 However, it should be noted (1A recommendation).83
that alcohol also produces a concomitant increase in TG It appears that a successful 10% weight loss may
and VLDL production and therefore raises non-HDL-C result in a significant decrease in TC of 30.5 mg/dl
levels. Moreover, excessive use of alcohol raises blood (-13.2%), LDL-C 15.1 mg/dl (-11.3%), VLDL-C 15.5 mg/
pressure and is potentially addictive, and can contribute dl (-36.5%), and TG 58.4 mg/dl (-32.2%); HDL-C ini-
to major health problems in addition to increasing risk of tially declines during the active weight loss phase and
accidents and violent death. Thus, it is considered unethi- then increases 5.5 mg/dl (+12.6%) after weight stabili-
cal to encourage non-drinkers to start using alcohol for zation. This represents about a 0.35 mg/dl increase in
prevention of CHD. HDL-C for every kg of weight lost.86 In a meta-analysis,
Nordmann et al.87 compared the effects of a reduced-fat
diet to a low-carbohydrate diet (i.e., the Atkin’s diet) in
4.8 WEIGHT MANAGEMENT 5 studies on weight loss and cardiovascular risk factors.
The fat content of the reduced-fat diets was limited to
Health consequences associated with excess body weight 25–35% (current recommendation) of daily energy in
include dyslipidemia, all components of the metabolic syn- four of these studies and to 10% in one study. The low-
drome, and thereby an increased risk of type 2 diabetes and carbohydrate diet was unlimited in protein and fat intake.
CHD.81 Thus, weight reduction is a critical component in The mean weight loss at six months was significantly
the management of dyslipidemia. Obesity results generally greater on the low-carbohydrate diet, while at 12 months
from a combination of overeating and sedentary lifestyle, there was no statistically significant difference between
causing a positive energy balance and thus an increase in the low-carbohydrate and the reduced-fat diets. However,
lipogenesis and fat storage. In order to lose weight, a sus- the reduction in TC and LDL-C was more favorable on
tained negative energy balance must be achieved. The ATP the low-fat diets compared to the low carbohydrate diets,
III43 the AHA,82 the AHA/ACC/TOS Guidelines for the (mean difference in LDL-C between diets was −5.4 mg/
Management of Overweight and Obesity in Adults,83 and dl). Interestingly, changes in HDL-C (+4.6 mg/dl) and TG
the American College of Sports Medicine84 recommend (-22.1 mg/dl) were significantly more favorable on the
a sustained weight reduction effort by achieving a mod- low-carbohydrate diets. A recent meta-analysis by Hu
est negative energy balance of 500 to 1000 kcal/d. This and colleagues of 23 trials found that patients who fol-
is expected to result in a one-to-two lb (0.45 to 0.99 kg) lowed low-carbohydrate diets compared to low-fat diets
weight loss per week. The initial goal is to achieve a 5–10% experienced a small but statistically significant lower
weight loss over a six-month period. If this weight loss is reduction in TC (2.7 mg/dL) and LDL-C (3.7 mg/dL) but
achieved via dietary changes only, about 75% of this loss a greater increase in HDL-C (3.3 mg/dL) and a greater
is generally from fat and 25% is from fat-free mass (FFM). decrease in TG (-4 mg/dL), but these findings were not
If exercise is combined with a reduced energy intake, FFM examined for long-term effects.88
is generally better preserved during weight reduction, and A randomized study89 investigated the effects of weight
weight regain appears to be less likely.65–67 loss and blood lipid changes in three diets—a low-carbohy-
It is essential to include behavioral modification of eat- drate, non-restricted calorie diet with a reduced fat (<35%
ing habits and regular PA to successfully achieve and main- of daily energy); a restricted-calorie diet, following AHA
tain a more desirable body weight.81,82,85 Bariatric surgery guidelines; and a restricted calorie Mediterranean-type
commonly results in a substantial weight loss, however diet. The mean weight loss after the two-year follow-up
there are serious risks associated with the surgical proce- was 2.9 kg for the AHA diet, 4.4 kg for the Mediterranean
dures, including postsurgical complications related to the diet, and 4.7 kg for the low-carbohydrate diet. There was
induced nutrient malabsorption. The 2013 AHA/ACC/ a mean increase in HDL-C of 8.4 (+22.4%), 6.3, and
TOS Guidelines for the Management of Overweight and 6.4 (+16%) mg/dl for the low-carbohydrate, AHA, and
Obesity in Adults recommends level IIA bariatric surgery Mediterranean diets, respectively. TG reduction (23.7 mg/
for adults with BMI > 40 or BMI > 35 with obesity-related dl) also was significantly more favorable with the low-
comorbid conditions who are motivated to lose weight and carbohydrate diet. Surprisingly, in this study there was no
have not responded to behavioral interventions.83 significant change in LDL-C in any group.
60 Chapter 4 Clinical Strategies for Managing Dyslipidemias
The combination of dietary modification and regular exercise training100 that appears to be related to genetic
exercise has consistently been shown to be the most effec- factors as well as weight change.101–105 Additionally, indi-
tive approach for achieving and maintaining long-term viduals with a low baseline level of HDL-C or sedentary
weight reduction (~1 kg/wk greater weight loss than diet- women with genetically high HDL-C levels appear less
ing alone).81,82,85 Aerobic exercise (as well as resistance likely to respond to exercise training.84 Exercise-induced
exercise) may attenuate FFM loss that will occur with reductions in LDL-C and TG appear to be rare in the
weight loss.85 Regular aerobic exercise for 60–90 min- absence of an associated weight loss.96–99 The majority of
utes per day is critical for preventing weight regain.90,91 well-controlled studies on the effect of exercise on blood
However, exercise alone is generally not effective for lipids have used a standard exercise prescription of a mod-
inducing sizable weight loss, unless one performs super- erate-to high-intensity aerobic exercise for 30–60 minutes
vised, large-volume, prolonged aerobic exercise five to three times per week, with a weekly energy expenditure
seven days/week.85 of 900–2000 kcal (or about 10–20 MET hrs.) for at least
12 weeks (~15–20 miles/wk of walking).96–99 The 2013
AHA/ACC Guideline on Lifestyle Management to Reduce
4.8.1 Exercise Effects (see also Cardiovascular Risk advises at a level IIa that to reduce
LDL-C and non-HDL-C, adults should participate in
chapter on Physical Activity physical activity three to four times per week of 40 min-
and Fitness in the Prevention utes at moderate-to-vigorous intensity.49
of Cardiovascular Disease) Cigarette smoking has been associated with reduced
Apo-A-I and HDL-C levels about 4 to 6 mg/dl, or 11–14%
It has been well established that increased physical activity
lower than nonsmokers.106–108 More importantly, smok-
and exercise training reduce morbidity and mortality from
ing cessation appears to results in a rapid improvement
CHD through multiple cardioprotective effects, includ-
in HDL-C (an average 6–8 mg/dl increase).109 In addition,
ing reducing dyslipidemia.92–95 Studies have consistently
smokers have been reported to have slightly higher LDL-C
shown that aerobic exercise training results on the average
levels than nonsmokers. These adverse effects of smoking
in a modest increase in HDL-C of two to three mg/dl, or
on blood lipids are postulated to be due both to nicotine
about 4–5%, with an associated increase in apo A-I and
and carbon monoxide exposure.110
LPL activity.96–99 However, it should be noted that there is
a great deal of variability the response of HDL-C following
4.9 CONCLUSIONS AND
TABLE 4.5 Clinical applications
TG (and
RECOMMENDATIONS
Dietary component Non- Therapeutic lifestyle components are major contributors to
or TLC change TC LDL-C HDL-C HDL-C) dyslipidemia and resulting CHD, particularly eating hab-
Decrease SFAs, trans ↓↓ ↓↓ ↓ ↓ its and low levels of physical activity. The high consump-
fats, and cholesterol tion of red and processed meat, high-fat milk and dairy
Increase omega-6 ↓ ↓ → → products, fried and salty foods, refined grain products,
PUFAs ↓ and sugar-laden desserts and soft drinks are principally
responsible to for the obesity epidemic and associated dys-
Increase omega-3 → → ↑ ↓↓ lipidemia in this country.111–114 It has been well established
PUFAs ↑ →
that eating patterns associated with reduced rates of dys-
Increase MUFAs → → ↑ ↓ lipidemia and CVD include:
↓ ↓ →
Increase Soluble ↓ ↓ → → • Vegetarian and near-vegetarian diets115,116
Fiber • Mediterranean-style diets4,50,51,117,118
Moderate Alcohol → → ↑↑ ↑↑
• The Dietary Approach to Reduce Hypertension
(DASH) diet119–121,49
Phytosterols ↓ ↓ → → • The “Prudent Heart Healthy Diet,” advocated by
Soy Proteins ↓ ↓ → ↓ the AHA (formerly the AHA Step II Diet), ATP III,
and the U.S. Department of Agriculture (USDA)
Vitamin E (recycled _ ↓ OxLDL _ _ and U.S. Department of Health and Human
by vitamin C)
Services (DHHS), Dietary Guidelines for Americans
Negative Energy ↓ ↓ ↑ ↓↓ 2005,43,121–123 and the AHA diet124
balance (Wt. loss)
Aerobic Exercise ↓ ↓ ↑ → Successful dietary patterns to improve blood lipid pro-
→ → file should be characterized by (1) a low intake of saturated
fat, trans fat, and dietary cholesterol through a reduction
Smoking Cessation → → ↑ ↓
in consumption of red meat, hard fats, full-fat milk, and
↑ = Increase, ↓ = Decrease, → = No change (2) an increased intake of whole grains, legumes, fruits,
References 61
Total fat: 25%–35% and vegetables, and a moderate intake of fish and poul-
4
try and low-fat or fat-free milk and dairy products (see
Saturated fat: <7% also Chapter 8 on Nutrition and Cardiovascular Disease).
Trans fats: <1% The recommended macronutrient content of this eat-
ing pattern, as a percentage of daily energy intake, is as
Monounsaturated fats: 15% follows:43,125
Polyunsaturated fats 10% or less The combination of a proper dietary plan and regular
aerobic exercise has been reported to lower TC, LDL-C,
(with an omega-6 to 3 ratio of 3 to 4 to 1)
and TG by 7–18%, and TG by 4–18%, while increas-
Cholesterol: ≤200 mg/d ing HDL-C 2–18%.126 Weight management is critically
Protein: About 15% important in improving blood lipid profile. Table 4.5
summarizes the effects of specific dietary components and
Carbohydrates 50–60% other TLC reviewed in this chapter on dyslipidemia.
REFERENCES
1. Mercado, C, DeSimone, AK, Odom, E, disease. Current and future prospective. patients with cardiovascular disease. N.
et al. Prevalence of cholesterol treatment Circulation 2008;52:132–134. Engl. J. Med. 2017;376(18):1713.
eligibility and medication use among 12. Thomopoulos, C, Skalis, G, 22. Robinson, JG, Farnier, M, Krempf,
adults – United States, 2005–2012. Michalopoulou, H, Tsioufis, C, and M, et al. Efficacy and safety of ali-
MMWR Morb. Mortal. Wkly. Rep. Makris, T. Effect of low-density lipopro- rocumab in reducing lipids and car-
2015;64(47):1305–1311. tein cholesterol lowering by ezetimibe/ diovascular events. N. Engl. J. Med.
2. Brown, MS and Goldstein, JL. Familial simvastatin on outcome incidence: 2015;372(16):1489–1499.
hypercholesterolemia defective binding Overview, meta-analyses, and meta- 23. Ridker, PM, Revkin, J, Amarenco, P, et
of lipoproteins to cultured fibroblatis regression analyses of randomized trials: al. Cardiovascular efficacy and safety of
with impaired regulation of 3-hydroxy-3 Effect of LDL-C lowering on outcomes. bococizumab in high-risk patients. N.
methylglutanyl coenzyme A reductase Clin. Cardiol. 2015;38(12):763–769. Engl. J. Med. 2017;376(16):1527–1539.
activity. Proc. Natl. Acad. Sci. USA 13. LaRosa, JC, He, J, and Vuppututi, 24. Gordon, D, Probstfield, J, Garrison, RJ,
1974;71:788–792. S. Effects of statins on risk of coro- et al. High-density lipoprotein cholesterol
3. Keys, A. Coronary heart disease nary heart disease: A meta-anal- and cardiovascular disease: Four pro-
– The global picture. Atherosclerosis ysis of randomized trials. JAMA spective American studies. Circulation
1975;22:149–152. 1999;282:23430–2346. 1989;79:8–19.
4. Keys, A. Coronary heart disease 14. Ray, KK and Cannon, CP. The potential 25. deGoma, EM, Leeper, NJ, and Heidenreich,
in seven countries. Circulation relevance of the multiple lipid-independent PA. Clinical significance of high-density
1970;41(S1):118–139. (pleiotropic) effects of statins in manage- lipoprotein cholesterol in patients with low
5. Kannel, WB, McGee, D, and Gordon, ment of the acute coronary syndrome. J. low-density lipoprotein cholesterol. J. Am.
T. A general cardiovascular risk profile: Am. Coll. Cardiol. 2005;46:1425–1433. Coll. Cardiol. 2008;51(1):49–55.
The Framingham Study. Am. J. Cardiol. 15. Reilly, SD, Litovsky, SH, Seinkamp, MP, 26. Rubins, HR, Robins, SJ, Collins, D,
1976;38:46–51. and Caulfield, JB. Statins improve human et al. Gemfibrozil for the secondary
6. The Pooling Project Research Group. coronary arteriosclerotic plaque morphol- prevention of coronary heart disease
Relationship of blood pressure, serum cho- ogy. Tex. Heart Inst. J. 2008;35:99–103. in men with low levels of high-density
lesterol, smoking habits, relative weight and 16. Cannon, CP, Blazing, MA, Giugliano, lipoprotein cholesterol. Veteran’s Affairs
ECG abnormalities to incidence of major RP, et al. Ezetimibe added to statin ther- High-Density Lipoprotein Intervention
coronary events. Final Report of the Pooling apy after acute coronary syndromes. N. Trial Study Group. N. Engl. J. Med.
Project. American Heart Association Engl. J. Med. 2015;372(25):2387–2397. 1999;34:410–418.
Monograph Number 60. American Heart 17. Baigent, C, Landray, MJ, Reith, C, et al. 27. Assmann, G and Noter, JR.
Association, Dallas, TX, 1978 (also in J. The effects of lowering LDL choles- Atheroprotective effects of high-
Chronic Dis. 1978;31:201–306). terol with simvastatin plus ezetimibe density lipoprotein. Ann. Rev. Med.
7. Stamler, J, Wentworth, D, and Neston, in patients with chronic kidney disease 2003;54:321–341.
JD. Is the relationship between serum (Study of Heart and Renal Protection): 28. Dansky, HM and Fischer, EA. High-
cholesterol continuous and graded? A randomised placebo-controlled trial. density lipoprotein and plaque regression.
Findings from the Multiple Risk Factor Lancet 2011;377(9784):2181–2192. The good cholesterol gets even better.
Intervention Trial (MRFIT). JAMA 18. Lloyd-Jones, DM, Morris, PB, Circulation 1999;100:1767–1763.
1986;256:2823–2828. Ballantyne, CM, et al. 2017 Focused 29. Briel, M, Ferreira-Gonzalez, I, You,
8. Mudd, JO, Borlaug, BA, Johnson, PV, update of the 2016 ACC expert consensus JJ, et al. Association between change
et al. Beyond low-density lipoprotein decision pathway on the role of non- in high density lipoprotein cholesterol
cholesterol. J. Am. Coll. Cardiol. Statin therapies for LDL-Cholesterol and cardiovascular disease morbid-
2007;50:1735–1741. lowering in the management of athero- ity and mortality: Systematic review
9. Batter, PJ, Ballantyne, CM, Carhona, R, sclerotic cardiovascular disease risk: and meta-regression analysis. BMJ
et al. APO B versus cholesterol in estimat- A Report of the American College 2009;338(7693):522–526.
ing cardiovascular risk and in guiding of Cardiology Task Force on Expert 30. Baymes, JW and Dominiczac, MH.
therapy: Report of the thirty-one person/ Consensus Decision Pathways. J. Am. Lipids and lipoproteins. In: Medical
thirty-country panel. J. Intern. Med. Coll. Cardiol. 2017;70(14):1785. Biochemistry, 2nd Edition. Elsevier
2006;259:247–258. 19. Phan, BAP, Dayspring, TD, and Toth, PP. Mosby, Philadelphia, 2005. pp. 225–243.
10. Committee on Diet and Health, Food Ezetimibe therapy: Mechanism of action 31. Nissen, SE, Tardif, JC, Nichols, SJ, et al.
and Nutrition Board, Commission on and clinical update. Vasc. Health Risk Effect of torcetrapib on the progression
Life Science, National Research Council. Manag. 2012;8:415–427. of coronary atherosclerosis. N. Engl. J.
Fats and other lipids. In: Diet and Health 20. Page, MM and Watts, GF. PCSK9 Med. 2007;156:1014–1015.
Implications for Reducing Chronic inhibitors – Mechanisms of action. 32. Kastelein, JJ, van Leuven, SI, Burgess,
Disease Risk. National Academy Press, Aust. Prescr. 2016;39(5):164–167. L, et al. Effects of torcetrapib on
Washington, DC, 1989. pp. 154–288. doi:10.18773/austprescr.2016.060 carotid atherosclerosis in familial
11. Bergland, L and Anuurad, E. Role 21. Sabatine, MS, Sever, PS, Wang, H, et al. hypercholesterolemia. N. Engl. J. Med.
of apoprotein (a) in cardiovascular Evolocumab and clinical outcomes in 2007;256:1620–1630.
62 Chapter 4 Clinical Strategies for Managing Dyslipidemias
33. Van der Steeg, WA, Holme, I, Boekholdt, Clinical Endocrinologists and American Determination Regarding Partially
SM, et al. High-density lipoprotein cho- College of Endocrinology guidelines for Hydrogenated Oils (Removing Trans Fat).
lesterol, high-density lipoprotein particle management of dyslipidema and preven- [WebContent]. 2018; https://www.fda
size, and apolipoprotein A-1: Significance tion of cardiovascular disease. Endocr. .gov/Food/IngredientsPackagingLabeling/F
for cardiovascular risk. The IDEAL Pract. 2017;23(Suppl 2):1–87. oodAdditivesIngredients/ucm449162.htm.
and EPIC-Norfolk Studies. J. Am. Coll. 49. Eckel, RH, Jakicic, JM, Ard, JD, et al. 2013 Accessed February 23, 2018.
Cardiol. 2008;51:634–640. AHA/ACC Guideline on lifestyle manage- 66. Graf, PA, Lemke, S, and Di Rienzo,
34. Barter, PJ, Caulfield, M, Eriksson, M, ment to reduce cardiovascular risk: A report M. Reducing the trans-fatty acids
et al. Effects of torcetrapib in patients at of the American College of Cardiology/ content of foods regulatory and food
high risk for coronary events. N. Engl. J. American Heart Association Task Force industry approaches. Nutr. Today
Med. 2007;357(21):2109–2122. on Practice Guidelines. Circulation 1008;43(2):46–51.
35. Genest, J. The Yin and Yang of high-den- 2014;129(25_Suppl_2 Suppl 1):S76–S99. 67. Stender, S, Dyerberg, J, Holme, RG,
sity lipoprotein cholesterol. J. Am. Coll. 50. Trichopoulous, A, Costaco, T, Bamia, C, et al. The influence of trans fatty
Cardiol. 2008;51:643–646. and Trichopoulous, D, Mediterranean acids on health: A report from the
36. Chiesa, G and Sirtori, CR. diet and survival in a Greek population. Danish Nutritional Council. Clin. Sci.
Apolipoprotein A-1 Milano: Current N. Engl. J. Med. 2003;348:2599–2608. 1995;375–392.
perspectives. Curr. Opin. Lipidol. 51. deLorgeri, M, Renaud, S, Manelle, 68. Bettridge, DJ and Morrell, JM.
2003;14:159–163. M, et al. Mediterranean alpha linoleic Clinician’s Guide to Lipids and
37. Zarraga, IGE and Schman, ER. Impact acid rich diet in secondary preven- Coronary Heart Disease, 2nd Edition.
of dietary patterns and intervention tion of coronary heart disease. Lancet Arnold, London, 2003. pp. 101–235.
on cardiovascular health. Circulation 1994;343:1454–1459. 69. Brown, L, Rosner, B, Willett, WW, and
2006;114:961–973. 52. Keys, A and Parling, RW. Serum choles- Sachs, FM. Cholesterol-lowering effects
38. Gotto, AM, Jr. Contemporary Diagnosis terol response to dietary lipids. Am. J. of dietary fiber: A meta-analysis. Am. J.
and Management of Lipid Disorders, Clin. Nutr. 1966;19:171–181. Clin. Nutr. 1999;69:30–42.
3rd Edition. Newton, PA: Handbooks in 53. Jones, PJH. Regulation of cholesterol 70. Pereira, MA, O’Reilly, E, Augustsson, K,
Healthcare, 2004. pp. 7–42. biosynthesis by diet in humans. Am. J. et al. Dietary fiber and risk of coro-
39. Tanaka, A, Ai, M, Kobayashi, Y, et al., Clin. Nutr. 1997;66:438–446. nary heart disease: A pooled analysis
Metabolism of triglyceride-rich lipopro- 54. Fernandez, JL and West, KL. of cohort studies. Arch. Intern. Med.
tein and their role in atherogenesis. Ann. Mechanisms by which dietary fatty 2004;164:370–376.
N. Y. Acad. Sci. 2001;947:207–213. acids modulate plasma lipids. J. Nutr. 71. Jacobs, DR, Jr. and Gallaher, DD.
40. Sarwar, N, Danesh, J, Elrlksdotir, 2005;135:2075–2078. Whole grain intake and cardiovascular
G, et al. Triglyceride and the risk of 55. Breslow, JL. n-3 fatty acids and car- disease: A review. Curr. Atheroscler. Rep.
coronary heart disease;10,158 incident diovascular disease. Am. J. Clin. Nutr. 2004;6:415–423.
cases among 262,525 participants in 29 2006;83(Suppl.):1477S–1482S. 72. Dauchet, L, Amouyel, P, Hercberg, S,
Western prospective studies. Circulation 56. Artherburn, L, Hall, EB, and Oken, H. and Dallonguille, J. Fruits and vegetables
2007;15:450–458. Distribution, interconversion, and dose consumption and risk of coronary heart
41. Hokanson, JE and Austin, MA. Plasma tri- response of n-3 fatty acids. Am. J. Clin. disease: A meta-analysis of cohort stud-
glyceride level is a risk factor for cardiovas- Nutr. 2006:83(Suppl.);1467S–1476S. ies. J. Nutr. 2006;136:2588–2593.
cular disease independent of high-density 57. Bang, HO and Dyerberg, J. Lipid 73. Law, M. Plant sterol and stanol marga-
lipoprotein cholesterol level: A meta-analy- metabolism and ischemic heart disease in rine and health. BMJ 2000;320:861–864.
sis of population-based prospective studies. Greenland Eskimos. In: Draper, HH (ed). 74. Miettingen, T, Puska, P, Gylling, H, et
J. Cardiovasc. Risk 1996;5:213–219. Advances in Nutrition Research. New al. Reduction of serum cholesterol with
42. Miller, M, Cannon, C, Murphy, SA, et al. York, Plenum Publishing, 1980. pp. 1–22. sitosterolester margarine in a mildly
Impact of triglyceride levels beyond low 58. He, K, Song, Y, Daviglus, ML, et al. hypercholesterolemic population. N.
density lipoprotein cholesterol after an Accumulated evidence on fish consump- Engl. J. Med. 1995;333:1308–1312.
acute coronary syndrome in the PROVE tion and coronary heart disease: A meta- 75. Fletcher, B, Berra, K, Braun, L, et al.
IT-TIMI trial. J. Am. Coll. Cardiol. analysis of cohort studies. Circulation Managing abnormal blood lipids. A
2008;51:724–730. 2004;109:2705–2711. collaborated approach. Circulation
43. Adult Treatment Panel III. Executive 59. Von Schacky, C. n-3 fatty acids 2005;112:3184–3209.
summary of the third report of the and the prevention of coronary ath- 76. Hooper, L, Ness, AR, and Smith, GD.
National Cholesterol Education Program erosclerosis. Am. J. Clin. Nutr. Meta-analysis of effect of high versus low
(NCEP). Expert panel on the detec- 200;71(Suppl):224S–227S. vitamin E intake on cardiovascular mor-
tion, evaluation, and treatment of high 60. Harris, WS. n-3 fatty acids and lipo- tality for observational and interventional
blood cholesterol in adults. JAMA proteins: Comparison of results from studies. Lancet 2001;357:1705–1706.
2001;285:2486–2497. human and animal studies. Lipids 77. Myung, S-K, Ju, W, Cho, B, et al.
44. Pischon, T, Girman, CT, Sacks, FM, et al. 1996;31:243–252. Efficacy of vitamin and antioxidant
Non-high density lipoprotein cholesterol 61. Holub, BU. Clinical nutrition: 4. supplements in prevention of cardiovascu-
and apolipoprotein B in the predic- Omega-3 fatty acids in cardiovascular lar disease: Systematic review and meta-
tion of coronary heart disease in men. care. JAMC 2002;116:608–615. analysis of randomised controlled trials.
Circulation 2005;112:3375–3383. 62. Davidson, MH, Stein, EA, and Bay, BMJ 2013;346(7893):12–12.
45. Kasterlein, JP, Van Der Steig, WA, HE. Efficacy and tolerability of adding 78. McCullough, ML, Peterson, JJ, Patel,
Holme, I, et al. Lipids, apolipoproteins, prescription omega-3 fatty acids 4 g/d to R, Jacques, PF, Shah, R, and Dwyer,
and their ratios in relationship to cardio- simvastatin 40 mg/d in hypertriglyceri- JT. Flavonoid intake and cardiovascu-
vascular events with statin treatment. demic patients: An 8-week, randomized, lar disease mortality in a prospective
Circulation 2008;117:3002–3009. double-blind, placebo-controlled trial. cohort of US adults. Am. J. Clin. Nutr.
46. Snidermann, AD. Apoliprotein B versus Clin. Ther. 2007;29:1354–1367. 2012;95(2):454–464.
non-high-density lipoprotein choles- 63. Wang, C, Harris, WS, Chung, M, et 79. Peterson, JJ, Dwyer, JT, Jacques, PF, and
terol and the winner is…. Circulation al. n-3 Fatty acids from fish or fish-oil McCullough, ML. Do flavonoids reduce
2005;112:3366–3373. supplements, but not α-linolenic acid, cardiovascular disease incidence or
47. Stone, NJ, Robinson, JG, Lichtenstein, benefit cardiovascular disease outcomes mortality in US and European popula-
AH, et al. 2013 ACC/AHA guideline in primary- and secondary-prevention tions? Nutr. Rev. 2012;70(9):491–508.
on the treatment of blood cholesterol to studies: A systematic review. Am. J. Clin. doi:10.1111/j.1753-4887.2012.00508.x
reduce atherosclerotic cardiovascular Nutr. 2006;84(1):5–17. 80. Law, M and Wald, N. The relative risk
risk in adults: A report of the American 64. Gordner, CD and Kraemer, HC. of CHD death according to alcohol
College of Cardiology/American Heart Monounsaturated versus polyunsatu- consumption in the five largest cohort
Association Task Force on Practice rated fat and serum lipids: A meta-anal- studies. Br. Med. J. 1999;318:1471–1480.
Guidelines. J. Am. Coll. Cardiol. ysis. Arteroscler. Thromb. Vasc. Biol. 81. National Institute of Health. Clinical
2014;63(25 Pt B):2889. 1995;15:1917–1927. Guidelines on the Identification,
48. Jellinger, PS, Handelsman, Y, Rosenblit, 65. Food and Drug Administration. Evaluation and Treatment of Overweight
PD, et al. American Association of Food Additives & Ingredients – Final and Obesity in Adults. The Evidence
References 63
Report. NIH Publication, No. 98-408, Scientific Statement. Circulation antihypertensive medication. Circulation
Bethesda, MD, 1998. 2005;111:369–376. 2000;114:160–167.
82. Klein, S, Burke, LE, Bray, GA, et al.
Clinical implications of obesity with
specific focus on cardiovascular disease.
96. Kodama, S, Tanaka, S, Saito, K, et al.
Effects of aerobic exercise training on
serum levels of high-density lipopro-
112. Iestra, JA, Kromhout, D, Van der
Schouw, YT, et al. Effect size of life-
style and dietary changes on all-cause
4
A statement for professionals from the tein cholesterol. A meta-analysis. Arch. mortality in coronary artery disease
American Heart Association Council on Intern. Med. 2007;167:999–1008. patients. A systematic review. Circulation
Nutrition, Physical Activity and metabo- 97. Durstine, SL, Grandjean, PW, Cox, CA, 2005;112:924–939.
lism. Circulation 2004;110:2952–2967. and Thompson, PD. Lipids, lipopro- 113. Heidemamn, C, Schulze, MB, Franco,
83. Jensen, MD, Ryan, DH, Apovian, CM, teins, and exercise. J. Cardiopul. Rehab. OH, et al. Dietary patterns and risk of
et al. 2013 AHA/ACC/TOS guideline for 2002;22:389–398. mortality from cardiovascular disease,
the management of overweight and obe- 98. Leon, AS and Sanchez, OA. Response cancer, and all-causes mortality in a
sity in adults: A report of the American of blood lipids to exercise train- prospective cohort of women. Circulation
College of Cardiology/American Heart ing alone or combined with dietary 2008;118:230–237.
Association Task Force on Practice intervention. Med. Sci. Sports Exerc. 114. Appel, LJ. Dietary patterns and longevity.
Guidelines and The Obesity Society. 2001;33(Suppl):S502–S15. Expanding the blue zones. Circulation
Circulation 2014;129(25_Suppl_2 Suppl 99. Leon, AS, Rice, R, Mandel, S, et al. 2008;118:214–215.
1):S102–S138. Blood lipid response to 20 weeks of 115. Position of the American Dietetic
84. Riebe, D, Ehrman, JK, Liguori, G, supervised exercise in a large biracial Association and Dieticians of Canada.
and Magal, M. American College of population: The HERITAGE Family Vegetarian diets. J. Am. Diet. Assoc.
Sports Medicine. ACSM’s Guidelines Study. Metabolism 2001;49:S13–S20. 2003;103:748–765.
for Exercise Testing and Prescription. 100. Leon, AS, Gaskill, SE, Rice, T, et al. 116. Sabate, J. The contribution of veg-
Wolters Kluwer Health/Lippincott Variability in the response of HDL etarian diets to health and disease:
Williams & Wilkins, Philadelphia, 2018. cholesterol to exercise training in the A paradigm shift? Am. J. Clin. Nutr.
85. Jakicic, JM, Clark, K, Coleman, E, et al. HERITAGE Family Study. Int. J. Sports 2003;78(Suppl):502S–507S.
American College of Sports Medicine. Med. 2001;22:1–9. 117. Mitrow, FN, Kipnis, V, Thiebaut, ACM,
Position Stand. Appropriate intervention 101. Rice, T, Deprés, J-P, Pérusse, L, et al. et al. Mediterranean dietary patterns and
strategies for weight loss and prevention Familial aggregation of blood lipid prediction of all-cause mortality in a US
of weight regain for adults. Med. Sci. response to exercise training in the populations Results from the NIH-AARP
Sports Exerc. 2001;12:2145–2156. Health Risk Factors, Exercise Training, Diet and Health Study. Arch. Intern.
86. Danttilo, AM and Kris-Etherton, PM. and Genetics (HERITAGE) Family Study. Med. 2004;167:2461–2468.
Effects of weight reduction on blood Circulation 2002;105:1904–1908. 118. Knoops, KTB, de Groot, LCPGM,
lipids and lipoproteins: A meta-analysis. 102. Stefanick, M. Physical activity for Kromhout, D, et al. Mediterranean
Am. J. Clin. Nutr. 1992;56:320–328. preventing and treating obesity-related diet, lifestyle factors, and 10-year
87. Nordmann, AL, Nordmann, A, Briel, M, dyslipoproteinemias. Med. Sci. Sports mortality in elderly European men and
et al. Effects of a low-carbohydrate vs. Exerc. 199;31(Suppl):S609–S618. women. The HALE Project. JAMA
low fat diet on weight loss and cardio- 103. Santiago, MC, Leon, AS, and Serfass, 2004;292:1433–1439.
vascular risk factors: A meta-analysis RC. Failure of 40 weeks of brisk walk- 119. Fung, TT, Chiuve, SE, McCullough,
of randomized controlled trials. Arch. ing to alter blood lipids in normoli- ML, et al. Adherence to DASH-style diet
Intern. Med. 2006;166:285–293. pemic women. Canad. J. Appl. Phys. and risk of coronary heart disease and
88. Hu, T, Mills, KT, Yao, L, et al. Effects of 1995;20:417–428. stroke in women. Arch. Intern. Med.
low-carbohydrate diets versus low-fat diets 104. Sopko, G, Leon, AS, Jacobs, DR, Jr., et 2008;168:713–720.
on metabolic risk factors: A meta-analysis al. The effect of exercise and weight loss 120. Sacks, FM, Appel, LJ, Moore, TJ, et al.
of randomized controlled clinical trials. on plasma lipids in obese young men. A dietary approach to prevent hyperten-
Am. J. Epidemiol. 2012;176(7):S44–S54. Metabolism 1988;34:227–236. sion: A review of the Dietary Approach to
89. Shai, I, Schwarzfuchs, D, Henkin, Y, et 105. Wood, PD, Haskell, WL, Blair, SN, et Stop Hypertension (DASH) Study. Clin.
al. Weight loss with a low-carbohydrate, al. Increased exercise level and plasma Cardiol. 1999;22(Suppl):III-6–III-10.
Mediterranean or low fat diet. N. Engl. J. lipoprotein concentration: A one year 121. Lichenstein, AH, Appel, LJ, Brands, M,
Med. 2008;359:229–241. randomized, controlled study in sed- et al. Diet and lifestyle recommendations
90. Klem, ML, Wing, RA, McGuire, MT, entary middle-aged men. Metabolism revision 2006. A scientific statement from
et al. A descriptive study of individuals 1983;32:31–39. the Nutrition Committee. Circulation
successful at long term maintenance of 106. Kannell, WB. Update on the role of ciga- 2006;114:82–96.
substantial weight loss. Am. J. Clin. Nutr. rette smoking in coronary artery disease. 122. Yu-Poth, S, Zhao, G, Etherton, T, et
1997;66:239–246. Am. Heart J. 1981;101:319–328. al. Effects of the National Cholesterol
91. Saris, WH, Blair, SN, van Baak, MM, 107. Goldbourt, J and Medalie, JH. Education Program’s step 1 and step 2
et al. How much physical activity is Characteristics of smokers, nonsmokers, dietary intervention programs on cardio-
enough to prevent unhealthy weight and exsmokers among 10,000 adult males vascular risk factors. A meta-analysis. Am.
gain? Outcome of the IASO 1st Stock in Israel II. Physiologic biochemical, and J. Clin. Nutr. 1999;69:632–646.
Conference and Consensus Statement. genetic characteristics. Am. J. Epidemiol. 123. U.S. Department of Agriculture and
Obes. Rev. 2003;4:101–114. 1997;105:75–84. U.S. Department of Health and Human
92. Dishman, RK, Washburn, RA, and 108. Craig, W, Palomaki, G, and Haddow, Services. Dietary Guidelines for
Heath, GW. All-cause and coronary J. Cigarette smoking and serum Americans, 2005. Available at www.
heart disease mortality. In: Physical lipids and lipoprotein concentra- healtierus.gov/dietary guidelines
Activity Epidemiology. Human Kinetics, tions: Analysis of published data. BMJ 124. Lichtenstein, AH, Appel, LJ, Brands, M,
Champaign, IL, 2004. pp. 71–117. 1989;298(6676):784–788. et al. Diet and lifestyle recommendations
93. Clark, AM, Harling, L, Vandermeer, 109. Gottto, A and Powenall, H. Manual of revision 2006: A scientific statement
B, and McAlister, FA. Meta-analysis: Lipid Disorders. Reducing Its Risk of from the American Heart Association
Secondary prevention programs for Coronary Heart Disease, 2nd Edition. Nutrition Committee. Circulation
patients with coronary heart disease. Williams and Williams, Baltimore, MD, 2006;114(1):82–96.
Ann. Intern. Med. 2005;143:659–672. 1999. p. 179. 125. U.S. Department of Health and Human
94. Leon, AS and Bronas, U G. 110. Harats, D, Ben-Nain, M, Dabach, Y, et Services. Your Guide to Lowering
Pathophysiology of coronary heart al. Cigarette smoke renders LDL suscep- Cholesterol with TLC (Therapeutic
disease and biological mechanisms for tible to peroxidative modification and Lifestyle Changes). NIH Publication No.
the cardioprotective effects of regular enhanced metabolism by macrophages. 06-523S, Bethesda, MD, 2009.
aerobic exercise. Am. J. Lifestyle Med. Artherosclerosis 1989;79:245–252. 126. Varady, KA and Jones, PJH. Combination
2009;3(5):379–385. 111. Chiuve, SE, McCullough, ML, Sacks, diet and exercise interventions for the
95. Leon, AS, Franklin, BA, Costa, F, et al. FM, and Rimm, EB. Healthy lifestyle treatment of dyslipidemia: An effective
Cardiac rehabilitation and secondary factors in the prevention of coronary preliminary strategy to lower cholesterol
prevention of coronary heart dis- heart disease among men. Benefits among levels? J. Nutr. 2005;135:1829–1835.
ease. An American Heart Association users and nonusers of lipid-lowering and
5
CHAPTER
early after approximately three years of follow-up, due to depending on the setting of blood pressure measurement.
a lower all-cause mortality in the intensive treatment BP The guideline supports with a level IA recommendation
target group (hazard ratio 0.73, 95% CI .6-.9, p=.003) that out-of-office blood pressure measurements are needed
and a lower incidence (1.65%/year vs. 2.19%/year) of the to confirm a diagnosis of hypertension and when titrating
composite outcome (myocardial infarction, acute coro- medications.8 The guideline provides corresponding blood
nary syndrome, stroke, heart failure, or death) compared pressure levels for patients, depending on the type and
to the standard target group.9 Unfortunately, the intensive duration of measurement.8 For example, a patient noted to
treatment-lowering target group had significantly higher have a blood pressure of 160/100 mmHg has been found
rates of adverse events than the standard target group.9 to correspond to a home blood pressure of 145/90 mmHg
Although these results are promising, the study’s mea- and a nighttime ambulatory blood pressure measurement
surement of BP through research methods (the mean of of 140/85 mmHg.8
three readings after five minutes of rest without a staff
member present during readings) and the applicabil-
ity of the results to populations excluded from the trial
(CHF, severe CKD, secondary HTN, the institutionalized 5.3 ETIOLOGY OF HYPERTENSION
elderly, and those with low cardiovascular risk) has caused AND RELATIONSHIP TO
controversy on the applicability of the results to routine
clinical practice.10 –12 CARDIOVASCULAR DISEASE
Primary or essential hypertension, the most common type
5.2 MEASUREMENT OF of hypertension in the United States (90–95%) has no
specific known underlying cause, while secondary hyper-
BLOOD PRESSURE tension results from medical conditions such as chronic
kidney disease, renal artery stenosis, or adrenal tumors
The 2017 ACC/AHA Guideline for the Prevention, (e.g., pheochromocytoma, primary aldosteronism, and
Detection, Evaluation, and Management of High Blood Cushing’s disease).13,14 Essential hypertension cannot
Pressure in Adults emphasizes the proper technique of be cured, but it can be controlled with therapeutic life-
blood pressure measurement and differences that may style changes (TLC) and/or pharmacotherapy.1,13,14 Non-
arise between blood pressure monitoring conducted in modifiable risk factors for essential hypertension include
different settings. The reader is referred to the 2017 ACC/ a positive family history (generally via a polygenic mode
AHA Guideline for the Prevention, Detection, Evaluation, of inheritance), age (>30 years old in men), sex (more
and Management of High Blood Pressure in Adults for common in men than women), and ethnicity (more com-
an in-depth explanation of blood pressure measurement. mon in blacks than in non-blacks). Modifiable risk fac-
In summary, the guideline recommends proper measure- tors are excess weight (BMI > 25 kg/m 2); excess alcohol
ment of blood pressure at an IC level.8 It is recommended consumption; a sodium-rich diet low in calcium, potas-
that blood pressure is measured according to six clearly sium, and magnesium; and physical inactivity.1,13–18 Any
defined steps: proper patient preparation, proper tech- physiological factor that increases cardiac output or total
nique, proper measurements, proper documentation, peripheral vascular resistance can result in an elevation of
averaging of readings, and providing readings to patients.8 blood pressure, since blood pressure level is determined
These six steps highlight the importance of five minutes hemodynamically by the product of these two variables.
of rest before measurement, the use of correct cuff size Other contributing factors to an increase in blood pres-
applied to the skin, arm placement, bilateral arm measure- sure levels include endothelial dysfunction, increased
ment, and utilizing the average of more than two readings sympathetic nervous system activation, and renin-angio-
obtained on at least two occasions.8 tensin-aldosterone system (R-A-A) activity. It is postulated
The 2017 ACC/AHA Guideline for the Prevention, that a sustained elevation in blood pressure from any of
Detection, Evaluation, and Management of High Blood these physiological disturbances results in a resetting of
Pressure in Adults also highlights the important differ- the baroreceptors, hypertrophy of the arteriolar smooth
ences that may be noted in a patient’s blood pressure muscle, and an increase in peripheral vascular resistance,
5.4 Physical Activity, Exercise, and Hypertension 67
the principal hemodynamic disturbances associated with principle recommended for patients with hypertension to
5
essential hypertension.13 Hypertension-induced LVH (a participate in aerobic exercise of any exercise type on most
major cardiac consequence of hypertension) is postulated if not all days per week at a moderate intensity (40–<60%
to be related to both an increase in pre-load and after- VO2max) for 30–60 accumulated minutes per day as well
load (i.e., chronic volume and pressure overload), result- as dynamic resistance exercise of any resistance type two
ing in eccentric or concentric volumetric ventricular to three days per week at a moderate intensity for 10–12
changes associated with dysfunctional systolic contrac- repetitions of 8–10 exercises.53
tion.13–16 The reader is referred to a review on the topic by Moreover, immediately following cessation of each
Rosendorff et al.13 bout of aerobic exercise there is a temporary reduction
in systolic (5–15 mm Hg) and diastolic (4–6 mm Hg)
blood pressure that appears to last several hours (up to
24 hours). 52,54 –56 The mean acute post-exercise reduction
5.4 PHYSICAL ACTIVITY, EXERCISE, in blood pressure levels of hypertensive individuals has
AND HYPERTENSION been reported to be higher in controlled settings (15/4 mm
Hg) than in uncontrolled settings (~5/4 mm Hg). 52 It is
Observational studies also have reported an inverse asso- postulated that the mechanism of this acute blood pres-
ciation between leisure time physical activity, physical sure reduction following each exercise session includes the
fitness (relative risk 1.5–1.9), and development and sever- following:
ity of hypertension even after adjusting for other risk
factors.19–31 For example, Kokkinos et al. 32 reported in a • Immediate decrease in sympathetic adrenergic stim-
cross-sectional study an 8–9 mm Hg lower systolic and ulation of the precapillary vessels
4–5 mm Hg diastolic mean 24-hour ambulatory blood • Attenuated response to alpha-adrenergic stimulation
pressure in individuals with high and moderate physical • Laminar flow-mediated release of endothelial-
fitness, compared to persons with low fitness levels. These derived vasodilatory chemicals (e.g., nitric oxide,
studies suggest that increased levels of physical activity prostacyclin, and adenosine)
and moderate physical fitness result in ~ 5 mm Hg lower • Resetting of the arterial and cardiopulmonary baro-
systolic blood pressure level, compared to age- and sex- receptor operating points
matched individuals who are less active and less fit. 31 • Neural adaptations involving central vasopressin V1
A recent review by Liu and colleagues found that there receptors and substance P receptors55– 60
is a dose-related response related to physical activity and
hypertension prevention, with relative risk reduction of Resistance exercise training has been reported in
6% for every 10 MET hours per week of leisure time some studies to result in a reduction in blood pressure ~
physical activity.33 7/6 mm Hg, while in other studies it failed to result in
The effect of exercise training on blood pressure lev- a blood pressure reduction. 51,52,61 However, meta-analy-
els has been well established in over 70 randomized con- ses on the effect of resistance training on mean resting
trolled trials and over 15 meta-analyses. 34 –50 In general, blood pressure have reported a blood pressure reduction
these studies have shown that a moderate-intensity aero- of approximately 3–5/3.5–3.9 mm Hg in normotensive
bic exercise training program of 30–60 minutes per ses- individuals. 51,61,62 However, it should be noted that only
sion three times per week for 12–16 weeks lowers elevated the diastolic pressure reduction reached statistical sig-
blood pressure levels. 51,52 These studies have indicated a nificance in the largest meta-analysis. The current rec-
mean reduction in resting blood pressure levels in normo- ommendation for resistance exercise training is that it
tensive individuals of 2.6–4.7 mm Hg in systolic and 1.8– should only be used as a supplement and not a substitute
3.1 mm Hg in diastolic blood pressure and a reduction in for aerobic exercise training, and the strength of the evi-
systolic of 6 to 10 mm Hg and diastolic blood pressure dence of these recommendations are weak overall.53 The
of 2.4–7.6 mm Hg in patients with diagnosed hyperten- 2017 ACC/AHA Guideline for the Prevention, Detection,
sion, with one review reporting a mean blood pressure Evaluation, and Management of High Blood Pressure in
reduction of 11/5 mmHg with moderate-to-high-intensity Adults recommends 90–150 minutes per week of dynamic
aerobic activity. 50 There also appears to be a significant resistance exercise, and three sessions per week of isomet-
difference in blood pressure reduction between moderate ric resistance exercise, class 1A evidence base.8 The reader
or vigorous-exercise intensity training, and based on BMI, is referred to the American College of Sports Medicine’s
sex, and age.34 – 49,51,52 guidelines and contraindications to exercise testing and
Aerobic exercise training also appears to reduce mean training in patients with hypertension.63
24-hour systolic BP of 6–10 mm Hg and diastolic BP of There have been many postulated and plausible mech-
5–8 mm Hg in hypertensive participants, and 3.0–3.3 mm anisms for the blood pressure-reducing effects of exercise
Hg systolic and 3.3–3.5 diastolic in normotensive indi- training. Poiseuille’s law explains that a small change in
viduals,36,51,52 although no change was found in overnight vessel diameter has a large effect on resistance to fluid flow
blood pressure.51 It is concluded from these data that mod- (i.e., inversely proportional to the fourth power of the ves-
erate-intensity (40–70% of maximal aerobic capacity) aer- sel radius). 52 Therefore, it appears that a reduction in total
obic exercise training 30–60 minutes three to five days per peripheral vascular resistance, specifically by a change in
week is effective for both prevention and for management small vessel diameter is responsible for at least one part of
of hypertension. In a recent systematic review, the dose of the observed blood pressure reduction with exercise train-
exercise based on the FITT (frequency, intensity, time, type) ing (7.1% reduction). 51 The exercise-induced reduction in
68 Chapter 5 Lifestyle Management and Prevention of Hypertension
OF HYPERTENSION mm Hg.
* Adapted from reference.69
+ Adapted from reference.82
In meta-analyses, healthier diets have been found to be
associated with a decreased likelihood of developing levels ~11.4/5.5 mm Hg in hypertensive participants
hypertension (OR=.81, p=.02).76 Dietary-induced preven- versus 3.5/2.2 mm Hg in prehypertensive participants.
tion and management of hypertension through a combi- Interestingly, it appeared to be more effective in lower-
nation of sodium-intake reduction, increased intake of ing BP in black as compared to white study participants
potassium, calcium, and magnesium, and moderation of (6.9/3.7 mm Hg and 3.3/2.4 mm Hg, respectively).78
alcohol consumption have been shown to be very effec- Other dietary studies have reported 6–10 mm Hg
tive and are strongly supported by evidence from ran- blood pressure reductions in normotensive participants
domized controlled trials.77–80 The most effective dietary versus a 12–16 mm Hg reduction in participants with
intervention for blood pressure control and reduction to hypertension following a diet high in fruits and plants, as
date are those that are rich in fruit, vegetables, whole well as either diets high in carbohydrate, protein, or unsat-
grains, legumes, seeds, nuts, fish, and dairy and low in urated fat.77,80 Moreover, an increased dietary fiber intake
meat, sweets, and alcohol, such as the Nordic diet, the of 11.5–14 g per day found in whole grains, fruits and
Mediterranean diet, and the DASH diet, which is dis- vegetables, beans, nuts, and legumes is associated with a
played in Table 5.2.78,81 small reduction in systolic (1.1–1.6 mm Hg), and diastolic
The DASH diet was shown in a randomized controlled blood pressure levels (1.3–2.0 mm Hg).83–85 Currently, it
study to be very effective in reducing blood pressure is recommended that for BP management, an appropriate
5.6 Weight Management 69
diet is one rich in fruits, vegetables, and whole grains, as combination of a diet rich in potassium and low in
5
found in the DASH dietary pattern, USDA Food Pattern, sodium does not appear to be additive.77 Currently, it is
or the AHA Diet.7,8 recommended that a 4.7 g per day dietary intake of potas-
sium should be consumed via a dietary eating pattern
similar to that of the DASH diet instead of by potassium
5.5.1 Effect of Sodium Restriction supplement use.77,78 However, patients with medical con-
Observational prospective and cross-sectional studies, ditions that are associated with impaired urinary excre-
animal studies, clinical trials, and meta-analyses have tion of potassium (e.g., renal disease), or patients who
established a positive independent association between are using medications that reduce potassium excretion
sodium (and table salt) intake and blood pressure (e.g., angiotensin-converting enzyme (ACE)-inhibitors),
levels.41,86,87 The largest dose-response sodium restriction- should consume a lower daily potassium intake to avoid
blood pressure trial to date was the DASH-Sodium Trial. hyperkalemia.1,77
This randomized study compared three levels of reduced
sodium intake (150, 100, 50 mmol/day) with changes in 5.5.3 Effects of Alcohol Consumption
blood pressure levels. This study found an apparent dose-
response relationship between reduced sodium intake and A J-shaped dose-dependent association between alcohol
systolic blood pressure reduction.79 consumption and blood pressure levels has been demon-
Generally, sodium restriction reduces elevated sys- strated in clinical trials. It appears that relatively light alco-
tolic blood pressure levels by 4.7–7 mm Hg and elevated hol consumption has no effect on blood pressure, whereas
diastolic blood pressure levels by 2.5–2.7 mm Hg, and higher daily alcohol consumption increases blood pres-
reduces the risk of progression of prehypertension to sure levels.86,95–98 Controlled trials have demonstrated that
hypertension (a relative risk reduction of 20%). Further, 50–70% reduction of daily alcohol consumption indepen-
it potentiates pharmacological treatment.41,77,86–91 It is dently reduces blood pressure levels approximately 3.5/3
important to note that there is a great inter-individual mm Hg. On the other hand, a 10 g/day increase in alcohol
variability in blood pressure response to sodium restric- consumption is associated with an increase in blood pres-
tion. In general, black, middle-aged, older individuals, and sure of 2/1 mm Hg.41,98 Current recommendations are for
patients with over-activity of the R-A-A system appear to individuals who consume alcohol to limit their intake to
respond best to sodium restriction with large reductions in no more than two drinks per day for men and no more
blood pressure.77,79,90,91 The current American diet is high than one drink per day for women to reduce the risk of
in sodium levels, mostly from commonly used processed adverse effects of alcohol on blood pressure levels. A drink
foods, therefore making it difficult for many Americans is defined as a serving of either a 12 oz beer, 5 oz wine, or
to achieve a lower sodium goal. The AHA/ACC Guideline 1.5 oz of 80-proof distilled spirits.1,77
on Lifestyle Management, which is advocated for by the
JNC-8 report, recommends 2.4 g/day as the upper limit of
sodium intake for blood pressure control. It further rec- 5.5.4 Effect of Omega-3
ommends that reduction of sodium intake to 1500 mg per Polyunsaturated Fatty Acids
day can result in an even greater reduction in blood pres-
sure.1,6,7,77 However, the 2017 ACC/AHA Guideline for Fatty fish and fish oil supplements are rich in long-chain
the Prevention, Detection, Evaluation, and Management omega-3 polyunsaturated fatty acids, which are postu-
of High Blood Pressure in Adults and the previous JNC-7 lated to play an essential role in blood pressure regula-
recommends reducing sodium chloride intake to 1.5 g per tion via the production of eicosanoids and prostaglandins.
day limit sodium chloride intake.1,8 Small-scale studies in patients with hypertension using
large doses of fish supplements (>3 g/day) have reported
an associated blood pressure reduction of 2.3–4.0 mm Hg
5.5.2 Effects of Increased Dietary and 2.2–2.5 mm Hg in systolic and diastolic blood pres-
sure, respectively.41,99–101 The current recommendations is
Potassium Intake to consume fatty fish two or more times per week, for
Fluid homeostasis in the body is in part controlled via cardio-protective effects, but omega-3 fish oil supplements
sodium and potassium balance. In general, serum sodium are only for secondary prevention of coronary heart dis-
levels increase to promote fluid retention in response to a ease and sudden cardiac death.6,102
reduction in serum potassium levels, whereas increased
serum potassium levels lead to an increase in renal
sodium excretion (natriuresis) and an associated diuresis. 5.6 WEIGHT MANAGEMENT
Although clinical trials have reported mixed blood pres-
sure response to increased dietary potassium intake, there The association of obesity and hypertension had been
is in general a trend between increased potassium intake well established by both observational studies and clinical
from 1.3–4.7 g per day and reduced systolic blood pres- trials.77,103 In general, it appears that a reduction in body
sure (2.42–4.4 mm Hg) and diastolic blood pressure (1.5– weight of 5–10 kg in overweight individuals reduces blood
2.5 mm Hg) in patients with hypertension. In general, a pressure levels approximately 6–12/5–8 mmHg.41,77,104 –108
greater blood pressure-reducing effect of increased potas- Exercise training remains an important component for
sium intake is observed in black as compared to matched weight management, although exercise training alone gen-
white hypertensive individuals.41,77,78,92–94 However, the erally results only in a 2 kg weight loss. Regular exercise
70 Chapter 5 Lifestyle Management and Prevention of Hypertension
training improves maintenance of lost weight and reduces studies confirm current guidelines and the value of com-
the loss of lean body mass associated with weight loss.109–111 prehensive therapeutic lifestyle interventions for the pre-
Exercise training appears to selectively reduce visceral vention and management of hypertension.1,89
abdominal fat, thereby potentiating blood pressure reduc-
tion. In fact, it appears that the combination of exercise
and a reduction in energy intake generally results in a
greater blood pressure reduction than either alone.111,112
5.6.1 Complementary Therapies
In a recent Cochrane review, weight loss diets alone were Complementary therapies are also proposed to have a role
found to reduce body weight and blood pressure (mean in the management of hypertension through lifestyle mod-
difference SBP –4.5 mmHg [–7.2–1.8 95% CI], mean dif- ification. Through meta-analysis of ten randomized con-
ference DBP –3.2 mm Hg [–4.8 to –1.5 mm Hg 95% CI]), trolled trials, music interventions (music of various types,
but this review included a limited number of studies with music with breathing, etc.) have been found to show a
a small number of participants.113 Currently, the AHA trend towards decreased blood pressure (144 [95% CI:
recommends that overweight adults with hypertension 137–152] to 134 SBP [95%CI: 124–144], 84 [95%CI:78–
are counseled to begin lifestyle changes (diet, exercise) to 89] to 78 [95%CI:73–84].117 The role of yoga in improving
achieve a sustained weight loss of 3–5% to achieve clini- blood pressure level has been explored through systematic
cally meaningful health benefits.7,114 review. Seventeen studies, although with unclear or a high
Intervention trials that utilized comprehensive lifestyle risk of bias, found yoga had a significant but small effect
modification programs to lower blood pressure levels have on SBP (–4.17, p=.0002) and SBP (–3.62, p=.0001).118
in general had very encouraging results. The most notable Transcendental meditation was similarly found across
large-scale trials are the PREMIER115 and the Exercise eight systematic reviews and meta-analyses to have a
and Nutritional Interventions for Cardiovascular Health potentially small effect on lowering SBP levels (–4.26,
(ENCORE)116 studies. These randomized controlled stud- 95% CI) and DBP levels (–2.33, 95% CI).119 Garlic has
ies have reported a mean reduction in blood pressure in also been explored as having a novel role in the reduction
hypertensive individuals of 11–16 and 6–10 mm Hg in of blood pressure.120 –123 Meta-analyses have found that
systolic and diastolic blood pressure, respectively, follow- garlic has been found to reduce blood pressure.120 –123 The
ing comprehensive lifestyle intervention (including weight largest of these meta-analyses, which included 17 random-
reduction). In addition, the ENCORE trial reported a ized controlled trials, found that garlic reduced SBP by
significant reduction in mean 24-hour ambulatory blood 3.75 mm Hg (p < 001) and SBP by 3.39 mmHg (p=.004)
pressure in the comprehensive intervention group. These compared to controls.122
5.7 PHARMACOLOGICAL usually prescribed as the initial drug choice for patients with
5
Stage 1 hypertension without CKD, whereas a two-drug
MANAGEMENT OF HYPERTENSION combination is usually the initial prescription for patients
with Stage 2 hypertension (e.g., a thiazide diuretic along
The JNC-8 recommendations of 2014 advocated for ini- with an ACE-inhibitor or AR-blocker, or beta-adrenergic
tiation of pharmacotherapy, in addition to continuing blocking agent, or calcium channel inhibitor depending on
lifestyle modification, when the SBP is > 150 mmHg or comorbidities, race, and age).1,6,8 Generally, multiple antihy-
DBP > 90 mmHg in adults over the age of 60 and when the pertensive drugs are required to achieve the therapeutic tar-
SBP is > 140 mmHg or DBP > 90 mmHg in adults under get level, so it is imperative that the prescribing clinician pay
60, patients with DM, and patients with chronic kidney particular attention to contraindications, drug interactions,
disease (CKD).6 The current 2017ACC/AHA guidelines and comorbidities when selecting antihypertensive drug
recommend initiation of antihypertensive medications therapy. The reader is referred to the JNC-7 report,1 JNC-8
when the BP is 130–139/80–89 and the patient has clini- report, and the ACC/AHA 2017 guidelines for a more com-
cal atherosclerotic heart disease or an estimated ten-year plete discussion of pharmacological therapy.6,8 To potentiate
cardiovascular disease risk of greater than 10%.8 the efficacy of pharmacotherapy, initiation of the previously
Numerous different types of antihypertensive drugs described lifestyle modifications is strongly recommended.6,8
are available, including thiazide and potassium-sparing Summary of Conclusions, The available evidence is
diuretics, beta-adrenergic blockers, alpha-adrenergic block- robust in supporting therapeutic lifestyle changes for
ers, angiotensin-converting enzyme (ACE)-inhibitors, the prevention and management of hypertension, and as
AR-blockers, calcium channel inhibitors, centrally acting adjuncts to pharmacotherapy of hypertension, as summa-
drugs, and direct-acting vasodilators.1 A thiazide diuretic is rized in Table 5.3.
REFERENCES
1. Chobanian AV, Bakris GL, Black HR, College of Cardiology/American Heart 16. Matthews CE, Pate RR, Jackson KL, et
et al. The seventh report of the joint Association Task Force on Clinical al. Exaggerated blood pressure response
national committee on prevention, detec- Practice Guidelines. Hypertension 2017. to dynamic exercise and risk of future
tion, evaluation, and treatment of high doi:10.1161/HYP.0000000000000066 hypertension. J. Clin. Epidemiol.
blood pressure: The JNC 7 report. JAMA 9. Wright JJT, Williamson JD, Whelton PK, 1998;51:29–35.
2003;289:2560–2572. et al. A randomized trial of intensive ver- 17. Singh JP, Larson MG, Manolio TA, et al.
2. Levy D, Larson MG, Vasan RS, Kannel sus standard blood-pressure control. N. Blood pressure response during treadmill
WB, and Ho KK. The progression from Engl. J. Med. 2015;373(22):2103–2116. testing as a risk factor for new-onset
hypertension to congestive heart failure. doi:10.1056/NEJMoa1511939 hypertension. The Framingham Heart
JAMA 1996;275:1557–1562. 10. Agarwal R. Implications of blood Study. Circulation 1999;99:1831–1836.
3. Stamler J, Stamler R, and Neaton JD. pressure measurement technique for 18. Manolio TA, Burke GL, Savage PJ,
Blood pressure, systolic and diastolic, and implementation of systolic blood pressure Sidney S, Gardin JM, and Oberman A.
cardiovascular risks. US population data. intervention trial (SPRINT). J. Am. Heart Exercise blood pressure response and
Arch. Intern. Med. 1993;153:598–615. Assoc. 2017;6(2):e004536. doi:10.1161/ 5-year risk of elevated blood pres-
4. Klag MJ, Whelton PK, Randall BL, JAHA.116.004536 sure in a cohort of young adults: The
et al. Blood pressure and end-stage 11. Oparil S and Lewis CE. Should CARDIA study. Am. J. Hypertens.
renal disease in men. N. Engl. J. Med. patients with cardiovascular risk 1994;7:234–241.
1996;334:13–18. factors receive intensive treatment 19. Kokkinos PF, Giannelou A, Manolis A,
5. Merai R, Siegel C, Rakotz M, et al. CDC of hypertension to < 120/80 mm Hg and Pittaras A. Physical activity in the
grand rounds: A public health approach target? A Protagonist View from the prevention and management of high
to detect and control hypertension. SPRINT Trial (Systolic Blood Pressure blood pressure. Hellenic J. Cardiol.
MMWR Morb. Mortal. Wkly. Rep. Intervention Trial). Circulation 2009;50:52–59.
2016;65(45):1261–1264. doi:10.15585/ 2016;134(18):1308–1310. doi:10.1161/ 20. Thijs L, Den Hond E, Nawrot T, and
mmwr.mm6545a3 CIRCULATIONAHA.116.023263 Staessen JA. Prevalence, pathophysiol-
6. James PA, Oparil S, Carter BL, et al. 12. Williamson JD, Supiano MA, Applegate ogy and treatment of isolated systolic
2014 Evidence-based guideline for WB, et al. Intensive vs standard blood hypertension in the elderly. Expert Rev.
the management of high blood pres- pressure control and cardiovascular Cardiovasc. Ther. 2004;2:761–769.
sure in adults: Report from the panel disease outcomes in adults aged ≥75 21. Paffenbarger RS, Jr, Wing AL, Hyde RT,
members appointed to the Eighth Joint years: A randomized clinical trial. JAMA and Jung DL. Physical activity and inci-
National Committee (JNC 8). JAMA 2016;315(24):2673–2682. doi:10.1001/ dence of hypertension in college alumni.
2014;311(5):507–520. doi:10.1001/ jama.2016.7050 Am. J. Epidemiol. 1983;117:245–257.
jama.2013.284427 13. Rosendorff C, Black HR, Cannon CP, 22. Haapanen N, Miilunpalo S, Vuori I, Oja
7. Eckel RH, Jakicic JM, Ard JD, et al. et al. Treatment of hypertension in the P, and Pasanen M. Association of leisure
2013 AHA/ACC guideline on lifestyle prevention and management of ischemic time physical activity with the risk of
management to reduce cardiovascular heart disease: A scientific statement from coronary heart disease, hypertension and
risk: A Report of the American College of the american heart association council diabetes in middle-aged men and women.
Cardiology/American Heart Association for high blood pressure research and Int. J. Epidemiol. 1997;26:739–747.
Task Force on Practice Guidelines. the councils on clinical cardiology and 23. Reaven PD, Barrett-Connor E, and
Circulation 2014;129(25_Suppl_2 epidemiology and prevention. Circulation Edelstein S. Relation between leisure-
Suppl 1):S76–S99. doi:10.1161/01. 2007;115:2761–2788. time physical activity and blood
cir.0000437740.48606.d1. 14. Debakey M and Gotto A. The New Living pressure in older women. Circulation
8. Whelton PK, Carey RM, Aronow WS, Heart, Vol. 1. Hobrook, MA: Adams 1991;83:559–565.
et al. 2017 ACC/AH A/AAPA/ABC /ACP Media Corporation, 1997. pp. 169–180. 24. Staessen JA, Fagard R, and Amery A. Life
M/AGS/APhA/ASH/A SPC/N MA/PC NA 15. Miyai N, Arita M, Miyashita K, Morioka style as a determinant of blood pres-
guideline for the prevention, detection, I, Shiraishi T, and Nishio I. Blood pres- sure in the general population. Am. J.
evaluation, and management of high sure response to heart rate during exer- Hypertens. 1994;7:685–694.
blood pressure in adults: Executive cise test and risk of future hypertension. 25. Gibbons LW, Blair SN, Cooper KH, and
summary: A Report of the American Hypertension 2002;39:761–766. Smith M. Association between coronary
72 Chapter 5 Lifestyle Management and Prevention of Hypertension
heart disease risk factors and physical fit- 41. Dickinson HO, Mason JM, Nicolson DJ, 57. Patil RD, DiCarlo SE, and Collins
ness in healthy adult women. Circulation et al. Lifestyle interventions to reduce HL. Acute exercise enhances nitric
1983;67:977–983. raised blood pressure: A systematic oxide modulation of vascular response
26. Blair SN, Goodyear NN, Gibbons LW, review of randomized controlled trials. J. to phenylephrine. Am. J. Physiol.
and Cooper KH. Physical fitness and Hypertens. 2006;24:215–233. 1993;265:H1184–H1188.
incidence of hypertension in healthy 42. Kelley GA, Kelley KA, and Tran ZV. 58. Collins HL, Augustyniak RA, Ansorge
normotensive men and women. JAMA Aerobic exercise and resting blood pres- EJ, and O’Leary DS. Carotid baroreflex
1984;252:487–490. sure: A meta-analytic review of random- pressor responses at rest and during
27. Paffenbarger RS, Jr, Thorne MC, and ized, controlled trials. Prev. Cardiol. exercise: Cardiac output vs. regional
Wing AL. Chronic disease in former 2001;4:73–80. vasoconstriction. Am. J. Physiol. Heart
college students. VIII. Characteristics 43. Kelley GA, Kelley KS, and Tran ZV. Circ. Physiol. 2001;280:H642–H648.
in youth predisposing to hyperten- Walking and resting blood pressure 59. Collins HL, Rodenbaugh DW, and
sion in later years. Am. J. Epidemiol. in adults: A meta-analysis. Prev. Med. DiCarlo SE. Central blockade of
1968;88:25–32. 2001;33:120–127. vasopressin V(1) receptors attenu-
28. Lee IM, Hsieh CC, and Paffenbarger RS, 44. Whelton SP, Chin A, Xin X, and He ates postexercise hypotension. Am. J.
Jr. Exercise intensity and longevity in J. Effect of aerobic exercise on blood Physiol. Regul. Integr. Comp. Physiol.
men. The Harvard Alumni Health Study. pressure: A meta-analysis of random- 2001;281:R375–R380.
JAMA 1995;273:1179–1184. ized, controlled trials. Ann. Intern. Med. 60. Chen CY, Munch PA, Quail AW, and
29. Palatini P, Graniero GR, Mormino P, et 2002;136:493–503. Bonham AC. Postexercise hypoten-
al. Relation between physical train- 45. Kelley G and McClellan P. sion in conscious SHR is attenuated by
ing and ambulatory blood pressure in Antihypertensive effects of aerobic blockade of substance P receptors in
stage I hypertensive subjects. Results of exercise. A brief meta-analytic review NTS. Am. J. Physiol. Heart Circ. Physiol.
the HARVEST trial. Hypertension and of randomized controlled trials. Am. J. 2002;283:H1856–H1862.
ambulatory recording Venetia study. Hypertens. 1994;7:115–119. 61. Kelley GA and Kelley KS. Progressive
Circulation 1994;90:2870–2876. 46. Kelley G and Tran ZV. Aerobic exer- resistance exercise and resting blood
30. Sawada S, Tanaka H, Funakoshi M, cise and normotensive adults: A pressure: A meta-analysis of random-
Shindo M, Kono S, and Ishiko T. Five meta-analysis. Med. Sci. Sports Exerc. ized controlled trials. Hypertension
year prospective study on blood pressure 1995;27:1371–1377. 2000;35:838–843.
and maximal oxygen uptake. Clin. Exp. 47. Kelley GA. Effects of aerobic exercise in 62. Inder JD, Carlson DJ, Dieberg G,
Pharmacol. Physiol. 1993;20:483–487. normotensive adults: A brief meta-ana- McFarlane JR, Hess NC, and Smart NA.
31. Kokkinos PF, Holland JC, Pittaras lytic review of controlled clinical trials. Isometric exercise training for blood
AE, Narayan P, Dotson CO, and South. Med. J. 1995;88:42–46. pressure management: A systematic
Papademetriou V. Cardiorespiratory 48. Kelley GA. Aerobic exercise and resting review and meta-analysis to optimize
fitness and coronary heart disease risk blood pressure among women: A meta- benefit. Hypertens. Res. 2016;39(2):88.
factor association in women. J. Am. Coll. analysis. Prev. Med. 1999;28:264–275. doi:10.1038/hr.2015.111
Cardiol. 1995;26:358–364. 49. Kelley GA and Sharpe Kelley K. Aerobic 63. Pescatello LS and American College
32. Kokkinos P, Pittaras A, Manolis A, et al. exercise and resting blood pressure in of Sports M. ACSM’s Guidelines for
Exercise capacity and 24-h blood pres- older adults: A meta-analytic review Exercise Testing and Prescription, 9th ed.
sure in prehypertensive men and women. of randomized controlled trials. J. Philadelphia: Wolters Kluwer/Lippincott
Am. J. Hypertens. 2006;19:251–258. Gerontol. A Biol. Sci. Med. Sci. Williams & Wilkins Health, 2013.
33. Liu X, Zhang D, Liu Y, et al. Dose– 2001;56:M298–M303. 64. Cleroux J, Kouame N, Nadeau A,
response association between physical 50. Börjesson M, Onerup A, Lundqvist Coulombe D, and Lacourciere Y.
activity and incident hypertension: S, and Dahlöf B. Physical activity and Aftereffects of exercise on regional and
A systematic review and meta-anal- exercise lower blood pressure in indi- systemic hemodynamics in hypertension.
ysis of cohort studies. Hypertension viduals with hypertension: Narrative Hypertension 1992;19:183–191.
2017;69(5):813–820. doi:10.1161/ review of 27 RCTs. Br. J. Sports Med. 65. Higashi Y, Sasaki S, Sasaki N, et al. Daily
HYPERTENSIONAHA.116.08994 2016;50(6):356–361. doi:10.1136/ aerobic exercise improves reactive hyper-
34. Hagberg JM and Brown MD. Does exer- bjsports-2015-095786 emia in patients with essential hyperten-
cise training play a role in the treatment 51. Fagard RH and Cornelissen VA. Effect sion. Hypertension 1999;33:591–597.
of essential hypertension? J. Cardiovasc. of exercise on blood pressure control in 66. Tanaka H and Safar ME. Influence of
Risk 1995;2:296–302. hypertensive patients. Eur. J. Cardiovasc. lifestyle modification on arterial stiffness
35. Hagberg JM, Park JJ, and Brown MD. Prev. Rehabil. 2007;14:12–17. and wave reflections. Am. J. Hypertens.
The role of exercise training in the treat- 52. Pescatello LS, Franklin BA, Fagard 2005;18:137–144.
ment of hypertension: An update. Sports R, et al. American college of sports 67. Somers VK, Conway J, Johnston J, and
Med. 2000;30:193–206. medicine position stand. Exercise and Sleight P. Effects of endurance training
36. Cornelissen VA and Fagard RH. Effects hypertension. Med. Sci. Sports Exerc. on baroreflex sensitivity and blood pres-
of endurance training on blood pres- 2004;36:533–553. sure in borderline hypertension. Lancet
sure, blood pressure-regulating mecha- 53. Pescatello LS, MacDonald HV, Lamberti 1991;337:1363–1368.
nisms, and cardiovascular risk factors. L, and Johnson BT. Exercise for hyper- 68. Urata H, Tanabe Y, Kiyonaga A, et al.
Hypertension 2005;46:667–675. tension: A prescription update integrat- Antihypertensive and volume-depleting
37. Fagard RH. Physical fitness and ing existing recommendations with effects of mild exercise on essential hyper-
blood pressure. J. Hypertens. Suppl. emerging research. Curr. Hypertens. Rep. tension. Hypertension 1987;9:245–252.
1993;11:S47–S52. 2015;17(11):87. 69. Kingwell BA. Nitric oxide-mediated met-
38. Fagard RH. Physical activity in the 54. Floras JS, Sinkey CA, Aylward PE, abolic regulation during exercise: Effects
prevention and treatment of hyperten- Seals DR, Thoren PN, and Mark AL. of training in health and cardiovascular
sion in the obese. Med. Sci. Sports Exerc. Postexercise hypotension and sympatho- disease. FASEB J. 2000;14:1685–1696.
1999;31:S624–S630. inhibition in borderline hypertensive men. 70. Wiegman DL, Harris PD, Joshua IG,
39. Fagard RH. Exercise characteristics and Hypertension 1989;14:28–35. and Miller FN. Decreased vascular
the blood pressure response to dynamic 55. Halliwill JR, Taylor JA, and Eckberg DL. sensitivity to norepinephrine follow-
physical training. Med. Sci. Sports Impaired sympathetic vascular regulation ing exercise training. J. Appl. Physiol.
Exerc. 2001;33:S484–S492; discussion in humans after acute dynamic exercise. 1981;51:282–287.
S493–S494. J. Physiol. 1996;495(Pt 1):279–288. 71. Maeda S, Miyauchi T, Kakiyama T,
40. Halbert JA, Silagy CA, Finucane P, 56. Pinto A, Di Raimondo D, Tuttolomondo et al. Effects of exercise training of 8
Withers RT, Hamdorf PA, and Andrews A, Fernandez P, Arnao V, and Licata weeks and detraining on plasma levels of
GR. The effectiveness of exercise training G. Twenty-four hour ambulatory blood endothelium-derived factors, endothe-
in lowering blood pressure: A meta- pressure monitoring to evaluate effects lin-1 and nitric oxide, in healthy young
analysis of randomised controlled trials on blood pressure of physical activity in humans. Life Sci. 2001;69:1005–1016.
of 4 weeks or longer. J. Hum. Hypertens. hypertensive patients. Clin. J. Sport Med. 72. Kohno K, Matsuoka H, Takenaka K, et
1997;11:641–649. 2006;16:238–243. al. Depressor effect by exercise training is
References 73
associated with amelioration of hyperin- DASH-sodium trial. Ann. Intern. Med. 103. Kaplan NM. Hypertension curriculum
sulinemia and sympathetic overactivity. 2001;135:1019–1028. review: Lifestyle modifications for preven-
73.
Intern. Med. 2000;39:1013–1019.
Edwards MT and Diana JN. Effect
of exercise on pre- and postcapil-
88. He FJ and MacGregor GA. Effect of
modest salt reduction on blood pressure:
A meta-analysis of randomized trials.
tion and treatment of hypertension. J. Clin.
Hypertens. (Greenwich) 2004;6:716–719.
104. Neter JE, Stam BE, Kok FJ, Grobbee DE,
5
lary resistance in the spontaneously Implications for public health. J. Hum. and Geleijnse JM. Influence of weight
hypertensive rat. Am. J. Physiol. Hypertens. 2002;16:761–770. reduction on blood pressure: A meta-
1978;234:H439–H446. 89. Whelton PK, Appel LJ, Espeland MA, analysis of randomized controlled trials.
74. Wilmore JH, Stanforth PR, Gagnon et al. Sodium reduction and weight Hypertension 2003;42:878–884.
J, et al. Heart rate and blood pressure loss in the treatment of hypertension in 105. Staessen J, Fagard R, Lijnen P, and
changes with endurance training: The older persons: A randomized controlled Amery A. Body weight, sodium intake
HERITAGE family study. Med. Sci. trial of nonpharmacologic interven- and blood pressure. J. Hypertens. Suppl.
Sports Exerc. 2001;33:107–116. tions in the elderly (TONE). TONE 1989;7:S19–S23.
75. Rankinen T, Rice T, Perusse L, et al. collaborative research group. JAMA 106. Gordon NF, Scott CB, and Levine BD.
NOS3 Glu298Asp genotype and blood 1998;279:839–846. Comparison of single versus multiple
pressure response to endurance train- 90. Tuck ML. Role of salt in the con- lifestyle interventions: Are the antihyper-
ing: The HERITAGE family study. trol of blood pressure in obesity and tensive effects of exercise training and
Hypertension 2000;36:885–889. diabetes mellitus. Hypertension diet-induced weight loss additive? Am. J.
76. Wang C-J, Shen Y-X, and Liu Y. 1991;17:I135–I142. Cardiol. 1997;79:763–767.
Empirically derived dietary pat- 91. Imanishi M, Yoshioka K, Okumura M, 107. MacMahon S, Cutler J, Brittain E, and
terns and hypertension likelihood: et al. Sodium sensitivity related to albu- Higgins M. Obesity and hypertension:
A meta-analysis. Kidney Blood minuria appearing before hypertension Epidemiological and clinical issues. Eur.
Press. Res. 2016;41(5):570–581. in type 2 diabetic patients. Diabetes Care Heart J. 1987;8(Suppl B):57–70.
doi:10.1159/000443456 2001;24:111–116. 108. Blumenthal JA, Sherwood A, Gullette
77. Appel LJ, Brands MW, Daniels SR, et 92. Cutler JA, Follmann D, Elliott P, and EC, et al. Exercise and weight loss reduce
al. Dietary approaches to prevent and Suh I. An overview of randomized trials blood pressure in men and women
treat hypertension: A scientific statement of sodium reduction and blood pressure. with mild hypertension: Effects on
from the American Heart Association. Hypertension 1991;17:I27–I33. cardiovascular, metabolic, and hemody-
Hypertension 2006;47:296–308. 93. Geleijnse JM, Kok FJ, and Grobbee DE. namic functioning. Arch. Intern. Med.
78. Appel LJ, Moore TJ, Obarzanek E, et al. Blood pressure response to changes in 2000;160:1947–1958.
A clinical trial of the effects of dietary sodium and potassium intake: A metare- 109. National Institute of Health. Clinical
patterns on blood pressure. DASH collab- gression analysis of randomised trials. J. Guidelines on the Identification,
orative research group. N. Engl. J. Med. Hum. Hypertens. 2003;17:471–480. Evaluation and Treatment of Overweight
1997;336:1117–1124. 94. Whelton PK, He J, Cutler JA, et al. and Obesity in Adults. The Evidence
79. Sacks FM, Svetkey LP, Vollmer WM, et Effects of oral potassium on blood Report. Bethesda, MD: NIH Publication,
al. Effects on blood pressure of reduced pressure. Meta-analysis of random- No. 98-408, 1998.
dietary sodium and the dietary approaches ized controlled clinical trials. JAMA 110. Klein S, Burke LE, Bray GA, et al.
to stop hypertension (DASH) diet. DASH- 1997;277:1624–1632. Clinical implications of obesity with
sodium collaborative research group. N. 95. Okubo Y, Miyamoto T, Suwazono Y, specific focus on cardiovascular
Engl. J. Med. 2001;344:3–10. Kobayashi E, and Nogawa K. Alcohol disease. A statement for professionals
80. Appel LJ, Sacks FM, Carey VJ, et al. consumption and blood pressure in from the American Heart Association
Effects of protein, monounsaturated Japanese men. Alcohol 2001;23:149–156. Council on Nutrition, Physical
fat, and carbohydrate intake on blood 96. Okubo Y, Suwazono Y, Kobayashi E, and Activity and Metabolism. Circulation
pressure and serum lipids: Results of the Nogawa K. Alcohol consumption and 2004;110:2952–2967.
OmniHeart randomized trial. JAMA blood pressure change: 5-Year follow- 111. Jakicic JM, Clark K, Coleman E, et al.
2005;294:2455–2464. up study of the association in normo- American College of Sports Medicine.
81. Ndanuko RN, Tapsell LC, Charlton KE, tensive workers. J. Hum. Hypertens. Position stand. Appropriate intervention
Neale EP, and Batterham MJ. Dietary 2001;15:367–372. strategies for weight loss and prevention
patterns and blood pressure in adults: 97. Klatsky AL, Friedman GD, Siegelaub AB, of weight regain for adults. Med. Sci.
A systematic review and meta-analysis and Gerard MJ. Alcohol consumption Sports Exerc. 2001;12:2145–2156.
of randomized controlled trials. Adv. and blood pressure kaiser-permanente 112. Cox KL, Puddey IB, Morton AR,
Nutr. (Bethesda, Md.) 2016;7(1):76–89. multiphasic health examination data. N. Burke V, Beilin LJ, and McAleer M.
doi:10.3945/an.115.009753 Engl. J. Med. 1977;296:1194–1200. Exercise and weight control in sedentary
82. National Heart, Lung, and Blood 98. Xin X, He J, Frontini MG, Ogden LG, overweight men: Effects on clinic and
Institute. DASH Eating Plan Website. Motsamai OI, and Whelton PK. Effects ambulatory blood pressure. J. Hypertens.
https: //www.nhlbi.nih.gov/ healt h-topics/ of alcohol reduction on blood pressure: A 1996;14:779–790.
dash-eating-plan. Accessed February 13, meta-analysis of randomized controlled 113. Semlitsch T, Jeitler K, Berghold A,
2018. trials. Hypertension 2001;38:1112–1117. et al. Long-term effects of weight-
83. Whelton SP, Hyre AD, Pedersen B, Yi 99. Geleijnse JM, Giltay EJ, Grobbee DE, reducing diets in people with hyperten-
Y, Whelton PK, and He J. Effect of Donders AR, and Kok FJ. Blood pressure sion. Cochrane Database Syst. Rev.
dietary fiber intake on blood pres- response to fish oil supplementation: 2016;3:CD008274.
sure: A meta-analysis of randomized, Metaregression analysis of randomized 114. Jensen MD, Ryan DH, Apovian CM, et
controlled clinical trials. J. Hypertens. trials. J. Hypertens. 2002;20:1493–1499. al. 2013 AHA/ACC/TOS guideline for
2005;23:475–481. 100. Appel LJ, Miller ER, 3rd, Seidler AJ, the management of overweight and obe-
84. Streppel MT, Arends LR, van’t Veer P, and Whelton PK. Does supplementa- sity in adults: A Report of the American
Grobbee DE, and Geleijnse JM. Dietary tion of diet with ‘fish oil’ reduce blood College of Cardiology/American Heart
fiber and blood pressure: A meta-analysis pressure? A meta-analysis of controlled Association Task Force on Practice
of randomized placebo-controlled trials. clinical trials. Arch. Intern. Med. Guidelines and the Obesity Society.
Arch. Intern. Med. 2005;165:150–156. 1993;153:1429–1438. Circulation 2014;129(25_Suppl_2
85. He J and Whelton PK. Effect of dietary 101. Morris MC, Sacks F, and Rosner B. Does Suppl 1):S102–S138. doi:10.1161/01.
fiber and protein intake on blood pres- fish oil lower blood pressure? A meta- cir.0000437739.71477.ee
sure: A review of epidemiologic evidence. analysis of controlled trials. Circulation 115. McGuire HL, Svetkey LP, Harsha
Clin. Exp. Hypertens. 1999;21:785–796. 1993;88:523–533. DW, Elmer PJ, Appel LJ, and Ard JD.
86. He J and Bazzano LA. Effects of lifestyle 102. Fretts AM, Lichtenstein AH, Kris- Comprehensive lifestyle modification
modification on treatment and prevention Etherton PM, et al. Omega-3 polyunsatu- and blood pressure control: A review of
of hypertension. Curr. Opin. Nephrol. rated fatty acid (fish oil) supplementation the PREMIER trial. J. Clin. Hypertens.
Hypertens. 2000;9:267–271. and the prevention of clinical cardiovas- (Greenwich) 2004;6:383–390.
87. Vollmer WM, Sacks FM, Ard J, et al. cular disease: A science advisory from the 116. Effects of the DASH Diet Alone and in
Effects of diet and sodium intake on American Heart Association. Circulation Combination With Exercise and Weight
blood pressure: Subgroup analysis of the 2017;135(15):e867–e884. Loss on Blood Pressure and Cardiovascular
74 Chapter 5 Lifestyle Management and Prevention of Hypertension
Biomarkers in Men and Women With High meta-analysis. Evid. Based Complement. 121. Silagy CA and Neil HA. A meta-analysis
Blood Pressure: The ENCORE Study. Altern. Med. 2013;2013:1–13. of the effect of garlic on blood pressure.
Blumenthal JA, Babyak MA, Hinderliter A, doi:10.1155/2013/649836 J. Hypertens. 1994;12(4):463–468.
Watkins LL, Craighead L, Lin PH; Caccia 119. Ooi SL, Giovino M, and Pak SC. doi:10.1097/00004872-199404000-
C, Johnson J, Waugh R, Sherwood A Transcendental meditation for lower- 00017
Arch Intern Med. 2010;170(2):126–135. ing blood pressure: An overview of 122. Wang H-P, Yang J, Qin L-Q, and Yang
117. Kühlmann AYR, Etnel JRG, Roos- systematic reviews and meta-analyses. X-J. Effect of garlic on blood pressure:
Hesselink J, Jeekel H, Bogers A, and Complement. Ther. Med. 2017;34:26. A meta-analysis. J. Clin. Hypertens.
Takkenberg H. Systematic review and doi:10.1016/j.ctim.2017.07.008 2015;17(3):223.
meta-analysis of music interventions 120. Rohner A, Ried K, Sobenin IA, Bucher 123. Xiong XJ, Wang PQ, Li SJ, Li XK, Zhang
in hypertension treatment: A quest for HC, and Nordmann AJ. A systematic YQ, and Wang J. Garlic for hypertension:
answers. BMC Cardiovasc. Disord. review and metaanalysis on the effects A systematic review and meta-analysis of
2016;16(1):69. of garlic preparations on blood pres- randomized controlled trials. Phytomed.
118. Hagins M, States R, Selfe T, and sure in individuals with hypertension. Int. J. Phytother. Phytopharmacol.
Innes K. Effectiveness of yoga for Am. J. Hypertens. 2015;28(3):414–423. 2015;22(3):352–361. doi:10.1016/j.
hypertension: Systematic review and doi:10.1093/ajh/hpu165 phymed.2014.12.013
II
PA RT
75
6
CHAPTER
77
78 Chapter 6 The Concept of Nutritional Status and Its Measurement
concept of nutritional status, an overview of the methods disease states. Human beings all need the same nutri-
for evaluating it, and the various tools that are available ents but they also differ somewhat from one another in
to make inferences about nutritional status from dietary the amounts they need. We never know precisely what
intakes and other data. This chapter focuses primarily on an individual’s quantitative requirement for a nutrient
the dimensions of diet and nutritional status. The nutri- is. However, extensive experimentation and observation
ent standards for dietary intakes in the United States and over the past century have revealed that human nutrient
Canada, known as the Dietary Reference Intakes (DRI) requirements generally conform to a normal, Gaussian
are discussed. Next, some terms used in describing deliv- distribution, and the estimated required amounts have
ery mechanisms for the nutrients and other bioactives in been determined experimentally. Therefore, it is possible
healthy diets are described at the level, first, of foods and to use statistical techniques to predict recommended nutri-
then as food groups and eating patterns. The most well- ent intake amounts that are generous enough to suffice for
known guide for healthy eating in the United States, the virtually all healthy people.
Dietary Guidelines 2015–2020 is described. Next, the “Conditionally essential nutrients” are organic com-
nutrition information on food labels is summarized. We pounds not required in the diet of most people but that
conclude with some comments on healthy dietary patterns must be supplied to certain individuals who do not synthe-
and personalized nutrition. size them in adequate amounts, such as those with specific
genetic defects; those with pathologies such as infection,
disease, or trauma with nutritional implications; and
6.2 CONCEPT OF NUTRITIONAL developmentally immature infants. Those individuals
have special nutritional requirements that exceed those of
STATUS normal individuals. For example, inositol, taurine, argi-
nine, and glutamine may be needed by premature infants.
Nutritional status represents the bodily state resulting Additional information on the DRI, biomarkers of dietary
from the intake, absorption, utilization, and metabolism intakes, the uses of the DRI, and other issues involving the
of the diet the individual consumes. It can be measured at DRI are discussed later in this chapter.
both the individual and group level. Disordered nutritional
status runs the gamut from undernutrition (i.e., malnutri-
tion or nutrient deficiency) to over-nutrition—excess in
energy or nutrient intakes—and collectively these devia-
6.2.2 Special Nutrient Requirements
tions from normal are referred to as malnutrition. The concept that some individuals have “special nutri-
tional requirements” relates to the fact that there are cer-
tain genetic, epigenetic, or other causes that lead to much
6.2.1 Nutrient Requirements higher (or lower) amounts of one or more nutrients in
their diets. Phenylketonuria is an example of such a con-
Nutrients are substances that are not synthesized in suf- dition; those afflicted with this single gene defect require
ficient amounts in the body and therefore must be supplied less of the amino acid phenylalanine for health than do
by the diet. Their absence leads to growth impairment, those without the condition. A rather common folate poly-
organ dysfunction, and failure to maintain nitrogen bal- morphism or genetic variant, (MTHFR 677 C T), results
ance or adequate status of protein and other nutrients. in higher requirements for folate to maintain serum folate,
For good health, human beings require energy-providing red blood cell folate, and homocysteine.1 Similarly, vitamin
nutrients (protein, fat, and carbohydrate), alcohol (which B6 dependency, another single gene defect, is a condition
is not an essential nutrient but provides energy), vitamins, requiring very much higher amounts of a nutrient than
minerals, and water. Requirements for organic nutrients normal. Common chronic diseases such as cardiovascular
include nine essential amino acids, several fatty acids, disease, hypertension, and other conditions such as depres-
glucose, four fat-soluble vitamins, ten water-soluble vita- sion involve multiple genes as well as environmental and
mins, dietary fiber, and choline. Several inorganic sub- other influences. Whether individuals with these conditions
stances, including four minerals, seven trace minerals, require levels of some nutrients that are far outside of the
three electrolytes, and the ultra-trace elements, must also normal range is a topic of active research. But the evidence
be supplied by diet. Dietary protein consists of both essen- that they do is not yet definitive enough to have clinical
tial and nonessential amino acids that are required for implications.
protein synthesis. The nine essential amino acids are histi-
dine, isoleucine, leucine, lysine, methionine/cysteine, phe-
nylalanine/tyrosine, threonine, tryptophan, and valine.
When energy intake is inadequate, protein intake must be
6.2.3 Bioactive Food Components
increased, because ingested amino acids are diverted into Foods contain many constituents other than nutrients,
pathways of glucose synthesis or oxidation. In extreme such as pesticides, contaminants, phytochemicals, zooch-
energy deprivation, protein-calorie malnutrition may emicals, and microbial products that may also have
therefore ensue. Certain amino acids, such as alanine, can health effects. These constituents are sometimes collec-
also be used for gluconeogenesis as well as for energy and tively referred to as “bioactives.” Some examples include
are therefore called glucogenic amino acids. the polyphenols, flavonoids, glucosinolates, lutein, and
The amounts of essential nutrients required by indi- omega-3 fatty acids. These bioactives may have benefi-
viduals differ by their age and physiologic state such as cial functions in particular organs or organ systems even
growth, pregnancy, lactation, inflammation, and certain though they are not considered essential nutrients. For
6.3 Measurement of Nutritional Status 79
example, flavonoids may slightly reduce the risk of car- and dietary measures as well as food-related quality of
6
diovascular disease, as they have been shown to modulate life. The components involved in the assessment of nutri-
flow-mediated dilation, a measure of vascular rigidity that tional status are often summarized with an alphabetic
may be associated with blood pressure, although the evi- acronym—the ABCDEFs—that cover the breadth of indi-
dence is not yet considered definitive. cators: anthropometry; biochemical (biomarkers); clinical
status; dietary intake; energy expenditure; and functional
status. We propose adding a G to this rubric to include
6.3 MEASUREMENT OF genetic data as well, since genetic polymorphisms with
NUTRITIONAL STATUS implications for nutrient requirements or their metabo-
lism are becoming increasingly important.
Table 6.1 shows that multiple nutrition indicators may
6.3.1 Overview be necessary to describe nutritional status. Because each
Nutritional status is an inclusive term, and its assessment method has its limitations, several different measures that
usually includes anthropometric, biochemical, clinical, tap many characteristics and different levels of effects are
TABLE 6.1 Forms of malnutrition and clinical terms used to describe them
Form and cause of
malnutrition Clinical terms to describe it Comments
Dehydration: Inadequate Dehydration Often occurs secondary to fever, exertion, very
fluid intake to meet bodily warm, dry climate, or because of diets with high
needs solute loads or drugs that have diuretic effects.
Starvation: Virtually totally Marasmus, emaciation, cachexia Occurs with prolonged fasting; withholding of
inadequate intakes of all fluids worsens its effects.
nutrients
Protein-Calorie Kwashiorkor, protein calorie malnutrition Often occurs secondary to disease and
Malnutrition infection, probably via cytokine mediated
responses to acute infection or trauma.
Examples include HIV/AIDS. Sarcopenia due to
inadequate intake of protein and/or cytokine-
mediated responses to insults.
Vitamin, mineral, or other Pellagra (niacin/tryptophan), scurvy (ascorbic acid These deficiencies often occur secondarily to
specific nutrient deficiency), rickets and osteomalacia (vitamin D inadequate food intake or inadequate dietary
deficiencies deficiency in children and adults, respectively), iron quality. May also occur as conditioned
deficiency anemia (iron deficiency), nutritional anemia deficiencies secondary to disease.
(iron, vitamin B-6, folic acid or vitamin B-12
deficiency), essential fatty-acid deficiency
Imbalances: Increased Excess of saturated fat, cholesterol, and other Imbalances or excesses of energy-yielding
diet-related chronic disease atherogenic and thrombogenic dietary lipids nutrients or related substances may give rise to
risk factors due to (hyperlipidemias and perhaps altered clotting factors). metabolic aberrations and increase risks of ill
imbalances of nutrients Excess of salt and/or sodium (blood pressure risk health, especially in those with certain genetic
factors) profiles.
Obesity: Excess food Excess food energy regardless of source gives rise to Physical inactivity may increase likelihood of
energy intake and/or obesity and overweight excess energy intakes.
insufficient energy output
Alcohol excess Alcoholism, problem drinking At very high levels of alcohol intake, all persons
develop physical signs of chronic disease; at
lower levels of intake some individuals are
particularly susceptible.
Excess of other specific Specific toxicities vary: hypervitaminosis A (vitamin A), Intakes that exceed the upper level of the
nutrients (vitamins, hypervitaminosis D (vitamin D), fluorosis (fluoride), etc. Dietary Reference Intakes generally increase risk
minerals, others) of compromising one or more functions. The
possible functions vary from nutrient to nutrient.
Toxicity: Excesses of other Names vary depending on substance; lead poisoning, Many substances other than nutrients in food
constituents in food, drink, lathyrism, etc. and supplements may cause illness.
or supplements
Food-Borne Disease Food poisoning or food intoxication: Salmonellosis, Food is the carrier for a microorganism, virus, or
Botulism, Staphylococcal food poisoning, others. parasite.
Parasites such as beef tapeworm may cause
problems. Prions or viruses as in Bovine Spongiform
Encephalopathy (BSE)
80 Chapter 6 The Concept of Nutritional Status and Its Measurement
usually employed. Evaluation of nutritional status for clin- the absence or presence of signs of malnutrition and its pos-
ical purposes also considers the individual’s eating hab- sible causes by evaluating the diet and other anthropomet-
its, metabolically relevant health characteristics, and the ric, biochemical, and clinical data, since some disease states
presence of disease as well as environmental and living affect the bioavailability, requirements, use, or excretion of
conditions, exposure to pathogens, and socioeconomic specific nutrients. In order to be effective, nutritional status
conditions that may have an impact. assessment must be followed by the process of planning
and implementing appropriate dietary and other medical
measures based on the evidence and then later reassessing
6.3.2 Malnutrition intakes to make sure that intakes are more appropriate.
Table 6.2 shows the various forms of malnutrition, which
include deficiencies, excesses, and imbalances of nutrients.
While intakes must provide needed nutrients to prevent
6.3.3 Evaluating the Diet
deficiencies, the presence of disease, excesses of nutrients This chapter focuses primarily on one aspect of nutri-
or other bioactives, and imbalances between nutrients may tional status: dietary status. Dietary status refers to an
also cause health problems over the long term. Nutritional individual’s consumption of nutrients, foods, food groups,
assessment describes the specific form of malnutrition pres- or food patterns. It is a factor that can be altered to affect
ent, the stage in the development of malnutrition, and the nutritional status, while many other determinants of mal-
severity of the problem. Several forms are present together nutrition cannot. Dietary status and nutritional status are
in some instances, such as obesity and iron-deficiency ane- not synonymous, because food consumption is only one of
mia. Malnutrition occurs not only primarily and because many factors influencing whether an intake will suffice to
of dietary deficiencies, imbalances, and excesses but sec- maintain health. Intake is used as a proxy for nutritional
ondarily due to or in conjunction with disease, and the one status because it is less expensive and easier to obtain than
may exacerbate the other. Thus, in many cases, both nutri- a full-fledged nutritional status assessment and can often
tional and other disease treatments are often necessary to provide enough useful information to remedy problems.
restore nutritional status and health. For example, it can identify those who are very under-
The clinical signs of malnutrition, and their effects on nourished because they are eating too little, too much,
weight, organ function, and the activities of daily living or imbalanced amounts of foods and nutrients. Dietary
and quality of life, are usually the end result of a patho- assessment also helps to clarify and strengthen assump-
logical process of malnutrition that starts much earlier. tions about the presumed causes of changes in nutritional
This preclinical phase of malnutrition can often be iden- status when it is synchronized with anthropometric, bio-
tified by the use of dietary measures and biochemical, chemical, clinical information, and measures of functional
hematological, or other biomarkers in blood, urine, or status characteristics such as activities of daily living and
other bodily secretions, as well as by changes in individual environmental factors. Dietary assessment alone suffices
cells, tissues, and organ systems. If diet is the cause of the for many practical purposes, such as planning or assessing
malnutrition, food intake alterations are usually apparent what has been eaten and for informing dietary guidance
for days, weeks, or months before metabolism is altered and public health policy. 2
and changes in biochemical measurements are present. Dietary assessment is theoretically an extremely sensi-
Therefore, if the goal is to prevent malnutrition and to tive indicator of malnutrition, since it reflects a very early
do it as early as possible, dietary assessment is not only stage in the development of the pathology. However, by
worthwhile but essential. itself it is not useful for some purposes, such as describing
The appropriate treatment of malnutrition is an itera- nutritional status. This is because it measures only what
tive process that involves screening and then establishing an individual eats and not what is actually absorbed and
TABLE 6.2 Why multiple indicators of nutritional status are needed to diagnose malnutrition
Multiple forms of malnutrition exist.
See Table 6.1 for some examples.
The causes of malnutrition vary.
Some are due to deficient quality or quantity of diet alone (primary malnutrition), but most are secondary to disease or social or
psychological problems, and may occur even in the face of adequate and appropriate food in the environment. Many different pieces
of information are necessary to arrive at an understanding of how these causes interact.
No single indicator for all the forms of malnutrition exists.
The most sensitive, least costly, and most specific indicators of malnutrition vary from nutrient to nutrient.
Even for a specific form of malnutrition, indicators vary with respect to how sensitive, specific, valid, and reliable they are.
Severity of malnutrition varies.
Milder forms require different and more sensitive indicators (e.g., measures of tissue or blood stores) than the more severe (which may
be evident with anthropometric or clinical measures alone).
6.3 Measurement of Nutritional Status 81
metabolized, and so dietary assessment may miss other biased estimator of calories and protein from foods in
6
causes of poor nutritional status, such as malabsorption, adults than a frequency-based instrument.8
when disease is present. This makes it difficult to deter- Various dietary screeners are available to rapidly eval-
mine whether reported deficits in intake are actually due uate nutrient intake, nutrition risk, food group intakes,
to the diet itself or to errors in reporting. and food-related behaviors.3 Dietary screeners are avail-
able to assess overall diet quality and dietary in some
population groups,9,10 intakes of certain food groups like
fruits and vegetables,11 macronutrients,12 and micronutri-
6.3.4 Dietary Assessment Methods ent intakes.13 Checklists of foods have also been used for
The most important characteristics of diet for assessing identifying malnutrition.14,15
intakes are the amount of food eaten; what nutrients the The use of dietary supplements can be measured with
food contains; the forms in which they are present (e.g., some of the same techniques as dietary assessment of
food, beverages, supplements, or nutrient-containing foods. Dietary supplements have been measured through
medications, because the form may affect absorption and both specific and non-specific methods. Specific methods
metabolism); and the presence of other bioactives in food that assess only supplement use include frequency-based
known to have beneficial or harmful effects. The many questionnaires, in-home inventory methods, and short
methods for assessing dietary intake are reviewed in detail screening tools. Non-specific methods that assess both
elsewhere.3 Briefly, dietary assessment can be done on a supplement use and foods and beverages in the diet include
short- or long-term basis. Short-term instruments aim to 24-hour dietary recall (24 HR), food-frequency question-
gather short-term data on recent diet intakes (e.g., previ- naires (FFQs), and multiple-day food diaries. Currently,
ous 24 hours) whereas long-term instruments aim to cap- the National Health and Nutrition Examination Survey
ture dietary data over a longer period of time (i.e., the (NHANES) in-home supplement inventory protocol pro-
time frame can range from 30 days to the previous year). vides the perceived “gold standard” for measuring supple-
Which method is chosen to assess the diet depends both ment use: an in-home visit in which supplement containers
on the purpose and the time frame of the assessment, with are visualized and recorded by trained interviewers (spe-
consideration also given to practicality and cost. cific) in tandem with two 24-hour recalls that include
A food record is a detailed list of all foods and bever- supplement use (non-specific).
ages consumed within a specified period of time. Ideally, Technology in the field of dietary assessment is rapidly
foods and beverages are either weighed or measured; evolving. Web-based 24-hour dietary recalls are available
usually three to four days of intake are recorded as par- for research purposes by the National Cancer Institute at
ticipant burden generally causes a decline in the qual- no cost and perform reasonably well when compared with
ity of information recorded if more days are recorded.4 interview-administered 24-hour dietary recalls.16 Mobile
A 24-hour recall is a means to assess an individual’s intake applications, cameras, and wearables are some direct means
over the previous 24 hours; subjects are asked to recall all of assessing the diet.17,18 Digital images have been used to
food and beverages consumed. The use of probing ques- help respondents more accurately record portion sizes.16
tions aids the ease of responses and has been shown to
enhance data accuracy. 5 Multiple 24-hour recalls are rec-
ommended based on day-to-day variability in intake. Day
of the week, mode of interview (telephone or in-person),
6.3.5 Usual Diets and Total Intakes
and the sequence of the 24-hour recall are known to influ- Often health professionals and researchers are interested
ence reported energy intakes. Reported intakes of mac- in the long-term dietary intakes of a person or group
ronutrients from 24-hour recalls, which are consumed in because dietary recommendations are intended to be met
large amounts every day, are generally more stable than over time.19 Substantial variability in daily nutrient intake
those for micronutrients.6 The food record and the dietary occurs. Nutrients can also be stored in the body, mak-
recall capture recent or short-term information and are ing it unnecessary to meet recommendations daily—but
often used in population surveys. long-term or usual intake is necessary for other reasons
The food frequency questionnaire (FFQ) is an instru- we describe below.19
ment designed to reflect longer-term intakes that is often Today the majority of individuals in high-income
used in large cohort or case-control studies. FFQs assess countries live into old age and die of chronic diseases,
dietary intake over a specified period of time and queries many of which are diet related. Chronic degenerative dis-
how frequently a person consumes multiple food items eases take years or decades to develop, and over this time
aggregated into groups with similar nutrient profiles. dietary intakes taken on several occasions and energy
FFQs can be quantitative, semi-quantitative, or quali- outputs often change considerably. In order to link diet
tative.7 FFQs offer a more cost-effective alternative to over decades with health outcomes, longitudinal measures
the 24-hour recall since they can be self-administered. of dietary intake are needed to provide better measures
However, the FFQ limits the scope of foods that can be of exposure. Very large numbers of individuals must be
queried. The FFQ may create participant burden, and it tracked, because these diseases are relatively rare and
may be difficult or confusing to complete. This technique multifactorial, with diet being only one of many possible
requires literacy and physical ability to complete. Most causes. The use of semi-quantitative food frequency ques-
importantly, the accuracy of nutrient profiles determined tionnaires in epidemiological studies was an important
by FFQs has been questioned. The 24-hour recall admin- innovation, because they are relatively easy and inex-
istered on multiple occasions has been shown to be a less pensive to administer to large numbers of people. They
82 Chapter 6 The Concept of Nutritional Status and Its Measurement
permitted investigators to obtain information on the (USDA) National Nutrient Database for Standard
dietary intakes of large numbers of individuals and to Reference is the basis for USDA Food and Nutrient
better examine the associations of diet with health and Database for Dietary Studies (FNDDS) values that are
disease than ever before. However, these questionnaires used in analyzing NHANES data.35 It is critical that the
alone do not suffice, because errors and biases are very values for the nutrient content of foods used be kept up-to-
large. Advances in technology now make it feasible to date. The National Food and Nutrient Analysis Program
consider collecting multiple granular short-term recalls or (NFNAP) is a federally funded research program that pro-
records over time in addition to food frequency question- vides funds for analyses of new and reformulated foods to
naires among all participants in large cohort studies, or to enhance the analytical estimates of the nutrient content of
collect multiple 24-hour recalls. foods and dietary supplements.
Most health effects depend on usual or habitual intake The Dietary Supplement Ingredient Database (DSID) is
over relatively long periods of time, and yet it is very dif- a federally funded program to determine the analytically
ficult for people to remember what they have eaten from derived content of commonly used dietary supplements
one day to the next, much less from one week, month, relative to the labeled level. The DSID uses a complex
year, or decade to another. Therefore, usual intakes can- sampling program to ensure that products represent the
not be directly captured by any method of dietary assess- U.S. market for products. The DSID data suggest that
ment, and statistical procedures are used instead to adjust overages occur when analytical levels are compared with
for the within-person variation in daily reports to make analytic levels.
them reflective of usual intakes. 20–24 In the evaluation of For many years there have been calls for a branded
nutrition status, most links between diet and health are foods database in the United States, since even pack-
revealed only by examining habitual or usual dietary aged foods in the same categories differ greatly from
intakes of nutrients. It is these dietary determinants one another in their nutrient contents. In 2016 the U.S.
that may ultimately result in malnutrition and ill health. Department of Agriculture, in a public–private part-
Therefore, it is increasingly important to describe the nership with the International Life Sciences Institute of
long-term associations between dietary intake, nutritional North America (ILSI NA) and other groups, launched a
status, and risk of chronic disease. 25 voluntary program for manufacturers to submit the nutri-
ent composition of their foods into a public-use database.
As of 2017 a greatly expanded branded foods nutrient
6.3.6 Acute or Very Short-Term Intakes database for public use is available. It provides more pre-
cise estimates of the content of several nutrients of public
While long-term intake is usually the most important for health significance on the labels of branded foods. This
connecting dietary intakes with health, in some instances innovative database effort provides a solid basis for inves-
recent or usual dietary exposures are of interest. For tigating differences between foods for nutrients that are
example, the effects of food intoxication are often obvious listed on the food label. It can be accessed at https://ndb.
within hours or days after consuming the food causing the nal.usda.gov/ndb/.
poisoning accident. The acute event, along with details on
how the food was prepared and stored, often reveals the
cause of the foodborne illness.
6.3.9 Measurement Error in
Dietary Assessment
6.3.7 Total Nutrient Intakes All dietary assessment methods are subject to error.8,36,37
Total nutrient intake is the umbrella term for describing It is now recognized that the error in self-reported dietary
the reality that today nutrients come from all sources: assessment instruments must be considered in the analy-
foods, beverages, dietary supplements, and some medi- sis and interpretation of findings.2 The type of errors vary
cations. Since dietary supplement use is pervasive, 26–29 with the method used. Measurement error is defined as a
knowledge of the nutrients and bioactives in them is criti- measurement that deviates from the truth. It can be either
cal for determining nutritional status. In adults, but not in random or systematic. Random errors will decrease preci-
children, those who use dietary supplements tend to have sion of an instrument.38 Random errors, but not system-
significantly higher intakes of vitamins and minerals from atic errors, can be minimized by increasing the number of
food sources alone, so it is always important to include observations. Both types of errors can be reduced if pro-
assessment of dietary supplements.30,31 Dietary data with- cedures are built into an assessment method.38 Random
out the inclusion of dietary supplements overestimates the errors occur for all subjects, whereas systematic errors
prevalence of inadequacy and underestimates the preva- may occur only in certain respondents. For example, over-
lence of potentially excessive intakes. 32–34 weight individuals tend to underreport energy intakes to
a greater degree than normal weight persons. This would
lead to a systematic error occurring only in those that are
overweight.
6.3.8 Food and Supplement Databases Several common errors exist in dietary assessment:
All self-reported dietary data are also limited by the accu- respondent bias, interviewer bias, memory problems,
racy and currency of the databases that are employed to errors in estimating portion size, and the “flat-slope”
estimate energy and nutrient intakes from foods and bev- syndrome. Errors also occur when a researcher is collect-
erages reported. The U.S. Department of Agriculture’s ing or entering dietary data.38Therefore, information on
6.3 Measurement of Nutritional Status 83
dietary intakes is never perfectly accurate and should be exposures, they are less accurate in providing information
6
considered as a reasonable approximation and not abso- on the absolute amounts of nutrients or bioactives that
lute truth when assessing nutritional status. are consumed on a usual basis than they are at report-
The major problem with self-reported dietary data is ing what has been eaten over the past 24 hours. Dietary
that people do not recall or remember everything that was data are considered to be less precise and reliable than bio-
consumed, or they fail to accurately estimate the portion chemical and anthropometric indices because they have
sizes of what was consumed. Certain foods are often for- measurement bias, especially for estimates of energy. No
gotten, or the portion sizes are misjudged, particularly validation studies have compared the different methods
sweets, alcoholic beverages, and snacks. A common error for assessment of dietary supplement use. However, since
is failure to mention dietary supplements, which, in coun- dietary supplement consumption can be habitual (daily) or
tries such as the United States, often contribute substan- episodic (contextual), it may be ideal to use a frequency-
tially to dietary intakes. 2,30,39 based questionnaire to obtain the appropriate reference
Respondent bias also may arise because of social desir- period. Self-reported dietary data is most useful when it
ability to overreport foods that are healthy and under- is combined with the other types of indicators, such as
report less healthy foods—this has been referred to as biomarkers of nutritional status.49
“talking a good diet”.40 Likewise, an interviewer may be Recovery biomarkers provide insights on how far
the source of bias. Interviewers may ask subjects the same self-reported diet deviates from the “truth.” However,
question in different ways, may or may not probe for more recovery biomarkers of intake only exist for energy, pro-
information when necessary, and may introduce errors tein, sodium, and potassium. Energy underreporting is a
when coding or entering the data. known limitation with all methods of self-reported diet. 50
Assessing and recalling portion sizes is a necessary A pooled analysis of five large validation studies compar-
part of most dietary assessment techniques. Various strat- ing self-reported dietary data from 24-hour recalls and
egies are employed to help recall of portion sizes, includ- FFQs has provided a foundation for our understand-
ing visualization, estimations, and the use of measurement ing of deviations from “truth”.36 Doubly labeled water
aids (e.g., food models).41 Guthrie et al. found that perva- (D2O18) suggests that 24-hour recalls are much less biased
sive errors occurred in accurately reporting portion size for energy intakes than FFQs, 36 and this work also sug-
without measurement aids.42 Eight to 68% of respondents gests that 24-hour recalls perform better for the protein,
were able to estimate individual items within +/− 25% sodium, and potassium than FFQs. The 24-hour recall
of the actual amount. Zero to 67% overestimated por- can be enhanced with the use of the USDA’s Automated
tion size (greater than 51% above the consumed amount), Multiple-Pass Method (AMPM) that provides triggers for
whereas zero to 25% underestimated portion size by more memory and lists of typically forgotten foods; it is used in
than 51%.42 The “flat slope” syndrome refers to estima- the NHANES survey. 51,52
tion of portion sizes. A tendency exists toward overesti- The AMPM has been validated to the extent possible.
mation of portion size by those who eat small portions Energy underreporting using AMPM revealed underre-
and underestimation by those who eat large portions.43,44 porting of 3% in normal weight adults and 11% in over-
Faggiano et al. found that the magnitude of the overesti- weight adults. 52 The AMPM also indicates underreporting
mation and underestimation of portion sizes was 20% in in the range of 0%–4% for potassium and 4%–13% for
a sample that used pictures of foods as a guide for esti- sodium. From AMPM validation studies, reporting accu-
mation.43 Some research indicated subject training does racy, calculated as the ratio of reported sodium intake to
result in better portion estimation of some foods. Bolland that estimated from the urinary biomarker, was 0.93 (95%
et al. and others found significant differences in portion CI, 0.89–0.97) for males and 0.90 (95% CI, 0.87–0.94)
size estimation when comparing groups trained to esti- for females on average. 53
mate portion size to untrained groups.45,46 Because of the limited availability of nutrient recov-
One reason that portion sizes may be hard to estimate ery biomarkers, the use of other biomarkers to estimate
is that people do not notice that they have changed over nutritional status and exposures is a routine practice and
time. Portion sizes are increasing for both foods prepared is discussed in section 3.7.
in the home and those consumed outside of the home
(i.e., at restaurants). Nationally representative data indi-
cate that portion sizes increased in America between the
years 1989–1991 to 1994–1996.47 Significant increases in 6.3.11 Biomarkers of Nutritional Status
portion size for many foods were observed: beer, coffee, Because there are many problems involved in obtaining
carbonated sodas, orange juice, bananas, cereals, pasta, accurate information on food intakes, if precise esti-
coffee, and tea. Fewer foods and smaller magnitudes of mates of intakes are necessary, as is the case in research
decreased portion sizes were observed for margarine, studies, surrogate biomarkers of intake are often used.
mayonnaise, pizza, carrots, and chicken. Portion sizes are Biomarkers are reliable and accurate biochemical or other
directly related to weight status.48 measurements that can be objectively measured and evalu-
ated. They can be indicators of intake, normal biologi-
cal processes, nutritional status, pathological processes,
pharmacological responses to an intervention, or health
6.3.10 Validity of Dietary Data outcomes. 54,55 The National Institutes of Health defines
The major shortcoming of most dietary assessment meth- biomarkers as any biological measurements that indicate
ods is that while they furnish a general profile of dietary “normal biological processes, pathogenic processes, or
84 Chapter 6 The Concept of Nutritional Status and Its Measurement
pharmacologic responses to therapeutic intervention.”54 example, blood pressure is used to assess the risk of later
While a wide range of surrogate biomarkers are available stroke and other cardiovascular disease.
for use, their utility depends on the purpose for its use. 56 Dietary biomarkers are used to assess dietary intakes/
Nutritional biomarkers are biochemical, functional, or exposures without having to rely on the bias and errors
clinical indices of nutrient intake, status, or their func- that are involved in self-reported dietary intakes. Some
tional effects that can reveal information about biological dietary biomarkers, such as markers for caffeine, citrus
or physiological responses to dietary behavior or patho- fruit intake, cocoa, garlic, and wine are available and pro-
logical processes. They are also used to monitor responses vide indications of intake, not quantitative estimates of
to therapeutic interventions and to provide information intake. Many more of these biomarkers are needed.59 For
on inter-individual differences in the response to diet and example, development of a biomarker to assess intakes of
nutrition. 57 Nutritional biomarkers are obtained from dietary sugars is underway.60
blood, urine, bone, saliva, skin, adipose tissue, and some- Some biomarkers of nutritional status are also avail-
times for some nutrients from fingernails and toenails. able, and some, such as 25 OH D, to measure not only
However, other nutritional biomarkers may be used to intake but vitamin D status and various blood measures of
perform functional assessment of health parameters such folate and iron status, are now collected on a fairly regular
as immune function or grip strength (used to help assess basis in the National Health and Nutrition Examination
frailty). Some examples of nutritional biomarkers can be Survey (NHANES).
found in Table 6.3. Recently a biomarker resource has been developed by
Nutritional biomarkers are categorized by those that federal scientists to assist in selecting appropriate tools
reflect nutritional exposures (i.e., intake), those that for different purposes The federally led effort, known
reflect nutritional status, and those that can be used to as Biomarkers for Nutrition in Development, provides
predict health outcomes, often referred to as surrogate extensive information on selected nutritional biomark-
biomarkers of end points. 58 The relevant time frame that ers, including vitamin A,61 folate,62 zinc,63 and iodine.64
biomarkers reflect is a key issue to address when select- The Biomarkers Reflecting Inflammation and Nutritional
ing one to measure. For example, surrogate biomarkers Determinants of Anemia is another informative resource
are often used to reflect diseases with long latencies—for for biomarkers of iron status.65–67
TABLE 6.3 Some biochemical biomarkers of intake (exposure) and/or nutritional status
Nutrient Biomarker Comments
Iron Hemoglobin Low specificity (many different causes of anemia decrease hemoglobin, not just
iron). Cutoffs vary by age, sex, and ethnicity. This is a good indicator for
monitoring improvement in iron status if the individual is iron deficient.
Serum plasma ferritin This is an acute phase protein, and it is non-specific; it increases independently
due to acute or chronic inflammation, infection, malignancy, hyperthyroidism,
liver disease, heavy alcohol use.
Serum transferrin receptor A specific indicator of iron-deficient erythropoiesis that is not affected by
inflammation.
TIBC (total iron binding capacity) Nonspecific and varies over the day.
ZnPP erythrocyte zinc protoporphyrin A sensitive indicator for diagnosis of the deficiency. However, the specificity is
limited since it is affected by lead poisoning, the anemia of chronic disease,
chronic infection, inflammation, hemoglobinopathy, and hemolytic anemias.
Zinc Serum plasma zinc Responds to zinc supplementation, but it is easily affected by contamination and
is also affected by inflammation, fasting, estrogen use, hemolysis, and chronic
illness.
B-12 Serum/plasma total zinc Measures total biologically active B-12. Poor correlation with dietary zinc. Also
cutoffs are uncertain and kits for the test vary.
Serum/plasma methylmalonic acid Cutoffs are uncertain. Test is sensitive.
MMA
Serum/plasma holotranscobalamin
HoloTC
Folate Serum/plasma folate Varies with recent intake, and kits to test vary.
Erythrocyte folate Kits vary. Samples are difficult to prepare and cannot be stored.
Serum/plasma total homocysteine Depends on B-2 status, B-12 status, B-6 status, and MTHR polymorphism state.
Hcys
Vitamin A Serum retinol Sensitive to intake, but only if stores are low. It is not very sensitive because it is
under homeostatic control.
6.4 Guidelines for Energy and Nutrient Intakes 85
6.3.12 Issues Arising in Interpreting judgment is involved in choosing that which is the most
6
relevant and best supported by the available evidence. The
Biomarkers of Nutritional Status amount of evidence and the criteria vary from nutrient to
In order to be useful, nutritional biomarkers must be nutrient. The Dietary Reference Intakes are the authorita-
analytically valid. Although they are very helpful in the tive energy and nutrient standards for the United States
assessment of nutritional status, there are many biological and Canada; however, the World Health Organization
and methodologic issues that must be considered before and many other groups also make dietary recommenda-
they can be considered to be valid.58 Not all nutrients tions that are used in other countries.
have a biomarker that can be used in assessment. Some
nutrients with appropriate biomarkers, such as iron, are
still extremely difficult, time-consuming, and expensive 6.4.1 The Dietary Reference Intakes (DRI)
to use.68 For some nutritional biomarkers, factors such
as hydration status, inflammation, and diurnal variations The Dietary Reference Intakes (DRI) are a broad group of
influence measurements. Furthermore, the cost can be high quantitative standards for nutrient reference intakes that
for assessing nutrition status through biomarkers, which are used for planning and assessing the diets of healthy
is often why dietary data are used instead. The use of cut- individuals (Table 6.4). The DRI consist of multiple ref-
points to determine nutritional status is also difficult.69 For erence recommendations that serve as dietary standards
example, very different prevalence estimates of B-vitamin for dietary adequacy and excess.75–83 Recommendations
risk have been documented within the same data set when are available for vitamins, minerals, choline, protein, fat,
different cut-points are used to determine nutritional sta- carbohydrate, and water, electrolytes, and total energy
tus of these vitamins.70,71 Some biomarkers, like folate, are (calorie) intake. The DRIs are based on the best evidence
well represented by dietary intakes,72 whereas estimates of available for intake levels of nutrients that are compatible
vitamin D from the diet differ from serum 25(OH) D.73,74 with good health. They consist of multiple reference val-
A complete review of the available nutritional biomark- ues that are used as standards for nutrient intakes and are
ers with their fit for purpose and limitations is available the basis for other recommendations, such as the Dietary
elsewhere.59 Guidelines for Americans, that provide food-based dietary
guidance, and for food labels.84,85 The DRIs are periodi-
cally updated when newer data and/or funds are available
6.4 GUIDELINES FOR ENERGY to commission a report.
A comprehensive guide to using the DRIs in dietary
AND NUTRIENT INTAKES assessment can be found elsewhere.86 The DRIs include
the estimated average requirement (EAR) and the Al
The criteria for adequacy upon which estimates of nutri- Dietary Reference Intake values are publicly available
ent needs are based are critical. There are often several on the Internet.87 The recommended dietary allowance
criteria that conceivably might be chosen, and so expert (RDA) is calculated based on the EAR to take into account
TABLE 6.4 The Dietary Reference Intakes and their description and uses
EAR The Estimated Average Requirement (EAR) is the amount of a nutrient that is estimated to meet the requirement of half of the
healthy individuals in a specific life-stage and sex group. The EAR is used to assess adequacy of intakes of population
groups, and along with knowledge of the distribution of requirements, to develop Recommended Dietary Allowances.
RDA The Recommended Dietary Allowance (RDA) is the average daily dietary intake level that is sufficient to meet the nutrient
requirements of nearly all (e.g., 97%–98%) of healthy persons of a specific sex at a particular stage of life or physiological
condition, such as pregnancy or lactation. The only use of the RDA is to serve as a goal for individuals. The RDA is the value
that should be used for planning individual intakes. The RDA is not appropriate for assessing the diets of either individuals or
groups, or for planning diets for groups.
AI The adequate intake (AI) is a recommended daily intake level based on observed or experimentally determined estimates of
nutrient intake in a group of healthy people. The main use of the AI is as a goal for the nutrient intake of individuals. It is used
when an RDA cannot be determined. The AI is usually based on observed levels of intake that appear to maintain an
acceptable level of health or growth.
UL The tolerable (or safe) upper intake level (UL) is the highest level of chronic and usual daily nutrient intake that is likely to pose
no risks of adverse health effects to almost all individuals in the general population. The UL is not an intended level of a
nutrient to be consumed. Moreover, the UL is not a level at which there is a beneficial effect. It instead describes the intake
level at which there is a high probability that the dose of the nutrient can be tolerated biologically.
EER The Estimated Energy Requirement (EER) is the average energy intake needed to maintain energy balance in an adult, for
growth in infants and children, to sustain fetal development in pregnancy, and to produce milk in lactating women. For adults,
the EER is estimated using equations that consider the person’s sex, age, weight, height, and level of physical activity. The
EER can be used at the individual level to appropriately plan energy intakes to maintain, lose, or gain body weight.
AMDR The Acceptable Macronutrient Distribution Range (AMDR) is the recommended range of percent of total energy intake from
five macronutrients: total fat, n-6 polyunsaturated fatty acids (linoleic acid), n-3 polyunsaturated fatty acids (alpha-linolenic
acid), carbohydrate, and protein. The AMDRs represent intakes that minimize the risk of chronic disease and permit an
adequate intake of essential nutrients.
86 Chapter 6 The Concept of Nutritional Status and Its Measurement
differences between individuals in requirements. If the or criteria of adequacy, and the rationale is provided with
EAR and RDA cannot be calculated because appropriate extensive documentation of the evidence available to set it.
data are unavailable, an adequate intake (AI) based on These criteria include the best level to use for estimating the
intakes of healthy people is provided (Table 6.5). The EAR, risk of an individual’s nutrient stores becoming deficient.
RDA, and AI are all defined with reference to specific cri- These are critical for making estimates of nutrient needs.
teria of nutrient adequacy. A Tolerable Upper Intake Level The criteria (called functional indices or functional criteria)
(UL) is also set.88 The UL is defined to be a level below used vary but often include the level at which the risk of an
that of excess, as defined by specific indicators of excess individual’s nutrient stores are adequate for nutrient needs.
when they are available. Recommendations for acceptable For example, the criterion of adequacy for folic acid among
macronutrient distribution ranges (AMDR) and energy women in the childbearing years is based on a combination
needs as assessed by total energy expenditures (TEE) are of three biochemical indicators, primarily red blood cell
also provided. These AMDR are based largely on epide- foliate, and secondarily plasma homocysteine and serum
miological rather than experimental evidence. The refer- folate levels. Other criteria relate to reducing the risk of dis-
ence weights and heights for the adults and children for ease if they are available, although often they are not. For
whom the dietary recommendations are designed are based example, a separate recommendation for folic acid is made
on recent population-based surveys of the U.S. population. for women capable of becoming pregnant on a criterion
related to reducing the level of neural tube defects. There
are often several functional criteria that conceivably might
6.4.2 Criteria for Setting Dietary be chosen. Expert judgment is always involved in choosing
the criterion that is the most relevant and best supported
Reference Intake Recommendations by the available evidence. The amount of evidence and the
Nutrients affect many bodily functions. In setting intake rec- criteria vary from nutrient to nutrient. Each EAR, RDA,
ommendations, it is desirable to choose intakes that support and AI is described in terms of a selected criterion or some-
all of them. The criterion for defining a level of a nutrient times, if a single criterion is not definitive, a few criteria of
at which some function is declared adequate involves selec- adequacy combined.
tion of a functional index or functional criteria. Each EAR, Prevention of chronic disease is a focus of some
RDA, and AI is described in terms of a selected criterion other nutrient adequacy criteria such as the association
TABLE 6.5 Healthy dietary patterns in the 2015–2020 Dietary Guidelines Advisory Committee Report
Component Healthy U.S. Healthy Mediterranean-Style DASH Healthy Vegetarian
Total fruit (whole not juice) 2 2.5 4 2
Total vegetables (cups) 2.5 2.5 4.0 2.D5
Dark green 1.5/wk 2.5/wk 1.5/wk
Red/orange 5.5 5.5 5.5
Starchy 5.0 5.0 5.0
Legumes 1.5 1.5 3.0
Total Grains (oz equivalent) 50% 6 6 6 6
Whole grain
Dairy, cups 3 2 3 3
Protein foods (oz equivalent) 5.5 6.5 – 3.5
Nuts/seeds 4/wk 4/wk 4–5/wk 7/wk
Red and processed meats 12.5/wk 12.5/wk ≤6/wk –
Poultry 10.5 10.5 – –
Seafood 8/wk 15/wk = =
Eggs 3/wk 3/2k = 3/wk
Processed soy (tofu) 0.5/wk 0.5/wk = 8/wk
Fats
Solid fats, g (tsp) 18 (2) 17(0.9) 2–3 21(2.3)
Oils g (tsp) 27(3) 27 (3) – 27 (3)
Sweets, added sugars g(tsp) 30 (7.5) 29(7.25) – 36(()
Sugar-sweetened beverages/fruit juice – – <5/wk =
6.4 Guidelines for Energy and Nutrient Intakes 87
between fluoride and risk of dental caries. The associa- at risk of every disease; the prevalence varies, with evi-
6
tions between nutrient intakes and risk of most chronic dence being strongest for dental caries, then osteoporo-
degenerative diseases have proven to be more difficult to sis, followed by coronary heart disease, kidney stones,
establish and remain an area of controversy and research. and lastly, cancers. Dietary intake exposures occur long
before the chronic disease occurs, and experimental stud-
ies would take many years to give definitive answers. The
6.4.3 The DRI Framework for use of observational studies to establish recommenda-
tions based on chronic disease outcomes has many prob-
Chronic Disease Risk lems and makes causal inference weak. Dietary exposures
Although the DRI are designed as recommendations for occur long before these chronic degenerative diseases,
healthy individuals, more than half of all Americans and diet is only one of many causative factors that vary
have one or more chronic conditions, and their number in strength from one person to another. There are also
is growing as the population ages. Many of the common many problems with measures of outcomes. Morbidity
chronic diseases such as cardiovascular disease, diabetes measures are often imprecise, and mortality takes many
mellitus, and some types of cancer may be caused in part years to collect. Surrogate or intermediate markers rather
or made more severe by diet, while others such as arthri- than these outcomes are often lacking or invalid, and
tis, asthma, gastrointestinal disease, chronic renal insuf- some intermediate markers may not even be on the causal
ficiency, and chronic obstructive pulmonary disease have pathway to the disease outcome.
nutritional implications in their treatment. Prevention of In the existing DRIs, only five nutrients were assigned
chronic disease is a focus of some other nutrient adequacy reference values based on chronic disease end points. They
criteria, such as the association between fluoride and risk were calcium and vitamin D with osteoporosis and frac-
of dental caries. The associations between nutrient intakes tures; fluoride and dental caries; dietary fiber and coro-
and risk of most chronic degenerative diseases have proven nary heart disease; and potassium and a combination of
to be more difficult to establish and remain an area of end points, including salt sensitivity (a risk factor for
controversy and research.89 For example, the criterion hypertension), kidney stones, and blood pressure. Chronic
for the amount of calcium and vitamin D recommended degenerative disease end points do not fit well into the
was based on the amount sufficient to provide retention existing DRI paradigm since they are multifactorial, and
of calcium during growth and to minimize bone loss many dietary and non-dietary factors contribute to each
during adulthood. It is hoped that this measure of bone of them. Chronic disease risk reduction is often only
health will decrease risk of osteoporosis. For dietary fiber, associated with small responses to increased doses of the
decreases in serum cholesterol were chosen as the criterion nutrient. By definition, the EAR is the intake to achieve
in the hope that this would help to decrease risks of coro- absolute risk reduction of 50% (that is, the probability of
nary artery disease. For potassium and sodium, adequate getting a disease over a certain time). But this depends on
intakes were established but not on the basis of an associa- the relative frequency of the presence of risk factor, and
tion with chronic disease end points, because data were absolute risk is not 100% even for everyone who has a
judged insufficient to do so. The evidence base for provid- given chronic disease. One hundred percent of the popula-
ing recommended levels of protein, phosphorus, magne- tion is at risk of a dietary deficiency disease if the nutrient
sium, the B-vitamins, and choline was judged insufficient dietary component is provided, but adding the nutrient
to define a function in preventing chronic disease, and so or other dietary constituent does not prevent the chronic
the estimation of the requirement depended on other cri- degenerative disease in 100% of the population. In fact,
teria, such as mineral balance. The measures upon which risk of the chronic degenerative disease probably ranges
the EAR for protein is established, nitrogen balance, is from very high to very low. Risk reduction is almost never
judged by some scientists to be inadequate because they 50%, as is the case when a nutrient is provided in a dietary
lack a close enough association with protein functions in deficiency disease with an EAR. It is therefore likely that
the body such as maintenance of muscle mass or immune instead of focusing on single nutrients, patterns of nutri-
function. However, measures of protein nutritional status ents or food intake patterns will be more useful in linking
that are valid, reliable, and more reflective of these than diet to chronic disease end points. The challenge is how to
nitrogen balance are still being vigorously debated and as best do this.
yet another marker has not been settled upon. As new and For individuals who are ill, the best recommendations
better functional indices are developed that are closely for nutrient intakes at present depend on how the disease
associated with risk of chronic disease, functional indices itself affects the absorption, metabolism, storage, and/or
and estimates of nutrient requirements may also change. excretion of specific nutrients. In cases where one or more
A major challenge is to how to assess the links of these factors are affected, requirements may change.
between dietary constituents and chronic disease end Recommendations are best set by medical specialists for
points as outcomes. Since the major causes of morbid- the diseases involved. Usually only a few rather than all
ity and mortality in highly industrialized countries are nutrient needs are affected, and for the unaffected nutri-
chronic degenerative diseases, in order to have an impact ents the DRI for healthy individuals can be used until
on delaying morbidity and reducing premature mortality, better data are available. Not only disease but also medi-
it is essential to act upon them. Even small reductions in cations may affect nutrient requirements. Many members
diet-related risks would have potent effects at the popula- of the population in countries like the United States and
tion level. However, it is difficult to develop the evidence Canada are medicated for one or more chronic diseases.
that diet-chronic disease outcomes exist. Not everyone is When effects of common medications are known, dietary
88 Chapter 6 The Concept of Nutritional Status and Its Measurement
groups. A recent project to examine various recommended certain food groups and points for intakes also stressing
dietary patterns found that there were common elements nutrients to avoid and nutrients to limit that are in line
among them.106 It would also be of interest to compare with the Dietary Guidelines for Americans.110 Figure 6.1
nutrient profiles in these patterns to detect similarities and presents the components of the HEI 2015 scoring system;
differences. a “perfect” score is 100. Dietary intakes when assessed
Dietary patterns such as those in the Dietary with previous versions of this index rarely scored above
Guidelines for Americans, the Dietary Approaches to 70 and often much lower than this.111–113 Several years ago
Stop Hypertension (DASH), the Mediterranean Diet a survey of U.S. diets rated an average HEI of 50, so there
are also increasingly being used to describe intakes and is much that needs to be improved. However, it has been
compare diets across different cohorts.106 DASH107 and suggested that present U.S. food supplies are insufficient
PREDIMED (Prevención con Dieta Mediterránean)108 are to meet the dietary recommendations114 and that the cost
two examples of successful dietary pattern clinical inter- of meeting dietary recommendations is relatively high.115
ventions using the whole diet approach. More research is needed on those points.
Adequacy:
Component Maximum points Standard for maximum score Standard for minimum score of zero
6
Total Fruits 2
5 ³0.8 cup equiv. per 1,000 kcal No Fruit
Whole Fruits 3
5 ³0.4 cup equiv. per 1,000 kcal No Whole Fruit
Total Vegetables 4
5 ³1.1 cup equiv. per 1,000 kcal No Vegetables
Greens and Beans 4
5 ³0.2 cup equiv. per 1,000 kcal No Dark Green Vegetables or Legumes
Whole Grains 10 ³1.5 oz equiv. per 1,000 kcal No Whole Grains
Dairy 5
10 ³1.3 cup equiv. per 1,000 kcal No Dairy
Total Protein Foods 6
5 ³2.5 oz equiv. per 1,000 kcal No Protein Foods
Seafood and Plant Proteins 6,7
5 ³0.8 oz equiv. per 1,000 kcal No Seafood or Plant Proteins
Fatty Acids 8
10 (PUFAs + MUFAs)/SFAs ³ 2.5 (PUFAs + MUFAs)/SFAs £ 1.2
Moderation:
Refined Grains 10 £1.8 oz equiv. per 1,000 kcal ³4.3 oz equiv. per 1,000 kcal
Sodium 10 £1.1 gram per 1,000 kcal ³2.0 grams per 1,000 kcal
Added Sugars 10 £6.5% of energy ³26% of energy
Saturated Fats 10 £8% of energy ³16% of energy
1: Intakes between the minimum and maximum standards are scored proportionately.
5: Includes all milk products, such as fluid milk, yogurt, and cheese, and fortified soy beverages.
7: Includes seafood, nuts, seeds, soy products (other than beverages), and legumes (beans and peas).
8: Ratio of poly- and monounsaturated fatty acids (PUFAs and MUFAs) to saturated fatty acids (SFAs).
Figure 6.1 Healthy Eating Index (HEI 2015): Components and Scoring Standards.
6.6.1 Energy Density and Nutrient Density Nevertheless, nutrient density is also relevant to health
since nutrient-dense foods are more likely to “carry their
Energy density and nutrient density are two characteristics own weight” with nutrients to accompany the food energy
of foods that are associated with nutritional health. Energy they provide, ensuring that nutrient as well as energy needs
density (also referred to as caloric density) is defined in a will be met. There is good evidence that the nutrient den-
number of different ways in the literature.116,117 Most com- sity of usual American dietary intakes is much lower than
monly, energy density is defined as calories per gram of all that suggested in the Dietary Guidelines for Americans and
foods and beverages in the diet, while other calculations other recommendations.118
do not include beverages at all.117 Sometimes the energy
density of diets is calculated on all foods and beverages
that provide calories, and in other instances it is calculated 6.6.2 Determining Nutrient Quality
only on foods, making the literature extremely confusing.
Energy density is linked to energy intake in that it is easier
of Foods and Diets
to consume too much of high energy density items like There are many indices and scores of diet quality.
alcohol and fatty/sugary foods than foods that are lower Communication of scores for individual foods is difficult to
in energy density and higher in bulk and water, like fruits do without demonizing certain foods and elevating others
and vegetables. unduly, but measures of overall dietary quality are more
Nutrient density is another commonly used term. It appealing and could be helpful. Most such measures are
refers to nutrients per some unit; however, the unit is not based on profiles of the macronutrients and tend to over-
always entirely clear and can refer to nutrients per calo- look micronutrients. There has been some work done
rie or per gram, and in others it refers to per unit vol- recently on nutritional profiles combining both macronutri-
ume or nutrients in a food or diet compared to nutrient ents and micronutrients, and on foods or food groups that
requirements/recommendations for these same nutrients. may be more helpful measures of overall dietary quality.
92 Chapter 6 The Concept of Nutritional Status and Its Measurement
Nutrient profiles are one way of measuring the nutri- applied to the development of the entire NRF family of
tional quality/contribution of foods to overall nutritional nutrient profile models. First, the NRF models included
needs.119 Appropriately constructed nutrient profile scor- nutrients to encourage as well as nutrients to limit.
ing systems can be helpful in identifying both processed Second, NRF model performance was repeatedly tested
and unprocessed foods that are nutrient dense.120–123 against the Healthy Eating Index (HEI), an independent
When this information is combined with other metrics measure of a healthy diet. HEI values were calculated
such as calorie content and overall energy intakes they can for participants in the 1999–2002 NHANES.124 Models
be used to identify appealing and affordable food items based on 100 kcal and serving sizes performed better than
that are also healthy to eat. However, it is necessary to those based on 100 g. Formulas based on sums and means
refine measures of dietary quality rather than simply focus performed better than those based on ratios. The nutrient
on maximizing the nutrients per gram or per serving in density of foods using this or some similar profiling sys-
each food. Drewnowski has done a great deal of work tem, paired with a comprehensive program of consumer
in developing various methods for nutrient profiling.124 education, can become the foundation of dietary recom-
According to him, “[N]utrient profiling is the technique of mendations and guidelines.124,125
rating or classifying foods on the basis of their nutritional
value. Foods that supply relatively more nutrients than
calories are defined as nutrient dense. Nutrient profile 6.7 NUTRIENT INFORMATION
models calculate the content of key nutrients per 100 g,
100 kcal, or per serving size of food.” For maximum ON FOOD LABELS
effectiveness, Drewnowski suggests that nutrient profile
models be transparent, based on publicly accessible nutri- Individual foods differ in the nutrients and other bioac-
ent composition data, and validated against independent tives they contain, and therefore it is useful to know their
measures of a healthy diet.122 Nutrient profiling systems composition. Food labels that assess nutrient content of
are useful when approaches based on nutrients are taken individual food products have been used to assist consum-
to categorizing foods rather than approaches based solely ers in making better food choices when they are buying
on food groups to eat. Thus, nutrient profiling of food them. Nutrition Facts labels on packaged and other foods
groups and overall diets may help to harmonize nutrient in the United States provide information on various nutri-
labeling approaches that focus on individual foods with ents, and similar labels are provided on the supplement
dietary recommendations based solely on descriptions of facts panel for dietary supplements. Regulatory agencies
food patterns or food groups to emphasize. both in the United States and elsewhere in the world use
nutrient composition data to determine whether single
food products can be claimed to be low in fat, high in
calcium or the like.
6.6.3 Nutrient-Rich Foods Index The nutrition information on labels is an important aid
Several indices are used to identify nutrient-rich foods, for helping individuals choose foods wisely. Packaged and
but one of the first, best known and best researched of processed food products have included ingredient labeling
them is the Nutrient-Rich Foods (NRF) Index, devel- for many years, with ingredients listed in order by weight.
oped by Drewnowski from the 2005 Dietary Guidelines These ingredient lists are helpful for people who want to
for Americans, which identified nutrient density as a key include or avoid certain food ingredients in their diets for
component of diet quality.125 The notion was that “every health or cultural reasons. Nutrient labeling is more recent.
calorie should count” by being accompanied by other Food labels, regulated under the federal Food, Drug, and
nutrients that were also needed by the body. The NRF Cosmetic Act (and its related amendments), are required
Index ranks or classifies foods based on their nutrient for all packaged and prepared foods and beverages, but
composition, assigning each food a single unitary score it is still voluntary for produce.127 The Nutrition Labeling
that best reflects its total nutrient quality. The concept and Education Act of 1990 (NLEA) amended the federal
has gone through several iterations, but the latest NRF Food, Drug and Cosmetic Act of 1938 to require addi-
9.3 Index is based on nine beneficial nutrients (protein; tional nutrition information on almost all processed pack-
fiber; vitamins A, C, and E; calcium; iron; potassium; and aged foods, and the U.S. Department of Agriculture issued
magnesium) and on three nutrients to limit (saturated fat, similar regulations shortly thereafter for meat, poultry, and
added sugar, and sodium)126 as specified in the DGA. The other products regulated by that agency. Now virtually all
NRF 9.3 algorithm for scoring is the unweighted sum of perishable foods and commodities have nutrient labels.
percentage daily values (DVs) for nine nutrients to encour- New regulations for nutrient labeling of foods and
age, minus the sum of percentage maximum recommended dietary supplements were finalized by the Food and Drug
values (MRVs) for three nutrients to limit, calculated for Administration (FDA) in 2016 and will go into effect in
the reference amount and capped at 100% DV. 2020. Nutrition Facts and Supplement Fact panels con-
The NRF Index successfully ranks foods based on forming to the finalized regulations of 2016 have been
their nutritional value and can be applied to individual widely adopted by food manufacturers, with changes
foods, meals, menus, and even the daily diet.121,125 Higher to the new format required by all entities in 2020 (note
NRF 9.3 scores are associated with lower energy density that the original deadlines have been moved up). Many of
and more nutrient-rich diets. The standards of transpar- the major food manufacturers in the United States have
ency, use of publicly accessible data and validation against already made changes and launched the new labels on
independent measures of a healthy diet as standards were packaged foods.
6.7 Nutrient Information on Food Labels 93
6
consumers compare food choices and identify healthier
foods at a glance. Some focus on single nutrients, while
others provide a composite or “traffic light” statement
reflecting several nutrients and an implicit recommenda-
tion. In the United States they are not required by law
but are voluntary. Many food manufacturers also include
the front-of-pack Facts Up Front label on their packages
The section below describes the major characteristics and
regulations of the food label and label claims.
years, the mean intakes are 14.3 ± 0.2%, for teens 9–18 The other claims, B, C, and D, are called “qualified
years, 16.2 ± 0.2%, and among young adults ≥ 19 years, “health claims to indicate that the evidence stating a con-
13.1 ± 0.2%, with the major sources being sweetened bev- nection must be qualified because it is less certain than the
erages and sweetened bakery items.128 Note also that the unqualified claims that are well supported by scientific evi-
definitions of added sugars found in U.S. regulations and dence. Qualified health claims have been approved for a
the “free sugars” referred to in European regulations are variety of foods and nutrients in which the scientific evi-
not synonymous; the latter include 100% fruit juice. dence is less conclusive. These claims that are lower down
The most recent revisions of the labels also include in the evidence hierarchy, for which there is less scientific
serving sizes updated to reflect the amounts of food people agreement about the association are also allowed, but only
are actually eating and drinking today, and display calo- with additional explanation, qualifications, or disclaimers
ries much more prominently than in years past. Another to avoid misleading consumers. They all require a state-
change is harmonizing the units used to declare vitamins ment that the claims are not endorsed by the Food and
A, E, and D; they have been changed from “international Drug Administration. These claims must also make it clear
units,” or “I.U.” to a metric measure—milligrams or that the evidence is not strong. For example, the claim for
micrograms. walnuts and coronary heart disease must state: “Supportive
but not conclusive research shows that eating 1.5 ounces
per day of walnuts, as part of a low saturated fat and
6.7.2 Label Claims low cholesterol diet and not resulting in increased caloric
intake, may reduce the risk of coronary heart disease.
In addition to Nutrient Facts and Supplement Facts labels Sometimes this grading system is referred to as the
that provide energy and nutrient contents per serving, health claim “report card,” indicating the caveats or
additional information in the form of claims can be made qualifications that are necessary for these less well-sup-
on packaged foods and dietary supplements.129 Three ported claims. The qualifying language is usually stated
types of claims are regulated by the FDA and include as follows:
nutrient content claims, health claims, and structure/func-
tion claims. Each type of claim has specific guidelines on A: “There is significant scientific agreement for [the
what they mean and how they can be used, and all are claim].”
regulated by the FDA. B: “Although there is some scientific evidence support-
ing [the claim], the evidence is not conclusive.”
C: “Some scientific evidence suggests [the claim].
6.7.3 Nutrient Claims However, the F.D.A. has determined that this evi-
Regulated under the Nutrition Labeling and Education dence is limited and not conclusive.”
Act of 1990, specific claims on the label that reference the D: “Very limited and preliminary scientific research
amount of energy or nutrients in a product are permitted. suggests [the claim]. The F.D.A. concludes that there
Nutrient content claims characterize the amount of energy is little scientific evidence supporting this claim.”
or a nutrient is provided by a serving of specific products.
Words used to describe nutrient content include a “good
source,” “high,” “low,” “free,” or describe a product, for 6.7.5 Structure/Function Claims
example, as “reduced” or “light.” Each of these descrip-
Structure/function claims describe how an association
tors has a regulatory definition associated with it so that
with a particular nutrient or food component and a body
the standard adjectives can be used to make comparisons
structure or function. These claims are evidence-based and
across products.
regulated by the FDA. An example of a claim referring to a
“structure” is: “The protein in [name of food] helps main-
tain strong muscles” (e.g., the structure). An example of a
6.7.4 Health Claims claim referring to a “function” is: “The vitamin A in [name
Two major types of health claims exist: health claims that of food] helps promote normal vision” (e.g., the function).
meet “significant scientific agreement” and “qualified If a structure/function claim is made for a nutrient that is
health claims.” Health claims are graded by the FDA on not one required to be listed on the Nutrition Facts label,
the quality and amount of the scientific evidence provided the FDA recommends that the manufacturer voluntarily
to support the claim. The claims are not endorsed by the list the amount and the %DV.
FDA below the level of an A rating (an A meaning the
claim has strong scientific agreement). There currently are
only 12 approved health claims that meet significant sci- 6.7.6 Voluntary and Front of
entific agreement. These include claims about the role of
nutrients and foods on health and disease. For example, a
Package Labeling
claim regarding folic acid and neural tube defects might be In addition to mandatory regulations specifying nutri-
worded as follows: “Healthful diets with adequate folate ent labeling, there are voluntary systems that may also
may reduce a woman’s risk of having a child with a brain be included on some foods in the United States to help
or spinal cord birth defect.” This statement is allowed on consumers make choices or to determine if a food is a
packages of food containing 100% or less of the DV for healthy option. Front of Package (FOP) labeling provides
folate. information on the front of food packages with various
6.7 Nutrient Information on Food Labels 95
criteria and symbols with the aim of helping consumers 6.7.9 Other Labeling Systems
6
make more healthy food choices. Recent developments
have been well summarized in a recent publication.130 Several voluntary labeling systems have evolved that are
used quite widely on foods in addition to the government-
mandated schemes. Their content and merits have been
6.7.7 Facts Up Front the subject of much discussion and debate over the past
decade. For example, the Smart Choices Program, which
The “Facts Up Front” label in 2010 was developed by the was developed under the leadership of the Keystone Center
Grocery Manufacturers Association, representing food and launched in 2009 with the backing of a coalition of
manufacturers, and the Food Marketing Institute, repre- food companies, public health associations, and scientific/
senting food retailers, after a request of the then-First Lady regulatory experts, was never implemented. The program
Michelle Obama to develop a front-of-package labeling included criteria for specific food categories; each category
system to enable shoppers to make informed decisions was required to meet a set of “qualifying criteria” which
when they shopped. The Facts Up Front is a voluntary included benchmarks for nutrients to limit and/or nutri-
front-of-package label system now widely used on con- ents to encourage, using a front-of-package label. The
sumer packaged foods produced by major manufacturers scheme received much criticism for foods qualifying for
to take key information from the nutrition label and pres- the label that were not perceived to be healthful choices.
ent it in an easy-to-read format on the front of the package. The FDA, the relevant regulatory agency, informed the
Four items are presented in the standard format: calories, leaders of the Smart Choices program that the “FDA and
saturated fat, sodium, and sugar. Manufacturers can add FSIS (U.S. Food Safety and Information Service) would be
up to two additional “nutrients to encourage” if the food is concerned if any front-of-packaging labeling systems used
a “good” source, meaning it contains at least 10% DV per criteria that were not stringent enough to protect consum-
serving. On small food packages, just a single icon show- ers against misleading claims; were inconsistent with the
ing the calories per serving can be used. The FDA issued Dietary Guidelines for Americans; or had the effect of
a letter of enforcement discretion in 2011, indicating it encouraging consumers to choose highly processed foods
had no objection to use of this program if certain criteria and refined grains instead of fruits, vegetables, and whole
were fulfilled. This front-of-package label system is now grains.” The program was abandoned by its sponsors at
used on many packaged foods. At nearly the same time, that point and a new initiative was launched that eventu-
the Food and Nutrition Board of the National Academy of ally resulted in the more successful and widely adopted
Sciences issued a report on a nutrition rating system that Facts Up Front FOP label described above.
was slightly different than the Facts Up Front. That differ- There are also other more limited third-party endorse-
ent system was adopted by the large supermarket chain ment labeling systems in the United States that are used on
Walmart in its Great for You labeling program. some foods to highlight an ingredient or ingredients. It is
still not clear how consumers use and understand various
types of front-of-package labeling and shelf-tag systems,
6.7.8 Heart Check including those that use one symbol to summarize all the
The Heart Check program of the American Heart nutritional attributes and systems that feature or those
Association was designed to help consumers find and that rate foods as being low, medium, or high in specific
choose “heart-healthy” foods in grocery stores and meals nutrients, similar to the traffic light system used in the
in restaurants. It uses a stamp or check symbol as a third- United Kingdom.
party endorsement of a food if certain requirements are
met for total fat, saturated fat, trans fat, cholesterol,
sodium, and a set of “beneficial nutrients” (vitamins A 6.7.10 Supermarket Scoring
and C, iron, calcium, protein, and fiber). Products with
Heart Check must also meet regulatory requirements for Systems and Icons
a heart-healthy claim. The symbol is allowed on foods Voluntary labeling schemes for nutrients also include many
that meet the Heart-Check Food Certification Nutrition different supermarket scoring systems and icons. Many
Requirements, which limit the amount of fat, saturated supermarkets and other food retailers have adopted vari-
fat, cholesterol, and sodium allowed per serving. It also ous systems of their own for labeling foods they consider
requires that the food contain at least 10% DV of one or to be particularly healthful or desirable. The proprietary
more of six key nutrients: vitamin A, vitamin C, iron, cal- systems for assessing and labeling the “nutrient quality”
cium, protein, or fiber. There are additional requirements of various foods use various nutrient profiling systems and
in specific food categories. Heart Check’s criteria were include those used by large supermarket chains, such as
called into question in recent years by advocacy groups, Wal-Mart’s Great for You program and private groups
and it was reformulated to include added sugar. The costs that rate products. These are often displayed on shelves
to manufacturers for obtaining the label are consider- or with special markers rather than on the food package
able, and so some companies have ceased using it, espe- itself. The criteria for them vary, and they are not endorsed
cially since the advent of the new Nutrition Facts label. or regulated by the FDA. Some are relatively straightfor-
However, the program is still in effect, and it has been ward and easy to discern, while others rely on proprietary
shown that food intake patterns assessed using the Heart formulas and other data that are not readily available to
Check label criteria identify better diets and lower cardio- consumers. No one system has dominated the field and
metabolic risk. consumers may be confused by the different offerings.131
96 Chapter 6 The Concept of Nutritional Status and Its Measurement
6.8 PERSONALIZED NUTRITION a fee that interpret the data, make personalized nutritional
recommendations, and give feedback to participants. They
are interesting and fun to explore. However, the tests vary
6.8.1 Definition in quality and whether they include DNA or simply bio-
Three major causes of differences between healthy people chemical measures.
are age, diet, and genetics. The three factors interact with The tests that include blood biomarkers often include
each other and the larger environment as well as with blood levels of a few nutrients and other values such as
other exposures such as disease and trauma over the life serum cholesterol, and glucose levels that are usually
course. No discussion of nutrition today would be com- assessed in batteries of clinical tests. They may contribute
plete without mention of personalized nutrition. Briefly, little as markers of risk of chronic disease over what can be
personalized medicine uses information about a person’s obtained from standard clinical tests such as LDL choles-
genetic makeup to tailor strategies for the detection, treat- terol or hemoglobin A1c. Since evidence for specific clinical
ment, or prevention of diseases. Its proponents hope to use effectiveness is vital for all tests, and even reliable tests are
various molecular profiling technologies to assess DNA, not always helpful or valid, this is important.
RNA, protein, and metabolites to tailor medical care. The Among the tests that include DNA, the number and
personalized nutrition approach is just a subset of person- which genes they include, the number of alleles or vari-
alized medicine, which aims to do the same thing—deliver ants they include, and the analytical techniques that are
the right therapy or medication dose for the right indica- used to analyze for them vary. DNA tests measure risk and
tion to the right patient at the right time. Both of these not the outright expression of diseases. Risk and predictive
strategies certainly hold great promise and deserve care- values are low with specific single genes for most chronic
ful study. The question many people ask today is whether diseases, and even when several genes are tested together
their genes, as determined by some genetic test, can tell for the common multigenic chronic diseases of greatest
them how to focus their diet for disease prevention. What interest, predictive values are quite low. However, the tests
is the utility of such direct-to-consumer (DTC) tests today are improving as the number of genes included increases
of biomarkers or of DNA, and is it time for consumers and costs decline, and this is an area that deserves careful
to adopt the personalized diets and supplements that are watching. The utility of a specific single nucleotide poly-
recommended? morphism (SNP) depends on the frequency of SNPs in a
population. For example, in a group within the population
already known to have an 80% prevalence of lactase defi-
6.8.2 Potential of Personalized Nutrition ciency, there is no need for a DNA test to show this, and
There is no question that genes and interactions among its clinical utility to change therapy is likely to be trivial.
them and the environment set the stage for chronic dis- That is, the phenotype itself is often sufficient to show risk
eases such as cardiovascular disease and some cancers, and to lead to early action. Also, family history and other
among others. Also, there is already evidence that sug- known risk factors and laboratory tests are just as good
gests that it may be possible to tailor one’s diet to one’s as a single allele and other multiple allele genetic tests for
genes with good results. For example, it has been known type 2 diabetes mellitus and hypertension. Also, the pres-
for many years that it is possible to prevent mental retar- ence of a particular genotype does not mean that it will be
dation with a special diet low in phenylalanine when a expressed phenotypically. The genetic tests help the most
baby is born with phenylalanine hydroxylase deficiency. when they are predictive, confirmatory, and provide needed
However, phenylketonuria is a rare single gene defect. The motivations to encourage people who are at high risk to
larger and more difficult question that must be answered take preventive actions on risk factors they can modify
is whether the common chronic diet-related degenerative early. There are also legal and ethical issues that must be
diseases, such as cardiovascular disease, stroke, diabetes, considered with genetic tests. DNA tests contain sensitive
and cancer are amenable to the same strategy. The chronic information that may be used incorrectly by some people
degenerative diseases are all disorders with multiple genes to promote a false sense of security or lead others to undue
involved and multifactorial causes, of which genetics is worry and a feeling that they are predestined to ill health,
but one, and thus they are much more complicated to deal leading them to abandon preventive measures. There are
with than single-gene disorders. However, only about also legal implications with DNA tests; for example, their
5% of the variation in chronic diseases can currently be presence may be used as evidence that a person seeking
explained by genetics. Therefore, it is unclear how much insurance has a preexisting condition and therefore should
of that variation can be ameliorated by changing dietary pay a higher premium.
habits. But it is certainly worth trying to do so. With all the biochemical and DNA tests now on the
market, the larger question is whether they help indi-
viduals make changes in their diet-related and other
behaviors that might ultimately improve their health?
6.8.3 What Is Available Today The Food4Me study of 1,200 adults in seven countries
Today there are a number of personalized nutrition kits in the European Union attempted to answer that ques-
sold directly to consumers over the Internet that offer to tion. The targeted diseases were those related specifically
assess an individual’s profile with respect to biomarkers to salt, saturated fat, dietary fiber, folate, and polyun-
of nutrients or DNA in blood or saliva, sometimes with saturated fat in the diet. The study involved a Web-based
measurement of dietary intake, and sometimes not. Some collection of dietary phenotypic and genotypic data. In
of the kits that are sold then go on to provide services for the four-armed study, one group (the control) was given
References 97
non-personalized public health eating advice. The first to best measure dietary exposures for use in nutritional
6
intervention group received a Web-based assessment of genomics explores some interesting other issues.133
current diet and provided counseling over the Web on
their diets, weight, body mass index (BMI), and physical
activity. The second intervention group, the phenotype 6.9 CONCLUSIONS
group, received the diet information plus information
on waist circumference and blood biomarkers from a This brief introduction to some basic concepts and appli-
mail-in dried blood sample of glucose, total cholesterol, cations of nutrition in lifestyle medicine has only skimmed
carotenes, and their omega-3 index). The last (genotype) the surface of many important topics in the field. The inter-
intervention group gave a buccal smear for genetic data ested reader may find a companion chapter by us entitled
and received the diet plus phenotype plus information “Nutrition 101” elsewhere.134 It discusses additional infor-
on several genetic markers, including markers of folate mation on biomarkers of dietary intakes, the DRI and its uses,
(MtHFR), diabetes (TCF7L2), cardiovascular disease additional sources of nutritional guidance for consumers.
(APOE 4), and coronary heart disease and atopy (FADS1). These include more information on the Dietary Guidelines
Changes were assessed for all the intervention groups for Americans, the USDA food pattern, USDA’s My Plate,
versus the general public health advice and for each inter- nutrient labeling, and other resources such as Healthy
vention group specifically. It is clear that regardless of People (health promotion and disease prevention guidelines
the dietary changes that were examined, there were more for Americans) and the Healthy Eating Index (HEI), which
dietary changes at six months than with simply giving assesses dietary intakes. Taken together, “Nutrition 101”
general advice. It is also clear that more targeted indi- and this chapter provide a basic introduction to the tools
vidual health advice based on defined risks and signs of nutritionists use and the field of applied nutrition.
disease does a better job of motivating individuals than
general advice alone. However, and surprisingly, the phe-
notypic and genotypic data did not add very much over CLINICAL APPLICATIONS
diet alone. Nevertheless, it is important to stay tuned,
since the costs of identifying and testing gene SNPs are Nutritional status provides a complete picture of the asso-
falling rapidly, and the situation may change rapidly, ciations of dietary intake and health; dietary intake pro-
particularly in cardiovascular disease.132 vides useful but more limited information
In summary, the predictive value of genetic tests and The Recommended Dietary Allowance (RDA)
phenotypic markers is limited today, but it is improv- adjusted for age, sex, and life stage is the dietary standard
ing rapidly. Direct-to-consumer blood and genetic tests for nutrient intakes of healthy individuals. It is the start-
require professional interpretation of the results to min- ing point for making adjustments in cases where disease
imize the possible harms of misinformation and ensure alters requirements for one or more nutrients and where
that the implications of this sensitive personal information the default for nutrients that are not so affected
are properly understood. Giving very specific and rigorous The Dietary Guidelines for Americans provide dietary
dietary advice and recommendations based on inconclu- recommendations that promote health and prevent diet-
sive knowledge is harmful when it results in unnecessary related chronic degenerative disease.
restrictions in lifestyle or sows worry with only doubt- At present, personalized regimes for food and dietary
ful health effects. There is little evidence that medicaliz- supplement intakes for healthy people that are based on
ing diet with elaborate food plans is effective; it promotes over-the-counter genetic tests have not proven to be more
“healthism” and needless worries. A commentary on how effective dietary patterns than the Dietary Guidelines.
REFERENCES
1. Strain, J.J., et al., B-vitamins, homocys- individuals. Hum. Nutr. Appl. Nutr., and vegetable intake: The National
teine metabolism and CVD. Proc. Nutr. 1986. 40(5): p. 347–64. Cancer Institute’s food attitudes and
Soc., 2004. 63(4): p. 597–603. 7. Heady, J.A., Diets of bank clerks. behaviors survey. J. Acad. Nutr. Diet.,
2. Subar, A.F., et al., Addressing current Development of a method of classifying 2012. 112(10): p. 1570–77.
criticism regarding the value of self-report the diets of individuals for use in epide- 12. Thompson, F.E., et al., Development
dietary data. J. Nutr., 2015. 145(12): p. miologic studies. J. R. Statist. Soc., 1961. and evaluation of a short instrument to
2639–45. 124: p. 336–61. estimate usual dietary intake of percent-
3. Thompson, F.E., et al., The National 8. Subar, A.F., et al., Using intake biomark- age energy from fat. J. Am. Diet. Assoc.,
Cancer Institute’s Dietary Assessment ers to evaluate the extent of dietary misre- 2007. 107(5): p. 760–67.
Primer: A resource for diet research. porting in a large sample of adults: The 13. Yang, Y.J., B.R. Martin, and C.J. Boushey,
J. Acad. Nutr. Diet., 2015. 115(12): p. OPEN study. Am. J. Epidemiol., 2003. Development and evaluation of a brief
1986–95. 158(1): p. 1–13. calcium assessment tool for adolescents. J.
4. Thompson, F.E. and T. Byers, Dietary 9. Bailey, R.L., et al., Dietary screening Am. Diet. Assoc., 2010. 110(1): p. 111–15.
assessment resource manual. J. Nutr., tool identifies nutritional risk in older 14. Leung, J. and J. Dwyer, Renal determine
1994. 124(11 Suppl): p. 2245S–317S. adults. Am. J. Clin. Nutr., 2009. 90(1): p. nutrition screening tools for the identifi-
5. Campbell, V.A. and M.L. Dodds, 177–83. cation and treatment of malnutrition. J.
Collecting dietary information from 10. Bailey, R.L., et al., A dietary screening Ren. Nutr., 1998. 8(2): p. 95–106.
groups of older people. J. Am. Diet. questionnaire identifies dietary patterns 15. White, J.V., et al., Nutrition screening
Assoc., 1967. 51(1): p. 29–33. in older adults. J. Nutr., 2007. 137(2): p. initiative: Development and implementa-
6. Marr, J.W. and J.A. Heady, Within- and 421–26. tion of the public awareness checklist
between-person variation in dietary sur- 11. Yaroch, A.L., et al., Evaluation of three and screening tools. J. Am. Diet. Assoc.,
veys: Number of days needed to classify short dietary instruments to assess fruit 1992. 92(2): p. 163–67.
98 Chapter 6 The Concept of Nutritional Status and Its Measurement
16. Kirkpatrick, S.I., et al., The use of digital in children and adolescents? J. Pediatr., of energy intakes. Am. J. Clin. Nutr.,
images in 24-hour recalls may lead to less 2012. 161(5): p. 837–42. 2008. 88(2): p. 324–32.
misestimation of portion size compared 35. U.S. Department of Agriculture, 53. Rhodes, D.G., et al., The USDA auto-
with traditional interviewer-administered Composition of Foods Raw, Processed, mated multiple-pass method accurately
recalls. J. Nutr., 2016. 146(12): p. Prepared USDA National Nutrient assesses population sodium intakes. Am.
2567–73. Database for Standard Reference, J. Clin. Nutr., 2013. 97(5): p. 958–64.
17. Arab, L. and A. Winter, Automated Release 25, 2012. [cited 2012 December 54. Strimbu, K. and J.A. Tavel, What are bio-
camera-phone experience with the fre- 4]. Available from: http://www.ars.usda. markers? Curr. Opin. HIV AIDS, 2010.
quency of imaging necessary to capture gov/SP 2UserFiles /Place/1235450 0 /Data / 5(6): p. 463–66.
diet. J. Am. Diet. Assoc., 2010. 110(8): p. SR25/sr25_doc.pdf 55. Raiten, D.J., et al., Executive summary-
1238–41. 36. Freedman, L.S., et al., Pooled results biomarkers of nutrition for development:
18. Boushey, C.J., et al., New mobile meth- from 5 validation studies of dietary Building a consensus. Am. J. Clin. Nutr.,
ods for dietary assessment: Review of self-report instruments using recovery 2011. 94(2): p. 633S–50S.
image-assisted and image-based dietary biomarkers for potassium and sodium 56. Labbe, R.F. and A. Dewanji, Iron assess-
assessment methods. Proc. Nutr. Soc., intake. Am. J. Epidemiol., 2015. 181(7): ment tests: Transferrin receptor vis-a-vis
2017. 76(3): p. 283–94. p. 473–87. zinc protoporphyrin. Clin. Biochem.,
19. National Cancer Institute, The 37. Kipnis, V., et al., Bias in dietary-report 2004. 37(3): p. 165–74.
Measurement Error Webinar Series. http: instruments and its implications for nutri- 57. Combs, G.F., Jr., et al., Biomarkers in
//risk factor.cancer.gov/measurementerror tional epidemiology. Public Health Nutr., nutrition: New frontiers in research and
/, 2011. Available from: http://risk fact 2002. 5(6A): p. 915–23. application. Ann. N. Y. Acad. Sci., 2013.
or.cancer.gov/measurementerror/ 38. Gibson, R.S., Principles of Nutritional 1278: p. 1–10.
20. National Research Council, Nutrient Assessment. New York, NY: Oxford 58. Potischman, N. and J.L. Freudenheim,
Adequacy. Washington, DC: National University Press, 1990. Biomarkers of nutritional exposure and
Academy Press, 1986. 39. Bailey, R.L., et al., Dietary supplement nutritional status: An overview. J. Nutr.,
21. Nusser, S., et al., A semiparametric trans- use is associated with higher intakes of 2003. 133(Suppl 3): p. 873S–74S.
formation approach to estimating usual minerals from food sources. Am. J. Clin. 59. Hedrick, V.E., et al., Dietary biomarkers:
daily intake distributions. J. Am. Stat. Nutr., 2011. 94(5): p. 1376–81. Advances, limitations and future direc-
Assoc., 1996. 91: p. 1440–49. 40. Dwyer, J.T., et al., Memory of food tions. Nutr. J., 2012. 11: p. 109.
22. Subar, A.F., et al., The food propensity intake in the distant past. Am. J. 60. Tasevska, N., Urinary sugars-a biomarker
questionnaire: Concept, development, Epidemiol., 1989. 130(5): p. 1033–46. of total sugars intake. Nutrients, 2015.
and validation for use as a covariate in 41. Chambers, E.T., S.L. Godwin, and F.A. 7(7): p. 5816–33.
a model to estimate usual food intake. Vecchio, Cognitive strategies for report- 61. Tanumihardjo, S.A., et al., Biomarkers
J. Am. Diet. Assoc., 2006. 106(10): p. ing portion sizes using dietary recall of Nutrition for Development (BOND)-
1556–63. procedures. J. Am. Diet. Assoc., 2000. Vitamin a review. J. Nutr., 2016. 146(9):
23. Tooze, J.A., et al., A new statistical 100(8): p. 891–97. p. 1816S–48S.
method for estimating the usual intake of 42. Guthrie, H.A., Selection and quantifica- 62. Bailey, L.B., et al., Biomarkers of nutri-
episodically consumed foods with appli- tion of typical food portions by young tion for development-folate review. J.
cation to their distribution. J. Am. Diet. adults. J. Am. Diet. Assoc., 1984. 84(12): Nutr., 2015. 145(7): p. 1636S–80S.
Assoc., 2006. 106(10): p. 1575–87. p. 1440–44. 63. King, J.C., et al., Biomarkers of Nutrition
24. Dodd, K.W., et al., Statistical methods 43. Faggiano, F., et al., Validation of a for Development (BOND)-Zinc review. J.
for estimating usual intake of nutrients method for the estimation of food por- Nutr., 2016.
and foods: A review of the theory. J. Am. tion size. Epidemiology, 1992. 3(4): p. 64. Rohner, F., et al., Biomarkers of nutrition
Diet. Assoc., 2006. 106(10): p. 1640–50. 379–82. for development-iodine review. J. Nutr.,
25. Yetley, E.A., D.L. DeMets, and W.R. 44. Gersovitz, M., J.P. Madden, and H. 2014. 144(8): p. 1322S–42S.
Harlan, Jr., Surrogate disease markers as Smiciklas-Wright, Validity of the 24-hr. 65. Mei, Z., et al., Adjusting total body
substitutes for chronic disease outcomes Dietary recall and seven-day record for iron for inflammation: Biomarkers
in studies of diet and chronic disease rela- group comparisons. J. Am. Diet. Assoc., Reflecting Inflammation and Nutritional
tions. Am. J. Clin. Nutr., 2017. 106(5): p. 1978. 73(1): p. 48–55. Determinants of Anemia (BRINDA) proj-
1175–89. 45. Bolland, J.E., J.A. Yuhas, and T.W. ect. Am. J. Clin. Nutr., 2017. 106(Suppl
26. Bailey, R.L., et al., Dietary supplement Bolland, Estimation of food portion sizes: 1): p. 383S–89S.
use in the United States, 2003–2006. J. Effectiveness of training. J. Am. Diet. 66. Namaste, S.M., et al., Adjusting fer-
Nutr., 2011. 141(2): p. 261–66. Assoc., 1988. 88(7): p. 817–21. ritin concentrations for inflammation:
27. Kantor, E.D., et al., Trends in dietary 46. Howat, P.M., et al., Validity and reliabil- Biomarkers Reflecting Inflammation and
supplement use among US adults from ity of reported dietary intake data. J. Am. Nutritional Determinants of Anemia
1999–2012. JAMA, 2016. 316(14): p. Diet. Assoc., 1994. 94(2): p. 169–73. (BRINDA) project. Am. J. Clin. Nutr.,
1464–74. 47. Smiciklas-Wright, H., et al., Foods 2017. 106(Suppl 1): p. 359S–71S.
28. Bailey, R.L., et al., Why US adults use commonly eaten in the United States, 67. Suchdev, P.S., et al., Overview of the
dietary supplements. JAMA Intern. Med., 1989–1991 and 1994–1996: Are portion Biomarkers Reflecting Inflammation and
2013. 173(5): p. 355–61. sizes changing? J. Am. Diet. Assoc., Nutritional Determinants of Anemia
29. Bailey, R.L., et al., Why US children use 2003. 103(1): p. 41–47. (BRINDA) Project. Adv. Nutr., 2016.
dietary supplements. Pediatr. Res., 2013. 48. Ledikwe, J.H., J.A. Ello-Martin, and B.J. 7(2): p. 349–56.
74(6): p. 737–41. Rolls, Portion sizes and the obesity epi- 68. Pfeiffer, C.M. and A.C. Looker,
30. Bailey, R.L., et al., Examination of vita- demic. J. Nutr., 2005. 135(4): p. 905–09. Laboratory methodologies for indicators
min intakes among US adults by dietary 49. Elmadfa, I. and A.L. Meyer, Developing of iron status: Strengths, limitations, and
supplement use. J. Acad. Nutr. Diet., suitable methods of nutritional status analytical challenges. Am. J. Clin. Nutr.,
2012. 112(5): p. 657–63 e4. assessment: A continuous challenge. Adv. 2017. 106(Suppl 6): p. 1606S–14S.
31. Bailey, R.L., et al., Do dietary supple- Nutr., 2014. 5(5): p. 590S–98S. 69. Raghavan, R., F.S. Ashour, and R. Bailey, A
ments improve micronutrient sufficiency 50. Schoeller, D.A., L.G. Bandini, and W.H. review of cutoffs for nutritional biomark-
in children and adolescents? J. Pediatr., Dietz, Inaccuracies in self-reported intake ers. Adv. Nutr., 2016. 7(1): p. 112–20.
2012. 161(5): p. 837–42. identified by comparison with the doubly 70. Bailey, R.L., et al., Monitoring of vitamin
32. Bailey, R., et al., Dietary supplement labelled water method. Can. J. Physiol. B-12 nutritional status in the United
use is associated with higher intakes of Pharmacol., 1990. 68(7): p. 941–49. States by using plasma methylmalonic
minerals from food sources. Am. J. Clin. 51. Blanton, C.A., et al., The USDA auto- acid and serum vitamin B-12. Am. J.
Nutr., 2011. 94(5): p. 1376–81. mated multiple-pass method accurately Clin. Nutr., 2011. 94(2): p. 552–61.
33. Bailey, R., et al., Examination of vitamin estimates group total energy and nutri- 71. Pfeiffer, C.M., et al., Applying inappro-
intakes among US adults by dietary ent intake. J. Nutr., 2006. 136(10): p. priate cutoffs leads to misinterpretation
supplement use. J. Acad. Nutr. Diet., 2594–99. of folate status in the US population. Am.
2012. 112(5): p. 657–63 e4. 52. Moshfegh, A.J., et al., The US depart- J. Clin. Nutr., 2016. 104(6): p. 1607–15.
34. Bailey, R., et al., Do dietary supple- ment of agriculture automated multiple- 72. Bailey, R.L., et al., Correspondence
ments improve micronutrient sufficiency pass method reduces bias in the collection of folate dietary intake and biomarker
References 99
data. Am. J. Clin. Nutr., 2017. 105(6): p. Principles of Internal Medicine, A.S. 103. Jacques, P.F. and K.L. Tucker, Are dietary
1336–43. Fauci, et al., Editors. New York, NY: patterns useful for understanding the role
73. Bailey, R.L., et al., Estimation of total
usual calcium and vitamin D intakes in
the United States. J. Nutr., 2010. 140(4):
McGraw-Hill Medical, 2008, p. 449.
89. Yetley, E.A., et al., Options for basing
Dietary Reference Intakes (DRIs) on
of diet in chronic disease? Am. J. Clin.
Nutr., 2001. 73(1): p. 1–2.
104. Freeland-Graves, J.H., et al., Position of
6
p. 817–22. chronic disease endpoints: Report from a the academy of nutrition and dietetics:
74. Schleicher, R.L., et al., The vitamin D joint US-/Canadian-sponsored working Total diet approach to healthy eating.
status of the US population from 1988 to group. Am. J. Clin. Nutr., 2017. 105(1): J. Acad. Nutr. Diet., 2013. 113(2): p.
2010 using standardized serum concen- p. 249S–85S. 307–17.
trations of 25-hydroxyvitamin D shows 90. World Health Organization, A Model 105. Hu, F.B., Dietary pattern analysis: A new
recent modest increases. Am. J. Clin. for establishing Upper Levels of Intake direction in nutritional epidemiology.
Nutr., 2016. 104(2): p. 454–61. for Nutrients and Related Substances: A Curr. Opin. Lipidol., 2002. 13(1): p. 3–9.
75. Food and Nutrition Board, Dietary Report of a Joint FAO/WHO Technical 106. Liese, A.D., et al., The dietary patterns
Reference Intakes For Calcium, Workshop on Food Nutrient Risk methods project: Synthesis of findings
Phosphorus, Magnesium, Vitamin D Assessment. Geneva, Switzerland: World across cohorts and relevance to dietary
and Floride. Washington, DC: National Health Organization, 2006. guidance. J. Nutr., 2015. 145(3): p.
Academy Press, 1997. 91. Institute of Medicine Food Nutrition 393–402.
76. Food and Nutrition Board, Dietary Board, Dietary Reference Intakes: A 107. Appel, L.J., et al., A clinical trial of
Reference Intakes For Thiamin, Risk Assessment Model for Establishing the effects of dietary patterns on blood
Riboflavin, Niacin, Vitamin B 6, Folate, Upper Intake Levels for Nutrients, pressure. DASH Collaborative Research
Vitamin B12 , Pantothenic Acid, Biotin, in Dietary Reference Intakes: A Risk Group. N. Engl. J. Med., 1997. 336(16):
and Choline. Washington, DC: National Assessment Model for Establishing p. 1117–24.
Academy Press,1998. Upper Intake Levels for Nutrients. 108. Estruch, R., et al., Effects of a
77. Food and Nutrition Board, Dietary Washington, DC: National Academies Mediterranean-style diet on cardiovascu-
Reference Intakes For Vitamin C, Press, 1998. lar risk factors: A randomized trial. Ann.
Vitamin E, Selenium, and Carotenoids. 92. Brannon, P.M., et al., Scanning for new Intern. Med., 2006. 145(1): p. 1–11.
Washington, DC: National Academy evidence to prioritize updates to the 109. Raiten, D.J., et al., Executive summary:
Press, 2000. dietary reference intakes: Case studies Evaluating the evidence base to support
78. Food and Nutrition Board, Dietary for thiamin and phosphorus. Am. J. Clin. the inclusion of infants and children
Reference Intakes For Vitamin A, Nutr., 2016. 104(5): p. 1366–77. from birth to 24 mo of age in the dietary
Vitamin K, Arsenic, Boron, Chromium, 93. Patterson, R.E., P.S. Haines, and B.M. guidelines for Americans – “The B-24
Copper, Iodine, Iron, Molybdenum, Popkin, Diet quality index: Capturing a Project”. Am. J. Clin. Nutr., 2014. 99(3):
Nickel, Silicon, Vanadium and Zinc. multidimensional behavior. J. Am. Diet. p. 663S–91S.
Washington, DC: National Academy Assoc., 1994. 94(1): p. 57–64. 110. Kennedy, E.T., et al., The healthy eating
Press, 2001. 94. Ioannidis, J.P., We need more random- index: Design and applications. J. Am.
79. Food and Nutrition Board, Dietary ized trials in nutrition-preferably large, Diet. Assoc., 1995. 95(10): p. 1103–08.
Reference Intakes for Energy, long-term, and with negative results. Am. 111. Krebs-Smith, S.M., et al., Americans
Carbohydrate, Fiber, Fat, Fatty Acids, J. Clin. Nutr., 2016. 103(6): p. 1385–86. do not meet federal dietary recom-
Cholesterol, Protein, and Amino Acids 95. Daly, A., American Diabetes Association, mendations. J. Nutr., 2010. 140(10): p.
(Macronutrients). Washington, DC: and American Dietetic Association. 1832–38.
Institute of Medicine, 2002/2005. Choose Your Foods: Exchange Lists 112. Guenther, P.M., et al., Update of the
80. Food and Nutrition Board, Dietary For Diabetics. Chicago, IL: American healthy eating index: HEI-2010. J. Acad.
Reference Intakes: Applications in Diabetes Association, American Dietetic Nutr. Diet., 2013. 113(4): p. 569–80.
Dietary Planning. Washington, DC: Association, 2008. 113. Guenther, P.M., et al., The healthy eat-
Institute of Medicine, 2003. 96. Wheeler, M., Academy of Nutrition and ing index-2010 is a valid and reliable
81. Food and Nutrition Board, Dietary Dietetics, and A.D. Association, Choose measure of diet quality according to the
Reference Intakes for Water, Potassium, Your Foods: Food Lists For Weight 2010 dietary guidelines for Americans. J.
Sodium, Chloride, and Sulfate. Management. Chicago, IL: American Nutr., 2014. 144(3): p. 399–407.
Washington, DC: Institute of Medicine, Diabetes Association, American Dietetic 114. Miller, P.E., et al., The United States
2004. Association, 2014. food supply is not consistent with dietary
82. Food and Nutrition Board, Dietary 97. Nutrition Evidence Library, A Series of guidance: Evidence from an evaluation
Reference Intakes: The Essential Guide Systematic Reviews on the Relationship using the healthy eating index-2010.
to Nutrient Requirements. Washington, Between Dietary Patterns and Health J. Acad. Nutr. Diet., 2015. 115(1):
DC: Institute of Medicine, 2006. Outcomes. Alexandria, VA: U.S. p. 95–100.
83. Food and Nutrition Board, Dietary Department of Agriculture, Center for 115. Rehm, C.D., P. Monsivais, and A.
Reference Intakes for Calcium and Nutrition Policy and Promotion, 2014. Drewnowski, Relation between diet cost
Vitamin D. Washington, DC: National 98. Bailey, R.L., et al., Assessing the effect of and healthy eating index 2010 scores
Academy Press, 2011. underreporting energy intake on dietary among adults in the United States 2007–
84. Murphy, S., Dietary Standards in the patterns and weight status. J. Am. Diet. 2010. Prev. Med., 2015. 73: p. 70–75.
United States, in Present Knowledge in Assoc., 2007. 107(1): p. 64–71. 116. Kant, A.K. and B.I. Graubard, Energy
Nutrition, B. Bowman and R. Russell, 99. Funtikova, A.N., et al., Effect of energy density of diets reported by American
Editors. Washington, DC: ILSI Press, under-reporting on secular trends of adults: Association with food group intake,
2006, p. 859–75. dietary patterns in a Mediterranean nutrient intake, and body weight. Int. J.
85. Dietary Guidelines Advisory Committee, population. PLoS One, 2015. 10(5): p. Obes. (Lond.), 2005. 29(8): p. 950–56.
Report of the Dietary Guidelines Advisory e0127647. 117. Ledikwe, J.H., et al., Dietary energy
Committee on the Dietary Guidelines 100. Krebs-Smith, S.M., A.F. Subar, and J. density determined by eight calculation
for Americans, 2010, to the Secretary of Reedy, Examining dietary patterns in methods in a nationally representative
Agriculture and the Secretary of Health relation to chronic disease: Matching United States population. J. Nutr., 2005.
and Human Services. Washington, measures and methods to questions of 135(2): p. 273–78.
DC: Agricultural Research Service US interest. Circulation, 2015. 132(9): p. 118. Britten, P., et al., Impact of typical rather
Department of Agriculture, 2010. 790–93. than nutrient-dense food choices in
86. Food and Nutrition Board, Dietary 101. Gleason, P.M., et al., Publishing nutri- the US department of agriculture food
Reference Intakes Applications in tion research: A review of multivariate patterns. J. Acad. Nutr. Diet., 2012.
Dietary Assessment. Washington, DC: techniques-part 3: Data reduction meth- 112(10): p. 1560–69.
National Academy Press, 2000. ods. J. Acad. Nutr. Diet., 2015. 115(7): p. 119. Drewnowski, A., Concept of a nutri-
87. Board, I.o.M.F.a.N., Dietary Reference 1072–82. tious food: Toward a nutrient density
Intakes Tables and Application, June 10, 102. Playdon, M.C., et al., Identifying score. Am. J. Clin. Nutr., 2005. 82(4): p.
2015. biomarkers of dietary patterns by using 721–32.
88. Dwyer, J., Nutritional Requirements metabolomics. Am. J. Clin. Nutr., 2017. 120. Drewnowski, A. and V. Fulgoni, 3rd,
and Dietary Assessment, in Harrison’s 105(2): p. 450–65. Nutrient profiling of foods: Creating
100 Chapter 6 The Concept of Nutritional Status and Its Measurement
a nutrient-rich food index. Nutr. Rev., foods. Am. J. Clin. Nutr., 2010. 91(4): p. in Front-of-Package Nutrition Rating
2008. 66(1): p. 23–39. 1095S–101S. Systems and Symbols: Phase I Report, E.A.
121. Drewnowski, A. and V. Fulgoni, 3rd, 126. Drewnowski, A., Defining nutrient Wartella, A.H. Lichtenstein, and C.S. Boon,
Comparing the nutrient rich foods index density: Development and validation of Editors. Washington, DC, 2010.
with “Go,” “Slow,” and “Whoa,” foods. the nutrient rich foods index. J. Am. Coll. 131. Miller, L.M., et al., Misunderstanding of
J. Am. Diet. Assoc., 2011. 111(2): p. Nutr., 2009. 28(4): p. 421S–26S. front-of-package nutrition information
280–84. 127. Administration, F.A.D., Food labeling: on US food products. PLoS One, 2015.
122. Drewnowski, A. and V.L. Fulgoni, 3rd, Revision of the nutrition and supple- 10(4): p. e0125306.
Nutrient density: Principles and evalua- ment facts labels. Fed. Regist., 2016: p. 132. Celis-Morales, C., et al., Effect of personal-
tion tools. Am. J. Clin. Nutr., 2014. 99(5 33741–999. ized nutrition on health-related behaviour
Suppl): p. 1223S–28S. 128. Bailey, R., et al., Sources of added sugars change: Evidence from the Food4Me
123. Drewnowski, A., et al., Nutrient-rich in young children, adolescents, and adults European randomized controlled trial. Int.
foods: Applying nutrient navigation with low and high intakes of added sug- J. Epidemiol., 2017. 46(2): p. 578–88.
systems to improve public health. J. Food ars. Nutrients, 2018. 10(1): p. 102. 133. Tucker, K.L., et al., Quantifying diet for
Sci., 2008. 73(9): p. H222–28. 129. Food and Drug Administration, Label nutrigenomic studies. Annu. Rev. Nutr.,
124. Fulgoni, V.L., 3rd, D.R. Keast, and A. Claims for Conventional Foods and 2013. 33: p. 349–71.
Drewnowski, Development and valida- Dietary Supplements. Available from: 134. Dwyer, J. and R.L. Bailey, Nutrition
tion of the nutrient-rich foods index: A https: //www.fda.gov/Food/I ngred ient 101: The Concept of Nutritional Status
tool to measure nutritional quality of sPackaging L abeli ng/LabelingNutrition / and Guides for Nutrient Intakes, Eating
foods. J. Nutr., 2009. 139(8): p. 1549–54. ucm111447.htm Patterns, and Nutrition, in Nutrition in
125. Drewnowski, A., The nutrient rich foods 130. Institute of Medicine, Purpose and Merits of Lifestyle Medicine, J.M. Rippe, Editor.
index helps to identify healthy, affordable Front-of-Package Nutrition Rating Systems, New York, NY: Springer, 2016, p. 13–49.
7
CHAPTER
TABLE 7.1 Facts about nutrition and physical activity-related health conditions in the United States
Health condition Facts
Overweight and Obesity • For more than 25 years, more than half of the adult population has been overweight or obese.
• Obesity is most prevalent in those ages 40 years and older and in African American adults, and is
least prevalent in adults with highest incomes.
• Since the early 2000s, abdominal obesitya has been present in about half of U.S. adults of all
ages. Prevalence is higher with increasing age and varies by sex and race/ethnicity.
• In 2009–2012, 65% of adult females and 73% of adult males were overweight or obese.
• In 2009–2012, nearly one in three youth ages 2 to 19 years were overweight or obese.
Cardiovascular Disease (CVD) • In 2010, CVD affected about 84 million men and women ages 20 years and older (35% of the
and Risk Factors: population).
• Coronary heart disease • In 2007–2010, about 50% of adults who were normal weight, and nearly three-fourths of those
• Stroke who were overweight or obese, had at least one cardiometabolic risk factor (i.e., high blood
• Hypertension pressure, abnormal blood lipids, smoking, or diabetes).
• High total blood cholesterol • Rates of hypertension, abnormal blood lipid profiles, and diabetes are higher in adults with
abdominal obesity.
• In 2009–2012, almost 56% of adults ages 18 years and older had either prehypertension (27%) or
hypertension (29%).b
• In 2009–2012, rates of hypertension among adults were highest in African Americans (41%) and
in adults ages 65 years and older (69%).
• In 2009–2012, 10% of children ages 8 to 17 years had either borderline hypertension (8%) or
hypertension (2%).c
• In 2009–2012, 100 million adults ages 20 years or older (53%) had total cholesterol levels ≥ 200
mg/dL; almost 31 million had levels ≥ 240 mg/dL.
• In 2011–2012, 8% of children ages 8 to 17 years had total cholesterol levels ≥ 200 mg/dL.
Diabetes • In 2012, the prevalence of diabetes (type 1 plus type 2) was 14% for men and 11% for women
ages 20 years and older (more than 90% of total diabetes in adults is type 2).
• Among children with type 2 diabetes, about 80% were obese.
Cancerd • Breast cancer is the third leading cause of cancer death in the United States.
• Breast cancer • In 2012, an estimated 3 million women had a history of breast cancer.
• Colorectal cancer • Colorectal cancer is the second leading cause of cancer death in the United States.
• In 2012, an estimated 1.2 million adult men and women had a history of colorectal cancer.
Bone Health • A higher percentage of women are affected by osteoporosis (15%) and low bone mass (51%)
than men (about 4% and 35%, respectively).
• In 2005–2010, approximately 10 million (10%) adults ages 50 years and older had osteoporosis
and 43 million (44%) had low bone mass.
a Abdominal obesity, as measured by waist circumference, is defined as a waist circumference of > 102 centimeters in men and > 88 centimeters in women.
bFor adults, prehypertension was defined as a systolic blood pressure of 120–139 mm mercury (Hg) or diastolic blood pressure of 80–89 among those who were not currently
being treated for hypertension. Hypertension was defined as systolic blood pressure (SBP) >140 mm Hg, diastolic blood pressure (DBP) >90 mm Hg, or taking antihyperten-
sive medication. Since this analysis was conducted the American College of Cardiology and American Heart Association issued new blood pressure guidelines which elimi-
nated the category of prehypertension and lowered the definition of high blood pressure to allow for earlier intervention. Thus, the number of individuals who may now be
diagnosed with hypertension would be expected to increase.
c For children, borderline hypertension was defined as systolic or diastolic blood pressure at the 90th percentile or higher but lower than the 95th percentile or as blood pres-
sure levels of 120/80 mm Hg or higher (but less than the 95th percentile). Hypertension was defined as a systolic or diastolic blood pressure at the 95th percentile or higher.
d The types of cancer included here are not a complete list of all diet- and physical activity-related cancers.
reduce the risk of chronic disease throughout all stages Dietary Guidelines is required under the 1990 National
of the lifespan. The 2015–2020 Dietary Guidelines for Nutrition Monitoring and Related Research Act,
Americans2 reflects this evidence through its recommen- which states that every five years, the U.S. Department
dations. The goal of the Dietary Guidelines is to make of Health and Human Services (HHS) and the U.S.
recommendations about the components of a healthy and Department of Agriculture (USDA) must jointly publish
nutritionally adequate diet to help promote health and a report containing nutritional and dietary informa-
prevent chronic disease for current and future generations. tion, and guidelines for the general public. The statute
(Public Law 101-445, 7 U.S.C. 5341 et seq.) requires
that the Dietary Guidelines be based on the prepon-
7.2 BACKGROUND derance of current scientific and medical knowledge.
The 2015–2020 edition of the Dietary Guidelines
Every five years since 1980, a new edition of the Dietary builds from the 2010 edition with revisions based on
Guidelines for Americans has been published. The the Scientific Report of the 2015 Dietary Guidelines
7.3 Overview of the Dietary Guidelines for Americans, 2015–2020 103
Advisory Committee 3 and consideration of Federal need to make shifts in their food and beverage choices to
7
agency and public comments. achieve a healthy pattern, and acknowledge that all seg-
The Dietary Guidelines is designed for profession- ments of our society have a role to play in supporting
als to help all individuals ages two years and older and healthy choices. These Guidelines also embody the idea
their families consume a healthy, nutritionally adequate that a healthy eating pattern is not a rigid prescription but
diet. The information in the Dietary Guidelines is used an adaptable framework in which individuals can enjoy
in developing Federal food, nutrition, and health policies foods that meet their personal, cultural, and traditional
and programs. It also is the basis for Federal nutrition preferences and fit within their budget.
education materials designed for the public and for the
nutrition education components of HHS and USDA food
programs. Additional audiences who may use Dietary 7.3.1 The Guidelines
Guidelines information to develop programs, poli-
Follow a healthy eating pattern across the lifespan.
1.
cies, and communication for the general public include
All food and beverage choices matter. Choose a
health professionals, businesses, schools, community
healthy eating pattern at an appropriate calorie level
groups, media, the food industry, and state and local
to help achieve and maintain a healthy body weight,
governments.
support nutrient adequacy, and reduce the risk of
Although many of its recommendations have
chronic disease.
remained relatively consistent over time, the Dietary
Focus on variety, nutrient density, and amount. To
2.
Guidelines has evolved as scientific knowledge has
meet nutrient needs within calorie limits, choose a
grown. Previous editions of the Dietary Guidelines
variety of nutrient-dense foods across and within all
focused primarily on individual dietary components
food groups in recommended amounts.
such as food groups and nutrients. However, people do
Limit calories from added sugars and saturated
3.
not eat food groups and nutrients in isolation but rather
fats and reduce sodium intake. Consume an eat-
in combination, and the totality of the diet forms an
ing pattern low in added sugars, saturated fats, and
overall eating pattern. The components of the eating
sodium. Cut back on foods and beverages higher in
pattern can have interactive and potentially cumulative
these components to amounts that fit within healthy
effects on health. These patterns can be tailored to an
eating patterns.
individual’s personal preferences, enabling Americans to
Shift to healthier food and beverage choices.
4.
choose the diet that is right for them. A growing body
Choose nutrient-dense foods and beverages across
of research has examined the relationship between over-
and within all food groups in place of less-healthy
all eating patterns, health, and risk of chronic disease,
choices. Consider cultural and personal prefer-
and findings on these relationships are sufficiently well
ences to make these shifts easier to accomplish and
established to support dietary guidance. As a result, eat-
maintain.
ing patterns and their food and nutrient characteristics
Support healthy eating patterns for all. Everyone
5.
are a focus of the recommendations in the 2015–2020
has a role in helping to create and support healthy
Dietary Guidelines.
eating patterns in multiple settings nationwide, from
home to school to work to communities.
Consume a healthy eating pattern that accounts for all foods and beverages within an appropriate calorie level.
A healthy eating pattern includes:
• A variety of vegetables from all of the subgroups—dark green, red and orange, legumes (beans and peas), starchy, and other
• Fruits, especially whole fruits
• Grains, at least half of which are whole grains
• Fat-free or low-fat dairy, including milk, yogurt, cheese, and/or fortified soy beverages
• A variety of protein foods, including seafood, lean meats and poultry, eggs, legumes (beans and peas), nuts, seeds, and soy
products
• Oils
A healthy eating pattern limits:
• Saturated fats and trans fats, added sugars, and sodium
Key Recommendations that are quantitative are provided for several components of the diet that should be limited. These components
are of particular public health concern in the United States, and the specified limits can help individuals achieve healthy eating patterns
within calorie limits:
• Consume less than 10 percent of calories per day from added sugarsa
• Consume less than 10 percent of calories per day from saturated fatsb
• Consume less than 2,300 milligrams (mg) per day of sodiumc
• If alcohol is consumed, it should be consumed in moderation—up to one drink per day for women and up to two drinks per day for
men—and only by adults of legal drinking age.d
In tandem with the recommendations above, Americans of all ages—children, adolescents, adults, and older adults—should meet the
Physical Activity Guidelines for Americans4 to help promote health and reduce the risk of chronic disease. Americans should aim to
achieve and maintain a healthy body weight. The relationship between diet and physical activity contributes to calorie balance and
managing body weight. As such, the Dietary Guidelines includes a Key Recommendation to
• Meet the Physical Activity Guidelines for Americans.e
a The recommendation to limit intake of calories from added sugars to less than 10 percent per day is a target based on food pattern modeling and national data on intakes
of calories from added sugars that demonstrate the public health need to limit calories from added sugars to meet food group and nutrient needs within calorie limits. The
limit on calories from added sugars is not a Tolerable Upper Intake Level (UL) set by the Institute of Medicine (IOM). For most calorie levels, there are not enough calories
available after meeting food group needs to consume 10 percent of calories from added sugars and 10 percent of calories from saturated fats and still stay within calorie
limits.
b The recommendation to limit intake of calories from saturated fats to less than 10 percent per day is a target based on evidence that replacing saturated fats with unsatu-
rated fats is associated with reduced risk of cardiovascular disease. The limit on calories from saturated fats is not a UL set by the IOM. For most calorie levels, there are not
enough calories available after meeting food group needs to consume 10 percent of calories from added sugars and 10 percent of calories from saturated fats and still stay
within calorie limits.
c The recommendation to limit intake of sodium to less than 2,300 mg per day is the UL for individuals ages 14 years and older set by the IOM. The recommendations for
children younger than 14 years of age are the IOM age- and sex-appropriate ULs.
d It is not recommended that individuals begin drinking or drink more for any reason. The amount of alcohol and calories in beverages varies and should be accounted for
within the limits of healthy eating patterns. Alcohol should be consumed only by adults of legal drinking age. There are many circumstances in which individuals should not
drink, such as during pregnancy.
e The Physical Activity Guidelines for Americans were first released in 2008. The second edition is now available at www.health.gov/paguidelines.
TABLE 7.2 Composition of the healthy U.S.-style, healthy mediterranean-style, and healthy vegetarian eating patterns at
the 2000-calorie level, with daily or weekly amounts from food groups, subgroups, and components
Healthy U.S.-Style Eating Healthy Mediterranean- Style Eating Healthy Vegetarian Eating
7
Food Groupa Pattern Pattern Pattern
Vegetables 2½ c eq/day 2½ c eq/day 2½ c eq/day
--Dark green 1½ c eq/week 1½ c eq/week 1½ c eq/week
--Red and orange 5½ c eq/week 5½ c eq/week 5½ c eq/week
--Legumes (beans and peas) 1½ c eq/week 1½ c eq/week 3 c eq/week
--Starchy 5 c eq/week 5 c eq/week 5 c eq/week
--Other 4 c eq/week 4 c eq/week 4 c eq/week
Fruits 2 c eq/day 2½ c eq/day 2 c eq/day
Grains 6 oz eq/day 6 oz eq/day 6½ oz eq/day
--Whole grains ≥ 3 oz eq/day ≥3 oz eq/day ≥3½ oz eq/day
--Refined grains ≤ 3 oz eq/day ≤3 oz eq/day ≤3 oz eq/day
Dairy 3 c eq/day 2 c eq/day 3 c eq/day
Protein Foods 5 ½ oz eq/day 6½ oz eq/day 3½ oz eq/day
--Seafood 8 oz eq/week 15 oz eq/week --
--Meat, poultry, eggs 26 oz eq/week 26 oz eq/week 3 oz eq/week (eggs)
--Nuts, seeds, soy products 5 oz eq/week 5 oz eq/week 14 oz eq/week
Oils 27 g/day 27 g/day 27 g/day
Limit on Calories for Other 270 kcal/day (14%) 260 kcal/day (13%) 290 kcal/day (15%)
Uses (% of calories)b
Note: The total eating pattern should not exceed Dietary Guidelines limits for intake of added sugars, saturated fats, and alcohol and should be within the Acceptable
Macronutrient Distribution Ranges (5) for calories from protein, carbohydrate, and total fats. Most calorie patterns do not have enough calories available after meeting food
group needs to consume 10 percent of calories from added sugars and 10 percent of calories from saturated fats and stay within calorie limits. Values are rounded. See
Appendices 3 and 4 in the 2015–2020 Dietary Guidelines for all 12 calorie levels of the Patterns.
a Food group amounts shown in cup (c eq) or ounce equivalents (oz eq). Oils are shown in grams (g). Amounts will vary for those who need < 2000 or > 2000 calories per day.
to eat more than the recommended amount of nutrient-dense foods are accounted for under this category.
range is for sedentary individuals; the high end of the range information on estimated calorie needs per day by age, sex,
is for active individuals. Due to reductions in basal meta- and physical activity level are provided in Appendix 2 of
bolic rate that occur with aging, calorie needs generally the 2015–2020 Dietary Guidelines.
decrease for adults as they age. Estimated needs for young
children range from 1,000 to 2,000 calories per day, and
the range for older children and adolescents varies sub-
stantially from 1,400 to 3,200 calories per day, with boys 7.3.5 Shifts Needed to Align with
generally having higher calorie needs than girls. These esti- Healthy Eating Patterns
mates are based on the Estimated Energy Requirements
The typical eating patterns currently consumed by many
(EER) equations,5 using reference heights (average) and
in the United States do not align with the recommenda-
reference weights (healthy) for each age–sex group.* More
tions in the 2015–2020 Dietary Guidelines. Healthy
Eating Index (HEI) scores, a measure of how food choices
* For children and adolescents, reference height and weight vary. For align with the Dietary Guidelines, are low. On a scale
adults, the reference man is 5 feet 10 inches tall and weighs 154 from 0–100, the average score is 59. Children ages 6–11
pounds. The reference woman is 5 feet 4 inches tall and weighs 126 years and 12–17 years have the lowest scores (53), and
pounds. adults ages 18–64 and young children ages 2–5 years
106 Chapter 7 Dietary Guidelines for Americans, 2015–2020: National Nutrition Guidelines
score 58 and 60, respectively. Adults ages 65 and older • Shift to make half of all grains consumed be whole
have the highest score at 66 out of 100.* grains.
• Shift to consume more dairy products in nutrient-
When compared to the Healthy U.S.-Style Pattern: dense forms.
• Shift to increase variety in protein food choices and
• About three-fourths of the population has an eating to make more nutrient-dense choices.
pattern that is low in vegetables, fruits, dairy, and • Shift from solid fats‡ to oils.
oils. • Shift to reduce added sugars consumption to less
• More than half of the population is meeting or than 10 percent of calories per day.
exceeding total grain and total protein foods recom- • Shift to reduce saturated fats intake to less than 10
mendations, but are not meeting the recommenda- percent of calories per day.
tions for the subgroups within each of these food • Shift food choices to reduce sodium intake.
groups. • Shift to eating more vegetables, fruits, whole grains,
• Most Americans exceed the recommendations for and dairy to increase intake of nutrients of public
added sugars, saturated fats, and sodium.† health concern.
Figure 7.1 A Social-Ecological Model for Food and Physical Activity Decisions Data Sources: Adapted from1 Centers
for Disease Control and Prevention. Division of Nutrition, Physical Activity, and Obesity. National Center for Chronic Disease
Prevention and Health Promotion. Addressing Obesity Disparities: Social-Ecological Model. Available at: https://www.cdc.gov/
nccdphp/dnpao/state-local-programs/health-equity/index.html. Accessed October 19, 2015.2 Institute of Medicine. Preventing
Childhood Obesity: Health in the Balance, Washington (DC): The National Academies Press; 2005, page 85.3 Story M, Kaphingst
KM, Robinson-O’Brien R, Glanz K. Creating healthy food and eating environments: Policy and environmental approaches. Annu
Rev Public Health 2008; 29:253–272.
can influence the cultural norms and values that govern values to embrace, support, and maintain healthy eat-
thoughts, beliefs, and behaviors related to nutrition and ing and physical activity behaviors. It is important to
physical activity. In addition, education that takes into note that no one action is likely to be the primary driver
account the individual’s unique characteristics is another to improve individual and population lifestyle choices.
important way that health professionals can influence Evidence demonstrates that multiple changes both
health outcomes. Education to improve individual food within and across all levels of the Social-Ecological
and physical activity choices can be delivered by a wide Model are needed to increase the effectiveness of inter-
variety of professionals either working alone or as part of ventions. The following examples of strategies demon-
a multidisciplinary team. strate the concerted action needed from the sectors and
To help Americans shift from current eating and settings level down to the individual:
physical activity patterns to those outlined in the
Dietary Guidelines, collective action is needed across • Sectors: Identify and support policies and/or pro-
all segments of society. These actions must involve a grams that promote healthy eating and physical
broad range of sectors, occur across multiple settings, activity patterns.
and address the needs of individuals, families, and • Sectors: Foster partnerships with food producers,
communities. These actions include identifying and suppliers, and retailers to increase access to healthy
addressing successful approaches for change; improv- foods and beverages.
ing knowledge of what constitutes healthy eating and • Settings: Adopt organizational changes and prac-
physical activity patterns; enhancing access to adequate tices, including those that increase the availability,
amounts of healthy, safe, and affordable food choices; accessibility, and consumption of healthy foods and
and promoting change in social and cultural norms and beverages.
108 Chapter 7 Dietary Guidelines for Americans, 2015–2020: National Nutrition Guidelines
* For more information, see: U.S. Department of Agriculture, † For more information, see: U.S. Department of Agriculture,
ChooseMyPlate.gov: https://www.choosemyplate.gov/. Accessed ChooseMyPlate.gov, Communicator’s Guide: https : //ww
w.cho
March 9, 2018. osemyplate.gov/communicators-guide. Accessed March 9, 2018.
7.6 Looking Ahead to 2020—Expanding Guidance 109
links to a variety of existing nutrition education materials will require comprehensive and coordinated system-wide
7
from the USDA and HHS. approaches across the nation; health professionals are
The section, “Translating the Dietary Guidelines into vital to this endeavor and provide a uniquely influential
Consumer Messages” may be the most useful for health role in behavioral and systems change.
professionals who are looking for more guidance on how
to develop consumer-friendly messages based on the sci-
ence underpinning the Dietary Guidelines. This section 7.5 ALIGNING WITH THE DIETARY
provides overarching communication points to keep in
mind when developing consumer-friendly resources. It GUIDELINES: WHAT DOES
also provides 11 tables that address topics ranging from
healthy eating patterns to the five food groups, as well
THIS MEAN IN PRACTICE?
as oils, sodium, saturated fats, added sugars, and bever- The Dietary Guidelines describes adaptable eating pat-
ages. Each table also provides the key recommendation terns that can help promote health and reduce risk of
of the Dietary Guidelines related to the topic and its cor- chronic disease across the lifespan. It presents an array of
responding consumer-friendly message. It also links to options that can be tailored to income levels and that can
corresponding consumer-friendly materials that provide accommodate cultural, ethnic, traditional, and personal
“how-to” tips and advice as well as topical information preferences.
that seamlessly links back to the Dietary Guidelines. All segments of society—individuals, families, com-
Dietary Guidelines Toolkit for Health Professionals. munities, businesses and industries, organizations, govern-
The Office of Disease Prevention and Health Promotion ments, and others—can and should “align with the Dietary
within HHS serves the needs of health professionals, Guidelines.” In practice, the goal is to take the following
including doctors, nurses, dietitians, and policy and pro- actions in their entirety and maintain them over time:
gram planners who work in a variety of settings. With
this audience in mind, it developed a suite of resources • Make food and beverage choices that meet the Key
for professionals based on the Dietary Guidelines.* Recommendations for food groups, subgroups,
These resources are designed to help health professionals nutrients, and other components in combination to
quickly understand and incorporate key concepts from contribute to overall healthy eating patterns.
the Dietary Guidelines into practices. The toolkit also • Meet nutritional needs primarily through foods. In
provides resources that health professionals can share some cases, fortified foods and dietary supplements
with patients that communicate dietary behavior change may be useful in providing one or more nutrients
in small steps; explain the relationship between diet and that otherwise may be consumed in less-than-rec-
health outcomes; translate the Dietary Guidelines into ommended amounts or that are of particular con-
simple, actionable messages; and address general nutrition cern for specific population groups.
concepts as well as specific topics such as added sugars. • Establish and maintain settings (e.g., homes,
The toolkit includes an executive summary and an “at- schools, worksites, restaurants, stores) that sup-
a-glance” document that allows health professionals to port and encourage food and beverage choices
quickly and easily understand the new guidelines. It also that help individuals make shifts to meet the Key
includes conversation starters for health professionals and Recommendations for healthy eating patterns.
a series of patient handouts that can be used as takeaways • Ensure that food is kept safe to eat by using the prin-
in their interactions with patients and clients on topics ciples of clean, separate, cook, and chill.
such as healthy eating patterns, making healthy shifts in • Establish and maintain sectors and settings that
food and beverage choices, and how to cut down on added support and encourage regular physical activity as
sugars, saturated fat, and sodium. part of a healthy lifestyle.
As providers, health professionals engage in direct
interactions with the American public and can therefore
All of these actions are important individually, but
serve as message purveyors. Resources based on system-
they are intended to be taken together. Aligning with the
atic reviews of scientific evidence, such as the Dietary
Dietary Guidelines by taking these actions is powerful
Guidelines and the Physical Activity Guidelines for
because it can help change social norms and values and
Americans, provide the foundation for nutrition and pub-
ultimately support a new prevention and healthy lifestyle
lic health professionals to develop programs and materi-
paradigm that will benefit the U.S. population today as
als that can help individuals enhance their knowledge,
well as future generations.
attitudes, and motivation to make healthy choices. The
ultimate goal of the Dietary Guidelines is to improve the
health of the nation’s current and future generations by
facilitating and promoting healthy eating and physical 7.6 LOOKING AHEAD TO 2020—
activity choices among all individuals. Meeting this goal
EXPANDING GUIDANCE
* For more information, see: U.S. Department of Health and Human Traditionally, the Dietary Guidelines has focused on indi-
Services. https: //health.gov/dietaryguidelines /2015/resources.asp. viduals ages two and older in the United States, includ-
Accessed March 9, 2018. ing those who are at increased risk of chronic disease. This
110 Chapter 7 Dietary Guidelines for Americans, 2015–2020: National Nutrition Guidelines
is the focus of the recommendations in the 2015–2020 found at websites such as www.DietaryGuidelines.gov,
Dietary Guidelines as well. However, the relationship of www.healthfinder.gov, www.nutrition.gov, and www.
early nutrition to health outcomes throughout the lifespan ChooseMyPlate.gov. Additional information on vitamin,
has grown as a public health interest, and it is expected mineral, and macronutrient recommendations are avail-
that evidence will become sufficiently robust to support able in the Dietary Reference Intakes, accessible at https: //
additional dietary guidance in the future. As mandated ww w.nal.usda.gov/fnic/dietar y-reference-intakes. Finally,
by Congress in the Agricultural Act of 2014, the Dietary best practices that can be used to increase healthy and
Guidelines will expand to include more comprehensive safe food options for employees can be found in the Food
guidance for infants and toddlers from birth to 24 months Service Guidelines for Federal Facilities at https : //ww
as well as additional guidance for women who are preg- w.cdc.gov/obesit y/strategies/food-serv-guide.html.
nant beginning with the 2020–2025 edition. USDA and
HHS are looking to take a life stage approach—from birth
through older adulthood— for the upcoming edition.
CLINICAL APPLICATIONS
• Assist individuals with identifying an eating pattern
7.7 ADDITIONAL RESOURCES that is right for them based on their calorie needs,
personal health, cultural, ethnic, and traditional
The 2015–2020 Dietary Guidelines also provides 14 and personal preferences. Also to be considered are
appendices as resources that can be used in developing an individual’s budget and other issues of accessibil-
policies, programs, and educational materials. Examples ity, such as access to healthy food.
of information provided in these appendices include the • Encourage food and beverage choices that meet the
Physical Activity Guidelines for Americans; a table of Key Recommendations for food groups, subgroups,
nutritional goals for age–sex groups (based on Dietary nutrients, and other components in combination to
Reference Intakes and Dietary Guidelines recommenda- contribute to overall healthy eating patterns.
tions); estimated calorie needs by age, sex, and physical • Help individuals become more aware of the foods
activity level; alcoholic drink-equivalents of select bever- and beverages that make up their own or their fam-
ages; food sources of the nutrients of concern (potassium, ily’s eating patterns and identify areas, such as modi-
calcium, vitamin D, and dietary fiber); and the four basic fying recipes and/or food selections in order to make
food safety principles to reduce the risk of foodborne ill- shifts to align with the Dietary Guidelines.
ness—clean, separate, cook, and chill. • Establish and maintain sectors and settings that sup-
These resources are intended to complement existing port healthy eating patterns and encourage regular
federal nutrition information and guidance that can be physical activity as part of a healthy lifestyle.
REFERENCES
1. Centers for Disease Control and 2015/Guidel ines. Accessed March 11, 4. U.S. Department of Health and Human
Prevention (CDC). Chronic Disease 2018. Services. 2008 Physical Activity Guidelines
Overview. August 26; 2015. Available at: 3. Dietary Guidelines Advisory Committee. for Americans. Washington, DC: U.S.
http://www.cdc.gov/ch ronicdisease/overvi Scientific Report of the 2015 Dietary Department of Health and Human Services;
ew/. Accessed March 11, 2018. Guidelines Advisory Committee: Advisory 2008. ODPHP Publication No. U0036.
2. U.S. Department of Health and Report to the Secretary of Health and Available at: http://www.health.gov/pagu-
Human Services and U.S. Department Human Services and the Secretary of idelines. Accessed March 11, 2018.
of Agriculture. 2015–2020 Dietary Agriculture. Washington, DC: U.S. 5. Institute of Medicine. Dietary Reference
Guidelines for Americans. 8th Edition. Department of Agriculture, Agricultural Intakes for Energy, Carbohydrate, Fiber,
Washington, DC: U.S. Government Research Service; 2015. Available at: https Fat, Fatty Acids, Cholesterol, Protein,
Printing Office; 2015. Available at: http: ://health.gov/dietaryguidelines/2015-sci and Amino Acids. Washington, DC: The
//www.healt h.gov/diet arygu ideli nes/ entific-report/. Accessed March 11, 2018. National Academies Press; 2002.
8
CHAPTER
111
112 Chapter 8 Nutrition and Cardiovascular Disease
significant role in many of the components of either posi- maintaining healthy weight and, thereby, further reducing
tive or negative lifestyle decisions or practices. risk of CVD. 2,3,5
This chapter will focus on nutrition. Nutrition will The national guidelines on nutrition and cardiovascu-
be placed, however, in a broader lifestyle context with an lar health are also consistent with each other with regard
emphasis on physical activity as well as energy balance to overall strategies for reducing cardiovascular health
and weight maintenance. This overall approach to life- risk factors. For example, the AHA Strategic Goals for
style medicine is consistent with the approach taken by 2020 and Beyond offer some specific guidance in the area
the American Heart Association (AHA) in multiple docu- of nutrition. 3 While recognizing that recommending an
ments and scientific statements, 2,3 the Dietary Guidelines optimal pattern for CVD risk reduction is a complicated
for Americans 2015–2020, 5 and multiple mission state- task, the 2020 Strategic Plan defines dietary goals as “in
ments and position statements from the Academy of the context of a diet that is appropriate in energy balance
Nutrition and Dietetics.14 pursuing an overall dietary plan consistent with DASH
Moreover, nutritional guidelines offered by the AHA 2 (Dietary Approaches to Stop Hypertension)”. Eating plans
and other evidence-based documents, such as the 2013 recommended by the AHA include, but are not limited to
AHA/American College of Cardiology (ACC) Guidelines the following recommendations:
on Lifestyle Management to Reduce Cardiovascular
Risk,6 the AHA 2020 Strategic Plan for Improving • Fruits and vegetables ≥ 4.5 cups/day
Cardiovascular Health and Lowering Cardiovascular • Fish ≥ two 2.5 ounce servings/week (preferably oily
Risk, 3 and the report from the Dietary Guidelines fish)
Advisory Committee 2015–2020, 5 are very similar. All • Fiber rich/whole grain ≥ 1.1 grams fiber/10 grams
place an emphasis not only on nutrition but on a broader carbohydrate, three one-ounce equivalent servings/
approach toward positive lifestyle factors to improve car- day
diovascular health and reduce the risk of CVD. • Sodium ≤ 1500 milligrams/day
• Sugar-sweetened beverages ≤ 460 calories (36
ounces)/week
8.2 BACKGROUND
These recommendations represent a reasonable start-
Consensus statements and recommendations from a vari- ing point and have been expanded upon in other guide-
ety of organizations issued over the past ten years regard- lines and recent reviews.
ing nutritional strategies for improving cardiovascular Dietary guidance over the last 20 years has moved
health are very similar. Often these recommendations from specific foods and nutrients to a greater emphasis on
have drawn upon the same database, in general, particu- dietary patterns. Thus, dietary patterns will be discussed
larly large epidemiologic studies. These guidelines have in some detail in this chapter.
often referred to each other. These published consensus Emphasis in nutrition guidelines have also shifted to
statements form the basis of the recommendations made the critical aspect of implementing recommendations.16 It
in this chapter and include the following: is clear that nutrition plays a key role in many aspects of
preventing CVD, but it is also recognized that despite con-
• Diet and Lifestyle Recommendations Revision sistent recommendations and guidelines for many decades,
2006: A Scientific Statement from the American a distinct minority of Americans are following most of
Heart Association Nutrition Committee. 2 these guidelines. For example, with regard to nutrition
• Defining and Setting National Goals for and hypertension, less than 20% of individuals with
Cardiovascular Health Promotion and Disease high blood pressure currently follow the DASH diet.17 It
Reduction: American Heart Association Strategic has also been estimated that less than 30% of adults in
Impact Goals through 2020 and Beyond.3 the United States consume the recommended number of
• 2013 AHA/ACC Guidelines for Lifestyle fruits and vegetables.18 The problem of how to encourage
Management to Reduce Cardiovascular Risk: people to actually implement heart-healthy guidelines in
A Report of the American College of Cardiology/ their daily lives remains an important topic which will be
AHA. Task Force on Practice Guidelines.6 discussed toward the end of this chapter. There has also
• Dietary Guidelines 2015 Advisory Committee been an increased emphasis on how to incorporate behav-
Report.15 ioral medicine techniques into nutrition and other positive
• Dietary Guidelines for Americans 2015–2020.7 aspects of a positive lifestyle. This is another area of con-
siderable ongoing research.
These consensus statements consistently recommend
a dietary pattern higher in fruits and vegetables, whole
grains (particularly high fiber), non-fat dairy, seafood, 8.3 DIETARY PATTERNS
legumes, and nuts. The guidelines further recommend that
those who consume alcohol (among adults) do so in mod- The 2015–2020 Dietary Guidelines for Americans (DGA)
eration. The guidelines are also consistent in recommend- focused on integrating available science and systematic
ing diets lower in red and processed meats, refined grains, reviews of scientific research, food pattern modeling,
sugar-sweetened foods, and saturated and trans fats. All and analysis of the current intake of the U.S. popula-
of these guidelines have also emphasized the importance tion to develop the “Healthy U.S.-Style Eating Pattern”.7
of balancing calories and physical activity as a strategy for This approach allowed the blending of the overall diet,
8.3 Dietary Patterns 113
including constituent foods, beverages, nutrients, and The Healthy U.S.-Style Eating Pattern is also
8
health outcomes. In addition, the food pattern model- designed to meet recommended daily allowances
ing allowed more flexibility in amounts of foods from all (RDA), adequate intakes of potential nutrients,
food groups to establish healthy eating patterns which and acceptable macronutrient distribution ranges
met nutrient needs and accommodated limitations such (AMDR) set by the Food and Nutrition Board of the
as those for saturated fats, added sugars, and sodium. Institute of Medicine (IOM). Flexibility within the
Finally, this approach allowed for analysis of current dietary pattern also allows for minor modifications
intakes, which identified areas of potential public health to allow the Mediterranean diet or DASH diet to be
concern. With this approach, the Dietary Guidelines for followed within these overall guidelines.17–21
Americans 2015–2020 stated the following: • Low-Fat Diets
Lower-fat diet consumption has been generally
• Within this body of evidence, higher intakes of veg- accepted in clinical guidelines for CVD prevention.
etables and fruits consistently have been identified This pattern forms the basis of numerous other diets
as characteristics of healthy eating patterns; whole to be discussed in this chapter.
grains have been identified as well, although with Briefly, low-fat diets are based on total fat con-
slightly less consistency. Other characteristics of sumption of 25–35% of total calories with saturated
healthy eating patterns have been identified with fat (SFA) of no more than 7–10%; trans fat (TFA) of
less consistency and include fat-free or low-fat dairy, less than 1%; unsaturated fat, mainly monounsatu-
seafood, legumes, and nuts. Lower intakes of meats, rated fats (MUFA); and Omega-3 polyunsaturated
including processed meats; processed poultry; sugar- fat (N-3 PUFA) consisting of the rest of the calories
sweetened foods, particularly beverages; and refined from fat. This diet also calls for dietary cholesterol
grains have often been identified as characteristics of less than 300 milligrams/day. 2,22,23
of healthy eating patterns. These recommendations can be met by empha-
sizing fruits and vegetables, low-fat dairy prod-
Additionally, DGA 2015–2020 provided input on vari- ucts, including 1% milk, and low-fat meat. Some
ous dietary and health related components. controversy remains about the type and amount of
carbohydrates consumed. It should also be noted
• Healthy U.S.-Style Eating Pattern17 that the food matrix for SFAs has been an area of
Following the guidelines outlined in the preceding recent research, with some suggestion SFAs coming
paragraph the U.S. Dietary Guidelines for Americans from dairy products are less likely to cause adverse
2015–2020 developed the U.S.-Style Healthy Eating increase in risk factors for CVD compared to other
Pattern for the 2000-calorie level, including daily or sources of SFAs. 24,25
weekly amounts from various food groups and com- • Low-Carbohydrate Diet
ponents which are found in Figure 8.1. Low-carbohydrate diets are typically defined as
The DGA 2015–2020 Guidelines also emphasize containing up to or less than 45% of total calories
that calories should be balanced and that intake from carbohydrates (30–130 grams of carbohy-
of calories from added sugars, saturated fats, and drates/day). Studies of low-carbohydrate diets have
alcohol should be limited to not exceed acceptable shown a reduction in triglycerides (TG) and an
macronutrient distribution ranges for calories from increase in HDL cholesterol (HDL-C). 26,27
protein, carbohydrates, or total fats. One study which compared low-carbohydrate
to low-fat and Mediterranean diets found greater
Food Group Amount in the
weight loss in the low-carbohydrate diet over the
2,000-Calorie-Level Pattern course of one year. A two-year dietary interven-
tion, the randomized controlled (DIRECT) trial, 28
Vegetables 2½ c-eq/day which involved 322 moderately obese participants
Dark green 1½ c-eq/wk and compared low-fat to low-carbohydrate and
Red and orange 5½ c-eq/wk Mediterranean diets, found that the low-carbohy-
Legumes (beans and peas) 1½ c-eq/wk
Starchy 5 c-eq/wk
drate diet was most effective in short-term weight
Other 4 c-eq/wk loss, decreasing TG, and increasing HDL-C levels.
Fruits 2c-eq/day At the four-year follow-up, however, there were no
Grains 6 oz-eq/day significant differences among the three arms.
Whole grains ≥ 3 oz-eq/day There is insufficient data from long-term trials to
Refined grains ≤ 3 oz-eq/day demonstrate the benefits of a low-carbohydrate diet
Dairy 3c-eq/day compared to the low-fat and Mediterranean diets
Protein Foods 5½ oz-eq/day for reduction of risk of CVD.
Seafood 8 oz-eq/wk
Meats, poultry, eggs 26 oz-eq/wk
• Mediterranean Diet
Nuts, seeds, soy products 5 oz-eq/wk The Mediterranean diet was originally described
Oils 27 g/day as the one typically consumed in countries bordering
the Mediterranean Sea.29,30 It is characterized by rela-
Figure 8.1 Healthy U.S.-Style Eating Pattern at the tively high fat intake (40–50% of total daily calories)
2,000-Calorie Level, with Daily or Weekly Amounts from of which SFA comprises ≤ % and MUFA supplies
Food Groups, Subgroups, and Components. 15–25% of calories. The Mediterranean diet is also
114 Chapter 8 Nutrition and Cardiovascular Disease
characterized by high Omega-3 fatty acid intake from risk. 35–38 Few randomized controlled trials (RCTs)
fish and plant sources and low Omega-6–Omega-3 have been performed on vegetarian diets, and
ratios. It features seasonal, local fresh vegetables, they have usually been small. They have typically
fruits, whole bread, grains, legumes, nuts, and olive resulted in lower blood pressure compared to usual
oil. Red meat is avoided. Moderate amounts of low- Western diets. Some observational studies have sug-
fat dairy products as well as eggs, chicken, and fish gested that vegetarians experience improved health
are allowed. Small-to-moderate quantities of wine outcomes compared to non-vegetarians.39 However,
are encouraged with meals in non-Islamic countries. a variety of characteristics of vegetarian diets could
A recent, multicenter, randomized intervention account for these findings, including fewer meats
study in Spain in individuals with high cardiovas- and inclusion of plant-based foods. Furthermore,
cular risk, but no overt evidence of cardiovascular vegetarians are often more health-conscious than
disease at enrollment, was divided into three diets as other individuals, although other factors could con-
follows: the Mediterranean diet supplemented with tribute to the lower reported incidence of CVD.
extra-virgin olive oil, the Mediterranean diet supple- • Japanese Diet
mented with mixed nuts, or a control diet (advised There has been recent interest in Japanese diets,
to reduce dietary fat).31 The primary end point was particularly those from Okinawa, which has among
an incidence of major cardiovascular events such as the lowest CVD rates in the world.40 The traditional
myocardial infarction, stroke, or death from cardio- Japanese diets emphasize fish, soybean products,
vascular causes. seaweed and vegetables, fruits and green tea, and
The two Mediterranean diets resulted in a are low in meat. It should be noted the Japanese
decrease of approximately 30% in major cardiovas- diets often contain high sodium from soy sauce and
cular events compared to the control diet, providing have been linked to higher risk of strokes.41 There
strong evidence that a Mediterranean diet supple- have been relatively few studies of Japanese diets, so
mented with extra-virgin olive oil or nuts reduces many issues remain to be determined.
the risk of major CVD events. • Prudent Diet
• DASH Diet17 In a sense the low-fat diet, the Mediterranean
The Dietary Approach to Stop Hypertension diet, the DASH diet, and the vegetarian diet all
(DASH), initially formulated in the 1990s,17 has would fit in what has been called the “Prudent diet”
undergone several modifications and iterations since category. A recent publication compared this diet
that time.32,33 The initial goal was to lower blood pattern, which contains high levels of fruits, veg-
pressure and CVD incidence by nutritional means. etables, legumes, fish, poultry, and whole grains
The DASH diet features vegetables and fruits as well to a typical Western pattern which contains higher
as low-fat dairy products, whole grains, chicken, intakes of red meat, processed meat, refined grains,
fish, and nuts. It is low in fat, red meat, sweets, and French fries, and sweets/desserts.42 In this study, the
soft drinks. The DASH diet provides more calcium, Western pattern was associated with a higher risk of
potassium, magnesium, dietary fat, and less fat and mortality from cardiovascular disease (22% higher;
sodium than the typical Western diet.33 Typical 25% CI, 1–48), cancer (15%; 95% CI, 3–30), and
composition of the DASH diet is found in Table 8.1. all causes (21%; 95% CI, 12–32).
Subsequent studies have substituted some of the • Plant-Based Diets
carbohydrates with MUFAs and have also further There has been a recent surge in evidence and
decreased sodium in the diet. All of these modified publications concerning “plant-based” diets.43
DASH diets have significantly reduced both systolic Essentially, these diets are defined by an emphasis
and diastolic blood pressure by 7 to 9 mmHg com- on plants, including fruits and vegetables. Low-fat
pared to the typical Western diet. diets and low-carbohydrate diets can both be turned
A study combining the DASH diet with a lifestyle into plant-based diets. The Mediterranean diet,
program aiming to reduce overweight and increase DASH diet, vegetarian, and Japanese diets are all,
physical activity and restrict sodium and alcohol in essence, plant-based diets since they emphasize
intake (the PREMIER Trial)34 showed additional fruits and vegetables, legumes, and nuts, and limit
decreases in both systolic and diastolic blood pres- the amount of red meat, processed meat, sweets,
sure which were reduced by 14.2 mmHg and 17.4 and oils.
mmHg, respectively.
Unfortunately, even in individuals with high
blood pressure, less than 20% are currently follow- 8.4 INDIVIDUAL FOOD ITEMS
ing the DASH diet.17
• Vegetarian Diet Numerous studies, including RCTs of risk factors for
A variety of vegetarian diets are available, includ- CVD as well as prospective cohort studies of disease end
ing vegan (consuming no animal products), lacto- points provide consistent and strong evidence for the car-
ovo vegetarian (consuming milk and eggs), and diovascular effects of certain specific foods in contrast to
pesco vegetarians (individuals who consume fish individual nutrients. These studies represent the combined
along with a vegetarian diet). benefits of composite effects and interactions of mul-
There are no data to suggest that one form of veg- tiple factors within foods rather than isolated nutrients.
etarian diet is superior to others with regard to CVD Most foods which fit into dietary patterns that have been
8.4 Individual Food Items 115
demonstrated to lower the risk of CVD will be empha- and diastolic blood pressure, and resting heart rate. Based
sized in this section. on these physiologic benefits, regular fish consumption is
associated with lower incidence of CVD and risk of car-
diac death. 53 For this reason, the AHA dietary recom-
8.4.1 Fruits and Vegetables mendations include the consumption of two fish meals
RCTs with diets that emphasize consumption of fruits and (preferably oily fish) per week. 2,3 It is not clear whether
vegetables have been repeatedly shown to produce sub- the benefits of eating fish can be reproduced by consuming
stantial improvements in risk factors for CVD, including fish oil supplements.
lipid levels, blood pressure, insulin resistance, inflammatory
biomarker levels, and weight control.2,3,5,44 These same ben-
efits have not been duplicated with supplements and are 8.4.4 Nuts
not dependent on dietary macronutrient composition (e.g.,
fat, protein, or carbohydrates). These benefits appear to Nuts, including tree nuts and peanuts, are nutrient-dense
result from phytochemicals and fiber found in fruits and foods which are high in unsaturated fats and other bio-
vegetables as well as increased bioavailability of these nutri- active compounds as well as high-quality vegetable pro-
ents in their natural state and replacement of less healthful tein, fiber, minerals, tocopherols and phytosterols, and
food in the diet. Both cohort studies and RCTs together sup- phenolic compounds. 54 While peanuts are not techni-
port strong evidence that fruit and vegetable consumption cally tree nuts, and are typically considered ground nuts
lowers CVD risk.2,3,5,44 Considerable research is currently or legumes, they are widely identified in research and in
underway to determine which specific types of fruits and the consumer mind as in the same grouping as tree nuts.
vegetables are most beneficial to lower CVD risk. Additionally, peanuts have a nutrient profile similar to
tree nuts.
Epidemiologic studies have consistently shown a nega-
tive association between nut consumption and CVD risk. 55
8.4.2 Whole Grains and Dietary Fiber Numerous research studies have shown that consumption
Whole grains contain the endosperm, bran (the outer layer of nuts can lower LDL-C concentration by approximately
of the whole grain), and germ in relative proportions as 10 mg/dL, while not significantly changing HDL-C levels.
they exist in the intact grain.45 Refined grains, in con- Triglycerides have also been shown to be reduced by > 20
trast, retain only the endosperm. Dietary fiber consists of mg/dL in subjects with elevated blood cholesterol, though
the remnants of edible plant lignin, polysaccharides, and not in those with normal TG levels.
associated substances that are resistant to digestion by the
human gastrointestinal tract and enzymes.46 Fiber includes
the following:1 insoluble fiber (including cellulose and lig- 8.4.5 Meat
nin), which is found in some vegetables, some fruits, and
whole grains (including wheat germ), and 2 soluble fiber, Dietary patterns that include lower consumption of red
which includes pectin, fruits, guar gum, and mucioag.47 meat have consistently been demonstrated to lower CVD
Soluble fiber also is found in oat bran and legumes. Eating risk. 56,57 Various constituents of red meat, including SFAs,
whole grains decreases total cholesterol by between 7–8 cholesterol, and in processed meat, high levels of salt have
mg/dL and LDL-C levels by 6.9 mg/dL, according to a been shown to increase factors for CVD. In one research
recent Cochrane analysis.48 study, both unprocessed and processed meat consumption
The National Cholesterol Program (ATP III),49 was associated with higher CVD risk. Such consumption
American Heart Association (AHA), and Academy of replaced foods with cardiac health benefits such as nuts,
Nutrition and Dietetics (AND)50 all have guidelines which fish, and low-fat dairy products. Consumption of red meat
include recommendations to increase fiber intake. Whether and processed meats has also been associated with weight
or not added fiber when used as a food supplement can gain, which may also increase risk of CVD.
similarly lower risk factors for CVD is controversial.
The Food and Drug Administration (FDA) has
approved a health claim for the soluble fiber from whole 8.4.6 Dairy Products
oats, whole grain barley products, and barley beta fiber. 51
Dairy products are rich in minerals such as calcium, potas-
The DRI recommends 25 grams of fiber for adult women
sium and magnesium, protein (caseine and whey), and
and 38 grams for adult men per day. This corresponds to
vitamins (riboflavin and Vitamin B-12), and may exert
14 grams of dietary fiber/1000 kcals.47
potential benefits by effectively lowering risk for CVD.
The presence of saturated fat in full-fat dairy products has
raised concern related to potential adverse CVD effects.58
8.4.3 Fish For this reason, most dietary guidelines recommend low-
Fish and other seafood contain a variety of healthful sub- fat dairy products rather than full-fat dairy products.
stances, including unsaturated fat, vitamin D, selenium, The inclusion of low-fat dairy products as part of an
and long-chain Omega-3 polyunsaturated fatty acids overall heart-healthy diet has been demonstrated to sig-
(PUFAs). Some studies have suggested that fish oil has nificantly lower blood pressure, lipid levels, and insulin
direct anti-arrhythmic effects, but studies in individuals resistance independent of changes in weight.59,60 Due to
with preexisting arrhythmias have been inconsistent. 52 the multicomponent nature of such trials, however, it is
Fish oil has been shown to lower triglyceride levels, systolic difficult to sort out the specific benefits of dairy products.
8.4 Individual Food Items 117
Recent research has suggested that the matrix in dairy health consequences such as motor vehicle accidents.75
8
products may make the SFAs in them less hazardous to Conversely, moderate alcohol consumption (up to two
CVD risk than other SFAs. 24,25 The DGAs 2015–2020 drinks/per day for men and one drink/day for women) has
recommend adults consume three cups of low-fat milk or been shown to result in lowering the incidence of CVD
the equivalent on a daily basis.7 This is far greater than the and diabetes (DM).76 These effects may be the result of
average serving of one cup per day consumed by adults in moderate alcohol consumption raising HDL-C, reducing
the United States. Children and adolescents also consume systematic inflammation, or improving insulin resistance.
far below recommended levels.
The health effects of other dairy products such as
yogurt, cheese, and butter are subject of considerable 8.4.10 Coffee and Caffeine
research and require further study. Coffee is consumed throughout the world and is a lead-
ing source of caffeine. Other sources of caffeine include
primarily tea, cocoa products, cola beverages, and
8.4.7 Soy “energy drinks”.77 Caffeine is the best characterized com-
The protein found in soybeans is typically referred to as pound in coffee. It has been estimated that 80–90% of
“soy” and is often used to replace animal protein in indi- adults regularly consume caffeine-containing beverages
vidual diets.61 Soybeans contain no cholesterol, are low in and food. Coffee consumption had long been suspected
saturated fat, and contain considerable protein. Soy is the of being a contributing factor to development of CVD.
only vegetable to contain all eight amino acids. The effect Accumulating data over the past few years, however, have
of soy on CVD risk has been inconsistent. suggested no harm, possibly even a protective association,
between moderate coffee drinking and CVD mortality.78
Furthermore, a recent study reported that type 2 diabetes
was lowered in individuals who consumed four or more
8.4.8 Sugar Sweetened Beverages (SSBs) cups of coffee a day compared to those who drank less
The effect of sugar-sweetened beverages on cardiovascu- than two cups per day.79
lar disease risk is controversial. Some epidemiologic stud-
ies have suggested that increased consumption of SSBs
increased the risk of heart disease, diabetes, and obesity.62–64 8.4.11 Tea
These studies, however, have not been supported by a num- Tea is also widely consumed throughout the world. A vari-
ber of randomized controlled trials.65,66 The American ety of teas is available. Most of the tea is consumed in
Heart Association recommends that adult males consume Western countries (78%) is black tea, while 20% is green
no more than 150 kcals/day in sugar-sweetened beverages tea, which is the most commonly consumed tea in Asian
and adult females no more than 100 kcals/day in SSBs.67 The countries, and Oolong tea (2%), which is mainly con-
2020 Strategic Plan from the AHA recommends no more sumed in Southern China. Several studies have suggested
than 360 kcals/week from sugar-sweetened beverages.3 The that tea consumption may protect against the incidence
DGAs 2015–2020 recommend no more than 10% of calo- and progression of CVD.80,81 These findings may result
ries from added sugars,5 a recommendation also mirrored from improvement of endothelial function from the inter-
by the FDA.68 This recommendation is exceeded by over action between tea components and nitric oxide (NO).82
80% of the population in the United States. This interaction appears to be the result of polyphenol-
It should be noted that while the consumption of like flavonoids known as catechins in the tea, resulting in
added sugar has increased the past 40 years in the United the increased bioavailability of NO, which plays a signifi-
States,69 this increase is relatively less than the increase in cant role in endothelial function and arterial dilation.
the consumption of fats and flour products. The consump-
tion of all added sugars combined actually decreased from
19% of total calories in 1972 to 17% of total calories in 8.4.12 Eggs
2010.70
Over many years, the public had been cautioned to limit
SSBs may be an indication of an overall poor-quality
egg consumption due to high cholesterol content of egg
diet. It thus seems reasonable to recommend no more
yolks and the potential association with CVD.83 However,
than moderate consumption of SSBs in an overall cardiac-
subsequent research has demonstrated that in contrast to
healthy diet.
SFAs and TFAs, dietary cholesterol, in general, and cho-
lesterol in eggs, in particular, have minimal effects on
blood cholesterol.84 Eggs are also a good source of high-
8.4.9 Alcohol value protein and a variety of vitamins and minerals.
Alcohol consumption has been demonstrated in various DGA Guidelines 2015–2020 have, nonetheless, continued
studies to have both beneficial and adverse cardiovas- to recommend restriction of dietary cholesterol to less
cular outcomes.71–73 Heavy alcohol consumption (three than 300 milligrams/day. 5
alcoholic drinks/day or more for men and two or more
alcoholic drinks/day for women) has been associated with
increased risk of cardiomyopathy and higher risk rates of
8.4.13 Garlic
atrial fibrillation.74 Heavy alcohol consumption is also Garlic preparations have been investigated for both pre-
associated with a variety of other non-cardiac, adverse vention and treatment of cardiovascular disease. Studies
118 Chapter 8 Nutrition and Cardiovascular Disease
have included raw garlic, garlic powder tablets, oil of with preexisting late-stage atherosclerosis were found in
garlic, and aged garlic extract. Long-term observational individuals receiving antioxidant supplements with vita-
studies, however, for garlic are not available. In view min E or C.93
of short-term trials on the effect of garlic on factors for
CVD showing modest effects,85 it appears that garlic may
reduce platelet aggregation, but its effect on other CVD 8.6 AHA DIET AND LIFESTYLE
risk factors is controversial.
RECOMMENDATIONS
In 2006, the AHA summarized diet and lifestyle rec-
8.4.14 Chocolate ommendations in a Scientific Statement from the
Cocoa is similar to green teas with regard to the content AHA Nutrition Committee. 2 These recommendations
of polyphenols. It is important to recognize that chocolate were extended and updated in 2013 with the AHA/
and cocoa are not the same thing.86 While cocoa powder is ACC Guideline for Lifestyle Management to Reduce
used in the production of chocolate, fat, and sugar are the Cardiovascular Risk, which also provided specific clinical
major components of chocolate, creating a higher caloric guidelines.6 Subsequent studies and research have refined
content. Although the polyphenols from the cocoa may these goals, but the basic framework from these two docu-
have some benefit for reducing risk factors for CVD, it is ments has stood the test of time and will be utilized in
more appropriate to potentially recommend cocoa rather this chapter as a point of departure. Since many of the
than chocolate due to the increased calories from sugar recommendations of these two documents have already
and fat in chocolate. been discussed in the sections on “Dietary Patterns” and
“Individual Food Items,” specific recommendations will
be handled with brief summaries.
8.5 NUTRITIONAL SUPPLEMENTS The AHA documents started from the fundamen-
tal premise that improving diet and lifestyle represents a
critical component in an overall strategy to prevent CVD.
8.5.1 Salt and Sodium Both documents differ from previous guidelines in recom-
Virtually every heart-healthy dietary plan recommends mending a broader approach to not just diet but overall
a reduction in sodium. 2,3,5 Dietary sodium may come lifestyle. The combination of diet and physical activity, in
in a variety of forms, including processed food (a major particular, has been emphasized. Both documents empha-
source of sodium), table salt, snacks, and so on. As dietary size both public health and clinical application. With this
sodium intake increases, so does blood pressure. in mind, the following goals have been outlined.
A number of studies have shown that reduction in salt
intake lowers the risk of CVD. 2,3,5,87–89 For this reason,
the AHA established the interim goal of 2300 mg/day of 8.6.1 Consume an Overall Healthy Diet
sodium and less than 1500 mg/day in individuals with
This recommendation starts from the premise that we
hypertension, African Americans, and middle or older
need to move from individual nutrients to overall dietary
age Americans.90 However, the current average intake
patterns such as already discussed in this chapter. It was
of sodium in the United States is 3.4 grams/day. Several
recognized that randomized controlled trials of the whole
studies have suggested that lower intakes or higher intakes
diet are difficult and expensive to conduct. Numerous
both increase the risk of CVD compared to the average
cohort and other epidemiologic studies support the con-
amount currently being consumed by Americans.91 Thus,
cept that dietary patterns consisting of a variety of fruits
considerable controversies remain in the area of sodium
and vegetables, whole grains, fat-free and low-fat dairy
consumption and CVD risk.
products, legumes, poultry, lean meats and fish (prefer-
ably oily fish) consumed at least twice a week, have been
associated with lower risk of CVD. 2,3,5,94–97 This pat-
8.5.2 Vitamin D tern is consistent with the U.S. Healthy Eating Plan, the
Vitamin D consumption is associated with decreased risk Mediterranean Diet, and the DASH diet, which have
of bone disease based on well-designed studies. Vitamin already been discussed in this chapter.
D may also play a role in a variety of other health issues,
including lowering the risk of CVD.92 At the current
time, however, there are insufficient data to recommend 8.6.2 Aim for a Healthy Body Weight
increased consumption of vitamin D as a strategy for low-
ering the risk of heart disease. The AHA Guidelines utilize the framework from the
Institute of Medicine establishing healthy body weight as
defined as a body mass index (BMI) of 18.5–24.9 kg/m 2 .
Overweight is defined as defined as a BMI between
8.5.3 Antioxidant Vitamins E and C 25–29.9 kg/m 2 , and obesity is defined as a BMI of ≥ 30
Some observational studies initially suggested that anti- kg/m 2 . This goal also recognizes that obesity is related
oxidant vitamins E and C were associated with lower risk to multiple other risk factors for CVD, such as dyslipid-
of CVD. However, RCTs in this area have been largely emias, high blood pressure, and diabetes, and that obesity
disappointing. In fact, in several cases increased mortality in and of itself represents a risk factor for CVD.98,99 Issues
8.7 Specific AHA Nutrition and Lifestyle Recommendations 119
related to obesity management are handled in detail in the DASH diet. Other dietary modifications that have
8
Chapters 36–42. been shown to lower high blood pressure include reducing
salt intake, establishing a caloric deficit to induce weight
loss in overweight or obese individuals, moderate alco-
8.6.3 Aim for a Desirable Lipid Profile hol consumption (among those who drink alcohol), and
increased potassium intake. Physical activity is also an
Elevations in total cholesterol as well as LDL cholesterol
important recommendation and acts synergistically with
are established risk factors for CVD. As levels of LDL cho-
diet to further lower blood pressure.
lesterol increase, so does the risk of developing CVD. The
following levels of LDL have been defined: optimal (less
than 100 mg/dL); near or above optimal (100–129 mg/dL);
borderline/high (130–159 mg/dL); high (160–189 mg/dL);
8.6.5 Be Physically Active
very high (> than 190 mg/dL).49,100 Several different guide- All of the major guidelines for nutritional intervention to
lines have been published for managing LDL. However, reduce the risk of CVD also incorporate the recommen-
dietary changes such as following an overall AHA Healthy dation to increase physical activity.2,3,5 Increased levels of
Diet Plan are foundational to nutritional approaches to moderate or vigorous physical activity have repeatedly been
managing total cholesterol and LDL cholesterol. shown to lower the risk of cardiovascular disease. Guidelines
Triglycerides and HDL cholesterol levels are also such as the AHA/ACC Lifestyle Recommendations, the
related to CVD risk and can be affected by both diet and DGA 2015–2020, and the 2006 Nutrition Guidelines
body weight. Triglyceride levels of > 150 mg/dL are con- from AHA all recommend increased physical activity in
sidered abnormal.101 Major diet determinants of low diet addition to heart-healthy nutritional plans. The best sin-
HDL cholesterol are hyperglycemia, diabetes, hyperglyceri- gle source of information related to physical activity and
demia, and a very low-fat diet (<15% of energy as fat) as reduced CVD and other chronic diseases may be found in
well as excess body weight. Elevated triglycerides and low the 2008 U.S. Department of Health and Human Services
HDL are often seen together and are components of the “Physical Activity Guidelines for Americans.”10 This docu-
metabolic syndrome.102,103 Dietary recommendations for ment was designed to complement the Dietary Guidelines
elevated triglycerides are virtually the same as those for for Americans. More physical activity is associated not only
low HDL cholesterol and elevated LDL cholesterol. with lowering the risk of CVD but also with specific CVD
risk factors, including blood pressure, lipid profiles, and
blood sugar. Specific recommendations for physical activity
8.6.4 Aim for a Normal Blood Pressure may be found in Chapters 11–14.
Elevated blood pressure represents a significant risk fac-
tor for both CVD and stroke. Nutrition clearly plays a 8.6.6 Avoid Use and Exposure
significant role in blood pressure control. Issues related to Tobacco Products
to optimum levels of blood pressure control have become
somewhat controversial. Recommendations from the Joint Overwhelming evidence exists from multiple sources that
National Commission VII (JNC VII) defined a normal cigarette smoking and the use of tobacco products or expo-
blood pressure as < 120/80 mmHg, and defined a diastolic sure to cigarette smoke increase the risks for both CVD
blood pressure of 80–89 mmHg and 120–139 mmHg sys- and stroke.106 This evidence has been summarized in mul-
tolic as prehypertension with > 140/90 mmHg as “hyper- tiple other locations, including the AHA 2020 Strategic
tension”.104 These were also the recommendations made Plan3 and the AHA/ACC Diet and Lifestyle Clinical
by the AHA 2020 Strategic Plan. Recommendations and Goals. Unfortunately, over 23% of
The committee appointed to develop the JNC VIII U.S. adults still smoke cigarettes, and the rate of decline
Guidelines made somewhat different recommendations. of cigarette smoking has significantly slowed over the past
They issued the following statement: “There is strong evi- 20 years.107 Risks of cigarette smoking for women are cur-
dence to support treating hypertensive individuals aged 60 rently equivalent to men. Substantial benefits, however, in
or older to a BP goal of < 150/90 mmHg and hyperten- the reduction of risk of CVD accrue to the individual who
sive persons 30–59 years of age to a diastolic goal of < 90 stops smoking cigarettes. These benefits accrue over a very
mmHg. However, there is insufficient evidence in hyper- brief period of time.107
tensive persons younger than 60 years for a systolic goal
or in those younger than 30 years for a diastolic goal, so
the panel recommends a BP of < 140/90 mmHg for those
groups based on expert opinion.”105 These guidelines also
8.7 SPECIFIC AHA NUTRITION AND
emphasize that clinical judgement should prevail when LIFESTYLE RECOMMENDATIONS
considering hypertensive therapy.
It should be emphasized that both of these sets of rec- The AHA has listed specific diet and lifestyle recommen-
ommendations support nutritional intervention as a key dations to reduce CVD risks. These were recommenda-
component of the overall prevention and treatment of high tions made in the AHA Scientific Statement from the
blood pressure. A nutritional pattern consistent with the Nutrition Committee in 2006. 2 Multiple studies since that
DASH diet has been clearly demonstrated to help control time have helped further clarify and fine-tune these rec-
blood pressure.95 Unfortunately, a distinct minority of ommendations. These recommendations are included in
individuals who have high blood pressure actually follow multiple guidelines from the American Heart Association
120 Chapter 8 Nutrition and Cardiovascular Disease
REFERENCES
1. Rippe JM and Angelopoulos TM. 2. Lichtenstein AH, Appel LJ, Brands Circulation 2006;114:82–96. Epub
Lifestyle strategies for cardiovascu- M, et al. Diet and lifestyle recom- 2006/06/21.
lar risk reduction. Curr. Atheroscler. mendations revision 2006. A scientific 3. Lloyd-Jones DM, Hong Y, Labarthe D,
Rep. 2014;16:1–7. doi: 10.1007/ statement from the American Heart et al. Defining and setting national goals
s11883-014-0444-y. Association Nutrition Committee. for cardiovascular health promotion
References 121
and disease reduction: The American and vascular biology, council on cardio- and meta-analysis. Am. J. Clin. Nutr.
Heart Association’s strategic impact goal vascular nursing, council on epidemiol- 2010;92:1189–1196.
4.
through 2020 and beyond. Circulation
2010 Feb 2;121(4):586–613.
Mozaffarian D, Appel LJ, and Van
ogy and prevention, and council for high
blood pressure research. Circulation
2009;119(8):1161–1175.
31. Estruch R, Ros E, Salas-Salvadó J, et al.
Primary prevention of cardiovascular
disease with a Mediterranean diet. N.
8
Horn L. Components of a cardiopro- 17. Appel LJ, Brands MW, Daniels SR, et Engl. J. Med. 2013;368:1279–1290.
tective diet: New insights. Circulation al. Dietary approaches to prevent and 32. Sacks FM, Obarzanek E, Windhauser
2011;123(24):2870–2891. treat hypertension: A scientific statement MM, et al. Rationale and design of the
5. U.S. Department of Health and from the American Heart Association. Dietary Approaches to Stop Hypertension
Human Services and U.S. Department Hypertension 2006;47(2):296–308. trial (DASH): A multicenter controlled
of Agriculture. 2015–2020 Dietary 18. Scientific Advisory Committee on feeding study of dietary patterns to
Guidelines for Americans, 8th Edition, Nutrition. SACN Carbohydrates and lower blood pressure. Ann. Epidemiol.
2015. Available at: http://health.gov/di Health Report. www.gov.uk, 2015. 1995;5:108–118.
etaryg uidelines/ 2015/guidelines /. Epub Accessed: February 4, 2019. 33. Appel LJ, Champagne CM, Harsha DW,
December 2015. 19. Ockene JK, Schneider KL, Lemon SC, et et al. Effects of comprehensive lifestyle
6. Eckel RH, Jakicic JM, Ard JD, et al. al. Can we improve adherence to preven- modification on blood pressure control:
2013 AHA/ACC guideline on lifestyle tive therapies for cardiovascular health? Main results of the premier clinical trial.
management to reduce cardiovascular Circulation 2011;124(11):1276–1282. JAMA 2003;289:2083–2093.
risk. A report of the American College of 20. Stuart-Shor EM, Berra KA, Kamau MW, 34. Blumenthal JA, Babyak MA, Hinderliter A,
Cardiology/American Heart Association et al. Behavioral strategies for cardiovas- et al. Effects of the DASH diet alone and
task force on practice guidelines. cular risk reduction in diverse and under- in combination with exercise and weight
Circulation 2014;129:S76–S99. served racial/ethnic groups. Circulation loss on blood pressure and cardiovascular
7. Rippe JM and Angelopoulos TA. 2012;125(1):171–184. biomarkers in men and women with high
The Role of Nutrition and Lifestyle 21. Eilat-Adar S, Sinai T, Yosefy C, et al. blood pressure: The ENCORE study. Arch.
in the Prevention and Treatment of Nutritional recommendations for cardio- Intern. Med. 2010;170:126–135.
Cardiovascular Disease. Nutrition in vascular disease prevent. Nutrients 2013 35. Hakala P and Karvetti RL. Weight
Lifestyle Medicine. New York, NY: Sep;5(9):3646–3683. reduction on lactovegetarian and mixed
Humana Press, 2017. 22. Perk J, de Backer G, Gohlke H, et al. diets: Changes in weight, nutrient intake,
8. McGuire S. Institute of Medicine. European guidelines on cardiovascular skinfold thicknesses and blood pressure.
2012. Accelerating Progress in Obesity disease prevention in clinical practice Eur. J. Clin. Nutr. 1989;43:421–430.
Prevention: Solving the Weight of (version 2012). The fifth joint task force 36. Barnard ND, Cohen J, Jenkins DJ, et al.
the Nation. Washington, DC: The of the European Society of Cardiology A low-fat vegan diet and a conventional
National Academies Press. Adv. Nutr. and other societies on cardiovascular diabetes diet in the treatment of type
2012;3:708–709. disease prevention in clinical practice 2 diabetes: A randomized, controlled,
9. Hubert HB, Feinleib M, McNamara (constituted by representatives of nine 74-wk clinical trial. Am. J. Clin. Nutr.
PM, et al. Obesity as an independent societies and by invited experts). Eur. 2009;89:1588S–1596S.
risk factor for cardiovascular disease: A Heart J. 2012;33:1635–1701. 37. Burke LE, Styn MA, Steenkiste AR,
26-year follow-up of participants in the 23. Hooper L, Summerbell CD, Thompson et al. Randomized clinical trial testing
Framingham Heart Study. Circulation R, et al. Reduced or modified dietary treatment preference and two dietary
1983;67:968–977. fat for preventing cardiovascular options in behavioral weight manage-
10. U.S. Department of Health and Human disease. Cochrane Database Syst. Rev. ment: Preliminary results of the impact of
Services. 2008 Physical Activity 2012;5:CD002137. diet at 6 months: PREFER study. Obesity
Guidelines for Americans. Washington, 24. de Oliveira Otto MC, Mozaffarian D, (Silver Spring) 2006;14:2007–2017.
DC: U.S. Department of Health and Kromhout D, et al. Dietary intake of 38. Burke LE, Hudson AG, Warziski MT,
Human Services, 2008. ODPHP saturated fat by food source and incident et al. Effects of a vegetarian diet and
Publication No. U0036. Available at: cardiovascular disease: The multi-ethnic treatment preference on biochemical and
http://www.health.gov/paguidelines. study of atherosclerosis. Am. J. Clin. Nutr. dietary variables in overweight and obese
Accessed April 25, 2017. 2012;96(2):397–404. Epub 2012/07/05. adults: A randomized clinical trial. Am. J.
11. Liu S, Stampfer MJ, Hu FB, et al. 25. Forouhi NG, Koulman A, Sharp SJ, et al. Clin. Nutr. 2007;86:588–596.
Whole-grain consumption and risk of Differences in the prospective association 39. Key TJ, Fraser GE, Thorogood M, et al.
coronary heart disease: Results from the between individual plasma phospholipid Mortality in vegetarians and non-vege-
Nurses’ health study. Am. J. Clin. Nutr. saturated fatty acids and incident type 2 tarians: A collaborative analysis of 8300
1999;70:3412–3419. diabetes: The EPIC-InterAct case-cohort deaths among 76,000 men and women
12. Stampfer MJ, Hu FB, Manson JE, et al. study. Lancet Diabetes Endocrinol. in five prospective studies. Public Health
Primary prevention of coronary heart dis- 2014;2(10):810–818. Epub 2014/08/12. Nutr. 1998;1:33–41.
ease in women through diet and lifestyle. 26. Nordmann AJ, Nordmann A, Briel M, et 40. Willcox DC, Willcox BJ, Todoriki H, et
N. Engl. J. Med. 2000;343:16–22. al. Effects of low-carbohydrate vs. low-fat al. The Okinawan diet: Health implica-
13. Ford ES, Ajani UA, Croft JB, et al. diets on weight loss and cardiovascular tions of a low-calorie, nutrient-dense,
Explaining the decrease in US deaths risk factors. A meta-analysis of random- antioxidant-rich dietary pattern low
from coronary disease, 1980–2000. N. ized controlled trials. Arch. Intern. Med. in glycemic load. J. Am. Coll. Nutr.
Engl. J. Med. 2007;356:2388–2398. 2006;166:285–293. 2009;28(Suppl):500S–516S.
14. American Dietetic Association. Position 27. Santos FL, Esteves SS, da Costa Pereira 41. Shimazu T, Kuriyama S, Hozawa A, et
of the academy of nutrition and dietet- A, et al. Systematic review and meta-anal- al. Dietary patterns and cardiovascular
ics: Use of nutritive and nonnutri- ysis of clinical trials of the effects of low disease mortality in Japan: A prospec-
tive sweeteners. J. Acad. Nutr. Diet. carbohydrate diets on cardiovascular risk tive cohort study. Int. J. Epidemiol.
2012;112:739–758. factors. Obes. Rev. 2012;13:1048–1066. 2007;36:600–609.
15. Millen BE, Abrams S, Adams-Campbell 28. Shai I, Schwarzfuchs D, Henkin Y, et al. 42. Heidemann C, Schulze MB, Franco
L, et al. The 2015 Dietary Guidelines Weight loss with a low-carbohydrate, OH, et al. Dietary patterns and risk of
Advisory Committee scientific report: mediterranean, or low-fat diet. N. Engl. mortality from cardiovascular disease,
Development and major conclusions. J. Med. 2008;359:229–241. cancer, and all causes in a prospective
Adv. Nutr. May 2016;7(3):438–444. 29. Vardavas CI, Linardakis MK, Hatzis CM, cohort of women. Circulation 2008 Jul
16. Gidding SS, Lichtenstein AH, Faith MS, et al. Cardiovascular disease risk factors 15;118(3):230–237.
et al. Implementing American Heart and dietary habits of farmers from Crete 43. Greger M. Plant-based diets for the
Association pediatric and adult nutrition 45 years after the first description of the prevention and treatment of disabling
guidelines: A scientific statement from Mediterranean diet. Eur. J. Cardiovasc. diseases. AJLM 2015;9(5):336–342.
the American Heart Association nutrition Prev. Rehabil. 2010;17:440–446. 44. Dauchet L, Amouyel P, Hercberg S, et
committee of the council on nutrition, 30. Sofi F, Abbate R, Gensini GF, et al. al. Fruit and vegetable consumption
physical activity and metabolism, council Accruing evidence about benefits of and risk of coronary heart disease: A
on cardiovascular disease in the young, adherence to the Mediterranean diet on meta-analysis of cohort studies. J. Nutr.
council on arteriosclerosis, thrombosis health: An updated systematic review 2006;136:2588–2593.
122 Chapter 8 Nutrition and Cardiovascular Disease
45. De Moura FF, Lewis KD, and Falk MC. 61. Sabaté J, Oda K, and Ros E. Nut con- alcohol consumption in patients with
Applying the FDA definition of whole sumption and blood lipid levels: A pooled cardiovascular disease. Circulation
grains to the evidence for cardiovas- analysis of 25 intervention trials. Arch. 2010;4:1951–1959.
cular disease health claims. J. Nutr. Intern. Med. 2010;170:821–827. 75. Corrao G, Bagnardi V, Zambon A, et al.
2009;139:2220S–2226S. 62. Mozaffarian D, Hao T, Rimm EB, et al. A meta-analysis of alcohol consumption
46. Prosky L. When is dietary fiber con- Changes in diet and lifestyle and long- and the risk of 15 diseases. Prev. Med.
sidered a functional food? Biofactors term weight gain in women and men. N. 2004;38:613–619.
2000;12:289–297. Engl. J. Med. 2011;364(25):2392–2404. 76. Goldberg IJ, Mosca L, Piano MR, et al.
47. Slavin JL. Position of the American 63. Teff KL, Grudziak J, Townsend RR, et al. AHA Science Advisory: Wine and your
Dietetic Association: Health implica- Endocrine and metabolic effects of con- heart: A science advisory for health-
tions of dietary fiber. J. Am. Diet. Assoc. suming fructose- and glucose-sweetened care professionals from the Nutrition
2008;108:1716–1731. beverages with meals in obese men and Committee, Council on Epidemiology and
48. Brown L, Rosner B, Willett WW, et al. women: Influence of insulin resistance Prevention, and Council on Cardiovascular
Cholesterol-lowering effects of dietary on plasma triglyceride responses. J. Clin. Nursing of the American Heart Association.
fiber: A meta-analysis. Am. J. Clin. Nutr. Endocrinol. Metab. 2009;94(5):1562– Circulation 2001;103:472–475.
1999;69:30–42. 1569. Epub 2009/02/12. 77. Cornelis MC and El-Sohemy A. Coffee,
49. Expert Panel on Detection, Evaluation, 64. Antar MA, Little JA, Lucas C, et al. caffeine, and coronary heart disease.
and Treatment of High Blood Cholesterol Interrelationship between the kinds of Curr. Opin. Lipidol. 2007;18:13–19.
in Adults. Executive summary of the dietary carbohydrate and fat in hyperlipo- 78. De Koning Gans JM, Uiterwaal CS, van
third report of the National Cholesterol proteinemic patients. 3. Synergistic effect der Schouw YT, et al. Tea and coffee
Education Program (NCEP) expert panel of sucrose and animal fat on serum lipids. consumption and cardiovascular morbid-
on detection, evaluation, and treat- Atherosclerosis 1970;11(2):191–201. ity and mortality. Arterioscler. Thromb.
ment of high blood cholesterol in adults Epub 1970/03/01. Vasc. Biol. 2010;30:1665–1671.
(Adult Treatment Panel III). JAMA 65. Sievenpiper JL, Tappy L, and Brouns 79. Muley A, Muley P, and Shah M. Coffee
2001;285:2486–2497. F. Fructose as a driver of diabetes: An to reduce risk of type 2 diabetes? A
50. Marlett JA, McBurney MI, Slavin JL, incomplete view of the evidence. Mayo systematic review. Curr. Diabetes Rev.
et al. Position of the American Dietetic Clin. Proc. 2015;90(7):984–988. 2012;8:162–168.
Association: Health implications of 66. Kaiser KA, Shikany JM, Keating KD, 80. Kuriyama S. The relation between green
dietary fiber. J. Am. Diet. Assoc. et al. Will reducing sugar-sweetened tea consumption and cardiovascular
2002;102:993–1000. beverage consumption reduce obesity? disease as evidenced by epidemiological
51. Food and Drug Administration, HHS. Evidence supporting conjecture is strong, studies. J. Nutr. 2008;138:1548S–1553S.
Food labeling: Health claims; soluble but evidence when testing effect is weak. 81. Wang ZM, Zhou B, Wang YS, et al.
fiber from certain foods and risk of Obes. Rev. 2013;14(8):620–633. Black and green tea consumption and
coronary heart disease. Interim final rule. 67. Johnson R, Appel L, Brands M, et al. the risk of coronary artery disease:
Fed. Regist. 2008;25:9938–9947. American heart association nutrition A meta-analysis. Am. J. Clin. Nutr.
52. Leaf A, Kang JX, Xiao YF, et al. committee of the council on nutrition, 2011;93:506–515.
Clinical prevention of sudden cardiac physical activity, and metabolism and the 82. Deka A and Vita JA. Tea and cardiovascu-
death by n-3 polyunsaturated fatty council on epidemiology and prevention. lar disease. Pharmacol. Res. 2011;64:36–
acids and mechanism of prevention of Dietary sugars intake and cardiovascular 145. doi: 10.1016/j.phrs.2011.02.008
arrhythmias by n-3 fish oils. Circulation health: A scientific statement from the 83. Kritchevsky SB and Kritchevsky D. Egg
2003;107:2646–2652. American Heart Association. Circulation consumption and coronary heart disease:
53. Wang C, Harris WS, Chung M, et al. n-3 2009;120:1011–1020. An epidemiologic overview. J. Am. Coll.
Fatty acids from fish or fish-oil supplements, 68. Rule document issued by the Food and Nutr. 2000;19:549S–555S.
but not α-linolenic acid, benefit cardiovas- Drug Administration (FDA). Food 84. Jones PJ. Dietary cholesterol and the risk
cular disease outcomes in primary- and Labeling: Revision of the Nutrition and of cardiovascular disease in patients: A
secondary-prevention studies: A systematic Supplement Facts Labels. May 27, 2016. review of the Harvard Egg Study and
review. Am. J. Clin. Nutr. 2006;84:5–17. Docket ID: FDA-2012-N-1210-0875. other data. Int. J. Clin. Pract. Suppl.
54. Brufau G, Boatella J, and Rafecas M. Available at: https: //www.regu lations.g 2009;63:28–36.
Nuts, source of energy and macronutri- ov/document?D=FDA-2012-N-1210- 0875 85. Ackermann RT, Mulrow CD, Ramirez G,
ents. Br. J. Nutr. 2006;96:S24–S28. 69. Rippe J. Sievenpiper J, Le K-A, et al. et al. Garlic shows promise for improving
55. Sabaté J and Ang Y. Nuts and health out- What is the appropriate upper limit some cardiovascular risk factors. Arch.
comes: New epidemiologic evidence. Am. for sugars consumption? Nutr. Rev. Intern. Med. 2001;161:813–824.
J. Clin. Nutr. 2009;89:1643S–1648S. 2017;75(1):18–36. 86. Ding EL, Hutfless SM, Ding X, et al.
56. Mente A, de Koning L, Shannon HS, et 70. US Department of Agriculture, Economic Chocolate and prevention of cardiovas-
al. A systematic review of the evidence Research Service. Calories Average Daily cular disease: A systematic review. Nutr.
supporting a causal link between dietary per Capita Calories from the US Food Metab. (Lond.) 2006;3:3–2.
factors and coronary heart disease. Arch. Supply, Adjusted for Spoilage and other 87. He FJ and MacGregor GA. Effect of
Intern. Med. 2009;169:659–669. Waste. Loss-Adjusted Food Availability modest salt reduction on blood pressure:
57. Micha R, Wallace S, and Mozaffarian Documentation. Available at: http://www A meta-analysis of randomized trials:
D. Red and processed meat consumption .ers.usda.gov/data-products/food-availab Implications for public health. J. Hum.
and risk of incident coronary heart dis- ility-(per-capita)-data-system/loss-adju Hypertens. 2002;16:761–770.
ease, stroke, and diabetes: A systematic sted-foodavailability-documentation.aspx 88. Taylor RS, Ashton KE, Moxham T, et
review and meta-analysis. Circulation . Updated August 24, 2016. Accessed al. Reduced dietary salt for the preven-
2010;121:2271–2283. October 5, 2016. tion of cardiovascular disease. Cochrane
58. Jakobsen MU, O’eilly EJ, Heitmann 71. Marmoy M and Brunner E. Alcohol and Database Syst. Rev. 2011;7:CD009217.
BL, et al. Major types of dietary fat and cardiovascular disease: The status of the 89. IOM Committee Report on Sodium
risk of coronary heart disease: A pooled U-shaped curve. BMJ 1991;303:565–568. Intake in Populations. [(Accessed on 25
analysis of 11 cohort studies. Am. J. Clin. 72. Ronksley PE, Brien SE, Turner BJ, et al. August 2013)]. Available at: http://www
Nutr. 2009;89:1425–1432. Association of alcohol consumption with .iom.edu/Reports /2013/Sodium-Intake
59. Miller ER, Erlinger TP, and Appel LJ. selected cardiovascular disease outcomes: -in-Populations-Assessment-of-Evidence.a
The effects of macronutrients on blood A systematic review and meta-analysis. spx. Accessed on 24 April 2017.
pressure and lipids: An overview of the BMJ 2011;342:d671. 90. Mozaffarian D, Fahimi S, Singh GM, et
DASH and OmniHeart trials. Curr. 73. Mukamal KL, Maclure M, Muller JE, al. Global sodium consumption and death
Atheroscler. Rep. 2006;8:460–465. et al. Binge drinking and mortality after from cardiovascular causes. N. Engl. J.
60. Al-Solaiman Y, Jesri A, Mountford WK, acute myocardial infarction. Circulation Med. 2014;371(7):624–634.
et al. DASH lowers blood pressure in 2005;112:3839–3845. 91. O’Donnell M, Mente A, and Yusuf S.
obese hypertensives beyond potassium, 74. Costanzo S, di Castelnuovo A, Sodium and cardiovascular disease. N.
magnesium and fibre. J. Hum. Hypertens. Donati MB, et al. Cardiovascular and Engl. J. Med. 2014;371(22):2137–2138.
2009;24:237–246. overall mortality risk in relation to Epub 2014/11/27.
References 123
92. Holick MF. Evidence-based d-bate on diabetes mellitus in U.S. men. Ann. Intern. 103. Howard BV, Ruotolo G, and Robbins DC.
health benefits of Vitamin D revisited. Med. 2002;136:201–209. Obesity and dyslipidemia. Endocrinol.
Dermato-Endocrinology 2012;4:83–90.
93. Bjelakovic G, Nikolova D, Gluud LL,
et al. Antioxidant supplements for
98. Rippe J and Angelopoulos T. Obesity
and Heart Disease. In Rippe JM and
Angelopoulos TA (eds). Obesity:
Metab. Clin. North Am. 2003;32:855–867.
104. Chobanian AV, Bakris GL, Black HR,
et al. The seventh report of the joint
8
prevention of mortality in healthy Prevention and Treatment. Boca Raton, national committee on prevention,
participants and patients with various FL: CRC Press, 2012. detection, evaluation, and treatment of
diseases. Cochrane Database Syst. Rev. 99. Rashid MN, Fuentes F, Touchon RC, et high blood pressure: The JNC 7 Report.
2012;3:CD007176. al. Obesity and the risk for cardiovascu- JAMA 2003;289(19):2560–2572. Epub
94. Knoops KT, de Groot LC, Kromhout lar disease. Prev. Cardiol. 2003;6:42–47. 2003/05/16.
D, et al. Mediterranean diet, life- 100. Stone NJ, Robinson JG, Lichtenstein AH, 105. James PA, Oparil S, Carter BL, et al.
style factors, and 10-year mortal- et al. 2013 ACC/AHA guideline on the 2014 evidence-based guideline for
ity in elderly European men and treatment of blood cholesterol to reduce the management of high blood pres-
women: The HALE project. JAMA atherosclerotic cardiovascular risk in sure in adults: Report from the panel
2004;292:1433–1439. adults: A report of the American College members appointed to the Eighth Joint
95. Appel LJ, Moore TJ, Obarzanek E, et al. of Cardiology/American Heart Association National Committee (JNC 8). JAMA
A clinical trial of the effects of dietary task force on practice guidelines. Circulation 2014;311(5):507–520. Epub 2013/12/20.
patterns on blood pressure. DASH collab- 2014;129(25 Suppl 2):S1–S45. Epub 106. Office on Smoking and Health. The Health
orative research group. N. Engl. J. Med. 2013/11/14. Consequences of Smoking: A Report of
1997;336:1117–1124. 101. Miller M, Stone NJ, Ballantyne C, et the Surgeon General. Atlanta, GA: US
96. Appel LJ, Sacks FM, Carey VJ, et al. al. Triglycerides and cardiovascular Department of Health and Human Services,
The effects of protein, monounsaturated disease a scientific statement from the Centers for Disease Control and Prevention,
fat, and carbohydrate intake on blood American Heart Association. Circulation National Center for Chronic Disease
pressure and serum lipids: Results of the 2011;123:2292–2333. Prevention and Health Promotion, 2004.
OmniHeart randomized trial. JAMA 102. Wilson PW and Grundy SM. The meta- 107. Jha P, Ramasundarahettige C, Landsman V,
2005;294:2455–2464. bolic syndrome: A practical guide to ori- et al. 21 st-century hazards of smoking and
97. van Dam RM, Rimm EB, Willett WC, et gins and treatment: Part II. Circulation benefits of cessation in the United States.
al. Dietary patterns and risk for type 2 2003;108:1537–1540. N. Engl. J. Med. 2013;368:341–350.
9
CHAPTER
125
126 Chapter 9 Optimal Nutrition Guidance for Older Adults
years of age to 1200 mg/day for both females and males advance in years. In general, with increasing years total
above the age of 70 years of age.16 The DRIs for vitamin B6 energy needs decrease to compensate for diminished
increased from 1.3 mg/day and 1.4 mg/day for females and requirements associated with lower levels of physical
males, respectively, between 51 and 70 years of age to 1.5 activity, a higher proportion of fat mass relative to lean
mg/day and 1.7 mg/day, respectively, for both females and muscle mass, and a lower basal metabolic rate.18,19 Similar
males above the age of 70 years.9 Emerging evidence sug- or slightly higher nutrient needs must be met within the
gests future revisions in the DRIs for individuals over the context of reduced food intake, and commensurate with
age of 70 years may be necessary,17 but any recommenda- lower energy requirements. This can be accomplished by
tions must await a thorough review of the new literature. intentionally selecting nutrient-dense foods (high nutrient
Although the DRIs for most nutrients do not increase content per calorie). An icon summarizing salient points
with advancing age, with the exceptions of vitamin D, related to dietary modification for older adults has been
calcium, and vitamin B6, it can become increasingly dif- developed to provide specific guidance, termed MyPlate
ficult to achieve the recommended intakes as individuals for Older Adults (Figure 9.2). Differences from the
MyPlate Food Guide for the general population include blood clotting, muscle contraction, and nerve function.
9
examples that emphasize nutrient-dense foods within each The richest naturally occurring and bioavailable source
category, illustrations of foods that are particularly con- of calcium is dairy products. A wide range of low-fat
venient for older adults (e.g., bags of frozen vegetables), and nonfat dairy products are currently available. There
shift of the dairy group into the protein segment to pro- are two factors to take into consideration when recom-
vide a broader range of protein-rich food options, greater mending dairy products to older adults. The first is lac-
emphasis on fluid by depicting a variety of choices in a tose intolerance. With increasing age, the rate of lactose
separate segment, incorporation of suggestions for regular intolerance increases. 29–31 Fortunately, a wide range
physical activity as an integral part of the icon, addition of lactose-free and low-lactose dairy products are now
of a segment at the center of the plate to emphasize the available, as well as enzyme preparations (lactase) that
importance of including healthy oils in the diet and using can be taken when consuming foods containing lactose to
seasonings (spices and herbs) as an alternative to salt, and decrease the symptoms of lactose intolerance. Although
knife and fork on the side of the plate to encourage a focus the prevalence of lactose intolerance increases with age,
on enjoying food when eating rather than focusing atten- intolerance symptoms among lactose maldigesters tend
tion on a hand-held device. 20 to decrease with age, suggesting that as people get older
they may have more, rather than less, flexibility in their
choice of calcium-rich dairy foods. 30 The second consid-
9.3 NUTRIENTS OF CONCERN eration with regard to dairy products is saturated fat.
Dairy products can be a major source of saturated fat.
Adequacy of some nutrients can be a concern for all adults, Saturated fat intake is associated with an increased risk
particularly older adults. “Nutrients of public health con- of developing cardiovascular disease. 32,33 Older adults
cern” are divided into two categories—those of concern due should be encouraged to take advantage of reduced-fat
to overconsumption and those of concern due to undercon- versions of dairy foods and incorporate sources of unsat-
sumption. The criteria used by the 2015 Dietary Guidelines urated fat, such as soybean and canola oils, as alternative
Advisory Committee to identify nutrients of public health fats in their diets. Additional sources of dietary calcium
concern are that population intakes are below or above are fortified drinks such as calcium-fortified orange juice
the estimated average requirement or adequate intake and and soy milk.
there is corroborating evidence of low or high intakes on
the basis of biochemical markers of nutrient status. Current
nutrients of public health concern for underconsumption 9.3.3 Potassium
are vitamin D, calcium, potassium, fiber, and iron (not a
concern for older adults); for overconsumption, nutrients Potassium functions as a critical electrolyte in the body,
of concern are sodium and saturated fat. along with sodium, chloride, calcium, and magnesium. It
is also involved with proper heart function and skeletal
and smooth muscle contraction. Rich dietary sources of
9.3.1 Vitamin D potassium include fish and plant foods inlcuding legumes,
vegetables, and fruits. Higher fruit and vegetable intakes
Adequate vitamin D intake is of concern for older adults.21 have been associated with a number of positive health out-
There are a number of factors that may compromise their comes, including bone health, blood pressure, metabolic
vitamin D status with advancing years. These include syndrome, stroke, and cardiovascular disease.34–43
decreased efficiency of skin to synthesize vitamin D after
exposure to sunlight and the tendency to spend less time
outdoors to accumulate sun exposure.22 Limited sun expo-
sure due to latitude or concern about sun exposure because
9.3.4 Fiber
of skin cancer risk can minimize endogenous vitamin D A major function of dietary fiber is its laxative effect in
synthesis.23,24 Additionally, overweight and obese individu- the gut. Whole vegetables and fruits are a good source of
als tend to have lower circulating vitamin D concentrations, dietary fiber, as are whole grains and whole grain prod-
potentially due to sequestration in the adipose tissue. As ucts. For this reason, older adults should be encouraged to
rates of overweight and obesity increase in the older popu- consume fruits and vegetables in their natural state rather
lation,18,25 this factor may also contribute to compromised than the juice form. They should also be encouraged to
vitamin D status.26 Up until recently, fluid milk was the only choose whole grain products rather than refined and pro-
reliable food source of vitamin D in the United States.21 cessed grain products such as those commonly available
Recent changes to the vitamin D fortification regulation in large food markets. In general, fiber supplements are
have resulted in an increased availability of vitamin D- not routinely recommended because excessive fiber can
and calcium-fortified juices and juice drinks, and vitamin decrease the bioavailability of calcium, iron, zinc, copper,
D-fortified dairy products other than fluid milk.27,28 and magnesium.44
9.3.2 Calcium 9.3.5 Sodium
The vast majority of calcium in the body resides in bone Under normal circumstances, small amounts of dietary
and teeth. Much smaller but no less important amounts sodium, along with potassium, help maintain normal
of calcium are critical for the regulation of cell signaling, blood pressure as well as muscle and nerve function.
128 Chapter 9 Optimal Nutrition Guidance for Older Adults
9.4.2 Taste and Smell can decrease preparation and cooking times, and is adapt-
9
able to preparation of individual small portions. Older
Retaining the desire to eat a variety of foods is integral to adults may not automatically take advantage of newer
ensuring optimal nutrition for older adults. This issue is forms of common food items (e.g., prewashed greens, pre-
of particular concern because diminished taste and smell- cut fruit, shredded cheese) and require some regular guid-
ing acuity associated with aging can lead to poor appetite. ance in this area.
This change includes loss of taste bud acuity, primarily
with respect to salty and sweet food items, and a resulting
greater sensitivity to acid and bitter food items.48 Other
changes frequently observed in older adults include a
9.4.4 Social Factors
diminished sense of smell. Older adults with poor odor In addition to declines in physical capacity associated
perception have lower nutrient intakes than those with with the aging process, there are also changes in the social
good odor perception.49–51 environment of older adults that can have an impact on
nutritional status (Table 9.3). With increasing years, the
loss of a spouse or other family members with whom an
9.4.3 Vision, Dexterity, and Mobility individual shared and prepared meals is common. This
can lead to social isolation, especially during mealtime,
Diminished vision, dexterity, and mobility can make and diminished desire to prepare well-balanced and var-
food acquisition and preparation difficult, which can ied meals. Due to deterioration in mental or economic sta-
severely alter the variety and quality of foods consumed tus, older adults are frequently faced with having to adapt
(Table 9.2). Difficulty opening jars, cans, or packaged to a new living environment. This can result in dramatic
foods due to arthritis or diminished strength can lead to changes in meal times, food preparation, and foods avail-
decreased variety and ability to consume preferred foods. able. The onset of chronic disease can further limit food
Small accommodations in an individual’s environment choices and make older adults susceptible to the lures of
such as ergonomically designed kitchen aids (e.g., can food fads or dietary supplements promising a fountain
openers and scissors), kitchen reorganization (e.g., elimi- of youth. Succumbing to these claims can drain scarce
nating clutter and moving frequently used items to most resources from food purchases and result in overconsump-
accessible places), and shifts to the use of partially pre- tion of individual nutrients. The latter can interfere with
pared foods can minimize a decline in diet quality. For prescription drug actions or the utilization of essential
example, resealable bags of frozen vegetables and fruits nutrients. Depression frequently accompanies the aging
are particularly good choices for older adults because process in individuals without adequate support to make
they allow for easy apportioning of single or double serv- the necessary adaptations that come with advancing age.
ings, minimize pre-preparation (which can be difficult or
even painful with advanced years), eliminate waste due
to spoilage, reduce the need for frequent trips to the mar- TABLE 9.3 Psychosocial factors contributing to
ket, and provide variety during long periods of inclement compromised food intake in older adults
weather. Likewise, purchasing boneless chicken breasts
Factor Change
Companionship ↑ Loss of spouse
TABLE 9.2 Activity of daily life factors that may contribute
to compromised food intake in older adults ↑ Social isolation
Factor Change ↑ Loss of companions
Oral cavity ↑ Peritoneal disease ↓ Social interaction secondary to ↓ mobility
↑ Ill-fitting dentures Mental State ↑ Depression
↓ Salivary gland secretions ↑ Mental deterioration (dementia)
Mobility ↓ Physical activity ↑ Alcoholism
↓ Respiratory capacity ↑ Loneliness
↓ Lean muscle mass (strength, physical disability) ↑ Chronic disease
↑ Physical isolation Economic ↑ Fixed income (poverty)
Senses ↓ Acuity (taste, smell, sight) ↓ Choice and availability
Dexterity ↑ Arthritic involvement finger and hand joints ↓ Quantity needs
↑ Tremor ↓ Variety
↓ Manual dexterity Nutrition ↑ Susceptibility to food fads
knowledge
Energy ↓ Energy requirements ↑ Susceptibility to nutrient supplement claims
needs
↓ Caloric intake Housing ↑ Change in status (loss of home)
↓ Volume ↓ Independence
130 Chapter 9 Optimal Nutrition Guidance for Older Adults
Older adults are also at increased risk of alcohol abuse. All lifetime risk of experiencing an osteoporotic fracture over
of these factors may contribute to poor food consumption the age of 50 is 27%.61 Age-associated bone loss is attrib-
patterns. 52 uted to diminished estrogen production, decreased cal-
cium absorption from the gastrointestinal tract, decreased
calcium resorption by the kidney, decreased rates of
9.5 PHYSIOLOGICAL CHANGES OF physical activity, compromised vitamin D status, and
decreased calcitriol production secondary to hyperpara-
CONCERN IN OLDER ADULTS thyroidism.61,62 In older adults, calcium balance is favor-
ably affected by vitamin D intake and negatively affected
Nutrient-related chronic diseases particularly prevalent by high sodium, protein, alcohol, and caffeine intakes.62
in middle and later years include cardiovascular disease, Supplemental calcium and vitamin D in postmenopausal
cancer, type 2 diabetes, hypertension, osteoporosis, dis- women living in northern latitudes (42°N) may minimize
orders of dentition and associated senses, and declines bone loss.63 Because serum osteocalcin, calcidiol, and vita-
in immune function. In some cases, the goals of nutrient min D fluctuate seasonally due to sun exposure, vitamin
recommendations for older adults are aimed at delaying D intake is particularly important during the period of
the onset of chronic disease, while in other cases they are winter and spring in this group. These data strongly sup-
intended to treat or accommodate the disorder. port routinely screening older adults for vitamin D status.
9.5.3 Osteoporosis
Age-related or type II osteoporosis (bone loss) is positively
9.5.7 Cancer
associated with the aging process. Osteoporosis is esti- The incidence of cancer shows tremendous variability on
mated to affect 200 million women worldwide—approxi- the basis of worldwide distribution, type, and site in the
mately one-tenth of women aged 60, one-fifth of women body. The incidence of all types of cancer increases with
aged 70, two-fifths of women aged 80, and two-thirds of age. Support for a diet/cancer incidence link comes from
women aged 90.61 In men, it is estimated that the residual data suggesting associations between markedly divergent
References 131
food consumption patterns and incidence rates of cancer relationship between the nutrient quality of the diet and
9
among different population groups.72 Some data have been survival rates. Due to decreased levels of physical activ-
reported for associations involving the following dietary ity, decreased metabolic rates, and increased proportions
component: alcohol intake (laryngeal), calcium and vita- of fat to lean muscle mass, energy requirements decline
min D intake (stomach, colon, breast), fat intake (breast, with advancing years, yet nutrient requirements remain
colon, prostate), fiber intake (breast), and antioxidant unchanged or increase. This situation requires a greater
vitamin and/or orange and dark green vegetable intake— emphasis on choosing nutrient-dense foods within each
vitamin A and beta-carotene, vitamin C, vitamin E, food category. Special attention needs to be given to
and trace elements (wide range of sites).72–76 Results from adapting living environments with advancing years to
randomized controlled trials are limited.77 At this time, retain the ability to acquire and prepare food. Changes in
the general dietary guidance to reduce cancer risk is con- social situations that could impact on food intake should
sistent with the dietary guidance to prevent the onset of be monitored on a regular basis. Evidence suggests that
chronic diseases of concern in the twenty-first century. diet and lifestyle interventions can forestall the onset of
cardiovascular disease, osteoporosis, diabetes, hyperten-
sion, immune function, and possibly some types of cancer.
9.6 CONCLUSIONS There are no data to suggest a person is too old to benefit
from improvements in diet quality. The definitions for old
The aim of dietary guidance specifically targeted for age and expectations for the period of time individuals
older adults is to maintain optimal health and forestall can remain active, productive, and live independently are
the onset of chronic disorders. The actual dietary recom- expanding. Efforts toward improving diet quality and lev-
mendations, for the most part, are consistent throughout els of physical activity with advancing years should keep
the adult life cycle. Evidence suggests that there is a direct up with this trend.
CLINICAL APPLICATIONS
• The major goal of dietary guidance specifically targeted for older adults is to maintain optimal health and forestall the onset of
chronic disorders.
• Diet quality is directly related to physical and cognitive functioning in later years. The adoption of healthy lifestyle practices should
be encouraged.
• Nutrient requirements either stay the same or increase with advancing years, whereas energy requirements decrease. Attention
needs to be given to ensuring adequate nutrient intake and avoiding excess energy intake.
• Advancing years is often accompanied by declines in sensory perception such as taste, smell, vision and dexterity, and mobility.
Such alterations may necessitate added attention to dietary behaviors in older adults.
• Special attention should be given to adapting living environments with advancing years to retain the ability to acquire and prepare
food.
REFERENCES
1. de Groot LC, van Staveren WA, 6. Studenski S, Perera S, Patel K, Rosano 12. IOM. Dietary Supplements: A
Burema J. Survival beyond age 70 in C, Faulkner K, Inzitari M, et al. Gait Framework for Evaluating Safety.
relation to diet. Nutrition Reviews speed and survival in older adults. JAMA Committee on the Framework for
1996;54(7):211–212. 2010;305(1):50–58. Evaluating the Safety of Dietary
2. Sahyoun NR, Jacques PF, Russell RM. 7. IOM. How Should the Recommended Supplements. National Academy of
Carotenoids, vitamins C and E, and Dietary Allowances Be Revised? Sciences, Washington, DC, 2004.
mortality in an elderly population. National Academy of Sciences, 13. IOM. Dietary Reference Intakes:
American Journal of Epidemiology Washington, DC, 1994. Energy, Carbohydrate, Fiber, Fat, Fatty
1996;144(5):501–511. 8. IOM. Dietary Reference Intakes: Acids, Cholesterol, Protein and Amino
3. Houston DK, Johnson MA, Daniel TD, Calcium, Phosphorus, Magnesium, Acids. National Academy of Sciences,
Poon LW. Health and dietary character- Vitamin D and Fluoride. National Washington, DC, 2005.
istics of supplement users in an elderly Academy of Sciences, Washington, DC, 14. IOM. Dietary Reference Intakes, Water,
population. International Journal 1997. Potassium, Sodium, Chloride and
for Vitamin and Nutrition Research 9. IOM. Dietary Reference Intakes: Thiamin, Sulfate. National Academy of Sciences,
1997;67(3):183–191. Riboflavin, Niacin, Vitamin B6, Folate, Washington, DC, 2005.
4. Anderson AL, Harris TB, Tylavsky FA, Vitamin B12, Pantothenic Acid, Biotin and 15. Otten JJ, Hellwig JP, Linda DM, IOM.
Perry SE, Houston DK, Hue TF, et al. Choline. National Academy of Sciences, Dietary Reference Intakes: The Essential
Dietary patterns and survival of older Washington, DC, 1998. Guide to Nutrient Requirements.
adults. Journal of the American Dietetic 10. IOM. Dietary Reference Intakes: National Academy of Sciences,
Association 2010;111(1):84–91. Vitamin C, Vitamin E, Selenium and Washington, DC, 2006.
5. Blain H, Carriere I, Sourial N, Berard Carotenoids. National Academy of 16. IOM. Dietary Reference Intakes for
C, Favie F, Colvez A, et al. Balance and Sciences, Washington, DC, 2000. Calcium and Vitamin D. http://www
walking speed predict subsequent 8-year 11. IOM. Dietary Reference Intakes: Vitamin iomedu /Reports/2010/ Dietar y-Referen
mortality independently of current and A, Vitamin K, Arsenic, Boron, Chromium, ce-Intakes-for-Calciu m-and-Vita min-
intermediate events in well-functioning Copper, Iodine, Iron, Manganese, Daspx, 2010.
women aged 75 years and older. Molybdenum, Nickel, Silicon, Vanadium 17. Wolfe RR, Miller SL, Miller KB. Optimal
Journal of Nutrition and Health Aging and Zinc. National Academy of Sciences, protein intake in the elderly. Clinical
2010;14:595–600. Washington, DC, 2001. Nutrition 2008;27(5):675–684.
132 Chapter 9 Optimal Nutrition Guidance for Older Adults
18. Williamson DF. Descriptive epidemiol- of the American College of Cardiology/ 45. Malik VS, Pan A, Willett WC, Hu FB.
ogy of body weight and weight change in American Heart Association Task Sugar-sweetened beverages and weight
U.S. adults. Annals of Internal Medicine Force on Practice Guidelines. Journal gain in children and adults: A system-
1993;119(7 Pt 2):646–649. of the American College of Cardiology. atic review and meta-analysis. The
19. Bruins MJ, Van Dael P, Eggersdorfer M. 2014;63(25 Pt B):2889–2934. American Journal of Clinical Nutrition
The role of nutrients in reducing the risk 34. Sacks FM, Svetkey LP, Vollmer 2013;98(4):1084–1102.
for noncommunicable diseases during WM, Appel LJ, Bray GA, Harsha 46. Byrd D and Russell RM. Malabsorption
aging. Nutrients. 2019 Jan 4;11(1). D, et al. Effects on blood pres- in an elderly patient. Gastroenterologist
20. Lichtenstein AH, Rasmussen H, Yu sure of reduced dietary sodium and 1993;1(4):287–290.
WW, Epstein SR, Russell RM. Modified the Dietary Approaches to Stop 47. Hoffman N. Diet in the elderly. Needs
MyPyramid for older adults [Erratum Hypertension (DASH) diet. DASH- and risks. The Medical Clinics of North
appears in J Nutr. 2008 Jul;138(7):1400]. Sodium Collaborative Research Group. America 1993;77(4):745–756.
Journal of Nutrition 2008;138(1):5–11. New England Journal of Medicine 48. Lipson LG, Bray GA. Nutritional Aspects
21. Moore C, Murphy MM, Keast DR, 2001;344(1):3–10. of Aging, Vol. I, ed. L. H. Chen. CRC
Holick MF. Vitamin D intake in 35. Panagiotakos DB, Pitsavos C, Skoumas Press Inc., Boca Raton, FL, 1986.
the United States. Journal of the Y, Stefanadis C. The association 49. Griep MI, Collys K, Mets TF, Slop D,
American Dietetic Association between food patterns and the metabolic Laska M, Massart DL. Sensory detec-
2004;104(6):980–983. syndrome using principal components tion of food odour in relation to dental
22. MacLaughlin J, Holick MF. Aging analysis: The ATTICA study. Journal status, gender and age. Gerodontology
decreases the capacity of human skin to of the American Dietetic Association 1996;13(1):56–62.
produce vitamin D3. Journal of Clinical 2007;107(6):979–987. 50. Griep MI, Verleye G, Franck AH,
Investigation 1985;76(4):1536–1568. 36. Perez-Cornago A, Travis RC, Appleby Collys K, Mets TF, Massart DL.
23. Holick MF. Sunlight and vitamin D PN, Tsilidis KK, Tjønneland A, Olsen Variation in nutrient intake with dental
for bone health and prevention of A, et al. Fruit and vegetable intake and status, age and odour perception.
autoimmune diseases, cancers, and prostate cancer risk in the European European Journal of Clinical Nutrition
cardiovascular disease. American Prospective Investigation into Cancer and 1996;50(12):816–825.
Journal of Clinical Nutrition 2004;80(6 Nutrition (EPIC). International Journal 51. Griep MI, Mets TF, Collys K, Ponjaert-
Suppl):1678S–1688S. of Cancer 2017;141(2):287–297. Kristoffersen I, Massart DL. Risk
24. Holick MF. Vitamin D deficiency. 37. Takachi R, Inoue M, Sugawara Y, Tsuji of malnutrition in retirement homes
New England Journal of Medicine I, Tsugane S, Ito H, et al. Research elderly persons measured by the “mini-
2007;357(3):266–281. Group for the Development and evalu- nutritional assessment”. Journal of
25. Jensen GL. Obesity among older persons: ation of cancer prevention strategies in Gerontology A: Biological Sciences and
Screening for risk of adverse outcomes. Japan. Fruit and vegetable intake and Medical Sciences 2000;55(2):M57–M63.
The Journal of Nutrition and Health the risk of overall cancer in Japanese: 52. James WP, Nelson M, Ralph A, Leather
Aging 2006;10(6):510–521; discussion A pooled analysis of population-based S. Socioeconomic determinants of health.
21–22. cohort studies. Journal of Epidemiology. The contribution of nutrition to inequali-
26. Wortsman J, Matsuoka LY, Chen TC, 2017;27(4):152–162. ties in health. British Medical Journal
Lu Z, Holick MF. Decreased bio- 38. Erkkila AT, Booth SL, Hu FB, Jacques 1997;314(7093):1545–1549.
availability of vitamin D in obesity. PF, Lichtenstein AH. Phylloquinone 53. Papas AS, Joshi A, Giunta JL, Palmer
American Journal of Clinical Nutrition intake and risk of cardiovascular CA. Relationships among education,
2000;72(3):690–693. diseases in men. Nutrition Metabolism dentate status, and diet in adults. Special
27. FDA. Food additives permitted for & Cardiovascular Diseases Care in Dentistry 1998;18(1):26–32.
direct addition to food for human 2007;17(1):58–62. 54. Papas AS, Palmer CA, Rounds MC,
consumption; vitamin D3 and fruit 39. Dietary Guidelines for Americans. http: Russell RM. The effects of denture status
juices and juice drinks. Federal Register //www.cnpp.usda.gov/DGAs2010-D on nutrition. Special Care in Dentistry
2003;69:9000–9003. GACReport.htm, 2010. 1998;18(1):17–25.
28. FDA. Food additives permitted for direct 40. Steffen LM, Folsom AR, Cushman M, 55. Papas AS, Joshi A, Palmer CA, Giunta
addition to food for human consumption; Jacobs DR, Jr., Rosamond WD. Greater JL, Dwyer JT. Relationship of diet to
vitamin D3 and meal replacement bars, fish, fruit, and vegetable intakes are root caries. American Journal of Clinical
other type bars and soy-protein based related to lower incidence of venous Nutrition 1995;61(2):423S–429S.
meal replacement beverages. Federal thromboembolism: The longitudinal 56. NIDDK. NIH Publication No. 07-2754.
Register 2005;70:37255–37258. investigation of thromboembolism etiol- National Digestive Diseases Information
29. Lovelace HY, Barr SI. Diagnosis, symp- ogy. Circulation 2007;115(2):188–195. Clearinghouse. http://digestive.nidd k.ni
toms, and calcium intakes of individuals 41. Scarborough P, Rayner M, van Dis I, h.gov/ddiseases/pubs/constipation/20 07,
with self-reported lactose intolerance. Norum K. Meta-analysis of effect of July 2007.
Journal of the American College of saturated fat intake on cardiovascu- 57. AHA Centers for Health Metrics and
Nutrition 2005;24(1):51–57. lar disease: Over adjustment obscures Evaluation. Heart Disease and Stroke
30. Di Stefano M, Veneto G, Malservisi true associations. American Journal of Statistics 2018. https://healthmetrics.
S, Strocchi A, Corazza GR. Clinical Nutrition 2010;92(2):458–459; heart.org/at-a-glance-heart-disease-and-
Lactose malabsorption and intoler- author reply 9. stroke-statistics-2018/
ance in the elderly. Scandinavian 42. Pearson-Stuttard J, Bandosz P, Rehm 58. Jakobsen MU, O’Reilly EJ, Heitmann
Journal of Gastroenterology CD, Penalvo J, Whitsel L, Gaziano BL, Pereira MA, Balter K, Fraser
2001;36(12):1274–1278. T, et al. Reducing US cardiovascular GE, et al. Major types of dietary fat
31. Goulding A, Taylor RW, Keil D, Gold disease burden and disparities through and risk of coronary heart disease: A
E, Lewis-Barned NJ, Williams SM. national and targeted dietary policies: pooled analysis of 11 cohort studies.
Lactose malabsorption and rate of bone A modelling study. PLOS Medicine American Journal of Clinical Nutrition
loss in older women. Age & Ageing 2017;14(6):e1002311. 2009;89(5):1425–1432.
1999;28(2):175–180. 43. Stefler D, Pikhart H, Kubinova R, Pajak 59. Zong G, Li Y, Wanders AJ, Alssema M,
32. Lapointe A, Balk EM, Lichtenstein A, Stepaniak U, Malyutina S, et al. Fruit Zock PL, Willett WC, et al. Intake of
AH. Gender differences in plasma and vegetable consumption and mortal- individual saturated fatty acids and risk
lipid response to dietary fat. Nutrition ity in Eastern Europe: Longitudinal of coronary heart disease in US men and
Reviews 2006;64(5 Pt 1):234–249. results from the Health, Alcohol and women: Two prospective longitudinal
33. Stone NJ, Robinson JG, Lichtenstein AH, Psychosocial Factors in Eastern Europe cohort studies. BMJ. 2016;355:i5796.
Bairey Merz CN, Blum CB, Eckel RH, study. European Journal of Preventive 60. Mozaffarian D1, Micha R, Wallace
et al. American College of Cardiology/ Cardiology 2016;23(5):493–501. S. Effects on coronary heart disease
American Heart Association Task Force 44. Sandler R, Jorddan M, Shelton B. of increasing polyunsaturated fat in
on Practice Guidelines. 2013 ACC/AHA Demographic and dietary determina- place of saturated fat: A systematic
Guideline on the Treatment of Blood tions of constipation in the US popula- review and meta-analysis of random-
Cholesterol to Reduce Atherosclerotic tion. American Journal of Public Health ized controlled trials. PLOS Medicine
Cardiovascular Risk in Adults: A Report 1990;80:185–189. 2010;7(3):e1000252.
References 133
61. https: //www.iofbonehealth.org/facts- stat New England Journal of Medicine systematic review and meta-analysis
istics. 2001;344(18):1343–1350. of cohort studies. Nutrition Reviews.
62. Wirth K, Klenk J, Brefka S, Dallmeier
D, Faehling K, Roqué I, et al.
Biomarkers associated with sedentary
67. Knowler WC, Barrett-Connor E, Fowler
SE, Hamman RF, Lachin JM, Walker
EA, et al. Reduction in the incidence of
73.
2016;74(12):737–748.
Johnson K, Kligman EW. Preventive
nutrition: Disease-specific dietary
9
behaviour in older adults: A systematic type 2 diabetes with lifestyle intervention interventions for older adults. Geriatrics
review. Ageing Research Reviews 2017 or metformin. New England Journal of 1992;47(11):39–40.
May;35:87–111. Medicine 2002;346(6):393–403. 74. Turner ND, Lloyd SK. Association
63. Chung M, Balk E, Bendel M, Ip S, Lee 68. Sakane N, Sato J, Tsushita K, Tsujii S, between red meat consumption and
J, Lichtenstein AH, et al. The relation- Kotani K, Tsuzaki K, et al. Prevention of colon cancer: A systematic review of
ships of vitamin D and calcium intakes type 2 diabetes in a primary healthcare experimental results. Experimental
to nutrient status indicators and health setting: Three-year results of lifestyle Biology and Medicine (Maywood)
outcomes. Evidence Report AHRQ intervention in Japanese subjects with 2017;242(8):813–839.
Publication, Agency for Healthcare impaired glucose tolerance. BMC Public 75. Aune D, Keum N, Giovannucci E, Fadnes
Research and Quality, Rockville, MD, Health 2011;11:40–49. LT, Boffetta P, Greenwood DC, et al.
2009. Evidence Report/Technology 69. Meydani SN, Wu D. Nutrition and age- Nut consumption and risk of cardiovas-
Assessment 2009;(183):1–420. associated inflammation: Implications cular disease, total cancer, all-cause and
64. Ford ES, Ajani UA, Croft JB, Critchley for disease prevention. Journal of cause-specific mortality: A systematic
JA, Labarthe DR, Kottke TE, et al. Parenteral and Enteral Nutrition review and dose-response meta-analysis
Explaining the decrease in U.S. deaths 2008;32(6):626–629. of prospective studies. BMC Medicine
from coronary disease, 1980–2000. 70. Meydani SN, Wu D. Age-associated 2016;14(1):207.
New England Journal of Medicine inflammatory changes: Role of nutri- 76. Jevtic M, Velicki R, Popovic M,
2007;356(23):2388–2398. tional intervention. Nutrition Reviews Cemerlic-Adjic N, Babovic SS, Velicki
65. Ford ES, Li C, Zhao G, Pearson WS, 2007;65(12 Pt 2):S213–S216. L. Dietary influence on breast cancer.
Mokdad AH. Prevalence of the metabolic 71. Meydani SN, Leka LS, Fine BC, Dallal Journal of Balkon Union of Oncology
syndrome among U.S. adolescents using GE, Keusch GT, Singh MF, et al. 2010;15(3):455–461.
the definition from the International Vitamin E and respiratory tract infec- 77. Kushi LH, Byers T, Doyle C, Bandera
Diabetes Federation. Diabetes Care tions in elderly nursing home residents: EV, McCullough M, Gansler T, et al.
2008;31(3):587–589. A randomized controlled trial. JAMA American Cancer Society guidelines on
66. Tuomilehto J, Lindstrom J, Eriksson JG, 2004;292(7):828–836. nutrition and physical activity for cancer
Valle TT, Hamalainen H, Ilanne-Parikka 72. Schwedhelm C, Boeing H, Hoffmann prevention: Reducing the risk of cancer
P, et al. Prevention of type 2 diabetes G, Aleksandrova K, Schwingshackl L. with healthy food choices and physi-
mellitus by changes in lifestyle among Effect of diet on mortality and cancer cal activity. CA: A Cancer Journal for
subjects with impaired glucose tolerance. recurrence among cancer survivors: A Clinicians 2006;56(5):254–281.
10
CHAPTER
This chapter is based on a similar chapter entitled “Effects component in the human body, except in the very obese.
of an Active Lifestyle on Water Balance” written for This gives about 40–42 L of water in the average 70 kg
Nutrition in Lifestyle Medicine, Humana Press (New male: because of their generally higher body fat content,
York), 2016 also edited by James M. Rippe, MD. women normally have a lower body water content than
men of the same mass. A change—whether an increase
or decrease—of more than about 10% of this value car-
KEY POINTS ries a number of risks, but regulatory and behavioral
mechanisms normally intervene long before this point is
• Water is essential to life, and body water content is reached. Approximately two-thirds of this water is found
normally tightly regulated and remains relatively in intracellular compartments with the remaining third in
constant from day to day. extracellular compartments (Figure 10.1). Euhydration is
• The main factors influencing total body water con- defined as body water levels being within about 0.2% of
tent are body mass and body fatness (lean tissue has normal in temperate conditions and within about 0.5%
a higher water content than adipose tissue). when in the heat or during exercise.1 Individuals are con-
• Large excursions from euhydration are associated sidered to be hypohydrated or hyperhydrated outside these
with loss of functional capacity and, if sufficiently limits. Both of these conditions, if sufficiently severe, can
large, are potentially fatal. impair all aspects of physiological function and may prove
• Water losses are increased by increasing ambient fatal in extreme cases.
temperature and humidity, and by increasing levels Physical activity poses a number of challenges to water
of physical activity. and salt homeostasis, including increased rates of water
• A variety of foods and beverages normally contrib- and salt loss. These effects are amplified as the activity
ute to total daily water intake. level, ambient temperature, and environmental humidity
increase. Hard exercise, even if the duration is too short to
induce substantial sweat losses, also causes a redistribu-
10.1 INTRODUCTION tion of water between body water compartments because
of the large changes in osmolality within the active
The ability to regulate body water content and the osmo- muscles.
lality of tissues within a relatively narrow range is one of Those who are physically active—whether on a recre-
the defining characteristics of all animal life. Small excur- ational of occupational basis—should be aware of their
sions in these parameters are normal, but large changes body’s need for water and salt, and should not either
are incompatible with survival. This close regulation must ignore or consciously override the physiological signals.
be achieved in the face of a continuous, but variable, loss
of water and salts from the body. Humans can survive for
several weeks without food, but deprivation of water for 10.2 WATER BALANCE
even a few days is usually fatal, with survival time dic-
tated largely by the rate of water loss. Water comprises Water balance occurs when water intake matches water
about 50–70% of body mass, making it the most abundant losses, but water intake is episodic whereas water losses
135
136 Chapter 10 Effects of an Active Lifestyle on Water Balance and Water Requirements
environmental conditions. Maughan et al.11 studied elite is no agreement regarding the point at which a reduc-
10
football players during a training session in warm condi- tion in body water is likely to affect physiological func-
tions and observed a median pre-exercise urine osmolality tion. This is probably due to a variety of factors related to
of 666 mosm/kg (range of 103 to 1254 mosm/kg). During methodological issues in experimental design as well as
the 90-min training session, median fluid intake was 971 inter-individual variability, as the factors that limit exer-
mL with a range of 265 to 1661 mL and percentage body cise capacity will also differ.
mass loss was 1.4% with a range of 0.5–2.6%. In a simi- Case studies demonstrate that prolonged physical activ-
lar study performed in a cold environment, Maughan et ity without fluid ingestion, especially but not exclusively
al.12 observed that pre-exercise urine osmolality was 872 in hot environments, can lead to impaired physiological
mosm/kg (range: 481–1228 mosm/kg), fluid intake was function, hypernatremia, and collapse.18 Other case stud-
420 mL (range: 44–950 mL), and percentage body mass ies demonstrate that extreme over-ingestion of fluid during
loss was 1.6% (range: 0.9–2.5%). Similar results have exercise can also lead to impaired physiological function
been observed during competitive football matches13 and and hyponatremia, which can prove to be fatal.19 At some
throughout a competitive handball tournament.14 These level of dehydration, an effect must become apparent, but
studies demonstrate that some individuals are likely to this will depend on the exercise model, the environmental
begin exercise in a hypohydrated state, that there are large conditions, and the individual susceptibility.
inter-individual differences in sweat rate and fluid intake A recent review by Cheuvront and Kenefick 20 con-
during exercise, and that some individuals are likely to cluded that the majority of studies in this area have sug-
become significantly dehydrated by undertaking relatively gested that a reduction in body mass of 2% or more is
short but intense periods of physical activity. A few indi- likely to reduce endurance exercise performance particu-
viduals drink more than they sweat: often these are those larly when that exercise is performed in a hot environment.
who began exercise in a hypohydrated state. This agrees with the 2007 Position Stand on Exercise and
Sweat consists of water, minerals, and organic com- Fluid Replacement published by the American College of
ponents. Consequently, when sweat rate increases dur- Sports Medicine. 21
ing exercise, it is not just water that is lost. The main A number of physiological and psychological mecha-
electrolytes that are lost via sweat are sodium and chlo- nisms may contribute to the effect of hypohydration on
ride at concentrations of approximately 15–80 mmol/L. exercise performance. Gonzalez-Alonso et al. 22 reported
There is large inter-individual variation in the composi- that stroke volume was reduced and heart rate increased
tion of sweat, leading to large variations in electrolyte when dehydrated participants undertook exercise in a
loss between individuals.11,12 This, in addition to the large hyperthermic environment. In addition to the impact
variation in sweat loss, means that no single hydration of hypohydration on stroke volume and heart rate,
strategy is suitable for all physically active individuals, Gonzalez-Alonso et al. 23 also reported a reduction in skin
and that hydration advice should be tailored to the indi- blood flow during exercise in the hypohydrated state: this
vidual in question. will reduce the extent of heat loss and lead to increases
Body water turnover, or the replacement of water lost in core temperature. An individual’s perception of effort
over a given period, is approximately 5–10% of total body (RPE) at a given exercise intensity has been shown to
water content per day for a sedentary individual living in increase when exercising in a hypohydrated state com-
a temperate environment but can increase to 20–40% if pared to a euhydrated state, 24,25,26 which is likely to be
prolonged exercise is undertaken in a hot environment. another mechanism by which a reduction in body water
Water turnover is higher in children up to 15 years of age negatively influences exercise performance. Interestingly,
than in adults and higher in physically active individuals Fleming and James27 demonstrated that habituation to
than in age-matched sedentary individuals.15 Leiper et al.16 exercise in a hypohydrated state reduced the detrimental
reported that average median water turnover in a cool effects of a reduction in body water on endurance exercise
environment for a group of regular cyclists was higher (47 performance. This effect was not mediated by changes in
ml/kg/d) than in age-matched sedentary controls (36 ml/ cardiovascular system function but rather by habituation
kg/d), with the difference in water turnover due primarily reducing RPE.
to non-renal water losses. When similar measurements15 It has been suggested that a reduction in body water of
were made in recreational runners, water turnover rates 3–4% is required to induce detrimental effects on muscle
were higher (4673 ml/d) than in sedentary age-matched function. 28 A recent meta-analysis of 28 published studies29
controls (3256 ml/d), but the difference was due to an concluded that hypohydration results in meaningful
renal loss, suggesting that voluntary intake was increased reductions in non-body weight dependent muscle perfor-
beyond the needs dictated by sweat loss. mance and that the method of inducing a reduction in
body water was an important consideration. In particular,
hypohydration induced by passive means resulted in less of
10.4 HYDRATION STATUS AND an effect on muscular performance than those that
involved an active component. This meta-analysis also
PERFORMANCE concluded that body weight dependent muscular perfor-
mance may be improved by a reduction in body water of
Small changes in body water content occur throughout the 3% or more.
day and have no measurable effect on physiological func- Relatively mild levels of hypohydration have been shown
tion, but large changes clearly have an impact. Despite the to negatively affect cognition. Ganio et al. 30 observed
substantial volume of research in this area, however, there that mild hypohydration of approximately 1.5% body
138 Chapter 10 Effects of an Active Lifestyle on Water Balance and Water Requirements
mass resulted in reduced cognitive aspects such as visual rate, skin temperature, and hydration status, it is no sur-
vigilance and visual working memory when compared to prise that there is interest in determining whether an indi-
when euhydrated. Lindseth et al.31 reported that simu- vidual’s hydration status influences their perception of
lated flight performance and spatial cognition tests were effort during exercise.
reduced in pilots who were hypohydrated due to low levels An important methodological consideration is that
of fluid ingestion compared to those who were euhydrated few, if any, studies have been carried out to study the effect
with adequate levels of fluid ingestion. Watson et al. 32 of dehydration on RPE during exercise. Instead, RPE has
induced hypohydrated in their volunteers by a period of been measured as a secondary outcome measure in studies
fluid restriction that resulted in a reduction in body mass examining the effect of dehydration on other markers of
of 1.1%. During a two-hour simulated driving task, more physiological function. A further important methodologi-
minor driving errors were recorded when participants cal consideration is whether an individual begins exercise
were hypohydrated than when they performed the task in a dehydrated state or whether dehydration is accrued
having followed current drinking guidelines. These stud- throughout exercise.
ies suggest that even mild levels of hypohydration appear Cheuvront et al.38 induced dehydration via three hours
to have a negative impact on cognition. of heat exposure that resulted in a 3% reduction in body
mass prior to undertaking a 30-minute exercise trial at
50% VO2max and a 30-minute time trial. No differences in
10.5 HYDRATION FOR RPE were observed between the euhydrated or dehydrated
RECREATIONAL ACTIVITY states. Similarly, Kenefick et al.39 reduced body water by
1.7–1.8 L via 75 minutes of exercise in hot conditions before
(RPE, ENERGY BALANCE) a 75-minute heat tolerance test involving running. During
this heat tolerance test, there was little difference in RPE
Physical activity is known to induce numerous health when participants were euhydrated compared to when
benefits, and cardiorespiratory fitness is considered an dehydrated. Alternatively, Riebe et al.40 induced a level of
independent risk factor for a number of disease states. 4% dehydration via exercise in the heat before a period
Physical activity is therefore often prescribed to improve of rehydration or no fluid ingestion. During a subsequent
health. While physical activity alone does not appear to exercise test, RPE was significantly higher in the dehy-
induce large degrees of weight loss, it does have benefi- drated state compared to the euhydrated condition. Similar
cial effects on body composition, and the incorporation findings of an increase in RPE when previously dehydrated
of physical activity into a weight loss strategy that also compared to a euhydrated condition have been observed
includes caloric restriction is likely to produce the great- by Fleming and James27 and Gonzalez-Alonso et al.41
est degree of body mass loss.33 In addition, the extent of On balance, it would seem that beginning exercise in a
weight regain after a period of weight loss is likely to be dehydrated state is likely to lead to a small but meaningful
lower if physical activity is incorporated into the initial increase in RPE.
weight loss strategy.34 Adherence rates to exercise pro- Watson et al.42 reported a significant increase in RPE
grams are generally poor, however.35 An individual’s rat- when participants undertook an intermittent exercise trial
ing of perceived exertion (RPE) during physical activity at 55% VO2max in hot conditions without fluid ingestion
is a key regulator of self-selected exercise intensity and compared to when plain water was ingested to match sweat
will likely determine whether that individual continues or losses (i.e., dehydration was allowed to accrue). Similarly,
terminates an exercise session. Consequently, factors that Baker et al. 26 observed that three hours of treadmill walk-
alter an individual’s RPE during exercise are of interest in ing without fluid replacement led to an increase in RPE
ensuring compliance with exercise strategies used to pro- in comparison to when fluid replacement was allowed.
mote health. Ishijima et al.43 reported that 90 minutes of cycle exer-
An individual’s perception of effort during exercise is cise at 55% VO2max without fluid ingestion led to greater
a complex phenomenon involving numerous physiologi- RPE than when exercise was undertaken with fluid inges-
cal, psychological, and social factors36 and is typically tion. These observations would suggest that dehydration
assessed using a Borg scale. Briefly, the perception of effort accrued while exercising for longer than about 30 minutes
during exercise consists of physiological mediators such as may also lead to a small but meaningful increase in RPE.
ventilation, availability of energy substrate, and skin tem- The mechanisms underlying the effects of hypohydra-
perature activating neuromotor signals. This is processed tion on RPE may include both physiological and psycho-
by the sensory cortex, in combination with psychologi- logical factors. As discussed previously, hypohydration
cal factors (such as motivation, mood state, and experi- leads to a reduction in stroke volume and an increase in
ence), exertional symptoms (such as heavy breathing and heart rate22 as well as a reduction in skin blood flow. 23
sweat rate), and, in the case of elite athletes, performance Blood-brain-barrier permeability may be altered42 and
considerations. This results in a perceptual response that cerebral perfusion reduced44 in response to hypohydra-
will affect the perceived effort of exercise.37 The strongest tion, resulting in direct effects on the central nervous sys-
physiological mediators of RPE are respiratory rate, sen- tem. Hypohydration also leads to dryness of the mouth,
sation of strain in muscles and joints, perception of body thirst, and headaches which could ultimately affect mood
temperature, and limb movement speed. Changes in heart state and psychological factors that alter the perception
rate, blood lactate concentrations, and oxygen uptake do of effort.
not correlate as well with changes in RPE. 37 Given the A substantial body of evidence exists to sug-
close relationship between core body temperature, sweat gest that starting exercise in a hypohydrated state or
10.7 Hydration as Part of a Healthy Lifestyle 139
allowing hypohydration to occur during exercise results consideration when planning hydration strategies during
10
in an increased perception of effort. The effect of hypo- physical activity.
hydration on RPE is an important consideration for situa- As hypohydration is a common occurrence after exer-
tions of occupational activity as well as the prescription of cise, a large body of research on post-exercise rehydration
physical activity for health and well-being. Consequently, exists. If a single exercise session is completed during the
in these situations, individuals should be provided with the day, there is no need for an aggressive rehydration strategy
opportunity and education to ensure they are adequately to be implemented, as normal regulatory processes gov-
hydrated prior to beginning work or an exercise session to erning fluid intake will ensure that water balance is main-
minimize the effect of impaired hydration status on RPE. tained over a 24-hour period. If a second exercise session
is to be performed on the same day, a post-exercise rehy-
dration strategy may be needed to ensure that this session
10.6 IMPLICATIONS FOR DRINKING is not started while hypohydrated. The most important
factor to consider is the volume of fluid that is consumed.
STRATEGIES Shirreffs et al. 50 observed that a volume greater than that
lost during exercise is required to account for obligatory
Much attention has been given to strategies during exer- urine losses. This is typically translated as 1.5 L for every
cise that may optimize exercise performance. As previ- 1.0 L lost during exercise. It also seems as though the rate
ously discussed, small, acute reductions in body water at which fluid is ingested is an important consideration,
(as assessed by changes in body mass) are unlikely to with high rates of fluid ingestion less effective at main-
cause any negative effects on performance, and therefore taining fluid balance over a recovery period than low rates
a drinking strategy that restores all body water lost dur- of ingestion of the same volume.51 The composition of a
ing exercise is unnecessary. Similarly, generic advice to all rehydration solution is likely to alter the effectiveness of
physically active individuals is not appropriate due to the that solution to maintain fluid balance over a recovery
large individual differences in sweat losses that occur dur- period. The most important constituent of a rehydration
ing exercise solution is the sodium concentration, as this is the most
Two main drinking strategies have been promoted abundant ion in the extracellular fluid and therefore has
in recent years. The first strategy involves assessing a significant impact on plasma osmolality. The addition
water and electrolyte losses during training in response of sodium to a rehydration solution has been shown to
to different environmental conditions and devising a improve its effectiveness at maintaining fluid balance dur-
hydration protocol based on these observations so that ing a recovery period.52 The addition of carbohydrate and
an individual may avoid the reductions in body water protein to a solution may also be of benefit, as the addition
that may negatively influence exercise performance. 21 of these nutrients reduces the rate of gastric emptying and
Alternatively, while exercising, individuals can drink overall water absorption, ensuring that water loss is mini-
only when they are thirsty45 or ad libitum. Drinking to mized due to the avoidance of large changes in plasma
thirst relies solely on the thirst response whereas ad libi- volume.53,54 An additional consideration is whether food
tum involves other external cues in addition to thirst. The is ingested alongside a solution. Water is not considered
two pieces of terminology are used interchangable and to be an adequate rehydration solution when ingested
result in similar levels of water intake. Armstrong et al.46 on its own, as it is rapidly absorbed into the blood and
compared a drinking-to-thirst strategy to an ad libitum causes a relatively large reduction in plasma volume and a
strategy in trained cyclists completing a 164-km road diuresis, 55 but when ingested alongside a meal containing
cycle at an ambient temperature of 36°C. Although the adequate electrolytes, water may be a suitable rehydration
percentage body mass lost and fluid intake were the same, solution. 56
the authors concluded that an ad libitum strategy may be
easier to implement.
It seems clear that a single hydration strategy is not
appropriate for all individuals, and numerous confound-
10.7 HYDRATION AS PART OF
ing factors must be considered. These include the indi- A HEALTHY LIFESTYLE
vidual’s pre-activity hydration status, the extent of water
loss incurred, individual preference of taste and familiar- As outlined previously, moderate reductions in body water
ity with drinks, the ambient temperature, and the tem- are common as a result of physically active lifestyles, and
perature and composition of the drinks. An additional these reductions may lead to changes in cardiovascular
consideration is individual differences in gastrointestinal function as well as impairments of cognitive processes and
disturbance that may occur as a result of fluid ingestion mood. These observations are important for physical per-
during exercise. Relatively high-intensity exercise (>70% formance in elite athletes, for physically active members
VO2max) reduces the rate at which fluid is emptied from of the general public, and for those with occupations that
the stomach47 as does ingestion of solutions with relatively involve manual work. What is less clear, perhaps, is the
high carbohydrate concentration.48 Consequently, inges- effect of acute and chronic reductions in body water on
tion of large volumes of water and/or solutions containing health. The majority of work in this area has focused on
carbohydrate during exercise may lead to gastric discom- elderly populations.
fort in some individuals. While there is some evidence Chronic hypohydration is unlikely to result in severe
that it is possible to train the gastrointestinal system to physiological or cognitive health effects, as large devia-
the ingestion of these volumes,49 it is still an important tions in body water will be, at least partially, corrected
140 Chapter 10 Effects of an Active Lifestyle on Water Balance and Water Requirements
by mechanisms that regulate body water balance. deaths in London, 26.8% more deaths in Rome, and 33.6%
Consequently, the effects of chronic hypohydration are more deaths in Milan. In Mediterranean cities, where the
likely to be relatively mild. Conversely, large, acute reduc- heat wave had the largest impact on temperature, the per-
tions in body water could be relatively severe. Few studies centage increase in all-cause mortality compared to other
have adequately examined the effects of hydration status years was greatest in those aged 85 + years and was higher
on chronic disease, but there are some suggestions that low in females than males.
fluid intake (and, therefore, hypohydration) may be linked Similar observations have been made in Australia.
to urinary stones (urolithiasis), constipation, bladder and Nitschke et al.66 analyzed daily ambulance transports,
colon cancer, hypertension, and diabetic ketoacidosis. 57 hospital admissions, and mortality over a 13-year period
These observations should be treated with caution, how- from 1993 and compared heat waves to non-heat wave
ever, due to the lack of studies demonstrating causality. periods. Total mortality was unaffected during heat
The aging process results in a reduction in fat-free waves, but ambulance transports and hospital admis-
mass, reduction in bone mass, and a reduction in total sions increased by 4% and 7%, respectively. Total men-
body water as well as blunted thirst response, leading to tal health and renal health hospital admissions were
an increased risk of hypohydration in these individuals. increased by 7% and 13%, respectively. Similarly, Khalaj
Hydration status is known to be a factor in disease progres- et al.67 surveyed 1,497,655 emergency hospital admissions
sion for a number of medical disorders. Hypohydration is in sites across New South Wales. It was observed that on
thought to lead to infection which, in elderly populations, days of extreme heat, hospital admissions for heat illness,
can be fatal in up to 50% of cases if not diagnosed early. 58 dehydration, and electrolyte disturbance were increased,
In an analysis of UK death certificates between 2005 and whereas hospital admissions from other causes were not.
2009, it was observed that 667 deaths were due to dehy- Individuals with underlying medical conditions affecting
dration compared to 157 as a result of malnutrition: it is, the nervous, circulatory, respiratory, and/or renal sys-
however, difficult to determine whether dehydration was tems were particularly affected by the high environmental
the causative factors in these deaths. 59 temperatures.
Leiper et al.60 observed that water turnover, as assessed It seems clear that certain populations, particularly
via a deuterium oxide tracer, was significantly slower in the elderly and those with underlying medical conditions,
elderly individuals living in a nursing home than those are most at risk of high environmental temperatures and
who lived at home. Similarly, Wolff et al.61 reported that that this is likely to be at least partly due to the effect on
12% of elderly patients admitted to hospital from a nurs- hydration status. Warren et al.68 examined the economic
ing home were hypernatremic upon admission compared impact of hospital admissions due to hypohydration in
to 1.3% of elderly patients who lived at home. Extent elderly U.S. adults. Almost 7% of hospitalizations in 1991
of hypernatremia upon admission is related to likeli- had dehydration listed as a diagnosis, with 1.4% listed as
hood of in-hospital mortality and, consequently, patients the primary diagnosis. This resulted in $446 million in
from nursing homes had greater likelihood of in-hospital Medicare claims, suggesting that hypohydration-related
death than those who lived at home. Similar results were hospital admissions have a significant economic impact.
reported by El-Sharkawy et al.61 These observations indi- From these observations, it seems that the avoidance of
cate that elderly individuals, particularly those in nursing hypohydration in these situations is a relatively straight-
homes, should be targeted by nursing home staff to ensure forward but potentially effective intervention in certain
adequate water ingestion and avoidance of hypohydration. populations for improving public health.
Quality of life is of primary importance in elderly Much attention has been given to the acute and chronic
individuals and is often assessed as a profile of physi- effects of hypohydration, but large, acute increases in body
cal, psychological, independence, social relationships, water, though less common than hypohydration, can also
environmental, and spiritual domains. In a study of 82 be hazardous. Overhydration can occur as a result of the
residents of Australian nursing homes, Courtney et al.63 ingestion of water in excess of the amount needed to main-
reported that quality of life was positively correlated with tain euhydration, an electrolyte deficit, and/or an inabil-
clinical care indicators. The three main indicators that ity of the renal system to compensate for these changes
affected quality of life were poor hydration status, num- by appropriate adjustments of renal function. As with
ber of fall incidents, and depression. These areas may be chronic hypohydration, chronic overhydration is unlikely
targeted to improve quality of life in nursing homes, and to lead to serious health consequences in healthy individu-
improvements in hydration may be one of the easiest and als, but occasionally it can be fatal. If the concentration of
most cost-effective ways to achieve this. sodium in the extracellular space falls, water moves from
It seems clear from this evidence that certain popula- the interstitial space into the cellular compartment, lead-
tions, such as the elderly, are more susceptible to the impact ing to swelling of cells. In most tissues this is of little con-
that reductions in body water can have on health. Further sequence, though it may have implications for a number
evidence of this can be seen when examining the effects of of cellular functions.69 If sufficiently severe, however, an
changes in environmental temperature on morbidity and increase in intracranial pressure will result and symptoms
mortality. Sardon64 reports that temperatures throughout associated with “water intoxication,” including headache,
Europe were several degrees higher between June and nausea, confusion, and changes in behavior. If intracra-
September 2003 compared to other years. In an analysis nial pressure continues to increase, this can lead to central
of heatwave days in 2003 compared to the same dates in nervous system dysfunction, coma, and death. Exercise-
other years from 1990 to 2004, D’Ippoliti et al.65 observed associated hyponatremia, brought about by ingesting a
that there were 7.6% more deaths in Munich, 10.4% more greater volume of water than is lost via sweat, has been
References 141
associated with several deaths and was reported in 13% may have an impact on exercise performance as well as
10
of finishers of the Boston marathon in 2002 despite these self-selected exercise intensity. Some populations, such
individuals showing no clinical symptoms.70 A number of as the elderly, are more likely to become hypohydrated,
non-exercise cases of “water intoxication,” brought on and they and those who care for them, may need specific
due to excessive fluid ingestion, have also been described. hydration advice in order to avoid potential adverse health
These include cases from fraternity initiation practices, consequences.
co-ingestion of large volumes of fluid with recreational
drugs such as MDMA, water ingestion during weight loss
plans, and social competitions involving large volumes of CLINICAL APPLICATIONS
fluid intake.71
High levels of physical activity, especially in warm envi-
ronments, lead to increased sweat production and there-
10.8 CONCLUSION fore increased losses of water and salt from the body.
Hypohydration and hypernatremia are the normal
Despite the abundance of water in the human body, it is responses to prolonged exercise in the heat. Losses vary
important to maintain levels within narrow limits. This greatly between individuals, even under the same exer-
is achieved by matching water intake and water output. cise and environmental conditions, but are normally self-
An imbalance between water intake and output leads to limiting. Ingestion of water—especially with the addition
either hypohydration or overhydration. Chronic water of carbohydrate and salt—can help maintain physiologi-
imbalances are usually relatively mild; homeostasis will cal function and performance capacity. If sweat losses
be restored due to normal regulatory processes. Acute exceed about 2–3% of body mass, performance is usually
imbalances can, if sufficiently severe, lead to changes in impaired. Ingestion of plain water or other low-sodium
physiological function that can affect performance of drinks in excess of sweat loss can lead to hyperhydration
physical activity and, in extreme cases, can lead to seri- and the development of hyponatremia. Mild hyponatre-
ous health consequences. Some elite athletes, exercisers, mia is generally asymptomatic and harmless, but if severe
and manual workers have been shown to begin activities and treated inappropriately, it can—on rare occasions—be
in a hypohydrated state, even when there is a high risk of fatal. Medical support personnel at endurance events must
potentially harmful hypohydration. Sweat rates and fluid recognize that some of those requiring medical attention
intake during physical activity both vary greatly between may be severely hypohydrated, while others finishing (or
individuals. Undertaking physical activity in a hypohy- failing to finish) alongside them may be hyperhydrated
drated state leads to an increase in subjective effort, which and hyponatremic.
REFERENCES
1. Greenleaf JE. Problem: Thirst, drink- 8. Rolls BJ, Wood RJ, Rolls ET, Lind H, handball players during a 6-day com-
ing behavior, and involuntary dehydra- Lind W, and Ledingham JGG. Thirst fol- petitive tournament. Int. J. Sport Nutr.
tion. Med. Sci. Sports Exerc . 1992; 24: lowing water deprivation in humans. Am. Exerc. Metab . 2015; 25: 78– 88.
645– 656. J. Physiol . 1980; 239: R476– R482. 15. Shimamoto H and Komiya S. The
2. Baylis PH. Osmoregulation and control of 9. European Food Safety Authority (EFSA). turnover of body water as an indicator
vasopressin secretion in healthy humans. Panel on dietetic products, nutrition, and of health. J. Physiol. Anthropol. Appl.
Am. J. Physiol . 1987; 253: R671– R678. allergies (NDA): Scientific opinion on Human Sci . 2000; 19: 207– 212.
3. Robertson GL. Vasopressin in osmotic dietary reference values for water. EFSA 16. Leiper JB, Pitsiladis Y, and Maughan
regulation in man. Annu. Rev. Med . J . 2010; 8: 1459– 1507. RJ. Comparison of water turnover rates
1974; 25: 315– 322. 10. Institute of Medicine. Panel on Dietary in men undertaking prolonged cycling
4. Adolph EF, Barker JP, and Hoy PA. Reference Intakes for Electrolytes and exercise and sedentary men. Int. J. Sports
Multiple factors in thirst. Am. J. Physiol . Water, Dietary Reference Intakes for Med . 2001; 22: 181– 185.
1954; 178: 538– 562. Water, Potassium, Sodium, Chloride and 17. Leiper JB, Carnie A, and Maughan RJ.
5. Saunders CJ, de Milander L, Hew-Butler Sulfate . Washington, DC: The National Water turnover rates in sedentary and
T, Xenophontos SL, Cariolou MA, Academies Press, 2005. exercising middle aged men. Br. J. Sports
Anastassiades LC, Noakes TD, and Collins 11. Maughan RJ, Merson SJ, Broad NP, Med . 1996; 30: 24– 26.
M. Dipsogenic genes associated with and Shirreffs SM. Fluid and electrolyte 18. Noakes T, Mekler J, and Pedoe DT. Jim
weight changes during Ironman triathlons. intake and loss in elite soccer players Peters’ collapse in the 1954 Vancouver
Hum. Mol. Genet . 2006; 15: 2980– 2987. during training. Int. J. Sport Nutr. Exerc. Empire Games marathon. S. Afr. Med. J .
6. Yau MWA, Moss A, James LJ, Gilmore Metab . 2004; 14: 333– 346. 2008; 98: 596– 600.
W, Ashworth JJ, and Evans GH. The 12. Maughan RJ, Shirreffs SM, Merson SJ, 19. Noakes TD, Sharwood K, Collins M,
influence of angiotensin converting and Horswill CA. Fluid and electrolyte and Perkins DR. The dipsomania of great
enzyme and bradykinin B2 receptor balance in elite male football (soccer) distance: Water intoxication in an Ironman
gene variants on voluntary fluid intake players training in a cool environment. J. triathlete. Br. J. Sports Med . 2004; 38: E16.
and fluid balance in healthy men during Sports Sci . 2005; 23: 73– 79. 20. Cheuvront SN and Kenefick RW.
moderate intensity exercise in the heat. 13. Maughan RJ, Watson P, Evans GH, Dehydration: physiology, assessment, and
Appl. Physiol. Nutr. Metab . 2015; 40: Broad N, and Shirreffs SM. Water bal- performance effects. Compr. Physiol .
184– 190. ance and salt losses in competitive foot- 2014; 4: 257– 285.
7. Shirreffs SM, Merson SJ, Fraser SM, and ball. Int. J. Sport Nutr. Exerc. Metab . 21. Sawka MN, Burke LM, Eichner
Archer DT. The effects of fluid restric- 2007; 17: 583– 594. ER, Maughan RJ, Montain SJ, and
tion on hydration status and subjective 14. Cunniffe B, Fallan C, Yau A, Evans GH, Stachenfeld NS. Exercise and fluid
feelings in man. Br. J. Nutr . 2004; 91: and Cardinale M. Assessment of physical replacement. Med Sci Sports Exerc . 2007;
951– 958. demands and fluid balance in elite female 39: 377–390.
142 Chapter 10 Effects of an Active Lifestyle on Water Balance and Water Requirements
22. Gonzalez-Alonso J, Mora-Rodriguez R, 36. St Clair Gibson A, Baden DA, Lambert 51. Kovacs EMR, Schmahl RM, Senden
Below PR, and Coyle EF. Dehydration MI, Lambert V, Harley YXR, Hampson LMG, and Brouns F. Effect of high and
markedly impairs cardiovascular function D, Russell VA, and Noakes TD. The low rates of fluid intake on post-exercise
in hyperthermic endurance athletes dur- conscious perception of the sensation of rehydration. Int. J. Sports Nutr. Exerc.
ing exercise. J. Appl. Physiol . 1997; 82: fatigue. Sports Med . 2003; 33: 167– 176. Metab . 2002; 12: 14– 23.
1229– 1236. 37. Robertson R and Noble BJ. Perception 52. Shirreffs SM and Maughan RJ. Volume
23. Gonzalez-Alonso J, Calbet JA, and of physical exertion: Methods, mediators repletion following exercise-induced
Nielsen B. Muscle blood flow is reduced and application. Exerc. Sport Sci. Res . volume depletion in man: Replacement of
with dehydration during prolonged 1997; 25: 407– 452. water and sodium losses. Am. J. Physiol .
exercise in humans. J. Physiol . 1998; 513: 38. Cheuvront SN, Carter R III, Castellani 1998; 43: F868– F875.
895– 905. JW, and Sawka MN. Hypohydration 53. Evans GH, Shirreffs SM, and Maughan
24. Below PR, Mora-Rodrí g uez R, Gonzá lez- impairs endurance exercise performance RJ. Post-exercise rehydration in man: The
Alonso J, and Coyle EF. Fluid and carbo- in temperate but not cold air. J. Appl. effects of osmolality and carbohydrate
hydrate ingestion independently improve Physiol . 2005; 99: 1972– 1976. content of ingested drinks. Nutrition
performance during 1 h of intense 39. Kenefick RW, O’ Moore KM, Mahood 2009; 25: 905– 913.
exercise. Med. Sci. Sports Exerc . 1995; NV, and Castellani JW. Rapid IV versus 54. James LJ, Clayton D, and Evans GH.
27: 200– 210 oral rehydration: Responses to subse- Effect of milk protein addition to a carbo-
25. Murray SR, Michael TJ, and McClellan quent exercise heat stress. Med. Sci. hydrate-electrolyte solution ingested after
PD. The influence of fluid replacement Sports Exerc . 2006; 38: 2125– 2131. exercise in the heat. Br. J. Nutr . 2011;
rate on heart rate and RPE during 40. Riebe D, Maresh CM, Armstrong LE, 105: 393– 399.
exercise in a hot, humid environment. J. Kenefick RW, Castellani JW, Echegaray 55. Nose H, Mack GW, Shi XR, and Nadel
Strength Cond. Res. 1995; 9: 251– 254. ME, Clark BA, and Camaione DN. ER. Role of osmolality and plasma
26. Baker LB, Dougherty KA, Chow M, and Effects of oral and intravenous rehydra- volume during rehydration in humans. J.
Kenney WL. Progressive dehydration tion on ratings of perceived exertion and Appl. Physiol . 1988; 65: 325– 331.
causes a progressive decline in basket- thirst. Med. Sci. Sports Exerc . 1997; 29: 56. Maughan RJ, Leiper JB, and Shirreffs
ball skill performance. Med. Sci. Sports 117– 124. SM. Restoration of fluid balance after
Exerc . 2007; 39: 1114– 1123. 41. Gonzalez-Alonso J, Mora-Rodriguez R, exercise-induced dehydration: Effects
27. Fleming J and James LJ. Repeated famil- Below PR, and Coyle EF. Dehydration of food and fluid intake. Eur. J. Appl.
iarisation with hypohydration attenuates reduces cardiac output and increases sys- Physiol. Occup. Physiol . 1996; 73:
the performance decrement caused by temic and cutaneous vascular resistance 317– 325.
hypohydration during treadmill run- during exercise. J. Appl. Physiol . 1995; 57. Manz F and Wentz A. The importance
ning. Appl. Physiol. Nutr. Metab . 2014; 79: 1487– 1496. of good hydration for the prevention of
39:124– 129. 42. Watson P, Black KE, Clark SC, and chronic diseases. Nutr. Rev . 2005; 63:
28. Judelson DA, Maresh CM, Anderson JM, Maughan RJ. Exercise in the heat: Effect S2– S5.
Armstrong LE, Casa DJ, Kraemer WJ, of fluid ingestion on blood-brain barrier 58. Ferry M. Strategies for ensuring good
and Volek JS. Hydration and muscular permeability. Med. Sci. Sports Exerc . hydration in the elderly. Nutr. Rev . 2005;
performance – Does fluid balance effect 2006; 42: 2197– 2 204. 63: S22– S29.
strength, power and high-intensity endur- 43. Ishijima T, Hashimoto H, Satou K, 59. Maughan RJ. Hydration, morbidity and
ance? Sports Med . 2007; 37: 907– 921. Muraoka I, Suzuki K, and Hiquchi M. mortality in vulnerable populations.
29. Savoie FA, Kenefick RW, Ely BR, The different effects of fluid with and Nutr. Rev . 2012; 70: S152– S155.
Cheuvront SN, and Goulet EDB. Effect without carbohydrate ingestion on sub- 60. Leiper JB, Primrose CS, Primrose WR,
of hypohydration on muscle endurance, jective responses of untrained men during Phillimore J, and Maughan RJ. A com-
strength, anaerobic power and capacity prolonged exercise in a hot environ- parison of water turnover in older people
and vertical jumping ability: A meta-anal- ment. J. Nutr. Sci. Viaminol . 2009; 55: in community and institutional settings.
ysis. Sports Med . 2015; 45: 1207– 1227. 506– 510. J. Nutr. Health Aging 2005; 9: 189– 193.
30. Ganio MS, Armstrong LE, Casa DJ, 44. Carter, R III, Cheuvront SN, Vernieuw 61. Wolff A, Stuckler D, and McKee M.
McDermott BP, Lee EC, Yamamoto LM, CR, and Sawka MN. Hypohydration and Are patients admitted to hospitals from
Marzano S, Lopez RM, Jimenez L, Le prior heat stress exacerbates decreases care homes dehydrated? A retrospective
Bellego L, Chevillotte E, and Lieberman in cerebral blood flow velocity during analysis of hypernatremia and in-hospital
HR. Mild dehydration impairs cognitive standing. J. Appl. Physiol . 2006; 101: mortality. J. R. Soc. Med . 2015; 108:
performance and mood of men. Br. J. 1744– 1750. 259– 265.
Nutr . 2011; 106: 1535– 1543. 45. Noakes TD. Commentary: Role of hydra- 62. El-Sharkawy AM, Watson P, Neal KR,
31. Lindseth PD, Lindseth GN, Petros TV, tion in health and exercise. BMJ 2012; Ljungqvist O, Maughan RJ, Sahota O,
Jensen WC, and Caspers J. Effect of 345: e4171. and Lobo DN. Hydration and Outcome
hydration on cognitive function in pilots. 46. Armstrong LE, Johnson EC, Kunces LJ, in Older Patients admitted to hospital (the
Mil. Med . 2013; 178: 792– 798. Ganio MS, Judelson DA, Kupchak BR, HOOP prospective cohort study). Age
32. Watson P, Whale A, Mears SA, Reyner Vingren JL, Munoz CX, Huggins RA, Ageing 2015; 44: 943– 947.
LA, and Maughan RJ. Mild hypohydra- Hydren JR, Moyen NE, and Williamson 63. Courtney M, O’ Reilly M, Edwards H,
tion increases the frequency of driver KH. Drinking to thirst versus drinking and Hassall S. The relationship between
errors during a prolonged, monotonous ad libitum during road cycling. J. Athl. clinical outcomes and quality of life for
driving task. Physiol. Behav . 2015; 147: Train . 2014; 49: 624– 631. residents of aged care facilities. Aust. J.
313– 318. 47. Leiper JB, Broad NP, and Maughan RJ. Adv. Nurs . 2009; 26: 49– 57.
33. Wu T, Gao X, Chen M, and van Dam Effect of intermittent high-intensity exer- 64. Sardon JP. The 2003 heat wave. Euro.
RM. Long-term effectiveness of diet plus cise on gastric emptying in man. Med. Surveill . 2007; 12: 226.
exercise interventions vs diet only inter- Sci. Sports Exerc . 2001; 33: 1270– 1278. 65. D’ Ippoliti D, Michelozzi P, Marino C,
ventions for weight loss: A meta-analysis. 48. Vist GE and Maughan RJ. Gastric empty- de’ Donato F, Menne B, Katsouyanni
Obes. Rev . 2009; 10: 313– 323. ing of ingested solutions in man: Effect of K, Kirchmayer U, Analitis A, Medina-
34. Wang XW, Lyles MF, You TJ, Berry beverage glucose concentration. Med. Sci. Ramon M, Paldy A, Atkinson R, Kovats
MJ, Rejeski WJ, and Nicklas BJ. Sports Exerc . 1994; 26: 1269– 1273. S, Bisanti L, Schneider A, Lefranc A,
Weight regain is related to decreases 49. Jeukendrup AE. Training the gut for Iniguez C, and Perucci CA. The impact
in physical activity during weight loss. athletes. Sports Med . 2017; 47(Suppl 1): of heat waves on mortality in 9 European
Med. Sci. Sports Exerc . 2008; 40: S101– S110. cities: Results from the EuroHEAT proj-
1781– 1788. 50. Shirreffs SM, Taylor AJ, Leiper JB, and ect. Environ . Health 2010; 9: 37.
35. Dishman RK. The problem of exercise Maughan RJ. Post-exercise rehydration 66. Nitschke M, Tucker GR, and Bi P.
adherence: Fighting sloth in nations with in man: Effects of volume consumed and Morbidity and mortality during heat-
market economies. Quest 2001; 53(3): drink sodium content. Med. Sci. Sports waves in metropolitan Adelaide. Med. J.
279– 294. Exerc . 1996; 28: 1260– 1271. Aust . 2007; 187: 662– 665.
References 143
67. Khalaj B, Lloyd G, Sheppeard V, and among US elderly, 1991. Am. J. Public runners in the Boston marathon. N. Eng. J.
Dear K. The health impacts of heat waves Health 1994; 84: 1265– 1269. Med . 2005; 352: 1550– 1556.
in five regions of New South Wales,
Australia: A case-only analysis. Int.
Arch. Occup. Envrion. Health . 2010; 83:
69. Lang F. Mechanisms and significance of
cell volume regulation. J. Am. Coll. Nutr.
2007; 26(Suppl 5): 613S– 623S.
71. Hew-Butler T, Rosner MH, Fowkes-
Godek S, et al. Statement of the 3rd
International Exercise-Associated
10
833– 842. 0. Almond CSD, Shin AY, Fortescue EB,
7 Hyponatremia Consensus Development
68. Warren JL, Bacon WE, Harris T, McBean Mannix RC, Wypij D, Binstadt BA, Duncan Conference, Carlsbad, California, 2015.
AM, and Foley DJ. The burden and CN, Olson DP, Salerno AE, Newburger Clin. J. Sports Med . 2015; 25, 303– 320.
outcomes associated with dehydration JW, and Greenes DS. Hyponatremia among doi:10.1097/JSM.0000000000000221
III
PA RT
Physical Activity
Edward M. Phillips, MD
145
11
CHAPTER
147
148 Chapter 11 Implementation of the Exercise Prescription
rarely do clinicians directly refer patients to a facility; Various assessments can and should be done in order to
instead they verbally mention it (40%), provide a handout design a proper fitness plan, including but not limited to
to the patient (24%), refer them to another lifestyle pro- a preparticipation screening, submaximal aerobic exercise
gram (16%), or don’ t discuss fitness facilities at all with test, and muscular, flexibility, and body composition tests.
the patient (20%). Main barriers to referral included a Using such information will help the personal trainer
paucity of time, absence of protocol, perceived shortcom- develop appropriate cardiorespiratory, strength and con-
ings in patient compliance, lack of knowledge on the sub- ditioning, and stretching programs. These professionals
ject, and inadequate accessibility for the patient. also promote positive health behavior and motivate their
When physicians do write exercise prescriptions, clients.
they tend to recommend activities that they specifically According to the Institute for Credentialing Excellence,
are familiar with. Walking, followed by aerobic activity, there are 16 personal trainer certifying organizations
strength training, and cycling tend to be the most recom- accredited by the National Commission of Certifying
mended forms of activity and are associated with physi- Agencies (NCCA) (Institute for Credentialing).16 Among the
cians’ personal experiences with exercise.9 Interestingly, organizations offering a CPT certification are the American
although physicians reported being familiar with health College of Sports Medicine (ACSM), the National Academy
clubs and generally believed health clubs to be an appropri- of Sports Medicine (NASM), the National Strength and
ate venue for their patients, less than half of the physicians Conditioning Association (NSCA), and the American
recommend health clubs and only 20% recommended a Council on Exercise (ACE). Within these organizations,
personal trainer.10 Moreover, they believe access to and additional certifications may be offered for specific areas
cost of health clubs and personal trainers would present of expertise. For example, in addition to the CPT certifi-
an important barrier to their patients. cation, NSCA offers a Certified Strength and Conditioning
The physicians’ perceived barriers to patient compli- Specialist (CSCS) certification and ACSM offers an Exercise
ance with exercise prescription are important to consider Is Medicine® (EIM) credential.
in the referral system, particularly with regard to access CPTs generally work at gyms, fitness and community
and subsequent support. One physician mentioned that centers, and in corporate wellness programs. In addition
while she is convinced exercise prescription is effective at to CPTs, Group Exercise Instructors (GEI) play an inte-
treating chronic conditions, she believes that “ it’ s not easy gral role in fitness facilities.
to change a habit” .11 Furthermore, physicians have found Currently, there is not a standardized process for phy-
it difficult to motivate their patients to engage in physical sicians to refer patients to a CPT. However, ACSM has
activity, stating that many patients attribute their seden- started an initiative to create an exercise referral system
tary lifestyle to leading a busy life and that it is difficult through the Exercise is Medicine® (EIM) initiative. In
to work around such lifestyle barriers. Patient barriers are an effort to help connect PCPs with CPTs and to deliver
particularly important to consider because the physician physical activity prescriptions, EIM has created an exer-
will most likely not be the practitioner responsible for cise professional credential. Anyone who holds an NCCA
helping patients actually participate in exercise. As such, accredited fitness professional is eligible to obtain the
a robust referral network should include trained exercise EIM credential.17 In addition, the American Council on
and behavior change professionals to fill this role. Exercise offers an NCAA-accredited Certified Medical
Given that several obstacles make implementation of Exercise Specialist credential, which was created to help
the exercise prescription and referral process difficult— the train CPTs to create programs for clients with a range
most prominent barriers being a lack of certainty about of medical conditions. ACE Certified Medical Exercise
physicians’ ability to prescribe exercise, a need for more Specialists must hold a bachelor’ s degree in exercise sci-
structure and information in the process itself, and uncer- ence or a related field and have completed 500 hours of
tain access or motivation from the patient’ s perspective— it work experience designing and implementing exercise
is important to take a closer look at the current systems in programs for apparently healthy individuals and/or high-
place for effective referral. Specifically, it is critical that the risk individuals.
role of exercise professionals as well as successful commu-
nity programs are examined and that systems are under-
stood and best practices followed. Indeed, referral to an 11.1.1.2 Exercise Physiologist
exercise specialist can result in increased physical activity An exercise physiologist is a health professional who
for patients that are insufficiently active12 although results helps diagnose and treat a number of diseases through
are mixed.13 ,14 It is important to note, however, that these exercise. They work with clients and/or patients to pro-
systems are only just emerging and leave much room for vide exercise prescriptions based on health history and
expansion and improvement. physical assessment.15 Common areas of focus include
cardiovascular, pulmonary, and metabolic diseases.
Exercise physiologists can work in a number of set-
11.1.1 Exercise Professionals for Referral tings— both clinical and nonclinical. In addition to
hospitals and clinics, exercise physiologists can work in
11.1.1.1 Personal Trainer fitness and wellness centers as well as corporate, govern-
A certified personal trainer (CPT) is a fitness professional ment, and university settings.18
who works with mostly healthy individuals to achieve their In the United States, there are currently three certifi-
exercise goals.15 The job entails conducting fitness evalu- cations for exercise physiologists, all of which require a
ations and creating performance programs for clients. minimum of a bachelor’ s degree. The ACSM offers exams
11.1 Introduction 149
for the certified exercise physiologist (EP-C), certified certifications for PTs. The following are areas of special-
11
clinical exercise physiologist (CCEP), and the registered ization: cardiovascular and pulmonary, clinical electro-
clinical exercise physiologist (RCEP). While it is not nec- physiology, geriatrics, neurology, oncology, orthopedics,
essarily required for exercise physiologists to obtain a pediatrics, sports physical therapy, and women’ s health.
certification, many employers do require it. In countries Though a certification is not required to work in any par-
such as Australia, exercise physiologists play an integral ticular field, the goal of ABPTS is to promote high-quality
role in the prevention of noncommunicable diseases.19 In physical therapy through acknowledging the knowledge
response to the need for exercise physiologists, Australia and skill of specialty areas. 24
has made efforts to ensure that exercise physiologists A referral to PT is typically required under most
obtain certification through a more rigorous accreditation insurance companies. However, even with physician
process. referral, some copayments are exceeding $60 per visit. 25
One of the most popular areas of the exercise physi- Depending on an individual’ s insurance policy, physical
ology profession is cardiac rehabilitation. According to therapy can still be a financial burden. This barrier is cer-
the Clinical Exercise Physiology Association (CEPA), tainly a strong factor playing a role in the effectiveness
approximately 45% of exercise physiologists work in car- of treatment and patient compliance. An alternative to a
diac rehabilitation. Even though cardiac rehabilitation is physician referral, direct access to PT is when patients can
one of the largest venues for exercise physiologists, there seek physical therapy care directly without first seeing a
is evidence that it is not being used enough. According physician or physician assistant. 26 Studies report excellent
to the American Heart Association, “ [ D]espite being rec- patient outcomes with direct-access PT.
ommended by guidelines, rates of referral to cardiac reha- While physical therapy is often seen as a rehabilitation
bilitation are historically suboptimal.” 20 Referral rates profession, the job function of a PT includes preventative
depend highly on procedure type and where the procedure aspects. PTs are not only an excellent resource for preven-
was performed, as some institutions and/or departments tion of injury but are also in a good position to promote a
vary. physically active lifestyle. As reported by the APTA, PTs
Weight management and obesity are other areas where are knowledgeable and skilled professionals who can pro-
exercise physiologists may be employed. As part of the vide non-treatment physical activity advice. 27 As they are
EIM initiative, community centers are becoming recog- easily accessible to a number of populations, they could
nized as places to receive appropriate exercise guidance. have a more predominant role in public health.
A number of programs exist to help with weight loss. In
addition, cancer is a growing specialty for exercise physi-
ologists. The ACSM offers a certification in conjunction 11.1.1.4 Health Coach
with the American Cancer Society for becoming a Cancer A health coach is a certified professional trained in
Exercise Trainer (CET).15 The YMCA employs many patient-/client-centered behavior change. Typically, health
CETs in offering a physical activity program for cancer coaches work with individuals to facilitate healthy life-
survivors called LIVESTRONG. 21 style changes like achieving adequate physical activity,
improved nutrition, smoking cessation, and stress reduc-
tion. While health coaches do not diagnose conditions,
11.1.1.3 Physical Therapist prescribe treatments, or provide psychological interven-
According to the American Physical Therapy Association tions, they are able to work with individuals to provide
(APTA), the role of a physical therapist (PT) is to “ exam- guidance and personalized motivation to create behavior
ine each individual and develop a plan using treatment change strategies and goal setting. Specifically, coaches
techniques to promote the ability to move, reduce pain, “ assist clients to use their insight, personal strengths and
restore function, and prevent disability” .22 The PT pro- resources, goal setting, action steps and accountability
fession also involves working with patients in a preventive toward healthy lifestyle change” . 28 Often, health coaches
manner, as it can help prevent the loss of mobility before will hold multiple certifications or even content-relevant
it occurs through the development of an exercise program. degrees (e.g., Exercise Science or Nutrition) that aid in
Much like an exercise physiologist, a PT’ s job begins with their practice.
a patient assessment or evaluation. This includes taking According to the International Consortium for Health
a medical history and performing tests and measures to and Wellness Coaching (ICHWC), there are a plethora of
identify problems, both existing and potential. After a certification training and education programs sponsored
general review is conducted, PTs use the gathered infor- by academic institutions and privately owned certification
mation to design a plan of care. companies. Each organization is individually accredited
In the United States, the education requirement for and offers its own certification exam, but the ICHWC
PTs is a Doctorate of Physical Therapy (DPT). 23 Prior to formed a partnership with the National Board of Medical
the DPT degree, a Master’ s of Physical Therapy was the Examiners in May 2016 to launch a National Board
education required to practice. In addition to obtaining a Certification for Health & Wellness Coaches in 2017.
degree, PTs must pass a state licensure exam. PTs work in According to the Institute of Coaching (http://www.
a variety of settings, including but not limited to outpa- instituteofcoaching.org/ ), 29 “ [C]oaching as a practice is
tient clinics and offices, inpatient rehabilitation facilities, very young and is made up of practitioners from a wide
home care, research institutes, hospices, fitness cen- variety of disciplines and backgrounds, from business
ters, and sports training facilities. The American Board consulting, Human Relations (HR) and Organizational
of Physical Therapy Specialties (ABPTS) offers several Development (OD), and training, to sports, education, and
150 Chapter 11 Implementation of the Exercise Prescription
philosophy, to any number of psychological disciplines physicians can access at any time. To address the bar-
such as industrial/organizational (I/O) psychology, coun- rier of insufficient finances, many DPPs are now covered
seling psychology, clinical psychology, and social psychol- through Medicare and other health insurance providers,
ogy.” Coaches are often self-employed but can also work thus making the referral process easier and providing even
at gyms, fitness and community centers, in corporate well- more incentive to patients.
ness programs, and are also becoming part of integrated The YMCA DPP is one example of a program that
care teams in some health care settings. Currently, there is physicians can easily refer patients to. There are more
not a standardized process for physicians to refer patients than 200 YMCA sites throughout the country that run the
to a health coach. DPP, and there is a large body of evidence supporting the
program’ s effectiveness.31 For instance, an existing part-
nership between the YMCA, UnitedHealth Group, and
11.1.2 Successful Programs the CDC brought the DPP to nearly 30,000 participants
in more than 1,000 locations across the country.31
11.1.2.1 Referral Guides
A straightforward and effective strategy to use limited
clinical time for exercise referral may simply be to refer
11.1.2.3 SilverSneakers and Enhance
patients to a list of regionally offered community pro- Fitness for Older Adults
grams. Indeed, many community departments and health SilverSneakers is a no-cost gym membership for eligible
agencies have collected local information to develop seniors to which physicians can refer patients. 33 Targeted
resource collections, with the goal of increasing provider toward older adults, ages 65 and up, this is a fitness
awareness of the scope and array of existing community program covered by many Medicare Advantage plans.
resources. These resource collections can be utilized as Participants receive access to more than 15,000 gyms and
referral guides to provide contact information to patients fitness centers in the network, and includes fitness classes
in electronic or paper form. Some clinicians have dem- by SilverSneakers trained instructors.
onstrated concerns over the simplicity and usefulness Enhance Fitness (EF) is a nationally disseminated pro-
of referral guides30 and emphasize that the guides (1) gram for older adults that offers group-based exercise
do not eliminate the need for individualized counseling, classes in community settings.34 ,35 Each class lasts one
(2) must be updated frequently, and (3) may provide infor- hour and follows a set format, including exercises tar-
mation about programs unfamiliar to the practitioners. geting cardiovascular endurance (20– 25 min), strength
However, when utilized in practice, referral guides have (20 min), and balance and flexibility (10 min), all of
actually been shown to be effective and can be helpful which are adaptable to individual ability level. While EF
because “ providing patients with specific activity sugges- is not covered by Medicare, it is often subsidized by and
tions was more effective than providing general advice in integrated into health care systems (Table 11.1).
facilitating behavior change.”30 Moreover, as technology Programs like SilverSneakers and Enhance Fitness have
advances, there is the opportunity to utilize smartphone demonstrated positive benefits on overall physical func-
applications in conjunction with, or in addition to, refer- tion as well as fall prevention in older adults.36 In addition
ral guides in order to provide up-to-date and personalized to increased fitness and fall prevention, these programs
recommendations. have also been shown to be significant health care cost-
saving programs.37 ,38
11.1.2.2 Diabetes Prevention Program for
Patients with Prediabetes 11.1.2.4 Park Rx and OutdoorsRx for Families
Proven to be successful in preventing onset of type 2 dia- The National Park Rx Initiative consists of agencies and
betes, the Diabetes Prevention Program (DPP) is an evi- practitioners who wish to use nature and public lands to
dence-based program available nationwide that physicians promote health in individuals and the community (Park
can easily refer patients to. It is generally a 12-month pro- Rx Website). “ Park Prescription programs39 are designed
gram in which participants attend 16 weekly core sessions in collaboration among public land agencies, healthcare
and are subsequently followed month to month through providers, and community partners to encourage people
regular maintenance sessions. The goal of the DPP is to to utilize parks, trails, and open space for the purpose of
help individuals with prediabetes prevent the onset of improving individual and community health” (Park Rx
type 2 diabetes by making better food choices, increasing Website). Through these partnerships, physicians have
their level of physical activity, and losing excess weight. access to ‘ park prescription pads’ and take-home flyers
DPP programs have been shown to be twice as effective as in addition to the EMR system that they can use to pro-
approaches that are less structured.31 vide patients with concrete information to remind them
According to the American Medical Association to visit their local park. The Park Rx website provides
(AMA)32 website, the AMA and CDC recommend that several case studies from states across the country that
physicians take measures to prevent diabetes in their report their successes in connecting patients with nature
patients by screening them for prediabetes and referring and physical activity.
them to the DPP if positive. The CDC website provides a OutdoorsRx is an initiative of the Appalachian
list of available DPP programs across the nation, which Mountain Club and Massachusetts General Hospital40
Clinical Applications 151
REFERENCES
1. Barnes, P. M., & Schoenborn, C. A. Trends (2017). American Journal of Preventive in the physical therapy setting: Perspectives
in adults receiving a recommendation for Medicine , 53 (4), 490– 499. doi:10.1016/j. from practitioners and students. (2010).
exercise or other physical activity from amepre.2017.06.016. Physical Therapy , 90 (9), 1311– 1322.
a physician or other health professional. 13. Waterman, M. R., Wiecha, J. M., 28. International Consortium for Health &
(2012). NCHS Data Brief , (86), 1– 8. Manne, J., Tringale, S. M., Costa, E., & Wellness Coaching. ICHWC Health &
2. Centers for Disease Control and Wiecha, J. L. Utilization of a free fitness Wellness Coach Scope of Practice . (2017).
Prevention. Diabetes Programs and center-based exercise referral program Retrieved from http://ichwc.org/wp-content/
Initiatives . (2018). Retrieved from https:// among women with chronic disease risk uploads/2015/03/ICHWCHealthWellnessCo
www.cdc.gov/diabetes/programs/. factors. (2014). Journal of Community achScopeofPractice-FinalFeb12017.pdf.
3. Petrella, R. J., Koval, J. J., Cunningham, Health , 39 (6), 1179– 1185. doi:10.1007/ 29. Institute of Coaching. About Coaching .
D. A., & Paterson, D. H. Can primary s10900-014-9874-2. (n.d.). Retrieved from https://instituteofc
care doctors prescribe exercise to improve 14. Sø rensen, J. B., Kragstrup, J., Skovgaard, oaching.org/coaching-overview/about
fitness? The Step Test Exercise Prescription T., & Puggaard, L. Exercise on pre- -coaching.
(STEP) project. (2003). American Journal scription: A randomized study on 30. Seligman, H. K., Grossman, M. D., Bera, N.,
of Preventive Medicine , 24 (4), 316– 322. the effect of counseling vs counsel- & Stewart, A. L. Improving physical activity
4. Grandes, G., Sanchez, A., Sanchez- ing and supervised exercise. (2008). resource guides to bridge the divide between
Pinilla, R. O., Torcal, J., Montoya, I., Scandinavian Journal of Medicine the clinic and the community. (2009).
Lizarraga, K., Serra, J. Effectiveness of & Science in Sports , 18 (3), 288– 297. Preventing Chronic Disease , 6 (1), A18.
physical activity advice and prescription doi:10.1111/j.1600-0838.2008.00811.x. 31. Ackermann, R. T., Marrero, D. G., Hicks,
by physicians in routine primary care: A 15. American College of Sports Medicine. K. A., Hoerger, T. J., Sorensen, S., Zhang,
cluster randomized trial. (2009). Archives Guidelines for Exercise Testing and P., … Herman, W. H. An evaluation of
of Internal Medicine , 169 (7), 694– 701. Prescription . 9th edition. (2013). Baltimore, cost sharing to finance a diet and physical
doi:10.1001/archinternmed.2009.23. MD: Lippincott Williams & Wilkins. activity intervention to prevent diabetes.
5. Orrow, G., Kinmonth, A., Sanderson, 16. Institute for Credentialing Excellence. (2006). Diabetes Care , 29 (6), 1237– 1241.
S., & Sutton, S. Effectiveness of physical NCCA Accredited Organization Search . 32. American Medical Association.
activity promotion based in primary care: (n.d.). Retrieved October 28, 2017, from Advocatikng for Diabetes Prevention .
Systematic review and meta-analysis of http://www.credentialingexcellence.org/n (2017). Retrieved from https: //www.ama
randomised controlled trials. (2012). BMJ ccadirector y. -assn.org/delivering- care/advocating-dia
(Clinical Research Edition) , 344 , e1389. 17. Lobelo, F., Stoutenberg, M., & Hutber, betes-prevention.
doi:10.1136/bmj.e1389. A. The exercise is medicine global health 33. SilverSneakers. (2017). Retrieved from
6. Dasgupta, K., Rosenberg, E., Joseph, L., initiative: A 2014 update. (2014). British https: //www.silversneakers.com / learn /
Cooke, A. B., Trudeau, L., Bacon, S. L., Journal of Sports Medicine , 0 , 1– 8. gym-fitness/.
& Daskalopoulou, S. S. Physician step 18. Kerrigan, D. J., Verrill, D. E., Harding A. 34. Belza, B., Petrescu-Prahova, M., Kohn,
prescription and monitoring to improve W., & Drew, K. D. CEPA 2015 Clinical M., Miyawaki, C. E., Farren, L.,
ARTERial health (SMARTER): A ran- Exercise Physiology Practice Survey. Kline, G., & Heston, A. H. Adoption
domized controlled trial in patients with (2015). Journal of Exercise Physiology . of evidence-based health promotion
type 2 diabetes and hypertension. (2017). 19. Cheema B. S., Robergs, R. A., & Askew, programs: Perspectives of early adopters
Diabetes, Obesity & Metabolism , 19 (5), C. D. Exercise physiologists emerge as of Enhance ® Fitness in YMCA-affiliated
695– 704. doi:10.1111/dom.12874. allied healthcare professionals in the era sites. (2015). Frontiers in Public Health,
7. Leemrijse, C. J., de Bakker, D. H., Ooms, of non-communicable disease pandem- 2, 164.
L., & Veenhof, C. Collaboration of gen- ics: A report from Australia 2006– 2012. 35. Petrescu-Prahova, M., Belza, B., Kohn,
eral practitioners and exercise providers (2014). Sports Medicine , 44 , 869– 877. M., & Miyawaki, C. Implementation and
in promotion of physical activity a writ- 20. Beatty, A. L., Bradley, S. M., Maynard, maintenance of a community-based older
ten survey among general practitioners. C., & McCabe, J. M. Referral to cardiac adult physical activity program. (2016).
(2015). BMC Family Practice , 16 , 96. rehabilitation after percutaneous, Gerontologist, 56(4), 677–686.
doi:10.1186/s12875-015-0316-8. coronary intervention, coronary artery 36. Greenwood-Hickman, M. A., Rosenberg,
8. Smock, C., & Alemagno, S. Understanding bypass surgery, and valve surgery. (2017). D. E., Phelan, E. A., & Fitzpatrick, A.
health care provider barriers to hospital Circulation: Cardiovascular Quality and L. Participation in older adult physi-
affiliated medical fitness center facil- Outcomes , 10 (6), 1– 8. cal activity programs and risk for falls
ity referral: A questionnaire survey and 21. Irwin, L. M., Carmel, B., Harrigan, requiring medical care, Washington
semi structured interviews. (2017). BMC M., Sanft, B., Wong, C., & Hughes, State, 2005– 2011. (2015). Preventing
Health Services Research , 17 (1), 520. M. Impact of the LIVESTRONG at the Chronic Disease , 12 , E90. doi:10.5888/
doi:10.1186/s12913-017-2474-y. YMCA program on physical activity, pcd12.140574.
9. Pojednic, R. M., Polak, R., Arnstein, F., fitness, and quality of life in cancer 37. Petrescu-Prahova, M. G., Eagen,
Kennedy, M. A., Bantham, A., & Phillips, E. survivors. (2015). Journal of Clinical T. J., Fishleder, S. L., & Belza, B.
M. Practice patterns, counseling and pro- Oncology , 33 (15), 9508– 9508. Enhance ® Fitness dissemination and
motion of physical activity by sports medi- 22. American Physical Therapy Association. implementation, 2010–2015: A scop-
cine physicians. (2017). Journal of Science Role of a Physical Therapist . (2016). ing review. (2017). American Journal
and Medicine in Sport, 20(2), 123–127. Retrieved from https: //www.apta.org/ of Preventive Medicine, 52(3S3),
10. Pojednic, R., Bantham, A., Arnstein, F., PTCareers/ RoleofaPT/. S295–S299.
Kennedy, M. A., & Phillips, E. Bridging 23. American Physical Therapy Association. 38. Nguyen, H. Q., Ackermann, R. T.,
the gap between clinicians and fitness Fair Physical Therapy Copays . (2015). Maciejewski, M., Berke, E., Patrick, M.,
professionals: A challenge to implementing Retrieved from http://www.apta.org/ Williams, B., … LoGerfo, J. P. Managed-
exercise as medicine. (2018). BMJ Open StateI ssues /FairCopays/. Medicare health club benefit and reduced
Sport & Exercise Medicine, 4(1), e000369. 24. American Board of Physical Therapy health care costs among older adults. (2008).
11. Bélanger, M., Phillips, E. W., O’Rielly, Specialties. About Specialist Certifications . Preventing Chronic Disease , 5 (1), A14.
C., Mallet, B., Aubé, S., Doucet, M., (2017). Retrieved from http://www.abpt 39. Park Rx. Park Prescription Programs .
Couturier, J., Mallet, M., Martin, J., s.org/Certification/About/. (2016). Retrieved from http://www.park
Gaudet, C., Murphy, N., & Brunet, J. 25. American Physical Therapy Association. rx.org /park-prescription-progra ms.
Longitudinal qualitative study describ- Physical Therapist Education Overview . 40. James, A. K., Hess, P., Perkins,
ing family physicians’ experiences with (2015). Retrieved from http://www.apta M. E., Taveras, E. M., & Scirica,
attempting to integrate physical activity .org/ P TEducation /Over view/. C. S. Prescribing outdoor play:
prescriptions in their practice: ‘It’s not 26. Ojha, H. A., Snyder, R. S., & Davenport, Outdoors Rx. (2017). Clinical
easy to change habits’. (2017). BMJ Open T. E. Direct access compared with Pediatrics , 56 (6), 519– 524.
7(7), e017265. referred physical therapy episodes of care: doi:10.1177/0009922816677805.
12. James, E. L., Ewald, B. D., Johnson, N. A., A systematic review. (2014). Physical 41. OutdoorsRx. (2018). http://www.out-
Stacey, F. G., Brown, W. J., Holliday, E. G., Therapy , 1 (1), 14– 30. doorsrx.org/.
Plotnikoff, R. C. Referral for expert physi- 27. Shirley, D., van der Ploeg, H. P., & 42. Exercise is Medicine Greenville. (2016).
cal activity counseling: A pragmatic RCT. Bauman, A. E. Physical activity promotion Retrieved from http://eimgreenville.org/.
12
CHAPTER
medicine in the ancient world, when a strong emphasis compiled and used as a scorecard indicator to describe
was placed on health rather than disease. That remained a country’s overall PA competence.15 According to the
true through the early part of the 20th century when, in organization behind this effort, the Global Observatory
Western medicine, the major area of focus shifted to treat- for Physical Activity (GoPA), 37 countries have published
ment of disease rather than its prevention. This shift had a specific national plans for promotion of physical activity.16
significant impact on successfully reducing the prevalence The first U.S. National Activity Plan was released in
of infectious disease; however, with less attention paid 2010 following three years of development; an updated
to preventive lifestyle behaviors such as physical activity, version of this plan was subsequently released in 2016.7
the reduction of infectious disease was accompanied by a The healthcare sector represents one of the nine major
steady rise in the prevalence of chronic disease. In the early areas of focus identified in the U.S. plan. This follows
1900s, infectious diseases represented the top three causes the lead of priorities outlined in plans from several other
of death in the United States and accounted for 30% of all countries used to shape the U.S. version.17 The strategies
deaths.9 In contrast, 2014 figures report seven of the top outlined for the healthcare sector are as follows:1 priori-
10 causes of death were attributable to chronic disease.10 tize efforts in healthcare to promote physical activity, 2
The first two—heart disease and cancer—represented recognize physical inactivity and insufficient activity as
nearly 46% of all deaths, while infectious diseases have all preventable and treatable conditions with health and cost
but disappeared from the list. Treating these chronic dis- implications, 3 partner across sectors to improve access to
eases currently accounts for the majority of the country’s physical activity-related services, particularly for disad-
healthcare expenditures. In 2010, more than 85% of the vantaged populations with limited access, and4 expand
nearly $3 trillion in annual healthcare expenditures were education on physical activity in the training of all health-
spent treating chronic diseases.11 Lifestyle changes have care professionals. The tactics designed to support these
the potential to greatly reduce these costs.12 Experts have strategies are described in Table 12.1.
suggested exercise needs to start being viewed as effec-
tive medication that is universally prescribed as a first-line
treatment for virtually every chronic disease.13 12.1.4 Professional Organizations
Set Expectations
12.1.2 A Call to Action The call for involvement from the healthcare sector in PA
promotion is supported from within the medical commu-
The need to bring prevention back as a central focus in
nity itself. Several professional organizations have issued
healthcare has been gaining momentum over the past
statements encouraging their members to address physical
several decades. One of the first to call attention to the
activity with patients, including the American Academy
need for this shift in focus was the landmark report
of Geriatrics and the American College of Preventive
Healthy People: The Surgeon General’s Report on Health
Medicine. A joint statement from the American Academy
Promotion and Disease Prevention issued by U.S. Surgeon
of Pediatrics and the American Academy of Orthopedic
General Julius Richmond in 1979.14 This comprehensive
Surgeons has also been issued.18 While each targets a dif-
assessment expressed a strong need to dramatically recast
ferent segment of the population, each notes the impor-
the nation’s public health policy to emphasize prevention,
tance of providing patients with information, advice,
setting quantifiable objectives and goals for improvement.
and/or a prescription for PA. The most comprehensive
Physical activity was a major theme throughout the report,
of these recommendations comes from a joint initiative
as well as the influential role the healthcare sector has
of the American Medical Association (AMA) and the
in its successful promotion. The Healthy People report,
American College of Sports Medicine (ACSM): Exercise
along with its objectives and goals, has been revised and
is Medicine® (EIM).19
updated every decade since the original was released. The
EIM is a call to action “for the healthcare community
importance of physical activity and the necessity to engage
to make physical activity a standard part of the medical
the healthcare sector in its promotion have remained cen-
paradigm for the prevention and treatment of non-com-
tral themes. Healthy People 2020, the most recent version
municable diseases (NCDs) in healthcare systems”. 20 The
of the report, includes two specific objectives suggesting a
initiative was introduced in the United States in 2007;
role for the healthcare sector in PA promotion.6 The first:
its evolution is described in Lobelo et al.’s “The Exercise
“[I]ncrease the proportion of physician visits made by all
is Medicine Global Health Initiative: a 2014 update”. 21
child and adult patients that include counseling about
Due to high demand from scientific, public health, and
exercise,” and the second: “[I]ncrease the proportion of
medical associations across the world, EIM has evolved
office visits made by patients with a diagnosis of cardio-
into a global initiative with a presence in more than 40
vascular disease, diabetes, or hyperlipidemia that include
countries. There are currently seven regional and 43
counseling or education related to exercise.”
national EIM centers located across the world. ACSM
is responsible for the ongoing coordination and manage-
ment of EIM.
12.1.3 National Physical Activity Plans The initial work of the global EIM initiative (2010–
In recognition of the critical role of physical activity in 2013) was to raise awareness regarding the importance
health, several countries have created comprehensive plans of integrating physical activity promotion into health-
to specifically address the pandemic of inactivity. The care. The current work is focused on implementation of
existence of these plans across the world has recently been the EIM Solution model, described as “a standardized
12.1 Physical Activity Promotion and the Healthcare Sector 155
TABLE 12.1 U.S. national physical activity plan healthcare sector strategies and tactics
Strategy 1
Healthcare systems should increase the priority of physical activity assessment, advice, and promotion.
12
• Use a systems approach to implement, evaluate, and fund interventions that are effective in improving physical activity in both
children and adults.
• Make physical activity a patient “vital sign” that all healthcare providers assess and discuss with their patients.
• Integrate a physical activity vital sign into electronic health records.
• Develop physical activity as a healthcare quality measure for adult patients ages 18 to 64 years, similar to the existing measures for
children and older adults.
• Develop, implement, and evaluate strategies to integrate into healthcare settings objective measures of physical activity that are
derived from wearable devices and smart phone apps.
• Encourage healthcare professionals to be role models for active lifestyles for patients.
Strategy 2
Healthcare systems and professional societies should recognize physical inactivity and insufficient physical activity as treatable
and preventable with profound health and cost implications.
• Expand the evidence on the cost-effectiveness of promoting physical activity in inactive patients with and without chronic disease,
including evidence on the effect of therapeutic physical activity for existing conditions on patient outcomes and costs of care.
• Embed physical activity promotion in clinical guidelines where sufficient evidence exists for both positive health and cost outcomes.
• Ensure that priority is given to treatment of physical inactivity in population groups with the lowest levels of physical activity.
Strategy 3
Healthcare systems should partner with other sectors to promote access to evidence-based physical activity-related services
that increase health equity.
• Establish partnerships with state and local health departments to fund and implement inclusive physical activity policies and
programs for underserved groups, and ensure that they are tailored to the cultures and needs of these groups.
• Partner with faith-based organizations to increase access to physical activity opportunities and programs.
• Support the capacity of school-based health clinics and programs to promote physical activity.
• Develop partnerships with community-policing groups, government units, and other community organizations to promote safe
access to opportunities to walk, bicycle, swim, and play outdoors.
• Partner with community planners to ensure equitable access to active transportation and to expand opportunities for active
transportation and recreational activity.
• Partner with providers of community physical activity services to form referral networks that increase opportunities for physical
activity and ensure equal access of their patients to community resources, including patients living in rural areas.
• Reduce financial barriers to use of community physical activity services by including reimbursement to community providers as part
of healthcare benefit packages, including funding of programs likely to reach diverse populations in the community and subgroups
with lowest levels of physical activity.
Strategy 4
Universities, postgraduate training programs, and professional societies should include basic physical activity education in the
training of all healthcare professionals.
• Include basic physical activity education during assessment, brief counseling, and referrals as part of the required curriculum in
medical school.
• Foster health professional student interest in physical activity.
• Include physical activity content in licensing exams and in board certification exams for clinicians involved in physical activity
promotion.
• Provide an array of evidence-based curricular resources to support physical activity education throughout all health professional
training.
• Include physical activity content in continuing education professional development programs.
this solution. Dacey et al. revealed healthcare providers be easily incorporated into an Electronic Medical Record
12
self-reported an increased knowledge and confidence for (EMR) system, which can automatically complete the mul-
discussing exercise with patients after attending a relevant tiplication and display the final result for view along with
course.41 Several CME opportunities in the field of PA pro- the other recorded vital signs.44
motion and Lifestyle Medicine exist. Physicians may seek Several medical systems have successfully incorpo-
out those that meet their specific learning needs. A list rated the PAVS into their system of usual care, includ-
of reputable organizations offering a variety of learning ing Kaiser Permanente, Greenville Health System in
opportunities throughout the year can be found in the South Carolina, and Intermountain Healthcare System in
“Resources” section at the end of this chapter. Utah.43 Kaiser Permanente has detailed their PAVS imple-
mentation methodology,44 noting that medical assistants
(MAs) are responsible for collecting the information.
12.2.2 Know the PA Guidelines The PAVS is included at every patient intake when tra-
ditional vital signs are checked. The MA asks the PAVS
The U.S. Physical Activity Guidelines for Americans
questions and enters the answers directly into the EMR;
(PAGA), first published in 2008 and updated in 2018, pro-
the final result is displayed along with other vital signs
vide the framework physicians need to discuss physical
in the computerized chart for review by the appropriate
activity with their patients.42 They are written for an audi-
healthcare provider prior to meeting with the patient. The
ence of health professionals and offer simple guidance on
PAVS process is reported to take less than one minute to
how to best utilize PA to promote health. The U.S. PAGA
complete. In a 2012 validation study, Kaiser Permanente
are the result of a comprehensive review of the scientific
Southern California (KPSC) reported 86% of all eligible
literature and serve as the foundation for all evidence-
patients had a PAVS recorded in their EMR after 1.5 years
based PA assessment and advice. Briefly, adults should
of implementation.45
accumulate 150 minutes of moderate intensity aerobic PA
There have been some noted criticisms of the PAVS
or 75 minutes of vigorous intensity aerobic PA per week
tool. One is that it has not been widely used in diverse
(or an equivalent combination) to achieve health benefits.
populations nor been adapted for use in children.46 More
For further benefit, adults should increase these levels to
work needs to be done to address these issues. Another
300 minutes of moderate or 150 minutes of vigorous (or
concern is regarding PAVS reliance on self-report infor-
an equivalent combination). Additionally, adults should
mation, which is widely known to have issues regarding
include muscle-strengthening activities for all major
accuracy in the physical activity domain.47 A 2017 inte-
muscle groups at least two days per week. Physicians and
grated review by Wald et al. investigated this issue, and
healthcare providers should be familiar with these pre-
the results were promising.46 The review was designed to
scriptive numbers (as is standard with other measures that
assess the performance and integration of the PAVS tool.
have health implications, such as blood pressure and body
The authors concluded that preliminary evidence suggests
mass index (BMI)) in order to effectively assess and pre-
the PAVS tool can help clinicians identify patients who
scribe PA to patients.43 Achievement of the guidelines has
are not meeting PA guidelines. Furthermore, Dr. Robert
important implications for overall health. 2
Sallis, the physician who conceptualized the EIM initia-
tive during his tenure as president of ACSM, argues, in
a 2011 editorial published by the British Association of
12.2.3 Record PA as a Vital Sign Sport and Exercise Medicine, that despite the known
A patient’s level of PA can serve as an important indica- issues with self-report PA data, medical providers have
tor of health that can be monitored over time to provide an ethical obligation to ask patients about their PA and
valuable insight regarding the well-being of a patient. As inform them of the dangers of being inactive.44 The PAVS
such, there has been a call to include PA levels as part of tool provides a resource to frame this conversation.
the usual battery of vital signs recorded during a patient The PAVS tool has shown great promise in offer-
visit.43 The standard of measure in the United States is ing a user-friendly, consistent method of addressing PA
based on the PA Guidelines. Both the U.S. NPAP and the with patients. It offers a time-effective solution for busy
EIM initiatives have identified the Physical Activity Vital physicians to gather and keep track of valuable patient
Sign (PAVS) as a main part of their agenda (see Table 12.1). health information. Additionally, PAVS results provide
EIM provides a sample PAVS tool as a resource for physicians a benchmark for discussion regarding physical
healthcare providers.23 The tool consists of two questions:1 activity with each patient. Exercise prescriptions and/or
On average, how many days per week do you engage referrals can be made based on the physician’s individual
in moderate-to-strenuous physical activity (like a brisk time and/or knowledge-dependent barriers.
walk)?2 On average, how many minutes do you engage
in exercise at this level? The product of these two num-
bers provides physicians an approximation of how closely
a patient comes to meeting the 150 minutes per week of
12.2.4 Provide a Prescription
moderate-intensity activity recommended for adults by the In order to be effective, PA advice needs to have a level
U.S. Physical Activity Guidelines. An optional third ques- of specificity that guides a patient to engage in types and
tion recommended by EIM is3 How many days a week do amounts of activities that have health-promoting ben-
you perform muscle- strengthening exercises, such as body- efits. Currently, it appears when physicians do provide PA
weight exercises or resistance training? Adults should be advice, the advice is generic and lacks a level of specific-
including these activities two days each week. The tool can ity that has been shown to more effectively elicit change
158 Chapter 12 What Physicians Need to Know, Do, and Say to Promote Physical Activity
according to the health behavior literature.48 A 2016 in health outcomes come from moving people from
national survey of nearly 1,800 Australian adults illus- the category of “inactive” to “moderately inactive”.52
trates this issue.31 Of the 18.2% (n = 328) of respondents • Episodes of activity can be accumulated in shorter
who reported receiving PA advice from their physician, duration bouts to count toward meeting the guidelines.
nearly half (53%) reported that they were advised how It has been established that PA sessions of 10 minutes
much total activity they should complete; however, nearly or more are beneficial.53 Emerging evidence suggests
one-quarter (24%) did not receive a specific recommenda- shorter durations (1–9 minutes) are also effective.54
tion for the type of activity, and a majority of respondents Patients should take advantage of any opportunity
(61%) did not receive specific information regarding dura- they have throughout a day to be active, as every min-
tion and frequency of activity. ute of activity seems to be beneficial for health.
There is a growing evidence base to support the con- • The benefits of physical activity outweigh the risks of
cept of providing patients with a written prescription for injury and heart attack. While patients with known
PA as a standard protocol. The “Green Prescription” pro- symptoms of disease do require extra precaution before
gram, introduced in New Zealand in 1998, is one example physical activity can be safely prescribed, many people
of an effective model.49 In this model, the health profes- do not require additional screening before increasing
sional (usually the primary care physician) issues a patient levels of PA—especially at non-vigorous intensity lev-
with a written or electronic green prescription that con- els. Recent updates to the ACSM Recommendations
tains specific directives on the type and amount of activity for Exercise Pre-participation Health Screening rein-
the patient should strive to complete. Evidence from this force this message.55 The new recommendations were
program suggests that a written prescription provides a created in an effort to eliminate unnecessary barriers
key reminder to the patient that PA is more than a “good for an individual to begin an exercise program.
thing to do,” it is therapeutic and has been directed to be
completed by their physician. 50
There are four key components that should be included
in every PA prescription: frequency, intensity, time, and 12.2.6 Refer to Experts
type. Together they are commonly referred to by their acro- It is common practice in medicine for physicians to provide
nym FITT. This structure offers directives for PA prescrip- a referral to a professional with expertise in a given content
tion efforts. The goals are set by the U.S. PA Guidelines: area (e.g., dietician, psychologist, other medical specialists)
in an effort to better serve a patient’s specific concerns;
• Frequency: How often should the activity be done? physical activity can be managed the same way. It has been
• Intensity: How hard should the activity feel? established that few physicians receive adequate training
• Time: How many minutes of activity should be regarding PA.35,37,56 As the field of exercise physiology con-
completed? tinues to define best practices for using PA to treat and
• Type: What activities are most appropriate for this manage of specific diseases, an evidence base is develop-
patient? ing to prescribe exercise like a medicine to treat/manage
specific conditions.57 Physicians need not maintain a level
Utilizing a prescription template can assist physicians of expertise across the spectrum of all diseases. Instead, a
in completing the prescription process, alerting them to physician can refer to the professionals who have the time
the key components and helping them to complete it in a and expertise to manage a patient’s individual concerns:
timely manner. Evidence from a three-hour exercise pre- exercise physiologists.58 Expert referrals are especially
scription workshop for clinicians that provided education appropriate for patients who need extra support and/or
along with practical tools (including the EIM prescription are managing one or more chronic conditions and require
pad template) showed a significant increase in prescrip- more specific exercise advice. While physicians readily
tion rates one month post-intervention. 51 The prescription refer to other licensed health professionals (e.g., dieticians,
pad template used in this study is available in the EIM physical therapists, or medical specialists), one noted bar-
“Healthcare Provider Action Guide” (see the “Resources” rier to PA referrals has been a level of distrust between the
section). This EIM template provides simple check boxes medical community about the knowledge base and level of
to help write each component of the prescription. It also expertise among exercise professionals.59 The wide variety
includes descriptive information about each component of fitness professionals and accrediting organizations can
and the targets specified by the U.S. PA Guidelines. make it confusing to navigate. To clarify, exercise physi-
ologists are allied health professionals who have demon-
strated a level of competence in using exercise interventions
12.2.5 Provide Guidance on Filling for persons who are at high risk of developing, or who
have existing chronic or complex medical conditions.60
the Prescription The accrediting organization and specific requirements to
Some of the key guiding principles used to inform the U.S. receive this credential vary by country. In the United States,
PA guidelines offer insight into how to best advise patients the ACSM Certified Clinical Exercise Physiologist (CEP)
to “fill” their prescriptions. 2 certification is the gold-standard certification. An ACSM-
CEP certification identifies people who have a minimum of
• Some physical activity is better than none. The most a university degree (i.e., bachelors (BA) or masters (MS))
important message for patients is to avoid inactivity. in exercise science or a related field, who have 1200 (BS)
Research has demonstrated the biggest improvements or 600 (MS) hours of experience in several content areas
12.4 Conclusion 159
addressing patients across a range of chronic conditions, that analyzed the relationship between personal PA habits
12
who have current CPR certification, and who have passed and counseling practices.38 Of those, nearly 80% (n = 19)
a rigorous examination testing their knowledge and skill demonstrated a statistically significant positive associa-
levels.61 A database of ACSM-CEP professionals is avail- tion. This finding was consistent across a variety of spe-
able through ACSM’s website to help identify these exer- cialties, geographic locations, and clinical settings. The
cise professionals.62 authors noted the importance of this finding, given the
A major challenge to expert referral in the United States myriad barriers (personal and otherwise) associated with
is insurance companies’ lack of recognition of exercise the frequency of counseling.
physiologists as health professionals. As such, an ACSM- The rationale for physicians to engage in PA extends
CEP’s time is not recognized as billable and patients need beyond its influence on their counseling practices; PA has
to pay out-of-pocket for these services. This can present been shown to help reduce physician burnout as well.67
an insurmountable barrier for patients, especially in vul- Burnout is described as “a syndrome of emotional exhaus-
nerable populations where care is most needed. 58 As the tion, loss of meaning in work, feelings of ineffectiveness,
need for exercise expertise grows, it is imperative to work and a tendency to view people as objects rather than
toward a solution to overcome this issue and make profes- human beings”.68 Currently more than half of U.S. physi-
sional exercise more accessible. cians report experiencing substantial symptoms of burn-
The Australian model offers a solution for consideration. out.69 This rate has climbed nearly 10% in just three years
Their professionals are designated as Accredited Exercise (2011–2014) and represents a prevalence nearly twice as
Physiologists (AEP).60 They have obtained a university- high as U.S. workers in other fields.70 Burnout has sig-
level degree and have been certified through Exercise and nificant implications for patient care, as a strong correla-
Sports Science of Australia (ESSA). Medicare Australia, the tion has been established between burnout and increased
nation’s taxpayer-funded universal healthcare system, has medical errors, lower patient adherence to chronic disease
recognized AEPs as allied health professionals since 2006.63 management plans, and other poor standards of practice.71
This designation allows patients with a chronic condition While most of burnout is related to institutional factors
to receive a referral from their primary care provider to an such as electronic health records (EHR) and productivity
AEP and have the cost of these services covered by Medicare. standards, self-care, including PA, appears to play a role in
The AEP referral program has demonstrated a high return decreasing symptoms of burnout. In an attempt to clarify
on investment in treating people with chronic conditions.60 the relationship of PA in burnout, a 2014 survey compared
As an example, people with type 2 diabetes who receive an symptoms of burnout and level of PA in nearly 80 internal
AEP-led exercise intervention have an expected annual sav- medicine residents.67 The results suggest an inverse rela-
ing in health system expenditure of approximately $5,100 tionship—residents who reported meeting the U.S. guide-
AUD (~$3,900 USD) per person.64 lines for PA were less likely to be burned out than those
Expert referral directly addresses the lack of time, who failed to achieve the recommended levels of activity.
knowledge, and confidence physicians have cited as Reported levels of burnout and PA were consistent with
reasons for not promoting PA in their practice. A 2016 national rates (burnout prevalence = 53%; failure to meet
randomized controlled trial (RCT) compared physician guidelines = 41%).
referral of insufficiently active patients to AEPs (either 13 Finally, patients’ perceptions of their physicians’ PA
weeks of face-to-face or telephone counseling) to usual behaviors seems to play a role in the decision about
care.65 Both interventions were effective at improving PA whether or not to engage in PA. In their 2014 review of
levels by approximately 70 minutes per week 12 months the evidence in supporting physicians as PA role models,
following the intervention. Lobelo and Garcia de Quevedo discuss findings revealing
While work continues to be done to overcome the bar- a majority of patients reported being more willing to exer-
riers of cost and access, expert referral offers a promis- cise if their physician also exercised regularly. 38
ing way to increase PA promotion that directly addresses Additional work needs to be done to more clearly
the lack of knowledge, confidence, and time expressed by understand how to leverage this relationship in an effort
physicians. Prioritizing patients who can benefit the most to improve clinical practices. Across the board, the role
from expert guidance (e.g., those with complex medical of a physician’s personal health habits appears to be an
conditions) may improve efficacy. Additionally, regular important factor in patient care.
follow-up with patients regarding this referral is key to
successful implementation. 58
12.4 CONCLUSION
12.3 HEALTHY DOCTOR, HEALTHY Overcoming the major public health threat of physical
PATIENT inactivity requires participation from multiple sectors of
society.7 With the direct link between PA and disease man-
agement and prevention, the healthcare sector is strategi-
12.3.1 Be a Role Model cally positioned to play a central role in working toward a
Evidence suggests a strong relationship exists between phy- solution. As is evidenced by this chapter, the best practices
sicians’ personal health habits and their related counseling for this still need to be defined. However, evidence is reveal-
practices (e.g., smoking cessation, vaccination, screening ing that the barriers to implementation are not insurmount-
practices).66 This appears to hold true for PA counseling able. Physicians have an influential role, but they do not
as well. A 2014 review by Lobelo et al. included 24 studies need to do all of the work themselves. Including support
160 Chapter 12 What Physicians Need to Know, Do, and Say to Promote Physical Activity
staff (e.g., nurses, MAs) in initiatives such as collecting a 3. Clinicians who incorporate PA into their lives are
PAVS or providing a patient with a referral can reduce the better equipped to provide patients with PA coun-
time burden. Additionally, several resources are available seling. Incorporating personal PA opportunities for
to fill the knowledge gap in providing generally healthy medical staff may be a useful strategy to encourage
patients with basic PA prescriptions (see the “Resources” their participation in counseling.
section). Finally, establishing a network of trusted exercise
resources can provide patients with the expertise needed
to treat complex health concerns with exercise. Utilizing
these strategies as we continue to define best practices will
RESOURCES
keep us moving forward, which is key, as exemplified in American College of Lifestyle Medicine
the words of U.S. Surgeon General Julius Richmond in his
groundbreaking 1979 report: “We cannot afford to wait • Annual Conference, Online CMEs + Residency
for perfect solutions before beginning to act.”14 Curriculum: https://lifestylemedicine.org/
REFERENCES
1. Warburton DE, Nicol CW, and 8. Berryman JW. Exercise is medicine: A Bethesda, MD: US Government Printing
Bredin SS. Health benefits of physi- historical perspective. Current Sports Office, 1979.
cal activity: The evidence. Canadian Medicine Reports 2010;9(4):195–201. 15. Activity GOfP. Available from: http://
Medical Association Journal 9. Cohen ML. Changing patterns www.globalphysicalactivityobservatory.
2006;174(6):801–809. of infectious disease. Nature com/.
2. Physical Activity Guidelines Advisory 2000;406(6797):762–767. 16. Varela AR, Pratt M, Powell K, Lee I-M,
Committee. Physical Activity Guidelines 10. Prevention CfDCa. Chronic Disease Bauman A, Heath G, et al. Worldwide
Advisory Committee Report, 2008. Overview [Internet], 2017 [updated June surveillance, policy, and research
Washington, DC: U.S. Department of 28, 2017; November 30, 2017]. Available on physical activity and health: The
Health and Human Services, 2008. from: https: //www.cdc.gov/chronicdis global observatory for physical activity.
3. President’s Council on Fitness Sports and ease/overview/index.htm Journal of Physical Activity and Health
Nutrition. Facts and Statistics: Physical 11. Agency for Healthcare Research and 2017;14(9):701–709.
Activity [Internet]. US Department Quality. Multiple Chronic Conditions 17. Bornstein DB, Pate RR, and Pratt M. A
of Health and Human Services, 2017 Chartbook: 2010 Medical Expenditure review of the national physical activity
[updated January 26, 2017; cited 2017 Panel Survey Data. Available from: https:// plans of six countries. Journal of Physical
November 29, 2017]. Available from: www.ahrq.gov/sites/default/files/wysiwyg/ Activity and Health 2009;S245–S264.
https: //www.hhs.gov/fitness/resource -cen professionals/prevention-chronic-care/dec 18. Bornstein DB and Pate RR. From physical
ter/facts-and-statistics/i ndex.html ision/mcc/mccchartbook.pdf. activity guidelines to a national activity
4. Blair SN. Physical inactivity: The big- 12. Bauer UE, Briss PA, Goodman RA, plan. Journal of Physical Education,
gest public health problem of the 21 st and Bowman BA. Prevention of chronic Recreation and Dance 2014;85(7):17–22.
century. British Journal of Sports Medicine disease in the 21 st century: Elimination 19. American College of Sports Medicine.
2009;43(1):1–2. of the leading preventable causes of pre- Exercise is Medicine. Available from:
5. Organization WH. Interventions on Diet mature death and disability in the USA. http://exerciseismedicine.org/
and Physical Activity: What Works: sum- The Lancet 2014;384(9937):45–52. 20. Sallis RE. Exercise is medicine and physi-
mary report, 2009. 13. Sallis R, Franklin B, Joy L, Ross R, cians need to prescribe it! British Journal
6. Organization of Disease Prevention and Sabgir D, and Stone J. Strategies for of Sports Medicine 2009;43(1):3–4.
Health Promotion. Healthy People 2020. promoting physical activity in clinical 21. Lobelo F, Stoutenberg M, and Hutber
Available from: https: //www.healthyp practice. Progress in Cardiovascular A. The exercise is medicine global
eople.gov/2020/topics-objectives/topic/p Diseases 2015;57(4):375–386. health initiative: A 2014 update. British
hysical-activit y/objectives 14. United States Surgeon General and Journal of Sports Medicine 2014. doi:
7. National Physical Activity Plan. Availabl Richmond JB. Healthy People: The bjsports-2013-093080
from: http://physicalactivityplan.org/ Surgeon General’s Report on Health 22. American College of Sports Medicine.
docs/2016NPAP_Finalforwebsite.pdf Promotion and Disease Prevention. What is the EIM Solution? Available
References 161
from: http://www.exerciseismedicine.org/ systematic review. Academic Medicine 51. Windt J, Windt A, Davis J, Petrella R,
support _page.php/the-eim-solution5/. 2012;87(7):956. and Khan K. Can a 3-hour educational
23. American College of Sports Medicine
Exercise is Medicine. Healthcare
Providers’ Action Guide [Internet].
37. Dacey ML, Kennedy MA, Polak R, and
Phillips EM. Physical activity counseling
in medical school education: A system-
workshop and the provision of prac-
tical tools encourage family physi-
cians to prescribe physical activity as
12
[November 30, 2017]. Available from: atic review. Medical Education Online medicine? A pre–post study. BMJ Open
http://exerciseismedicine.org/assets /pag 2014;19(1):24325. 2015;5(7):e007920.
e_docu ments /HCP_ Action_Guide%2 38. Lobelo F and de Quevedo IG. The 52. Ekelund U, Ward HA, Norat T, Luan Ja,
85%29.pdf. evidence in support of physicians and May AM, Weiderpass E, et al. Physical
24. Phillips EM and Kennedy MA. The health care providers as physical activ- activity and all-cause mortality across
exercise prescription: A tool to improve ity role models. American Journal of levels of overall and abdominal adipos-
physical activity. Physical Medicine and Lifestyle Medicine 2014;1:E15. doi: ity in European men and women: The
Rehabilitation 2012;4(11):818–825. 55982761352012. European Prospective Investigation into
25. Jadczak AD, Dollard J, Mahajan N, 39. Solmundson K, Koehle M, and McKenzie Cancer and Nutrition Study (EPIC). The
and Visvanathan R. The perspec- D. Are we adequately preparing the next American Journal of Clinical Nutrition
tives of pre-frail and frail older people generation of physicians to prescribe 2015;101(3):613–621.
on being advised about exercise: A exercise as prevention and treatment? 53. Haskell WL, Lee I-M, Pate RR, Powell
qualitative study. Family Practice Residents express the desire for more KE, Blair SN, Franklin BA, et al. Physical
2017;35(3):330–335. training in exercise prescription. activity and public health: Updated
26. McLean G, Croteau K, and Schofield G. Canadian Medical Education Journal recommendation for adults from the
Trust levels of physical activity infor- 2016;7(2):e79. American College of Sports Medicine
mation sources: A population study. 40. Lifestyle Medicine Education and the American Heart Association.
Health Promotion Journal of Australia Collaborative. Home [Internet]. Available Circulation 2007;116(9):1081.
2005;16(3):221. from: http://lifestylemedicineeducation. 54. Jefferis BJ, Sartini C, Lee I-M, Lennon
27. Kreuter MW, Chheda SG, and Bull FC. org/. LT, Whincup PH, Wannamethee SG,
How does physician advice influence 41. Dacey M, Arnstein F, Kennedy MA, et al. Does duration of physical activity
patient behavior? Evidence for a prim- Wolfe J, and Phillips EM. The impact of bouts matter for adiposity and metabolic
ing effect. Archives of Family Medicine lifestyle medicine continuing education syndrome? A cross-sectional study of
2000;9(5):426. on provider knowledge, attitudes, and older British men. International Journal
28. O’Brien MW, Shields CA, Oh PI, counseling behaviors. Medical Teacher of Behavioral Nutrition and Physical
and Fowles JR. Health care provider 2013;35(5):e1149–e1156. Activity 2016;13(1):36.
confidence and exercise prescrip- 42. Office of Disease Prevention and Health 55. Riebe D, Franklin BA, Thompson PD,
tion practices of exercise is medicine Promotion. Physical Activity Guidelines Garber CE, Whitfield GP, Magal M,
Canada workshop attendees. Applied for Americans [Internet]. Available from: et al. Updating ACSM’s recommenda-
Physiology, Nutrition, and Metabolism https: //health.gov/paguidelines /guidelin tions for exercise preparticipation health
2016;42(4):384–390. es/. screening. Medicine & Science in Sports
29. Pinto BM, Goldstein MG, DePue JD, and 43. Sallis RE, Matuszak JM, Baggish AL, & Exercise 2015;47(11):2473–2479.
Milan FB. Acceptability and feasibility Franklin BA, Chodzko-Zajko W, Fletcher 56. Hebert ET, Caughy MO, and Shuval K.
of physician-based activity counseling: BJ, et al. Call to action on making physi- Primary care providers’ perceptions of
The PAL project. American Journal of cal activity assessment and prescription a physical activity counselling in a clinical
Preventive Medicine 1998;15(2):95–102. medical standard of care. Current Sports setting: A systematic review. British
30. Patricia M. Barnes MA, and Schoenborn, Medicine Reports 2016;15(3):207–214. Journal of Sports Medicine 2012;46. doi:
CA. Trends in Adults Receiving a 44. Sallis R. Developing healthcare systems 10.1136/bjsports-2011-090734
Recommendation for Exercise or other to support exercise: Exercise as the fifth 57. Nunan D, Mahtani KR, Roberts N,
Physical Activity from a Physician vital sign. British Association of Sport and Heneghan C. Physical activity
or Other Health Professional, 2012. and Exercise Medicine 2011;473–474. for the prevention and treatment of
Available from: https: //www.cdc.gov/ 45. Coleman KJ, Ngor E, Reynolds K, major chronic disease: An overview of
nchs/data/databriefs/db86.pdf. Quinn VP, Koebnick C, Young DR, et systematic reviews. Systematic Reviews
31. Short CE, Hayman M, Rebar AL, Gunn al. Initial validation of an exercise “vital 2013;2(1):56.
KM, De Cocker K, Duncan MJ, et al. sign” in electronic medical records. 58. Thornton JS, Frémont P, Khan K, Poirier
Physical activity recommendations from Medicine & Science in Sports & Exercise P, Fowles J, Wells GD, et al. Physical
general practitioners in Australia. Results 2012;44(11):2071–2076. activity prescription: A critical opportu-
from a national survey. Australian and 46. Wald A and Garber CE. A review of nity to address a modifiable risk factor
New Zealand Journal of Public Health current literature on vital sign assess- for the prevention and management
2016;40(1):83–90. ment of physical activity in primary of chronic disease: A position state-
32. Geense WW, van de Glind IM, Visscher care. Journal of Nursing Scholarship ment by the Canadian Academy of
TL, and van Achterberg T. Barriers, 2018;50(1):65–73. Sport and Exercise Medicine. British
facilitators and attitudes influencing 47. Prince SA, Adamo KB, Hamel ME, Journal of Sports Medicine 2016. doi:
health promotion activities in general Hardt J, Gorber SC, and Tremblay M. A bjsports-2016-096291
practice: An explorative pilot study. BMC comparison of direct versus self-report 59. De Lyon AT, Neville RD, and Armour
Family Practice 2013;14(1):20. measures for assessing physical activity in KM. The role of fitness professionals in
33. Nadler M, Bainbridge D, Tomasone J, adults: A systematic review. International public health: A review of the literature.
Cheifetz O, Juergens RA, and Sussman J. Journal of Behavioral Nutrition and Quest 2017;69(3):313–330.
Oncology care provider perspectives on Physical Activity 2008;5(1):56. 60. Smart N, Williams A, and Lyndon K.
exercise promotion in people with cancer: 48. Locke EA and Latham GP. Building a The role and scope of accredited exercise
An examination of knowledge, practices, practically useful theory of goal setting physiologists in The Australian Healthcare
barriers, and facilitators. Supportive Care and task motivation: A 35-year odyssey. System. Journal of Clinical Exercise
in Cancer 2017;25(7):2297–2304. American Psychologist 2002;57(9):705. Physiology 2016;5(2):16–20.
34. Tuso P. Strategies to increase physi- 49. Ministry of Health New Zealand. How 61. American College of Sports Medicine.
cal activity. The Permanente Journal the Green Prescription Works. [updated ACSM Certified Clinical Exercise
2015;19(4):84. September 19, 2017; November 30, Physiologist [Internet]. [February 12,
35. Institute of Medicine. IOM Report: 2017]. Available from: https: //www.hea 2019]. Available from: https://www.acsm.
Improving Medical Education— lth.govt.n z /our-work /preventative-health org/get-stay-certified/get-certified/cep.
Enhancing the Behavioral and Social -wellness/physical-ac tivit y/green-prescr 62. American Collegeof Sports Medicine.
Science Content of Medical School iptions/how-green-prescription-works. ACSM ProFinder [Internet]. [November
Curricula, Bethesda, MD, 2004. 50. Handcock P and Jenkins C. The green 30, 2017]. Available from: https: //cer tifi
36. Hauer KE, Carney PA, Chang A, and prescription: A field of dreams? The cation 2.acsm.org /profi nder?_ga = 2.15705
Satterfield J. Behavior change counsel- New Zealand Medical Journal (Online) 8107.1006239571.1511156005-18715853
ing curricula for medical trainees: A 2003;116(1187):1–6. 34.1505721550.
162 Chapter 12 What Physicians Need to Know, Do, and Say to Promote Physical Activity
63. Department of Health Australia. Chronic 66. Wells KB, Lewis CE, Leake B, and Ware with work-life balance in physicians
Disease Management – Individual JE. Do physicians preach what they and the general US working popula-
Allied Health Services under Medicare practice? A study of physicians’ health tion between 2011 and 2014. In Mayo
– Provider Information. [November 30, habits and counseling practices. JAMA Clinic Proceedings (Vol. 90, No. 12, pp.
2017]. Available from: http://www.heal 1984;252(20):2846–2848. 1600–1613). Elsevier, 2015.
th.gov.au/i nternet/main/publish ing.nsf/ 67. Olson SM, Odo NU, Duran AM, Pereira 70. Dyrbye LN, Shanafelt TD, Sinsky CA,
content /health-medicare-health_pro-g AG, and Mandel JH. Burnout and physical Cipriano PF, Bhatt J, Ommaya A, West
p-pdf-allied-cnt.htm. activity in Minnesota internal medicine CP, and Meyers D. Burnout among health
64. Economics DA. Value of Accredited resident physicians. Journal of Graduate care professionals: A call to explore and
Exercise Physiologists in Australia. Medical Education 2014;6(4):669–674. address this underrecognized threat to
Brisbane, QLD: Exercise & Sports 68. Montero-Marín J, García-Campayo J, safe, high-quality care. NAM (National
Science Australia, 2015. p. 96. Mera DM, and del Hoyo YL. A new Academy of Medicine) Perspective 2017.
65. Maiorana A, Levinger I, Davison K, Smart definition of burnout syndrome based on 1. American Academy of Family Physicians.
7
N, and Coombes J. Exercise prescription is Farber’s proposal. Journal of Occupational Family Physician Burnout, Well-Being, and
not just for medical doctors: The benefits Medicine and Toxicology 2009;4(1):31. Professional Satisfaction (Position Paper)
of shared care by physicians and exercise 69. Shanafelt TD, Hasan O, Dyrbye LN., [Internet]. [February 12, 2019]. Available
professionals. British Journal of Sports Sinsky C, Satele D, Sloan J, and West from: https://www.aafp.org/about/policies/
Medicine 2016. doi: bjsports-2016-096994 CP. Changes in burnout and satisfaction all/physician-burnout.html.
13
CHAPTER
163
164 Chapter 13 Physical Fitness Evaluation
metabolism, and extracting energy without utilizing oxy- Since the relationship between the increase in work-
gen has been referred to as anaerobic metabolism. load and oxygen consumption is linear, oxygen require-
However, it is important to note that muscle cells are ments also increase. At some point the individual reaches
never entirely aerobic or anaerobic. Their energy require- a volitional fatigue end point, and the test is terminated.
ments are met through the harmonious interaction of the This level is referred to as the maximal aerobic capac-
two systems instead, with the energy contribution of each ity of the individual. The oxygen utilized by the body at
system depending largely on the intensity of activity. In the point of fatigue is referred to as the VO2 max. The
general, high-intensity activities derive their energy mainly measurement of VO2 max implies that an individual’s
independent of oxygen, while low-intensity activities uti- physiological limit has been reached. True VO2 max has
lize oxygen to meet their energy requirements. Therefore, historically been defined by a plateau in VO2 between the
aerobic fitness refers to the ability to provide the required final two exercise work rates and requires that maximal
energy for a specific task in which the body’s cardiopulmo- effort be achieved and sustained for a specified period.
nary system adequately supplies the needed oxygen to the Because this determination is subjective, can be difficult to
working muscle cells. Conversely, anaerobic fitness refers define, and is rarely observed when patients with cardio-
to the body’s ability to provide the required energy for a vascular or pulmonary disease are tested, the term peak
specific task independent of oxygen. Aerobic activities con- VO2 is more commonly used clinically to express exercise
sist of repetitive, low-resistance movements (e.g., walking or capacity. Conversely, the term VO2 max is more often used
cycling) that last over a relatively extended period of time to describe exercise capacity in apparently healthy indi-
(generally five minutes or more). Anaerobic activities on viduals, in whom achievement of a maximal physiological
the other hand are characterized by bursts of intense activ- response is more likely. VO2 max is expressed in millili-
ity lasting a comparatively short period of time (sprinting, ters of oxygen per minute (ml/min) or ml of oxygen per
lifting of a heavy weight, jumping, etc.). It is important to kilogram (kg) of body weight per minute (ml/kg/min). The
emphasize that these two energy systems (aerobic and anaer- latter is usually the preferred expression since it allows
obic) are almost always working together in a harmonious comparisons between subjects of different weights.
way, sharing the responsibility for providing the energy The direct measurement of VO2 max is most often
requirements for the working muscles and the entire body. used for research purposes and has a number of important
However, one is likely to be the predominant system to pro- clinical applications for patients with cardiovascular or
vide most of the energy for the particular activity at hand.5 pulmonary disease. However, it is not often practical for
The most commonly used methods to assess fitness metrics someone who simply wishes to know the appropriate exer-
in the United States are described in Table 13.1. cise intensity during his or her training. For this purpose,
exercise intensity can be easily determined by the heart
rate that corresponds to the appropriate percentage of
13.3 DETERMINING EXERCISE oxygen consumption. Since heart rate and oxygen uptake
are continuously recorded during the metabolic test, one
CAPACITY: DIRECT METHOD- can easily match a desired percentage of heart rate to the
OPEN CIRCUIT SPIROMETRY corresponding oxygen consumption. The advantage of the
direct method is that it is highly accurate. It allows an
The “true” maximum aerobic capacity is the maximum accurate assessment of the exercise intensity of an indi-
amount of oxygen (referred to as maximal oxygen uptake vidual based on directly measured rather than estimated
or VO2 max) the body can utilize during work. This is aerobic capacity. However, it is an elaborate method that
assessed in laboratories by open circuit spirometry. requires expensive equipment and trained personnel and
VO2 max is usually determined by a graded exercise test is therefore cost-prohibitive for large populations. It is
(GXT). A brief description and rationale for this proce- mostly used in individuals with specific clinical needs and
dure is as follows: for research purposes.5
The individual breathes room air via a mouthpiece
(nose occluded), or a face mask, connected to an auto-
mated system (often termed a metabolic cart) by plastic 13.4 DETERMINING AEROBIC FITNESS
tubes. The mouthpiece or mask is designed in such a way
that it allows the measurement of the volume of expired
BY STANDARDIZED TESTS
air, while a small sample of the expired air enters the meta- USING INDIRECT METHODS
bolic cart and is analyzed for its oxygen and carbon diox-
ide (CO2) content. Oxygen uptake is determined by the The need for more practical methods to assess aerobic
product of ventilation and the difference between the O2 capacity for large populations led to the development of
content of the ambient and expired air. After resting sam- standardized exercise tests and the common practice of
ples are taken, the individual is subjected to a standard- estimating energy requirements from different workloads.
ized exercise protocol on a treadmill or stationary bike. An indirect method for estimating the fitness level of an
The exercise begins at a very low workload and increases individual is based on the same principle as that for the
progressively until volitional fatigue or until a clinical direct assessment of VO2 max with one exception: oxy-
indication for stopping is reached. The rate of increase in gen consumption is not directly measured. Instead, it is
external work depends on the exercise protocol used, but estimated based on treadmill speed and grade utilizing
it is typically recommended that the test be individualized equations derived from the direct assessment of VO2 max.
to last between 8 and 12 minutes. The actual procedure is similar to that described for the
13.4 Determining Aerobic Fitness by Standardized Tests using Indirect Methods 165
assessment of VO2 max with the exception that the indi- individual’s age, health and fitness status, and walking
13
vidual is not connected to a metabolic cart (no breathing efficiency and handrail use.9,10 Therefore, the accuracy
apparatus). While an ECG is monitored, the individual of the equation is compromised when applied to compute
undergoes a standardized exercise protocol on a treadmill non-steady-state workloads. In addition, the most com-
or stationary cycle ergometer. Exercise begins at a very monly used equations for walking and running speeds,
low workload and increases every 1–3 minutes depend- referred to as the American College of Sports Medicine
ing on the exercise protocol. The workload is determined (ACSM) equations, are based on <100 young (19–26
either from the speed and elevation of the treadmill or the years old) participants, use a specific protocol, and were
resistance of a cycle ergometer. The heart rate is continu- developed nearly four decades ago. These factors contrib-
ously monitored and recorded during the entire test, and uted to the well-documented overestimation of VO2 max
blood pressure is recorded every 2–3 minutes. 2,5 (MET levels) by these equations during a progressive exer-
The O2 consumption for each exercise stage is esti- cise test, especially at higher workloads.9,11
mated based on regression equations for walking and The ACSM equations for walking and running speeds
running speeds. These equations were based on directly are presented below. 2,9,12
measured energy requirements at submaximal, steady ACSM Walking Equation (Speed 1.9–3.7 miles per
states (defined as a constant VO2) and subsequently used hour) ACSM Walking Equation (Speed 1.9–3.7 miles per
to estimate VO2 at maximal, non-steady state work rates hour)
during a progressive exercise test. 2 This estimated meta-
bolic demand for a given work rate has conventionally
been expressed in metabolic equivalents (METs). One VO2 max = éëTreadmill Speed ( m/min ) *0.1ml/kg/min ùû
MET represents the amount of oxygen used during resting
conditions (approximately 3.5 ml of oxygen per kg of body + Speed ( m/min ) *Treadmill Grade ( decimal )
weight per minute). Thus, any increase beyond the 1-MET
level represents higher total body oxygen consumption, *1.8 ml/min/m] + 3.5ml/kg/min
directly associated with a higher workload. Based on this
rationale, several standardized exercise protocols have The accuracy of the walking equation is best for treadmill
been developed to assess the MET level of individuals speeds between 1.9 and 3.7 miles per hour or 50–100 m/
for clinical and other reasons. The MET level achieved min (1 mile/hr = 26.8 m/min). Walking economy changes
upon termination of the test (the individual reaches voli- above this speed range, and the accuracy of the equation
tional fatigue) represents an estimate of the peak aerobic declines.
capacity of the individual. Because each MET is equal to ACSM Running Equation (Speed>5.0 mph)
approximately 3.5 ml O2 /kg/minute, VO2 max can be esti-
mated by multiplying the MET level achieved by 3.5. 2,5 VO2 max = éëTreadmill Speed ( m/min ) *0.2 ml/kg/min ùû
It is important to note that exercise capacity assessed by
such exercise tests is in part related to the physical activity
+ Speed ( m/min ) *Treadmill Grade ( decimal )
status of the individual. However, the ability to perform
aerobic work is also determined by age and gender as well
*0.9 ml/min/m] + 3.5ml/kg/min
as an important genetic component.6,7
As indicated, the regression equations developed to
estimate VO2 at maximal, non-steady state work rates Generally, the accuracy of the running equation is best
were based on submaximal, steady states. 2,8,9 for treadmill speeds >5 mph or 134 m/min. However, the
However, the steady state assumed by these equations height of the individual influences the speed at which one
is influenced significantly by several factors, including the changes from walking to running. Thus, some individuals
TABLE 13.2 Measured and Estimated Oxygen Consumption Based on the American College of Sports Medicine (acsm)*
and the Fitness Registry and the Importance of Exercise National Database (Friend) Equations (mean ± standard
deviation)
Measured
Maximal Oxygen FRIEND
Uptake Maximal % Error ACSM % Error
PROTOCOL N Age Oxygen Uptake FRIEND Equations ACSM
BALKE 353 54±14 24.8±8.5 25.0±5.6 5.3±17.8 29.9±9.3 23.0±19.6
BRUCE 936 40±13 40.2±11.1 38.4±7.7 –1.7±15.4 45.9±9.0 17.6±20.3
BRUCE-RAMP 2,224 48±13 31.3±9.6 33.8±6.4 12.8±21.0 42.0±8.3 39.8±26.4
RAMP 230 54±16 26.3±11.7 26.0±9.7 4.3±24.4 26.7±14.0 1.8±32.3
MODIFIED BALKE 108 56±9 16.2±2.8 16.0±2.3 –0.8±4.6 11.1±3.3 –32.0±5.1
MODIFIED BRUCE 38 53±14 28.3±9.7 29.3±8.6 6.7± 20.0 35.1±10.8 27.3±24.9
MOD-NAUGHTON 407 57±9 23.6±5.3 23.7±2.5 3.8±17.1 26.5±5.6 14.0±16.1
MANUAL-I 3017 43±11 37.9±10.7 37.5±9.0 1.2±14.2 42.9±11.5 14.4±17.2
MANUAL-II 670 56±15 20.4±8.5 21.6±7.8 9.1± 18.6 23.5±10.2 15.8±20.1
ENTIRE COHORT 7,983 47±14 32.9±11.8 33.3±9.7 5.1±18.3 39.0±12.6 21.4±24.9
may choose to run at speed as low as 3.7 mph.12 We recently exercise testing guidelines is that the protocol be individ-
developed a new equation to estimate VO2 max, using ualized for the patient being tested.8,9,14 For example, a
directly measured VO2 max, instead of steady state.13 This maximal, symptom-limited test on a relatively demanding
equation (FRIEND Equation presented below) is based protocol would not be appropriate (or very informative)
on 7,983 healthy individuals: men (n=4,798) and women for a severely limited patient. Likewise, a very gradual
(n=3,183) age ≥20 years (mean age 47±13 years), who protocol might not be useful for an apparently healthy,
participated in The Fitness Registry and the Importance active person. Use of submaximal testing, gas exchange
of Exercise National Database (FRIEND), established in techniques, the presence of a physician, and the exercise
2014. mode and protocol should be determined by considering
FRIEND Equation for Exercise Protocols Using the person being tested and the goals of the test.
Treadmill Commonly used exercise protocols, their stages, and
the MET level for each stage are outlined in Table 13.3.
VO2 max in ml O2 • kg −1 • min −1 The most suitable protocols for clinical testing should
include a low-intensity warm-up phase followed by pro-
= Speed ( m/min )* ( 0.17 + Fractional Treadmill Grade*0.79) gressive, continuous exercise in which the demand is ele-
vated to a patient’s maximal level within a total duration
+3.5 of 8–12 minutes.8,9,14–17 In the absence of gas exchange
techniques, it is important to report exercise capacity in
Comparisons between the predicted values based on the METs rather than exercise time, so that exercise capac-
ACSM equations and the FRIEND equation revealed that ity can be compared uniformly between protocols. METs
the ACSM equations overestimated VO2 max, as previ- can be estimated from any protocol using standardized
ously reported, 2,9,12 with a percent error for the entire equations that have been put into tabular form.8,9,18 In
cohort of 21.4% (21.4 ± 24.9) versus 5% (5.1±18.3) for general, 1 MET represents an increment on the tread-
the FRIEND equation. When different protocols were mill of approximately 1.0 mph or 2.5% grade. On a cycle
considered, the percent error ranged from –32.0% ±5.1 ergometer, 1 MET represents an increment of approxi-
to 39.8% ± 26.4. In contrast, the percent error for the mately 20 W (120 kgm/min) for a 70-kg person. The
FRIEND equation ranged from – 1.7 ± 15.4 to 12.8 ± 21.0 assumptions necessary for predicting MET levels from
(Table 13.2). treadmill or cycle ergometer work rates (including not
holding the handrails, that oxygen uptake is constant
[i.e., steady-state exercise is performed], that the subject
13.5 PROTOCOLS is healthy, and that all people are similar in their walk-
ing efficiency) raise uncertainties as to the accuracy of
The purpose of the test and the person tested are important estimating the work performed for an individual patient.
considerations in selecting the protocol. Exercise testing For example, the steady-state requirement is rarely met
may be performed for diagnostic purposes, for functional for most patients on most exercise protocols; most clinical
assessment, or for risk stratification. An often ignored testing is performed among patients with varying degrees
but nevertheless consistent recommendation in the recent of cardiovascular or pulmonary disease; and people vary
13.5 Protocols 167
TABLE 13.3 Commonly used Treadmill and Bicycle Exercise Protocols (Continued )
Stage Minutes Speed (MPH) % Grade METS
22 3 3.3 22 13.5
23 3 3.3 23 14.0
24 3 3.3 24 14.4
25 3 3.3 25 14.9
26 3 3.3 26 15.4
Balke
1 2 3.0 2.5 4.3
2 2 3.0 5 5.4
3 2 3.0 7.5 6.4
4 2 3.0 10 7.4
5 2 3.0 12.5 8.5
6 2 3.0 15 9.5
7 2 3.0 17.5 10.5
Naughton
1 2 1 0 1.8
2 2 2 0 2.5
3 2 2 3.5 3.5
4 2 2 7.0 4.5
5 2 2 10.5 5.4
6 2 2 14.0 6.4
7 2 2 17.5 7.4
8 2 2 21.0 8.3
Standard Bicycle Protocol
Stage Minutes Revolutions per Resistance Resistance METS
Minute (kg.m-min –1) (Watts)
1 2 or 3 50 150 25 3.1
2 2 or 3 50 300 50 4.2
3 2 or 3 50 450 75 5.3
4 2 or 3 50 600 100 6.4
5 2 or 3 50 750 125 7.5
6 2 or 3 50 900 150 8.6
widely in their walking efficiency.18 It has therefore been or athletic individuals, appropriate work rate increments
recommended that a patient be ascribed a MET level only might typically be between 40 and 50 W/stage. Most
for stages in which all or most of a given stage duration modern, electronically braked cycle ergometers have con-
has been completed.19 trollers that permit ramp testing, in which the work rate
increments can be individualized in continuous fashion
(see next section).
13.6 CYCLE ERGOMETER PROTOCOLS
Although there are specific bicycle protocols named for 13.7 RAMP TESTING
early researchers in Europe, such as Astrand, 20 bicycle
ergometer protocols tend to be more generalized than for An approach to exercise testing that has gained interest in
the treadmill. For example, 15- to 25-W increments per recent years is the ramp protocol, in which work increases
2-minute stage are commonly used for patients with car- constantly and continuously. In 1981, Whipp and col-
diovascular disease, whereas for apparently healthy adults leagues21 first described cardiopulmonary responses to
13.9 Walk Tests for Cardiorespiratory Fitness Assessment 169
a ramp test on a cycle ergometer, and many of the gas assumptions are met: (1) the workload is reproducible; (2)
13
exchange equipment manufacturers now include ramp a steady-state heart rate is obtained during each stage; and
software. Treadmills have also been adapted to conduct (3) a linear relationship exists between heart rate and oxy-
ramp tests.17,22,23 The ramp protocol uses a constant and gen consumption over a wide range of values. Examples of
continuous increase in metabolic demand that replaces the submaximal tests used to estimate peak VO2 include the
“staging” used in conventional exercise tests. The uniform YMCA test, the Astrand test, and others. 20,28,29
increase in work allows for a steady increase in cardiopul-
monary responses and permits a more accurate estima-
tion of oxygen uptake.17 The recent call for “optimizing” 13.9 WALK TESTS FOR
exercise testing8,14,16,19 would appear to be facilitated by
the ramp approach, because large work increments are CARDIORESPIRATORY
avoided and increases in work are individualized, per-
mitting test duration to be targeted. Because there are no
FITNESS ASSESSMENT
stages per se, the errors associated with predicting exer- A number of walking tests have also been developed for
cise capacity alluded to previously are lessened.8,9,17 estimating cardiorespiratory fitness or assessing the func-
tional status of patients with cardiovascular or pulmo-
nary disease in clinical settings. Advantages of walk tests
13.8 SUBMAXIMAL TESTING include the fact that they are easy to perform and are rela-
tively inexpensive, and thus can be applied to large pop-
In general, maximal, symptom-limited tests are not con- ulations. Walk tests include: (1) the 6-minute walk test;
sidered appropriate until one month after myocardial (2) the Cooper 12-minute test; (3) the 1.5-mile test; and
infarction (MI) or cardiac surgery. Thus, submaximal the (4) Rockport One-mile Fitness Walking Test. 2
exercise testing has an important role clinically for pre- The 6-minute walk test is popular for assessing func-
discharge, post-MI, or post-bypass surgery evaluations. tional status in clinical settings and is mostly used among
Submaximal tests have been shown to be important in diseased populations such as patients with heart failure,
risk stratification 23–26 for making appropriate activity rec- stroke, and peripheral vascular disease. The objective of
ommendations, for recognizing the need for modification the test is to cover the greatest distance by walking in six
of the medical regimen, or for further interventions in minutes. Its obvious advantages are that it requires practi-
patients who have sustained a cardiac event. A submaxi- cally no equipment (other than a stopwatch) and little time.
mal, pre-discharge test appears to be as predictive for Although the association between 6-minute walk per-
future events as a symptom-limited test among patients formance and exercise capacity is only modest, peak VO2
less than one month after MI. Submaximal testing is also can be estimated from 6-minute walk distance by the
appropriate for patients with a high probability of serious following multivariate equation along with other readily
arrhythmias. The testing end points for submaximal test- available information:
ing have traditionally been arbitrary but should always be
based on clinical judgment. A heart rate limit of 140 beats
per min and a MET level of 7 are often used for patients
Peak VO2 = éë0.02*distance ( m ) ùû - éë0.191*age ( yr ) ùû
younger than age 40 years, and limits of 130 beats per min
and a MET level of 5 are often used for patients older than - éë0.07*weight ( kg ) ùû
40 years. For those using beta-blockers, a Borg perceived
exertion level in the range of 7 to 8 (1 to 10 scale) or 15 to
16 (6 to 20 scale) are conservative end points. The initial ë (
+ éë0.09*height ( cm ) ùû + é0.26*RPP *10 -3 ù
û )
onset of symptoms, including fatigue, shortness of breath,
m = meter; kg = kilogram; cm = centimeters; yr = year
or angina, is also an indication to stop the test. A low-level
protocol should be used, that is, one that uses no more
than 1-MET increments per stage. The Naughton proto- RPP = rate pressure product
col 27 is commonly used for submaximal testing. Ramp
testing is also ideal for this purpose because the ramp rate (systolic blood pressure [mm Hg ]*heart rate )
(such as 5 METs achieved over a 10-minute duration) can
be individualized depending on the patient tested.17 The Cooper 12-minute test is based on a similar concept
Submaximal testing can also be used to assess the (covering the greatest distance in 12 minutes), while the
capacity of apparently healthy individuals to exercise safely objective of the 1.5 mile test is to run the distance (1.5
or to estimate VO2 max by extrapolation. The premise miles) in the shortest period of time. Unlike the 6-min-
of estimating VO2 max from a submaximal test is based ute walk test, both of these tests are more suitable for
on the linear relationship between heart rate and oxygen healthy, younger individuals. They also require little or
consumption, provided that the work is aerobic in nature. no additional equipment and can be administered to large
In submaximal test protocols, the HR at each work- populations.
load is plotted against the workload and extrapolated to The Rockport One-mile Fitness Walking Test involves
VO2 max at an age-predicted maximal heart rate (typi- covering a 1-mile distance in the shortest period of time.
cally 220-age). VO2 max can be calculated using pre- However, in addition to the time required to cover the
diction equations2 or estimated from values obtained 1-mile distance, the test utilizes peak heart rate achieved
by commonly used exercise protocols if the following during the last minute of the walk, and an estimate of
170 Chapter 13 Physical Fitness Evaluation
peak VO2 is derived. If heart rate monitoring is not an McAuley et al.37 performed a follow-up study in a group
option during the test, a 10-second heart rate obtained of veterans referred for exercise testing for clinical reasons
immediately after the completion of the test can be used who were followed for a mean of 4.5 years. Expressed in
as an alternative. However, this is likely to overestimate tertiles, age-adjusted relative risks for all-cause mortality
peak VO2 compared to that calculated when heart rate is using the VSAQ were 1.0 (low CRF, referent), 0.54 (mod-
obtained during the last minute of the walk. erate CRF), and 0.22 (low CRF) (p for trend <001). Each
1-MET increase in the VSAQ conferred a 10% survival
benefit. Similarly, the DASI was developed in a cohort of
13.10 NON-EXERCISE consecutive subjects undergoing exercise testing for clini-
cal reasons, and consists of a 12-item scale related to a
TEST ESTIMATES OF patient’s ability to perform daily activities. The DASI
CARDIORESPIRATORY FITNESS has been shown to be strongly correlated with peak VO2
(r = 0.80), and studies have reported it to be a good predic-
The recent call for the inclusion of fitness as a clinical tor of risk for adverse outcomes in a variety of populations
vital sign30 has placed a renewed focus on non-exercise (32,45,46). Both the VSAQ and DASI have been widely
test methods to estimate CRF. This is due to the fact that used both to estimate exercise capacity and to estimate
although CRF has been increasingly recognized as a criti- long-term risk in a wide range of clinical populations, and
cal factor in stratifying risk, objective measures of CRF are both have been translated into several languages.31,32,44–49
rarely available during a routine clinical encounter. Thus, In a combined analysis using eight British cohorts that
the ability to estimate CRF without performing a formal included 32,319 individuals, a non-exercise test estimate
exercise test is attractive because it can be obtained quickly of CRF was performed using age, gender, BMI, resting
and inexpensively, without exposing an individual to the heart rate, and self-reported physical activity level.42 CVD
risk and discomfort of an exercise test. Many non-exercise and all-cause mortality were determined over a mean of
test based equations have been proposed using commonly 9 years. In men and women, respectively, 9.4% and 7.4%
available information during a typical clinic visit. Non- lower risks of all-cause and 15.6% and 16.9% lower risks
exercise test regression equations have typically included of CVD death per 1-MET increase were observed. In the
age, gender, BMI, and self-reported physical activity Norwegian HUNT study,36 a similar algorithm was used
patterns, although many other health metrics have been to estimate CRF among 37,112 individuals who were fol-
employed. In addition to being quick and simple to obtain, lowed for a mean duration of 24 years. After adjustment
these equations have a surprisingly robust correlation with for potential confounders, each 1-MET higher CRF was
objective fitness measures, typically in the range of 0.50 to associated with 21% lower CVD mortality for both men
0.80, and they have also been reported to strongly predict and women who were younger than 60 years at baseline;
outcomes.31–41 However, limitations of these tools include the corresponding lower risks for all-cause mortality were
the fact that they are subjective and that they lack the abil- 15% for men and 8% for women. Thus, although these
ity to assess symptoms, ECG, and hemodynamic responses non-exercise test estimates of CRF are likely population-
that are available during a formal exercise test. In addition, specific and should not be viewed as a replacement for an
they tend to underestimate and overestimate CRF at the exercise test when it is clinically necessary, they provide the
upper and lower ends of the distribution, respectively. clinician with a platform for counseling a patient regard-
A systematic review of this issue was performed using 13 ing the importance of physical activity. When an exercise
non-exercise test equations developed using various combi- test is unavailable or impractical, they also serve to identify
nations of age, gender, body weight (or BMI, percentage of individuals with low CRF who are at increased risk.
body fat, or waist circumference), physical activity patterns
(self-reported or measured), smoking, resting heart rate, or
perceived functional ability as predictors of CRF.34 The R2 13.11 MUSCULAR FITNESS
values (with measured or estimated peak VO2 as the depen-
dent variable) ranged from 0.50 to 0.86. Non-exercise The American College of Sports Medicine defines mus-
CRF estimates have been shown to be similar in accu- cular fitness as the ability of the muscle to perform tasks
racy to submaximal exercise prediction models.34,35,40,41 that require muscular strength or muscular endurance.
Although most of these studies have focused on healthy Strength is an important component of fitness assessment
asymptomatic populations, non-exercise test approaches since it has implications for an individual’s functional
that include assessment of symptoms during daily activities capabilities, disability, bone health, and insulin resistance,
are more applicable to clinically referred populations. The and has been shown to have a strong association with
latter include the Veterans Specific Activity Questionnaire long-term outcomes. 50
(VSAQ) and Duke Activity Status Index (DASI) and simi-
larly correlate well with measured exercise capacity.31,32
Estimates of CRF using these tools have also been 13.12 MUSCULAR STRENGTH
shown to provide valid estimates of long-term risk, includ-
ing mortality. 34,35,40–43 The VSAQ involves a one-page Muscular strength is defined as the ability of the muscle or
assessment of symptoms during daily activities prior to an muscle groups to exert force during a voluntary contrac-
exercise test. When combined with age in a regression for- tion.1 The maximal force a muscle or group of muscles can
mula, the VSAQ correlates strongly with exercise capac- exert is traditionally assessed by tests that require maxi-
ity as determined by an exercise test (multiple R = 0.82). mum effort against the greatest resistance one can move
13.15 Body Composition 171
through the full range of motion once. This is known as the conditions. They are both considered to be leading risk fac-
13
1-repetition maximum (1-RM). A percentage of the 1-RM tors for a number of chronic health conditions, including
is then used to determine the number of repetitions one diabetes, hypertension, coronary heart disease, and prema-
should perform to enhance the strength for a specific mus- ture mortality in developed countries. Although the mecha-
cle. Generally, 8–12 repetitions at 40% to 60% of 1-RM nisms and causes of obesity are poorly understood, experts
are sufficient to enhance muscular strength. An appropriate agree that obesity is largely the result of a chronic imbalance
resistance training regimen involves performing these 8–12 between caloric intake and caloric expenditure. This imbal-
repetitions 1–3 sets, 2–3 times per week. While intensities ance is likely the outcome of a complex interaction between
as much as 80% and relatively low repetitions (such as 3–5) genetic and environmental factors.54
have been shown to be quite effective for rapid strength
gains, this approach is generally limited to athletes whose
performance requires great amounts of force. 13.15.1 Definition, Assessment,
It is important to note that intensity for resistance and Classification of
exercise is not always easy to determine, and the 1-RM Overweight and Obesity
does not depict a true intensity. The number of repetitions
and the percentage of resistance based on 1-RM differ sig- Body composition is comprised of three major structural
nificantly between individuals and muscle groups. Thus, components: muscle, bone, and fat. Obesity is defined as
the 1-RM should only be used as a general guideline. 2 the accumulation of excess body fat, usually ≥25% of
the total body weight for men and ≥33% for women. 55
Assessing body fat is not a simple task. Several methods
13.13 MUSCULAR ENDURANCE have been developed with mixed success. The most com-
monly used methods, and their strengths and weaknesses,
Muscular endurance is defined as the ability of the muscle are presented below.
or muscle groups to perform repetitive contractions over a
period of time against resistance, such as lifting a set amount 13.15.2 Hydrodensiometry or
of weight several times.2 Muscular endurance is assessed by
tests requiring more than 12 repetitions. A simple test of
Underwater Weighing
muscular endurance is the maximum number of push-ups One of the historically common assessments of body com-
or sit-ups one can execute without rest.2 position is hydrodensiometry or underwater weighing.
This method is based on Archimedes’ principle, which
states that the weight an object loses when immersed in
13.14 TESTS OF ANAEROBIC POWER water is equal to the weight of the displaced water result-
ing from that immersion. The method is still widely used,
Because anaerobic power is an important determinant but is less common today given the advent of Dual-Energy
of athletic performance requiring high levels of exertion X-Ray Absorptiometry (DXA) and the fact that the
over short periods, tests have been developed to measure method is highly dependent on proper technique.
the capacity of the anaerobic energy systems. One of the Percent body fat is estimated from body density, know-
more common tests of this type is the Wingate test, which ing that lean mass (bone and muscle) is denser than body
involves 30 to 120 seconds of high-intensity effort on a fat. The density of fat is estimated to be 0.90 g/cm−3 and
cycle ergometer. The resistance is based on body mass 1.10 g/cm−3 for fat-free tissue. 56
(originally 0.075 kp per kg body mass, though this may The following two most commonly used equations for
vary) and is applied after initial inertia and unloaded estimating body composition from underwater weighing
resistance are overcome. Peak power is considered to rep- were developed in the late 1950s and early 1960s56,57 and
resent the highest mechanical power generated during any are still in use:
3- to 5-second period during the test; average power is the
average of the total power generated during the test. An Percent Body Fat = ( 495/Body density ) - 450 ( Siri )
underlying assumption of the Wingate test is that peak
power reflects the energy-generating capacity of the oxy-
Percent Body Fat = ( 457/Body Density ) - 414.2 ( Brozek )
gen-independent high energy phosphates, whereas average
power is a representation of one’s glycolytic capacity. 51,52
For example, if a person weighs 100 kg on land and 5 kg
In studies comparing the Wingate test results to athletic
submerged in water, the body density of this person is com-
performance and laboratory findings, it has been dem-
puted as mass divided by volume:
onstrated to be a good index of these energy systems,
although studies are mixed in terms of its ability to predict
success in events requiring high exercise intensity. 52 Body density = 100,000 g/95,000 cm 3 = 1.0526
In the United States and most of the industrialized world, Percent Body Fat = ( 495/1.0526 ) - 450
obesity has reached epidemic proportions.53 Overweight and
obesity are not simply cosmetic problems, but serious health = 470.26 - 450 = 20.26
172 Chapter 13 Physical Fitness Evaluation
Percent Body Fat = ( 457/1.0526 ) - 414.2 Please note that body density is inversely related to
the water temperature. Body density at 4 degrees C or
= 434.16 - 414.2 = 19.96 39.2 degrees F is 1.0 and declines as water temperature
increases. For practical reasons, warmer temperatures are
Lean body mass (LBM) is then calculated by subtracting used and the appropriate density value is applied.
body fat from total body weight. Thus, the lean body mass It is important to emphasize that the generalized density
of this individual weighing 100 kg is approximately 80 kg. values of 1.10 for fat free (1.10 g/cm−3) and fat (0.90 g/cm−3)
are based on young and middle-age white men. The den- The estimated BMI for different weights and heights is
13
sity of LBM is higher for blacks (1.113) than whites. This presented in Table 13.5.
leads to an overestimation of LBM and underestimation of A set of cut-points at 5 BMI intervals to classify overweight
body fat for black. Thus, the following modification of the and obesity has been adapted by the National Heart, Lung,
Siri formula has been proposed for blacks. 58 and Blood Institute and the World Health Organization.55
Based on this classification, men and women with a BMI
Percent Body Fat = ( 437.4/Body Density ) -392.8 ≥30 kg/m2 are considered obese (Table 13.6). However, it
is important to keep in mind that BMI may not accurately
reflect true adiposity for some populations. For example, a
relatively muscular male weighing 100 kg, 1.80 meters in
13.15.3 Other Methods height and approximately 20% actual body fat, has a BMI
Direct assessment of body fat by densitometry is one of the of 30.86 (BMI = 100/1.802). Conversely, a male 1.80 m tall,
most accurate methods, but it is generally not practical for weighing 80 kg, with 30% actual body fat, has a BMI of
large populations. Thus, several indirect techniques have 24.7. According to the classification system commonly used
been developed over the years to assess body composi- (Table 13.6), these individuals will be misclassified as obese
tion. The most commonly used methods for estimating and normal weight, respectively.5
or assessing body composition, and their advantages and From: ACSM Position Stand on Appropriate
disadvantages, are described in Table 13.4. 5 Intervention Strategies for Weight Loss and Prevention of
Because direct body-fat assessment is impractical for Weight Regain for Adults.62
large populations, the American Heart Association (AHA)
and other health organizations have adopted body mass
index (BMI) as a practical clinical indicator of adipos- 13.16 WAIST CIRCUMFERENCE
ity. 54 BMI, calculated as weight [kg] divided by height [m]
squared (kg/m 2), correlates well with total body fat and Evidence supports the concept that excess accumulation of
is related to cardiovascular and all-cause mortality. 59–61 adipose tissue in the abdomen, characteristic of male type fat
TABLE 13.5 Body Mass Index (BMI) Based on Weight and Height
Body Weight (lbs)
HT
(inches) 120 130 140 150 160 170 180 190 200 210 220 230 240 250
58 25 27 29 31 33 36 38 40 42 44 46 48 50 52
59 24 26 28 30 32 34 36 38 40 42 44 46 48 50
60 23 25 27 29 31 33 35 37 39 41 43 45 47 49
61 23 25 26 28 30 32 34 36 38 40 42 43 45 47
62 22 24 26 27 29 31 33 35 37 38 40 42 44 46
63 21 23 25 27 28 30 32 34 35 37 39 41 43 44
64 21 22 24 26 27 29 31 33 34 36 38 39 41 43
65 20 22 23 25 27 28 30 32 33 35 37 38 40 42
66 19 21 23 24 26 27 29 31 32 34 36 37 39 40
67 19 20 22 23 25 27 28 30 31 33 34 36 38 39
68 18 20 21 23 24 26 27 29 30 32 33 35 36 38
69 18 19 21 22 24 25 27 28 30 31 32 34 35 37
70 19 20 22 23 24 26 27 29 30 32 33 34 36
71 18 20 21 22 24 25 26 28 29 31 32 33 35
72 18 19 20 22 23 24 26 27 28 30 31 33 34
73 18 20 21 22 24 25 26 28 29 30 32 33
74 18 19 21 22 23 24 26 27 28 30 31 32
75 19 20 21 22 24 25 26 27 29 30 31
76 18 19 21 22 23 24 26 27 28 29 30
77 18 19 20 21 23 24 25 26 27 28 30
Body mass index <18 is associated with poor health outcomes, therefore these values are not represented in this table.
174 Chapter 13 Physical Fitness Evaluation
TABLE 13.6 Classification of Body Weight and Obesity Based on BMI and Waist Circumference
Obesity Class BMI (kg/m2) Waist Circumference Associated Health Risk
Underweight <18.5
Normal 18.5—24.9 Average
Overweight 25.0—29.9 Men: ≥94 cm Increased
Women: ≥80 cm
Obesity Class I 30.0—34.9 Men: ≥102 cm Moderate
Women: ≥88 cm
Moderate Obesity II 35.0—39.9 High
Severe Obesity III ≥40 Very High
distribution (android, abdominal, or central obesity) is asso- total body fat is subcutaneous fat and the remaining is vis-
ciated with a higher risk for mortality than peripheral distri- ceral fat. Thus, skinfold thickness parallels total body fat
bution of body fat.63 This is because fat that surrounds the and is another method often used to estimate body com-
internal organs, known as visceral fat, is most closely associ- position. Because proportionally more fat is deposited vis-
ated with metabolic disorders that increase cardiovascular cerally with advancing age, age-adjusted equations should
risk, including insulin resistance, lipid abnormalities, and be used in older men and women. Assuming that the
heightened markers of inflammation. Since BMI also fails appropriate technique is used and factors that contribute
to take body fat distribution into account, waist circumfer- to measurement error are controlled, the technique corre-
ence provides a practical method for assessing mortality risk lates fairly well with hydrodensiometry (r = 0.70 to 0.90).
associated with central distribution of fat, if a direct body fat Accuracy is also compromised with extremely obese or
assessment is not available. Waist circumference correlates extremely lean individuals.
more strongly with abdominal fat than BMI. Waist circum- Over the years, several sites and techniques have
ferences >102 cm for men and >88 cm for women are asso- been identified and used to assess body composition
ciated with increased cardiovascular risk.64,65 via skinfolds. A thorough review of anthropometric
assessments related to skinfolds is recommended for
those interested in a more detailed description of this
13.17 SKINFOLD ASSESSMENT methodology. 66 These techniques are also reviewed
in the ACSM Guidelines for Exercise Testing and
Body composition estimated by skinfold measurements is Prescription. 2
based on the premise that approximately one-third of the
REFERENCES
1. Caspersen CJ and Kristenson GM. on level of habitual physical activity and Rehabilitation, and Prevention of the
Physical activity, exercise, and physical exercise participation. Am. J. Epidemiol. Council on Clinical Cardiology and the
fitness: Definitions and distinctions for 1989;129(5):1012–1022. Council on Cardiovascular Nursing.
health-related research. Public Health 8. Gibbons RJ, Balady GJ, Bricker JT, et Circulation 2007;116:329e343.
Rep. 1985;100:126–131. al. ACC/AHA 2002 guideline update for 12. Glass S and Dwyer GD, eds. ACSM
2. Whaley BPH, Mitchel H, and Otto exercise testing. A report of the ACC/ Metabolic Calculations Handbook.
Robert M, eds. ACSM’s Guidelines for AHA task force on practice guidelines Baltimore, MD: Lippincott Williams &
Exercise Testing and Prescription, 7th ed. (committee on exercise testing). J. Am. Wilkins, 2007.
New York, NY: Lippincott Williams & Coll. Cardiol. 2002;40:1531–1540. 13. Kokkinos P, Kaminsky LA, Arena R,
Wilkins, 2006. 9. ACSM’s Guidelines for Exercise Testing et al. Equation for predicting maxi-
3. Kokkinos P, Myers J, Faselis C, et al. and Prescription, 10th ed. Baltimore, mal oxygen uptake (from the fitness
Exercise capacity and mortality in MD: Wolters Kluwer, 2017. registry and the importance of exercise
older men: A 20-year follow-up study. 10. Myers J, Kaminsky L, Lima R, et al. A national database). Am. J. Cardiol.
Circulation 2010;122:790–797. reference equation for normal standards 2017;120:688–692.
4. Kokkinos P and Myers J. Exercise for VO2 max: Analysis from the fitness 14. Myers J and Froelicher VF. Optimizing
and physical activity: Clinical out- registry and the importance of exercise the exercise test for pharmacologic
comes and applications. Circulation database (FRIEND registry). Prog. studies in patients with angina pectoris.
2010;112:1637–1648. Cardiovasc. Dis. 2017. http://dx.doi.o In D. Ardissino, S. Savonitto, & L.H.
5. Kokkinos P. Physical Activity and rg/10.1016/j.pcad.2017.03.002 Opie (Eds.). Drug Evaluation in Angina
Cardiovascular Disease Prevention. 11. Arena R, Myers J, Williams MA, et al. Pectoris. Pavia, Italy: Kluwer Academic,
Sudbury, MA: Jones and Bartlett, 2010; American Heart Association Committee 1994, pp. 41–52.
pp. 19-–50. on Exercise, Rehabilitation, and 15. Webster MWI and Sharpe DN. Exercise
6. Bouchard C, Daw EW, Rice T, et al. Prevention of the Council on Clinical testing in angina pectoris: The impor-
Familial resemblance for VO2max in Cardiology; American Heart Association tance of protocol design in clinical trials.
the sedentary state: The HERITAGE Council on Cardiovascular Nursing. Am. Heart. J. 1989;117:505–508.
family study. Med. Sci. Sports Exerc. Assessment of functional capacity in 16. Buchfuhrer MJ, Hansen JE, Robinson
1998;30(2):252–258. clinical and research settings: A scientific TE, et al. Optimizing the exercise proto-
7. Perusse L, Tremblay A, Leblanc C, et al. statement from the American Heart col for cardiopulmonary assessment. J.
Genetic and environmental influences Association Committee on Exercise, Appl. Physiol. 1983;55:1558–1564.
References 175
17. Myers J, Buchanan N, Walsh D, et al. 33. Tomazi Neves LM, Neto AK, Pasquale 48. Kojima S, Wang DH, Tokumori K, et al.
Comparison of the ramp versus standard Arenas K, et al. Translation and cross-cul- Practicality of Veterans Specific Activity
exercise protocols. J. Am. Coll. Cardiol.
1991;17:1334–1342.
18. Myers J. Essentials of Cardiopulmonary
tural adaptation of the Duke activity sta-
tus index to Brazilian Portuguese. Fisioter.
Mov. Curitiba July/Sept. 2013;26(3).
Questionnaire in evaluation of exercise
capacity of community-dwelling Japanese
elderly. Environ. Health Prev. Med.
13
Exercise Testing. Champaign, IL: Human 34. Maranhao Neto Gde A, Lourenco PM, 2006;11:313–320.
Kinetics, 1996. and Farinatti Pde T. Prediction of aerobic 49. Maranhão-Neto Gde A, Leon AC, and
19. Arena R, Myers J, Williams MA, et al. fitness without stress testing and applicabil- Farinatti Pde T. Validity and equivalence
Assessment of functional capacity in ity to epidemiological studies: A systematic of the Portuguese version of the Veterans
clinical and research settings: A scientific review. Cad. Saude Publica 2004;20:48–56. Specific Activity Questionnaire. Arq.
statement from the American Heart 35. Mailey EL, White SM, Wojcicki TR, et Bras. Cardiol. 2011;97:130–135.
Association Committee on Exercise, al. Construct validation of a non-exercise 50. Artero EG, Lee DC, Ruiz JR, et al.
Rehabilitation, and Prevention of the measure of cardiorespiratory fitness Prospective study of muscular strength
Council on Clinical Cardiology and the in older adults. BMC Public Health and all-cause mortality in men with
Council on Cardiovascular Nursing. 2010;10:59. hypertension. J. Am. Coll. Cardiol.
Circulation 2007;116:329–343. 36. Nes BM, Vatten LJ, Nauman J, et al. 2011;57:1831–1837.
20. Astrand PO and Rodahl K. Textbook of A simple nonexercise model of cardio- 51. Vandewalle D, Gilbert P, and Monod H.
Work Physiology, 3rd ed. New York, NY: respiratory fitness predicts long-term Standard anaerobic tests. Sports Med.
McGraw-Hill, 1986. mortality. Med. Sci. Sports Exerc. 1987;4:268–289.
21. Whipp BJ, Davis JA, Torres F, et al. A 2014;46:1159–1165. 52. Bar-Or O. The Wingate anaerobic test:
test to determine parameters of aerobic 37. McAuley P, Myers J, Abella J, et al. An update on methodology, reliability and
function during exercise. J. Appl. Physiol. Evaluation of a specific activity ques- validity. Sports Med. 1987;4:381–394.
1981;50:217–221. tionnaire to predict mortality in men 53. Seidell JC. Time trends in obesity: An epi-
22. Myers J, Buchanan N, Smith D, et referred for exercise testing. Am. Heart J. demiological perspective. Horm. Metab.
al. Individualized ramp treadmill: 2006;128:e1–e7. Res. 1997;29(4):155–158.
Observations on a new protocol. Chest 38. Wier LT, Jackson AS, Ayers GW, et 54. Eckel RH and Krauss RM. American
1992;101:2305–2415. al. Nonexercise models for estimat- Heart Association call to action: Obesity
23. Porszasz J, Casaburi R, Somfay A, et al. ing VO2max with waist girth, percent as a major risk factor for coronary heart
A treadmill ramp protocol using simulta- fat, or BMI. Med. Sci. Sports Exerc. disease. AHA Nutrition Committee.
neous changes in speed and grade. Med. 2006;38:555–561. Circulation 1998;97(21):2099–2100.
Sci. Sports Exerc. 2003;35:1596–1603. 39. Martinez-Gomez DG-CP, Hallal PC, 55. WHO. Obesity: Preventing and
24. Chang JA and Froelicher VF. Clinical Lopez-Garcia E, et al. Nonexercise Managing the Global Epidemic. Geneva:
and exercise test markers of progno- cardiorespiratory fitness and mortality WHO, WHO/NUT/NCD/98.1, 1998.
sis in patients with stable coronary in older adults. Med. Sci. Sports Exerc. 56. Siri WE. Body composition from fluid
artery disease. Curr. Probl. Cardiol. 2014;47:568–574. spaces and density. Univ. Calif. Donner
1994;19:533–538. 40. Jackson AS, Sui X, O’Connor DP, et al. Lab. Med. Phys. Rep. 1956.
25. Froelicher ES. Usefulness of exercise test- Longitudinal cardiorespiratory fitness 57. Brozek J, Grande F, Anderson JT, et al.
ing shortly after acute myocardial infarc- algorithms for clinical settings. Am. J. Densitometric analysis of body com-
tion for predicting 10-year mortality. Am. Prev. Med. 2012;43:512–519. position: Revision of some quantitative
J. Cardiol. 1994;74:318–323. 41. George JD, Stone WJ, and Burkett LN. assumptions. Ann. N. Y. Acad. Sci.
26. Olona M, Candell-Riera J, Permanyer- Non-exercise VO2max estimation for 1963;110:113–140.
Miralda G, et al. Strategies for prog- physically active college students. Med. 58. Cote KD and Adams WC. Effect of bone
nostic assessment of uncomplicated Sci. Sports Exerc. 1997;29:415–423. density on body composition estimates in
first myocardial infarction: 5-Year 42. Stamatakis E, Hamer M, O’Donovan young adult black and white women. Med.
follow-up study. J. Am. Coll. Cardiol. G, et al. A non-exercise testing method Sci. Sports Exerc. 1993;25:290–296.
1995;25:815–822. for estimating cardiorespiratory fitness: 59. Lee IM, Manson JE, Hennekens CH, et
27. Naughton J, Balke B, and Nagle F. Associations with all-cause and cardio- al. Body weight and mortality. A 27-year
Refinements in methods of evaluation and vascular mortality in a pooled analysis follow-up of middle-aged men. JAMA
physical conditioning before and after of eight population-based cohorts. Eur. 1993;270(23):2823–2828.
myocardial infarction. Am. J. Cardiol. Heart J. 2013;34:750–758. 60. Manson JE, Willett WC, Stampfer
1964;14:837–843. 43. Artero EG, Jackson AS, Sui X, et al. MJ, et al. Body weight and mortal-
28. Maritz JS, Morrison JF, and Peter J. Longitudinal algorithms to estimate ity among women. N. Engl. J. Med.
A practical method of estimating an cardiorespiratory fitness: Associations 1995;333(11):677–685.
individual’s maximal oxygen uptake. with nonfatal cardiovascular disease and 61. Stevens J, Cai J, Pamuk ER, et al. The
Ergonomics 1961;4:97–122. disease-specific mortality. J. Am. Coll. effect of age on the association between
29. Golding LA. YMCA Fitness Testing and Cardiol. 2014;63:2289–2296. body-mass index and mortality. N. Engl.
Assessment Manual. Champaign, IL: 44. Ravani R, Kilb B, Bedi H, et al. The J. Med. 1998;338(1):1–7.
Human Kinetics, 1989. Duke Activity Status Index in patients 62. Jakicic JM, Clark K, Coleman E, et al.
30. Ross R, Blair S, Arena R, et al. with chronic kidney disease: A reliabil- American College of Sports Medicine
Importance of assessing cardiorespiratory ity study. Clin. J. Am. Soc. Nephrol. position stand. Appropriate intervention
fitness in clinical practice: A case for fit- 2012;7:573–580. strategies for weight loss and prevention
ness as a clinical vital sign. An American 45. Wessel TR, Arant CB, Olson MB, et al. of weight regain for adults. Med. Sci.
Heart Association Scientific Statement Relationship of physical fitness vs body Sports Exerc. 2001;33(12):2145–2156.
from the Committee on Physical Activity mass index with coronary artery disease 63. Kannel WB, Cupples LA, Ramaswami R,
and the Council on Lifestyle and and cardiovascular events in women. et al. Regional obesity and risk of cardio-
Cardiometabolic Health. Circulation JAMA 2004;292:1179–1187. vascular disease; the Framingham study.
2016;134:e653–e699. 46. Bashour CA, Yared JP, Ryan TA, et J. Clin. Epidemiol. 1991;44(2):183–190.
31. Myers J, Do D, Herbert W, et al. A al. Long-term survival and functional 64. Rosenbaum M, Leibel RL, and
nomogram to predict exercise capac- capacity in cardiac surgery patients after Hirsch J. Obesity. N. Engl. J. Med.
ity from a specific activity question- prolonged intensive care. Crit. Care Med. 1997;337(6):396–407.
naire and clinical data. Am. J. Cardiol. 2000;28:3847–3853. 65. van der Kooy K, Leenen R, Seidell JC, et
1994;73:591–596. 47. Cook JW, Pierson LM, Herbert WG, al. Waist-hip ratio is a poor predictor of
32. Hlatky MA, Boineau RE, Higginbotham et al. The influence of patient strength, changes in visceral fat. Am. J. Clin. Nutr.
MB, et al. A brief self-administered aerobic capacity and body composition 1993;57(3):327–333.
questionnaire to determine functional upon outcomes after coronary artery 66. Lohman TG. Advances in Body
capacity (the Duke Activity Status Index). bypass grafting. Thorac. Cardiovasc. Composition Assessment. Human
Am. J. Cardiol. 1989;64:651–654. Surg. 2001;49:89–93. Kinetics. 1992; pp. 1–150.
14
CHAPTER
Key Take-Home Points............................................................... 177 14.3.2 Amount of Resistance; Repetitions and Sets........ 183
14.1 Physical Activity Recommendations.................................. 178 14.3.3 Frequency of Training.......................................... 183
14.2 Exercise Prescription........................................................ 179 14.3.4 Rate of Progression............................................. 183
14.2.1 Physical Fitness Parameters.................................. 179 14.4 Flexibility Training........................................................... 183
14.2.2 Exercise Training Principles................................... 179 14.5 Warm-Up and Cool-Down............................................... 184
14.2.2.1 Progressive Overload............................ 179 14.6 Physical Activity Adherence............................................ 184
14.2.2.2 Specificity............................................ 179 14.6.1 Exercise Prescription for Special Populations........ 184
14.2.2.3 Reversibility......................................... 180 14.7 Children and Adolescents............................................... 184
14.2.2.4 Cardiorespiratory Endurance Training......180 14.8 Older Adults.................................................................... 185
14.2.2.5 Type (Mode) of Exercise........................ 180 14.9 Pregnancy and Postpartum............................................. 185
14.2.2.6 Intensity of Exercise............................. 180 14.10 Diabetes Mellitus............................................................ 186
14.2.2.7 Time (Duration) of Exercise................... 181 14.11 Cancer............................................................................ 187
14.2.2.8 Frequency of Exercise.......................... 181 14.12 Arthritis........................................................................... 188
14.2.2.9 Overall Exercise Volume....................... 182 14.13 Disabilities...................................................................... 188
14.2.2.10 Rate of Progression.............................. 182 14.14 Summary........................................................................ 188
14.3 Resistance Training........................................................... 182 Clinical Applications................................................................... 188
14.3.1 Type of Resistance................................................ 182 References................................................................................ 189
177
178 Chapter 14 Exercise Prescription for Apparently Healthy Individuals and for Special Populations
* From 2018 Physical Activity Guidelines Advisory Committee. 2018 Physical Activity Guidelines Advisory Committee Scientific Report. Washington, DC: U.S. Department of
Health and Human Services, 2018. Available at: https://health.gov/paguidelines/second-edition/report/pdf/PAG_Advisory_Committee_Report.pdf.
*Although physical fitness is dichotomized into health- and skill-related categories, overlap exists between the two (see text).
†From Corbin CB, Lindsey R. Concepts in Physical Education with Laboratories (8th edition). Dubuque, IA: Times Mirror Higher Education Group, 1994.
added back to the product to yield the target VO2 . An complicated, it may result in a more appropriate intensity
14
example of this procedure is presented in Table 14.4. prescription, particularly among the elderly. Regardless of
Knowing the MET (“metabolic equivalent”) levels of the formula used, it is important to realize that HR max
various activities can be useful in prescribing physical has a standard deviation of 10–12 beats per minute (bpm)
activity after a target VO2 range has been determined. across the adult age span. This can obviously limit the
One MET is an estimation of a person’s energy expen- value of using age-predicted HR max in determining a target
diture when seated at rest (3.5 mL.kg−1.min−1). As an heart rate. As such, many professionals prescribe HRtarget
example, if a person performs an activity that requires as a range of 10% HR reserve or so. A person’s subjective
six times the energy requirement of sitting at rest, that feeling of effort should also be taken into account dur-
activity would carry a MET level of six, requiring a VO2 ing exercise. On a scale of 0 to 10, where sitting is 0 and
of approximately 21 mL.kg−1.min−1 (6 x3.5 = 21). The maximal effort is 10, moderate-intensity activity should
Compendium of Physical Activities (https://sites.googl yield a rating of 5 or 6 and vigorous-intensity activity of 7
e.com/site/compendiumofphysicalactivities/) has been or 8.3 Such ratings are particularly useful for people who
published to provide the MET requirements of more than have clinical conditions or take medications that affect the
800 leisure-time and occupational activities.9 Table 14.5 heart rate response to exercise.
includes examples of MET levels for some of the most As an alternative to the HR reserve method, exercise
common activities. If a target MET range has been deter- intensity may be prescribed using a straight percentage
mined (METtarget = VO2target ÷3.5), the Compendium can be of HR max (65–90% HR max is approximately equivalent to
used to identify activities of appropriate intensity. 50–85% HR reserve). However, many professionals prefer
Many professionals find it more practical to prescribe the HR reserve method, as it is more individualized due to its
exercise intensity by heart rate rather than VO2 . Since taking HR rest into account.
heart rate and VO2 have a linear relationship during
graded exercise, a given percentage of heart rate reserve
(HR reserve) parallels the same percentage of VO2reserve and 14.2.2.7 Time (Duration) of Exercise
therefore may be used in its place. When available, it is For improvement in cardiorespiratory fitness, 20–60 min-
preferable to use the maximal heart rate (HR max) attained utes per session is recommended, with duration and inten-
from a maximal graded exercise test. If a true HR max is not sity interacting with one another. For example, 20–30
available, an age-predicted value may be used. Just as with minutes of exercise at a higher intensity can yield similar
the VO2reserve method, HR rest is subtracted from HR max to benefits to 50–60 minutes of exercise at a lower intensity.
obtain HR reserve. The target heart rate is then derived by Similar health and fitness benefits are recognized regardless
multiplying HR reserve by the desired percentage and adding of whether exercise is performed continuously or intermit-
HR rest to the product (Table 14.4). tently throughout the day in bouts of ten minutes or more.
The most common formula for estimating HR max in
adults is “HR max = 220-age”. It is most accurate at the
age of 40 years, and over- and underestimates HR max 14.2.2.8 Frequency of Exercise
in younger and older people, respectively. A more accu- Three to five days of exercise have traditionally been rec-
rate formula, “HR max = 206.9 − (0.67xage)”, has recently ommended for the improvement of cardiorespiratory fit-
been introduced.10 While this formula is slightly more ness. While six or seven days per week may be practiced to
TABLE 14.4 Calculation of target oxygen consumption (VO2target ) and target heart rate (HRtarget ) by reserve method
VO2target* HRtarget
Step 1: Calculate VO2reserve. Step 1: Estimate HRmax.†
VO2reserve = VO2max-VO2rest HRmax = 220-age#
Step 2: Multiply VO2reserve by the desired percentage. Step 2: Calculate HRreserve.
VO2fraction = VO2reservexTarget Percentage HRreserve = HRmax-HRrest
Step 3: Calculate VO2target by adding VO2rest to VO2fraction. Step 3: Multiply HRreserve by the desired percentage.
VO2target = VO2fraction+VO2rest HRfraction = HRreservexTarget Percentage
Example – You want a person with a VO2max of 35 mL.kg−1.min−1 to Step 4: Calculate HRtarget by adding HRrest to HRfraction.
exercise at 65% VO2reserve: HRtarget = HRfraction+HRrest
Step 1: Calculate VO2reserve. Example – You want a 50-year-old person with a HRrest of 70
VO2reserve = 35.0-3.5 = 31.5 mL.kg−1.min−1 bpm to exercise at 65% HRreserve:
Step 2: Multiply VO2reserve by the desired percentage. Step 1: Estimate HRmax.†
VO2fraction = 31.5x0.65 = 20.5 mL.kg−1.min−1 HRmax = 220-50 = 170 bpm#
Step 3: Calculate VO2target by adding VO2rest to VO2fraction. Step 2: Calculate HRreserve.
VO2target = 20.5+3.5 = 24.0 mL.kg−1.min−1 HRreserve = 170-70 = 100 bpm
Step 3: Multiply HRreserve by the desired percentage.
HRfraction = 100x0.65 = 65 bpm
Step 4: Calculate HRtarget by adding HRrest to HRfraction.
HRtarget = 65+70 = 135 bpm
TABLE 14.5 Sample metabolic equivalent (met) levels of common physical activities*
Activity METs Activity METs
Walking, 2 miles per hour 2.8 Aerobic dancing 5.0–9.5
Walking, 3 miles per hour 3.5 Golf, using power cart 3.5
Walking, 4 miles per hour 5.0 Golf, walking, pulling/carrying clubs 4.3–5.3
Running, 6 miles per hour 9.8 Tennis 4.5–8.0
Running, 7.5 miles per hour 11.5 Soccer 7.0–10.0
Running, 9 miles per hour 12.8 Washing and waxing car 2.0
Bicycling, 5.5 miles per hour 3.5 Most housecleaning activities 2.5–3.5
Bicycling, 9.4 miles per hour 5.8 Gardening 2.3–5.8
Bicycling, 15 miles per hour 10.0 Mowing lawn, riding mower 2.5
Swimming, sidestroke 7.0 Mowing lawn, walk, power mower 4.5–5.0
Swimming, crawl, ~50 yards per min 8.3 Mowing lawn, walk, hand mower 6.0
Swimming, crawl, ~75 yards per min 10.0 Shoveling dirt or snow 5.3–7.8
* From: Ainsworth BE, Haskell WL, Hermann SD, et al. The Compendium of Physical Activities Tracking Guide. Healthy Lifestyles Research Center, College of Nursing and
Health Innovation, Arizona State University. https://sites.google.com/site/compendiumofphysicalactivities/.
accumulate the moderate-intensity guidelines of 150–300 exercise duration (5–10 minutes per session), as they are
minutes per week, such a frequency of vigorous-intensity usually well-tolerated and may be less likely to negatively
exercise will likely increase one’s chance of injury while affect exercise adherence. Depending upon a person’s
yielding few additional health or fitness benefits. Therefore, beginning exercise volume and his or her goals, frequency
as with other exercise prescription parameters, exercise and/or intensity may then be increased. Although some-
frequency should vary with goals. For example, daily or what anecdotal, the “ten percent rule” is a good rule of
near-daily physical activity is advocated for weight loss or thumb; exercise volume (usually quantified by distance
maintenance while “recovery days” of rest or lighter activity or time) should not be increased by more than 10% per
are usually necessary between more intense workouts. week. Overtraining symptoms (e.g., upper respiratory
infection, muscle/joint pain) should be recognized, and a
reduction of training volume and/or a change of exercise
14.2.2.9 Overall Exercise Volume modality should be implemented. Additionally, periodiza-
The 1996 Report of the Surgeon General recommended tion (changing intensity, duration, and/or overall train-
1,000 kilocalories as the minimum weekly energy expen- ing volume within and across weeks) can enhance fitness
diture necessary to accrue health benefits. 2 This recom- improvement and reduce overtraining symptoms.
mendation is congruent with the 150 weekly minutes of
moderate-intensity or 75 minutes of vigorous-intensity
physical activity recommended in the Physical Activity
Guidelines for Americans. 3 The concept of a dose-
14.3 RESISTANCE TRAINING
response relationship is more evident in the more recent The Physical Activity Guidelines for Americans recom-
recommendations, that is, a greater amount of physi- mend that muscle-strengthening (resistance) activities that
cal activity will yield greater health and fitness benefits. involve all major muscle groups be performed on two or
Therefore, the Guidelines recognize that 300 weekly min- more days per week.3 Benefits of resistance training include
utes of moderate-intensity physical activity is superior to maintenance or increases in bone mass, insulin sensitivity,
150 minutes for most people (and 150 weekly minutes of and skeletal muscle mass, the latter being important for
vigorous-intensity physical activity may be superior to 75 those attempting to lose weight. Maintenance or gain in
minutes). Further health benefits from physical activity strength can also be important in preserving physical func-
quantities above those recommended in the Guidelines tion in the elderly and persons with certain disabilities.
are not well documented. In addition, while greater fitness
benefits may result from higher volumes of exercise, the
risk of overtraining symptoms also increases.
On the other end of the continuum, some people may
14.3.1 Type of Resistance
be deconditioned to the extent that they have difficulty Dynamic resistance exercises alternately overcome (con-
attaining the minimal physical activity recommendations. centric contractions) and accommodate (eccentric con-
Such people should do as much physical activity as they can tractions) a given force. This force is often in the form
without undue fatigue, with the goal of progressing into of weights (either “free” weights or stacked weights on
the range recommended in the Guidelines, which state: various machines) but can also exist in other forms, such
“For all individuals, some activity is better than none”.3 as elastic bands or one’s own body weight. The type of
resistance to be used in training depends largely upon the
goals of the participant, and a combination of resistance
14.2.2.10 Rate of Progression modes is often employed. More “controlled” modes (e.g.,
Training volume can be increased through alteration of weight machines, resistance bands) are generally safer and
exercise frequency, intensity, and/or duration. Many less likely to require a spotter, while less controlled modes
professionals first choose to implement small changes in (e.g., free weights) require more balance and tend to mimic
14.4 Flexibility Training 183
real-life movement more. In addition, lifting in a more sta- to fatigue on a regular basis will almost always result in
14
ble position (e.g., from a bench) allows for more weight to strength gains. In time, additional sets will likely be neces-
be lifted, resulting in greater strength gain. Lifting from sary for further improvement.3 The American College of
less stable surfaces (e.g., stability balls) requires lowering Sports Medicine (ACSM) recommends that 2–4 sets be
of the training resistance and will likely result in lower performed with each muscle group. However, more than
specific-strength gain but causes adaptation over a wider one exercise may be employed for a given muscle group.
range of motor units, resulting in a more functional train- For example, both the bench press and dips involve the
ing effect. As such, the greatest performance gains may pectoralis and tricep muscles but require different move-
result from employing a combination of resistance modes. ment patterns. Therefore, completing a single set of both
Regarding exercise adherence, preference of exercise type of these exercises would satisfy this recommendation for
should also be taken into account. these muscle groups.8 In short, the number of sets to be
For the purposes of safety and effectiveness (i.e., speci- performed depends upon the goals of the participant.
ficity), proper technique (e.g., keeping back straight, con- Health and functional benefits can be recognized with a
trolling eccentric portion of exercise) should be stressed minimum number of sets, while athletes commonly exceed
with any type of exercise. In addition, unless the devel- the number of sets recommended by health organizations.
opment of isometric (static) strength is a specific training
goal, resistance exercises should be dynamic, generally
taking the involved joints through the fullest range of
motion possible. This allows a greater number of motors
14.3.3 Frequency of Training
units to be trained, creating more functional benefits. To allow sufficient recovery, resistance training ses-
Regardless of the mode(s) of resistance used, all major sions should be spaced at least 48 hours apart from one
muscle groups should be exercised. At least 8–10 different another.8 Therefore, 2–3 days per week of resistance
exercises are generally required to target all of the major training is recommended. If time constraints do not per-
muscle groups. Accordingly, to encompass the entire body mit all exercises to be performed in a given day, then the
and lessen the chances of strength imbalances, oppos- same muscle groups should not be exercised on consecu-
ing (antagonistic) muscle groups should be exercised. For tive days (e.g., train the upper body one day and the lower
example, if the abdominal muscles are focused upon in body the next).
one exercise, another exercise should target the lower back
muscles; both the biceps and triceps should be targeted in
separate exercises, etc. For practical purposes, multi-joint 14.3.4 Rate of Progression
exercises (e.g., bench press, squat) that simultaneously
train more than one muscle group are preferred over sin- As mentioned above, resistance training sets should be
gle-joint exercises (e.g., triceps extension, leg extension) performed to fatigue in order for muscular fitness gains
because they are more time-efficient and tend to repre- to be achieved. A person should increase the resistance
sent real-life movements more. However, single-joint exer- of an exercise when he or she can perform one or two
cises can still serve as useful adjuncts, particularly if they extra repetitions with good form. To remain in the desired
mimic a particular movement in a sport or other activity repetition range (e.g., 8–12), increases of 2.5 to 5 pounds
for which a person is training. are generally appropriate for smaller muscle groups, and
increases of 5 to 10 pounds are generally appropriate for
larger ones.
Even when the above criteria are followed, people
14.3.2 Amount of Resistance; training for larger gains in muscle size and strength often
Repetitions and Sets plateau, or fail to experience continued improvement,
To achieve improvements in both muscular endurance and after many months. In this case, periodization, the fre-
strength, completion of 8 to 12 repetitions of each exer- quent alteration of training intensity, repetitions, sets,
cise to a point of fatigue (not necessarily failure) is rec- and/or resistance mode, can be useful. While beyond the
ommended. Lifting to fatigue implies that an additional scope of this chapter, the ACSM has published a position
repetition would be difficult to perform without help.3 stand addressing this topic.11
Performing 8–12 repetitions to fatigue generally requires a
resistance of 60–80% of a person’s 1-repetition maximum
(1RM; the maximum amount of weight that can be lifted 14.4 FLEXIBILITY TRAINING
in a single effort in that same exercise).8 Performing fewer
than 8–12 repetitions to fatigue (which would employ a Maintenance of flexibility, the range of motion around
greater resistance) will result in more strength gain than a joint, can be important for the prevention of low back
gain in endurance, while performing more than 8–12 pain and for the maintenance of activities of daily living.
repetitions (requiring less resistance) will result in more While stretching might help prevent injury in activities
improvement in muscular endurance. where one’s range of motion is taken to its limits (e.g.,
The compilation of repetitions of an exercise performed gymnastics), there is no conclusive evidence that stretching
at one time (e.g., 8–12) is termed a set. Multiple sets of prevents injury in activities requiring less range of motion
an exercise may be performed with two to three minutes’ (e.g., jogging) or that it prevents muscle soreness.12,13
rest in between being recommended. For beginners, per- Nevertheless, since flexibility decreases with aging,
forming a single set of an exercise for 8–12 repetitions stretching is an important component of a well-rounded
184 Chapter 14 Exercise Prescription for Apparently Healthy Individuals and for Special Populations
fitness program. Unless ballistic (bouncing) movement is facilitate delivery of prudent physical activity information
part of an activity for which a person is training, static by health care providers, the ACSM and the American
stretching, where a person holds a stretch for an extended Medical Association launched an educational web site,
period (15 seconds or more), is recommended. Stretching Exercise is Medicine, in 2007 (http://exerciseismedicine.
is more effective, and possibly safer, after a person has org).16
gone through a warm-up period. In fact, unless a person
is getting ready to perform activities that challenge their
range of motion, stretching is usually most effective at the 14.6.1 Exercise Prescription for
end of an exercise session rather than at the beginning. If
stretching before exercise, a person should still warm up
Special Populations
first (see section below). Prior to activities that challenge With rare exceptions, everyone should be physically
one’s range of motion, dynamic stretching (e.g., gently active. However, physical limitations and safety issues
swinging one’s arms back and forth, high knee-stepping) sometimes necessitate that the “normal” exercise pre-
may serve as an alternative or segue to ballistic stretch- scription described above be altered. As such, this next
ing. The ACSM recommends that stretching exercises be section discusses recommendations for children and older
performed at least four repetitions per stretch for at least adults, pregnant women, and people with some of the
15 seconds each (for a total of 60 seconds per stretch) on more prevalent chronic diseases. This discussion is only
at least 2–3 days weekly.8 introductory in nature; other sources dedicated to the sub-
ject of clinical exercise physiology are available and cover
a wider variety of chronic conditions in greater detail.17,18
14.5 WARM-UP AND COOL-DOWN Exercise prescription for individuals with cardiovascular
disease and obesity is detailed elsewhere in this textbook.
Both before (warm-up) and after (cool-down) the condi-
tioning phase of an exercise session, at least 5–10 minutes
of low-intensity physical activity should be performed.
The increased blood flow and body temperature resulting
14.7 CHILDREN AND ADOLESCENTS
from the warm-up period allows the muscle and connec- Proper physical activity can help develop and maintain
tive tissue to become more pliable, reducing the chance a healthy body weight and cardiometabolic risk profile,
of injury during vigorous activities. It also allows a more can reduce symptoms of anxiety and depression, and can
gradual cardiovascular adaptation to the stress of exer- instill positive habits that may carry over into adulthood.
cise, which is particularly important for people who are The Physical Activity Guidelines for Americans recom-
more likely to experience cardiac events. Similarly, a mend that youth accumulate at least 60 minutes of moder-
proper cool-down period helps prevent venous pooling in ate- and vigorous-intensity physical activity daily.3 These
the lower extremities, thereby facilitating venous return to 60 minutes should include a combination of aerobic activi-
the heart and brain. Muscular endurance activities, such ties (e.g., bicycling, dancing) and short bursts of activity
as abdominal exercises, and stretching may also be better (e.g., playing tag, soccer) as well as activities that promote
performed during the cool-down phase. muscular fitness (e.g., climbing trees or playground equip-
ment) and bone health (impact activities such as running
or jumping rope). The Guidelines can be met through
14.6 PHYSICAL ACTIVITY ADHERENCE structured sports, games, and exercise classes and/or
unstructured play.
Specific strategies for enhancing physical activity par- Adults can facilitate physical activity among youth
ticipation are detailed elsewhere in this book. In gen- by providing ample opportunity for participation. Two
eral terms, the clinician should recognize that a good bit examples of how to do this are by limiting screen time
of flexibility exists in how a person can choose to meet (television, video games, and computers) and increasing
physical activity guidelines (i.e., wide ranges exist in the the amount of time dedicated to physical activity during
components of FITT), and that physical activity may be the school day. Academic performance is not sacrificed
practiced in a variety of settings (e.g., at home, outside, when students are provided with opportunities for daily
in a fitness facility, etc.). In addition, leisure-time physical physical activity in school, such as daily recess, physical
activity may be practiced alone, with a partner, or in a education classes, or implementation of physically active
group setting. Everyone should be encouraged to experi- learning opportunities in other classes.19 Many youths
ment with a variety of exercise regimens and to continue will choose to be active when given ample opportunity.
to practice the one(s) they enjoy the most. However, some cohorts that tend to be less active (ado-
Approximately 56% of American adults fail to meet lescent girls, obese) may benefit from structured exercise
current physical activity recommendations.14 As patients programs that include like peers and focus on a variety of
are more likely to be physically active when such behavior activities that are popular within a given gender and age
is endorsed by their physicians, the initiative of Healthy group (e.g., dance for adolescent girls).
People 2020 is to “increase the proportion of physician Compared to adults, a couple of physiological differ-
office visits that include counseling or education related ences in children are worth noting. First of all, children
to physical activity.”15 However, most physicians have sweat less than adults and do not acclimatize to heat expo-
received little education on physical activity counseling as sure as quickly. They also possess a delayed thirst response.
part of their medical training. Appropriately, in order to Therefore, it is important to gradually expose children to
14.9 Pregnancy and Postpartum 185
following intense or prolonged exercise. Persons taking damage they encountered due to the cancer and treat-
14
insulin or insulin secretagogues should consume a carbo- ments and how far they are into remission.
hydrate snack before participating in physical activity if In 2010, the ACSM sponsored an expert roundtable
their glucose level is <100 mg.dL −1. 26 Regardless of medi- that generated exercise training guidelines for cancer
cation type, all diabetic patients should be aware of hypo- patients, including suggested contraindications for exer-
glycemic symptoms (weakness, nervousness, etc.). cise training.7,29 These contraindications include fever,
With some important alterations, the exercise prescrip- extreme fatigue, significant anemia, and ataxia. A more
tion for persons with diabetes should be very similar to complete list of these contraindications appears in the
that for healthy adults. Overall volume of physical activity referenced sources.7,29 More severe subjective side effects
should be 150 minutes per week or greater, recognizing of cancer and its treatments that will necessitate medical
the importance of a dose-response relationship, especially attention and a break from physical activity include severe
as far as weight management is concerned. Although pre- cachexia, bone/joint pain (particularly in spinal region),
viously inactive persons should begin exercise at a mod- declines in functional status (strength, balance, etc.), gas-
erate intensity, progression to mostly vigorous-intensity trointestinal disorders (vomiting, diarrhea, severe nausea,
exercise may lead to a greater improvement in blood glu- etc.), and cardiovascular and pulmonary symptoms (chest
cose concentration. 28 Since exercise-induced alterations in pain, severe dyspnea, etc.).30 Vigorous-intensity (and
insulin sensitivity can begin to reverse within a few days possibly moderate-intensity) exercise should generally
of inactivity, it is recommended that no more than two be avoided on the day of intravenous chemotherapy and
days of inactivity be allowed between exercise bouts. 27 In within 24 hours after treatment.
fact, daily or near-daily physical activity of similar inten- Due to a wide variety of cancers and treatments,
sity and duration can be useful in maintaining a balance there are numerous potential precautions to take when
among the glycemic effects of physical activity, diet, and prescribing exercise. In general terms, exercise prescrip-
medications. Due to beneficial effects on insulin sensitiv- tion and progression need to be highly individualized
ity, resistance training is recommended at least two, and and should vary day-to-day as patients deal with the side
preferably three, days per week in patients without reti- effects of their treatments and the disease itself. Fatigue
nopathies. 27 With both aerobic and resistance training, will commonly persist for days, and often for weeks or
increases in exercise volume should occur gradually to more, following chemotherapy and radiation. Although
avoid disruptions in glycemic control. exercise is generally good for bone health, bone of can-
Finally, although cardiac reactivity to physical activ- cer patients may be more susceptible to fracture due to
ity should be normal in most persons with diabetes, radiation therapy and/or cancer metastases. As such,
autonomic neuropathy may result in a blunted heart-rate higher-impact activities should be avoided during can-
response in some patients. Unless a maximal heart rate cer treatment and, if desired, should be introduced very
has been obtained through graded-exercise testing, calcu- gradually during recovery. Due to the risk of contami-
lation of a target heart rate using an age-predicted maxi- nation, bone-transplant patients and patients with low
mum is inappropriate in patients with known or suspected white blood cell counts should take care to exercise in a
neuropathy. Use of subjective feelings of exertion should clean environment. Post-mastectomy patients experienc-
be employed instead. ing lymphedema should obtain physician consent before
performing upper-body exercise, should wear compres-
sion sleeves, and should begin with light-to-no resistance
14.11 CANCER and progress slowly. Also, although water exercise can be
very beneficial to some patients, it should be avoided in
Whether currently undergoing treatment or in remission, those with indwelling catheters or central lines and feed-
regular physical activity can yield both physiological and ing tubes and for those receiving radiation. In addition,
psychological benefits for most cancer patients. Physical patients undergoing radiation therapy may develop severe
activity can help reduce the decline of functional capac- skin irritations. Therefore, comfortable clothing should
ity during treatment. Even during palliative care, properly be worn and the skin should be kept dry and clean dur-
practiced physical activity may prolong independent func- ing and after exercise.8 In the majority of cases, cancer
tion and can reduce depressive symptoms and generate a patients will benefit from beginning their exercise pro-
greater sense of control. During recovery, in addition to gram in a medically supervised setting with an exercise
contributing to a faster and more complete restoration physiologist possessing specialized training.
of physical function, proper physical activity can reduce In general, the ACSM recommends that cancer patients
the chances of the reoccurrence of certain cancers, par- perform aerobic physical activity 3–5 days per week
ticularly those of the breast and colon. Additionally, since for 20–60 minutes, realizing that a patient’s condition
some cancer treatments increase the likelihood of future may necessitate periodic adaptation. Although a moder-
CVD and diabetes, the practice of physical activity is ate intensity of 40–60% VO2reserve or HR reserve is recom-
important in the management of cardiometabolic risk. mended, some patients will find this difficult and should
Exercise prescription should vary based on the type adjust their intensity accordingly. One to three sets of
and severity of cancer. Since the side effects of cancer 10–15 repetitions of resistance exercise at 40–60% 1RM
treatments can in some cases be nearly as severe as the dis- is recommended on 2–3 nonconsecutive days per week.
ease itself, the type and time-course of treatment should Flexibility training, which can be particularly beneficial
be taken into account as well. Similarly, during recovery, a following some surgeries, is recommended 2–7 days per
person’s capacity to exercise will be affected by any tissue week. Four repetitions of 10–30 seconds are suggested.8
188 Chapter 14 Exercise Prescription for Apparently Healthy Individuals and for Special Populations
With the exception of high-impact activities, a wide range patients should not be pushed to a point where they are
of exercise types can be used to meet a patient’s goals. In less likely to continue to stay active.
addition, some exercise modalities, such as tai chi, offer
the opportunity to complete moderate-intensity exercise
in a supportive group atmosphere. 14.13 DISABILITIES
Depending on the type and extent of disability, proper
14.12 ARTHRITIS physical activity may improve physical fitness and func-
tional abilities and may reduce a person’s risk for car-
Both osteoarthritis and rheumatoid arthritis result in diometabolic diseases. The range of disabilities (cerebral
pain with movement. This often sets up a vicious cycle in palsy, spinal cord injury, stroke, etc.) is too wide to permit
which a person moves less due to pain. In turn, stamina a thorough discussion of exercise prescription for each
and neuromuscular conditioning decline, which can even- disability here. However, a few points are important to
tually result in a decreased ability to perform activities remember across many conditions. For example, disabili-
of daily living. As functional tolerance deteriorates and ties resulting in autonomic impairment will yield abnor-
arthritic pain increases, physical activity levels will most mal cardiovascular responses to exercise and impaired
likely decline further, making the individual less function- thermoregulation. Therefore, perceived exertion may be a
ally tolerant and more susceptible to hypokinetic diseases. better gauge of exercise intensity, and special precautions
As such, a major objective of exercise in individuals with should be taken to prevent hyper- or hypothermia. In addi-
arthritis is to increase and preserve physical function. tion, adaptions in equipment or clothing may be needed to
Although physical activity may cause acute pain, when help persons with particular disabilities perform common
practiced with regularity, it can actually reduce joint pain exercises. For example, persons with impaired gripping
and stiffness, resulting in a higher quality of life. Also, as ability may benefit from Velcro gloves when performing
arthritis is common in overweight and obese individuals, resistance exercises or arm ergometry. Shorter bouts of
physical activity can also serve as a means of weight con- physical activity spread throughout the day may be neces-
trol and cardiometabolic disease risk-factor management. sary for persons with very low physical tolerance.
Exercise levels recommended for the general popula- When possible, persons with disabilities should per-
tion also increase physical fitness and produce health form the same physical activity recommended for more
benefits in persons with arthritis.8 However, certain able-bodied adults.3 When this is not possible, they
adaptations may make physical activity more tolerable should perform as much physical activity as they are able
and increase compliance. While adequate warm-up is to accomplish without undue fatigue. Aerobic, resistance,
important in all cases, it is particularly important with and flexibility exercise should all be practiced. Even when
arthritis, as the increased blood flow warms the joints exercise tolerance is very low, physical inactivity should be
and makes movement easier and less painful. Since many avoided to maintain as much functional independence as
arthritic patients experience more stiffness and pain in the possible and to avoid hypokinetic diseases.
morning, exercise later in the day is often wise, especially
after morning medications have had time to reach their
peak effects. In addition, many patients find warm water 14.14 SUMMARY
(83–88°F, 28–31°C) exercise to be more comfortable than
exercise in other environments. Out of the water, prop- Current physical activity guidelines advocate a well-bal-
erly fitting shoes with adequate stability and cushioning anced exercise program to include aerobic, resistance, and
may help prevent excessive knee, hip, and/or back pain. flexibility training. To allow for individual preferences
Custom-made orthotics may be beneficial for persons and abilities, these guidelines allow a good bit of flexibil-
with biomechanical abnormalities. ity among frequency, intensity, and duration of physical
To increase and maintain functional ranges of motion, activity as long as a critical overall volume is met. Health
flexibility exercises are particularly important for patients and fitness-related benefits can also be obtained with a
with arthritis. Although resistance training can increase variety of exercise modalities. The chosen modalities
strength and stability around affected joints, maximal iso- should be safe for a given individual and should be enjoy-
metric contractions, practiced at a few angles per joint, able, which will enhance program adherence.
may be preferable to dynamic contractions in persons who In addition, disease or disability should not inhibit
experience higher levels of joint pain. As this becomes less anyone from being physically active. Individuals who are
painful, patients can then advance to dynamic exercise not able to meet the physical activity levels recommended
with lighter resistance, increasing the resistance as toler- for the general public should still strive to be as active as
ated. With aerobic training, people with more pain and/ possible within the confines of any disease or disability.
or less functional tolerance may need to exercise intermit- Everyone can benefit from physical activity.
tently in the beginning but should be able to progress to
more continuous activity.
Some pain during exercise is to be expected with CLINICAL APPLICATIONS
arthritis. However, if joint pain persists more than two
hours following exercise, the volume of training should be • About one-half of Americans do not meet cur-
reduced.8 Pain makes physical activity less enjoyable and is rent recommendations for physical activity, mak-
likely to negatively affect exercise compliance. Therefore, ing physical activity one of the most prevalent risk
References 189
factors for a number of prevalent chronic diseases in activities that they enjoy in an unintimidating
14
and conditions. environment. Including physical activity as part of
• A strong recommendation from a health care pro- their daily schedule is also important.
vider can be a key factor in convincing a patient to • The U.S. Centers for Disease Control and Prevention
make lifestyle changes. Although an exercise pre- offer useful resources for patients wishing to begin
scription might need to be quite precise to attain a physical activity program (http s://w
w w.cd
c.gov
high levels of specific fitness parameters, the health /physicalactivit y/basics/index.htm). In addition,
care provider need not be intimidated in providing the American College of Sports Medicine sponsors
health-related physical activity recommendations, Exercise is Medicine, which offers resources for
as wide ranges of exercise intensity and duration health care providers wishing to promote physical
allow one to improve their health and fitness. A key activity to their patients (http://www.exerciseismed-
factor for adherence is for the patient to participate icine.org/).
REFERENCES
1. 2018 Physical ActivityGuidelines 10. Gellish RL, Goslin BR, Olson RE, Diseases and Disabilities, 3rd ed.
Advisory Committee. 2018 Physical et al. Longitudinal modeling of the Champaign, IL: Human Kinetics, 2009,
Activity Guidelines Advisory Committee relationship between age and maximal pp. 38–46.
Scientific Report. Washington, DC: heart rate. Med. Sci. Sports Exerc. 21. American College of Obstetricians
U.S. Department of Health and Human 2007;39:822–829. and Gynecologists. ACOG Committee
Services, 2018. Available at: https: //he 11. Kraemer WJ, Adams K, Cafarelli Opinion: Exercise during pregnancy and
alth.gov/paguidelines /second-ed ition /rep E, et al. American College of Sports the postpartum period. Int. J. Gynecol.
ort/pd f/PAG _Advisory_Committee _ Repo Medicine Position Stand: Progression Obstet. 2002;77:79–81.
rt.pdf models in resistance training for 22. Brankston GN, Mitchell BF, Ryan EA,
2. U.S. Department of Health and Human healthy adults. Med. Sci. Sports Exerc. et al. Resistance exercise decreases the
Services. Physical Activity and Health: A 2002;34:364–380. need for insulin in overweight women
Report of the Surgeon General. Atlanta, 12. Gremion G. Is stretching for sports with gestational diabetes mellitus. Am. J.
GA: U.S. Department of Health and performance still useful? A review Obstet. Gynecol. 2004;190:188–193.
Human Services, Centers for Disease of the literature. Rev. Med. Suisse 23. de Barros MC, Lopes MAB, Francisco
Control and Prevention, National Center 2005;1:1830–1834. RPV, et al. Resistance exercise and
for Chronic Disease Prevention and 13. Herbert RD and Gabriel M. Effects of glycemic control in women with gesta-
Health Promotion, 1996. stretching before and after exercising tional diabetes mellitus. Am. J. Obstet.
3. U.S. Department of Health and Human on muscle soreness and risk of injury: Gynecol. 2010;203:556.e1–e6.
Services. 2008 Physical Activity Systematic review. BMJ 2002;325:468. 24. Lovelady CA. The impact of energy
Guidelines for Americans [Internet]. 14. Carlson SA, Fulton JE, Galuska DA, et restriction and exercise in lactat-
Washington, DC: ODPHP Publication al. Prevalence of self-reported physi- ing women. Adv. Exp. Med. Biol.
No. U0036, 2008. Available at: https: //he cally active adults – United States, 2007. 2004;554:115–120.
alth.gov/paguidelines /pdf /paguide.pd f MMWR 2008;57:1297–1300. 25. Lovelady CA, Bopp MJ, Colleran HL,
4. President’s Council on Physical Fitness 15. U.S. Department of Health and et al. Effect of exercise training on
and Sports: Physical Fitness Research Human Services. Healthy People loss of bone mineral density through
Digest. Series 1, No. 1. Washington, DC: 2020 Objectives. Washington, DC: lactation. Med. Sci. Sports Exerc.
U.S. Government Printing Office, 1971. Department of Health and Human 2009;41:1902–1907.
5. Caspersen CJ, Powell KE, and Services, 2010. Available at: http://www 26. Knowler WC, Barrett-Conner E, Fowler
Christenson GM. Physical activity, exer- .healt hypeople.gov/2020/topicsobjectives SE, et al. Reduction in the incidence of
cise and physical fitness: Definitions and 2020/pdfs/ H P2020 objec tives.pdf. type 2 diabetes with lifestyle interven-
distinctions for health-related research. 16. American College of Sports Medicine. tion or metformin. N. Engl. J. Med.
Public Health Rep. 1985;100:126–131. Exercise is Medicine. Indianapolis, IN: 2002;346:393–403.
6. Pate RR, Pratt M, Blair SN, et al. American College of Sports Medicine, 27. Colberg SR, Albright AL, Blissmer BJ, et
Physical activity and public health. A 2007. Available at: http://exerciseismedi- al. American College of Sports Medicine/
recommendation from the Centers for cine.org/index.htm. American Diabetes Association Joint
Disease Control and Prevention and the 17. Moore GE, Durstine JL, and Painter Position Statement: Exercise and type
American College of Sports Medicine. PL, eds. ACSM’s Exercise Management 2 diabetes. Med. Sci. Sports Exerc.
JAMA 1995;273:407–407. for Persons with Chronic Diseases and 2010;42:2282–2303.
7. Blair SN, Cheng Y, and Holder JS. Is Disabilities, 4th ed. Champaign, IL: 28. Boulé NG, Kenny GP, Haddad E, et al.
physical activity or physical fitness Human Kinetics, 2016. Meta-analysis of the effect of structured
more important in defining health 18. Ehrman JK, Gordon PM, Visich PS, et exercise training on cardiorespira-
benefits? Med. Sci. Sports Exerc. al., eds. Clinical Exercise Physiology, tory fitness in type 2 diabetes mellitus.
2001;33:S379–S399. 3rd ed. Champaign, IL: Human Kinetics, Diabetalogia 2003;46:1071–1081.
8. American College of Sports Medicine. 2013. 29. Schmitz KH, Courneya KS, Matthews
ACSM’s Guidelines for Exercise Testing 19. Rasberry CN, Lee SM, Robin L, et al. C, et al. American College of Sports
and Prescription, 10th ed. Philadelphia, The association between school-based Medicine roundtable on exercise guide-
PA: Wolters Kluwer, 2018. physical activity, including physical lines for cancer survivors. Med. Sci.
9. Ainsworth BE, Haskell WL, Hermann education, and academic performance: A Sports Exerc. 2010;42:1409–1426.
SD, et al. The Compendium of Physical systematic review of the literature. Prev. 30. McNeely ML, Peddle C, Parliament
Activities Tracking Guide. Tempe, Med. 2011;52:S10–S20. M, et al. Cancer rehabilitation:
AZ: Healthy Lifestyles Research 20. Riner WF and Sabath RJ. Physical Recommendations for integrating
Center, College of Nursing and Health activity for children and adolescents. exercise programming in the clinical
Innovation, Arizona State University. In: Durstine JL, Moore GE, Painter PL, practice setting. Curr. Cancer Ther. Rev.
Available at: https: //sites.google.com/site/ and Roberts SO, eds. ACSM’s Exercise 2006;2:351–360.
compendiumofphysicalactivities/. Management for Persons with Chronic
IV
PA RT
Behavioral Medicine
Elizabeth Pegg Frates, MD
191
15
CHAPTER
Behavior Change
Elizabeth Pegg Frates, MD and James E. Eubanks Jr., DC, MS
193
194 Chapter 15 Behavior Change
studying behavior change. Dr. Glanz is Director of the to know. Albert Bandura, PhD, created this theory, and
UPenn Prevention Research Center at the University of it explains human behavior using a three-way dynamic
Pennsylvania and Senior Editor of the textbook, Health which includes (1) personal factors, (2) behaviors, and
Behavior and Health Education: Theory, Research, and (3) environmental influences. Dr. Bandura’s theory high-
Practice.1 She has been designated a highly cited author, in lights the importance of reciprocity among these three
the top 0.5% of authors in the field, over a 20-year period. factors. Each one influences the others. When lifestyle
Four theories that Dr. Glanz highlights in her elec- medicine practitioners are counseling a patient, they need
tronic resource on behavior change include the Health to account for personal factors, including personality,
Belief Model, the Transtheoretical Model of Change, the preferences, beliefs, strengths, and weaknesses. Behaviors
Social Cognitive Theory, and the Social Ecological Model that are being reinforced currently and triggers for those
of Change. 2 These are four theories that every lifestyle behaviors need to be addressed with patients. The envi-
medicine practitioner needs to understand. In the Health ronmental influences surrounding the patient are critical
Belief Model, the theory states that people’s beliefs about and play a role in the behavior change process as well.
the risks and benefits of changing behavior influence their Examining the patient’s social environments is one of
readiness to change. If a patient believes that quitting the main points in the Social Ecological Model of Change.
smoking will actually help them to prevent lung cancer, In this model, the patient is at the center. Surrounding his
then they are more likely to be interested in quitting. If is the interpersonal circle, which includes his social net-
they believe that, since no smokers in their family were work at work, school, home, or on the internet. Around
diagnosed with lung cancer, they are somehow protected that is the organizational level of influence, including the
from cancer, that person is less likely to consider quit- ethos of his home, work, neighborhood, city, state, and
ting. Using the Health Belief Model in practice requires country. Beyond that level is the community influence
that healthcare practitioners hold conversations with their which factors in cultural values and norms for the patient.
patients in which they ask open-ended questions that invite The last level or sphere of influence, the most far-reach-
patients to talk and share their beliefs. Understanding the ing, is the public policy level, where laws impact behavior
beliefs of the patient is key to successful behavior change and require strict guidelines to be followed. This model of
counseling. change helps practitioners work to set the patient up for
The Transtheoretical Model of Change (reviewed in success in their daily lives by exploring the world in which
detail in Chapter 18 by Dr. James Prochaska) describes the patient lives. It is important to know about the patient,
Five Stages of Change that a patient can transition through and it is equally important to know about the patient’s
for a particular behavior. A patient can be in different environment and the external influences on that patient.
stages of change for different behaviors. The stages are: Taking all these factors into consideration is critical for
lasting behavior change.
• Pre-Contemplation Looking at the research in the medical literature helps
• Contemplation practitioners to share findings from a wide variety of
• Preparation sources about other practitioners helping patients to adopt
• Action healthy habits. Specific studies use different patient popu-
• Maintenance lations and different behavior change techniques. Review
studies collect a number of research articles and examine
In pre-contemplation, the patient is not even think- them for similarities and differences.
ing of change, whereas in contemplation, as the name In terms of nutrition and diet counseling, a study in the
suggests, the patient is contemplating change. They are Journal of the American Dietetic Association reported
ambivalent about it. Some people stay in contemplation that effective counseling techniques were cognitive behav-
for years, called Chronic Contemplation. Those in prepa- ioral therapy (CBT), motivational interviewing, self-mon-
ration want to change and have an intention to change. itoring, meal replacement and or structured meal plans,
They are not ambivalent anymore, but they have yet to goal setting, problem solving, and social support. Working
take action. Action is the next phase. When the patient with the patient in these areas with these strategies helped
makes strides to adopt the new behavior and starts prac- them to adopt healthy eating habits. In terms of ineffec-
ticing the behavior, they are in action. After action comes tive strategies, the authors state, “Compelling evidence
maintenance. If the patient has been practicing the new exists to demonstrate that financial reward strategies are
healthy behavior for over six months, they are in mainte- not effective.” These extrinsic rewards like money or gift
nance. With each stage comes a set of specific strategies for certificates might motivate patients, but that motivation
the healthcare practitioner to use to help the patient move rarely lasts after receiving the reward and it is not compat-
along through the stages. These are outlined in Chapter 18. ible with sustainable change. 3
Patients do not necessarily move through the stages in a In a review article that included 22 studies, researchers
stepwise fashion. This is not a straightforward staircase specifically looked at patients of retirement age to iden-
but more of a spiral staircase where the patient might tify the most effective techniques to help this population
slip while in action and wind up in contemplation or slip increase fruit and vegetable consumption. According to
during maintenance and land in preparation. Asking the the review article, the most useful strategies include barrier
patient about their readiness to change is key in behavior identification, problem solving, social support, goal set-
change counseling. ting, use of follow-up prompts, and providing feedback on
The Social Cognitive Theory is another behavior performance.4 There are some consistent messages that are
change theory that lifestyle medicine practitioners need found in different populations and for different behaviors.
Take Home Points 195
Continuing to examine the research will result in highlight- providers. In one review that included 17 studies examin-
15
ing those strategies that are effective across populations ing childhood obesity with regard to changing physical
and which are best for targeting healthy habits. activity and eating, the researchers identified several effec-
Patients with diabetes have been the focus of attention tive techniques and only a few ineffective techniques. The
nationally in the public media and in academic institu- effective techniques included providing information about
tions with various research studies. In one review article the consequences of the behavior to that specific individ-
that included research studies from 1975–2015, 14 ran- ual (personalized information), providing environmental
domized controlled studies were included that examined restructuring, giving prompt practice, identifying a role
patients with diabetes and their physical activity levels as model or position advocate, working on stress manage-
well as their dietary patterns. This review identified four ment and emotional control training, and focusing on
behavior change techniques that were repeatedly utilized communication training. Ineffective techniques included
successfully. They included instruction on how to per- providing information on the consequences of the behav-
form the behavior, behavior rehearsal, demonstration of ior in general, providing rewards contingent on successful
the behavior, and action planning. Strategies that helped behavior, and facilitating social comparisons.9
patients to adopt and sustain these two healthy behav- Putting this all together, the focus for sensible behav-
iors included supervised physical activity, group sessions, ioral change in healthcare must be balanced by a sound
contact with an exercise physiologist, and contact with scientific base and practical solutions that will reach the
a dietician. In addition, this review pointed out that the intended audience. Behavior change techniques must be
more sessions and the greater the frequency of sessions, effective, and counseling strategies must support specific
the better the results of the trials. 5 goals. The general approach to behavior change includes
Another diagnosis that has received much attention, elements of goal setting, follow-up, self-monitoring, action
from the media as well as from academic researchers, is planning, problem solving, and social support. Each of
obesity. In a review article specifically looking at patients these process components has a vital role in facilitating
with obesity and how to increase their levels of physical the development of goal behaviors.
activity, the results were split into two areas (1) how to Empathy is an important factor among clinicians, not
increase self-efficacy and (2) how to increase the behav- only for the mutual understanding and respect it engen-
ior. In order to increase self-efficacy (a belief held by the ders among patients but also for the determination of
patient that they could perform the physical activity suc- clinical outcomes. Hojat and colleagues found that high
cessfully), the strategies that were most effective included empathy scores among physicians supporting patients
action planning, time management, prompt self-monitor- with diabetes also led to better control of HbA1c and
ing of behavioral outcome, and planned social support. LDL-c in their patients.10 When physicians take time to
For increasing the behavior of physical activity, prompt connect with their patients and learn more about them on
self-monitoring of the behavioral outcome, planned social a personal level, patients are also more likely to endorse
support, teaching to use prompts, prompt practice, and their medical care as “excellent.”11 Key aspects of empathy
prompt rewards contingent on effort, not on progress include the development of a trusting, caring relationship,
towards behavior, were found to be the most effective.6 self-reflection, listening, and being respectful, supportive,
In another review article that included overweight and and non-judgmental.
obese individuals, there were similar results. Effective While motivation is a required component for any
behavior change techniques in the short term included behavioral change effort, it is the alignment between
goal setting and self-monitoring of behavior. Effective motivation and goals that allows goals to be achieved.
behavior change techniques in the long term included Once initial motivation for a behavior change is identified,
goal setting, self-monitoring, feedback on outcome of motivational interviewing can be employed to support
behavior, implementing graded tasks, and adding objects patients as they identify additional reasons for seeking
to the environment like a step counter. Using the Social and sustaining change efforts. Central to the skilled use of
Cognitive Theory and the Social Ecological Model of motivational interviewing is the ability to use open-ended
Change concepts that the individual is influenced by their questions that help patients appreciate their priorities in
environment is key for sustaining behavior change. In life. Using motivational interviewing in the clinical setting
addition, autonomy supportive, person-centered counsel- has been shown to improve patient mood and even reduce
ing, including motivational interviewing, was found to be mortality among stroke patients.12
the most effective counseling strategy to help maintain Confidence building empowers behavior change by
behavior change over time in this population of patients.7 providing sequentially stronger foundations from which
In another review of 35 studies which included adult new actions can be carried out. It includes asking about
patients and focused on weight change as well as physi- strengths so that patients reflect on moments in their per-
cal activity behavior, the results revealed that higher sonal lives when they achieved a goal. Relating to a time
autonomous motivation, higher self-efficacy, and higher when they could carry out the tasks necessary to achieve a
self-regulation skills like self-monitoring were the best goal allows them to appreciate the potential for applying
predictors of beneficial weight and physical activity out- similar behaviors in the present moment.
comes. Specifically for weight control, a positive body SMART goals are specific, measurable, action-ori-
image and flexible eating restraint were identified as ented, realistic, and time-sensitive. This general strat-
important factors.8 egy ensures that behavior change efforts are achievable
Changing the age of the population and looking at the through each step along the pathway by breaking actions
pediatric population reveals important information for down. Each smaller step in the change pathway should
196 Chapter 15 Behavior Change
contain an element of accountability, which allows for the the office focuses on this behavior change if healthy habits
follow-through needed to complete the behavior change are going to stick. On average, it takes about 60 days or
process. Once an immediate step along the process of two months for a new behavior to become habit. If the
change is achieved, the conditions are maintained to pro- patient is in the maintenance stage of change according
ceed to the next. Since behavior change involves incre- to the Transtheoretical Model of Change, then the clini-
mental changes over time, setting up an accountability cian can continue to encourage the healthy habit by asking
structure that includes a positive and motivating support about it and pointing out all the positive outcomes that are
system increases the chance of success and reinforces the a result of the habit. Keeping on track with healthy habits
confidence needed to continue moving forward. In addi- is the key for patients, and lifestyle medicine practitioners
tion to the strong social support system, it is important for can empower patients to do this by following evidence-
the practitioner to check in with patients and to encour- based behavior change strategies.
age self-monitoring as well as the use of tracking systems
as appropriate to help patients enjoy continued, long-term
success with their healthy habits. CLINICAL APPLICATIONS
As created by one of the authors and first described
in 2011 in the Archives of Physical Medicine and • Use the 5 Step Cycle13 in your clinical encounters,
Rehabilitation,13 the 5 Step Cycle for Behavior Change focusing on making a connection and fostering
uses the key elements of behavior change to enable prac- collaboration.
titioners to experience success with lifestyle counsel- • Catch yourself using the expert approach when
ing. Physicians and clinicians can work through the 5 working on behavior change and redirect your
step process with their patients by following these steps: efforts to using a more collaborative style of coun-
(1) be empathetic, (2) align motivation, (3) build confidence, seling that is consistent with the coach approach.
(4) set SMART goals—those that are specific, measurable, • Work on making SMART goals with patients that
action-oriented, realistic, and time-sensitive—and finally, are specific, measurable, action oriented, realistic,
5) set accountability so that benchmarks are available to and time-sensitive.
measure success or the need for adjustments in strategies • Make sure there is built-in accountability for the
and planning to ensure the goal is achievable. patient; have them check in with you at the next visit or
Behavior change counseling takes time. It is usually have them buddy up with a family member or friend.
not accomplished in one visit of 10 or 15 minutes. It takes • If you do not have the interest or time to counsel
follow-up and repeated visits. If the practitioners are too patients on behavior change, consider hiring some-
busy and do not have the time to do the behavior change one with this expertise or consider having someone
counseling themselves, then they can hire a nurse, social in your practice trained in motivational interview-
worker, health coach, therapist, or behavior change expert ing and behavior change so that they can spend the
to work with the patient. It is important that someone in time needed to empower people to change.
REFERENCES
1. Glanz K, Rimer BK, and Viswanath K. 5. Cradock KA, OLaighin G, Finucane FM, review of self-regulation mediators. BMC
Health Behavior and Health Education: et al. Behaviour change techniques target- Med. 2015 Apr 16;13:84.
Theory, Research, and Practice. 4th Ed. ing both diet and physical activity in 9. Martin J, Chater A, and Lorencatto F.
Jossey-Bass. 2008. type 2 diabetes: A systematic review and Effective behaviour change techniques in
2. Glanz K. “Social and Behavioral meta-analysis. Int. J. Behav. Nutr. Phys. the prevention and management of child-
Theories: Important Theories and Their Act. 2017 Feb 8;14(1):18. hood obesity. Int. J. Obes. (Lond.) 2013
Key Constructs”. e-Source. 2017. http:// 6. Olander EK, Fletcher H, Williams S, et al. Oct;37(10):1287–1294.
www.esourceresearch.org / Defau lt.aspx?T What are the most effective techniques in 10. Hojat M, Louis DZ, Markham FW, et al.
abId=730. changing obese individuals’ physical activ- Acad. Med. 2011 Mar;86(3):359–364.
3. Spahn JM, Reeves RS, Keim KS, et al. ity self-efficacy and behavior: A systematic 11. Pace EJ, Somerville NJ, Enyioha C, et al.
State of the evidence regarding behavior review and meta-analysis. Int. J. Behav. Effects of a brief psychosocial interven-
change theories and strategies in counsel- Nutr. Phys. Act. 2013 Mar 3;10:29. tion on inpatient satisfaction: A random-
ing to facilitate health and food behavior 7. Samdal GB, Eide GE, Barth T, et al. ized controlled trial. Fam. Med. 2017
change. J. Am. Diet. Assoc. 2010 Effective behaviour change techniques Oct;49(9):675–678.
Jun;110(6):879–891. for physical activity and healthy eating in 12. Watkins CL, Wathan JV, Leathley MJ,
4. Lara J, Evans EH, O’Brien N, et al. overweight and obese adults: A system- et al. The 12-month effects of early moti-
Association of behavior change tech- atic review and meta-regression analyses. vational interviewing after acute stroke:
niques with effectiveness of dietary inter- Int. J. Behav. Nutr. Phys. Act. 2017 Mar A randomized controlled trial. Stroke
ventions among adults of retirement age: 28;14(1):42. 2011;42:1956–1961.
A systematic review and meta-analysis of 8. Teixeira PJ, Carraca EV, Marques MM, 13. Frates EP, Moore MA, Lopez CN, et al.
randomized controlled trials. BMC Med. et al. Successful behavior change in obe- Coaching for behavior change in phys-
2014 Oct 7;12:177. sity interventions in adults: A systematic iatry. Am. J. Phys. Med. Rehab. 2011
Dec;90(12):1074–1082.
16
CHAPTER
197
198 Chapter 16 Applying Psychological Theories to Promote Healthy Lifestyles
16.1 INDIVIDUAL LEVEL significant criticism and has not held up to rigorous sci-
entific examination in these contexts. Indeed, a recent
meta-analysis of studies using HBM constructs to longi-
16.1.1 Health Belief Model tudinally predict health behavior concluded that utilizing
The Health Belief Model (HBM),6–8 depicted in the direct effects model may not be useful because the two
Figure 16.1, was initially developed in the 1950s in an primary constructs (perceived severity and perceived sus-
attempt to understand and explain why many individu- ceptibility) only weakly predicted behavior.12
als were not participating in preventive health services, Although the HBM has been one of the most utilized
even when they were offered at no cost. The HBM pro- models in health behavior research,13 many concerns about
poses that the likelihood that individuals will engage in the model remain. For example, the relationships among
any given health behavior largely depends on their percep- the model’s constructs are not clearly delineated, measure-
tions of the following variables: severity of the illness(es) it ments of some HBM constructs are not standardized, and
helps prevent, their susceptibility to the illness(es), benefits some of its constructs (especially “cues to action”) are diffi-
of engaging in the behavior, and barriers to engaging in cult to empirically test.12,14 Furthermore, other models have
the behavior. According to the HBM, individuals are more exhibited stronger predictive ability of health behavior than
likely to adopt the target health behavior if they believe the HBM.15 Thus, although some HBM constructs may be
the potential illness is serious, that they are highly suscep- helpful to consider in the prediction of health behavior, the
tible to it, and that the benefits of engaging in the behav- model as a whole may not be particularly useful except in
ior outweigh the associated barriers. The construct “cues the context of single or short-term behaviors.12
to action,” which are factors that prompt action (e.g.,
media campaigns, physician reminders), was later added
to the model to increase its explanatory power. Other fac-
tors, such as demographic characteristics (e.g., age, race, 16.1.2 Theory of Reasoned Action,
ethnicity, gender) and psychosocial variables (e.g., peer Theory of Planned Behavior,
influence, mood/affect) also exert considerable influence
over individuals’ decisions to engage in a specific health
Integrated Behavior Model
behavior, according to the HBM. Self-efficacy, described The Theory of Reasoned Action (TRA), developed by
as behavior-specific self-confidence,4,5,9 was later added Ajzen and Fishbein,16,17 stems from premises of cognitive
to the HBM in an attempt to increase its ability to accu- and social psychology. The TRA posits that individuals’
rately predict health behavior.9 Self-efficacy was not ini- likelihood of engaging in a particular health behavior can
tially included as an HBM construct because the model be predicted by the strength of their intentions to engage
was primarily used to predict one-time or short-term in that behavior. Intentions represent a combination of
health behaviors, such as getting a vaccination or health their own attitudes toward the behavior and their “social
screening, for which self-efficacy is not particularly rel- norms.” According to the TRA, attitudes are formed by
evant. Nevertheless, these modified or extended versions individuals’ beliefs about the consequences of the health
of the HBM have been utilized in relatively recent research behavior and the weight they place on those consequences.
examining the model’s ability to predict short-term behav- Likewise, social norms are products of individuals’ beliefs
iors such as breast self-examination among women with a about others’ expectations of them regarding the behavior
family history of breast cancer10 and human papillomavi- and their motivation to comply with those expectations.
ruses (HPV) vaccination initiation among adolescent girls Research examining the TRA has demonstrated that
in high-risk communities.11 it is most useful at predicting behaviors under volitional
The HBM has since been applied to longer-term health control; however, most behaviors are not completely
behaviors and habits, such as exercise, smoking cessa- within an individual’s control. Therefore, Ajzen18 pro-
tion, and dieting, with some success, but it has received posed an extension of the TRA called the Theory of
Perceived Likelihood of
susceptibility and Perceived threat behavior or
perceived severity adherence
Cues to action
Planned Behavior (TPB) in an attempt to better predict adolescents, 24 fruit and vegetable consumption, 25 and
16
health behaviors. The TPB incorporates TRA constructs physical activity maintenance. 26
and adds a construct called perceived behavioral control, The Integrated Behavior Model (IBM), developed by
which is defined as individuals’ perceptions of their ability Fishbein and colleagues, 27,28 is an extension of the TRA
to perform a given behavior.18 The TPB’s perceived behav- and TPB. It similarly posits that the most important deter-
ioral control construct is similar to the concept of self- minant of a given behavior is the intention to engage in the
efficacy4,5 and is defined in terms of control beliefs (the behavior. In addition to TRA and TPB, the IBM incor-
presence or absence of perceived facilitators and barriers porates variables from other notable theories, including
associated with a given behavior) and perceived power HBM8,29 and Social Cognitive Theory.4,5,30 According
(the impact of these facilitators and barriers). to the model (Figure 16.2), a behavior is likely to occur
Unlike the HBM, the TRA and TPB models clearly if (1) one has a strong intention to engage in the behav-
delineate the relationships between their individual con- ior, (2) has the required skills and abilities to perform it,
structs. As a result, research examining the predictive (3) the behavior is salient and has occurred before, and
abilities of these models has generally supported each of (4) there are no environmental constraints to impede
them as a whole.15 However, a major concern about the behavioral engagement.31 If, however, intentions to engage
models is that they do not incorporate any constructs that in the behavior have not been formed, the model suggests
allow for affective/emotional or psychosocial variability,19 that emphasis may need to be placed on three primary
which has also been a noted concern with the HBM. 20 determinants of intention: attitude towards the behav-
Furthermore, the models do not take into account the ior, perceived norms, and personal agency. The first con-
fact that some behaviors are so habitual that they are not struct, attitude toward the behavior, is a person’s overall
subject to planning or reasoning; in these cases, even the favorableness or unfavorableness towards engaging in the
strongest of intentions are not likely powerful enough behavior. Attitude is further divided into two dimensions
to overcome the automatic nature of well-established in the IBM. Experiential attitude or affect32 is the emo-
habits.19 tional response to the idea of engaging in the suggested
Although the TRA and TPB have received less atten- behavior. Individuals are unlikely to engage in the behav-
tion in health behavior research than some of the newer ior when strong negative emotional responses are elicited,
models in recent years, they consistently rank among the while individuals with a strong positive response are more
most utilized theories in the field and demonstrate consid- likely to engage in it. Instrumental attitude refers to beliefs
erable predictive value. 21 The TRA and/or TPB have been about the consequences of engaging in the behavior, as is
used as guiding frameworks for assessing, understanding, found in the TRA and TPB.
and influencing behavior change in diverse populations The second construct, perceived norms, is a reflection
with a variety of health behaviors, such as female condom of the social pressure to either engage in or not engage in
use among Chinese sex workers, 22 safer sex intentions a certain behavior. Fishbein32 describes normative influ-
and protected sex among heterosexual, HIV-negative ence as being composed of both subjective and descriptive
methamphetamine users, 23 family meal frequency among norms. Subjective norms (formerly social norms in TRA/
Attitude
Feelings about Experiential
behavior attitude Knowledge and
skills to perform
behavior
Behavioral Instrumental
beliefs attitude
Salience of
behavior
Perceived Norm
Other Factors
Personal Agency
Control Perceived Environmental
beliefs control constraints
TBA) are one’s beliefs about what others think about them health behaviors (e.g., fruit and vegetable consumption,48
engaging in the behavior and their motivation to comply weight control,49 condom and oral contraceptive use, 50,51
with others’ expectations, whereas descriptive norms are sunscreen use, 52 medical compliance, 53 cervical cancer
one’s perceptions of what others in their social network and mammography screening, 54,55 stress management, 56
are doing. intimate partner violence, 57,58 and exercise59,60); in diverse
The final construct, personal agency, has been previ- populations (e.g., college students,61 African American
ously described by Albert Bandura33 as exerting personal adolescents,48 and patients with severe mental illness,62
influence to impact one’s own functioning and environ- tuberculosis,63 HIV,64 and multiple sclerosis53); and in
mental conditions. In the IBM, two constructs make up many countries (e.g., Taiwan, 54 Nepal,64 Malaysia.63).
personal agency—self-efficacy and perceived control. However, several criticisms of this model have been
Self-efficacy refers to confidence in one’s ability to per- raised.65,66 For example, the complexity of health behav-
form a specific behavior in a given situation. Meanwhile, iors is an issue when considering stage-based behavior
perceived control (as previously described in TRA/TPB) change theories. Staging algorithms typically ask about
is one’s perceived amount of control over their ability to physical activity or diet in general, but motivational readi-
engage in a behavior, which is determined by one’s per- ness for change may vary for subcategories not fully cap-
ceived degree of difficulty in engaging in the behavior due tured by these algorithms (e.g., interested in walking and
to various environmental factors. vegetable consumption but not strength training or reduc-
The IBM indicates the aforementioned constructs com- ing fat intake). The TTM also focuses on stage progression
posing attitudes, perceived norms, and self-agency are all as a significant outcome, but this is not always associated
functions of underlying beliefs. For instance, experiential with actual behavior change.67,68 Nevertheless, the TTM
attitudes are a function of one’s feelings regarding the idea has been a highly influential theoretical framework com-
of engaging in a specific behavior. The more positively prised of a number of useful organizing constructs that
one feels about the behavior, the more likely a favorable have been shown to be meaningfully related in empirical
emotional response will be elicited when thinking about data and psychometric studies.
engaging in it. However, it is important to note that the
relative influence of the discussed variables is population-
and behavior-dependent. Therefore, it is necessary to first
determine the extent to which intention is influenced by 16.3 INTERPERSONAL LEVEL
attitudes, perceived norms, or self-agency.
Previous successful applications of the IBM include 16.3.1 Social Cognitive Theory
understanding behavioral intention and behavior for Social Cognitive Theory (SCT) is one of the most robust
condom use among injecting drug users and other HIV health behavior change theories.3,69 It evolved from Social
risk groups, 34,35 HIV/STD-prevention in Zimbabwe, 36,37 Learning Theory3,42 and originally focused on observa-
adolescent sexual behavior, 38 and road user behaviors in tional learning, or learning by watching others’ behavior
Vietnam.39 Moreover, IBM has been used as a theoreti- (also called modeling) and the reinforcements (both posi-
cal framework for Project Respect, a large, multisite, ran- tive and negative, internal and external) that help deter-
domized, controlled trial testing HIV/STD risk reduction mine whether or not one will repeat the behavior. Updated
strategies among participants visiting public health clinics by Bandura and colleagues, SCT posits that behavior
for STDs.40,41 change is influenced by internal individual factors (e.g.,
cognitive, affective, biological) as well as the social and
physical environment. The model is reciprocal in that
16.2 TRANSTHEORETICAL MODEL each of these factors affects the others in a continuous,
dynamic feedback loop (Figure 16.3).3
The Transtheoretical Model (TTM) is an integrative Self-efficacy is the main construct of SCT4 and, as
model of behavior change developed from many different mentioned previously in this chapter, is a powerful predic-
psychological theories, such as Social Cognitive Theory tor of behavior change that has been incorporated into
(SCT)30 and Learning Theory.42,43 Prochaska and col- numerous social and behavior science theories. 3,69 Self-
leagues first described this model after noting that people efficacy beliefs have been strongly associated with actual
vary in terms of motivational readiness to quit smoking44 performance of a diverse range of health behaviors.70,71
and move through specific stages of motivational readi- According to Bandura, self-efficacy can be increased
ness along the path to behavior change.45 The TTM is through mastery experiences, social modeling, improv-
extensively described in part IV, Chapter 4, of this book. ing physical and emotional states, and verbal persua-
This model is considered cyclical, accounting for peo- sion.69 Mastery experience is gained through succeeding
ple’s tendency to move back and forth through the stages in attainable, yet increasingly challenging health behavior
of change. Individuals may lose resolve and abandon new change goals and is considered to have the strongest influ-
behavior patterns, feel guilty, lose confidence, and revert ence on self-efficacy beliefs. 3,69,72 Modeling, as previously
to their previous routines, with probable recycling through discussed, can be accomplished by watching others per-
the earlier stages of precontemplation or contemplation. form the desired behavior; it is especially effective when
Thus, numerous cycles through the stages often happen relatable peer(s) perform the behavior. Finally, maintain-
before an adopted health behavior becomes a habit.46,47 ing an optimal level of physiological intensity (i.e., excited
Although the TTM originated in the addictions but not too anxious) for performing the behavior, which
research field, it has since been applied to numerous can be accomplished by using relaxation techniques and
16.4 Ecological Level 201
Behavior
(exercising, healthy eating)
16
positive self-talk as well as receiving encouragement from have shown that specific SCT concepts (e.g., self-efficacy)
others, can increase self-efficacy.3,69,72 are associated with behaviors, but such research does not
Self-regulation strategies are also used to enhance confirm the entire theory. Nevertheless, SCT provides a
confidence for behavior change and typically begin with strong foundation for health promotion research and
self-monitoring, or systematically observing, one’s current practice, using numerous strategies to address diverse
health behaviors.69 Data are collected with pedometers, public health issues. Furthermore, SCT has been suc-
food diaries, smoking logs, or other tools, depending on cessfully applied to a variety of health behaviors (e.g.,
the health behavior(s) being targeted. These objective data cardiovascular disease,74-78 cancer screening,79 tobacco
can then be reviewed to determine how specific health use,80–83 alcohol use,42,84–86 diet,87,88 obesity,89 physical
behaviors might be improved and to identify incremental activity,73,87,88,90,91 diabetes prevention,92 condom use93,94)
and long-term behavior change goals. Overlapping to a in a wide range of ages (including children,88 teens ,84
degree with the concept of mastery experience, self-reg- and elderly90) and underserved populations (e.g., African
ulation can also include establishing rewards for meeting Americans,80 Latinas,89,92 low-income individuals88,89),
behavior change goals and enlisting social support from and in several different countries (mostly in the United
family and friends for performing target behaviors.69 States, but also in China,94 Sweden,88 and Australia90).
Another important determinant of behavior accord-
ing to the SCT is outcome expectancies.3 This construct,
defined as the influence that the outcomes anticipated
from a health behavior exert on one’s willingness to per-
16.4 ECOLOGICAL LEVEL
form this behavior, makes intuitive sense and has been
supported in numerous research studies.73 According to
16.4.1 Socioecological Model
SCT, one’s expectations affect both initiation of and per- In more recent years, psychological theories and models
sistence of the behavior. Perceived self-efficacy can not have increasingly incorporated the broader contexts that
only have direct effects on initiating of activities but can affect health behaviors, recognizing that these external
also affect continuing efforts once they are initiated by factors are often as influential as internal factors.95–97
means of expectations of eventual success. Self-efficacy Socioecological models are based on four fundamental
determines how much effort people will expend and how principles that are critical to understanding health behav-
long they will persist when facing obstacles.4 SCT posits ior change98–100: (1) the environmental and personal factors
that a health behavior is more likely to be performed if that influence health behavior dynamically interact with
positive outcome expectancies are present, whereas nega- each other, (2) environments are multidimensional and
tive outcome expectancies reduce the likelihood of the complex, (3) people are multidimensional and complex,
health behavior being performed. For example, individu- and intervention designs should consider both the individ-
als will be much more inclined to run a mile if they antici- ual and the groups with which the individual is affiliated,
pate that doing so will energize them rather than cause and (4) people–environment interactions exert multiple
them to feel sore. The relative value of the anticipated out- levels of influence, such that individuals often modify
come also plays an important role in this decision-making their settings, and social features of settings influence
process. For example, an individual may view a positive individuals. Based on these principles, the Socialecological
anticipated outcome of smoking a cigarette (feeling more Model (SEM) framework suggests that health behavior
relaxed) as less important than a negative anticipated out- change strategies should consider both person-focused
come (smelling like smoke) and thus decide accordingly to and environment-focused strategies for health behavior
forgo the cigarette. change.99 Since multiple levels of factors influence behav-
SCT offers a comprehensive model of the behavior ior, interventions for health behavior change should also
change process. Some critics suggest that this model is be multilevel.101 Individual-focused strategies may include
overly broad and has not been tested as a whole in the way preventive screening programs, individual counseling, or
other theories are routinely examined.69 Rather, studies participation in lifestyle interventions. Environmental
202 Chapter 16 Applying Psychological Theories to Promote Healthy Lifestyles
strategies include both geographic (e.g., mixed-use com- As with all of the aforementioned models and theo-
munities) and sociocultural (e.g., integrating target health ries, some challenges arise in the application of the SEM
behaviors into organizational structures/cultures) aspects. to health behavior change interventions. Because the
The SEM has recently grown tremendously in popular- model is exceptionally comprehensive, its application is
ity, particularly in the public health realm. As the SEM inherently complex. For example, addressing the SEM’s
has gained attention, intervention strategies have extended multiple levels of influence, including regional (e.g., neigh-
their target factors to other levels such as community borhoods), structural (e.g., the physical environment),
participation,102 organizational policies for smoking ces- and institutional (e.g., government, worksite, family) fac-
sation,103 neighborhood resources for physical activity104 tors, on health behaviors is challenging due in large part
and healthy food,105 and comprehensive programs for to limitations on control over these external variables. In
diabetes care.106 The SEM differs from more traditional addition, additional research is required to help determine
psychological models in that it explicitly incorporates not which of the model’s multiple components are critical in
only the individual’s immediate external influences (e.g., the behavior change process. Despite its complexity, the
interpersonal relationships) but also more peripheral fac- SEM appears to be a promising model for an increasingly
tors (e.g., community, environment). Furthermore, rather multidisciplinary scientific community.
than predicting a specific order or direction in which
influences exert themselves, the SEM depicts the individ-
ual in the center of increasingly broader circles of influ-
ence that interact with one another in an ongoing process 16.5 THEORY-BASED HEALTHY
(Figure 16.4).
The SEM has been applied in assessment and inter-
LIFESTYLE INTERVENTION IN
vention research on a variety of health behaviors and/ RESEARCH AND PRACTICE
or in diverse populations, including fruit and vegetable
consumption among low-income African Americans,107 Research and practice are both producers and consumers
church-based health promotion interventions,108 physical of theory-based interventions, contributing to the evidence
activity promotion and fruit and vegetable intake,109 and base in lifestyle interventions, understanding the determi-
physical activity assessment within a variety of different nants of behaviors, testing behavior change strategies, and
populations.110–112 The SEM has also been used to identify implementing and disseminating effective interventions.
and classify barriers and facilitators individuals face in the Reviews of research on health behavior interventions have
adoption of health behaviors113–115 and the obstacles or aids shown that interventions that are designed based on the-
that affect participation of minorities in clinical trials.116 ory or theoretical constructs are more effective.
In the selection of strategies to change lifestyle in monitor his or her adherence to the newly adopted health
16
research and practice, some interventions focus on the behavior, continue the progress, or reconsider the plans
most effective constructs such as self-efficacy, intention, to meet the individual needs and capacities, if necessary.
planning, and self-regulatory skills regardless of theories Self-monitoring is a concurrent self-management strategy,
or models and evaluate the associations between them where the health behavior is continuously evaluated with
and the mechanism and effectiveness on behavior change. regard to the person’s behavioral goal or standard.
Others follow a defined structure according to a specific
theory or model such as HBM or SCT as a rationale for
choosing constructs and arranging their relationships and 16.6 SUMMARY
mechanisms in the process of analyzing and assessing out-
comes. The recognition of the wide range of health behav- In this chapter, we briefly discussed only a few of the
ior determinants can make the design and evaluation of numerous psychological models and theories that guide
intervention strategies a complex process. health behavior change interventions. We chose to focus
The use of psychological models or theories to bet- on some of the most frequently utilized models and theo-
ter understand, predict, and change behaviors is widely ries in the literature and to represent the range of general
accepted. Thus, they have been applied in the design of categories by which they are organized (i.e., individual,
health promotion interventions in both research and prac- interpersonal, ecological). Over the past few decades, the
tice. Psychologists have been using psychological factors fields of behavioral medicine, public health, and medicine
to predict behavior change for decades. In the HBM, (among others) have been gradually shifting from a sole
each step in the decision-making process is dependent focus on the individual to a progressively greater focus
on the previous decision or belief. The SCT is based on on the local and, to a growing extent, global environ-
the assumption that psychological constructs, namely, ment in which the individual resides.1,99 Although this
self-efficacy and outcome expectancy, serve as predic- shift recognizes and better accounts for the increasingly
tors of individuals’ behavior. The TPB postulates that a globalized world that undoubtedly influences individu-
central factor in performing a given behavior is an indi- als’ behavior more than ever before, these new ecologi-
vidual’s intention; the stronger the intention to engage cal models and theories are quite complex and somewhat
in a certain behavior, the more likely it will be accom- generic.98–100 Their numerous and relatively broadly
plished. According to the TPB, behavioral intention is the defined variables are often difficult to measure, rendering
most proximal antecedent of health-related behaviors.117 these models as a whole difficult to assess. However, they
Although intention is the strongest predictor of behavior, relieve individuals of at least some of the overwhelming
it is not sufficient to explain and predict behavior: not all amount of personal responsibility placed on them by the
of those who have the intention would perform a health individual and, to a somewhat lesser but still significant
behavior.118–120 This so-called Intention Behavior Gap is extent, interpersonal models and theories, which explic-
explicitly addressed in part IV, Chapter 6 of this book. itly or implicitly assert that individuals should engage in
Several behavioral constructs have been introduced to target health behaviors regardless of the external barriers
translate intentions to behavior, among which the most they may face. Moreover, the health problems and chal-
frequently used are goal setting,121 implementation inten- lenges for which health behavior change interventions are
tion,122 action and coping planning,123 and self-monitor- designed have also shifted from primarily acute and/or
ing.124 Goals affect individuals’ performance through four short-term illnesses (e.g., deadly viruses and infections) to
mechanisms; specifically, they (1) direct attention and predominantly chronic diseases (e.g., cardiovascular dis-
effort toward relevant activities, (2) energize action and ease and diabetes). As mentioned previously, one-time or
elicit greater effort, (3) increase persistence, and (4) affect short-term problems appear to be adequately addressed
action indirectly via motivation.125 Goal setting is con- by the individual-focused theories and models, whereas
sistent with SCT in the sense that both acknowledge the interventions for longer-term problems are more appro-
importance of goals and self-efficacy. The difference is priately designed using interpersonal (and presumably
that the emphasis of goal setting theory is on the process ecological) ones.
of defining clear properties of an effective goal in order to We then brought attention to the constructs that have
make it more achievable.121 shown to be most effective in translating behavioral inten-
When a person is inclined to adopt a particular tions into actual actions. Many other theories not included
health behavior, the intention has to be transformed into in this chapter also incorporate key concepts that help
detailed action plans of when, where, and how to per- explain and predict health behaviors. Perhaps the two big-
form the desired action and into coping plans on how to gest challenges facing the various disciplines involved in
overcome the barriers.123 Implementation intention122 is health behavior change research are (1) to match specific
another form of planning strategy that typically requires goal health behaviors with the models and theories that
that individuals specify their plans in an “if-then” format incorporate the most relevant and appropriate constructs
that explicitly links the anticipated situation to a specific in order to design and implement effective interventions,
response specified in the “then” part of the plan. and (2) to systematically incorporate and account for the
After taking up a health behavior, one has to focus on wide range of ecological factors that clearly influence
maintaining the behavior for the long term. This involves health behavior to an increasingly greater extent in the
continuous self-management, meaning the person needs to modern global world.
204 Chapter 16 Applying Psychological Theories to Promote Healthy Lifestyles
CLINICAL APPLICATIONS
• The focus of health promotion strategies has been implementing interpersonal and environmental
shifted from individuals to the local and global envi- models.
ronment in order to have a greater impact. • Health promotion programs should incorporate
• Short-term health problems are addressed by the the relevant and appropriate constructs instead of
individual-focused health care models, whereas models in order to design and implement effective
interventions for long-term health issues are interventions.
REFERENCES
1. National Cancer Institute, Theory At a 16. Ajzen, I. and M. Fishbein, Understanding 30. Bandura, A., Social Foundations of
Glance: A Guide for Health Promotion Attitudes and Predicting Social Thought and Action: A Social Cognitive
Practice. 2005, U.S. Dept. of Health and Behavior. 1980, Englewood Cliffs, NJ: Theory. 1986, Englewood Cliffs, NJ:
Human Services, Public Health Service, Prentice-Hall. Prentice Hall.
National Institutes of Health, National 17. Fishbein, M. and I. Ajzen, Belief, 31. Fishbein, M., et al., Factors influenc-
Cancer Institute. Attitude, Intention and Behavior: An ing behavior and behavior change, in
2. Glanz, K. and D.B. Bishop, The role of Introduction to Theory and Research. Handbook of Health Psychology, A.
behavioral science theory in development 1975, Reading, MA: Addison-Wesley. Baum and T. Revenson, Editors. 2001,
and implementation of public health 18. Ajzen, I., From intentions to actions: A Mahwah, NJ: Lawrence Erlbaum
interventions. Annu. Rev. Public Health, theory of planned behavior, in Action- Associates. p. 1–17.
2010. 31: p. 399–418. Control: From Cognition to Behavior, 32. Fishbein, M., A reasoned action
3. Glanz, K., B.K. Rimer, and National J. Kuhl and J. Beckmann, Editors. 1985, approach: Some issues, questions, and
Cancer Institute (U.S.), Theory At a Heidelberg: Springer. p. 11–39. clarifications, in Prediction and Change
Glance: A Guide for Health Promotion 19. Manstead, A.S.R., The benefits of a of Health Behavior: Applying the
Practice. NIH publication no. 97-3896. critical stance: A reflection on past papers Reasoned Action Approach, I. Ajzen,
1997, Bethesda, MD: U.S. Dept. of on the theories of reasoned action and D. Albarracin, and R. Hornik, Editors.
Health and Human Services, Public planned behaviour. Br. J. Soc. Psychol., 2007, Mahwah, NJ: Lawrence Erlbaum
Health Service, National Institutes of 2011. 50(3): p. 366–373. Associates, Inc. p. 281–295.
Health, National Cancer Institute. p. 48. 20. Kiviniemi, M.T., A.M. Voss-Humke, 33. Bandura, A., Toward a psychology of
4. Bandura, A., Self-efficacy: Toward a and A.L. Seifert , How do Ifeel about human agency. Perspect. Psychol. Sci.,
unifying theory of behavioral change. the behavior? The interplay of affective 2006. 1(2): p. 164–180.
Psychol. Rev., 1977. 84(2): p. 191. associations with behaviors and cognitive 34. Kenski, K., et al., Theoretical determinants
5. Bandura, A., Self-Efficacy: The Exercise of beliefs as influences on physical activity of condom use intentions for vaginal
Control. 1997, New York, NY: Freeman. behavior. Health Psychol., 2007. 26(2): p. sex with a regular partner among male
6. Becker, M.H. and L.A. Maiman, 152–158. and female injecting drug users. Psychol.
Sociobehavioral determinants of compliance 21. Armitage, C.J. and M. Conner, Efficacy Health Med., 2001. 6(2): p. 179–190.
with health care and medical care recom- of the theory of planned behaviour: A 35. von Haeften, I., et al., Analyzing data
mendations. Med. Care, 1975. 13: p. 10–24. meta-analytic review. Br. J. Soc. Psychol., to obtain information to design targeted
7. Rosenstock, I.M., Why people use health 2001. 40(4): p. 471–499. interventions. Psychol. Health Med.,
services. Milbank Mem. Fund. Q., 1966. 22. Gu, J., et al., Using the theory of planned 2001. 6(2): p. 151–164.
44(3): p. 94–127. behavior to investigate condom use 36. Kasprzyk, D. and D. Montano,
8. Rosenstock, I.M., Historical origins of behaviors among female injecting drug Application of an integrated behavioral
the health belief model. Health Educ. users who are also sex workers in China. model to understand HIV prevention
Monogr., 1974. 2(4): p. 328–335. AIDS Care, 2009. 21(8): p. 967–975. behavior of high-risk men in rural
9. Rosenstock, I.M., V.J. Strecher, and 23. Mausbach, B.T., et al., Predictors of safer Zimbabwe. 2007. p. 149–172.
M.H. Becker, Social learning theory and sex intentions and protected sex among 37. Montaño, D.E., et al., Evidence-based
the Health Belief Model. Health Educ. heterosexual HIV-negative methamphet- identification of key beliefs explaining
Q., 1988. 15: p. 175–183. amine users: An expanded model of the adult male circumcision motivation in
10. Norman, P. and K. Brain, An application Theory of Planned Behavior. AIDS Care, Zimbabwe: Targets for behavior change
of an extended health belief model to 2008. 21(1): p. 17–24. messaging. AIDS Behav., 2014. 18(5): p.
the prediction of breast self-examination 24. Eto, K., et al., Variables of the theory 885–904.
among women with a family history of of planned behavior are associated with 38. Bleakley, A., et al., Using the integrative
breast cancer. Br. J. Health Psychol., family meal frequency among adoles- model to explain how exposure to sexual
2005. 10(Pt 1): p. 1–16. cents. J. Nutr. Educ. Behav., 2011. 43(6): media content influences adolescent
11. Reiter, P.L., et al., Parents’ health beliefs p. 525–530. sexual behavior. Health Educ. Behav.,
and HPV vaccination of their adolescent 25. Blanchard, C.M., et al., Do ethnicity and 2011. 38(5): p. 530–540.
daughters. Soc. Sci. Med., 2009. 69(3): p. gender matter when using the theory of 39. Trinh, T.A. and T.T.A. Vo, Evaluating the
475–480. planned behavior to understand fruit and powerful prediction of integrated behav-
12. Carpenter, C.J., A meta-analysis of vegetable consumption? Appetite, 2009. ioral model for risky road behaviors.
the effectiveness of health belief model 52(1): p. 15–20. Procedia Eng., 2016. 142: p. 71–78.
variables in predicting behavior. Health 26. Armitage, C.J., Can the theory of 40. Kamb, M.L., et al., Efficacy of risk-
Commun., 2010. 25(8): p. 661–669. planned behavior predict the maintenance reduction counseling to prevent human
13. Painter, J., et al., The use of theory in of physical activity? Health Psychol., immunodeficiency virus and sexually
health behavior research from 2000 to 2005. 24(3): p. 235–245. transmitted diseases: A randomized
2005: A systematic review. Ann. Behav. 27. Fishbein, M., The role of theory in HIV controlled trial. Project RESPECT
Med., 2008. 35(3): p. 358–362. prevention. AIDS Care, 2000. 12(3): p. Study Group. JAMA, 1998. 280(13): p.
14. Harrison, J.A., P.D. Mullen, and L.W. 273–278. 1161–1167.
Green, A meta-analysis of studies of the 28. Fishbein, M. and J.N. Cappella, The role 41. Rhodes, F., et al., Using theory to under-
health belief model with adults. Health of theory in developing effective health stand how interventions work: Project
Educ. Res., 1992. 7(1): p. 107–116. communications. J. Commun., 2006. 56: RESPECT, condom use, and the integrative
15. Zimmerman, R.S. and D. Vernberg, p. S1–S17. model. AIDS Behav., 2007. 11(3): p. 393.
Models of preventative health behavior: 29. Janz, N.K. and M.H. Becker, The health 42. Bandura, A., Principles of Behavior
Comparison, critique, and meta-analysis. belief model: A decade later. Health Modification. 1969, New York, NY:
Adv. Med. Sociol., 1994. 4: p. 45–67. Educ. Q., 1984. 11(1): p. 1–47. Holt, Rinehart & Winston.
References 205
43. Skinner, B., Science and Human 58. Cismaru, M. and A.M. Lavack, Five-City Project. JAMA, 1990. 264(3):
Behavior. 1953, New York, NY: Free Campaigns targeting perpetrators of inti- p. 359–365.
Press.
44. DiClemente, C.C., J.O. Prochaska, and
S.K. Fairhurst, The process of smoking
mate partner violence. Trauma Violence
Abuse, 2011. 12(4): p. 183–197.
59. Nowlis, D.P. and N. Greenberg,
75. McAlister, A., et al., Theory and action
for health promotion illustrations from
the North Karelia Project. Am. J. Public
16
cessation: An analysis of the precontem- Empirical description of effects of exer- Health, 1982. 72(1): p. 43–50.
plation, contemplation, and prepara- cise on mood. Percept. Mot. Skills, 1979. 76. Perry, C.L., S.H. Kelder, and K.I. Klepp,
tion stages of change. J. Consult. Clin. 49(3): p. 1001–1002. Communitywide cardiovascular disease
Psychol., 1991. 59: p. 295–304. 60. Plow, M.A., M. Finlayson, and C. prevention with young people: Long-term
45. Prochaska, J.O., C.C. DiClemente, Cho, Correlates of stages of change for outcomes of the class of 1989 study. Eur.
and J.C. Norcross, In search of how physical activity in adults with multiple J. Public Health, 1994. 4(3): p. 188–194.
people change: Applications to addictive sclerosis. Res. Nurs. Health, 2011. 34(5): 77. Puska, P., Successful prevention of non-
behaviors. Am. Psychol., 1992. 47: p. p. 378–388. communicable disease: Twenty-five year
1102–1114. 61. Ward, R.M. and H.J. Schielke, Assessing experience with the North Karelia Project.
46. Pekmezi, D., B. Barbera, and B.H. the predictive ability of the transtheoreti- Public Health Med., 2002. 4(1): p. 5–7.
Marcus, Using the transtheoretical model cal model’s heavy episodic drinking con- 78. Puska, P., et al., A television format for
to promote physical activity. ACSMS structs among a population of underage national health promotion: Finland’s
Health Fit. J., 2010. 14(4): p. 8–13. students. Subst. Use Misuse, 2011. 46(9): “Keys to Health”. Public Health Rep.,
47. Prochaska, J.O., C.A. Redding, and K.E. p. 1179–1189. 1987. 102(3): p. 263–269.
Evers, The transtheoretical model and 62. Bezyak, J.L., N.L. Berven, and F. Chan, 79. Ramirez, A.G., et al., Advancing the role
stages of change, in Health Behavior and Stages of change and physical activity of participatory communication in the
Health Education, K. Glanz, B.K. Rimer, among individuals with severe mental diffusion of cancer screening among his-
and K. Viswanath, Editors. 2008, San illness. Rehabil. Psychol., 2011. 56(3): p. panics. J. Health Commun., 1999. 4(1):
Francisco, CA: Jossey-Bass. p. 97–122. 182–190. p. 31–36.
48. Di Noia, J., et al., Application of the 63. Awaisu, A., et al., The SCIDOTS project: 80. Houston, T.K., et al., The art and science
transtheoretical model to fruit and veg- Evidence of benefits of an integrated of patient storytelling-harnessing narra-
etable consumption among economically tobacco cessation intervention in tubercu- tive communication for behavioral inter-
disadvantaged African-American adoles- losis care on treatment outcomes. Subst. ventions: The ACCE Project. J. Health
cents: Preliminary findings. Am. J. Health Abuse Treat. Prev. Policy, 2011. 6: p. 26. Commun., 2011. 16(7): p. 686–697.
Promot., 2006. 20(5): p. 342–348. 64. Amiya, R.M., et al., Physicians are a 81. McAlister, A.L., et al., Telephone
49. Tuah, N.A., et al., Transtheoretical key to encouraging cessation of smoking assistance for smoking cessation: One
model for dietary and physical exercise among people living with HIV/AIDS: A year cost effectiveness estimations. Tob.
modification in weight loss manage- cross-sectional study in the Kathmandu Control, 2004. 13(1): p. 85–86.
ment for overweight and obese adults. valley, Nepal. BMC Public Health, 2011. 82. Meshack, A.F., et al., Texas tobacco
Cochrane Database Syst. Rev., 2011. 10: 11: p. 677. prevention pilot initiative: Processes and
p. CD008066. 65. Adams, J. and M. White, Are activ- effects. Health Educ. Res., 2004. 19(6):
50. Dempsey, A.R., S.S. Johnson, and C.L. ity promotion interventions based on p. 657–668.
Westhoff, Prediction oral contracep- the transtheoretical model effective? A 83. Shegog, R., et al., Use of interactive
tive continuation using the transtheo- critical review. Br. J. Sports Med., 2003. health communication to affect smoking
retical model of health behavior change. 37(2): p. 106–114. intentions in middle school students:
Perspect. Sex Reprod. Health, 2011. 66. Adams, J. and M. White, Why don’t A Pilot Test of the “Headbutt” Risk
43(1): p. 23–29. stage-based activity promotion interven- Assessment Program. Am. J. Health
51. Redding, C.A., et al., One session of tions work? Health Educ. Res., 2005. Promot., 2005. 19(5): p. 334–338.
TTM-tailored condom use feedback: A 20(2): p. 237–243. 84. Perry, C.L., et al., Project Northland high
pilot study among at-risk women in the 67. Callaghan, R.C., L. Taylor, and J.A. school interventions: Community action
Bronx. AIDS Care, 2011. 23(1): p. 10–15. Cunningham, Does progressive stage to reduce adolescent alcohol use. Health
52. Falk, M. and H. Magnusson, Sun pro- transition mean getting better? A test of Educ. Behav., 2000. 27(1): p. 29–49.
tection advice mediated by the general the Transtheoretical Model in alcoholism 85. Perry, C.L., et al., Project Northland:
practitioner: An effective way to achieve recovery. Addiction, 2007. 102(10): p. Long-term outcomes of community action
long-term change of behaviour and 1588–1596. to reduce adolescent alcohol use. Health
attitudes related to sun exposure? Scand. 68. Norris, S.L., et al., Effectiveness of Educ. Res., 2002. 17(1): p. 117–132.
J. Prim. Health Care, 2011. 29(3): p. physician-based assessment and counsel- 86. Worden, J.K., et al., Preventing alchohol-
135–143. ing for exercise in a staff model HMO. impaired driving through communty self-
53. Berger, B.A., H. Liang, and K.S. Prev. Med., 2000. 30(6): p. 513–523. regulation training. Am. J. Public Health,
Hudmon, Evaluation of software-based 69. McAlister, A.L., C.L. Perry, and G.S. 1989. 79(3): p. 287–290.
telephone counseling to enhance medica- Parcel, How individuals, environments, 87. Monteiro, S.M., et al., The protocol of a
tion persistency among patients with and health behaviors interact: Social randomized controlled trial for playgroup
multiple sclerosis. J. Am. Pharm. Assoc. cognitive theory, in Health Behavior and mothers: Reminder on Food, Relaxation,
(2003), 2005. 45(4): p. 466–472. Health Education, K. Glanz, B.K. Rimer, Exercise, and Support for Health
54. Lin, Z.C., et al., Designing a tailored and K. Viswanath, Editors. 2008, San (REFRESH) Program. BMC Public
web-based educational mammography Francisco, CA: Jossey-Bass. p. 167–188. Health, 2011. 11: p. 648.
program. Comput. Inform. Nurs., 2011. 70. O’Leary, A., Self-efficacy and health. 88. Nyberg, G., et al., A healthy school start
29(1): p. 16–23. Behav. Res. Ther., 1985. 23: p. 437–451. – Parental support to promote healthy
55. Tung, W.C., D.H. Nguyen, and D.N. 71. Stretcher, V.J., B. McEvoy-DaVellis, and dietary habits and physical activity in
Tran, Applying the transtheoretical M.H. Becker, The role of self-efficacy in children: Design and evaluation of a
model to cervical cancer screening in achieving health behavior change. Health cluster-randomised intervention. BMC
Vietnamese-American women. Int. Nurs. Educ. Q., 1986. 13(1): p. 73–91. Public Health, 2011. 11: p. 185.
Rev., 2008. 55(1): p. 73–80. 72. Pekmezi, D., E. Jennings, and B.H. 89. Drieling, R.L., J. Ma, and R.S. Stafford
56. Evers, K.E., et al., A randomized clinical Marcus, Evaluating and enhancing self- , Evaluating clinic and community-
trial of a population- and transtheoretical efficacy for physical activity. ACSMS basedlifestyle interventions for obesity
model-based stress-management interven- Health Fit. J., 2009. 13(2): p. 16–21. reduction in a low-income Latino neigh-
tion. Health Psychol., 2006. 25(4): p. 73. Williams, D.M., E.S. Anderson, and borhood: Vivamos Activos Fair Oaks
521–529. R.A. Winett, A review of the outcome Program. BMC Public Health, 2011. 11:
57. Babcock, J.C., et al., Applying the expectancy construct in physical activity p. 98.
transtheoretical model to female and research. Ann. Behav. Med., 2005. 29(1): 90. Gardiner, P.A., et al., Feasibility of reduc-
male perpetrators of intimate partner p. 70–79. ing older adults’ sedentary time. Am. J.
violence: Gender differences in stages 74. Farquhar, J.W., et al., Effects of com- Prev. Med., 2011. 41(2): p. 174–177.
and processes of change. Violence Vict., munitywide education on cardiovascu- 91. Keller, C., et al., Predictive ability of social
2005. 20(2): p. 235–250. lar disease risk factors. The Stanford cognitive theory in exercise research:
206 Chapter 16 Applying Psychological Theories to Promote Healthy Lifestyles
An integrated literature review. Online J 104. Humpel, N., N. Owen, and E. Leslie, 0–6 years of age: A systematic review of
Knowl Synth Nurs, 1999. 6: p. 2. Environmental factors associated with quantitative literature. Sports Med., 2017.
92. Trevino, R.P., et al., Bienestar: A diabetes adults’ participation in physical activity: A 47(7): p. 1349–1374.
risk-factor prevention program. J Sch review. Am. J. Prev. Med., 2002. 22(3): p. 115. Hesketh, K.R., R. Lakshman, and E.M.F.
Health, 1998. 68(2): p. 62–67. 188–199. van Sluijs, Barriers and facilitators to
93. Bandura, A., Social cognitive theory and 105. Glanz, K., et al., Healthy nutrition envi- young children’s physical activity and
exercise of control over HIV infection, in ronments: Concepts and measures. Am. J. sedentary behaviour: A systematic review
Preventing AIDS: Theories and Methods Health Promot., 2005. 19(5): p. 330–333. and synthesis of qualitative literature.
of Behavioral Interventions, C.C. 106. Larsen, D.L., W. Cannon, and S. Towner, Obes. Rev., 2017. 18(9): p. 987–1017.
DiClemente and J.L. Peterson, Editors. Longitudinal assessment of a diabetes 116. Salihu, H.M., et al., Socio-ecological
1994, New York, NY: Plenum. p. 25–59. care management system in an integrated model as a framework for overcoming
94. Li, X., et al., Effect of social cognitive health network. J. Manag. Care Pharm., barriers and challenges in randomized
theory-based HIV education prevention 2003. 9(6): p. 552–558. control trials in minority and underserved
program among high school students in 107. Robinson, T., Applying the socio- communities. Int. J. MCH AIDS, 2015.
Nanjing, China. Health Educ. Res., 2011. ecological model to improving fruit and 3(1): p. 85–95.
26(3): p. 419–431. vegetable intake among low-income 117. Fishbein, M. and I. Ajzen, Predicting
95. Baranowski, T., et al., Are current health African Americans. J. Commun. Health, and Changing Behavior: The Reasoned
behavioral change models helpful in 2008. 33(6): p. 395–406. Action Approach. 2010, New York, NY:
guiding prevention of weight gain efforts? 108. Campbell, M.K., et al., Church-based Psychology Press. p. 518.
Obesity, 2003. 11(S10). health promotion interventions: Evidence 118. Sheeran, P., Intention—Behavior rela-
96. Grzywacz, J.G. and J. Fuqua, The social and lessons learned. Annu. Rev. Public tions: A conceptual and empirical review.
ecology of health: Leverage points and link- Health, 2007. 28: p. 213–234. Eur. Rev. Soc. Psychol., 2002. 12(1): p.
ages. Behav. Med., 2000. 26(3): p. 101–115. 109. Richard, L., L. Gauvin, and K. Raine, 1–36.
97. King, A.C., et al., Theoretical approaches Ecological models revisited: Their uses 119. Godin, G. and G. Kok, The theory of
to the promotion of physical activity: and evolution in health promotion over planned behavior: A review of its applica-
forging a transdisciplinary paradigm. two decades. Ann. Rev. Public Health, tions to health-related behaviors. Am. J.
Am. J. Prev. Med., 2002. 23(2): p. 15–25. 2011. 32: p. 307–326. Health Promot., 1996. 11(2): p. 87–98.
98. Stokols, D., Establishing and maintain- 110. Casey, M.M., et al., Using a socioecologi- 120. Armitage, C.J. and M. Conner, Efficacy
ing healthy environments. Toward a cal approach to examine participation in of the theory of planned behaviour: A
social ecology of health promotion. Am. sport and physical activity among rural meta-analytic review. Br. J. Soc. Psychol.,
Psychol., 1992. 47: p. 6–22. adolescent girls. Qual. Health Res., 2009. 2001. 40(Pt 4): p. 471–499.
99. Stokols, D., Social ecology and behav- 19(7): p. 881–893. 121. Locke, E.A. and G.P. Latham, Building
ioral medicine: Implications for training, 111. Nelson, A., R. Abbott, and D. Macdonald , a practically useful theory of goal setting
practice, and policy. Behav. Med., 2000. Indigenous Austaliansand physical activity: and task motivation. A 35-year odyssey.
26: p. 129–138. Using a social–ecological model to review Am. Psychol., 2002. 57(9): p. 705–717.
100. Stokols, D., J. Allen, and R.L. Bellingham, the literature. Health Educ. Res., 2010. 122. Gollwitzer, P.M., Implementation inten-
The social ecology of health promotion: 25(3): p. 498–509. tions: Strong effects of simple plans. Am.
Implications for research and practice. Am. 112. Rhodes, R.E. and G. Nasuti, Trends and Psychol., 1999. 54(7): p. 493.
J. Health Promot., 1996. 10: p. 247–251. changes in research on the psychology 123. Sniehotta, F.F., et al., Action planning
101. Sallis, J.F., N. Owen, and E. Fisher, of physical activity across 20years: A and coping planning for long‐term
Ecological models of health behavior. quantitative analysis of 10 journals. Prev. lifestyle change: Theory and assessment.
Health Behavior: Theory, Research, and Med., 2011. 53(1): p. 17–23. Eur. J. Soc. Psychol., 2005. 35(4): p.
Practice. 5th ed. 2015, San Francisco, 113. Ma, P.H.X., Z.C.Y. Chan, and A.Y. Loke, 565–576.
CA: Jossey-Bass. p. 43–64. The socio-ecological model approach to 124. Karoly, P., Mechanisms of self-regulation:
102. Fisher, E.B., et al., Cigarette Smoking. 2004. understanding barriers and facilitators A systems view. Ann. Rev. Psychol.,
103. Brownson, R.C., D.P. Hopkins, and M.A. to the accessing of health services by 1993. 44(1): p. 23–52.
Wakefield, Effects of smoking restric- sex workers: A systematic review. AIDS 125. Wood, R.E. and E.A. Locke, Goal-setting
tions in the workplace. Ann. Rev. Public Behav., 2017. 21(8): p. 2412–2438. and strategy effects on complex tasks.
Health, 2002. 23(1): p. 333–348. 114. Hesketh, K.R., et al., Determinants of Res. Org. Behav., 1990. 12: p. 73–109.
change in physical activity in children
17
CHAPTER
Motivational Interviewing
and Lifestyle Change
Peter Fifield, EdD, LCMHC, MLADC, Joji Suzuki, MD,
Samantha Minski, PhD, and Jennifer Carty, PhD
207
208 Chapter 17 Motivational Interviewing and Lifestyle Change
Partnership. MI is practiced as a collaboration between already possess that will facilitate them in accomplishing
17
a clinician and patient. It maintains that there are two their goals.
experts in the room, both the clinician and the patient. Autonomy support. To fully accept an individual, their
While the clinician may be an expert in smoking cessa- attitudes and decisions must be appreciated and respected.
tion or diabetes management, for example, the patient Humans seem to possess a unique need to preserve their
is an expert on themselves and on implementing the rec- sense of autonomy, to maintain an internal locus of con-
ommended plan in their own lives. Therefore, the clini- trol, and to make decisions for themselves. Respecting and
cian must work alongside the patient to best help them. supporting autonomy is in direct contrast to convincing
A visual example of this was created by Jeff Allison,4 who someone to act in a certain way. Ultimately, an individual
described MI as an opportunity to “dance with a patient, will decide what changes to implement, and if they are
not wrestle.” This metaphor suggests that while the clini- maneuvered towards a direction they do not agree with,
cian may guide the session in a goal-oriented fashion, they they will advocate for the opposite behavior as a way of
are not in the position to convince or force their patient to demonstrating their free will.
make any choices. Another distinction of this partnership Accurate Empathy. This is another “critical condition
is the understanding that the clinician is not responsible for for change,” per Rogers. Clinicians need to prioritize their
all the answers, and that the individual ultimately knows patient’s perspective and purposely ask questions to better
what is best for them. This is in direct contrast to training understand their interests, views, and beliefs. It is impor-
models emphasizing the role of a professional to have all tant to distinguish our own opinions from those of our
the answers to problems their patients present to them. patients so that we can avoid imposing our views on them.
It is sometimes hard for clinicians to internalize that they Ultimately, it is difficult to respect patient autonomy if the
may be more responsible for the intervention than the clinician does not understand who they are, what they
outcome. believe in, and for what they hope.
Compassion. Compassion goes beyond having positive
regard for another and an understanding of their experi-
ences; it includes purposely prioritizing what is in anoth-
er’s best interest. The other three aspects of MI’s spirit can
17.2.1 Research and Evidence
be employed to serve the interests of the clinician, but with In the more than 30 years since MI was described, it
compassion, the emphasis is placed on doing what is best has had broad applicability, and the large body of MI
for the patient. Compassion underscores the importance research reflects this. MI has been utilized to address a
of being selfless and structuring communication around wide variety of behaviors, across multiple settings, and by
an individual’s personal goals, even if they do not align healthcare clinicians across training levels and disciplines.
with the clinician’s goals. Concerning health behaviors, MI has demonstrated effec-
Evocation. One of MI’s goals is to help the patient bet- tiveness for individuals with chronic pain, diabetes, HIV,
ter understand and recognize their own reasons for mak- poor contraceptive use, excess weight, and tobacco and
ing changes to their behavior. It suggests that the patient alcohol use.13–20
already has their own reasons for changing and MI’s role Overall, meta-analyses suggest that motivational
is to illuminate what these specific reasons are. By evok- interviewing improves outcomes by 10–20% in a variety
ing and strengthening change talk and suppressing sustain of conditions compared to no treatment and is equally
talk, a patient’s ambivalence may be resolved, allowing effective or more effective than active treatments. 21 These
them to focus on the preparation and planning it takes to effects hold based on severity of problem, patient gender,
make and sustain change. age, and ethnicity. Indeed, research has found that the
Acceptance. Four key components make up the princi- style of motivational interviewing might be a more cultur-
ple of acceptance and are based on work by Carl Rogers.12 ally sensitive form of psychotherapy, which might account
Together they explain that the clinician must accept a for the findings that motivational interviewing is more
patient, their choices, and what they have the capacity to do. effective in minority groups. 22 Interestingly, motivational
Absolute Worth. Rogers identified absolute worth interviewing is more effective when clinicians do not rig-
as unconditional positive regard. It communicates the idly follow a manual, perhaps because sticking too closely
importance of abstaining from judgement. Rogers sug- to a manual encourages clinicians into problem solving
gested that when people feel judged, they are less likely too quickly. 22 Rather than the traditional approach of
to change and grow. They may feel reluctant to attempt learning a new therapeutic technique via manuals and
change when their environment feels unsafe. In contrast, workshops, there is evidence that clinicians from a variety
when individuals feel valued it provides an opportunity for of backgrounds and training can attain proficiency in MI
them to explore themselves and the possibility of change. through a two-day intensive training or the equivalent of
Affirmation. Affirmations provide a way of communi- 12–16 hours of in-person didactic and role-playing oppor-
cating to another that you recognize their efforts as well tunities followed by continued coaching and supervision/
as their positive attributes.12 In many disciplines, clini- consultation. 21,23 In summary, sustained proficiency in MI
cians are trained to evaluate their patients for deficiencies has been shown with 14–16 hours of training followed
and inadequacies and to identify what is going wrong. by modest yet prolonged (i.e., 4–5 hours over six months)
However, affirmations intentionally focus on the oppo- supervision and coaching from an expert trainer.7
site—to identify and reflect on the strengths and resilience Motivational interviewing first garnered attention as
of the patient. Clinicians are encouraged to share with an effective technique for use in alcohol use disorder in
the patient the characteristics, traits, or behaviors they the early 1980s. Since then, research has continued to
210 Chapter 17 Motivational Interviewing and Lifestyle Change
suggest that it is an effective intervention for individuals established, the process of planning allows for a contin-
with alcohol use disorder. A recent meta-analysis of 22 ued journey in an entirely new direction, a direction of
randomized-controlled trials (RCTs) of MI in alcohol use change behavior. Clinicians should keep in mind that the
disorder found that MI had a small effect size in improv- journey of rowing the boat together can be a linear pro-
ing alcohol use. 24 Further, it appears that, for alcohol use cess. However, it more often than not can also be recur-
disorder, MI is just as effective and, in some cases, more sive, navigating and re-navigating the same exact waters
effective than other treatments, particularly in the short time and time again. The process becomes MI when the
term. 24 This is consistent for treatment of substance use communication style follows the MI spirit, when there
disorders in adolescents as well as adults, suggesting that is a focused goal, and when the practitioner evokes the
motivational interviewing can be an effective treatment patient’s motivations for change. Although MI can be
throughout the life span. 25 done without planning, that task often proves to be an
The effects of motivational interviewing extend to integral part of MI. In practice, behavior change often
many other health behavior changes. Within weight man- requires that the four processes be repeated in an iterative
agement literature, for example, MI research suggests it fashion over many weeks, months, and even years.
can be utilized effectively to contribute to weight loss as
well as improvements in eating and exercise behaviors. In
a review of 11 randomized-controlled trials evaluating 17.3.2 Engaging
MI for weight loss in overweight and/or obese adults, MI
demonstrated a medium effect size of 0.51 SDs for weight Motivational interviewing first seeks to create an appro-
loss compared to control interventions. 26 A similar meta- priate interpersonal environment that sets the stage for
analysis indicated that MI led to an increase in diet and the possibility of change to occur by intentionally working
exercise for overweight adults with an effect size of .56. 27 to create a strong and collaborative relationship between
Although originally utilized for an adult population, the patient and the clinician (i.e., by asking “shall we row
the effectiveness of MI extends to children and teenagers. together?”). According to Miller and Rollnick,4 the goals
Channon et al. 28 conducted a randomized control trial and of the engagement in MI are to establish a working rela-
evaluated the efficacy of MI compared to supportive coun- tionship with the patient, to create agreement on treat-
seling for 14–17-year-olds with type 1 diabetes. For the ment goals, and to collaborate on ways to achieve those
38 teenagers randomized to the intervention group, mean goals. This is in contrast to the medical model in which
A1C was significantly lower than in the control at 12 and the clinician takes on an authoritative educator role and
24 months (12 months, P = .04; 24 months, P = .003). The even to some psychotherapeutic models in which the clini-
impact of MI on children and teenagers is influenced by cian plays the role of the expert. It should be noted that
the specific health behavior it is targeting. A meta-analysis there are times that the educator and expert role is not
evaluating MI for pediatric health domains (e.g., sleep, only helpful but necessary in medicine and psychotherapy
dental hygiene, HIV/AIDS) suggests that MI has a small (e.g., when providing information about a medical proce-
but significant effect across behaviors (g = .282) compared dure or diagnosis, and when addressing acute and emer-
to alternative interventions. 29 Notably, the changes pro- gent medical or psychiatric problems); however, the MI
duced by MI were maintained as the effect did not sig- approach suggests that clinicians delay this role when it
nificantly decrease across follow-up evaluations. Of note, comes to discussions of behavior change until later in the
within this meta-analysis, most studies were found to conversation, and at minimum, until the patient and clini-
focus on obesity (12 out of 37). Together these findings are cian have engaged in a strong relationship. Focusing on
encouraging for the use of MI to improve health outcomes engagement in the relationship, as opposed to a fact-find-
for children and teenagers. ing mission, requires a different set of skills that are more
complex. The OARS (open-ended questions, affirmations,
reflections, and summaries) are a helpful toolset for devel-
17.3 FOUR PROCESSES oping engagement with the patient. These are described
more fully now.
Open-ended questions. Open-ended questions elicit
17.3.1 Introduction responses that require more than one- or two-word
In the current iteration of MI, there are four processes responses and typically elicit full sentence responses. The
of MI to which clinicians need to be mindful: Engaging, difference between open-ended and closed-ended ques-
Focusing, Evoking, and Planning. The use of a metaphor tions is relatively easy to spot, though much harder to
may be helpful in understanding the four processes of MI. change in communication patterns. Open-ended ques-
First, there is a boat, a vessel to hold both the practitio- tions encourage patients to give thoughtful and elaborate
ner and the patient. The patient is sitting in this boat and narrative-like responses to questions, and patients them-
through the process of engagement, invites the practitio- selves must choose what to disclose. They also allow the
ner in. Together, via the use of MI skills, or OARS (see patient to engage more collaboratively in the discussion.
section 2.3.2), the practitioner begins rowing the boat. Close-ended questions elicit one- to two-word responses.
With the utilization of focus, the two occupants of the These responses are often a “yes/no” or fact-based
boat decide on a direction to row. As the journey towards response. Use of close-ended questions is helpful when
the shared destination continues, the process of evocation a specific response is needed, and often these questions
is utilized to enhance and reinforce the motivation to con- are an important data-gathering tool. However, relying
tinue rowing. Once there has been substantial motivation too much on close-ended questions can be inefficient and
17.3 Four Processes 211
may also only reflect the clinician’s agenda rather than the My doctor really wants me to quit, but between work
patient’s (Table 17.1). and being a single parent, smoke breaks are my only
Affirmations. Affirmations are statements or reflec- time to myself.”
tions of an individual’s strengths or efforts and can be
simple (“Thank you for coming in on time today”) or com- Simple: In a simple reflection, the clinician may just
plex (“You are a resourceful person for dealing with this repeat back what the patient stated, “You’d like to quit
stress for so long”). The goal of making affirmative state- smoking and you’ve been thinking about it for a while.”
ments to the patient, according to Miller,9 is to enhance Although this can be useful, it is best in moderation, for
the patient’s self-esteem and self-efficacy. Increasing an it may become tiresome for both clinician and patient
individual’s self-efficacy has been shown to improve moti- if repeated multiple times. Simple reflections might also
vation for change.30 It is important that affirmations, as involve the clinician reflecting back a statement very
with any emphatic statement, are expressed genuinely. It is close to what the patient said but substituting synonyms
also best to avoid making the statements focused on your or slightly rephrasing what the patient offered. For
approval or praise of a patient’s behavior, which are con- example, “Your doctor wants you to quit smoking and
sidered compliments and not affirmations. In the end, such you don’t have a lot of alone time besides smoke breaks.”
statements put undue pressure on the patient to perform Clinicians might also utilize paraphrasing, which is when
for the clinician in the future. It may be difficult at times the clinician is listening for ways to infer the underly-
to think of an affirmation to say to a patient. For example, ing meaning in what the patient is saying and to reflect
a patient who has unmanaged diabetes with a high A1C; that meaning back to the patient. When this is done well,
is overweight, eats poorly, does not exercise, and albeit it helps the patient to continue their own thought pro-
late every visit continues to show up. An affirmation for cess rather than starting a new one. Paraphrasing in this
this individual could be, “You were determined to make example might look like, “Tackling something like quit-
it here today.” ting smoking seems difficult as a single parent, and part
Additional examples of affirmations: of you recognizes that this is an important part of your
health.”
“You are very good at caring for others.” Complex: In complex reflections, clinicians are reflect-
“You enjoy adventure and having fun.” ing the feelings that highlight the emotional aspect of what
“It is hard to get you down for long.” the patient is discussing. These are often more complex
“You are resilient.” versions of paraphrases. As clinicians become more skilled
at this type of reflection, they use both feeling statements
Reflections. Reflections are one of the most commonly (“you are scared”), as well as metaphors (“you feel like you
used skills in Motivational Interviewing (and many other are treading water”). In this example, the clinician might
therapeutic techniques). Like affirmations, reflections can reflect back, “You are really stressed and worried about
range from simple to complex. The goal of reflective state- losing the only alone time that you have.” See Table 17.2.
ments in MI is twofold: one goal is to convey empathy and Summaries. Summary statements are the final compo-
compassion to the patient, but the second, and perhaps nent of OARS and are used to tie together everything the
more unique goal of using reflections in MI, is to use these person has said throughout the interaction and to ensure
statements to elicit and guide the discussion to enhance that there is clear communication. It is often helpful to
motivation for change. Those who are just beginning to let the patient know that a summary is coming by using
practice MI may choose to focus on simple reflections statements such as, “Let me see if I understand so far,”
until they become more proficient. To best illustrate the or “To summarize, on the one hand, you feel … and on
range of reflections, let’s first look at a case example. the other hand ….” Summaries can also be used to link
together statements that the patients have made in previ-
Clinician: “Thank you coming in today. Your primary ous encounters or to tie together information you might
care physician told me a little bit about you and that have from other sources (e.g., medical chart, PCP, spouse,
you might be interested in quitting smoking, why if permission has been given). Summaries are also a help-
don’t you tell me in your own words what brings you ful device to transition focus to a different topic and to
in today?” probe the patient’s readiness to make a plan. It is helpful
Patient: “Well, I’d like to quit smoking and I’ve been to end a summary statement with an invitation such as,
thinking about it for a while, but I’m not sure I can. “Did I miss anything?” or “Anything you want to add or
212 Chapter 17 Motivational Interviewing and Lifestyle Change
correct?” This encourages the patient to continue to be like to provide education to a patient in an MI-consistent
collaborative and to have autonomy. A particularly useful way, typically when they only have a brief period of time.
way to incorporate summaries is to offer patients a sum- In this model, the clinician would first elicit what the
mary of their change talk, referred to as the “change talk patient already knows about condition X, if the patient
bouquet,” in which the change talk statements evoked are is interested in learning more, and if the clinician has
bundled into a summary. This could function as a transi- permission to share more information. This approach
tional summary that helps to move the conversation on to respects patient autonomy by asking permission and
the key question or to conclude the interview by highlight- assessing interest. If permission is given, the next step
ing the positives. would be to provide affirmation, feedback, advice, or one
Roadblocks for engaging. Despite our best efforts or two pieces of information to the patient. If permission
and intentions, there are often roadblocks to engaging is not granted (this may sound strange, but it happens),
with patients that are important to be aware of. Utilizing then do not continue with educating. If you do continue,
these “roadblock”-type communication skills can hin- that action can only damage the relationship you have cre-
der effective listening and engagement with the patient. ated to that point. Please keep in mind that the person’s
Motivational Interviewing is an approach to get around presence in the room with you is not necessarily implied
these roadblocks. In addition to the righting reflex consent for providing information. For the last step, the
described earlier in this chapter, below are twelve com- clinician would again elicit reactions, questions, and pos-
mon roadblocks that hinder effective communication sibly plan for next steps (Figure 17.1).4
(adapted from Thomas Gordon’s 12 Roadblocks):4 Additional traps that are common are spending the
majority of time during the intake or initial session to only
1. Ordering, directing, or commanding gathering information, as opposed to spending time con-
2. Warning, cautioning, or threatening necting to and understanding the patient. This can be a
3. Giving advice, making suggestions, or providing challenging balance for clinicians when certain informa-
solutions tion is required to be answered in an intake session. When
4. Persuading with logic, argument, or lecturing the clinician solely focuses on information gathering, they
5. Telling people what they should do; moralizing are more likely to be perceived as the expert in the relation-
6. Disagreeing, judging, criticizing, or blaming ship, and they risk prematurely defining the focus of the
7. Agreeing, approving, or praising interview or focusing on the clinician’s agenda rather than
8. Shaming, ridiculing, or labeling the patient’s.
9. Interpreting or analyzing An approach that can be used to safeguard against this
10. Reassuring, sympathizing, or consoling is the MI assessment sandwich.31 First, the clinician uses
11. Questioning or probing OARS to build rapport and engage with the individual (via
12. Withdrawing, distracting, humoring, or changing the elicit-provide-elicit model). This allows the patient to
the subject join with the clinician while simultaneously providing an
opportunity for the clinician to understand the patient’s
The 12 communication styles outlined above rely on readiness for change. Then, the clinician leads into the
being directive, educating, or judging rather than collab- information gathering portion of the session. This could
orative and supportive of autonomy, approaches that are include any number of assessment protocols. Finally, the
fundamental to MI. clinician focuses on eliciting change talk and working
A helpful alternative to these roadblocks is the Elicit- with the patient’s ambivalence to change and ultimately,
Provide-Elicit model, which is used when a clinician would if appropriate, creating a change plan.
17
cian but also being in a role where they are making an
The second process of MI, and a key one, is focusing. The importation recommendation about the patient. This type
clinician and the patient must know the direction toward of honest and open conversation can help to create the
which they are rowing the boat. That is to say, there must trust necessary to move forward in the interview. In these
be a statement of a clearly defined goal or focus of the con- particular cases, adopting equipoise can also be useful.
versation, and typically it will occur in the early stages of Equipoise calls for the clinician to take a neutral stance
the conversation. Without a specific orientation to a goal or regarding the desired outcome.4 Typically, in MI the cli-
a behavioral change, it can be difficult for both the patient nician is working towards moving the patient toward a
and the clinician to know where to focus their attention. particular goal which is typically clear (i.e. smoking less,
Learning how to collaboratively set an agenda becomes an losing weight, going to treatment). In equipoise, the clini-
important skill in this MI process. The clinician may have cian would maintain neutrality and allow the patient to
some hints from their setting (e.g., weight-loss clinic) or explore the pros and cons of each side of the potential out-
based on their own expertise about what the patient might come (i.e., to stay with a job or not, to leave a partner or
be expecting from them. In some cases, a patient might not). A clinician in this situation might choose to complete
also be very clear about their agenda for the visit (e.g., “I a decisional balance grid with the patient. To do this list
am here because I want to lose weight). When the goal is the Benefits/Pros and Costs/Cons in each category (mak-
clear, the clinician should feel free to move towards evok- ing a change and not making a change) and let this guide
ing. However, the art of focusing comes in when the patient a conversation to the next steps in the focusing process
is less clear about the goal or when there is not a preset (Figure 17.2).
focus for the visit. Clinicians should feel comfortable stay-
ing in focusing until a clear goal can be set. To help move
along the process when there is an unclear goal, Miller and
Rollnick4 suggest a tool called agenda mapping, which they
17.3.4 Evoking
describe this way: “Like looking at a map and seeing the As a patient makes their way towards change (the direc-
places you might go, perhaps like two people on a sail- tion they are rowing in) ambivalence is a natural and a
boat slowing down for a moment to agree on a new course very common place to get stuck. Concepts such as “change
(p. 106).” Agenda mapping starts by asking the patient for talk” and “sustain talk” help explain the two sides of
permission to take a step back to consider all of the topics ambivalence: reasons for changing and reasons for not
that the patient would like to be discussed. This technique changing. Miller and Rollnick4 hypothesized that self-
guides the patient to where you are going and supports motivational speech (change talk) is one mechanism of
their autonomy. Next, the patient and clinician create a list action in MI, and there is a strong body of evidence reli-
of possible options to talk about. The clinician should, in a ably linking change talk to positive health outcomes.32–34
collaborative manner, suggest topics that they think might Furthermore, there is evidence that MI-consistent clinician
be of importance for the patient to add to the list. Once this behaviors lead to change talk.35–37 Moyers et al. suggest
bird’s-eye view is created, the clinician guides the patient that change talk “[m]ediates the relationship between
back towards a specific focus. MI-consistent clinician behaviors and improved client out-
Another challenge to focusing is when there is a preset comes.”34 Change talk is the verbalization of the patient’s
goal to the visit (e.g., court-ordered substance use treat- internal motivation to change. Statements that represent
ment, therapy mandated by pain medication contract, movement towards change are precisely the language
evaluation of a living donor for liver transplant). In these clinicians should be focused on evoking, strengthening,
cases, it is important to acknowledge that the individual affirming, and validating. Clinicians must first build their
is being mandated to be at the appointment and might be awareness and ability to recognize change talk and then
reluctant to engage. It can also be helpful for the clinician work on responding to it.
Benefits/Pros Costs/Cons
Making a change
Recognizing Change Talk: Although sustain talk is nor- 1. “I really would like to be better at setting limits with
mal, focusing on it is not always helpful. Often clinicians myself around how much I eat.”
are habituated, or even trained, to identify the problems in 2. “Well, I know it is important to lose weight but I’m
a situation. With MI, it is necessary to shift the lens from really not that bad, my BMI is only 29.”
identifying and subsequently elaborating on the problem 3. I’m worried that if I do not start to lose weight soon,
(eliciting sustain talk) to seeking out the intrinsic want it will never be possible.”
and need to change (change talk). According to Miller and 4. It seems that I have wasted a lot of my life using
Rollnick,4 change talk is divided into two categories: pre- drugs and alcohol.”
paratory change talk and mobilizing change talk.
Preparatory Change Talk: Answers: (1). Yes. this is an example of a desire to
change. (2). No. This statement starts with a potential
Desires: “I really want to” … “I’m hoping that if”… change but reverts to sustain talk at the end. (3). Yes. This
“I really wish life was different.” is an example of a need to change. (4). Yes. The statement
Ability: “I know I can do this if” … “I have shows a reason for change.
changed like this in the past.” Being able to evoke change talk is an essential part
Reason: “If I could just lose ten pounds, I know of MI. Scaling-type questions are often used as a tool
I would feel better” … “I know what I’m doing is to evoke change talk. To do this, use an imaginary scale
not healthy” … “If I could just get started, I would ranging from 0–10. This importance ruler is integrated
feel more confident in other ways.” into change conversation by inquiring about how impor-
Need: “The doctor said I need to quit.” “I need tant it is to the patient to change a particular target behav-
to do this for me and my family”; “I’m always so ior. For example, the clinician could ask:
exhausted and I know it is affecting my work.”
On a scale from 0 to 10, where 0 is “not important
Mobilizing Change Talk: at all” and 10 is “extremely important,” how impor-
tant is it to you to ___________? (Figure 17.3)
Commitment: “I am willing to hear your advice on
what to do next” … “I’m going to start tracking This offers a baseline level of importance. From here
daily step count.” the clinician could begin eliciting change talk from the
Activation: “I’ve been considering how to tackle patient concerned about losing weight. Proceed by asking:
this bad habit” … “I’m ready to start.”
Taking Steps: “I have already bought a gym Tell me a bit about why you are at (the reported
membership” … “I called the smoking cessation number) and not at (a lower number)?
phone line and left a message” … “I talked to my
wife about what she thinks.” Keep in mind the importance of offering the patient-
reported number first, and then a lower number. When
It is important to remember that sustain talk is not the clinician approaches in this manner, the patient will
fundamentally bad or non-therapeutic. In fact, it is com- provide change talk by offering up reasons why it is impor-
pletely normal. The clinician’s goal, however, is to evoke tant. If this question was asked in reverse, you would be
and respond to change talk when they hear it. Miller and eliciting sustain talk from the patient where they would
Rollnick4 state that “[s]killful MI significantly strength- offer examples of roadblocks in the way of change; they
ens client change talk, which in turn predicts subsequent would be rationalizing reasons to stay the same. This last
change (p. 155).” When responding to change talk, it question can be followed up by:
is helpful to know which type of change talk it is that
is heard in order to facilitate movement forward. If the “What would it take to get you from (lower number)
patient is providing preparatory change talk, the clinician to (a number slightly higher)?”
then works on increasing the change talk regarding mov- The response will provide more change talk and
ing toward a plan. If the patient is providing mobilizing support the efforts and/or successes in the past. The
change talk, the clinician then works on increasing the above-mentioned importance ruler in Figure 17.3
change talk towards next steps. can also be used to investigate the patient’s level of
Practice: Examine the following statements and deter- confidence. To do this, simply replace importance
mine whether each statement is an example of change talk with confidence. The result will be the patient’s con-
and compare your conclusions to the answers provided fidence talk. Be sure to once again offer the patient’s
below: stated number first, followed by a lower number.
0<--------------------------------------------------------------------------> 10
17
reasons for their confidence including wants, needs, • Arguing
and even past successes. • Interrupting
Other provocative questions that could elicit • Ignoring
change talk are:
Discord can occur in any of the four processes of MI,
What is there about you that would help you be it discord in engaging, focusing, evoking, or plan-
do this? ning. Discord can be addressed by returning to the first
How might you go about it in order to succeed? process of MI—engaging. There are numerous ways to
How would you go about this change? approach the amelioration of discord. First, it can be
What have you done successfully in the past done by simply apologizing for the disconnect. A simple
that was like this in some way? “sorry” can go a long way in repairing the collabora-
What are the reasons for changing? tive relationship. A statement such as “You know, I’m
sorry I overstepped my bounds. I should not be telling
Responding to change talk is a critical component of MI. you what to do” can easily reduce the tension of dis-
Given that change talk represents internal motivation for cord. Affirming the patient is also an effective technique.
change, patients can be further strengthened by strategically A clinician who observes discord could offer, “You are
responding to them. Clinicians utilize OARS to respond to very sure of what has worked in the past.” Lastly, there
change talk. Strategies for Evoking Change Talk4 fall into is shifting focus. This technique is an implicit way for the
a commonly used and easy to remember mnemonic: EARS clinician and patient to agree to disagree and shift the
conversation away from the contentious topic you were
• Elaborate by asking open-ended questions such as
on. An example of shifting focus is: “You are right, my
“Why would you want to make this change or how
opinion is not important here, tell me what is important
might you go about it?” or use the importance/con-
about this to you.”
fidence ruler. Clinicians can also inquire about what
was successful in the past or what the client hopes to
achieve by this change in the future.
• Affirmations are given to agree with, encourage, or 17.3.5 Planning
support the patient.
Once a significant amount of change talk is present, it
• Reflect on what the patient has already said. If pos-
may now be appropriate to investigate a plan; it’s impor-
sible, offer a complex reflection, one that elaborates
tant to keep in mind not to get ahead of the patient’s level
on the change talk or emotional content.
of readiness. The planning is an ongoing, ever-changing
• Summarize: Here the clinician attempts to collect
process that requires the clinician to assess potential
the “bouquets” of change talk they have heard and
approaches to addressing the target behavior. First, the
provide it back to the patient in summary form.
clinician offers a summary in the form of a “change talk
Exercise: Identify the type of change talk and how to bouquet”—a collection of “flowers” (change talk) the cli-
respond to change-talk statements. nician has collected that is offered back to the client like a
bouquet. This can be followed by a simple question such
Ex. 1 “I really don’t want to stop smoking, but I as, “Where should we go from here?” This can transition
know that I should, I’ve tried before, and it’s really the clinician and patient from processing to planning.
hard.” (1) “You really don’t want to quit,” (2) “It’s This question may result in either a clear step forward,
pretty clear to you that you ought to quit,” or (3) a multitude of options forward, or a step forward with
“You don’t think you can quit.” no clear path. When there is a clear path to change, it is
Ex. 2 “I know you are worried that I might be helpful to focus on clarifying the goal and summarizing
addicted, and I guess I can understand where you are your current understanding of the progress. From here,
coming from, but I really do need more pain meds, you begin troubleshooting hurdles and speed bumps that
and if you won’t prescribe them, I’ll go to another could impede progress and narrowing down the discus-
doctor who will.” (1) “You understand my worry sion to obtain more specific details regarding the plan.
about dependence.” (2) “It’s hard to imagine how you Although not MI-specific, the acronym SMART is often
would get along without more medicine,” (3) “One helpful when creating goals.
way or another, you’re going to get more medicine.” Specific: Define the goal as much as possible including
interrogatives such as what, where, and when something
As mentioned above, sustain talk is the patient’s argu- will occur.
ment to maintain the status quo. This is a normal behav- Measurable: Ensure that the goal/behavior can be
ior that should be expected during the change process. tracked. For example, “I will exercise for 30 minutes 3
Sustain talk occurs when the patient has intrapersonal days a week.”
conflict (ambivalence) with changing a target behavior. Attainable: Ensure that the goal can be accomplished.
Discord, however, is very different. Discord occurs when Try to make the goal not too high or too low below the
there is an interpersonal conflict between the patient and patient’s standard performance.
clinician. Said otherwise, discord is behavior that reflects Relevant: Is the goal in line with other goals you have?
an issue or disharmony within the relationship. Discord Timely: Goals should have a start time, as well as a
shows up in numerous ways, including: time limit to accommodate for evaluation. After a certain
216 Chapter 17 Motivational Interviewing and Lifestyle Change
amount of time, such as one week, one month, or one These can help guide and focus the practitioner on the key
year, the goal will be evaluated for success. elements of the conversation; attempting to reduce sustain
Sometimes the path forward has many branches; the talk and increase change talk.
motivation is present but there could be a multitude of
options for the patient to choose from. For this situa-
tion, it is important to confirm the goal after you have 17.4 SUMMARY
provided a summary and provide a list of the different
options. After this, try to investigate the patient’s prefer- Motivational Interviewing is a “collaborative conversa-
ence and intuitions regarding next steps. Asking questions tion style for strengthening a person’s own motivation and
such as “If you could imagine being most successful in this commitment to change.”4 In this chapter, we discussed the
task, what three things of these options seem most likely four processes of MI, basic MI skills such as OARS, and
to move you forward?” or simply “Which one appeals to how to respond to change talk, sustain talk, and discord.
you most?” Then from there continue evoking change talk Proficiency in MI is attainable with training and coaching.
and troubleshooting further tasks. Lastly, there is the sce- As seen in research, using MI is typically better at improv-
nario where there is no clear plan at all. As with the clear ing outcomes than offering education only, wait-listing, or
plan and the plan with many options, the practitioner first treatment-as-usual interventions,6 and often better than
clarifies the plan after offering a summary. From here you using a directive style.38 Practicing MI takes time and
engage in a brainstorming session with the patient; offer- effort, and more than anything, practice. Clinicians are
ing up any option that is plausible. At this point, you want encouraged to explore how MI could be used not only to
to work with the patient’s ideas from general to specific. benefit their relationships with their patients but also to
Remember to use the DARN-CATS mnemonic (Desire, positively influence outcomes that may come from this
Ability, Reason, Need, Commitment, Action and Taking relationship. Clinicians should keep in mind that they are
Steps) as you explore ambivalence with you patients. more responsible for the interaction than the outcome.
REFERENCES
1. Brink, S. (2017, April 20). What 8. Miller, W. R., Taylor, C. A., & West, J. of Nursing Studies, 49(6), 637–644.
County Spends the Most (and Least) on C. (1980). Focused versus broad-spec- doi:http://dx.doi.org/10.1016/j.ijnurst
Healthcare Per Person? New Hampshire trum behavior therapy for problem drink- u.2011.11.011.
Public Radio. Retrieved from: http:// ers. Journal of Consulting and Clinical 17. Lindson-Hawley, N., Thompson, T. P., &
www.npr.org/sections/goatsandsoda Psychology, 48(5), 590. Begh, R. (2015). Motivational interview-
/2017/04/20 /5247 74195/what-country- 9. Miller, W. R., & Baca, L. M. (1983). ing for smoking cessation. Cochrane
spends-the-most-and-least- on-health- care Two-year follow-up of bibliotherapy and Database of Systematic Reviews, 3(3).
-per-person. therapist-directed controlled drinking doi:10.1002/14651858.CD006936.pub3.
2. World Health Organization. (2017). The training for problem drinkers. Behavior 18. Naar-King, S., Parsons, J. T., & Johnson,
Top 10 Causes of Death Worldwide: Fact Therapy, 14(3), 441–448. doi:http://dx. A. M. (2012). Motivational interview-
Sheet. Retrieved from: http://www.who. doi.org/10.1016/S0005-7894(83)80107-5. ing targeting risk reduction for people
int/mediacentre /factsheets /fs310/en /. 10. Miller, W. R., & Rollnick, S. (2009). with HIV: A systematic review. Current
3. Aubrey, A. (2017). Fresh Food by Ten things that motivational interview- HIV/AIDS Reports, 9(4), 335–343.
Prescription: This Health Care Firm is ing is not. Behavioural and Cognitive doi:10.1007/s11904-012-0132-x.
Trimming Costs – And Waistlines, 2017 Psychotherapy, 37(2), 129–140. 19. Smedslund, G., Berg, R. C., Hammerstrøm,
(May 8). Retrieved from: http://www.npr. doi:10.1017/s1352465809005128. K. T., Steiro, A., Leiknes, K. A., Dahl, H.
org/sections/thesalt/2017/05/08/52695265 11. Rollnick, S., & Miller, W. R. (1995). What is M., & Karlsen, K. (2011). Motivational
7/fresh-food-by-prescription-this-health motivational interviewing? Behavioural and interviewing for substance abuse. Cochrane
-care-firm-is-trimming-costs-and-waistline. Cognitive Psychotherapy, 23(4), 325–334. Database of Systematic Reviews, (5).
4. Miller, W. R., & Rollnick, S. (2013). 12. Rogers, C. (1995). A Way of Being. New doi:10.1002/14651858.CD008063.pub2.
Motivational Interviewing: Helping York, NY: Houghton Mifflin Harcourt. 20. Wilson, A., Nirantharakumar, K.,
People Change (3rd ed.). New York, NY: 13. Alperstein, D., & Sharpe, L. (2016). The Truchanowicz, E. G., Surenthirakumaran,
Guilford Press. efficacy of motivational interviewing in R., MacArthur, C., & Coomarasamy,
5. Pollak, K. I., Nagy, P., Bigger, J., adults with chronic pain: A meta-analysis A. (2015). Motivational interviews to
Bilheimer, A., Lyna, P., Gao, X., and systematic review. The Journal of improve contraceptive use in populations
Armstrong, S. (2016). Effect of teaching Pain, 17(4), 393–403. doi:http://dx.doi.o at high risk of unintended pregnancy:
motivational interviewing via com- rg/10.1016/j.jpain.2015.10.021. A systematic review and meta-analysis.
munication coaching on clinician and 14. Barnes, R. D., & Ivezaj, V. (2015). A European Journal of Obstetrics &
patient satisfaction in primary care and systematic review of motivational inter- Gynecology and Reproductive Biology,
pediatric obesity-focused offices. Patient viewing for weight loss among adults in 191, 72–79. doi:http://dx.doi.org/10.1016
Education and Counseling, 99(2), primary care. Obesity Reviews, 16(4), /j.ejogrb.2015.05.010.
300–303. doi:10.1016/j.pec.2015.08.013. 304–318. doi:10.1111/obr.12264. 21. Lundhahl, B., & Burke, B. L. (2009). The
6. Lundahl, B., Moleni, T., Burke, B. L., 15. Barnett, E., Sussman, S., Smith, C., effectiveness and applicability of motiva-
Butters, R., Tollefson, D., Butler, C., Rohrbach, L. A., & Spruijt-Metz, D. tional interviewing: A practice‐friendly
& Rollnick, S. (2013). Motivational (2012). Motivational interviewing for review of four meta‐analyses. Journal of
interviewing in medical care settings: adolescent substance use: A review of the Clinical Psychology, 65(11), 1232–1245.
A systematic review and meta-analysis literature. Addictive Behaviors, 37(12), doi:0.1002/jclp.20638.
of randomized controlled trials. Patient 1325–1334. doi:http://dx.doi.org/10.1016 22. Hettema, J., Steele, J., & Miller, W.
Education and Counseling, 93(2), 157– /j.addbeh.2012.07.001. R. (2005). Motivational interviewing.
168. doi:org/10.1016/j.pec.2013.07.012. 16. Chen, S. M., Creedy, D., Lin, H.-S., & Annual Review of Clinical Psychology,
7. Schwalbe, C. S., Oh, H. Y., & Zweben, Wollin, J. (2012). Effects of motivational 1, 91–111. doi:10.1146/annurev.
A. (2014). Sustaining motivational interviewing intervention on self-man- clinpsy.1.102803.143833.
interviewing: A meta-analysis of training agement, psychological and glycemic out- 23. de Roten, Y., Zimmermann, G., Ortega,
studies. Addiction, 109(8), 1287–1294. comes in type 2 diabetes: A randomized D., & Despland, J. N. (2013). Meta-
doi:10.1111/add.12558. controlled trial. International Journal analysis of the effects of MI training on
References 217
clinicians’ behavior. Journal of Substance A multicenter randomized controlled trial 34. Moyers, T. B., Martin, T., Christopher,
Abuse Treatment, 45(2), 155–162. of motivational interviewing in teenag- P. J., Houck, J. M., Tonigan, J. S., &
24.
doi:10.1016/j.jsat.2013.02.006
Vasilaki, E. I., Hosier, S. G., & Cox, W.
M. (2006). The efficacy of motivational 29.
ers with diabetes. Diabetes Care, 30(6),
1390–1395. doi:10.2337/dc06-2260.
Gayes, L. A., & Steele, R. G. (2014). A
Amrhein, P. C. (2007). Client language
as a mediator of motivational interview-
ing efficacy: Where is the evidence?
17
interviewing as a brief intervention for meta-analysis of motivational interview- Alcoholism: Clinical and Experimental
excessive drinking: A meta-analytic ing interventions for pediatric health Research, 31(10 Suppl), 40s–47s.
review. Alcohol & Alcoholism, 41(3), behavior change. Journal of Consulting doi:10.1111/j.1530-0277.2007.00492.x.
328–335. doi:10.1093/alcalc/agl016. and Clinical Psychology, 82(3), 521–535. 35. Catley, D., Harris, K. J., Mayo, M. S.,
25. Jensen, C. D., Cushing, C. C., Aylward, doi:10.1037/a0035917. Hall, S., Okuyemi, K. S., Boardman,
B. S., Craig, J. T., Sorell, D. M., & 30. Bandura, A. (1982). Self-efficacy T., & Ahluwalia, J. S. (2006).
Steele, R. G. (2011). Effectiveness of mechanism in human agency. American Adherence to principles of motiva-
motivational interviewing interventions Psychologist, 37(2), 122–147. tional interviewing and client within-
for adolescent substance use behavior doi:10.1037/0003-066X.37.2.122. session behavior. Behavioural and
change: A meta-analytic review. Journal 31. Martino, S., Ball, S. A., Gallon, S. L., Cognitive Psychotherapy, 34(1), 43–56.
of Consulting and Clinical Psychology, Hall, D., Garcia, M., Ceperich, S., doi:10.1017/S1352465805002432.
79(4), 433–440. doi:10.1037/a0023992. Hausotter, W. (2006). Motivational 36. Houck, J. M., & Moyers, T. B. (2008).
26. Armstrong, M. J., Mottershead, T. A., Interviewing Assessment: Supervisory What You Do Matters: Therapist
Ronksley, P. E., Sigal, R. J., Campbell, Tools for Enhancing Proficiency. Salem, Influence on Client Behavior dur-
T. S., & Hemmelgarn, B. R. (2011). OR: Northwest Frontier Addiction ing MI Sessions. Paper presented at
Motivational interviewing to improve Technology Transfer Center, Oregon the International Addiction Summit,
weight loss in overweight and/or obese Health and Science University. Melbourne, Australia.
patients: A systematic review and 32. Baer, J. S., Beadnell, B., Garrett, S. B., 37. Moyers, T. B., & Martin, T. (2006).
meta-analysis of randomized controlled Hartzler, B., Wells, E. A., & Peterson, P. Therapist influence on client language
trials. Obesity Reviews, 12(9), 709–723. L. (2008). Adolescent change language during motivational interviewing
doi:10.1111/j.1467-789X.2011.00892.x. within a brief motivational intervention sessions. Journal of Substance Abuse
27. Burke, B. L., Arkowitz, H., & and substance use outcomes. Psychology Treatment, 30(3), 245–251. doi:10.1016/j.
Menchola, M. (2003). The efficacy of Addictive Behaviors, 22(4), 570–575. jsat.2005.12.003.
of motivational interviewing: A doi:10.1037/a0013022. 38. Pollak, K. I., Alexander, S. C., Coffman,
meta-analysis of controlled clini- 33. Gaume, J., Gmel, G., Faouzi, M., & C. J., Tulsky, J. A., Lyna, P., Dolor, R.
cal trials. Journal of Consulting and Daeppen, J.-B. (2008). Counsellor J., Østbye, T. (2010). Physician commu-
Clinical Psychology, 71(5), 843–861. behaviours and patient language nication techniques and weight loss in
doi:10.1037/0022-006x.71.5.843. during brief motivational interven- adults: Project CHAT. American Journal
28. Channon, S. J., Huws-Thomas, M. V., tions: A sequential analysis of speech. of Preventive Medicine, 39(4), 321–328.
Rollnick, S., Hood, K., Cannings-John, R. Addiction, 103(11), 1793–1800. doi:https://doi.org/10.1016/j.amepre.20
L., Rogers, C., & Gregory, J. W. (2007). doi:10.1111/j.1360-0443.2008.02337.x. 10.06.005.
18
CHAPTER
Transtheoretical Model
James O. Prochaska, PhD and Janice M. Prochaska, PhD
219
220 Chapter 18 Transtheoretical Model
Individuals who are in the Precontemplation stage typi- Action is a stage in which individuals have made spe-
cally underestimate the benefits of change and overesti- cific, overt modifications in their lifestyle within the pre-
mate its costs but are unaware that they are making such ceding six months. Because action is observable, behavior
mistakes. If they are not conscious of making such mis- change often has been equated with action. But in the
takes, it is difficult for them to change. As a result, many Transtheoretical Model (TTM), Action is only one of six
remain stuck in the Precontemplation stage, with consider- stages. In this model, not all modifications of behavior
able resulting harm to their bodies, themselves, and others. count as action. An individual must attain a criterion that
There appears to be no inherent motivation for people to scientists and professionals agree is sufficient to reduce the
progress from one stage to the next. The stages are not risk of disease. With smoking, for example, only total absti-
like stages of human development, in which children have nence counts. With alcoholism and alcohol abuse, many
inherent motivation to progress from crawling to walking, believe that only total abstinence can be effective, whereas
even though crawling works very well and even though others accept controlled drinking as an effective action.
learning to walk can be painful and embarrassing. Instead, Maintenance is a stage in which individuals are work-
two major forces can move people to progress. ing to prevent relapse but do not need to apply change
The first is developmental events. In the authors’ processes as frequently as one would in the Action stage.
research, the mean age of smokers who reach the long-term Such persons are less tempted to relapse and are increas-
Maintenance stage is 39 years. Those who have passed ingly confident that he or she can sustain the changes
39 recognize it as an age to reevaluate how one has been made. Temptation and self-efficacy data suggest that
living and whether one wants to die from that lifestyle or Maintenance lasts from six months to about five years.
whether one wants to enhance the quality and quantity of One of the common reasons for early relapse is that the
the second half of life. The other naturally occurring force individual is not well prepared for the prolonged effort
is environmental events. A favorite example is a couple who needed to progress to Maintenance. Many persons think
were both heavy smokers. Their dog of many years died of the worst will be over in a few weeks or a few months. If,
lung cancer. This death eventually moved the wife to quit as a result, they ease up on their efforts too early, they are
smoking. The husband bought a new dog. So, even the same at great risk of relapse.
events can be processed differently by different people. To prepare such individuals for what is to come, they
A common belief is that people with health risks must should be encouraged to think of overcoming a bad habit
“hit bottom” before they are motivated to change. So fam- as running a marathon rather than a sprint. They may
ily, friends, and physicians wait helplessly for a crisis to have wanted to enter the Boston Marathon, but they know
occur. But how often do people turn 39 or have a dog die? they would not succeed without preparation and so would
When individuals show the first signs of a serious physi- not enter the race. With some preparation, they might
cal illness, such as cancer or cardiovascular disease, those compete for several miles but still would fail to finish the
around them usually become mobilized to help them seek race. Only those who are well prepared could maintain
early intervention. Evidence shows that early interventions their efforts mile after mile. Using the Boston Marathon
often are lifesaving, and so it would not be acceptable to metaphor, people know they have to be well prepared
wait for such a patient to “hit bottom.” In opposition to if they are to survive Heartbreak Hill, which runners
such a passive stance, a third force that has been created encounter at about mile 20. What is the behavioral
to help individuals progress beyond the Precontemplation equivalent of Heartbreak Hill? The best evidence available
stage is called planned interventions. suggests that most relapses occur at times of emotional
Contemplation is a stage in which an individual distress. It is in the presence of depression, anxiety, anger,
intends to take action within the ensuing six months. Such boredom, loneliness, stress, and distress that humans are
a person is more aware of the benefits of changing but at their emotional and psychological weak point.
also is acutely aware of the costs. When a smoker begins How does the average person cope with troubling
to seriously contemplate giving up smoking, their aware- times? He or she drinks more, eats more, smokes more,
ness of the costs of changing can increase. There is no and takes more drugs to cope with distress. It is not sur-
free change. This balance between the costs and benefits prising, therefore, that persons struggling to overcome
of change can produce profound ambivalence, which may risky behaviors will be at greatest risk of relapse when
reflect a type of love–hate relationship with risks and they face distress. Although emotional distress cannot be
thus can keep an individual stuck at the Contemplation prevented, relapse can be prevented if individuals have
stage for long periods of time. This phenomenon often is been prepared to cope with distress.
characterized as “chronic Contemplation” or “behavioral If so, many Americans rely on oral consumptive behav-
procrastination.” Such individuals are not ready for tradi- ior as a way to manage their emotions, what is the healthi-
tional action-oriented programs. est oral behavior they could use? Talking with others about
Preparation is a stage in which individuals intend to one’s distress is a means of seeking support that can help
take action in the immediate future (usually measured as prevent relapse. Another healthy alternative is exercise.
the ensuing month). Such persons typically have taken Physical activity helps manage moods, stress, and distress.
some significant action within the preceding year. They Also, 150 minutes per week of exercise can provide a per-
generally have a plan of action, such as participating in son with more than 70 health and mental health benefits.5
a weight-loss group, consulting a counselor, talking to a Exercise thus should be prescribed to all sedentary indi-
physician, buying a self-help book, or relying on a self-help viduals. A third healthy alternative is some form of deep
approach. It is these individuals who should be recruited relaxation, such as meditation, yoga, prayer, massage, or
for action-oriented treatment programs. deep muscle relaxation. Letting the stress and distress drift
18.3 Principles and Processes of Change 221
away from one’s muscles and one’s mind helps the indi- the costs in the Action stage. It should be noted that if raw
18
vidual move forward at the most tempting of times. scores are used to assess these patterns, it would appear
Termination is a stage in which individuals have zero that the rewards for changing are seen as greater than the
temptation and 100% self-efficacy. Whether they are costs, even by persons in the Precontemplation stage. It
depressed, anxious, bored, lonely, or stressed, such per- is only when standardized scores are used that clear pat-
sons are certain they will not return to their old unhealthy terns emerge, with the costs of changing always perceived
habits as a method of coping. It is as if they never acquired as greater than the rewards. This suggests that compared
the habit in the first place. In a study of former smokers with their peers at other stages of change, persons in the
and people with alcohol use disorders who were abstinent Precontemplation stage underestimate the rewards and
for less than five years, about 20% of each group had overestimate the costs of change.
reached the stage of no temptation and total self-efficacy.
This is an ideal stage that only a minority might reach.6
18.3.4 Principle 4
18.3 PRINCIPLES AND The strong principle of progress holds that to progress
from Precontemplation to effective Action, the rewards for
PROCESSES OF CHANGE changing must increase by one standard deviation (SD).8
Note: Social liberation has been found not to have differentiated emphasis across all five stages.
for changing. So consciousness raising should be would cause lung cancer. But I never imagined my
designed to increase the perceived gains for changing. wife would die from lung cancer.” Beneath his griev-
2.
Dramatic relief (pay attention to feelings) involves ing face appears this statistic: “50,000 deaths per
emotional arousal about one’s current behavior and year are caused by passive smoking.” In 30 seconds,
the relief that can come from changing. Fear, inspi- this message achieves consciousness raising, dramatic
ration, guilt, and hope are some of the emotions relief, and environmental reevaluation.
that can move persons to contemplate changing. 4.
Self-reevaluation (create a new self-image) combines
Psychodrama, role playing, grieving, and personal both cognitive and affective assessments of an image
testimonies are examples of techniques that can move of one’s self free from an unhealthy behavior. Imagery,
people emotionally. It should be noted that earlier healthier role models, and values clarification are
literature on behavior change concluded that inter- techniques that can move individuals in this type of
ventions such as education and fear arousal did not intervention. Individuals first look back and reevalu-
motivate behavior change. Unfortunately, many inter- ate how they have lived as unhealthy individuals. As
ventions were evaluated in terms of their ability to they progress into the Preparation stage, they begin to
move people to immediate action. However, processes develop a focus on the future as they imagine how life
such as consciousness raising and dramatic relief are could be if they were free of the unhealthy habit.
intended to move people to the Contemplation stage 5.
Self-liberation (make a commitment) involves both
rather than the Action stage. Therefore, their effec- the belief that one can change and the commitment
tiveness should be assessed according to whether they and recommitment to act on that belief. Techniques
lead to the expected progress. that can enhance such willpower include public rather
3.
Environmental reevaluation (notice your effect on than private commitments. Motivational research
others) combines both affective and cognitive assess- also suggests that individuals who have only one
ments of how an unhealthy behavior affects one’s choice are not as motivated as they could be when
social environment and how changing would affect they have two choices.10 Three choices are even bet-
that environment. Empathy training, values clarifica- ter, but four choices do not seem to enhance motiva-
tion, and family or network interventions can facilitate tion. Wherever possible, then, clients should be given
such reevaluation. For example, a brief media inter- three of the best choices for applying each process.
vention aimed at a smoker in the Precontemplation With smoking cessation, for example, there are at
stage might involve an image of a man clearly in grief least three good choices: quitting “cold turkey,” using
saying, “I always feared that my smoking would lead nicotine replacement therapy, and using nicotine fad-
to an early death. I always worried that my smoking ing. Asking clients to choose which alternative they
18.3 Principles and Processes of Change 223
believe would be most effective for them and which What is the result when all of these principles and pro-
18
they would be most committed to can enhance their cesses of change are combined to help clients and entire
motivation and their self-liberation. populations move toward the Action stage to reduce their
6. Counter conditioning (use substitutes) requires the health risks? A series of clinical trials applying stage-
learning of healthier behaviors that can substitute matched interventions offers lessons about the future
for the unhealthy behavior. Counter conditioning of behavioral health care generally and treatment of the
techniques tend to be quite specific to a particular bad habits specifically. In a large-scale clinical trial, the
behavior. They include desensitization, assertion, authors and colleagues compared four treatments: (a) a
and cognitive counters to irrational self-statements home-based action-oriented smoking cessation program
that can elicit distress. (standardized), (b) stage-matched manuals (individual-
7. Reinforcement management (use rewards) involves ized), (c) a computerized-tailored intervention (CTI) plus
the systematic use of reinforcements and punish- manuals (interactive), and (d) counselors plus CTI (per-
ments for taking steps in a particular direction. sonalized). Clients (739 smokers) were randomly assigned
Because successful self-changers rely much more on by stage to one of the four treatments.11
reinforcement than punishment, it is useful to empha- In the CTI treatment, participants completed 40 ques-
size reinforcements for progressing rather than pun- tions by mail or telephone. Their responses were entered
ishments for regressing. Contingency contracts, overt into a central computer, from which tailored feedback
and covert reinforcements, and group recognition reports were generated. These reports informed partici-
are methods of reinforcement and incentives that pants about their stage of change, the pros and cons of
increase the probability that healthier responses will changing, and change processes appropriate to their stages
be repeated. To prepare clients for the longer term, of change. At baseline, participants were given positive
they should be taught to rely more on self-reinforce- feedback on what they were doing correctly and guidance
ments than social reinforcements. Clinical experi- on which principles and processes they needed to apply to
ence shows that many individuals expect much more progress. In two progress reports delivered over the follow-
reinforcement and recognition from others than they ing six months, participants also received positive feedback
actually receive. Relatives and friends may take the on any improvement in any of the variables relevant to
Action stage for granted. They typically generate progress. Thus, demoralized and defensive smokers could
only a few positive consequences. Self-reinforcements begin to progress without having to quit and without hav-
obviously are much more under self-control and can ing to work too hard. Smokers in the Contemplation stage
be given more quickly and consistently when tempta- could begin to take small steps, such as delaying their first
tions to lapse or relapse are resisted. cigarette in the morning for an additional 30 minutes. They
8. Stimulus control (manage your environment) could choose small steps that would increase their self-effi-
involves modifying the environment to increase cues cacy and help them become better prepared for quitting.
that prompt healthy responses and decrease cues In the personalized treatment, smokers received four
that lead to relapse. Avoidance, environmental re- proactive counselor calls over the six-month intervention
engineering (such as removing addictive substances period. Three of the calls were based on the CTI reports.
and paraphernalia), and attending self-help groups When they didn’t have a CTI report, Counselors reported
can provide stimuli that elicit healthy responses and much more difficulty in interacting with participants
reduce the risk of relapse. without any progress data. Without scientific assessments,
9. Helping relationships (get support) combine caring, it was more difficult for both clients and counselors to
openness, trust, and acceptance, as well as support know whether any significant progress had occurred since
for changing. Rapport building, a therapeutic alli- their last interaction.
ance, coach calls, buddy systems, sponsors, and Figure 18.1 presents point-prevalence abstinence rates
self-help groups can be excellent resources for social for each of the four treatment groups over 18 months, with
support. If clients become dependent on such sup- treatment ending at six months. Results with the two self-
port to maintain change, the support will need to help manual conditions were parallel for 12 months, but
be carefully faded, lest termination of coaching the individualized stage-matched manuals achieved bet-
becomes a condition for relapse. ter results at 18 months. This is an example of a delayed
10. Social liberation (notice public support) is the pro- action effect, which often is observed with stage-matched
cess by which changes in society increase the options programs. It takes time for participants in early stages to
and opportunities to have healthier and happier progress all the way to Action. Therefore, some treatment
lives freer from risky behaviors. Social networks are effects as measured by action will be observed only after
examples of a dramatic increase in being able to par- considerable time has elapsed. But it is encouraging to find
ticipate in positive interactions free from pressures treatments producing therapeutic effects months and even
to rely on unhealthy habits. years after active treatment has ended. The CTI alone and
personalized counselor calls plus CTI treatments produced
comparable results for six months. The CTI alone produced
18.3.7 Principle 7 delayed action effects through 18 months. The effects of
Self-efficacy is the situation-specific confidence that people CTI plus counselors leveled off. One hypothesis is that
have while coping with high-risk situations without relaps- clients can become dependent on counselors. Counselors
ing to their unhealthy behavior. Self-efficacy increases as may need to phase out treatment gradually to reduce such
people move through the stages of change. dependence and enhance self-efficacy of clients.
224 Chapter 18 Transtheoretical Model
CTIs. 20 The secondary behaviors of fruit and vegetables criticism that addiction severity levels are better predictors
18
(F&V) intake and limited TV watching alternated between of long-term outcomes than stage of change, a series of
moderate and minimal (stage only) tailoring. Over the studies was conducted to determine which types of effects
course of the six-month treatment, there were significant predict long-term outcomes across multiple behaviors. To
treatment effects in each of the three behaviors, but only date, four such effects have been found.35 The first is sever-
changes in F&V were sustained at 12 months. Significant ity effect, in which individuals with less severe behavior
coaction was found for each pair of behaviors in the treat- risks at baseline are more likely to progress to the Action
ment group but not in the control group. or Maintenance stages at 24-month follow-up for smoking,
diet, and sun exposure. This effect includes the severity of
addiction that Farkas et al. and Abrams et al. preferred.21,22
The second is stage effect, in which participants in the
18.6 STUDIES CHALLENGING THE Preparation stage at baseline have better 24-month out-
TRANSTHEORETICAL MODEL comes for smoking, diet, and sun exposure than those in
the Contemplation stage, who do better than those in the
Critics of the TTM have several core concerns. These Precontemplation stage. This effect is what Farkas et al.
include how well TTM constructs predict outcomes com- and Abrams et al. criticized. The third is treatment effect, in
pared to non-TTM variables and whether TTM constructs which participants in treatment do better at 24 months than
(like processes of change) predict progress across stages of those randomly assigned to control groups for smoking,
change in the way that TTM should predict. Their con- diet, and sun exposure. The fourth is effort effects, in which
cerns are supported by some empirical studies, but some participants in both treatment and control groups who pro-
of the negative results in these studies can be explained by gressed to the Action and Maintenance stages at 24 months
inappropriate methodology. Others have stronger meth- were making better efforts by using the TTM variables like
odology and provide useful detail that can be used to pros and cons, self-efficacy, and processes at baseline. There
refine the TTM. were no consistent demographic effects across the three
Farkas et al. and then Abrams et al. compared addic- behaviors, indicating that no single demographic group did
tion variables to TTM variables as effective predictors of better across these multiple behaviors. What these results
cessation over 12 to 24 months. 21,22 Addiction variables, indicate is that either/or thinking (such as either severity or
including the number of cigarettes smoked and duration stage) is not as helpful as a more inclusive approach that
of prior quits (e.g., more than 100 days) were more effec- seeks to identify the most important effects, whether they
tive than TTM variables in predicting cessation rates, are based on TTM or on an addiction or severity model.
suggesting that addiction models were preferable to TTM. These four effects are now being applied in TTM-tailored
Responses to these comparative studies have included interventions for employees and other populations.
concerns that Farkas et al. compared 14 addiction-type
variables to just the single-stage variable from TTM. 23,24
The Abrams et al. study included self-efficacy and the 18.7 MULTIPLE DOMAINS OF WELL-
Contemplation Ladder—an alternative measure of readi-
ness or stage—as part of their addiction model but failed
BEING: FROM SUFFERING OR
to acknowledge that both of these constructs are part STRUGGLING TO THRIVING
of TTM. 22 Also, from an intervention perspective, the
amount of variance accounted for by predictor variables Motivated by a risky test philosophy of science, we keep
is less important than the amount of variance that can be raising the bar to have increasing impacts with vulnerable
controlled or changed through an intervention. For exam- populations, such as moving from changing a single behav-
ple, duration of previous quits (e.g., as 100 days) may be ior to a riskier goal of changing multiple risk behaviors.36
more predictive than stage; little can be done to change One of our most recent challenges has been to simultane-
this historical variable, while a dynamic variable like stage ously enhance multiple domains of well-being, e.g., physi-
is responsive to interventions. cal, emotional, social, and work well-being. Prochaska
In the first of a series of studies, Herzog and colleagues et al. conducted a project with 3,391 participants from
found that six processes of change were not adequate pre- 39 states who had an average of almost four chronic con-
dictors of stage progress over a 12-month period. 25 In a ditions and almost four risk behaviors, with 40% obese,
second report, processes predicted stage progress but only 35% overweight, and 0% exercising adequately or manag-
when the Contemplation Ladder was used. 26 In the third ing stress effectively. A majority had poor diets, were or
report, TTM measures predicted 12-month outcomes, had been smokers, and had problems with depression. 37
but self-efficacy and the Contemplation Ladder were not Compared to national norms, this population, with
counted as TTM variables. 22 These findings conflict with 59% women, a mean age of 48, and 48% unemployment,
other research that has found change processes and other had much lower scores on each domain of well-being.
TTM variables predict stage progress. 27–34 Johnson, J. L. Most striking was that a majority were suffering or strug-
et al. with their study explained some of the inconsisten- gling, and only a minority were thriving. The only time
cies in previous research by demonstrating better predic- this pattern was seen in the United States was with the
tions over 6 months vs. 12 months, and better predictions economic crash of 2008.38
using all 10 processes of change instead of just a subset.33 Random assignment to treatment and one control
One of the productive responses to studies critical of groups was made. One group had telephonic TTM CTI
the TTM is to conduct further research. In response to the coaching with exercise as the primary target and stress
226 Chapter 18 Transtheoretical Model
management as secondary. The second group received individuals who reach out for help. Unfortunately, there
CTI coaching with stress as the primary target and exer- is no experimental design that would make it possible to
cise as secondary. Compared to controls, both treatment assign study subjects randomly to proactive versus reac-
groups produced more multiple behavior change than con- tive recruitment programs. Thus, one is left with informal
trols and more improvement on multiple domains of well- but provocative comparisons. Results with multiple behav-
being. In all comparisons, the telephonic coaching that ior interventions using some type of TTM tailoring and
spent most of the time on exercise produced more positive proactive recruitment have found as good effects as when
changes than the CTI coaching that treated stress primar- smoking alone is treated. The results with the other treated
ily and exercise secondarily.37 behaviors were even better.
What was most rewarding was that the majority of If these results continue to be replicated, programs will
both treatment groups, but not the control groups, had be able to produce unprecedented effects on entire popu-
progressed from suffering or struggling to thriving. These lations. To do so will require scientific and professional
results led us to produce a follow-up book to Changing for shifts: (a) from an Action paradigm to a stage paradigm,
Good which for over 20 years has been a guide for many (b) from reactive to proactive recruitment, (c) from expect-
health coaches.39 Our new book, Changing to Thrive, is ing participants to match the needs of programs to having
designed to help both professionals, their clients, and other programs match the needs of clients, (d) from single- to
populations to reduce multiple risk behaviors, enhance multiple-behavior interventions, (e) from clinic-based to
multiple domains of well-being, and progress from suffer- population-based programs that apply individualized and
ing or struggling to thriving. 5 interactive intervention strategies, and (f) reducing mul-
tiple problem behaviors to enhance multiple domains of
well-being to help vulnerable populations to progress from
18.8 CONCLUSIONS suffering or struggling to thriving.
With the knowledge and tools needed to move for-
It seems clear that the future of health promotion pro- ward, we end with a final question for your consideration.
grams lies in stage-matched, proactive, interactive inter- How ready are you to integrate a stage approach in
ventions. Much greater effects can be generated through your work?
the use of proactive programs because participation rates
are increased, even if efficacy rates are lower. But proac- 1. I don’t intend to integrate a stage approach in my
tive programs also can produce outcomes comparable to work in the next six months (Precontemplation).
those of traditional reactive programs. Although it is coun- 2. I intend to integrate a stage approach in my work in
terintuitive to suggest that outcomes for groups that are the next six months (Contemplation).
proactively recruited can match those of individuals who 3. I intend to integrate a stage approach in my work in
reach out for help, that is what informal comparisons the next month (Preparation).
strongly suggest. For example, in a comparison of results 4. I have been integrating a stage approach in my work
at 18-month follow-ups for all subjects who received three for less than six months (Action).
CTIs in a study of reactive intervention and a study of 5. I have been integrating a stage approach in my work
proactive intervention, the abstinence curves were remark- for more than six months (Maintenance).
ably similar.40 The results with the counseling plus CTIs
were even more impressive. Proactively recruited smokers, Some ideas to guide your next steps:
working with both coaches and the CTI, achieved higher
rates of abstinence at each follow-up than did the smokers 1. If you are in Precontemplation, look for more infor-
who had called for help. These results are partially attrib- mation in using a stage approach and consider
utable to the fact that the proactive coaching protocol has how your work, your client interactions, and your
been revised and, it is to be hoped, improved on the basis colleagues might benefit by your adopting a stage
of previous data and experience. But the point is that if it approach. (See Table 18.2 regarding some of the
is possible to reach out and offer people improved behav- benefits.)
ior change programs that are appropriate for their stage 2. If you are in Contemplation, learn more about using
of readiness to change, it ought to be possible to produce a stage approach by talking with others who use
efficacy or abstinence rates at least equal to those seen with it and seeking additional training in the approach
TABLE 18.2 There are many benefits for integrating TTM into your practice
TTM:
• Prepares you to work with entire populations wherever they are in the stages of change.
• Helps you reduce resistance among your clients.
• Allows you to see and appreciate how your clients are making progress in stages.
• Enables you to set stage-matched goals with clients.
• Gets you to offer and prescribe behavior change programs that are stage-appropriate.
• Teaches you the principles and processes of change that are applicable across all health behaviors.
• Shows you an approach that’s successful at increasing engagement, increasing healthy behaviors, reducing multiple risks, and
enhancing multiple domains of well-being and productivity.
References 227
at www.prochange.com/elearning. Identify what Behavior Systems, Inc., in 1997 and sold it to the
18
barriers might be in your way and consider ways two lead staff in 2015. They now act as consultants
to overcome them. Feel inspired by how the stage from time to time.
approach has helped others to more successfully
engage patients. TTM has a broad range of clinical applications:
3. If you are in Preparation, make a commitment to
begin using a stage approach and share that com- • Doing multiple behavior change for the prevention
mitment with others. Build your confidence by role and management of chronic diseases like type 2
playing or practicing the approach with clients. Ask diabetes.
colleagues to support and assist your efforts, and • Medication adherence for lipids, changing diet, and
notice the benefit. increasing exercise to prevent and manage cardio-
4. or 5. If you are in Action or Maintenance, keep this vascular disease.
chapter and other training materials visible to make • Prevention and management of clinical depression
it easy to use a stage approach. Appreciate the ben- • Changing multiple behaviors and enhancing multi-
efits TTM offers you and your clients. Boost your ple domains of well-being in populations with mul-
confidence by using the approach even with resistant tiple chronic conditions.
clients.41 See a demo of a CTI at www.prochange. • Changing multiple behaviors to prevent severe types
com/demo. The authors cofounded Pro-Change of cancer.
REFERENCES
1. Khaw KT, Wareham N, Bingham 13. Prochaska JO, Velicer WF, Fava JL, et al. addiction: A replication and extension.
S, Welch A, Luben R, and Day N. Counselor and stimulus control enhance- Nicotine Tob. Res. 2000;2:223–229.
Combined impact of health behaviors and ments of a stage-matched expert system doi:10.1080/14622200050147484.
mortality in men and women: The EPIC- for smokers in a managed care setting. 23. Prochaska JO and Velicer WF. On mod-
Norfolk prospective population study. Prev. Med. 2000;32:39–46. els, methods and premature conclusions.
PLos Med. 2008;5(1):39–47. 14. Prochaska JO and Velicer WF. Addictions 1996;91:1281–1283. PMID:
2. Pronk NP, Lowry M, Kottke TG, Austin The transtheoretical model of 8854359.
E, Gallagher J, and Katz A. The associa- health behavior change. Am. J. 24. Prochaska JJ, Velicer WF, Prochaska JO,
tion between optimal lifestyle adherence Health Promot. 1997;12(1):38–48. Delucchi K, and Hall SM. Comparing
and short-term incidence of chronic con- doi:10.4278/0890-1171-12.1.38. intervention outcomes in smokers treated
ditions among employees. Popul. Health 15. Ruggiero L, Glasgow R, Dryfoos JM, for single versus multiple behavioral risks.
Manag. 2010;13:289–295. et al. Diabetes self-management: Self- Health Psychol. 2006;25(3):380–388.
3. Mehta N and Myrskla M. The popula- reported recommendations and patterns doi:10.1037/0278-6133.25.3.380.
tion health benefits of a healthy lifestyle: in a large population. Diabetes Care 25. Herzog TA, Abrams DB, Emmons
Life expectancy increased and onset 1997;20(4):568–576. doi:10.2337/ KA, Linnan L, and Shadel WG. Do
of disability delayed. Health Aff. 2017. diacare.20.4.568. processes of change predict stage
doi:10.1377/hlthaff.2016.1569. 16. Johnson SS, Paiva AL, Cummins CO, movements? A prospective analy-
4. Reeves MJ and Referty AP. Healthy life- et al. Transtheoretical model-based sis of the transtheoretical model.
style characteristics among adults in the multiple behavior intervention for weight Health Psychol. 1999;18:369–375.
United States, 2000. Arch. Intern. Med. management: Effectiveness on a popula- doi:10.1037/0278-6133.18.4.369.
2005;8:854–857. tion basis. Prev. Med. 2008;46:238–246. 26. Herzog TA, Abrams DB, Emmons KA,
5. Prochaska JO and Prochaska JM. doi:10.1016/y.ypmed.2007.09.010. and Linnan L. Predicting increases in
Changing to Thrive. Center City, MN: 17. Mauriello LM, Ciavatta MMH, Paiva readiness to quit smoking: A prospective
Hazelden Publishing, 2016. AL, et al. Results of a multi-media mul- analysis using the contemplation ladder.
6. Snow MG, Prochaska JO, and Rossi JS. tiple behavior obesity prevention program Psychol. Health 2000;15(3):369–381.
Stages of change for smoking cessa- for adolescents. Prev. Med. 2010;51:451– 27. Prochaska JO, DiClemente CC, Velicer
tion among former problem drinkers: A 456. doi:10.1016/j.ypmed.2010.08.004. WF, Ginpil S, and Norcross JC.
cross-sectional analysis. J. Subst. Abuse 18. Velicer WF, Redding CA, Paiva AL, et al. Predicting change in smoking sta-
1992;4:107–116. Multiple behavior interventions to pre- tus for self-changers. Addict. Behav.
7. Prochaska JO, Velicer WF, Rossi JS, et al. vent substance abuse and increase energy 1985;10:407–412. PMID: 4091072.
Stages of change and decisional balance balance behaviors in middle school stu- doi:10.1016/0306-4603(85)90036-X.
for twelve problem behaviors. Health dents. Transl. Behav. Med. Pract. Policy 28. Prochaska JO, Velicer WF, Guadagnoli
Psychol. 1994;13:39–46. Res. 2013;01:82–93. E, Rossi JS, and DiClemente CC. Patterns
8. Prochaska JO. Strong and weak principles 19. Prochaska JO, Butterworth S, Redding of change: Dynamic typology applied to
for progressing from precontemplation to C, Burden V, Perrin N, and Leo M. smoking cessation. Multivariate Behav.
action based on twelve problem behav- Initial efficacy of MI, TTM tailoring Res. 1991;26:83–107. doi:10.1207/
iors. Health Psychol. 1994;13:47–51. and HRI’s with multiple behaviors for s15327906mbr2601_5
9. Hall KL and Rossi JS. Meta-analytic employee health promotion. Prev. Med. 29. Prochaska JO, Velicer WF, Rossi JS,
examination of the strong and weak prin- 2008;45:226–231. et al. Impact of simultaneous stage-
ciples across 48 health behaviors. Prev. 20. Prochaska JO, Ever KE, Castle PH, matched expert system interventions
Med. 2008;46(3):266–274. et al. Enhancing multiple domains of for smoking, high fat diet, and sun
10. Miller WR. Motivation for treatment: A well-being by decreasing multiple health exposure in a population of parents.
review with special emphasis on alcohol- risk behaviors. Popul. Health Manag. Health Psychol. 2004;23(5):503–516.
ism. Psychol. Bull. 1985;98:84–107. 2012;15:276–286. doi:10.1037/0278-6133.23.5.503.
11. Prochaska JO, DiClemente CC, Velicer 21. Farkas AJ, Pierce JP, Zhu SH, 30. Prochaska JO, Wright JA, and Velicer
WF, and Rossi JS. Standardized, indi- et al. Addiction versus stages WF. Evaluating theories of health behav-
vidualized, interactive and personalized of change models in predict- ior change: A hierarchy of criteria applied
self-help programs for smoking cessation. ing smoking cessation. Addiction to the transtheoretical model. Appl.
Health Psychol. 1993;12:399–405. 1996;91:1271–1280. doi:10.1046/j.1360- Psychol. Int. Rev. 2008;57(4):561–588.
12. Edington DW. Emerging research: A view 0443.1996.91912713.x. doi:10.1111/j. 1454-0597.2008.00345x.
from one research center. Am. J. Health 22. Abrams DB, Herzog TA, Emmons KM, 31. DiClemente CC, Prochaska JO,
Promot. 2001;15(5):341–349. and Linnan L. Stages of change versus Fairhurst SK, Velicer WF, Valesquez
228 Chapter 18 Transtheoretical Model
MM, and Rossi JS. The processes of relapsers and non-quitters. Addict. Association for Psychological Science.
smoking cessation: An analysis of Behav. 2007;32:2707–2726. www.psychologicalscience.org.
precontemplation, contemplation, and 35. Blissmer B, Prochaska JO, Velicer 39. Prochaska JO, Norcross JC, and
preparation stages of change. J. Consult. WF, et al. Common factors predict- DiClemente CC. Changing for Good.
Clin. Psychol. 1991;59:295–304. ing long-term changes in multiple New York, NY: Morrow, 1994. Released
doi:10.1037/0022-006X.59.2.295. health behaviors. J. Health Psychol. in paperback by Avon, 1995.
32. Dijkstra A, Conijm B, and De Vries H. 2010;15:201–214. 0. Fiore MC, Jaén CR, Baker TB, et al.
4
A match-mismatch test of a stage model 36. Prochaska JO, Wright JA, and Treating tobacco use and dependence:
of behavior change in tobacco smok- Velicer WF. Evaluating theories of 2008 Update. Clinical Practice Guideline.
ing. Addiction 2006;101:1035–1043. health behavior change: A hierarchy Rockville, MD: U.S. Department of
doi:10.1111/j.1360-0443.2006.01419.x. of criteria applied to the transtheo- Health and Human Services, Public Health
3. Johnson JL, Regan R, Maddock JE,
3 retical model. Appl. Psychol. Int. Rev. Service, May 2008.
et al. What predicts stage of change for 2008;57(4):561–588. 41. Mauriello LM, Johnson SS, and
smoking cessation? Ann. Behav. Med. 37. Prochaska JO, Evers KE, Castle PH, et al. Prochaska JM. Meeting patients where
2000;22:S173 (Abstract). Enhancing multiple domains of well-being they are at: Using a stage approach to
34. Sun X, Prochaska JO, Velicer WF, by decreasing multiple health risk behav- facilitate engagement. In O’Donohue,
and Laforge RG. Transtheoretical iors: A randomized clinical trial. Popul. W., James, L., and Snipes, C. (Editors).
principles and processes for quitting Health Manag. 2012;15:1–11. Practical Strategies and Tools to Promote
smoking: A 24-month comparison of 38. Harter JK and Gurley VF. Measuring Treatment Engagement, NYC: Springer
a representative sample of quitters, Well-Being in the United States. International Publishing, 2017.
19
CHAPTER
229
230 Chapter 19 The Impact of Positive Psychology on Behavioral Change and Healthy Lifestyle Choices
our lives is central to our ability to survive and thrive as A meta-analysis of 60 studies performed by Rotegard
19
human beings. Since the publication of Frankl’s book, a et al. 28 found evidence that health assets mobilize indi-
large body of research has accrued indicating that people viduals to engage in decision making and attitude change
who believe their lives have meaning also attest to greater that can lead to Positive Health behaviors and improved
well-being and life satisfaction. 20 More recently, meaning health outcomes. This focus on building health assets was
in life has been associated with greater physical health 21 found to be a good fit for a patient-centered model of care.
and longevity. 22 Positive Health adds to the preventive medicine model by
Accomplishments. Setting goals and accomplishing fostering health assets that contribute to health promo-
them, even when they are small goals, provides us with tion as a much-needed counterpoint to the long-standing
a sense of fulfillment, satisfaction, and confidence in our focus on illness and disease, thereby providing healthy
ability to meet life’s challenges. Self-efficacy, our belief in targets for patients to move toward in addition to avoid-
our ability to accomplish the tasks we have before us, is ing known risk factors. 29 The theme that links Positive
associated with successful accomplishment of goals, as are Health to Positive Psychology is the idea that subjective
stress reduction and lower vulnerability to depression. 23 well-being—inclusive of the five aspects of the PERMA
More than just a means to an end, accomplishment, mea- model described above and measured by optimism and
sured as progress toward goals that are important to the other positive emotions—is a “health asset,” that protects
individual, is also correlated with subjective well-being in against risk of physical illness.
a meta-analysis of 85 studies. 24 In recent years, there has indeed been an increasing
pool of research evidence supporting a correlation between
subjective well-being and health outcomes. For example,
in a meta-analysis of 150 experimental and longitudinal
19.2 POSITIVE PSYCHOLOGY studies that tested the impact of well-being on objective
AND POSITIVE HEALTH health outcomes, well-being was found to be positively
related to both short- and long-term health outcomes.30
As practitioners working in the healthcare system, we must In addition, well-being has been associated with improved
remind ourselves what we are striving for each day and for disease or symptom control, especially immune system
each patient. The famous quote from the Constitution of response and pain tolerance. There is even evidence that a
the World Health Organization encourages us to consider positive emotional style can help prevent the common cold
health as a “state of complete physical, mental and social by lowering the risk of developing an upper-respiratory
well-being, and not merely the absence of disease or infir- illness. 31
mity”. 25 Yet what does this mean when we are faced with
a patient who is unwell and whose care we must prioritize?
As part of the answer to this question, from the 19.2.1 Positive Psychology Factors
burgeoning field of Positive Psychology, the concept of
Positive Health has arisen. Positive Health describes a
and Cardiovascular Disease
state beyond the mere absence of illness and focuses on A number of chronic disease studies have demonstrated
three independent health variables: subjective, biological, associations between well-being and improved health
and functional. 26 Positive subjective health describes the outcomes for patients with cardiovascular disease. In a
state when an individual feels great and frequently expe- review of the literature, authors from the Harvard School
riences vigor, hardiness, an internal health-related locus of Public Health found that subjective well-being consis-
of control, optimism, positive emotion, and high life sat- tently protects against cardiovascular disease (CVD), even
isfaction. The state of positive biological health looks at after controlling for traditional risk factors. 32 Specifically,
variables relevant to health, such as optimum heart rate in both healthy and patient populations, optimism was
variability, high levels of HDL, and cardiorespiratory found to be most reliably associated with a reduced risk of
fitness. Positive functional health includes both physical cardiac events. This review also found that higher levels
functionality (e.g., fitness and flexibility) and personal of positive psychological well-being were associated with
functionality (e.g., close friends and family, meaningful restorative health behaviors, increased physical activity,
work, and the ability to meet the demands of one’s chosen improved sleep, and reduced risk of smoking. In addition,
activities). a prospective study of almost 7,000 participants followed
Positive Psychology holds that one of the best ways for four years found that higher optimism was associ-
to address psychological problems is by leveraging psy- ated with a lower risk of heart failure after adjusting for
chological strengths. Similarly, Positive Health works to sociodemographic, behavioral, biological, and psycholog-
empirically identify and enhance health assets that predict ical covariates.33
health and illness over and above conventional risk fac- Subjective well-being (a construct that includes high
tors. According to Seligman et al., 27 a health asset is “an positive emotions, low negative emotions, and high life
individual factor that produces longer life, lower morbid- satisfaction) was found to be directly related to health-rel-
ity, lower health care expenditure, better prognosis when evant biological processes in a study that analyzed poten-
illness does strike, and/or higher quality of life.” This tial pathways through which positive affective states are
view endorses the importance of bolstering health assets protective.34 The results demonstrated that positive affect
as a method of disease prevention and health promotion in middle-aged men and women was associated with
rather than just viewing them as signals of the absence of reduced inflammatory neuroendocrine and cardiovascu-
risk factors or disease. lar activity. Specifically, cortisol (a key stress hormone
232 Chapter 19 The Impact of Positive Psychology on Behavioral Change and Healthy Lifestyle Choices
related to a range of pathologies) and plasma fibrinogen study demonstrated a direct relationship between posi-
(an inflammatory marker and predictor of future coro- tive affect and a 53% decreased likelihood of dying after
nary heart disease) were sampled during periods of relax- controlling for sociodemographic variables, major chronic
ation and stress, and compared to self-reported levels of conditions, body mass index (BMI), smoking and drink-
happiness. Positive affect was found to be inversely related ing status, and negative affect at baseline.42
to cortisol output over the day (32% lower for happier A French study43 that examined the influence of posi-
individuals), after controlling for age, gender, socioeco- tive affect, negative affect, and life satisfaction on mortal-
nomic position, body mass, and smoking. Plasma fibrino- ity in a cohort of 3,777 older adults found that positive
gen stress responses were also lower (over 12 times lower) affect predicted longevity. Participants in this study were
for individuals with high levels of happiness compared to tested at ten time intervals over a 22-year time period.
those with low levels of happiness. After controlling for various health conditions, higher
A recent study examined the contribution of several positive affect at each time interval continued to predict
factors of subjective well-being, including positive emo- survival at the next time interval.
tions and life satisfaction, to a set of measures of cardio- In a British observational study, subjective well-being
metabolic health known to reliably predict future coronary measures were obtained from a sample of over 9,000 men
heart disease.35 Cardiometabolic measures, which included and women age 50 and older at three time periods over a
diastolic and systolic blood pressure, HDL and LDL cho- decade.44 During the time period of the study, 1,310 deaths
lesterol, triglycerides, glycosylated hemoglobin, waist cir- occurred within the sample. Individuals in the group with
cumference, and C-reactive protein, were measured at two the highest well-being at Time 1 had the fewest deaths
time points between 8 and 11 years apart in approximately at Time 3 (after controlling for illness and depression at
800 midlife adults. Both positive emotions and life sat- Time (1), while the group with the lowest well-being at
isfaction at Time 1 predicted lower cardiometabolic risk Time 1 had the greatest number of deaths at Time 3. The
at Time 2, but when depression was controlled for, only authors caution that this is an observational study, so no
life satisfaction significantly predicted lower risk for the causality can be claimed, but the study can be considered
composite cardiometabolic risk at Time 2, suggesting that a contribution to the growing body of evidence that links
life satisfaction rather than positive emotions may be a well-being and life satisfaction with longevity.
more potent long-term health asset. Positive emotions at In a large prospective study, Lambiase and colleagues45
Time 1 did, however, predict lower levels of triglycerides, analyzed incidence of stroke over a mean of 16 years in
LDL cholesterol, and smaller waist circumference at Time over 6,000 individuals. They found that higher emo-
2. This confirms the findings of earlier studies regarding tional vitality was associated with lower stroke incidence.
positive emotions and their effect on certain heart health Emotional vitality was measured as a subscale of general
markers, such as the association between optimism and a well-being and included optimism, mastery, and positive
healthier lipid profile, including greater high-density lipo- emotions.
protein cholesterol and lower triglycerides.36 It is important to note that not all studies support
the association between well-being and longevity. The
UK Million Women Study, which followed over 700,000
19.2.2 Positive Psychology Factors women in a prospective study over a 12- to 16-year period,
and Diabetes recently reported findings related to mortality and positive
affect.46 Four percent of the sample died during the study
Positive health outcomes related to diabetes have also
period. The authors reported that unhappiness was asso-
been reported. In a meta-analysis of 80 studies that looked
ciated with self-rated poor health, but when this relation-
across diverse populations of age, race, geography, and dia-
ship was controlled for, happiness and well-being did not
betes type, the results showed that, across the lifespan, pos-
directly predict mortality.
itive personal characteristics (e.g., self-efficacy, self-esteem,
In summary, however, the preponderance of research
adaptive coping) and positive environmental factors (e.g.,
indicates that factors associated with positive psychol-
support) were associated with improved diabetes man-
ogy and well-being have a beneficial effect on a variety
agement and glycemic control.37 However, different from
of health conditions, including cardiovascular health,
the results for cardiovascular disease, life satisfaction and
diabetes, general mortality, and risk for stroke. At least
emotional vitality, but not optimism, were associated with
seven major reviews have examined the topic.30,39,40,47–50
reduced risk of physician-diagnosed diabetes.38
All have shown that positive affect and subjective well-
being have a beneficial effect for healthy populations or
19.2.3 Positive Psychology Factors those who are only mildly ill, suggesting that these factors
should be promoted as protective factors for public health.
and Mortality However, two of the reviews49,50 found that positive emo-
Ultimately, subjective well-being has been found to be tions and well-being do not predict longevity within sam-
associated with health, longevity, and reduced mortal- ples of those who are significantly ill. Therefore, Lamers
ity.39,40 This was true for both positive affect (e.g., joy, hap- et al.47 performed a meta-analysis on studies that assessed
piness, vigor) and positive trait-like dispositions (e.g., life the effect of positive affect and subjective well-being spe-
satisfaction, hopefulness, optimism). While there is some cifically on non-healthy samples. Their meta-analysis of
discrepancy in the research about whether the benefit is 17 studies revealed a small but significant positive effect
derived from lower levels of negative emotion or higher for positive emotions and well-being on the health of sick
levels of positive emotion,41 a large, two-year prospective populations.
19.3 Positive Psychology Interventions 233
19.2.4 Positive Psychology Factors and raise their level of positive emotions within the bounds
19
of the reality of their current situation. The next section
Additional Health Considerations describes positive psychology interventions that have been
In addition to the direct effects on health reviewed above, empirically tested, many in randomized controlled trials.
positive psychology factors appear to confer other health
benefits, including pain modulation and higher reported
quality of life in persons with chronic illness. A number
of studies have found that positive affect can reduce the 19.3 POSITIVE PSYCHOLOGY
experience of chronic pain. In a study of 98 adults with INTERVENTIONS
rheumatoid arthritis, researchers found that the average
level of reported pain was 14% lower when positive affect We have seen that factors related to positive psychology
was maintained at or above patient’s usual level than do in fact predict positive health conditions. However, can
when it was unregulated. 51 In a study of 124 women with these positive psychology factors be purposely enhanced
osteoarthritis or fibromyalgia, Zautra et al. 52 reported to benefit health? To date, a number of positive psychol-
that higher levels of overall positive affect predicted lower ogy interventions (PPIs) have been identified and tested.
levels of pain in subsequent weeks. Greater levels of posi- The field of positive psychology thus offers more than just
tive affect also resulted in lower levels of negative emo- a theoretic framework within which to approach patient
tions both generally and in relation to their chronic pain. health. It also offers a wide range of interventions that can
A rather large body of research has now investigated be effective in the enhancement of psychological well-being.
the effect of positive psychology factors on increasing PPIs have demonstrated improvements to well-being
the quality of life in patients with chronic diseases. The (including increased happiness and decreased depression)
results are fairly consistent in finding that positive emo- which have been maintained for a follow-up period of up
tions, well-being, and meaning-making decrease negative to six months.58,59 A meta-analysis that analyzed 51 positive
emotions, reduce the risk for depression, increase func- psychology interventions in over 4,000 participants revealed
tionality, help maintain positive relationships, and help enhanced well-being and decreased depressive symptoms
maintain compliance with medical regimens [e.g., 53–56]. upon intervention completion.60 These results are especially
While a positive attitude and positive emotions have salient to lifestyle medicine because depression is not only
been shown to help patients maintain a higher qual- a negative health outcome in and of itself but is also a risk
ity of life while dealing with severe health issues, other factor for coronary heart disease61 and type II diabetes.62 In
voices within the research field have suggested caution general, improvements in mental health and well-being are
in interpreting or promoting positive psychology factors assessed with validated self-report tools (see Table 19.2 for
as “cures” for serious illness. 57 The research support- a list of commonly used measures).
ing positive psychology factors as health assets is strong. PPIs can be delivered through a variety of modalities:
However, patients who are facing difficult health issues self-help (generally written instructions or online), group
may feel frustrated, misunderstood, or even hopeless if training, or individual therapy meetings. The majority of
confronted with what Aspinwall and Tedeschi have called interventions are delivered in a self-help format. While all
the “tyranny of optimism.”57 The goal is to help patients formats have demonstrated effectiveness, interventions
TABLE 19.2 Self-Report Measures Commonly Used to Test Positive Psychology Interventions
Measure and Reference Category Description
Center for Epidemiological Studies–Depression Depression 20 items on 4-point scale
Scale (CES-D)63
Flourishing Scale64 Well-Being 8 items on 7-point scale
Gratitude Questionnaire (GQ-6) 65 Gratitude 6 items on 7-point scale
Mindful Attention Awareness Scale (MAAS) 66 Mindfulness 15 items on 6-point scale
Life Orientation Test-Revised (LOT-R) 67 Optimism 10 items on 5-point scale
PERMA Profiler 104 Well-Being 23 items on 11-point scale
Positive and Negative Affect Schedule Emotions 20 items on 5-point scale
(PANAS)68
Psychological Well-Being Scales69 Well-Being 18 items on 6-point scale
Satisfaction with Life Scale (SwLS) 70 Well-Being 5 items on 7-point scale
Steen Happiness Inventory (STI) 59 Emotions 20 items on 5-point scale
Subjective Happiness Scale 71 Emotions 4 items on 7-point scale
Values in Action Inventory of Strengths Personal Strengths 240 items on 7-point scale
(VIA-IS)72
234 Chapter 19 The Impact of Positive Psychology on Behavioral Change and Healthy Lifestyle Choices
that are more intensive and include face-to-face interac- or weekly meditation. Individuals are generally
tions have been shown to generate larger effects. 58,60 instructed to relax and focus on the flow of their
Below we describe the most widely used evidence- breath or some other aspect of their current envi-
based PPIs. ronment for a period of 20 minutes, nonjudgmen-
tally acknowledging any passing thoughts and then
Gratitude visit. Individuals have one week to write letting them go.81 While the topic of mindfulness is
and then deliver a letter of gratitude in person to often associated with positive psychology,82 it is too
someone who has been especially kind to them but extensive to review in this chapter and is covered else-
whom they have never properly thanked. 59 This where in this volume. Numerous reviews have shown
intervention has been shown to provide an immedi- that mindfulness interventions can improve well-
ate bump in positive emotion as well as a decrease being in both patients and healthcare providers83–85;
in depressive symptoms that persisted at one month therefore, mindfulness meditations, along with PPIs,
follow-up. However, in the original study testing are recommended additions to any lifestyle medicine
this intervention, Seligman et al. 59 found that this practice.
effect had dissipated by the three-month follow-up.
Gratitude list (Counting blessings). Individuals are
instructed to write down between three and five 19.3.1 PPIs and Moderating Factors
things in their lives, large or small, that they are Several factors impact the effectiveness of PPIs, includ-
grateful for either each night for a period of two ing the patient’s level of depression at the beginning of
weeks or every week for a period of 10 weeks.73 This the intervention, age, motivation to improve, the format
intervention has been replicated in several studies of the intervention, and the appropriate patient/interven-
and has been shown to increase positive emotions tion match. Sin and Lyubomirsky60 found that patients
and mood extensively enough to be noticed by oth- who had symptoms of depression at the start of the inter-
ers, and to improve sleep quality.73–76 vention benefited more from PPIs than those who were
Three good things. Individuals are instructed to write not depressed, and that PPIs were effective in prevent-
down three things that went well each day for one ing relapse in previously depressed patients. These same
week. They are also asked to explain why each good researchers found that patients who were older benefited
thing happened. This intervention has been shown more than those who were younger, and that patients who
to result in long-lasting increases in positive emo- demonstrated a greater motivation to improve benefited
tions and reductions in depressive symptoms. 59 more from the interventions than those who were less
Using signature strengths: Individuals take an online motivated.
inventory of 24 character strengths that was devel- The intervention format significantly moderated the
oped by Christopher Peterson and colleagues.72 effectiveness of interventions, with greatest effect found
Their top five character strengths are considered for individual therapy, followed by group and then self-
their “signature” strengths. They are then instructed administered interventions. However, all forms of admin-
to use one of these signature strengths in a new and istration have been shown to be beneficial. The duration of
different way each day for one week. This interven- the intervention is also a factor, with longer interventions
tion has been shown to increase positive emotions demonstrating greater effectiveness. Finally, research sug-
and decrease depression for up to six months59 as gests that patient characteristics such as personality and
well as increase personal well-being.77 cultural background may impact the effectiveness of inter-
Best possible self. Individuals are instructed to think ventions: patients from cultures with interpersonal orien-
about their life in the future and imagine that every- tations, such as many Asian countries, have been shown to
thing has gone as well as it possibly could. They are benefit more from prosocial interventions, such as grati-
to imagine that they have worked hard and been tude visits and acts of kindness, than from self-focused
successful at accomplishing their life goals. They interventions such as best possible self.60,86–88
are then instructed to write about what they have
imagined for 20 minutes a day on four consecutive
days.78 This intervention has been shown across a 19.3.2 Positive Psychology
number of studies to increase positive emotions and
to decrease negative emotions and depression.76,78,79
Technological Devices
Acts of kindness. Individuals are instructed to per- Even when individuals are aware of their problems and
form five acts of kindness—all within one day of the are open to seeking help, assessment and intervention sup-
week—for six weeks. The acts can be anything that port is not always geographically, financially, or socially
makes others happy or that benefits others (such as accessible. While assessment tools have always been used
donating blood, visiting an elderly relative). This to screen, monitor, and evaluate treatment effectiveness,
intervention is associated with increased positive over time, technology-based interventions have shown
emotions immediately following the acts as well as their potential to make healthcare more accessible while
sustained increases in subjective well-being.48,80 reducing barriers to those seeking help.
Mindfulness meditation. Some reviews also include There are many types of positive psychology assess-
mindfulness interventions in their list of PPIs.60 ment and intervention tools offered through mobile
Mindfulness interventions cultivate non-judgmen- device apps and technological devices. Most health-based
tal awareness of the present moment through daily assessment and intervention tools fall under two broad
19.4 Incorporating Positive Psychology into the Lifestyle Medicine Practice 235
categories: active or passive. Active apps require direct concept that people learn through observing and model-
19
participation, such as completing mood logs or recording ing other people’s behavior, attitudes, and emotional reac-
subjective experiences. Passive apps do not require active tions.91 In a healthcare setting, modeling health behaviors
participation and can automatically gather data (e.g., calo- is a valuable method of promoting behavior change in oth-
ries burned, heart rate, steps taken) through a smartphone’s ers. Effective ways to model positive psychology principles
GPS, accelerometer, or other sensors.89 Most positive psy- in your practice include:
chology tools tend to fall in the active category of tools.
A plethora of positive psychology-related technologi- • Displaying positive emotions during interactions
cal devices and mobile apps are now available, but they with patients and with other staff (contentment,
aren’t all created equal. Many contain the word happy, hope, serenity, interest, amusement, inspiration)
happiness, or happier. While apps may enhance motiva- unless inappropriate to the situation. Not only will
tion or promote compliance with intervention protocols displays of positive emotions encourage positive emo-
(such as those described in this chapter), few empirical tions in others, but one experimental study found
studies or evidence-based evaluations have been con- that physicians in whom positive emotions had been
ducted to date, so practitioners should be cautious when induced made correct diagnoses more quickly than
deciding which intervention tools they choose to recom- those without the positive emotion induction.92 The
mend to their patients. According to Torous and Powell,89 study suggested that positive emotions may actually
any assessment or intervention tool should be empirically improve diagnostic decisions.
validated, widely used, focus on some aspect of positive • Expressing gratitude to staff within earshot of
human functioning, and be appropriate to the setting and patients for their positive work.
easy to interpret/administer. Stoyanov et al. developed the • Determining your own signature character
Mobile App Rating Scale (MARS), a useful tool to help strengths and using them on a regular basis in your
practitioners rate the degree to which a particular app work.
satisfies quality criteria.90 While at this time there are no • Discussing the personal meaning of health in your
apps that address the full range of MARS criteria, apps own life (e.g., lifestyle challenges you may have
are becoming more sophisticated and easy to use, and struggled with in the past and how you may have
they promise to provide positive benefits to providers and used positive psychology principles to help effect
patients in the future. positive lifestyle changes).
In summary, a number of positive psychology inter-
ventions have been developed, tested, and shown to be
effective in improving positive emotions and well-being 19.4.2 Having Positive Health
and in reducing depressive symptoms. Several moderating
factors that impact effectiveness have also been identified, Conversations with Patients
including the method of delivery. While the most effective One method of introducing positive psychology principles
method is one-on-one therapy, other methods (includ- into a lifestyle medicine practice is through both inciden-
ing Web-based self-help), although less effective, are still tal and more focused conversations that occur throughout
beneficial. New delivery methods, including mobile apps, the patient visit. Here are some examples:
are being developed, and with adequate testing may also
offer a beneficial form of positive psychology intervention • During examinations, ask open-ended questions
delivery. that focus on the patient’s strengths:
• What aspects of their health do they feel good
about?
19.4 INCORPORATING POSITIVE • What is their overall level of well-being?
• What are their capacities—strengths, interests,
PSYCHOLOGY INTO THE and resources—that they can bring to the table
LIFESTYLE MEDICINE PRACTICE if need be to help improve their health?
• What are their situational benefactors (e.g. sup-
There are several methods for incorporating positive psy- portive family, friends, good job)?
chology into the practice of lifestyle medicine. We dis- • Here are a few good questions to ask patients in
cuss four methods here: (1) modeling positive psychology order to encourage them to explore and share their
principles in your practice; (2) having positive health con- positive health attitudes and behaviors:
versations with patients; (3) prescribing positive psychol- • “When was the last time you felt well?”
ogy interventions; and (4) incorporating a health coach • “What have you done in the past that made you
trained in positive psychology principles into your prac- feel better?”
tice or clinic. • “Can you tell me about a time when you were
at your best? What strengths were you using at
that time?”
19.4.1 Modeling Positive • “It seems like this is very important to you. How
do you imagine your life would be different if
Psychology Principles you lost weight?”
Since Albert Bandura first introduced social learning the- • “What would be possible for you if you quit
ory over a half-century ago, research has supported the smoking?”
236 Chapter 19 The Impact of Positive Psychology on Behavioral Change and Healthy Lifestyle Choices
• When patients speak, employ active listening: When prescribing a PPI, as research indicates, it is
• Face your patients and put down any papers, pen- important to consider patient characteristics such as per-
cils, or equipment while they speak to you. Make sonality and cultural background.60,95 For example, Nelson
eye contact and nod to express that you hear them. and Lyubomirsky95 have pointed out that introverts may
Reflect back to them in your own words what you benefit more from reflective activities such as counting
heard them say (e.g., “If I understand you cor- blessings or meditation, while extraverts may prefer more
rectly, …” “It sounds like you’re feeling….” “What outgoing activities, such as acts of kindness. Likewise,
I hear you saying is…” “Is this correct?”). patients from a collectivist cultural background (e.g., some
• Active listening allows patients to feel heard and Asian cultures), where group happiness is emphasized, may
often helps them to understand their own symp- benefit more from one of the prosocial interventions, such
toms, condition, and potential for habit change as acts of kindness or writing a gratitude letter, than from
more clearly. an intervention targeting the individual, such as best pos-
• Encourage patients to avoid social comparisons sible self.60 Some research suggests that patients may have
(including comparisons with themselves as they used better results when matched with a self-selected interven-
to be when they were younger) and to focus on their tion with which they feel comfortable.96
own current strengths. It is also important to consider the modality of the pre-
• Remind patients to make mindful choices: every step scription. Self-motivated patients may benefit from a pre-
we take, every bite we eat, every activity we per- scription to simply perform an action, such as those listed
form, every reaction to an event we have, is a choice. in Table 19.3. However, less motivated patients may derive
Sometimes we forget that. It’s liberating to know we more benefit from a prescription to work one-on-one with
can mindfully choose so much about our lives! a trained positive psychology health coach.
• Engage in a short, realistic optimism process with
patients:
• First, help them to see their current health situa-
tion objectively rather than catastrophically.
19.4.4 Incorporating a Health Coach
• Second, help them brainstorm the best possible Trained in Positive Psychology
outcomes given their current situation. Principles into Your Practice
• Third, help them plan to move confidently and
Utilization of health coaches in primary care practices
positively toward those best possible outcomes.
offers positive psychology skill building for patients who
would benefit from lifestyle changes to improve their
19.4.3 Prescribing Positive health condition. Health coaches are professionals from
diverse backgrounds who work with individuals and
Psychology Interventions groups to facilitate and empower clients to achieve health-
Just as exercise can be prescribed for its health-enhancing related goals.97 They are an important part of an effective
and disease-preventing effects,93 positive psychology inter- collaborative care team model, and their use by practitio-
ventions (PPIs) can be prescribed for the same reasons.94 ners is poised to triple in the coming years.98 Health coach
Table 19.3 presents sample prescriptions for evidence- job tasks include: assessing readiness for change, collab-
based PPIs mentioned in the previous section. These PPIs oratively establishing client goals, evaluating successful
have been shown to increase positive emotions, decrease steps and self-limiting patterns, reassessing and modify-
negative emotions, and increase overall well-being. ing goals, articulating insights gained, and formulating a
your life goals. Write about what you have imagined for 20 minutes a day on four consecutive
days.
Acts of Kindness Pick one day of the week for the next six weeks and on that day each week perform five acts of 48,80
kindness (large or small) for other people that you would not have otherwise performed.
References 237
post-coaching plan to sustain changes that promote health there are growing bodies of research that connect positive
19
and wellness.99 emotions, optimism, and well-being with better cardio-
Research has shown that patients who received coach- vascular health, better diabetes management and glycemic
ing services demonstrated significant improvements in control, and lower mortality among healthy persons.
both physical and mental health,100 with reductions in While individual levels of optimism and well-being
chronic disease markers (HbA1c, blood pressure, LDL are, to an extent, trait-like factors, research has provided
cholesterol) that persisted one year after completion of the evidence that these factors can be enhanced through posi-
health coaching intervention.101 Health coaching with a tive psychology interventions. These interventions have
positive psychology emphasis has been found to improve centered on increasing positive emotions, self-efficacy, and
overall patient health, with a 19% decrease in patient- life satisfaction while decreasing negative emotions and
reported medical symptoms, and enhanced mental health stress. Some of the mechanisms employed in these inter-
strengths, including improved quality of life and increased ventions include expressing gratitude, understanding and
mastery of areas of well-being, such as maintaining trust- using one’s strengths to achieve goals and solve problems,
ing relationships and realizing one’s potential.102 In addi- focusing on and savoring positive events, and completing
tion, primary care clinicians reported that patients who small acts of kindness.
received health coaching were more empowered and less We have suggested several methods for implement-
demanding.103 Health and wellness coaches are becoming ing positive psychology principles and interventions in
fixtures in hospitals, clinics, private practices, and health a lifestyle medicine practice, including modeling these
clubs. principles in yourself and your practice, incorporating the
principles in discussions with patients, prescribing positive
psychology interventions as part of preventative or pal-
19.5 CONCLUSION liative care, and adding positive psychology coaching to
your practice or clinic. There is growing evidence for the
The advancement of positive emotions and well-being is physical health benefits of positive psychology practices
synergistic with the advancement of physical health. In for both physical and mental well-being. Practitioners of
this chapter, we have reviewed the evidence for a connec- lifestyle medicine are in an excellent position to promote
tion between positive emotions, optimism, and well-being overall well-being as an important part of comprehensive
with better health and longevity outcomes. In particular, health care.
REFERENCES
1. Seligman MEP and Csikszentmihalyi M. 5. Peterson C. A Primer in Positive bounce back from negative emotional
Positive psychology: An introduction. Psychology. New York, NY: Oxford experiences. J. Pers. Soc. Psychol. 2004;
Am. Psychol. 2000; 55(1): 5–14, p. 7. University Press, 2006. 86(2): 320–333.
2. Gable S and Haidt J. What (and why) is 6. Seligman MEP. Flourish: A Visionary 9. Fredrickson BL. The role of positive emo-
positive psychology? Rev. Gen. Psychol. New Understanding of Happiness and tions in positive psychology: The broaden-
2005; 9(2): 103–110. Well-Being. New York, NY: Free Press, and-build theory of positive emotions. Am.
3. Maslow AH. Motivation and Personality. 2011. Psychol. 2001; 56: 218–226.
New York, NY: Harper & Row, 1954. p. 7. Fredrickson BL. Positive emotions 0. Ong AD, Bergeman CS, Bisconti T, and
1
353. broaden and build. Adv. Exp. Soc. Wallace KA. Psychological resilience,
4. Seligman MEP. The president’s address: Psychol. 2013; 47(1): 53. positive emotions, and successful adapta-
1998 Annual Report. Am. Psychol. 1999; 8. Tugade MM and Barbara LF. Resilient tion to stress in later life. J. Pers. Soc.
54(8): 559–562. individuals use positive emotions to Psychol. 2006; 91(4): 730–749.
238 Chapter 19 The Impact of Positive Psychology on Behavioral Change and Healthy Lifestyle Choices
11. Csikszentmihalyi M. Flow: The concept analysis. Int. J. Nurs. Stud. 2010; longitudinal study of ageing. BMJ 2016;
Psychology of Optimal Experience. New 47: 513–525. 355: 6267.
York, NY: Harper & Row, 1990. 29. National Research Council.Positive 45. Lambiase MJ, Kubzansky LD, and
12. Nakamura J and Csikszentmihalyi M. health: Resilience, recovery, primary Thurston RC. Positive psychological
Flow theory and research. In Snyder prevention, and health promotion. health and stroke risk: The benefits of
CR, Lopez J, eds. Oxford Handbook of In Singer, BH, Ryff, CD, eds. New emotional vitality. Health Psychol. 2015;
Positive Psychology, 2nd ed. New York, Horizons in Health: An Integrative 34(10): 1043–1046.
NY: Oxford University Press, 2009. Approach. Washington DC: The National 46. Liu B, Floud S, Pirie K, et al. Million
13. Schmidt J. Correlates of reduced miscon- Academies Press, 2001. women study collaborators. Does happi-
duct among adolescents facing adversity. 30. Howell RT, Kern ML, and Lyubomirsky ness itself directly affect mortality? The
J. Youth Adolesc. 2003; 32: 439–452. S. Health benefits: Meta-analytically prospective UK Million Women Study.
14. Hirao K, Kobayashi R, Okishima K, and determining the impact of well-being Lancet 2016; 387: 874–881.
Tomokuni Y. Influence of flow experience on objective health outcomes. Health 47. Lamers S, Bolier L, Westerhof GJ, et al.
during daily life on health-related quality Psychol. Rev. 2007; 1(1): 83–136. The impact of emotional well-being on
of life and salivary amylase activity in 31. Cohen S, Alper CM, Doyle WJ, et al. long-term recovery and survival in physi-
Japanese college students. Jpn. J. Occup. Positive emotional style predicts resis- cal illness: A meta-analysis. J. Behav.
Med. Traumatol. 2011; 59: 13–18. tance to illness after experimental expo- Med. 2012; 5: 538–547.
15. Hirao K, Kobayashi R, Okishima K, and sure to rhinovirus or influenza a virus. 48. Lyubomirsky S, Sheldon KM, and
Tomokuni Y. Flow experience and health- Psychosom. Med. 2006; 68(6): 809–815. Schkade D. Pursuing happiness: The
related quality of life in community 32. Boehm JK and Kubzansky LD. The architecture of sustainable change. Rev.
dwelling elderly Japanese. Nurs. Health heart’s content: The association between Gen. Psychol. 2005; 9(2): 111–131.
Sci. 2012; 14(1): 52–57. positive psychological well-being and car- 49. Pressman SD and Cohen S. Does positive
16. Diener M and Diener McGavran MB. diovascular health. Psychol. Bull. 2012; affect influence health? Psychol. Bull.
What makes people happy? A develop- 138(4): 655–691. 2005; 131(6): 925–971.
mental approach to the literature on 33. Kim E, Smith J, and Kubzansky LD. 50. Veenhoven R. Health happiness: Effects
family relationships and well-being. In Prospective study of the association of happiness on physical health and the
Eid M, Larsen RJ, eds. The Science of between dispositional optimism and inci- consequences for preventative care. J.
Subjective Well-Being. New York, NY: dent heart failure. Circ. Heart Fail. 2014; Happiness Stud. 2008; 9(3): 449–469.
Guilford, 2008. 7(3): 394–400. 51. Connelly M, Keefe FJ, Affleck G, et al.
17. Uchino BN, Cacioppo JT, and Kiecolt- 34. Steptoe A, Wardle J, and Marmot M. Effects of day to day affect regulation
Glaser JK. The relationship between Positive affect and health-related neuro- on the pain experience of patients with
social support and physiological endocrine, cardiovascular, and inflam- rheumatoid arthritis. Pain 2007; 131:
processes: A review with emphasis on matory processes. Proc. Natl. Acad. Sci. 162–170.
underlying mechanisms and implications USA 2005; 102(18): 6508–6512. 52. Zautra A, Johnson LM, and Davis MC.
for health. Psychol. Bull. 1996; 119(3): 35. Boehm JK, Chen Y, Williams DR, Ryff Positive affect as a source of resilience for
488–531. CD, and Kubzansky LD. Subjective women in chronic pain. J. Consult. Clin.
18. Liu RT, Hernandez EM, Trout ZM, well-being and cardiometabolic health: Psychol. 2005; 73(2): 212–220.
Kleiman EM, and Bozzay ML. An 8-11year study of midlife adults. J. 53. Caprara GV, Castellani V, La Torre M,
Depression, social support, and long- Psychosom. Res. 2016; 85: 1–8. et al. Being positive despite illness: The
term risk for coronary heart disease in 36. Boehm JK, Williams DR, Rimm EB, et al. contribution of positivity to the quality
a 13-year longitudinal epidemiological Association between optimism and serum of life of cancer patients. Psychol. Health
study. Psychiatry Res. 2017; 251: 36–40. antioxidants in the midlife in the United 2015; 31(5): 524–534.
19. Frankl VE. Man’s Search for Meaning: States study. Psychosom. Med. 2013; 54. Casellas-Grau A, Font A, and Vives
An Introduction to Logotherapy. New 75(1): 2–10. J. Positive psychology interventions
York, NY: Washington Square Press, 37. Yi-Frazier JP, Hilliard M, Cochrane K, in breast cancer: A systematic review.
1963. and Hood KK. The impact of posi- Psycho-Oncology 2014; 23(1): 9–19.
20. Steger MF. Meaning in life. In Lopez tive psychology on diabetes outcomes: 55. Eaton RJ, Bradly G, and Morrissey S.
SJ, ed. Oxford Handbook of Positive A review. Psychology 2012; 3(12A): Positive predispositions, quality of life
Psychology, 2nd ed. Oxford, UK: Oxford 1116–1124. and chronic illness. Psychol. Health.
University Press, 2009, p. 679–687. 38. Boehm JK, Trudel-Fitzgerald C, Kivimaki Med. 2014; 19(4): 473–489.
21. Czekierda K, Banik A, Park CL, and M, and Kubzansky LD. The prospective 56. Hou WK, Law CC, and Fu YT. Does
Luszczynska A. Meaning in life and association between positive psycho- change in positive affect mediate and/
physical health: Systematic review and logical well-being and diabetes. Health or moderate the impact of symptom
meta-analysis. Health Psychol. Rev. 2017; Psychol. 2015; 34(10): 1013–1021. distress in psychological adjustment after
11(4): 387–418. 39. Chida Y and Steptoe A. Positive psy- cancer diagnosis? A prospective analysis.
22. Hill PL and Turiano NA. Purpose in life chological well-being and mortality: A Psycho. Health 2010; 25(41): 417–431.
as a predictor of mortality across adult- quantitative review of prospective obser- 57. Aspinwall LG and Tedeschi RG. The value
hood. Psychol. Sci. 2014; 2: 1482–1486. vational studies. Psychosom. Med. 2008; of positive psychology for health psychol-
23. Bandura A. Self-efficacy. In 70(7): 741–756. ogy: Progress and pitfalls in examining the
Ramachaudran VS, ed. Encyclopedia of 40. Diener E and Chan MY. Happy people relation of positive phenomena to health.
Human Behavior, vol. 4. New York, NY: live longer: Subjective well-being con- Ann. Behav. Med. 2010; 39: 4–15.
Academic Press, 1994, p. 71–81. tributes to health and longevity. Appl. 58. Bolier L, Haverman M, Westerhof GJ, et al.
24. Klug HJP and Maier GW. Linking goal Psychol. Health Well Being 2011; 3: Positive psychology interventions: A meta-
progress and subjective well-being: A 1–43. analysis of randomized controlled studies.
meta-analysis. J. Happiness Stud. 2014; 41. Ortega FB, Lee DC, Sui X, et al. BMC Public Health 2013; 13: 119.
6: 37–65. Psychological well-being, cardiorespira- 59. Seligman MEP, Steen TA, Park N, and
25. WHO. Constitution of the World Health tory fitness, and long-term survival. Am. Peterson C. Positive psychology in prog-
Organization: Principles, 1948 retrieved J. Prev. Med. 2010; 39(5): 440–448. ress. Empirical validation of interven-
August 20, 2017. Available from: http:// 42. Ostir GV, Markides KS, Black SA, and tions. Am. Psychol. 2005; 60: 410–421.
www.who.int/about/mission/en/ Goodwin JS. Emotional well-being pre- 60. Sin NL and Lyubomirsky S. Enhancing
26. Seligman MEP. Positive health. Appl. dicts subsequent functional independence well-being and alleviating depressive
Psychol. Int. Rev. 2008; 57(Suppl 1): and survival. J. Am. Geriatr. Soc. 2000; symptoms with positive psychology
3–18. 48(5): 473–478. interventions: A practice-friendly meta-
27. Seligman MEP, Peterson C, Barsky AJ, 43. Gana K, Broc G, Saada Y, et al. analysis. J. Clin. Psychol. 2009; 65(5):
et al. Positive health and health assets: Subjective wellbeing and longevity: 467–487.
Re-analysis of longitudinal datasets. Findings from a 22-year cohort study. J. 61. Lett HS, Blumenthal JA, Babyak MA, et
Positive Health, 2013. Philadelphia, PA: Psychosom. Res. 2016; 85: 28–34. al. Depression as a risk factor for coro-
University of Pennsylvania. 44. Zaninotto P, Wardle J, and Steptoe A. nary artery disease: Evidence, mecha-
28. Rotegard AK, Moore SM, Fagermoen Sustained enjoyment of life and mortality nisms, and treatment. Psychosom. Med.
MS, and Ruland CM. Health assets: A at older ages: Analysis of the English 2004; 66: 305–315.
References 239
62. Rotella F and Mannucci E. Depression intervention promoting wellbeing. 92. Estrada CA, Isen AM, and Young MJ.
as a risk factor for diabetes: A meta- Comput. Hum. Behav. 2009; 25: Positive affect facilitates integration of
analysis of longitudinal studies. J. Clin.
Psychiatry 2013; 74: 31–37.
63. Radloff LS. The CES-D scale: A self-
78.
749–760.
King LA. The health benefits of writing
about life goals. Pers. Soc. Psychol. Bull.
information and decreases anchoring in
reasoning among physicians. Organ. Behav.
Hum. Decis. Process. 1997; 72(1): 117–135.
19
report depression scale for research in the 2001; 27: 798–807. 93. Warburton DER, Nicol CW, and Bredin
general population. Appl. Psychol. Meas. 79. Sheldon KM and Lyubomirsky S. How SSD. Prescribing exercise as preventive
1977; 1: 385–401. to increase and sustain positive emotion: therapy. Can. Med. Assoc. J. 2006; 174:
64. Diener E, Wirtz D, Tov W, et al. New The effects of expressing gratitude and 961–974.
well-being measures: Short scales to assess visualizing best possible selves. J. Pos. 94. Hershberger PJ. Prescribing happiness:
flourishing and positive and negative feel- Psychol. 2006; 1: 73–82. Positive psychology and family medicine.
ings. Soc. Indic. Res. 2010; 97: 143–156. 80. Nelson SK, Layous K, Cole S, and Fam. Med. 2005; 37(9): 630–634.
65. McCullough ME, Emmons RA, and Lyubomirsky S. Do unto others or 95. Nelson SK and Lyubomirsky S. Finding
Tsang J. The grateful disposition: A con- treat yourself? The effects of prosocial happiness: Tailoring positive activities for
ceptual and empirical topography. J. Pers. and self-focused behavior on psycho- optimal well-being benefits. In Tugade
Soc. Psychol. 2002; 82: 112–127. logical flourishing. Emotion 2016; 16(6): M, Shiota M, Kirby L, eds. Handbook
66. Brown KW and Ryan RM. The benefits 850–861. of Positive Emotions. New York, NY:
of being present: Mindfulness and its role 81. Zeidan F, Johnson SK, Gordon NS, Guilford, 2012. pp. 275–292.
in psychological well-being. J. Pers. Soc. and Goolkasian P. Effects of brief and 96. Schueller SM. To each his own well-being
Psychol. 2003; 84: 822–848. sham mindfulness meditation on mood boosting intervention: Using preference to
67. Scheier MF, Carver CS, and Bridges MW. and cardiovascular variables. J. Altern. guide selection. J. Pos. Psychol. 2011; 6:
Distinguishing optimism from neuroti- Complement Med. 2010; 16: 867–873. 300–313.
cism (and trait anxiety, self-mastery, and 82. Ivtzan I, Lomas T, eds. Mindfulness in 97. Jordan M, Wolever RQ, Lawson K, and
self-esteem): A re-evaluation of the Life Positive Psychology: The Science of Moore M. National training and educa-
Orientation Test. J. Pers. Soc. Psychol. Meditation and Wellbeing. New York, NY: tion standards for health and wellness
1994; 67: 1063–1078. Routledge/Taylor & Francis Group, 2016. coaching: The path to national certifica-
68. Watson D, Clark LA, and Tellegen A. 83. Gotink RA, Chu P, Busschbach JJ, et al. tion. Glob. Adv. Health Med. 2015; 4(3):
Development and validation of brief Standardised mindfulness-based inter- 46–56.
measures of positive and negative affect: ventions in healthcare: An overview of 98. Institute of Functional Medicine
The PANAS scales. J. Psychol. 1988; 54(6): systematic reviews and meta-analyses of (IFM). Functional Medicine Practices:
1063–1070. RCTs. PloS One 2015; 10: e0124344. Opportunities, Challenges, and
69. Ryff C and Keyes C. The structure of 84. Keng SL, Smoski MJ, and Robins CJ. Emerging Trends (2016 Survey of
psychological well-being revisited. J. Pers. Effects of mindfulness on psychological Functional Medicine Practices). Federal
Soc. Psychol. 1995; 69: 719–727. health: A review of empirical studies. Clin. Way, WA: Institute for Functional
70. Diener E, Emmons RA, Larson RJ, and Psychol. Rev. 2011; 31: 1041–1056. Medicine, 2016.
Griffin S. The satisfaction with life scale. 85. Lomas T, Medina JC, Ivtzan I, et al. A 99. Wolever RQ, Jordan M., Lawson K, and
J. Pers. Assess. 1985; 49: 71–75. systematic review of the impact of mind- Moore M. Advancing a new evidence-
71. Lyubomirsky S and Lepper HS. A mea- fulness on the well-being of healthcare based professional in health care: Job
sure of subjective happiness: Preliminary professionals. J. Clin. Psychol. 2017; 00: task analysis for health and wellness
reliability and construct validation. Soc. 1–37. doi.org/10.1002/jclp.22515 coaches. BMC Health Serv. Res. 2016;
Indic. Res. 1999; 46: 137–155. 86. Boehm JK, Lyubomirsky S, and Sheldon 16: 205–205.
72. Peterson C and Seligman MEP. Character KM. A longitudinal experimental study 100. Butterworth S, Linden A, McClay W,
Strengths and Virtues: A Handbook and comparing the effectiveness of happiness- and Leo MC. Effect of motivational
Classification. Washington, DC: APA enhancing strategies in Anglo Americans interviewing-based health coaching on
Press and Oxford University Press, 2004. and Asian Americans. Cognition employees’ physical and mental health
73. Emmons RA and McCullough ME. Emotion 2011; 25: 1263–1272. status. J. Occup. Health Psychol. 2006;
Counting blessings versus burdens: An 87. Otake K, Shimai S, Tanaka-Matsumi J, et 11(4): 358–365.
experimental investigation of gratitude al. Happy people become happier through 101. Sharma AE, Willard-Grace R, Hessler D,
and subjective well-being in daily life. J. kindness: A counting kindness interven- et al. What happens after health coach-
Pers. Soc. Psychol. 2003; 84: 377–389. tion. J. Happiness Stud. 2006; 7: 361–375. ing? Observational study 1 year following
74. Froh JJ, Sefick WJ, and Emmons RA. 88. Layous K and Lyubomirsky S. The how, a randomized controlled trial. Ann. Fam.
Counting blessings in early adolescents: An why, what, when, and who of happiness. Med. 2016; 14(3): 200–207.
experimental study of gratitude and sub- In Gruber J, Moskowitz JT, eds. Positive 102. Scheinbaum S and Cook A. The Power
jective well-being. J. Sch. Psychol. 2008; Emotion: Integrating the Light Sides of Functional Medicine-Trained
46: 213–233. and Dark Sides. Oxford, UK: Oxford Doctors and Coaches to Create Patient-
75. Geraghty AWA, Wood AM, and Hyland University Press, 2014. pp. 473–495. Empowered Healthcare: A Pilot Study.
ME. Dissociating the facets of hope: 89. Torous J and Powell A. Current research Stanford Medicine X | ED Conference
Agency and pathways predict attrition and trends in the use of smartphone Poster Presentation, Stanford, CA:
from unguided self-help in opposite direc- applications for mood disorders. Internet Stanford University, 2017.
tions. J. Res. Pers. 2010; 44: 155–158. Interv. 2015; 2(2): 169–173. 103. Dubé K, Willard-Grace R, O’Connell B,
76. Manthey L, Vehreschild V, and Renner 90. Stoyanov SR, Hides L, Kavanagh DJ, et al. et al. Clinician perspectives on working
KH. Effectiveness of two cognitive inter- Mobile App Rating Scale: A new tool for with health coaches: A mixed methods
ventions promoting happiness with video- assessing the quality of health mobile apps. approach. Fam. Syst. Health 2015; 33(3):
based online instructions. J. Happiness JMIR mHealth uHealth 2015; 3(1): e27. 213–221.
Stud. 2016; 17(1): 319–339. 91. Bandura A. Social learning through 104. Butler J and Kern ML. The PERMA-
77. Mitchell J, Stanimirovic R, Klein B, imitation. In Jones MR, ed. Nebraska Profiler: A brief multidimensional
and Vella-Brodrick D. A randomized Symposium on Motivation. Lincoln, NE: measure of flourishing. Int. J. Well-Being
controlled trial of a self-guided internet University of Nebraska Press, 1962. 2016; 6(3): 1–48.
20
CHAPTER
241
242 Chapter 20 The Intention–Behavior Gap
medication adherence, especially the aspects of evidence- more physically active, while the rest (3 out of 10) will
based factors that might contribute to increase adherence not have intention: “The results suggest that, while some
to the prescription. people still require interventions changing intentions,
Thus, the purpose of this chapter is to introduce and much of the inactive population has positive intentions.”3
elucidate the intention–behavior gap (IBG). In addition, However, of those who did have intention to get more
we aim to investigate the efficacy of current proposed physical activity, only 54% were successful in performing
solutions to the IBG to provide the practitioner with the behavior, which would translate to about one out of
options to increase medication adherence when lifestyle every two patients who intend to be more physically active
is the medicine. will follow through with their intention. The rest, 46% of
the intenders who did not follow through with their inten-
tion, epitomize the IBG.
20.1.1 What Is the Intention– We find similar IBGs with fruit and/or vegetable (FV)
Behavior Gap? consumption. For example, authors of a systematic review
found that intention only predicted or explained 34%,
Traditionally, intention has been conceptualized as the 43%, and 31% of the variation in total FV intake, fruit
immediate antecedent to behavior. In other words, we intake, and vegetable intake, respectively. Other stud-
have intention to do something, then we do it (behave). ies have examined the relationships or correlations (r)
However, early examinations of behavior highlighted between intention and FV behavior, such as achieving
that intention did not always translate to behavior. Early previous public health recommendations of consuming
theories to explain this phenomenon were the predecessor 5 FV per day. Generally, on average, these correlations
of the more widely utilized Theory of Planned Behavior are weak: r+ = 0.27 in children/adolescents,4 –8 r+ = 0.36 in
(TPB) by Drs. Ajzen and Fishbein (see Chapter 16), which college students,9–11 r+ = 0.41 in adults,12,13 and r = 0.40 in
shed light on potential factors that either moderated or older adults.14 As a reminder, strong correlations typically
mediated the relationship of intention with behavior (e.g., surpass r ≥ 0.50 on the 0 to 1 scale.
habit, facilitating or constraining conditions, or social and A more recent review of studies of healthy eating found
affective factors). However, the intention–behavior gap that, on average across all studies, intention and behavior
remains enigmatic as it relates to physical activity (PA) or were only moderately correlated (r+ = 0.45).15 Also, stud-
healthy eating. ies were separated into those that directed participants to
After observing the IBG in practice, researchers consume health-promoting foods versus avoiding health-
uncovered that intention, even if it was high, was not compromising foods. Interestingly the intention–behavior
a reliable predictor of PA or dietary behavior.1 Clearly, relationship was weaker in the avoiding unhealthy food
there is variation in behavior—with some doing more, (r = 0.28) than in the promoting healthy food (r = 0.43).
some doing less, and some not changing over time. In These findings suggest that patients could have a higher
an ideal scenario, intention would explain all (100%) of probability of overcoming the IBG with healthy food-pro-
this variation, accounting for why some people increase, moting prescriptions (e.g., add another vegetable to your
some decrease, and some do not change their behavior. day) than with prescriptions aimed at avoiding unhealthy
We would be able to measure intention level and pre- foods (e.g., eat less sugar). Clearly, both prescriptions are
dict, perfectly, how much their behavior would change. important in lifestyle medicine practice, but the nuances
However, the TPB, which includes intention, was found of the IBG can help explain variation in medication adher-
to only predict 24% and 21% of the variation in physi- ence within patients.
cal activity and dietary behavior, respectively. 2 In other The IBG remains large, as intentions only get translated
words, somewhere between 75–80% of the variation in into action about half the time,1 which equates to the fact
behavior is not explained by intention and its related that 1 in 2 patients will succeed. In response, additional
predictors. theories have been utilized to help explain the IBG, such
In response, Rhodes and de Bruijn set out to explain as the Action Control Theory, the Precaution Adoption
how big the IBG gap was with leisure-time moderate-to- Process Model, the Temporal Self-Regulation Theory, and
vigorous physical activity that met current public health the Volitional Model of Goal-Directed Behavior. Rhodes
guidelines.3 They discovered that across ten studies pre- & Yao have provided an excellent review of 16 models,
sented, on average, approximately: hoping to better explain the IBG in physical activity, con-
cluding: “Whether these models will serve to improve
• 21% were non-intenders and were unsuccessful in our interventions and/or explain [physical activity] better
performing the behavior than the current state of research is unknown.”16 In other
• 2% were non-intenders but were successful in per- words, we have several models and factors that can help
forming the behavior us, but the future is bright with opportunity to innovate
• 36% were intenders but were unsuccessful in per- and properly evaluate old and new models to further our
forming the behavior understanding of the IBG. Until then, we can begin to put
• 42% were intenders and were successful in perform- the known concepts into practice, reducing the probability
ing the behavior of IBG occurrence in our patients. Many of the leading
concepts are summarized later in this chapter, alongside
If these results translate to practice, we can assume practical applications for you to implement—if you have
that about 7 out of 10 patients will have intention to be intention to do so.
20.2 Intention in Practice 243
20.2 INTENTION IN PRACTICE In this case, the ideal public health prescription (150
20
minutes of moderate-intensity physical activity per week)
would not be the proper prescription for this patient,
20.2.1 What Is Intention? because they are highly unlikely to follow through with
As it relates to the IBG, intention indicates how hard a the prescription. We would have to help the patient find
patient is willing to try, or how much effort they are will- an exercise prescription that he or she is more likely to do.
ing to put toward any given behavior.17 The assumption is For example,
that “the stronger a person’s intention, the more the person
is expected to try, and hence the greater the likelihood that “I intend to exercise for at least 30 minutes per day, 2 days per
the behavior will actually be performed.”18 Also, with such week for the next 2 weeks.”
desire and willingness, intention to do a behavior indicates
Unlikely : 1 : 2 : 3 : 4 : 5 : 6 : 7 : Likely
a more proximal time frame. They intend to behave very
soon, not later or in the coming months/years.
If the patient remains unlikely, regardless of the pre-
scription modification, then other tactics would need to
20.2.2 Intention in Practice be employed to help enhance intention.
In practice, patients might relay that they “intend” to be
more active or start eating healthier. However, this might
more resemble a statement of hope for some time in the 20.2.3 Intention Stability
future rather than an actual dedication to change. In this
Intention strength has also been conceptualized as inten-
case, they are not indicating that they are willing and ready
tion stability, which refers to the fluctuations in intention
to put forth vast amounts of effort to be more active and
across time.19,20 In those with high intention to engage in
eat healthier in the immediate future. So, by definition, they
more physical activity, for example, having more intention
do not have true intention to change. In a way, they are
stability could help. 20 Those with high intention-high sta-
saying, “I intend to” but really mean “I would like to” or
bility achieved twice the amount of physical activity than
“I hope to.” The semantics here are important, as they give
those with high intention–low stability. In other words,
insight into intention strength and the IBG in practice.
if a patient has high intention, ensuring that the inten-
For example, Dr. Ajzen has provided instructions
tion remains stable over time can be beneficial for behav-
for developing questionnaires to assess intention within
ior. If intention slips over time, then behavior could be
the context of the TPB; these instructions are accessible
negatively impacted—even if the patient initially had high
online at http://people.umass.edu/aizen/pdf/tpb.measure
intention to follow the lifestyle prescription.
ment.pdf. First, the behavior must be clearly defined in its
The largest effect, however, was seen in those with low
target, action, context, and time elements. In other words,
intention. Low intention-high stability participants did
we cannot simply ask patients about their intention to
not increase physical activity from baseline, as expected.
be more physically active. That is too general. We would
They did not have much intention to change and were sta-
need to more specifically define physical activity, such as
ble with their low intention over time. Yet, low intention-
“at least 30 minutes per day, 5 days per week for the next
low stability participants were more willing to change as
4 weeks.” Since intention is assuming a level of likelihood
their physical activity behavior increased. In this case,
of effort toward performing the behavior, “likely” or
their instability of intention was beneficial.
“unlikely” anchors are applied. Here is a final item that a
patient could be asked to answer.
20.2.4 When to Intend?
“I intend to exercise for at least 30 minutes per day, 5 days per
week for the next 4 weeks.” These findings highlight individual differences in inten-
tional response as well as the complexities of factors
Unlikely : 1 : 2 : 3 : 4 : 5 : 6 : 7 : Likely
that could influence intention and subsequent behavioral
success. The complex process that occurs from initial
As you can see, the specifics of the behavior, includ- intention through behavior is commonly referred to as
ing the type of behavior, the amount of behavior, and the self-regulation. On the other hand, self-regulatory failure
time frame, could greatly impact a patient’s level of inten- would be used to describe the inability to regulate one’s
tion. Although not a direct focus within this chapter, it own thoughts or actions. Self-regulation can be described
is important to note that lifestyle prescriptions can and as a process of monitoring and changing behavior when
should be modified to accommodate for inadequate levels normalcy is interrupted and has been previously detailed
of important factors, such as intention or self-efficacy (dis- elsewhere. 21–23
cussed later in the chapter). Normalcy for many patients is an inactive and stress-
For example, let’s say a patient responded to our first ful lifestyle, with unhealthy diets and poor sleep quality.
intention question with a “2”. The practitioner uses diagnoses, screenings, or self-mon-
itoring tools (e.g., pedometer, dietary log) to interrupt
“I intend to exercise for at least 30 minutes per day, 5 days per this normalcy by creating perceived discrepancies from a
week for the next 4 weeks.” desired standard. The hope is that such actions will trigger
or promote an important spark for change of behavior in
Unlikely : 1 : 2 : 3 : 4 : 5 : 6 : 7 : Likely
the patient (i.e., a medical trigger). However, in practice,
244 Chapter 20 The Intention–Behavior Gap
we realize that some patients respond with an initial level However, as with any plan, problems will be encoun-
of intention, whereas others have no intention to change. tered, and strategies are needed to invest conscious effort
This understanding highlights the complexity of intention for the purpose of solving problems or responding to per-
and behavior in patients as well as the need for the practi- ceived discrepancies in behavior. So, in relation to HAPA
tioner to better understand what other factors or concepts and implementation-intention strategies, coping planning
could moderate or affect the strength of the intention– takes place when an individual imagines a scenario that
behavior relationship. may hinder them in performing an intended behavior.
Coping planning is making a plan that anticipates diffi-
culties or barriers that might hinder the patient’s imple-
20.3 SOLUTIONS FOR THE IBG mentation of their intentions to live a healthy lifestyle. 26,27
A coping planning statement might look like, “If it is rain-
20.3.1 Action and Coping Planning ing or too cold in the morning, then I will go to the gym
instead of jogging in the neighborhood.”
20.3.1.1 Introduction
The health action process approach (HAPA; Figure 20.1)
model is a behavior change framework that allows for 20.3.1.2 Review
additional explanatory variables beyond the TPB. More Of all the potential moderators of the IBG, implementa-
specifically, it is a model “that explicitly includes post- tion intention (action planning) research is perhaps the
intentional mediators to overcome the intention–behavior most robust. For PA, a 2013 review examined 26 inde-
gap.”24 The motivation phase includes factors that lead up pendent studies and concluded that action planning could
to intention, while the volition phase describes the vari- help promote PA, but the effect size was relatively small
ables helping connect intention to behavior. A generic (d = 0.31) for measures of PA post-intervention and even
model example is shown in Figure 20.1. smaller for longer-term follow-up measures (d = 0.24). 28
When a patient has intention to adopt a particular The authors conclude that, “although implementation
health behavior, the action must be initiated and subse- intentions are viewed as a powerful strategy to overcome
quently maintained. As previously mentioned, the ensur- the above self-regulation problems, individuals might have
ing process of connecting intention–behavior requires to formulate specific plans not only for their [behavioral]
multiple factors and skills that facilitate successful self- resolution (e.g., if it is Sunday morning, then I will go to
regulation of one’s own behavior. The HAPA could allow the gym) but also for the management of barriers. Thus,
for an open architecture for multiple factors but empha- this aspect can lower the efficacy of implementation inten-
sizes self-efficacy (discussed in the next section) and tions for complex [behaviors], particularly if the manipu-
planning. The hypothesis relays that “good intentions lation of implementation intentions is less elaborate (i.e.,
are more likely to be translated into action when people only planning when, where and how).”28
develop success scenarios and preparatory strategies for A 2011 review and meta-analysis on healthy eating
approaching a difficult task.”24 Such planning is accom- and implementation intentions highlighted 14 studies that
plished through action planning and coping planning. investigated the efficacy of implementation intentions in
Action planning, or implementation intentions, is “a increasing healthy eating behaviors, while eight studies
form of planning that specify a critical condition linked were designed to reduce unhealthy eating behaviors.29 For
to goal-directed response.”25 Such plans provide “if-then” healthy eating patterns, implementation intentions appear
statements to help connect a patient’s intention to follow- to more effective in promoting the inclusion of healthy food
ing through with the behavior. For example, “If I wake up items (d = 0.51) than they are for diminishing unhealthy eat-
at 6:00 am tomorrow morning, then I will get ready and ing patterns (d = 0.29). However, the authors note that the
immediately go jogging in the neighborhood.” overall effect sizes of the results were small, perhaps due to
Action
Outcome Planning Action,
Intention
Expectancies Coping Behavior
Planning
Risk
Motivational Volitional
Perception Phase Phase
poor control groups or weak outcome measures. A 2017 regarding one’s competence to accomplish a specific task
20
review and meta-analysis of 12 empirical studies examin- in a particular context. In relation to the IBG, the HAPA
ing the effect of implementation intentions on reducing fat model provides three separate self-efficacy constructs:24
intake found a moderate effect size (d = 0.49),30 which fared
better than the effects found by Adriaanse and colleagues29 1.
Preaction or Action Self-Efficacy: This type of effi-
on reducing unhealthy eating behaviors (d = 0.29). cacy occurs before individuals have yet acted and
Coping planning, on the other hand, could help helps develop the motivation to do so. If high in
account for the weak effect sizes found with action plan- preaction self-efficacy, individuals imagine success,
ning’s effect on PA and healthy dietary behavior, since the anticipate potential outcomes of diverse strategies,
coping plan anticipates personal challenges or barriers to and are more likely to initiate a new behavior.
completing the action plan. In this way, the patient can 2.
Maintenance or Coping Self-Efficacy: Represents
create a sense of control over unwanted concerns or dis- optimistic beliefs about one’s capability to deal with
tractions to their behavior. Also, coping planning implies barriers that arise during the maintenance period.
action planning. 31 Research in physical activity suggests 3.
Recovery Self-Efficacy: addresses the experience of
that both action and coping planning could be used to failure, lapses, and setbacks.
help individuals connect intention to behavior in the short
term; however, coping planning appears to have a larger
effect on behavior over time. 27 20.3.2.2 Review
The HAPA model (Figure 20.1), with the various self-effi-
cacy constructs, is generally able to account for additional
20.3.1.3 Practical Application variance of behavior, beyond intention. For example, in
The practitioner can help the patient develop action and adults classified as obese, self-efficacy was found to be
coping plans. From this section, the main actionable ideas the main direct and indirect predictors of both intention
are that action control and action planning are related to and physical activity.34 Preaction self-efficacy had a direct
exercise.32 A beneficial way to employ this strategy would effect on intention, and in combination with outcome
be, for example, to instruct the patient to write down how expectations, predicted 30% of the variance in inten-
they plan to exercise, where they plan to exercise, and tion. Consistent with the model, maintenance/coping self-
when they plan to exercise. Similarly, this formula could efficacy predicted coping planning, which did not predict
be followed for planning how they will prepare vegeta- physical activity behavior. However, recovery self-efficacy
bles, where they plan to obtain them, and when they plan did, and in combination with social support, accounted
to consume them (meal time). Next, they can form coping for 18% of the variation in physical activity. In other
plans to help clarify, specifically, how they will deal/cope words, approximately 82% of variation physical activity is
with upcoming problems. Doing so is clearly beneficial. If unaccounted for by this model, despite self-efficacy being
a patient likes to walk outside, ask them what they will do a leading determinant.
if it is a rainy day. If they go to a restaurant with friends, The HAPA model was also applied to patients classi-
what will they order to be the healthiest? In this vein, con- fied as overweight and obese regarding intention to eat
versations are somewhat endless; however, having a few high-fat foods and their subsequent consumption two
discussions to plan and set up some contingencies could months later. 24 Recovery self-efficacy was the main pre-
help the patient stay on their journey towards health. dictor of consumption, with contribution from planning.
Here is a sample template for use in practice.33 This overall model accounted for 46% of the variation in
high-fat food consumption, which is a more substantial
1. My Goal predictive model than we saw with the previous physical
‘To eat 2 more fruit and vegetables per day this week.’ activity example at 18%.
‘To walk 3 afternoons this week.’ Additional studies have investigated self-efficacy in
2. My Plan regard to PA and the IBG.35–38 Only two of the four have
If/When I I will shown higher self-efficacy to be related to greater inten-
‘When I have lunch at work, I will have a piece of fruit.’ tion for PA.35,36 Rhodes and colleagues30 did show that
‘When I get off work, I will walk around the block.’ self-efficacy varied across various intention–behavior pro-
3. My Backup Plan files. First, because self-efficacy is context specific, one’s
If I I will confidence in being physically active was assessed with
‘If I go out to eat for lunch, I will eat the piece of fruit before I these contexts in mind. An example assessment is shown
leave.’ in Table 20.1.
‘If it is raining or too cold outside, I will walk on the treadmill in When measured in this way, “successful maintain-
the office gym.’
ers” of PA have a mean self-efficacy of 3.68 (on the 1 to 5
scale), indicating moderate-high confidence in their abili-
ties. The “nonintenders” and the “unsuccessful adopters”
20.3.2 Self-Efficacy had low-moderate self-efficacy ratings of 2.45 and 2.54,
respectively.
20.3.2.1 Introduction Self-efficacy also has an effect on planning, which
Self-efficacy is a mixture of value and personal belief in mediates the intention–behavior relationship. For exam-
one’s ability (i.e., confidence) to achieve intended results. ple, Luszczynska and colleagues showed that a six-month
Put another way, it is a personal expectation or judgment intervention to boost self-efficacy or self-efficacy combined
246 Chapter 20 The Intention–Behavior Gap
TABLE 20.2 Common executive functions and their definitions (with citations)
Executive function Definition 20
Attentional Control 46 The ability to willfully direct one’s focus on a given topic/subject.
Response Inhibition/Inhibitory Control
47 The ability to stop dominant or prepotent responses.
Planning48 The formulation, evaluation, and selection of a sequence of actions to achieve a desired outcome.
Problem Solving49 The procedure of deriving solutions to complex issues.
Working Memory47 A limited capacity system that is responsible for manipulating and holding temporary
information, especially when new information is presented.
Cognitive Flexibility50 Ability to adapt and face new and unexpected conditions in the environment.
to actively respond to stimuli presented on the screen, and Like inhibitory control, planning and problem solving
then quickly respond (“Go” signal) or inhibit their response have proposed implications for healthy behaviors, in that
(“No-Go” signal) based on the predetermined stimuli (e.g., greater inhibitory control and/or greater capacity for plan-
lower case letter =
“Go”, uppercase letter = “No Go”). ning and problem solving should lead to a higher probabil-
Such measures “predominantly tap one facet of executive ity of follow through of health behaviors. “The ability to
function that may be particularly pertinent to behavioral plan efficiently may be especially useful in health-protective
self-regulation: the ability to suspend prepotent responses [behaviors], for example setting aside time to prepare meals,
to external cues.”51 Clinically, such suspension of cues, and making plans to exercise.”54 Norman and Conner
thoughts, or actions that have been ingrained over time reported that one’s self-reported ability to plan was posi-
could be very helpful when overriding unhealthy habits to tively associated with exercise frequency in younger and
allow for healthier choices. older men and women.55 Reuter and colleagues used a voli-
Based on results from the Go/No-Go task, participants tional planning intervention within an ongoing, employee
were classified as having either strong or weak EF (i.e., health promotion program.56 Participants were asked to
attention/inhibitory control). Those with low intention to plan by simply writing down “when, where, and how you
increase PA or FV intake did not augment behavior, regard- will eat five portions of fruit and vegetables a day,” which
less of their EF categorization. In other words, when some- led to increased FV intake one month later.
one has low intention to change, whether they have strong However, the results of planning as a moderator are
or weak attention/inhibition, there was not an increased rather ambiguous, with other investigations reporting null
consumption of FV or minutes of PA. Only those with both findings regarding PA.57,58 Luckily, the research is relatively
high intention strength and strong EF scores bridged the nascent regarding the different facets of EF as they relate to
IBG with an increase in PA and FV intake. healthy behaviors. More investigation is warranted to further
In another study, Hall and colleagues, 52 investigated clarify the relationship between some aspects of EF and cer-
the role of EF with a sample of postmenopausal women tain health behaviors. One could hypothesize that some EFs
undergoing a self-regulation enhancement intervention of are more intuitively related to certain endeavors than others.
implementation-intentions (discussed above). They found For example, the ability to pass on donuts at the office could
that higher EF capacity in areas of inhibitory control, be related to inhibitory control. Planning/problem solving
working memory, and task switching (i.e., subconscious could be related to scheduling a week with sufficient time
ability to shift attention between one task and another) to attain 150 minutes of moderate exercise. However, there
was associated with an increased ability to employ the could be overlap. Proper planning/problem solving could
self-regulatory strategy, which led to higher self-reported mitigate the desire to even eat a donut, as in the case when
PA. In corroboration of these findings, poorer inhibitory an individual eats a breakfast filled with numerous fibrous
control is associated with higher saturated fat intake, fruits and vegetables, which helps control their blood sugar,
whereas higher working memory was found to be associ- subsequently leading to an attenuated hunger response.
ated with greater FV consumption. 53
However, inhibitory control has not been consistently
associated with health behaviors. For example, Wong and 20.3.3.3 Practical Application
Mullan reported that inhibitory control was not related to For the practitioner, it is important to have a sense of a
breakfast consumption.54 Wong and Mullan did report, how- patient’s EF capacity. If a practitioner was so inclined,
ever, that abilities to plan and problem solve, as measured they could download free software that offers numerous
with the Tower of Hanoi task, moderated the IBG for those EF-related tests from http://pebl.sourceforge.net/. Many
with low intention. Thus, breakfast consumption was not of the tests only take a few minutes to administer, the soft-
shown to be due to a deficit in inhibitory control; it is instead ware is relatively user-friendly, and the results are gener-
related to an individual’s capacity to plan. However, this ally simple to interpret. However, computerized tests are
data on breakfast consumption indicates that some behav- not compulsory to assess EF capacity.
iors might be pliable through some aspects of EF rather than For example, perhaps one of the tests that is the easiest
others, even within the same category of behaviors, such as to employ is the forward/reverse digit span task. This test
healthy eating (i.e., breakfast consumption vs. increasing FV). of working memory is as simple as it sounds; the tester
248 Chapter 20 The Intention–Behavior Gap
20.3.4 Emotional Response
simply recites numbers and the tested repeats the numbers
back in either forward or backward order. Normative val- 20.3.4.1 Introduction
ues are (Table 20.3):59 Consider doing a behavior that you believe will produce
Generally, people can hold between 4–6 numbers in negative or adverse feelings. Would this anticipation affect
their mind at any given time. However, if they are abnor- your intention? Intention does not predict behavior as well
mally stressed due to some recent life event, this can lower when a strong affective component (i.e., feelings) is pres-
the value, and should not necessarily be viewed as a defi- ent.75 Theoretically, an anticipation of the feelings that a
ciency in EF. Moreover, there are a few questionnaires behavior might produce could influence one’s intention to
that can provide a quick assessment concerning where an perform that behavior. This assumption is behind “antici-
individual lies on the EF capacity spectrum, such as the pated affective reactions” (AAR) or the positive affect
Web-Ex60 and the EF index.61 More research is needed to (e.g., exhilaration) or negative affect (e.g., regret) that is
provide normative values for the practitioner across mul- anticipated to follow performance or non-performance of
tiple EFs as well as simplified and valid ways of assessing a behavior.76,77 AAR is considered an emotional dimen-
EF in practice. sion of attitude (see TPB)78 but is proposed here with a
Also, it is possible for EF to be improved. Computerized, possible role in moderating the IBG.
home-based interventions have been successful for improv-
ing EF in long-term breast cancer survivors.62 Acute exer-
cise, chronic exercise, and plant-based diets also improve 20.3.4.2 Review
EF in a host of ages.63– 66 Researchers have also found Conner and colleagues put this possibility to the test.
that prayer,67 tai chi and meditation,68 positive feelings,69 They found that when intentions to perform various
self-affirmation,70 and even a short visit with nature71 can health behaviors (e.g., eat five fruits/vegetables a day, exer-
provide acute enhancement of various aspects of EF and cise regularly, use sunscreen) were based on anticipated
self-control. Alternatively, more Westernized diets and affective reactions to those behaviors.76 “In other words,
inactivity can negatively affect EF.72–74 Since unhealth- the stronger the correlation between the feeling of regret
ful behaviors can decrease EF, there is concern for a cycle associated with performing the behavior and intention,
where unhealthy actions decrease one’s capacity to imple- the more likely that intention was to predict health behav-
ment healthy actions, which in turn can make self-regula- iors.”76 These findings corroborated an earlier review that
tion of healthy behavior more difficult. found that the anticipation of negative affect following a
The above ideas are focused on improving EF, which behavior (or not performing a behavior), such as regret,
will likely take an extended period of time. Instead of worry, tension, and anxiety, was a significant correlate
improving EF, the practitioner should consider how pre- (r+ = .43) with intention, and predictor of an additional
scriptions could be modified. Individuals with lower EF 7% of the variation in intention beyond TPB variables
might require more guidance and planning than those with (R 2∆ = .07). Regret, in particular, has similar support for
higher EF scores. If EF is a constraint, then it is imperative other health-related behaviors.79,80 Brewer and colleagues
to configure an individualized plan where EF is not a lim- have provided a clear overview of the hypothesized rela-
iting factor. For example, the practitioner could provide tionships between anticipated regret and health behavior
a patient who is weak in planning and problem solving (Table 20.4).79
TABLE 20.4 Hypothesized relationships between anticipated regret and health behavior
Anticipated regret of
Action Inaction
Discourages health behavior Encourages health behavior
Example: anticipated regret of vaccination (if it led to side Example: anticipated regret of not getting the flu vaccine (if the person
effects) discourages vaccination. later got the flu) encourages vaccination.
Discourages risk behavior Encourages risk behavior
Example: anticipated regret of smoking (if it caused cancer) Example: anticipated regret of not trying cigarettes (if it led to being
discourages smoking. shunned by friends) encourages trying cigarettes.
Abraham and Sheeran manipulated anticipated regret and afternoon relaxation time on the couch, or to eat
20
by having participants in an experimental condition more fruits/vegetables and go for a 30-minute walk (the
focus on it through answering an anticipated regret item, behaviors). There could also be variation in the intention
“Would you regret it if you did not exercise in the next responses to action/approach prescriptions (e.g., start
two weeks?”81 Participants were then asked about their exercising, eat more vegetables) versus inaction/avoidance
intention to exercise over the following two weeks. A con- prescriptions (e.g., sit less, eat less sugar).87
trol group was asked their exercise intention, then their
anticipated regret. Those in the experimental condition
had nearly double the intention (M = 6.18 on an 8-point 20.3.4.3 Practical Application
scale) than the control group (M = 3.67). In this way, antic- In summary, anticipated affective responses to performing
ipating regret, a negative feeling, had a positive effect on (or not performing) a behavior have been shown to predict
intention, when made salient before exercise intentions are intention across multiple health behaviors, including PA
considered. The authors conclude that highlighting antici- and FV. Practitioners, then, should consider assessing and
pated regret in relation to not exercising could enhance highlighting perceived regret, in particular, within their
future interventions. patient interventions. As previous authors had suggested,
Similar results could be achieved in the FV domain, as “[I]f we want to help individuals act on their intentions,
a brief, leaflet-based motivational intervention of imple- then promoting greater correspondence between inten-
mentation intentions with anticipated regret (of not meet- tions and underlying anticipated affective reactions to the
ing daily recommended intake of FV) was able to predict target behavior, may be a useful approach.”76 In support,
intention to meet the intake of FV but was not related to Brewer and colleagues conclude that anticipated regret
FV intake.82 However, Godin and colleagues found that should be a standard variable assessed in studies of health
anticipated regret was positively correlated with FV con- behaviors.79 They also offer that anticipated regret should
sumption (r = .34) and intention (r = .59) in a sample of be measured with the following guidelines:
adult men and women classified as obese.13
Although receiving little attention in the literature, 1. Specify a negative consequence of the action or
negative anticipated affect or negative affective responses inaction.
to healthy behaviors could theoretically reduce intention. 2. Assess regret of the action or inaction but not the
For example, I have heard negative anticipatory response health consequence.
with both whole food, plant-based diets (e.g., “It will 3. Examine only anticipated regret without also assess-
taste like cardboard and grass,”) and exercise (e.g., “It ing other expected negative emotions.
will hurt me,” or “It will be boring,”). Also, if I try the 4. Have separate subscales for action and inaction.
healthy meal, and I do not enjoy it, then my intention 5. Include multiple items in each subscale if possible.
might be lower to try another healthy meal in the future.
Similarly, if I respond to a bout of exercise in a negative They also provide an example item that would meet
way, then I might have less or no intention to try it again. the first three criteria: “Imagine that you had an abnor-
Such responses are very feasible, as the affective and exer- mal Pap test, but the HPV vaccine might have prevented
cise relationship has been examined for decades,83 and the it. How much would you regret that you did not get the
affective response using the single-item Feeling Scale (very HPV vaccine?”79
bad to very good)84 to a single bout of exercise in seden- It is also important to manage emotional states so that
tary adults was able to predict their physical activity level a patient will stick with a prescription. The practitioner
12 months later.85 might ask the patient about their anticipated expectan-
The exercise–affect relationship might help explain cies and feelings surrounding the lifestyle prescription.
how exercise intensity could moderate the IBG. For The prescription can then be modified to encourage posi-
example, Rebar and colleagues found that it takes more tive feelings, feelings of self-efficacy, or even anticipated
intention to follow through with vigorous-intensity physi- regret, depending on the specific behavior. Making pre-
cal activity, than with moderate-intensity or walking.86 scriptions without consideration of the anticipated feelings
This could be due to numerous reasons, one of which of the patients, for both new behaviors and past behaviors
could be the physical demands of and affective responses they are being asked to do again, could be detrimental and
from more vigorous forms of physical activity. However, ineffective in increasing intention and bridging the IBG.
for the practitioner, this distinction could be helpful. As
the authors state, “The results of this study suggest that
focusing on activities of lesser intensity may help bridge 20.4 SUMMARY
the intention–behavior gap, thereby potentially enhancing
the effectiveness of intention-enhancing physical activity A phenomenon exists where intention to perform healthy
intervention.”86 behaviors does not translate into behavior, called the
The affect–behavior relationship might also help “intention–behavior gap.” Patients are faced with a chal-
explain how patients can have high intention for the lenge of (1) building intention to initiate healthy lifestyle
outcomes of behavior, but not the behaviors required behaviors, and (2) acquiring the self-regulatory abilities
to achieve that outcome. For example, a patient might to follow through with their intention. Unfortunately,
be very willing to put forth effort to reach a weight loss left alone, most patients will succumb to the intention–
goal or drop their blood sugar (outcomes) but less will- behavior gap, frustrating themselves and the practitioners
ing to put forth effort to give up their pizza, junk food, who desire to help them succeed with lifestyle medicine
250 Chapter 20 The Intention–Behavior Gap
REFERENCES
1. Sheeran P and Webb TL. The inten- A theory of planned behavior perspec- 18. Ajzen I and Madden T. Prediction of goal-
tion–behavior gap. Social and tive. Journal of Nutrition Education and directed behavior from attitudinal and nor-
Personality Psychology Compass Behavior 2009;41(1):3–10. mative variables. Journal of Experimental
2016;10(9):503–518. 10. Blanchard CM, Kupperman J, Sparling Social Psychology 1986;22:453–474.
2. McEachan RRC, Conner M, Taylor NJ, PB, et al. Do ethnicity and gender 19. Ajzen I. Perceived behavioral con-
and Lawton RJ. Prospective prediction matter when using the theory of trol, self‐efficacy, locus of control,
of health-related behaviours with the planned behavior to understand fruit and the theory of planned behavior.
theory of planned behaviour: A meta- and vegetable consumption? Appetite Journal of Applied Social Psychology
analysis. Health Psychology Review 2009;52(1):15–20. 2002;32(4):665–683.
2011;5(2):97–144. 11. De Bruijn G-J. Understanding college 20. Rhodes R, de Bruijn G-J, and Matheson
3. Rhodes RE and de Bruijn G-J. What pre- students’ fruit consumption. Integrating DH. Habit in the physical activity
dicts intention-behavior discordance? A habit strength in the theory of planned domain: Integration with intention
review of the action control framework. behaviour. Appetite 2010;54(1):16–22. temporal stability and action control.
Exercise and Sport Sciences Reviews 12. Brug J, de Vet E, de Nooijer J, and Journal of Sport and Exercise Psychology
2013;41(4):201–207. Verplanken B. Predicting fruit consump- 2010;32(1):84–98.
4. Bere E and Klepp K-I. Correlates of tion: Cognitions, intention, and habits. 21. Carver CS and Scheier MF. On the
fruit and vegetable intake among Journal of Nutrition Education and Self-Regulation of Behavior. New York:
Norwegian schoolchildren: Parental and Behavior 2006;38(2):73–81. Cambridge University Press, 2001.
self-reports. Public Health Nutrition 13. Godin G, Amireault S, Bélanger- 22. Faries MD. Why we don’t “Just Do It”
2004;7(8):991–998. Gravel A, Vohl M-C, Pérusse L, and understanding the intention-behavior gap
5. Branscum P and Sharma M. Comparing Guillaumie L. Prediction of daily fruit in lifestyle medicine. American Journal of
the utility of the theory of planned behav- and vegetable consumption among over- Lifestyle Medicine 2016;10(5):322–329.
ior between boys and girls for predicting weight and obese individuals. Appetite 23. Faries MD and Bartholomew JB.
snack food consumption: Implications 2010;54(3):480–484. Coping with weight-related discrep-
for practice. Health Promotion Practice 14. Sjoberg S, Kim K, and Reicks M. ancies: Initial development of the
2014;15(1):134–140. Applying the theory of planned behavior WEIGHTCOPE. Women’s Health Issues
6. Ickes MJ and Sharma M. Does behavioral to fruit and vegetable consumption by 2015;25(3):267–275.
intention predict nutrition behaviors older adults. Journal of Nutrition for the 24. Schwarzer R and Luszczynska A. How
related to adolescent obesity? ICAN: Elderly 2004;23(4):35–46. to overcome health-compromising
Infant, Child, & Adolescent Nutrition 15. McDermott MS, Oliver M, Svenson A, behaviors: The health action process
2011;3(1):38–48. et al. The theory of planned behaviour approach. European Psychologist
7. Lien N, Lytle LA, and Komro KA. and discrete food choices: A systematic 2008;13(2):141–151.
Applying theory of planned behavior to review and meta-analysis. International 25. Hagger MS, Luszczynska A, de Wit
fruit and vegetable consumption of young Journal of Behavioral Nutrition and J, et al. Implementation intention
adolescents. American Journal of Health Physical Activity 2015;12(1):1–12. and planning interventions in health
Promotion 2002;16(4):189–197. 16. Rhodes RE and Yao CA. Models account- psychology: Recommendations from
8. Murnaghan DA, Blanchard CM, Rodgers ing for intention-behavior discordance the Synergy Expert Group for research
WM, et al. Predictors of physical activ- in the physical activity domain: A user’s and practice. Psychology & Health
ity, healthy eating and being smoke-free guide, content overview, and review of 2016;31(7):814–839.
in teens: A theory of planned behav- current evidence. International Journal 26. Sniehotta FF, Schwarzer R, Scholz
iour approach. Psychology and Health of Behavioral Nutrition and Physical U, and Schüz B. Action planning and
2010;25(8):925–941. Activity 2015;12(1):9. coping planning for long‐term life-
9. Blanchard CM, Fisher J, Sparling PB, 17. Ajzen I. The theory of planned behavior. style change: Theory and assessment.
et al. Understanding adherence to 5 Organizational Behavior and Human European Journal of Social Psychology
servings of fruits and vegetables per day: Decision Processes 1991;50(2):179–211. 2005;35(4):565–576.
References 251
27. Scholz U, Schüz B, Ziegelmann JP, Lippke and maintenance of breast self-examina- intention-behavior relationships. Journal
S, and Schwarzer R. Beyond behavioural tion: A longitudinal study on self-regula- of Sport and Exercise Psychology
intentions: Planning mediates between inten-
tions and physical activity. British Journal of
Health Psychology 2008;13(3):479–494. 42.
tory cognitions. Psychology and Health
2003;18(1):93–108.
Schwerdtfeger AR, Schmitz C, and Warken
56.
2005;27(4):488–504.
Reuter T, Ziegelmann JP, Wiedemann AU,
and Lippke S. Dietary planning as a media-
20
28. Bélanger-Gravel A, Godin G, and M. Using text messages to bridge the inten- tor of the intention–behavior relation: An
Amireault S. A meta-analytic review of tion-behavior gap? A pilot study on the experimental‐causal‐chain design. Applied
the effect of implementation intentions use of text message reminders to increase Psychology 2008;57(s1):194–207.
on physical activity. Health Psychology objectively assessed physical activity in 57. Brickell TA, Chatzisarantis NL, and
Review 2013;7(1):23–54. daily life. Frontiers in Psychology 2012;3. Pretty GM. Using past behaviour and
29. Adriaanse MA, Vinkers CD, De Ridder 43. Faries MD and Abreu A. Medication spontaneous implementation intentions
DT, Hox JJ, and De Wit JB. Do imple- adherence, when lifestyle is the medicine. to enhance the utility of the theory of
mentation intentions help to eat a healthy American Journal of Lifestyle Medicine planned behaviour in predicting exercise.
diet? A systematic review and meta-anal- 2017;11(5):397–403. British Journal of Health Psychology
ysis of the empirical evidence. Appetite 44. Lippke S, Wiedemann AU, Ziegelmann 2006;11(2):249–262.
2011;56(1):183–193. JP, Reuter T, and Schwarzer R. Self- 58. Rise J, Thompson M, and Verplanken
30. Vilà I, Carrero I, and Redondo R. efficacy moderates the mediation of B. Measuring implementation intentions
Reducing fat intake using implementa- intentions into behavior via plans. in the context of the theory of planned
tion intentions: A meta‐analytic review. American Journal of Health Behavior behavior. Scandinavian Journal of
British Journal of Health Psychology 2009;33(5):521–529. Psychology 2003;44(2):87–95.
2017;22(2):281–294. 45. Jurado MB and Rosselli M. The 59. Orsini A, Grossi D, Capitani E,
31. Schwarzer R. Modeling health behavior elusive nature of executive func- Laiacona M, Papagno C, and Vallar
change: How to predict and modify tions: A review of our current under- G. Verbal and spatial immediate
the adoption and maintenance of standing. Neuropsychology Review memory span: Normative data from
health behaviors. Applied Psychology 2007;17(3):213–233. 1355 adults and 1112 children. The
2008;57(1):1–29. 46. Eysenck MW, Derakshan N, Santos R, Italian Journal of Neurological Sciences
32. Godinho CA, Alvarez M-J, and Lima and Calvo MG. Anxiety and cognitive 1987;8(6):537–548.
ML. Formative research on HAPA model performance: Attentional control theory. 60. Buchanan T, Heffernan TM, Parrott
determinants for fruit and vegetable Emotion 2007;7(2):336. AC, Ling J, Rodgers J, and Scholey
intake: Target beliefs for audiences at dif- 47. Miyake A, Friedman NP, Emerson MJ, AB. A short self-report measure of
ferent stages of change. Health Education Witzki AH, Howerter A, and Wager problems with executive function
Research 2013;28(6):1014–1028. TD. The unity and diversity of execu- suitable for administration via the
33. Gardner B, Lally P, and Wardle J. tive functions and their contributions to Internet. Behavior Research Methods
Making health habitual: The psychology complex “frontal lobe” tasks: A latent 2010;42(3):709–714.
of ‘habit-formation’and general practice. variable analysis. Cognitive Psychology 61. Spinella M. Self-rated executive function:
British Journal of General Practice 2000;41(1):49–100. Development of the executive func-
2012;62(605):664–666. 48. Willcutt EG, Doyle AE, Nigg JT, Faraone tion index. International Journal of
34. Parschau L, Barz M, Richert J, Knoll SV, and Pennington BF. Validity of the Neuroscience 2005;115(5):649–667.
N, Lippke S, and Schwarzer R. Physical executive function theory of attention- 62. Kesler S, Hosseini SH, Heckler C, et al.
activity among adults with obesity: Testing deficit/hyperactivity disorder: A meta- Cognitive training for improving execu-
the health action process approach. analytic review. Biological Psychiatry tive function in chemotherapy-treated
Rehabilitation Psychology 2014;59(1):42. 2005;57(11):1336–1346. breast cancer survivors. Clinical Breast
35. Rhodes RE, Plotnikoff RC, and Courneya 49. Zelazo PD, Carter A, Reznick JS, and Cancer 2013;13(4):299–306.
KS. Predicting the physical activity inten- Frye D. Early development of executive 63. Davis CL, Tomporowski PD, McDowell
tion–behavior profiles of adopters and function: A problem-solving frame- JE, et al. Exercise improves executive
maintainers using three social cognition work. Review of General Psychology function and achievement and alters
models. Annals of Behavioral Medicine 1997;1(2):198. brain activation in overweight children:
2008;36(3):244–252. 50. Canas J, Quesada J, Antolí A, and A randomized, controlled trial. Health
36. Courneya KS and McAuley E. Cognitive Fajardo I. Cognitive flexibility and Psychology 2011;30(1):91.
mediators of the social influence- adaptability to environmental changes in 64. Peiffer R, Darby LA, Fullenkamp A, and
exercise adherence relationship: A dynamic complex problem-solving tasks. Morgan AL. Effects of acute aerobic
test of the theory of planned behav- Ergonomics 2003;46(5):482–501. exercise on executive function in older
ior. Journal of Behavioral Medicine 51. Hall PA, Fong GT, Epp LJ, and Elias women. Journal of Sports Science &
1995;18(5):499–515. LJ. Executive function moderates the Medicine 2015;14(3):574.
37. Dzewaltowski DA, Noble JM, and Shaw intention-behavior link for physical activ- 65. Valls-Pedret C, Sala-Vila A, Serra-Mir
JM. Physical activity participation: Social ity and dietary behavior. Psychology and M, et al. Mediterranean diet and age-
cognitive theory versus the theories of Health 2008;23(3):309–326. related cognitive decline: A randomized
reasoned action and planned behavior. 52. Hall PA, Zehr C, Paulitzki J, and clinical trial. JAMA Internal Medicine
Journal of Sport and Exercise Psychology Rhodes R. Implementation intentions for 2015;175(7):1094–1103.
1990;12(4):388–405. physical activity behavior in older adult 66. Weng TB, Pierce GL, Darling WG, and
38. Terry DJ and O’Leary JE. The theory of women: An examination of executive Voss MW. Differential effects of acute
planned behaviour: The effects of per- function as a moderator of treatment exercise on distinct aspects of executive
ceived behavioural control and self‐effi- effects. Annals of Behavioral Medicine function. Medicine and Science in Sports
cacy. British Journal of Social Psychology 2014;48(1):130–136. and Exercise 2015;47(7):1460–1469.
1995;34(2):199–220. 53. Allom V and Mullan B. Individual dif- 67. Friese M and Wänke M. Personal prayer
39. Luszczynska A, Tryburcy M, and ferences in executive function predict buffers self-control depletion. Journal
Schwarzer R. Improving fruit and distinct eating behaviours. Appetite of Experimental Social Psychology
vegetable consumption: A self-efficacy 2014;80:123–130. 2014;51:56–59.
intervention compared with a combined 54. Wong CL and Mullan BA. Predicting 68. Hawkes TD, Manselle W, and Woollacott
self-efficacy and planning interven- breakfast consumption: An applica- MH. Cross-sectional comparison of
tion. Health Education Research tion of the theory of planned behav- executive attention function in normally
2006;22(5):630–638. iour and the investigation of past aging long-term T’ai chi, meditation,
40. Richert J, Reuter T, Wiedemann AU, behaviour and executive function. and aerobic fitness practitioners ver-
Lippke S, Ziegelmann J, and Schwarzer British Journal of Health Psychology sus sedentary adults. The Journal of
R. Differential effects of planning and 2009;14(3):489–504. Alternative and Complementary Medicine
self-efficacy on fruit and vegetable con- 55. Norman P and Conner M. The 2014;20(3):178–184.
sumption. Appetite 2010;54(3):611–614. theory of planned behavior and 69. Fredrickson B and Branigan C.
41. Luszczynska A and Schwarzer R. exercise: Evidence for the mediating Positive emotions broaden thought-
Planning and self-efficacy in the adoption and moderating roles of planning on action repertoires: Evidence for the
252 Chapter 20 The Intention–Behavior Gap
broaden-and-build model. Cognition and 76. Conner M, McEachan R, Lawton R, intervention promoting fruit and vegetable
Emotion 2005;19(3):313–332. and Gardner P. Basis of intentions as consumption. British Journal of Social
70. Schmeichel BJ and Vohs K. Self- a moderator of the intention–health Psychology 2005;10(4):543–558.
affirmation and self-control: Affirming behavior relationship. Health Psychology 83. Ekkekakis P, Hargreaves EA, and Parfitt
core values counteracts ego depletion. 2016;35(3):219. G. Invited guest editorial: Envisioning the
Journal of Personality and Social 77. Rivis A, Sheeran P, and Armitage CJ. next fifty years of research on the exer-
Psychology 2009;96(4):770. Expanding the affective and norma- cise–affect relationship. Psychology of
71. Berman MG, Kross E, Krpan KM, tive components of the theory of Sport and Exercise 2013;14(5):751–758.
et al. Interacting with nature improves planned behavior: A meta‐analysis of 84. Rejeski WJ, Best DL, Griffith P, and
cognition and affect for individuals anticipated affect and moral norms. Kenney E. Sex-role orientation and the
with depression. Journal of Affective Journal of Applied Social Psychology responses of men to exercise stress.
Disorders 2012;140(3):300–305. 2009;39(12):2985–3019. Research Quarterly for Exercise and
72. Francis H and Stevenson R. The longer- 78. Godin G. Importance of the emo- Sport 1987;58(3):260–264.
term impacts of Western diet on human tional aspect of attitude to predict 85. Williams DM, Dunsiger S, Ciccolo JT,
cognition and the brain. Appetite intention. Psychological Reports Lewis BA, Albrecht AE, and Marcus BH.
2013;63:119–128. 1987;61(3):719–723. Acute affective response to a moderate-
73. Lipnicki DM and Gunga H-C. Physical 79. Brewer NT, DeFrank JT, and Gilkey MB. intensity exercise stimulus predicts physi-
inactivity and cognitive function- Anticipated regret and health behavior: cal activity participation 6 and 12 months
ing: Results from bed rest studies. A meta-analysis. Health Psychology later. Psychology of Sport and Exercise
European Journal of Applied Physiology 2016;35(11):1264–1275. 2008;9(3):231–245.
2009;105(1):27–35. 80. Sandberg T and Conner M. Anticipated 86. Rebar AL, Dimmock JA, Jackson B, et al.
74. Pistell PJ, Morrison CD, Gupta S, regret as an additional predictor in A systematic review of the effects of non-
et al. Cognitive impairment follow- the theory of planned behaviour: A conscious regulatory processes in physical
ing high fat diet consumption is associ- meta‐analysis. British Journal of Social activity. Health Psychology Review
ated with brain inflammation. Journal Psychology 2008;47(4):589–606. 2016;10(4):395–407.
of Neuroimmunology 2010;219(1):25–32. 81. Abraham C and Sheeran P. Deciding to 87. Albarracín D, Wilson K, Chan M-pS,
75. Godin G and Kok G. The theory of exercise: The role of anticipated regret. Durantini M, and Sanchez F. Action and
planned behavior: A review of its British Journal of Social Psychology inaction in multi-behaviour recom-
applications to health-related behaviors. 2004;9(2):269–278. mendations: A meta-analysis of lifestyle
American Journal of Health Promotion 82. Kellar I and Abraham C. Randomized interventions. Health Psychology Review
1996;11(2):87–98. controlled trial of a brief research‐based 2018;12(1):1–24.
21
CHAPTER
253
254 Chapter 21 Enhancing Physical Activity
and maintenance, including which techniques and condi- adult PA and SB. The aim of this chapter is to describe cur-
tions might be effective (e.g., 5,6), by whom (e.g.,7) and for rent PA guidelines, the influence of emerging technologies
whom (e.g.,8,9). These reviews have also helped to further on PA assessment and interventions, the dissemination of
identify key areas in need of future research.10 A large interventions by peer leaders, and recent applications of
body of specific PA intervention literature now exists both frameworks to enhance community outreach. Our pur-
for adult and child populations. The literature on cur- pose is to illustrate the intervention approaches that have
rent approaches to PA intervention in youth has grown so demonstrated efficacy in promoting exercise and PA and
much in recent years that there are now specific reviews for in reducing SB in clinical and community settings. We
this population, including evaluation of school-based PA focus on interventions that are based on scientific stud-
interventions by gender and age group (e.g.,11), systematic ies of behavior and cognition. We do not attempt to pro-
evaluations of mobile apps for PA promotion in children vide another critical review of the literature since timely
and youth that consider app quality, interactive features, reviews are already available for the interested reader.
and behavior change techniques,12 and a review of reviews
of SB interventions in youth.13 The interested reader is
referred to these reviews for intervention approaches to 21.1.1 Overview of Current Physical
PA promotion in youth. Given the distinct literatures and
breadth of recent reviews, this chapter focuses only on PA
Activity Guidelines
and SB intervention in adults. Table 21.1 provides an overview of current major organiza-
In this chapter, we will provide an overview of the tional guidelines for PA that are used in public health rec-
findings reflected in recent reviews and seminal studies of ommendations as well as PA assessment and intervention
256 Chapter 21 Enhancing Physical Activity
studies. Notably, these guidelines and position state- the Template for Intervention Description and Replication
ments (“Physical Activity Guidelines for Americans,” (TIDieR), a checklist detailing the intervention delivery
the American Heart Association, the American Diabetes approaches. 21 Also of note is the fact that studies included
Association, and the American College of Sports Medicine in the review were conducted in a diverse representation
are presented here) have evolved in recent years to reflect of countries and intervention providers were mixed, most
new evidence on the importance and health benefits of var- frequently an instructor or student interventionist. The
ied types of PA (e.g., aerobic, strength training, flexibility, most common intervention settings were at a primary care
functional fitness) and the emerging data on the health exercise facility or at other locations via mail delivery.
risks of inactivity and SB. These guidelines have some Theoretical approaches varied, with the Transtheoretical
variability, and studies of PA intervention approaches Model used the most. A wide range of contact frequency
often reflect the differences in these recommendations. and duration was observed, ranging from one print con-
tact to 33 sessions over 14 months (mean length 21 weeks).
Unfortunately, only 12 of the 26 studies reported ethnicity,
21.1.2 Overview of Effective Physical with three-quarters of those reporting a majority of White
participants.15 The most frequently reported behavior
Activity Interventions change techniques were goal-setting behavior and social
The recent development of taxonomies and coding sys- support. Immediate post-intervention PA data suggested
tems related to effective behavior change techniques have that participants randomized to intervention conditions
facilitated detailed review of intervention components14 had significantly more PA compared to control partici-
in studies of PA interventions.15 A 2011 systematic review pants, although effects were on average relatively small
of existing reviews of intervention components graded (d = 0.32 (CI 0.16 to 0.48)). Interventions that were effec-
the evidence of reported analyses for diet and PA inter- tive yielded improvements ranging from 606–1849 steps
ventions using the Scottish Intercollegiate Guidelines per day and 31–247 minutes of PA per week. Evaluation
Network (SIGN) system to take methodological quality of follow-up data indicated that participants randomized
into account.16 The PA outcomes examined were quan- to interventions continued to engage in more PA, but the
tified changes, as measured by objective means such as effect was smaller (d = 0.21 (0.12 to 0.30)), with follow-
accelerometer, by self-report, or by changes in cardiore- up improvements ranging from 421–1370 steps per day
spiratory fitness. Theoretically based cognitive-behavioral and 5–95 minutes of PA per week. Intervention effective-
techniques, specifically self-monitoring, specific goal ness for PA maintenance was associated with the presence
setting, feedback on performance, use of prompts to be of BCT Taxonomy and indicated use of action planning,
active, and individual tailoring via provision of informa- specific performance instruction, use of prompts/cues,
tion or counseling,14,17 were all found to be associated behavior practice and rehearsal, graded tasks, and self-
with greater PA intervention effectiveness. A 2011 meta- rewards.15 Only one of the studies reported intervention
analysis of PA interventions included more than 100,000 treatment fidelity; the authors accordingly highlighted this
healthy adult participants18 and examined interventions as an important need in future examinations of PA inter-
ranging from group education to supervised activity ses- vention approach effectiveness.
sions, with a variety of experimental designs in both pub- This large-scale review highlights the continuing accu-
lished and nonpublished studies. This review revealed the mulation of evidence supporting the value of basic cogni-
demographic limitations of the literature, with the vast tive-behavioral strategies in promoting PA and the benefits
majority of participants being middle aged, women, and of emerging standardized taxonomies in evaluating evi-
only rarely ethnic minority. Examination of effect sizes dence across studies with different intervention compo-
generally supported the conclusions of the previously nents. The review also highlighted the need for future
described 2011 review16 finding that theoretically based intervention studies that include evaluation of adherence
cognitive-behavioral strategies such as goal setting, con- to intervention protocols (fidelity), have adequate sample
tracting, self-monitoring, and using cues or rewards were sizes, represent diverse ethnicities and racial groups, pres-
effective in increasing PA. ent complete sets of findings, and further evaluate diverse
Another recent large-scale systematic review and theoretical frameworks and cognitive approaches.
meta-analysis used state-of-the-art methods to exam-
ine randomized controlled trials of PA and SB interven-
tions conducted with healthy, inactive adults to assess the 21.2 EMERGING TECHNOLOGIES FOR
effectiveness of intervention in the promotion of behavior
change and maintenance.19 Findings indicated that PA
PHYSICAL ACTIVITY MONITORING
interventions were effective in PA behavior change and PA AND INTERVENTIONS
maintenance at follow-up.15 Unique aspects of this review
included the distinction made between behavior change A major influence on current PA trends and research
and maintenance of behavior, consideration of both PA approaches is the rapidly expanding access to technology
and SB interventions, and use of the Behavior Change for the monitoring of activity. The widespread adoption
Technique Taxonomy (BCT Taxonomy)20 for evaluating of mobile apps and wearable devices to promote PA has
active intervention ingredients using standardized defini- led to utilization of this data in research and allowed for
tions and descriptions. Additionally, to evaluate aspects of accompanying analyses, extending our knowledge of the
the interventions such as delivery mode, treatment delivery benefits of self-monitoring on PA and offering great poten-
(and fidelity), duration, and frequency, the researchers used tial for practice and research.
21.2 Emerging Technologies for Physical Activity Monitoring and Interventions 257
21
people and greater for those with slow or impaired gaits.
Today, the traditional use of self-management techniques Whether using simple pedometers or more sophisti-
such as diary keeping has mostly given way to the con- cated wearable trackers, users typically have PA goals,
venience and potentially greater accuracy of electronic and this often includes a target for steps per day. Over the
monitors. Before the advent of the many wearable devices past decade, a goal of 10,000 steps per day was widely
currently available, pedometers (step counters) were widely publicized and promoted as representing a level of activ-
used to assess PA levels in research and clinical interven- ity likely to meet the public health guidelines of at least
tions. Pedometers are easy to use and relatively inexpen- 30 minutes of moderate-intensity activity. Two articles by
sive and the data produced can provide objective, reliable, Tudor-Locke and her colleagues29,30 provide thoughtful
and valid estimates of walking-related PA. A meta-analy- reviews of research evidence regarding the 10,000 steps
sis by Bohannon affirmed the utility of pedometer-based per day and helpful suggestions for alternative lower and
PA assessment, citing the immediate feedback for exercis- higher step count goals that may be more appropriate in
ers and readily available normative values as primary ben- certain populations.
efits. 22 The systematic review of reviews of intervention A recently published meta-analysis examined the
components described above16 noted three reviews that important question of the effects of interventions using
examined activity interventions using pedometers. It was accelerometers on PA and weight loss.6 Data from 14 clini-
noted that most of the interventions reviewed in the meta- cal trials were analyzed for PA and from eleven trials for
analyses also included goals related to steps and/or diaries weight loss; both sets of analyses showed small but sig-
in addition to pedometers, highlighting the self-monitor- nificant positive effects. The authors noted that there was
ing aspect of pedometer use and the likely importance of substantial variation among studies; qualitative findings
coupling monitoring devices with goal-setting strategies. suggested that effects were greater when the interventions
Rapid improvements in technology have contributed included stronger emphasis on using device-driven feed-
to the current availability of activity trackers that are back. The results suggested diminishing effects of accel-
much more sophisticated than the simple pedometers used erometer use over time, which would be consistent with
in early PA research and healthy activity promotion pro- other types of self-monitoring research. Another finding
grams. Activity trackers now available for research and of note was that the results did not suggest accelerometers
commercially to the public offer many advantages over produced better effects than simple pedometers; this find-
pedometers, including the ability to detect lateral and ver- ing is encouraging for interventionists concerned about
tical movement and to measure the intensity of activity using the simplest and least expensive tracking devices.
as well as accumulating data over time.6 A carefully con-
ducted study with research-quality accelerometers found
that total activity counts (TAC), as well as activity meeting 21.2.2 Computer and Web-Based
criteria for moderate and vigorous intensity PA (MVPA),
correlated significantly with more favorable levels of a Interventions
variety of cardiometabolic and endocrine biomarkers in a The last decade has seen an acceleration of studies and
sample of more than 500 women. 23 TAC was significantly intervention programs utilizing the World Wide Web to
associated with lower proinsulin c-peptide, insulin, and promote PA. Benefits of web-based interventions include
leptin and with higher levels of adiponectin, leptin-Sr, and the convenience of home-based access to materials, ano-
insulin growth factor. These relationships were attenuated nymity, and the self-paced nature of websites. A 2009
after adjusting for body mass index (BMI), indicating the report on internet-based PA interventions among adults31
relationships were partly but not entirely accounted for by found fewer than 25 studies and observed that internet-
body fat. The correlations were also attenuated but not based PA interventions had success rates similar to those
eliminated by including self-reported PA in the models. of other more established effective interventions such as
This result is what is expected if accelerometer data is a print and telephone outreach. These early studies noted
more accurate assessment of the activity that influences that web-based formats were feasible and engaging, yield-
the biomarkers. However, although commercially avail- ing positive outcomes, although some studies noted greater
able activity trackers are generally well liked by users satisfaction with some face-to-face content, 32 suggesting
despite some technical issues, 24 the accuracy of their data that this approach might benefit from supplementation.
varies among models and is significantly affected by where A 2011 Cochrane review listed web-based communica-
they are worn on the body and the gait of the user.25,26 In tion strategies for increasing PA among six primary goals
a comparison of one popular commercial tracker with a for community health interventions, and a 2015 update
research-quality tracker, Brewer27 found that active min- reiterated a need for increased progress in this outreach
utes from the two devices for one day did not agree, but approach at a global level. 33 Since that time, increasingly
over seven days the results for active minutes were com- rapid advances in technology have opened up access to
parable. Another validation study28 found strong correla- the internet and widespread adoption of mobile devices.
tions between a commercial tracker and a research-quality Pew Research Center surveys have found that technology
tracker, but the commercial trackers tended to overesti- adoption has risen dramatically since the year 2000, with
mate step counts. Health and fitness professionals who are adult internet use in the United States climbing from 12%
evaluating activity using commercially available trackers to 90%. By 2016, U.S. adult home broadband access was
should not rely on only a single day’s data; use at least one 73%.34 Of note, two-thirds of U.S. adults age 65 and over
week’s data and be aware that actual activity may be less are also online, and over half have broadband at home, 35
258 Chapter 21 Enhancing Physical Activity
making internet-based interventions feasible in this age of messages a week (6) had greater decreases in PA and
group as a whole. greater increases in sedentary time. The authors noted
Online social networks would seem to offer a unique that “more is not better,” that the frequency of messaging
vehicle for PA intervention, and Facebook has been used might have been aversive and noted that incorporation of
for recruitment and intervention in a number of recent choice, behavioral strategies, and support and evaluation
PA studies. In one study, Facebook networks were used of aspects of social cognitive theory such as self-efficacy
to recruit online groups of adults, with 110 randomized and beliefs may be important conceptual issues for future
to a 50-day online social networking PA intervention or consideration in messaging interventions. A synopsis
a wait-listed control.36 PA intervention approaches previ- and commentary on the meta-analysis of mobile phone
ously shown to be effective (self-monitoring, social inter- PA interventions39 noted the potential for use of mobile
actions, use of pedometers) were incorporated into the phones for PA promotion by providing the advantages of
active intervention. High levels of engagement with the real-time monitoring and message tailoring with goal set-
intervention, particularly self-monitoring, were observed, ting, feedback, and support, with minimal disruption on
and the Facebook intervention resulted in significant daily routines. At the same time, the synopsis and com-
increases in total weekly MVPA relative to the wait-list mentary also highlighted substantial limitations in the
control, with particular increases observed in time spent data to date with respect to the designs, objectivity in out-
walking. However, these gains were not maintained at come measures, lack of theoretical underpinnings related
follow-up. Facebook was also used as a social network to using the technology for motivational intervention
tool for a walking intervention in a sample of female col- beyond as an assessment tool, understanding of media-
lege freshmen. 37 Sixty-three participants were randomly tors and moderators of PA change, and consideration of
assigned to a standard 8-week walking intervention or the potential dynamic potential of the mobile technol-
8-week Facebook support group intervention. Both groups ogy.41 An additional review of 11 PA studies based on
had weekly step goals and self-monitored daily steps using mobile devices also highlighted both the potential benefits
pedometers; the Facebook was also instructed to post on of these portable devices for intervention and the current
their daily steps and offer feedback to the group. Both limitations in methodologies used and called for improve-
groups increased steps, with the Facebook group showing ments in methodologies and in their use for PA promo-
greater increases, walking approximately 1.5 miles/day tion.42 Advances in this arena may be made via the use
more than those in the standard condition. These studies of mobile devices for Ecological Momentary Assessment
suggest that the online and social aspects of social media (EMA) research in PA.43 In EMA, smartphone technol-
PA interventions in tandem with known tools of self-mon- ogy may be used to assess real-time self-reports of PA and
itoring and goal setting can be engaging and effective for contextual information such as setting, emotions, per-
at least short-term increases in activity. ceptions, and attitudes. It may also be used to evaluate
the complex nature of and fluctuations in PA using novel
frameworks and statistical approaches.43 This can greatly
21.2.3 Mobile Phones and Devices aid efforts to develop new and effective interventions to
The widespread adoption of mobile phones and smart- promote PA adoption and maintenance.
phones (now used by over 77% of U.S. adults34) has The increased uptake of smartphone technology has
further enhanced PA intervention opportunities across led to the development of numerous apps for fitness pro-
the age spectrum. The use of smartphones by older U.S. motion. A 2015 review44 identified 100 top-ranked apps
adults nearly quadrupled between 2011 and 2016. 35 These for PA (25 paid and 25 free from iTunes and Google
ready access technologies have the advantage of portabil- Play marketplaces) and evaluated their content for use of
ity and minimizing time demands when used as tools for behavior change techniques using a comprehensive tax-
PA intervention. onomy of Behavior Change Techniques. 20 The taxonomy
Mobile phone messaging has been used for interven- reflects 93 possible techniques; 39 were coded across the
tions across a variety of preventive behaviors. 38 By 2012, 100 PA apps. The mean number of behavior-change strat-
a meta-analysis had been conducted to examine the egies was 6.6 (median 6), with no differences in number
use of mobile devices to increase PA. 39 Short messaging between paid and free apps. The most common behavior
(SMS) or personal digital assistants (PDA) were used in changes techniques represented were social support via
11 studies that reflected a wide time duration (2 weeks online communities (e.g., Facebook, Twitter), informa-
to 1 year) and overall resulted in a moderate beneficial tion on others’ approval, instructions on how to perform
effect on PA as assessed by outcomes such as pedometer the behavior and feedback on the behavior. Perhaps as a
steps and estimated caloric expenditure. A recent large result of apps using sensors for embedded accelerometers,
randomized control trial offering free text messaging to self-monitoring was relatively rare. The authors noted the
deliver health-related information to pregnant women importance of self-monitoring in PA intervention effec-
(Txt4baby) included an evaluation of the effectiveness and tiveness in other channels and suggested that this may be
optimal dose and timing of PA promotion messaging.40 an important addition to support behavior change.
Inactive pregnant women were randomly assigned to one The availability of wearable devices that interact with
of four groups differing in dose and timing of messag- smartphone apps has also greatly impacted the access
ing, and PA was measured using Fitbits. Unexpectedly, no to PA promotion technologies. A 2017 study of per-
increases in PA were observed, regardless of frequency or sonal experience using wearable activity trackers (e.g.,
time, and participants who received the highest number Fitbit, Garmin) noted that participants found them to
21.3 Expanding the Targets of Activity Promotion: Assessing and Targeting SB 259
be appealing and useful and that they valued real-time 21.3 EXPANDING THE TARGETS
21
feedback in particular. 24 Most reported experiencing
some difficulties in function such as technical problems OF ACTIVITY PROMOTION:
or battery life. Information on each of these apps will be
helpful, as recent reports suggest that individuals who ASSESSING AND TARGETING SB
have greater intentions to improve PA levels and those
Sedentary behavior (SB) defined by the Sedentary
who are already meeting PA guidelines are more likely
Behaviour Research Network as “any waking behavior
to have downloaded health apps than those who are not
characterized by an energy expenditure ≤1.5 metabolic
yet at this degree of change.45 A study of interest in and
equivalents while in a sitting or reclining posture.”4 is now
perceived value of PA intervention apps in a rural popu-
an area of intense interest for researchers and growing
lation also found that insufficiently active individuals
concern for practice, based on a rapidly growing evidence
were the least accepting of behavior change apps.46 The
base on the health risks of inactivity. 2 These advances
next few years will likely yield useful information on the
have led to the development of a network of SB research-
adoption and long-term use patterns of these wearable
ers, stakeholders, 3 and consensus statements on terminol-
technologies and their influence on PA maintenance of
ogy and methodology.4
PA over time.
A review of current evidence on the relationship
The studies available to date indicate that technology
between SB and cardiovascular outcomes by the American
ranging from computer/internet to messaging to mobile
Heart Association Science Advisory Group47 concluded
phone apps can be successfully integrated into PA interven-
that the evidence indicates that time spent in SB is associ-
tion efforts but may be best used with established behav-
ated with cardiovascular and all-cause mortality, and a
ioral approaches. The advent of integrative technological
growing body of prospective studies also points to asso-
approaches does not negate the relevance of more tradi-
ciations between SB and risk of developing type 2 diabe-
tional phone- and print-based methodologies to increase
tes.47 Accumulating evidence suggests that SB is distinct
PA. Within the past decade, these modalities have been
from a lack of MVPA, and studies increasingly exam-
just as prominent, if not more so, than their often more
ine MVPA, inactivity, and SB separately.47 Data from
expensive counterparts. While these technologies are not
the National Health and Nutrition Examination Survey
new, the communication they enable continues to be opti-
(NHANES) indicate that time spent in sedentary activities
mized to facilitate the dissemination of PA interventions.
may be equivalent in individuals who expend more energy
Both print and a range of technological resources that
in MVPA and those who have lower MVPA levels.48 At
have already been developed for PA promotion are now
this time, little is known about the potential biological
available for health provider and community access (see
mechanisms of action of the associations between SB and
Tables 21.2 and 21.3).
TABLE 21.2 Health Provider and Community Resources for Enhancing Physical Activity Participation
Topic Resource Access Information
Prescribing PA Exercise Is Medicine Campaign. Provides evidence information, clinical http://exerciseismedicine.org
and community resources, networking information, and other excellent https://www.exerciseismed
resources, including a detailed guide for providers, office posters and icine.org/support_page.php/
handouts, and an exercise vital sign questionnaire. healthcare-providers/
General Health Information NIH: Health Information. This website provides practical health news and http://health.nih.gov
tips based on National Institutes of Health research. A link to fitness
resources and campaigns is provided.
Health news and NHLBI: Education and Awareness. This website provides practical health http://www.nhlbi.nih.gov/
educational information news and education based on National Health, Lung, and Blood Institute health/educational
research.
Evidence-based health CDC: Healthy Living. This website provides health news and tips based on http://www.cdc.gov/
news and tips Centers for Disease Control and Prevention data and research. The PA site HealthyLiving
has links to guideline summaries for success stories from children, adults,
older adults, and pregnant or postpartum women. https://www.cdc.gov/physi
calactivity/basics/index.htm
Interactive website with Go4Life. From the National Institute on Aging (NIA) at NIH. This interactive https://go4life.nia.nih.gov/
educational information and website is designed to help older adults fit exercise and PA into daily life. https://go4life.nia.nih.gov/
activity promotion Addresses endurance, strength, balance, and flexibility. Provides PA get-started
approaches for older adults. videos, access to online goal setting, record keeping, progress tracker, https://go4life.nia.nih.gov/
coaching tips, and optional access to text/e-mail/twitter coaching and mygo4life
motivational tips.
Print materials with This print guide is the centerpiece of Go4Life, NIA’s national campaign. It https://go4life.nia.nih.gov/ex
educational information and is available in English and Spanish. Includes photos, detailed exercise ercise-guide
activity promotion instructions, worksheets to track progress, and tips. Downloadable as pdf.
approaches for older adults.
260 Chapter 21 Enhancing Physical Activity
TABLE 21.3 Physical Activity Prescription Template from Exercise Is Medicine® Campaign
morbidity and mortality, and pathophysiological changes sedentary time. A 2017 systematic review of non-worksite
that occur across the continuum of highly sedentary to interventions to reduce SB (targeting sitting time and/or
highly physically active states.47 breaks in prolonged inactivity)52 found that a combination
Examples of SBs often examined in the research lit- of self-monitoring and technological feedback may be use-
erature include screen time (e.g., computer use, televi- ful SB reduction strategies.
sion viewing), video games, time spent in transportation, The majority of interventions for SBs in adults have
and reading;47 SB measurement has yet to catch up to targeted the workplace. A meta-analysis51 in 2014 found
the rapid growth in the use of tablet and mobile devices successful reductions in both self-reported and objectively
with screens.49,50 The SBRN has identified 13 self-report measured workplace SB, with an average difference of
measures of SB which have been used in assessment and 91 minutes per day spent in sedentary activities between
interventions studies. 3 Objective measures such as accel- intervention and control groups.47 This review also con-
erometers and inclinometers have also been used to assess cluded that interventions focused solely on reducing sed-
SB outcomes and may capture time spent engaging in and entary time were more effective than interventions that
patterns of SB.47 Both self-report and objective measures included SB intervention as part of broader PA change
have strengths and limitations, and use of both may pro- targets. 51
vide the most complete picture of SB.47 Installations of active workstations such as sit-to-stand
Some intervention studies have attempted to focus desks, treadmills, and portable pedal machines have been
both on decreasing SB as well as increasing PA. Overall, evaluated in a wide range of settings; a recent meta-analy-
those focused specifically on SB seem to have been more sis found that 14 of 15 studies reported significant changes
successful reducing SB relative to those that have included in SBs. 53 Point-of-choice prompting technology to take
both foci.51 Studies also differ in whether the intervention standing breaks or get up and move (via prompting wrist-
aimed to reduce time spent in sedentary activities or tar- watches or computer prompting software installed onto
geted breaking up periods of sedentary time, such as by desktops) were also reported. 53 Most of the interventions
providing prompts to stand up and move after periods of were shorter than 90 days in duration, so the maintenance
21.4 Physical Activity Interventions in Racial /Ethnic Underserved Samples 261
of reductions in SBs in the workplace over time is unclear. to increase activity and fitness in African Americans. 57
21
The degree to which roles of employer or coworker sup- The majority of studies were conducted with women.
port or internal versus external factors influenced behav- Interventions included community-based approaches such
ior change in these worksite settings is unclear and these as delivering the intervention in community settings such
are important areas for further exploration since social as the YMCA, community centers, church, worksites,
support and monitoring have independently been shown and public housing projects. Cultural adaptations were
to influence PA. included in many of these studies. For example, several
Gardner and colleagues reviewed behavior change PA interventions with African American participants
strategies used in published SB reduction interventions were conducted in a church setting and included activity
with adults. 54 Twenty-six studies and 38 interventions instructors from the African American community, gospel
(53% worksite-based) were coded for use of discrete or “soul” music, and incorporated prayer. Hip-hop danc-
behavior change techniques in the interventions, using a ing was also represented. The culturally adaptive meth-
Behavior Change Coding Taxonomy. 55 The most com- ods of intervention were frequently paired with familiar
monly used behavior change techniques were goal setting, behavior change approaches, including monitoring, use
provision of social support, adding objects to the envi- of pedometers, peer phone contacts, supervised exercise
ronment, and action planning. Intervention approaches sessions, and social support via group walks in the local
were categorized very promising, quite promising, or non- neighborhood. The multiple approaches and study design
promising, according to the level of SB changes observed. limitations made it difficult to evaluate the specific influ-
Very or quite promising interventions were more likely ences of these culturally tailored approaches. However,
to directly target SB, rather than PA. The greatest degree examination of findings from individual studies showing
of behavior change was noted for approaches that used significant group differences led the authors to look for
environmental restructuring education or persuasion trends associated with “best practices.” Common factors
techniques. Particularly promising approaches were self- associated with the effectiveness of individual studies of
monitoring, problem solving, and changes to the social PA interventions in African Americans were use of ran-
or physical environment. 54 These findings are consistent domized controlled trial design, assessing PA using an
with reviews of the approaches to worksite environment objective measure, providing specific PA goals to partici-
modification approaches and behavioral self-monitoring pants, and including structured activity programs. These
approaches to PA. trends are consistent with other general reviews of activity
Recommendations for PA interventions and research have intervention studies.
increasingly incorporated SB as a target of behavior change, Promotion of PA in racial and ethnic minority popu-
and some major health organizations have also included lations has also successfully incorporated cultural values
inactivity in their position statements (see Table 21.1). and models by employing ethnically matched health edu-
However, much additional research is needed in this area. cators and interventionists. 56 Community-based outreach
At this time, it is not clear whether changes in SB will and bridging neighborhood and community approaches
lead to changes in other outcomes. Future studies with with the use of community health workers who are from
improved methodologies are necessary to further under- the target population have also been successful; these
standing of the thresholds for SB that influence health. promatoras have been widely used in culturally sensi-
Controlled intervention studies are needed to evaluate tive health interventions in U.S. Latina PA promotion
optimal approaches to reducing SB within certain contexts efforts. 56,58 Carefully controlled intervention studies are
and across the day and the degree to which reductions needed to more thoroughly examine the specific influences
in SB might impact well-being, biomarkers, and related of culturally adapted PA intervention approaches.
risk factors as well as health status, morbidity, and Studies also have shown that technology-based PA
mortality. interventions and different kinds of settings may be help-
ful in the delivery of PA interventions with low-income
minority populations, but care must be taken to under-
21.4 PHYSICAL ACTIVITY stand which approaches might provide the best reach and
INTERVENTIONS IN RACIAL / acceptability. In some demographic groups, omnipres-
ent internet access and mobile phone usage makes these
ETHNIC UNDERSERVED SAMPLES modes of intervention delivery ideal, but technology adop-
tion gaps remain for many lower-income groups. Pew
Reviews of both PA and SB interventions continue to high- Research data from 2016 showed that one-fifth of adults
light the need for additional studies that include racial and living in low-income households used only a smartphone
ethnic minority and underserved samples. While lower for internet access (including for tasks typically meant for
levels of MVPA are often observed in low SES popula- larger screens) because they did not have other types of
tions and in individuals from minority racial/ethnic back- internet access at home.34
grounds, these groups are still underrepresented in PA A six-month, culturally adapted, individually tailored,
interventions and evaluations due to inadequate planning internet-based PA intervention with sedentary, Spanish-
and conceptualization of recruitment approaches, barri- speaking U.S. Latinas was successful in increasing MVPA
ers to engagement and intervention response, and limited and achievement of national guidelines for PA. 59 Increased
interventions that have been specifically developed for MVPA was maintained at a six-month follow-up, 12
minorities or culturally adapted. 56 Whitt-Glover and col- months following the baseline.60 Acculturation and health
leagues conducted a systematic review of interventions literacy were not significant moderators of the impact of
262 Chapter 21 Enhancing Physical Activity
the intervention,60 highlighting the range of participants initiatives with the aim of producing long-lasting benefits
benefiting from this web-based intervention approach. for the community. They also operated at a series of lev-
A 2014 study of an e-health intervention aimed at pre- els to attempt to influence activity, such as environmen-
venting weight gain in a sample of low-income African tal changes, policy changes, and use of the media. Some
American women in a primary care setting used tele- studies found significant increases in the use of community
phone-based interactive voice technology (IVT) for self- resources such as trails and pathways, indicating that pro-
monitoring behavior change goals, including walking grams reached some segments of the targeted population
10,000 steps/day.61 This monitoring technology entailed but the effects did not translate to changes in the popula-
listening to a voice prompt and responding with a simple tion levels of PA. The review also provides a description
numerical answer and had the advantage of brief dura- of community-level strategies for outreach to many types
tion, low cognitive demand, and dynamic and immediate of disadvantaged groups. Many of the studies included
feedback messages, without the need for internet connec- some form of individual behavior change counseling by
tivity.61 Participants’ engagement in calls and adherence a health professional and delivery of content via social
to weekly IVR monitoring was high and associated with marketing via local mass media or other communication
positive study outcomes. outreach (posters, flyers, information booklets, websites,
The potential reach of home-based resources and maps) to raise awareness of the intervention program and
community-centered approaches to further impact public provide specific information. Many studies were conducted
health across a wide range of individuals, including those in specific settings that may have facilitated contact with
from disadvantaged groups, has led to efforts to translate individuals who have social disadvantages such as lack
what is known about effective components of and delivery of transportation and might otherwise be missed by tra-
approaches of PA interventions into accessible, commu- ditional outreach, for example, schools, senior centers,
nity settings and dissemination formats. Strategies that workplaces, community centers, homeless shelters, and
appear to be effective for PA promotion in underserved shopping malls. Environmental change strategies such as
populations include those that are delivered through creation of walking trails and partnering with legislative
home, church, or community-based channels, utilize tech- and fiscal leaders to promote planning for outreach to the
nologies appropriate to the population, include cultural broader population were also undertaken.
adaptations, incorporate staff or peer interventionists The Cochrane review33 also provides a useful overview
who reflect the community, and take advantage of oppor- of the types of recent community approaches and high-
tunities for environmental interventions. 56 lights the challenges inherent in attempting to identify key
components of effective community-based PA interven-
tions that broadly impact population level PA. The con-
21.5 COMMUNITY-WIDE PA clusions noted that many authors of the studies included
in the review identified reasons for lack of efficacy as due
INTERVENTIONS to being unable to penetrate the community, a relatively
short intervention duration, limited methodologies, and
As described in the sections above, print, telephone, inter- limited resources. Considering the recognized need for
net, mobile device, and peer delivery modalities all offer studies of adult PA promotion representing diverse popu-
opportunities for reaching a wide variety of individuals lation groups, these types of community-wide intervention
who may benefit from dissemination of these supported approaches offer tremendous potential to promote activ-
intervention approaches. A 2015 Cochrane review exam- ity, especially if advances in PA assessment methodologies
ined community-wide interventions aimed at increasing and in technology use for outreach allow researchers to
PA to evaluate their influence on population-level health.33 improve upon study designs and recruitment. More well-
Studies focused on community-wide interventions, with controlled evaluations of these approaches are needed and
at least six months of follow-up and at least two broad offer challenges for future community-wide PA interven-
PA intervention strategies aimed at the whole population. tion evaluations.
Thirty-three studies met criteria for review and represented
267 communities—25 conducted in high-income countries
and eight in low-income countries. The authors concluded 21.6 ENVIRONMENTAL FACTORS IN PA
that methodological issues precluded reaching clear con-
clusions regarding the effectiveness of community inter- An additional approach to addressing the needs of the
ventions, but the methodological review offers instructive broader community when developing PA interventions is
information about the types of community interventions to consider the role of the built environment and neigh-
that have been conducted and suggestions for future inter- borhood. The last decade has produced a body of studies
vention programs and research. A major concern identi- documenting that the physical environment and neighbor-
fied in the community-wide PA intervention literature hood factors play an influential role in PA.62,63 Reviews
was selection bias, particularly limited use of community have found that neighborhoods that are characterized
comparisons and randomization, and the quality and as walkable (those with mixed land use such as having
validity of assessments used to measure outcomes. Despite homes, schools, workplaces, and areas to shop accessible)
these limitations, it is encouraging to see that the major- can encourage walking to multiple destinations.62 King
ity of interventions included establishing partnerships and colleagues evaluated both social and built environ-
with local government or non-government local organiza- ment influences in the context of PA interventions across
tions. Community strategies generally involved planning five intervention trials.64 Features of the built environment
21.7 Maximizing Real-World Translation—Effective PA Intervention Dissemination 263
were assessed with a Neighborhood Walkability Scale. One aspect of the built environment that has been
21
Activity guidelines were more likely to be met by par- studied for the potential for low-cost PA intervention is
ticipants living in neighborhoods with more attractive the use of stairs in community and workplace settings.
scenery, ease of walking, and good traffic safety. These The presence of stairs across a variety of settings has
factors were related both to facilitating and impeding offered researchers the opportunity to assess the viability
activity. The role of environment and neighborhood on of using simple prompts to promote PA in public settings.
PA may be a particularly important consideration when A European intervention study, Romsas in Motion, used
developing individual or group interventions for low- theoretically developed, comprehensive approaches to
income or underserved populations and minority racial/ addressing individuals, groups, and the environment with
ethnic groups.65 A multilevel promatora-led intervention tailored strategies accounting for readiness for change in
aimed at promoting PA in a sample of 319 Latina women PA in a low-income, ethnically diverse population.67 PA
recruited from 16 churches examined the influence of levels increased, particularly in those with greatest needs,
neighborhood environment variables on intervention and simple exposure to low-cost poster prompts to use
effectiveness.66 Participants’ perception of their neighbor- stairs and walk an available path was highly effective.
hood aesthetics moderated intervention effects on both A recent systematic review of 50 eligible studies examined
self-reported leisure time PA and accelerometer-derived the effectiveness of stair-use interventions68 and found
moderate-to-vigorous activity, with those reporting more that they increased PA in 64% of worksite and 75% of
favorable aesthetics benefiting more. The authors of this public settings. Combining directional and motivational
study noted that less satisfying neighborhood aesthetics signs in worksite settings increased stair climbing by
could be associated with greater poverty and disorder and 83% and conducting a second phase in public settings
could hinder motivation for PA in this context. increased stair climbing 86%. A quasi-experimental study
Other studies have found that PA interventions were comparing use of general and specific stair messages to
more likely to help those who perceived more environmen- promote PA found that specific messages were more effec-
tal barriers to increasing their activity. In an examination tive.69 Future evaluations of this cost-effective approach in
of two randomized activity trials conducted with similar tandem with other known influences on PA may further
methodologies and recruitment, Kerr et al. explored the assist efforts to increase PA adoption and maintenance
interactions between changes in walking over time, life- across community settings using low-cost and practical
style PA intervention conditions, and the walkability of approaches.
participants’ neighborhoods.62 Examination of the inter-
actions between the built environment and interventions
revealed that men who resided in less-walkable neighbor- 21.7 MAXIMIZING REAL-WORLD
hoods (as assessed with a walkability index) who were in
the intervention group significantly increased their walk- TRANSLATION—EFFECTIVE PA
ing time, while men who resided in high-walkable neigh- INTERVENTION DISSEMINATION
borhoods decreased their walking over the course of the
study. Men in the control condition did not increase their The findings of the past decade have reinforced previous
walking time. For women, results showed similar trends, research on the efficacy of behavioral and cognitive inter-
with women living in low-walkable neighborhoods who ventions to promote PA, but the limitations in the study
were in the intervention group increasing their walking designs and results highlight the need for outreach to
the most, although results did not reach statistical signifi- diverse individuals and settings as well as the complexity
cance. Women who perceived an unsafe volume or speed of PA intervention efforts in a community context. A use-
of traffic had decreased walking time (22-minute daily ful framework has been developed to enhance the impact
decrease), while women who perceived that the traffic in of health interventions by addressing issues of real-world
their neighborhood was safer had increased walking time implementation of evidence-based approaches to be sure
(increased by 17 minutes) over the course of the study. that they actually reach diverse and underserved popula-
Findings of this study suggest a possible ceiling effect of tions and varied settings and are adopted and maintained
living in a highly walkable neighborhood. over time. The RE-AIM framework (Reach, Effectiveness,
These mixed findings on interactions between built and Adoption, Implementation, Maintenance)70 proposes five
neighborhood environment highlight the need for addi- steps for translating what is known from research studies
tional research to understand these results. Differences in into actual intervention action in the real world.70 –72
use of self-reported perceptions of neighborhood factors,
structured environmental space ratings, and noted gen- 1. Reach the target population: Interventions reach
der differences in interactions between built environment large groups of individuals in need, including those
issues and activity outcomes are intriguing and suggest from characteristically underserved or hard-to-
that personal appraisals of the neighborhood environ- reach settings.
ment are important to consider. Men and women may 2. Effective impact of the intervention (also referred to
have different perceptions of and responses to changes as efficacy of the intervention): Interventions make
at the built-environment level. The authors observed that an impact on important outcomes and consider
one encouraging implication of the study findings is that positive and negative influences, unanticipated out-
the pattern of results shows that behavior change inter- comes, quality of life, and even economic outcomes.
ventions can encourage walking even in less supportive 3. Adoption of the intervention approach in the real-
environments. world setting: Interventions are adopted by different
264 Chapter 21 Enhancing Physical Activity
settings and the number, proportion, and represen- greater benefits. These new USPSTF recommendations
tativeness of the settings and people who deliver the are consistent with much stronger recommendations
program are representative of those who would ben- by PA experts, including an initiative called Exercise is
efit from it. Medicine ® (EIM), first announced in the United States in
4. Implementation of the intervention is consistent: 2007 by the American College of Sports Medicine and
The intervention protocol is consistently delivered the American Medical Association and now spreading
as intended in the real-world setting. throughout the world.75
5. Maintenance of the intervention at the setting and Proponents of the EIM initiative observe that there
individual levels so that it is delivered and results are a lot of reasons why health care providers should be
in benefits over the long term: The intervention as concerned about low levels of PA as they are about
becomes sustainable and a part of the routine within smoking and obesity in their patients. If the standard of
the programs or organizations delivering it, and the care calls for provider counseling regarding smoking and
health-related behaviors and benefits are maintained obesity, they argue, providers should also be assessing PA
(and when appropriate, policies are maintained). levels in their patients and offering counseling to those
who do not meet the current public health guidelines of
The RE-AIM framework was used in an umbrella at least 150 minutes of moderate intensity PA per week.
review that considered implementation conditions for PA However, barriers currently exist both for providers who
interventions and policies (diet was also considered). 5 This would like to counsel all their patients about exercise and
systematic review considered both reviews and stakeholder for the patients who could benefit from changing their PA
(such as the World Health Organization) documents and behaviors. Recognizing the need to inform providers and
identified the evidence-based conditions that emerged as patients and help them overcome these barriers, experts
key for successful implementation of PA interventions. have developed a variety of high-quality suggestions
Ninety-five documents from scientific databases and 17 and resources for promoting increased activity. These
stakeholder documents met inclusion criteria. The review resources are now available not only as thoughtful reviews
identified 312 potential conditions for successful PA inter- in professional journals but also as engaging informa-
vention implementation, with 83 receiving empirical sup- tion pages and downloadable brochures and handouts
port. The RE-AIM criteria were used to categorize these on government and professional organization sponsored
conditions: 5 addressed efficacy of implementation pro- websites. We include a sample of expert suggestions for
cesses; 24 related to adoption by the staff, setting, or insti- health care provider PA counseling below but encourage
tutions; 43 were associated with costs, adaptions made, interested readers to explore the wider variety of excellent
and consistency in the implementation; and 3 were con- resources available.
cerned with maintenance over time. The identified condi- Articles by AuYoung76 and Shuval77 present models
tions are provided in a table in the research publication, for PA counseling by primary care providers based on the
which may be helpful in the development of interventions “5 A’s”, which include (1) having office staff assess PA of
and policies and in education provided for community patients in the waiting room, (2) giving advice to patients
stakeholders. on the amount, type, and intensity of recommended PA,
One more important arena for disseminating effective (3) having the patient and provider agree on a goal and
PA intervention approaches is in community-based clini- action plan; (4) assist the patient to identify potential
cal settings. This offers opportunities for reaching a range barriers to success of their plan and solutions to those
of populations and monitoring the adoption and mainte- problems, and (5) being prepared to arrange referrals to
nance of behavior change. community resources, including appropriately certified
fitness professionals. Both articles provide specific exam-
ples of exactly what to say to patients and how to work
21.7.1 Dissemination of Effective with them around common barriers to action.
Physical Activity Interventions As a spokesman for EIM, Sallis75 describes the ratio-
through Counseling for Preventive nale for this initiative and gives detailed suggestions for
effective health care provider actions to help their patients
Care in Clinical Settings achieve recommended PA goals. Sallis75 suggests consid-
Along with an updated scientific evidence report, the ering all patients as athletes and examining them with the
U.S. Preventive Services Task Force (USPSTF) published goal of clearing them for engaging in healthy PA or return-
in 2017 an updated recommendation statement regarding ing to regular activity if they are currently ill or injured.
healthy lifestyle counseling for adults without obesity or EIM resources include recommendations to help provid-
cardiovascular disease (CVD) risk factors.73,74 Preventive ers screen patients with chronic conditions for safe levels
lifestyle counseling covered in this review included of PA. To begin the counseling process, providers should
increased PA, decreased sedentary time, and improved use an “exercise vital sign” (EVS), which consists of two
diet, or any combination of these topics. The USPSTF questions: (1) “How many days per week do you engage
concluded behavioral counseling in primary care set- in moderate-to-vigorous activity like a brisk walk?” and
tings for prevention of CVD does have positive effects. (2) “On those days, how many minutes do you engage
The stringent evidence review indicated that, although in PA at that level?” The EVS can be administered by
the overall benefit was small, there was a dose–response clinic staff and/or self-administered by patients as they
effect, with greater counseling intensity resulting in wait for their appointment. Multiplying the number of
Clinical Applications 265
days of activity by the number of minutes per day yields PA are a continuing source of inspiration to researchers,
21
the total minutes per week. If the provider has only a min- health care providers, and others committed to finding
ute or less for counseling on PA, and the patient’s total more effective ways of encouraging all people to be physi-
activity is at 150 minutes or greater, simply praise them cally active and healthy. Health providers may employ
for this accomplishment and urge them to continue. If effective PA counseling techniques in clinical settings and
the total is less than 150 minutes, tell them you advise take advantage of free materials based on empirical evi-
them to increase their PA and link this advice to their cur- dence (see Tables 21.2 and 21.3). Health organizations
rent lab results, blood pressure, or other findings. Take a have updated PA recommendations to reflect advances in
few more seconds to suggest aids such as a fitness tracker, research (see Table 21.1).
getting involved in a community exercise facility, or pos- The advances and limitations highlighted in this
sibly working with a fitness professional. When providers review of behavioral and cognitive interventions for pro-
have five minutes or more to devote to counseling, they moting PA suggest some of the directions for future work.
can take the time to assess patients’ readiness for change In particular, we expect to see more studies that translate
and problem-solve with them to build on their reasons findings of efficacious interventions into a wide variety of
for increasing activity and to overcome specific barriers. settings and populations. New technologies are likely to
Templates for developing a written PA prescription for make monitoring of the spectrum of activity, from com-
patients may be downloaded from the EIM website (see plete rest to the most vigorous exertion, more accurate and
Table 21.3). less expensive. Telecommunications, internet, and mobile
communications will continue to provide new opportuni-
ties to connect people to PA promotion interventions, and
21.8 CONCLUSION we need to learn how to effectively and efficiently com-
bine the technology with the personal contacts that many
Early studies aimed at understanding the utility of cogni- people still desire. Genetic studies may help us understand
tive and behavioral approaches to enhancing exercise par- why some people enjoy and get more benefit from PA than
ticipation have been extended by exciting developments in others, and may point the way toward biological as well as
research approaches. Advances in behavioral science tax- behavioral and cultural tailoring of interventions to indi-
onomies for evaluating specific behavior change techniques viduals. There will also be unexpected challenges, but the
used in interventions have led to greater ability to evaluate scientific and creative advances of the past decade suggest
effective mechanisms of action in PA interventions. Self- that there will be exciting new progress to report in future
monitoring, social support, goal-setting, and feedback years.
with individual tailoring of content appear to be effective
techniques across PA intervention studies. Technology has
greatly enhanced the methods available for PA monitor- CLINICAL APPLICATIONS
ing and communications between interventionists and
program participants. The use of written diaries and logs • The use of established behavioral approaches such
is now often accompanied by accelerometers, step coun- as self-monitoring, goal-setting and feedback, and
ters, and a variety of wearable activity monitors. Activity individual tailoring of content and social support
program participants may access interventions through appears to enhance PA interventions and should be
peers, the internet, mobile phones, and various types of incorporated when promoting PA change.
structured telephone contact approaches in addition to— • PA may be evaluated and promoted with widely
or instead of—face-to-face contacts and printed materials. available technology such as websites, structured
Efforts to improve intervention approaches to encourage telephone contacts, social media, mobile apps, and
adoption of exercise are now more strongly enhanced by a wearable activity trackers. These may also be used
renewed emphasis on the importance of interventions that to promote communication between intervention-
promote maintenance of activity once it has been estab- ists and program participants and can be used in
lished. Recent advances in ecological momentary analysis addition to or instead of face-to-face contacts and
have allowed for longitudinal examination of the useful- printed materials.
ness of specific aspects of theoretically based intervention • SB poses health risks independent of MVPA and is
approaches, aiding in efforts to longitudinally examine a useful target for intervention. Approaches specifi-
the process of activity maintenance, cognitions and affect, cally targeting SB, rather than simply including SB
and relationships to intervention components. Recent as a component of broader PA interventions, may be
intervention studies have also addressed not only activity most successful in reducing SB.
per se but changes in the SBs that are encouraged, if not • Home-based and community settings can provide
enforced, by our modern lifestyles. greater reach to at-risk and underserved populations
Technological changes continue to introduce new ways and help to translate evidence-based intervention
of replacing active living with SB and suppress opportuni- approaches for promoting PA and decreasing SB in
ties for PA in almost every domain of modern life. The real-world settings.
obesity epidemic now threatens almost all population sub- • Health providers may promote PA through brief
groups and even less technologically advanced cultures. counseling approaches such as the 5 A’s and access
Although these public health challenges are undoubtedly free, evidence-based tools for change through the
powerful adversaries, new discoveries of the benefits of EIM website and other available resources.
266 Chapter 21 Enhancing Physical Activity
REFERENCES
1. Centers for Disease Control and review and meta-analysis. Transl. Behav. older adults and special populations. Int.
Prevention. Available: https: //www.cdc Med. 2019;19(1):147–157. J. Behav. Nutr. Phys. Act. 2011;8:80.
.gov/physicalactivit y/basics/pa-health/i 16. Greaves CJ, Sheppard KE, Abraham 31. Marcus BH, Ciccolo JT, and Sciamanna
ndex.htm. Accessed December 12, 2017. C, et al. Systematic review of reviews CN. Using electronic/computer interven-
2. Thorp AA, Owen N, Neuhaus M, et of intervention components associated tions to promote physical activity. Br. J.
al. Sedentary behaviors and subsequent with increased effectiveness in dietary Sports Med. 2009;43(2):102–105.
health outcomes in adults: A systematic and physical activity interventions. BMC 32. Steele R, Mummery KW, and Dwyer
review of longitudinal studies, 1996– Public Health 2011;11:119. T. Development and process evaluation
2011. Am. J. Prev. Med. 2011;41. 17. Stetson B, Cooper JM, and Dubbert of an internet-based physical activity
3. Sedentary Behavior Research Network. PM. Cognitive behavioral approaches behaviour change program. Patient Educ.
Available: www.sedentarybehaviour.org, to enhancing exercise participation. Couns. 2007;67(1–2):127–136.
Accessed 15 December 2017. In Rippe J. (Ed). Lifestyle Medicine. 33. Baker PR, Francis DP, Soares J, et al.
4. Tremblay MS, Aubert S, Barnes JD, et al. Shrewsbury, MA: Blackwell Science, Inc. Community wide interventions for
Sedentary Behavior Research Network 2013, 233–243. increasing physical activity. Cochrane
(SBRN) – Terminology consensus project 18. Conn VS, Hafdahl AR, and Mehr DR. Database Syst. Rev. 2015;1:Cd008366.
process and outcome. Int. J. Behav. Nutr. Interventions to increase physical activity 34. Pew Research Center. Internet/
Phys. Act. 2017;14(1):75. among healthy adults: Meta-analysis Broadband Fact Sheet. Available: http://
5. Horodyska K, Luszczynska A, Hayes CB, of outcomes. Am. J. Public Health www.pewinternet.org /fact-sheet/interne
et al. Implementation conditions for diet 2011;101(4):751–758. t-broadband /
and physical activity interventions and 19. Howlett N, Trivedi D, Troop NA, et 35. Pew Research Center. Tech Adoption
policies: An umbrella review. BMC Public al. What are the most effective behav- Climbs Among Older Adults. Available:
Health 2015;15:1250. iour change techniques to promote http://www.pewinternet.org/2017/05/17/te
6. Goode AP, Hall KS, Batch BC, et al. The physical activity and/or reduce seden- ch-adoption-climbs-among-older-adults/.
Impact of interventions that integrate tary behaviour in inactive adults? A 36. Maher C, Ferguson M, Vandelanotte
accelerometers on physical activity and systematic review protocol. BMJ Open C, et al. A web-based, social network-
weight loss: A systematic review. Ann. 2015;5(8):e008573. ing physical activity intervention
Behav. Med. 2017;51(1):79–93. 20. Michie S, Richardson M, Johnston M, et for insufficiently active adults deliv-
7. Ginis KA, Nigg CR, and Smith AL. Peer- al. The behavior change technique tax- ered via Facebook app: Randomized
delivered physical activity interventions: onomy (v1) of 93 hierarchically clustered controlled trial. J. Med. Internet Res.
An overlooked opportunity for physical techniques: Building an international 2015;17(7):e174.
activity promotion. Transl. Behav. Med. consensus for the reporting of behavior 37. Rote AE, Klos LA, Brondino MJ, et al.
2013;3(4):434–443. change interventions. Ann. Behav. Med. The efficacy of a walking intervention
8. Luoma KA, Leavitt IM, Marrs JC, et al. 2013;46(1):81–95. using social media to increase physical
How can clinical practices pragmatically 21. Hoffmann TC, Glasziou PP, Boutron I, activity: A randomized trial. J. Phys. Act.
increase physical activity for patients with et al. Better reporting of interventions: Health 2015;12(Suppl 1):S18–S25.
type 2 diabetes? A systematic review. Template for intervention description and 38. Vodopivec-Jamsek V, de Jongh T, Gurol-
Transl. Behav. Med. 2017;7(4):751–772. replication (TIDieR) checklist and guide. Urganci I, et al. Mobile phone messaging
9. Craike M, Hill B, Gaskin CJ, et al. BMJ 2014;348:g1687. for preventive health care. Cochrane
Interventions to improve physical activity 22. Bohannon RW. Number of pedometer- Database Syst. Rev. 2012;12:Cd007457.
during pregnancy: A systematic review assessed steps taken per day by adults: 39. Fanning J, Mullen SP, and McAuley E.
on issues of internal and external validity A descriptive meta-analysis. Phys. Ther. Increasing physical activity with mobile
using the RE-AIM framework. BJOG. 2007;87(12):1642–1650. devices: A meta-analysis. J. Med. Internet
2017;124(4):573–583. 23. Alessa HB, Chomistek AK, Hankinson Res. 2012;14(6):e161.
10. Lewis BA, Napolitano MA, Buman MP, SE, et al. Objective measures of physical 40. Huberty JL, Buman MP, Leiferman JA,
et al. Future directions in physical activ- activity and cardiometabolic and endo- et al. Dose and timing of text mes-
ity intervention research: Expanding our crine biomarkers. Med. Sci. Sports Exerc. sages for increasing physical activity
focus to sedentary behaviors, technol- 2017;49(9):1817–1825. among pregnant women: A randomized
ogy, and dissemination. J. Behav. Med. 24. Maher C, Ryan J, Ambrosi C, et al. controlled trial. Transl. Behav. Med.
2017;40(1):112–126. Users’ experiences of wearable activity 2017;7(2):212–223.
11. Owen MB, Curry WB, Kerner C, et al. trackers: A cross-sectional study. BMC 41. Johnston W, Hoffman S, and Thornton L.
The effectiveness of school-based physical Public Health 2017;17(1):880. Mobile health: A synopsis and comment
activity interventions for adolescent girls: 25. Alinia P, Cain C, Fallahzadeh R, et al. on “Increasing physical activity with
A systematic review and meta-analysis. How accurate is your activity tracker? mobile devices: A meta-analysis”. Transl.
Prev. Med. 2017;105:237–249. A comparative study of step counts in Behav. Med. 2014;4(1):4–6.
12. Schoeppe S, Alley S, Rebar AL, et al. low-intensity physical activities. JMIR 42. Muntaner A, Vidal-Conti J, and
Apps to improve diet, physical activity Mhealth Uhealth 2017;5(8):e106. Palou P. Increasing physical activity
and sedentary behaviour in children 26. Skender S, Ose J, Chang-Claude J, et al. through mobile device interventions:
and adolescents: A review of quality, Accelerometry and physical activity ques- A systematic review. Health Inform. J.
features and behaviour change tech- tionnaires – A systematic review. BMC 2016;22(3):451–469.
niques. Int. J. Behav. Nutr. Phys. Act. Public Health 2016;16:515. 43. Dunton GF. Ecological momentary
2017;14(1):83. 27. Brewer W, Swanson BT, and Ortiz assessment in physical activity research.
13. Biddle SJ, Petrolini I, and Pearson A. Validity of Fitbit’s active minutes Exerc. Sport Sci. Rev. 2017;45(1):48–54.
N. Interventions designed to reduce as compared with a research-grade 44. Yang CH, Maher JP, and Conroy DE.
sedentary behaviours in young people: accelerometer and self-reported mea- Implementation of behavior change
A review of reviews. Br. J. Sports Med. sures. BMJ Open Sport Exerc. Med. techniques in mobile applications for
2014;48(3):182–186. 2017;3(1):e000254. physical activity. Am. J. Prev. Med.
14. Glanz K and Bishop DB. The role of 28. Chu AH, Ng SH, Paknezhad M, et al. 2015;48(4):452–455.
behavioral science theory in development Comparison of wrist-worn Fitbit Flex 45. Carroll JK, Moorhead A, Bond R, et
and implementation of public health and waist-worn ActiGraph for measur- al. Who uses mobile phone health apps
interventions. Annu. Rev. Public Health ing steps in free-living adults. PloS One and does use matter? A secondary data
2010;31:399–418. 2017;12(2):e0172535. analytics approach. J. Med. Internet Res.
15. Howlett N, Trivedi D, Troop NA, et 29. Tudor-Locke C, Craig CL, Brown WJ, 2017;19(4):e125.
al. Are physical activity interventions et al. How many steps/day are enough? 46. Yang CH, Maher JP, and Conroy DE.
for healthy inactive adults effective in For adults. Int. J. Behav. Nutr. Phys. Act. Acceptability of mobile health interven-
promoting behavior change and main- 2011;8:79. tions to reduce inactivity-related health
tenance, and which behavior change 30. Tudor-Locke C, Craig CL, Aoyagi Y, et risk in central Pennsylvania adults. Prev.
techniques are effective? A systematic al. How many steps/day are enough? For Med. Rep. 2015;2:669–672.
References 267
47. Young DR, Hivert MF, Alhassan S, et al. Latinas. Int. J. Behav. Nutr. Phys. Act. 72. McGoey T, Root Z, Bruner M, et al.
Sedentary behavior and cardiovascular 2016;13:62. Evaluation of physical activity interven-
morbidity and mortality: A science advi-
sory from the American Heart Association.
Circulation 2016;134(13):e262–e279.
60. Hartman SJ, Dunsiger SI, Bock BC,
et al. Physical activity maintenance
among Spanish-speaking Latinas in
tions in children via the reach, efficacy/
effectiveness, adoption, implementation,
and maintenance (RE-AIM) framework:
21
48. Schuna JM, Jr., Johnson WD, and a randomized controlled trial of an A systematic review of randomized
Tudor-Locke C. Adult self-reported and internet-based intervention. J. Behav. Med. and non-randomized trials. Prev. Med.
objectively monitored physical activity and 2017;40(3):392–402. 2016;82:8–19.
sedentary behavior: NHANES 2005–2006. 61. Steinberg DM, Levine EL, Lane I, et 73. Patnode CD, Evans CV, Senger CA, et
Int. J. Behav. Nutr. Phys. Act. 2013;10:126. al. Adherence to self-monitoring via al. Behavioral counseling to promote a
49. Biddle SJH, Bengoechea García E, Pedisic interactive voice response technology in healthful diet and physical activity for
Z, et al. Screen time, other sedentary an eHealth intervention targeting weight cardiovascular disease prevention in
behaviours, and obesity risk in adults: gain prevention among Black women: adults without known cardiovascular
A review of reviews. Curr. Obes. Rep. Randomized controlled trial. J. Med. disease risk factors: Updated evidence
2017;6(2):134–147. Internet Res. 2014;16(4):e114. report and systematic review for the US
50. Ramsey Buchanan L, Rooks-Peck CR, 62. Kerr J, Norman GJ, Adams MA, et al. preventive services task force. JAMA
Finnie RKC, et al. Reducing recreational Do neighborhood environments moderate 2017;318(2):175–193.
sedentary screen time: A community the effect of physical activity lifestyle 74. Lin JS, O’Connor E, Evans CV, et
guide systematic review. Am. J. Prev. interventions in adults? Health Place al. Behavioral counseling to promote
Med. 2016;50(3):402–415. 2010;16(5):903–908. a healthy lifestyle in persons with
51. Prince SA, Saunders TJ, Gresty K, et 63. Sallis JF and Owen N. Ecological models cardiovascular risk factors: A sys-
al. A comparison of the effectiveness of of health behavior. In Glanz K, Rimer BK, tematic review for the U.S. Preventive
physical activity and sedentary behaviour and Viswanath K (Eds). Health Behavior: Services Task Force. Ann. Intern. Med.
interventions in reducing sedentary time Theory, Research & Practice. San Francisco, 2014;161(8):568–578.
in adults: A systematic review and meta- CA: Jossey-Bass/Pfeiffer, 2015, 43–64. 75. Sallis R. Exercise is medicine: A call
analysis of controlled trials. Obes. Rev. 64. King AC, Toobert D, Ahn D, et al. to action for physicians to assess and
2014;15(11):905–919. Perceived environments as physical prescribe exercise. Phys. Sports Med.
52. Thraen-Borowski KM, Ellingson LD, activity correlates and moderators of 2015;43(1):22–26.
Meyer JD, et al. Nonworksite interven- intervention in five studies. Am. J. Health 76. AuYoung M, Linke SE, Pagoto S, et
tions to reduce sedentary behavior among Promot. 2006;21(1):24–35. al. Integrating physical activity in
adults: A systematic review. Transl. J. 65. Franzini L, Taylor W, Elliott MN, et al. primary care practice. Am. J. Med.
Am. Coll. Sports Med. 2017;2(12):68–78. Neighborhood characteristics favorable to 2016;129(10):1022–1029.
53. Hutcheson AK, Piazza AJ, and Knowlden outdoor physical activity: Disparities by 77. Shuval K, Leonard T, Drope J, et al.
AP. Work site-based environmental inter- socioeconomic and racial/ethnic composi- Physical activity counseling in primary
ventions to reduce sedentary behavior: A tion. Health Place 2010;16(2):267–274. care: Insights from public health and
systematic review. Am. J. Health Promot. 66. Perez LG, Kerr J, Sallis JF, et al. Perceived behavioral economics. CA Cancer J. Clin.
2018;32(1):32–47. neighborhood environmental factors that 2017;67(3):233–244.
54. Gardner B, Smith L, Lorencatto F, et al. maximize the effectiveness of a multilevel 78. US Department of Health and Human
How to reduce sitting time? A review intervention promoting physical activity Services. 2008 Physical Activity
of behaviour change strategies used in among Latinas. Am. J. Health Promot. Guidelines for Americans. Washington,
sedentary behaviour reduction interven- 2017. doi:890117117742999. DC: U.S. Department of Health and
tions among adults. Health Psychol. Rev. 67. Jenum AK, Lorentzen CA, and Human Services, 2008.
2016;10(1):89–112. Ommundsen Y. Targeting physical activ- 79. American Heart Association. American
55. Michie S and Prestwich A. Are interven- ity in a low socioeconomic status popula- Heart Association Recommendations for
tions theory-based? Development of a tion: Observations from the Norwegian Physical Activity in Adults. Available:
theory coding scheme. Health Psychol. ‘Romsas in Motion’ study. Br. J. Sports http: //www.hear t.org / HEARTORG/
2010;29(1):1–8. Med. 2009;43(1):64–69. HealthyLivi ng/Physica lActivity/ Fitn
56. Mendoza-Vasconez AS, Linke S, Muñoz 68. Bellicha A, Kieusseian A, Fontvieille AM, essBasics/A meric an-Heart-A ssociatio
M, et al. Promoting physical activity et al. Stair-use interventions in worksites n-Recommend ations-for-Physical-Acti
among underserved populations. Curr. and public settings – A systematic review vity-i n-Adu lts_UCM_307976 _ Article.j
Sports Med. Rep. 2016;15(4):290–297. of effectiveness and external validity. sp#.WoCvA6i nE2x. Accessed January 15,
57. Whitt-Glover MC and Kumanyika SK. Prev. Med. 2015;70:3–13. 2018.
Systematic review of interventions to 69. Eckhardt MR, Kerr J, and Taylor WC. 80. Colberg SR, Sigal RJ, Yardley JE, et al.
increase physical activity and physical fit- Point-of-decision signs and stair use in Physical activity/exercise and diabetes:
ness in African-Americans. Am. J. Health a university worksite setting: General A position Statement of the American
Promot. 2009;23(6):S33–S56. versus specific messages. Am. J. Health Diabetes Association. Diabetes Care
58. Messias DK, Parra-Medina D, Sharpe Promot. 2015;29(5):291–293. 2016;39(11):2065–2079.
PA, et al. Promotoras de Salud: Roles, 70. Glasgow RE, Vogt TM, and Boles SM. 81. Garber CE, Blissmer B, Deschenes MR,
responsibilities, and contributions in a Evaluating the public health impact of et al. American college of sports medicine
multisite community-based randomized health promotion interventions: The position stand. Quantity and quality of
controlled trial. Hispanic Health Care RE-AIM framework. Am. J. Public exercise for developing and maintain-
Int. 2013;11(2):62–71. Health 1999;89(9):1322–1327. ing cardiorespiratory, musculoskeletal,
59. Marcus BH, Hartman SJ, Larsen BA, et 71. Gaglio B, Shoup JA, and Glasgow RE. and neuromotor fitness in apparently
al. Pasos Hacia La Salud: A randomized The RE-AIM framework: A systematic healthy adults: Guidance for prescrib-
controlled trial of an internet-delivered review of use over time. Am. J. Public ing exercise. Med. Sci. Sports Exerc.
physical activity intervention for Health 2013;103(6):e38–e46. 2011;43(7):1334–1359.
22
CHAPTER
then become reinforced by the interplay of social interac- Effective nutrition prescription implementation can
tions, cultural norms, and societal factors that make it only occur when patients are motivated to change.
difficult to change over a short-term period. Various strategies to achieve optimal motivation will
Since it is now widely accepted that a dietary pattern be discussed. Behavioral change theories for the life-
has a profound effect on overall health, the necessity of style medicine practitioner will be discussed. Strategies
incorporating behavioral strategies to promote health and for incorporating these principles along with effective
healing becomes even more vital to the lifestyle medicine behavioral counseling techniques within the clinic set-
practitioner. Among the major barriers of implementing ting will be reviewed. Since health behavior is dynamic
such strategies is a lack of confidence in behavior change and dependent upon various cultural, social, and com-
counseling, inadequate provider training in behavioral munity factors, content related to how to integrate these
counseling, and lack of time and reimbursement for coun- aspects into a behavioral plan to facilitate nutrition goals
seling services. Lack of confidence in behavioral coun- will be included. Unique to this text will be content
seling abilities seems to rank highest among health care in this chapter on practical culinary skills as they are
providers as the reason for not implementing behavioral directly related to behavioral change. This will help clini-
change strategies into their practice. 5 This lack of confi- cians guide their patients on real-life hands-on cooking
dence is not surprising when one considers that physicians techniques and recipe planning while helping to promote
are offered little to no training in counseling techniques, positive behavioral changes.
and most medical schools do not incorporate behavioral
modification into their curriculums.
Another barrier is the lack of standardization of 22.1 EDUCATING PATIENTS ON
behavioral counseling techniques. Currently, rigorously
tested behavioral change strategies do not exist. One NUTRITION BASICS, LAYING
reason for this could be that it is challenging to design
and conduct randomized controlled trials that can effec-
THE FOUNDATION
tively evaluate efficacy of behavioral techniques. The lack
of concrete evidence supporting specific behavioral tools
22.1.1 Nutrition, a Snapshot
designed to improve lifestyle habits leads to inadequate The challenge to teaching good nutrition to anyone is
advice given by providers, long counseling sessions, inap- that the message isn’t flashy. The message of balance and
propriate methods of behavioral advice delivery, and poor moderation is certainly not as exciting or enticing as the
follow-up.6 Furthermore, most behavioral programs fail new mocha-choco-pumpkin flavored iced coffee, gluten-
to incorporate specific guidance based on an individual’s free snack food, or fad diet that promises you to be as
unique ethnic, cultural, and socioeconomic status. This slim as you were when you were 17, complete with believ-
lack of personalized approach makes adherence to behav- able before and after photos. Herein lies possibly the
ioral change much more difficult to sustain. most important lesson: ignore the marketing and outside
As health care continues to change from an economic influences and listen to your body. This is a difficult les-
standpoint, more physicians are finding themselves even son, particularly in America, but for most, knowledge is
under more pressure to produce viable bottom-line num- power, so start there.
bers to meet growing health care costs and overhead as Macronutrients, or the large building blocks of our
well as earning a living. Therefore, many clinicians feel that nutritional intake, are carbohydrates, protein, fats,
the time they have with patients, already limited, must be and water. Carbohydrates come in two forms, complex
spent addressing symptoms rather than focusing on root and simple; they are an extremely important source of
causes such as suboptimal lifestyle habits. Additionally, energy for our bodies and our brains.7 The vast major-
reimbursement for lifestyle counseling is either nonexistent ity of carbohydrates we consume should be complex for
in many health care plans or simply not sustainable for maximum nutrient density along with slower digestion/
most physicians when considering “bottom lines.” energy absorption and feeling of satiety.7 Protein is found
Influences that help shape decisions made on health in many foods, from grains to meats. Protein is impor-
behavior occur within an individual’s personal life. Many tant for building and repairing tissues and is a building
of these decisions are directly influenced by relatives, block of hormones and enzymes.7 When educating about
friends, co-workers, and community members.5,6 Thus, protein, encourage lean sources of protein, and if vegetar-
all of these influences must be considered when construct- ian, ensure a complement of amino acids. Fats have got-
ing a nutrition prescription with motivation for behavior ten a bad reputation in recent history, but they are very
change as its foundation. important for providing energy, transporting vitamins,
The nutrition prescription must be goal-oriented in and helping you feel satisfied after meals. It is important
order for it to be successful. The acronym SMART has to remember that some fats are better than others for
been used in helping physicians to set such goals for health. Unsaturated fats and fats found in plants should
their patients. It is categorized as follows: S-specific, be included in a healthy diet, while saturated and “man-
M-measurable, A-action-oriented, R-realistic, and T-time- made” fats such as trans fats should be avoided.7,8 Lastly,
sensitive. It has been found that when these SMART goals water is not always included as a macronutrient, but we
are aligned with an individual’s life goals, the individual are giving it a level of importance here. One cannot sur-
will be more motivated to change behavior. 5,6 vive without water for longer than a few days8 (see also
This chapter will cover the key aspect to achieving the chapter on Hydration). Your body needs proper hydra-
a successful nutritional prescription: behavior change. tion for cells to work properly, maintain temperature, and
22.1 Educating Patients on Nutrition Basics, Laying the Foundation 271
lubricate joints. When discussing fluids, unsweetened bev- Start by evaluating your current food buying patterns.
22
erages should be encouraged. Think about how you can change your purchases and
Micronutrients, or the small building blocks of our migrate them towards the original source of the food (see
nutrition intake, are all the vitamins and minerals. These Table 22.1).
nutrients, along with phytonutrients, work together to If you think about the progression of these foods from
ensure numerous body functions work not just properly most processed on the left to least processed on the right,
but at the highest level of performance and efficiency.7,8 you’ll notice that what is removed is the “extra” we do not
These are the basics of nutrition that barely scratch the need. So, with the “juice” you move to 100% juice and
surface, and we are learning that good nutrition and well- lose the added sugar and when you move to whole fruit
ness is so much more than just nutrients and calories. We you lose the concentrate source of natural sugar and add
know and are learning that behaviors like sleep patterns, fiber, vitamins, and minerals. The other thing that hap-
moving your body, gut flora, how you eat your meals, and pens when you move from left to right on this table is that
the number of processed foods you consume all play a role. food preparation tends to increase. If food preparation
is a hurdle, pick and choose where to make the changes.
There are some convenience foods that still maintain the
22.1.2 Whole Foods you Recognize whole food and its nutrient composition. Examples include
ready-to-microwave brown rice, canned beans (rinse to
When thinking about changing nutrition behavior, a good decrease sodium), plain frozen veggies, plain frozen fruit,
first step is to take a look inside the refrigerator and the baby carrots, cherry tomatoes, pre-sliced grilled chicken,
pantry—do you recognize the foods? Do you recognize and individual frozen pieces of fish. These items take only
them as whole foods that were picked, plucked, pulled, slightly longer to prepare than popping a frozen meal into
and harvested? If you find mostly processed foods star- the microwave.
ing back at you, think about where or how those foods When you have a patient or client who does like to
started out. cook, encourage them to purchase a community supported
Let’s think about something that the majority of agriculture (CSA) share or go to a farmers market. Have
Americans have in their freezer that is the biggest con- them try one or more new vegetables (kohlrabi, jicama,
tributor of sodium intake: frozen pizza. The dough comes celery root, golden beets, arugula, etc.) and look up recipes
from wheat, sauce from tomatoes, and cheese from milk. for the new items in order to try them out!
Doesn’t sound too terrible right? However, to turn it into a
long-term stable frozen food, the wheat has been stripped
of the nutrients, the sauce has lots of salt, fat, and added
sugar, and the cheese, well, you don’t want to eat too
22.1.3 Portion Control
much cheese. So how can we turn that frozen pizza into Probably the most important thing to stress with
a “whole food” that is easy to prepare? Starting with the patients is portion control. As the message of balance
dough, I doubt many people have time to make their own and moderation is not complicated, it does allow for
whole wheat dough from scratch (if you do, by all means, some wiggle room both for treats and increasing nutri-
go for it!), but it is easy to purchase, or you could use a ent-dense intake. The challenging part about portion
whole wheat English muffin or try one of those fancy cau- control is that our baseline is all out of whack. Many
liflower crust or hollow out a zucchini for a pizza base. think and have the perception that a foot-long sub, a bag
Thinking about the sauce, the closest you can get to the of chips, and 20 oz of soda is a normal lunch. The real-
whole food is slicing the tomato up or try crushed toma- ity is, for most, that half of that sub, a piece of fruit and
toes or look at the nutrition label for the tomato sauce water is the correct portion. No one has the exact same
and select one with the smallest ingredient list. Lastly, calorie and nutrition needs as someone else. To evalu-
the cheese can be added a sparingly. A sprinkle of moz- ate and provide a close estimate of a patient’s calorie
zarella and a sprinkle of a strong cheese like parmesan needs, a dietitian should be consulted. However, there
will deliver the flavor while limiting the extra calories and are many guides to offer a patient to keep portion sizes
saturated fat that cheese adds. appropriate.
plant-based foods) is expensive, and those eating less food biological, psychosocial, cultural, economic, and environ-
22
or unhealthy foods may have less power and are of lower mental factors.
socioeconomic status. Gender disparities in cooking also It remains clear that food is ultimately inseparable
exist in food preparation. The traditional gender roles of as both a biological necessity and cultural conduit; cul-
the female counterpart preparing and serving meals are tural differences in diet and eating impart different dis-
historically common practice. Reality TV cooking and ease outcomes in patients. For instance, minorities have
chef shows also have popularized the art of cooking, an increased risk of obesity and comorbidities compared
adding prestige to the profession, which has also shaped to Caucasians.15 Weight loss interventions are less effec-
the perceptions of cooking. Cultural traditions addition- tive in these groups as well. 23 Cultures who consume
ally shape methods of cooking, what foods a person con- higher amounts of processed foods and animal products
sumes, and how they eat. This may include family recipes have increased incidence of hyperlipidemia as well.6 This
passed down through generations, weekly family dinners, indicates the role of culture in food consumption needs
eating a turkey for Thanksgiving in the United States, a to be addressed for effective weight management for
kosher diet observed by many in the Jewish community, minority patients. A focus solely on nutrition prevents a
and going to a restaurant for a meal to celebrate a spe- holistic approach to food that also encompasses cultural
cial occasion. Also, the foods consumed by individuals are sensitivity and considerations. Personalized nutrition with
those considered edible by a culture. Escargot is a well- a holistic regard for cultural competencies includes pro-
known French delicacy uncommonly found on menus in viders well versed in the culture and language of their
American restaurants. Further, sushi has become quite patients, family-oriented interventions, instructive mate-
popular in the Western world, but raw fish has not always rials in their native language, and social support within
been a staple of the American diet. their cultural community.15,22,24 Encompassing these indi-
Eating further plays a role in relationship dynamics. vidualities optimizes personalized nutrition as a tool for a
Food is fundamental to culture and serves to potentiate healthy diet. Thus, a holistic, culturally sensitive, and indi-
social relationships. People dine together as a family, go vidualized health approach may reinforce the effectiveness
out on a date for romantic pursuits, grab coffee to become of personalized nutrition in the primary care setting.
better acquainted, or invite friends and neighbors to break
bread together. These experiences promote closeness
among diners as well as the sharing of cultural practices
around food and nutrition. Moreover, people choose food 22.3 EFFECTIVE COUNSELING
based on their personal taste preferences. However, those
foods deemed tastier are not always healthy and nutri-
TECHNIQUES FOR THE
tious, so individuals selecting foods according to their NUTRITIONAL PRESCRIPTION
taste preferences may be at an increased risk for disease.
In French culture, the hedonistic value of food is held in The coaching mindset is the art and heart of behavior
high regard. Further, French consumers more negatively change. It is a co-creative process that engages the patient
rank foods displaying nutritional information and antici- in their own healing by illuminating a self-directed path.
pate these foods to be less enjoyable to eat. 20 This portrays In this model, the patient is the expert and the coach is the
the concern that emphasizing healthy food choices may guide. This patient-centered way of engaging with clients is
result in a utilitarian view of food as a necessity, over- a fundamental shift from the current model of care where
powering the view of food as a source of pleasure and the clinician dictates and directs. The coaching model is
comfort. 20 This could make food enjoyment incongruent a theory-based practice which emphasizes collaboration
with health practices of eating nutritious foods. and facilitation of the client’s desire for change. Emerging
There exists a tension between the science of food for studies show that behavior changes are enhanced when
health and how people relate to food physically, culturally, this self-directed partnership approach is utilized (see the
socially, and sensually.16 According to a 2016 food and chapter on Health Coaching and Behavior Change).
health survey on Americans’ food choices for the decade The coach-client relationship is a dynamic force that is
between 2006 and 2016, taste continued to have the great- pivotal to the change process. This relationship is built on
est impact on the decision to buy foods and beverages, trust, mutual respect, and partnership. At the core of this
followed by price, healthfulness, convenience, and sus- relationship is a deep understanding that clients have the
tainability. Also, it has been evident that scientific under- ability to discover their own answers and meaning. The
standing and use of the nutrition facts label can prompt pace and path toward wellness are created by the client
food purchases and choices. 21 For example, a person and facilitated by the coach. It’s a shift away from advis-
with hypertension attempting to lower their sodium lev- ing to illuminating. There are five main domains utilized
els may opt for sodium-free or low-sodium food options. in the coaching model. The first is Sharing Knowledge.
Additionally, diabetics may opt for sugar-free or sugar The coach asks permission before launching into a lecture
replacements to maintain lower blood sugars. However, about a topic. The client can choose how and when infor-
the frequency of use of nutritional labels in choosing mation is distributed. This puts the locus of control back on
food was in general low among low-income women on the client and fosters participation. The second domain is
WIC or risky populations. While the use of food labels Active Listening. The coach listens without an agenda. It’s
has increased in recent years from 32% in 2004 to 52% a mindful state of listening that creates empathy and fluid-
in 2008, 22 consumers still make their dietary decisions ness for the client. The third domain is Asking Questions.
through various determinants of food choices, including Open-ended profound questions emerge from the active
274 Chapter 22 Enhancing the Nutrition Prescription Using Behavioral Approaches
state of mindful listening. These deeper questions asked (MI). MI is a goal-oriented style of motivating that
by the coach provoke insight and self-awareness in the cli- focuses on the language of change. The communication
ent. The fourth domain is Addressing Problems. Problems with MI is designed to strengthen personal motivation
and blocks are viewed as opportunities for growth. The for a specific goal by eliciting and exploring the person’s
focus is on the learning and not the problem. Solutions reasons for change in an environment of acceptance and
are discussed in partnership with the client and the client compassion. The core MI skills are OARS. O: open-
makes the final call on which path to choose. The fifth ended questions which allow the client to go deeper into
domain is Taking Responsibility. Client participation is exploring and expressing feelings and desires for change.
essential to successful behavior change. Goals and agree- A: Affirmations, finding the positives, the strengths, or
ments are created based on the client’s agenda, thus foster- as Miller and Rollick like to call it, change talk, and
ing follow-through and self-responsibility. acknowledging it to enhance motivation. Change talk
Fostering self-awareness and insight is pivotal to the invites the client to give their own reasons for changing.
changes process. The coach strives to assist clients in dis- Questions that evoke change talk are ones like “What
covering their own answers by cultivating more meaning- would your life be like if you were meditating daily?”,
ful questions. The coach moves away from interpreting “How would losing 10 lb enhance your current situa-
and imposing meaning to asking questions such as, “What tion?”, or “I heard you mentioned you wanted to give up
does that mean to you?”, “What would that look like gluten—what makes you say that?” R: Reflective listen-
for you?”, “What did you mean by that?” These types ing, which is demonstrating understanding by repeating
of exploratory open-ended questions assist the client in or paraphrasing what you hear. S: Summarizing or reflect-
developing the self-awareness and insights necessary to ing back main points to establish rapport, connection, and
make permanent changes in behavior. facilitate the co-creation of client-centered goals.
I had a client who came in the other day and was seek- The third step in the five-step model for behavior change
ing to lose weight. We talked about eliminating certain and motivation is Building Confidence by identifying core
foods and cutting back on serving sizes, and she was very strengths. The coach explores a client’s core strengths by
receptive to making these changes. When we started talk- asking opened-ended questions about past success and
ing about exercise, I could see that her body language having the client identify which strengths they used and
began to change. She folded her arms across her heart how these strengths could be applied to their current health
and started biting her nails. I asked her what was going goals. The fourth step is co-creating SMART goals with
on inside of her at that moment and pointed out that her the client. SMART goals are Specific, Measurable, Action-
body language had changed when I started to talk about oriented, Realistic, and Time-sensitive. SMART goals take
exercise. She told me that talking about exercise made her a large goal such as, “I want to lose weight,” and breaks it
feel embarrassed. Instead of leaving her comments and down into smaller measurable chunks. How much weight?
moving on to another topic or imposing my own meaning What is the first step towards doing this? When will you
on why exercise made her embarrassed, I asked her what start this new behavior? These are the kinds of questions
she meant by that. She then told me that when she was in used by the coach to facilitate the creation of SMART goals
elementary school the gym teacher made the children race by the client. The fifth step is Set Accountability. The coach
against each other in class. One of her legs is slightly lon- and client mutually decide on the best method of tracking
ger than the other, which makes running difficult for her. and the frequency of communication and appointments.
She would usually come in last place and the other chil- Having a very specific tracking system motivates and
dren would tease her. She has avoided exercise ever since. enhances behavior change. With the evolution of technol-
Now we had the deeper meaning behind her exercise aver- ogy, it has become very convenient to measure and track
sion. The next step was to find a way to transform her old in the moment. This immediate feedback keeps clients
exercise wound into a new healthy pattern of movement. engaged with their goals and enhances behavior change.
This transformation needed to be an “inside job” and not Frequent follow-up appointments allow the client to cel-
something imposed by outside forces. I asked her how she ebrate successes and explore blocks and setbacks.
could move her body in a way that would make her feel For behavior change to be positive and permanent, the
comfortable and confident. She replied, without hesita- client’s participation in the change process is required. This
tion, dance! We explored this further and she revealed that essential truth is shifting the landscape of medicine and
she did not equate dancing with exercise, therefore her old health. The new emerging coaching model of collaboration
feelings of shame were not ignited when she danced. These and co-creation of client-centered goals in an environment
types of insights and awareness are essential to permanent of empathy and compassion has the potential to transform
behavior change and the creation of achievable goals. health and facilitates deeper engagement with life.
The five-step model for behavior change and motiva-
tion is a framework for successful coaching encounters.
The first step is to Be Empathetic. There are two key com-
ponents to empathy: listening with intention and accu- 22.4 NUTRITION COUNSELING AND
rately reflecting back narrative. The research on empathy
has shown that when patients rate their practitioner high
EDUCATION IN THE GROUP
on the Empathy scale it improves clinical outcomes and MEDICAL VISIT MODEL
changes biomarkers such as Hgb A1C and LDL choles-
terol. 25 The second step is Align Motivation. This is based A perfect fusion in the patient-centered medical home for
on Miller and Rollick’s book Motivation Interviewing empowering the patient. Why is this needed today?
22.4 Nutrition Counseling and Education in the Group Medical Visit Model 275
In 2005, a review of the daily clinical responsibilities reviewed group-based training for self-management strate-
22
and demands placed on physicians estimated that it would gies in people with type 2 diabetes mellitus and it showed
require primary care physicians 18 hours a day to deliver improvement in biomarkers. Improved decreased hemo-
evidence-based preventative and chronic disease manage- globin A1C at 6 months, 12 and 24 months; lower average
ment care. 25 Additionally, estimates vary but there is a fasting glucose at 1 year; improved weight loss at one year;
nutrition-related reason for at least 25% of all visits to lower systolic blood pressure at 6 months; decreased dia-
primary care providers. 26 Medical students and residents betic prescription use; and improved diabetic knowledge
receive, on average, 19.6 hours of nutrition education dur- at one year.
ing their training. 27 Additionally, only 20% (3.9 hours) of The health benefits of groups for medically ill included
the students’ contact hours focus formally on nutrition sci- decreased symptoms, improved compliance and adapta-
ence and its application. The rest of the education focuses tion to illness, and decreased use of emergency room visits
on integrated curriculum, clinical practice, biochemistry, and inpatient admissions. There was improved blood pres-
and physiology-biochemistry. 27 American physicians are sure, improved blood glucose levels, and improved access
deficient in nutrition education. 28 A model for primary to care. And most importantly, there was behavioral
care clinics to empower patients to help intervene in their change. The benefits of this type of education and visit for
chronic health conditions through changing modifiable the patient, clinic staff, nutrition educator or counselor,
lifestyle factors has emerged. It is the group or shared and provider are many Table 22.2.
medical visit where the clinician and the nutritionist or (3) Experience and modeling.
health education specialist educate and provide a clinical From the physicians’ perspective, there is increased
evaluation experience to help address the many issues of face-to-face time with patients. It is a more efficient
chronic illness. 29 The fusion of nutrition counseling and patient education model than one-on-one office visits, and
education with the clinician in primary care is the future it allows increased integration of lifestyle change. There
of health care delivery for chronic conditions.30 are a few models that have been recorded in the literature.
(1) Nutrition and the group (shared) medical visits: Two of these are the Scott model, which has an interdis-
Application to the primary care clinic. ciplinary team coordinating the group together, and the
In the patient-centered medical home model of clinics Noffsinger model, which has the physician leading the
in the United States, educators are being used alone or group. There are many variations. 28,33–35 The model needs
in conjunction with the clinician to allow more complete to adjust to the location, physical plant, clinic and edu-
lifestyle education in nutrition to modulate chronic cation personnel, and the client base. All group medical
disease. The five major modifiable lifestyle factors include visits are local, with their own characteristics.
diet and nutrition, sleep, exercise and movement, thoughts (4) What is the focus of the group medical visit?
and emotions, and relationships. There is a marked variety of focal points for the group
Maintenance of health and improvement in chronic medical visit. It can focus and concentrate on test results,
illness is modulated by addressing these modifiable general system issues, disease process, or on healthy
factors. This is a reimbursable model that has been used processes. As an example, at our primary care clinic in
successfully in a wide range of clinical settings. Ashland, Oregon, we have been using nutritionists, regis-
When compared to a one-on-one session with tered dieticians, physician assistants, nurse practitioners,
clinicians, the group medical visit model has shown and physicians for group medical visits. There are 10 vis-
efficacy by improving tracked outcome measures of its per month with three main topics: functional nutrition
compliance, biomarkers, follow-up, and lasting changes trimester-by-trimester obstetric care (healthy process), a
so patients can meet more nutrition benchmarks. cardiometabolic syndrome series (disease condition pro-
There are many different structures to the shared med- cess), and test reviews of carotid intimal-medial thick-
ical visit session. Different monographs are available to ness results, or advanced lipids and inflammatory panels.
help the clinician and clinic institute programs.31,32 The Nutrition and its effects on lifestyle, health, and chronic
main focus of the groups is to improve access, educate, illness are incorporated into all of the groups.
and promote behavioral change. When a form of medi-
cal visits was incorporated into patient care in the U.S.
Department of Veterans Affairs (VA), the focus was on TABLE 22.2 Benefits of the shared medical visit
diabetes self-management education using nurses or
health coaching and also on psychotherapy and patient 1. Enhanced patient care experience with more education and
peer-to-peer support groups. Outcomes, time to treatment empowerment.
change, empowerment of the patient, and the satisfaction 2. Improved patient satisfaction with the care they receive.
3. Improved clinician efficiency and job do-ability.
in their care improved. 4. Improved morale and job satisfaction of the clinical and
(2) Use in therapeutic programs for chronic disease. non-clinical support staff.
This is not a new concept. In 1907, tuberculosis 5. Enhanced access to care for the patients.
patients at Massachusetts General Hospital used groups 6. Physician ability to increase panel size and reopen closed
to improve education and treatment. This model has been practices to new patients.
used to improve treatment in diabetes, metabolic syn- 7. Cost-effectiveness of care improved.
8. Improved quality and safety of medical care delivered to
drome, hypertension, cardiac disease, asthma, arthritis, patients.
chronic pain, chronic headaches, stress management, sleep 9. Help providers avoid “burnout.”
disorders, and in the geriatric and the obstetric popula-
tion.31 A Cochrane collaboration systemic review in 2005 Adapted from.35,38
276 Chapter 22 Enhancing the Nutrition Prescription Using Behavioral Approaches
TABLE 22.4 Examples of topics for the group medical visit and nutrition intervention possibilities
Topic or focus Nutrition education/modifiable lifestyle factor 22
Test Specific: lipids, or advanced lipids, Foods and diet changes which improve lipids, blood sugars, or affect coagulation.
Coagulation – INR, blood sugars… The addition of herbs/spices that impact the process underlying the abnormalities
in the laboratory (co-decided by the clinician and the nutritionists).
Imaging or procedure-specific: Carotid Intima- Ways to impact inflammation and plaque. Helping people understand the root
Media Thickness, colonoscopy cause of the inflammation and how to keep your vessels healthy.
Ways to help restore the bowel flora balance with food and fermented foods and
how to help your bowel be healthy.
Process Specific: Inflammation, Detoxification, Discuss and inform on the role of macronutrients, micronutrients, and food choice
Malabsorption, autoimmunity, One-Carbon and preparation that improves:
Metabolism or methylation -Inflammation: (EFA, fermented foods, limiting simple carbohydrates, adequacy of
antioxidant-rich foods), -Detoxification or biotransformation: (adequacy of
color-rich vegetables rich in antioxidants, minerals, vitamins for phase 1
biotransformation and adequacy of protein and sulfur amino acid containing foods
for phase 2 biotransformation)
-Malabsorption: discuss timing, volume, combination of foods and preparation
that influences absorption. The effect of over-the-counter medications on
absorption.
-Autoimmunity or Allergies: foods and nutrients that help balance immunity; foods
rich in vitamin D, vitamin A, and minerals of zinc and iron.
-One Carbon Metabolism can focus on the interplay of adequacy of B vitamin,
essential fatty acid, mineral-rich foods that form the foundation of adequate one
carbon metabolism balance in the person with any of the chronic illnesses
associated with an imbalanced one carbon metabolism common in primary care.
Condition Specific: Cardiometabolic syndrome or A single class or a series of four or more which helps provide a consistent number
any of its components: Hyperglycemia, of group members.
hyperlipidemia, hypertension, High Body Fat. Determine the many aspects of food, diet, nutrition, and lifestyle that are focused
Obesity on during the session or series. All of the examples of the condition-specific
Arthritis chronic illnesses can be improved by changing the diet in a person-specific
Asthma fashion.
Chronic Obstructive Pulmonary Disease
Modifiable Lifestyle Components All of the modifiable lifestyle factors are influenced by food choice and lifestyle
Sleep, movement and exercise, Emotions-Stress, balance. Sleep and exercise or movement are more successful with adjustment of
and Relationship with yourself, others and food, diet and food choice. Emotions are affected by caffeine and alcohol intake, which
Diet and Nutrition change nutrient requirements. Relationships with food and others are affected by
the habits of food choice and consumption patterns. Disordered eating influences
all chronic disease conditions.
Specialty Specific: Promoting Healthy Balance Each of the different stages of pregnancy can have different foods and nutrients
Example: Obstetric Group Medical Visits: emphasized. This is a very empowering opportunity for clinician, nutritionist, and
preconception, first, second, third trimester patient alike, impacting pregnancy outcome and transgenerational health (Stone).
followed by lactation and introduction of foods to
the newborn and infant.
Grilling is cooking food items by a radiant heat source 3 tbsp. of fresh minced garlic
below the food item. The equipment can be gas, electric, 2 oz. of fresh basil or 1 oz. dried basil
charcoal, or wood. 13 lbs. of fresh tomatoes or 6 quarts of w/canned
Steaming is cooking an item with a vapor bath created liquids
by boiling water or stock. Salt as needed
Sauté is cooking in a small amount of fat quickly in a Black pepper as needed
sauté pan on the stove top or range. • Cornstarch plus cold slurry liquid to thicken 1 qt.
Useful Ratios of stock or sauces:
Stocks and sauces Approx. ¾ oz. (weight) cornstarch with just enough
cold stock or water to bring slurry mixture to
• Vegetable Stock Basic Formula: Yield: 1 Gallon the consistency of cream soups
Assorted non-starchy vegetables: 3 lb. • Vegetable Soup Basic Formula: Yield: 1 gal.
Water: 5 qt. Vegetables 3 lb.
• Tomato Sauce: Yield:1 Gallon Vegetable stock or broth if for non-vegetarian soup
1 fl. oz. of olive oil 1 gal.
14 oz. minced garlic • Cream Soup Basic Formula: Yield: 1 gal.
278 Chapter 22 Enhancing the Nutrition Prescription Using Behavioral Approaches
healthier and are starting with this remedy rather than • www.eatingwell.com.
22
medication. Walter Willet, MD, and David Eisenberg, • https: //www.hsph.harvard.edu/nutritionsou rce/
MD, both members of the Harvard School of Public healthy-eating-plate/
Health, have been bridging the gap between schools of
medicine and the culinary profession to create aware-
ness for the young, up-and-coming doctors to be more
aware of the correlation between medicine and healthy CLINICAL APPLICATIONS
eating.
5. Culinary resources • Optimal nutrition intervention is the cornerstone of
• Cooking websites and cookbooks well-regarded an effective lifestyle medicine prescription.
by health and nutrition authorities. • By taking into consideration the various cultural
• Techniques of Healthy Cooking by The Culinary factors involved in nutritional practices, the clini-
Institute of America (CIA), February 4, 2013. cian will be able to better design a lifestyle medicine
• The Professional Chef by The Culinary Institute program that patients will find easier to adhere to.
of America (CIA) September 13, 2011. • Implementation of effective health coaching can
• Cooking for Special Diets by Katherine Polenz promote patient compliance with dietary change.
and The Culinary Institute of America (CIA) • One way to provide efficient, cost-effective nutri-
March 10, 2014. tional counseling is through group medical visits.
• www.mass.gov/org s/mas sachu setts -grow nand • Dietary excellence first starts in the kitchen.
-fres
her: This is an example for the state of Therefore, a working knowledge of basic culinary
Massachusetts. skills is key to building healthy lifestyle habits.
REFERENCES
1. Lianov, L. and M. Johnson, Physician 14. Opara, E.I. and M. Chohan, Culinary Hispanic populations: The role of culture.
competencies for prescribing lifestyle herbs and spices: Their bioactive proper- J. Obes., 2013: p. 542736.
medicine. JAMA, 2010. 304(2): p. 202–3. ties, the contribution of polyphenols 24. Mier, N., M.G. Ory, and A.A. Medina,
2. Services, U.D.o.H.a.H., The Surgeon and the challenges in deducing their true Anatomy of culturally sensitive interven-
General’s Call To Action To Prevent and health benefits. Int. J. Mol. Sci., 2014. tions promoting nutrition and exercise
Decrease Overweight and Obesity. 2001, 15(10): p. 19183–202. in hispanics: A critical examination of
Rockville, MD: Office of the Surgeon 15. Broyles, S.L., et al., Cultural adaptation existing literature. Health Promot. Pract.,
General (US). of a nutrition education curriculum for 2010. 11(4): p. 541–54.
3. Dietary Guidelines 2015–2020. Chapter Latino families to promote acceptance. J. 25. Ostbye, T., et al., Is there time for man-
1 Key Recommendations: Components Nutr. Educ. Behav., 2011. 43(4 Suppl 2): agement of patients with chronic diseases
of Healthy Eating Patterns. 2015 [cited p. S158–61. in primary care? Ann. Fam. Med., 2005.
2017 December 20]; Available from: https 16. Nordstrom, K., et al., Food and health: 3(3): p. 209–14.
://health.gov/dietaryguidelines /2015/gui Individual, cultural, or scientific matters? 26. Kolasa, K.M., Developments and
delines/chapter-1/key-recommendations/. Genes Nutr., 2013. 8(4): p. 357–63. challenges in family practice nutrition
4. American College of Preventive Medicine, 17. Kaput, J., Nutrigenomics research for education for residents and practicing
Lifestyle Medicine – Evidence Review. personalized nutrition and medicine. physicians: An overview of the North
2009. Curr. Opin. Biotechnol., 2008. 19(2): p. American experience. Eur. J. Clin. Nutr.,
5. Castaldo, J., et al., Physician attitudes 110–20. 1999. 53(Suppl 2): p. S89–96.
regarding cardiovascular risk reduction: 18. Rust, R., Lifestyle Medicine 27. Adams, K.M., M. Kohlmeier, and S.H.
The gaps between clinical importance, Competencies Basic Curriculum Zeisel, Nutrition education in U.S. medi-
knowledge, and effectiveness. Dis. Nutrition. American College of Lifestyle cal schools: Latest update of a national
Manag., 2005. 8(2): p. 93–105. Medicine. survey. Acad. Med., 2010. 85(9): p.
6. Dysinger, W.S., Lifestyle medicine 19. Nielsen, D.E. and A. El-Sohemy, A 1537–42.
competencies for primary care physicians. randomized trial of genetic information 28. Devries, S., et al., A deficiency of nutri-
Virtual Mentor, 2013. 15(4): p. 306–10. for personalized nutrition. Genes Nutr., tion education in medical training. Am. J.
7. Groff, J.L., S.A.S. Gropper, and S.M. 2012. 7(4): p. 559–66. Med., 2014. 127(9): p. 804–6.
Hunt, Advanced Nutrition and Human 20. Gomez, P. and C.J. Torelli, It’s not just 29. Chambliss, M.L., et al., Adding health
Metabolism. 1995; 2nd ed. numbers: Cultural identities influence education specialists to your practice.
8. Nelms, M., et al., Nutrition Therapy and how nutrition information influences the Fam. Pract. Manag., 2014. 21(2): p. 10–5.
Pathophysiology. 2011. Brooks Cole. p. valuation of foods. J. Consum. Psychol., 30. Barnett, K.G., Group medical visits: The
1072. 2015. 25(3): p. 404–15. future of healthcare? Glob. Adv. Health
9. Prevention, C.f.D.C.a., Adult Obesity 21. Sonnenberg, L., et al., A traffic light food Med., 2015. 4(6): p. 6–7.
Facts. 2017. labeling intervention increases consumer 31. Eisenstat, S., et al., Putting Group Visits
10. Kessler, D.A., The End of Overeating: awareness of health and healthy choices Into Practice: A Practical Overview
Taking Control of the Insatiable at the point-of-purchase. Prev. Med., to Preparation, Implementation, and
American Appetite. 2010. Rodale Books. 2013. 57(4): p. 253–7. Maintenance of Group Visits at
11. Gupta, S.C., et al., Discovery of cur- 22. Wojcicki, J.M. and M.B. Heyman, Use Massachusetts General Hospital. 2012. p. 26.
cumin, a component of golden spice, and of food labels, awareness of nutritional 32. Theobald, M. and S. Masley, A Guide
its miraculous biological activities. Clin. programmes and participation in the spe- to Group Visits for Chronic Conditions
Exp. Pharmacol. Physiol., 2012. 39(3): p. cial supplemental program for Women, Affected by Overweight and Obesity. p.
283–99. Infants and Children (WIC): Results 16.
12. Han, E., 7 Ways to Eat & Drink from the National Health and Nutrition 33. American Academy of Family Physicians,
Turmeric. 2017. Examination Survey (2005–2006). AAFP Policy on Shared Medical
13. Ranasinghe, P., et al., Medicinal proper- Matern. Child Nutr., 2013. 9(3): p. Appointments/Group Visits. 2008 [cited
ties of ‘true‘cinnamon (Cinnamomum 299–308. 2017 December 20]; Available from: https
zeylanicum): A systematic review. BMC 23. Lindberg, N.M., V.J. Stevens, and R.O. ://www.aafp.org /about /policies/all/share
Compl. Altern. Med., 2013. 13: p. 275. Halperin, Weight-loss interventions for d-medical.html
280 Chapter 22 Enhancing the Nutrition Prescription Using Behavioral Approaches
34. Masley, S., J. Sokoloff, and C. Hawes, whom, and under what circumstances do underserved community. Glob. Adv.
Planning group visits for high-risk patients. they work? BMC Health Serv. Res., 2017. Health Med., 2015. 4(6): p. 27–60.
Fam. Pract. Manag., 2000. 7(6): p. 33–7. 17(1): p. 113. 38. Beck, A., et al., A randomized trial of
35. Noffsinger, E.B., Running Group Visits 37. Geller, J.S., J. Kulla, and A. Shoemaker, group outpatient visits for chronically ill
in Your Practice. 2009, Springer. p. 493. Group medical visits using an empow- older HMO members: The cooperative
36. Kirsh, S.R., et al., A realist review of erment-based model as treatment health care clinic. J. Am. Geriatr. Soc.,
shared medical appointments: How, for for women with chronic pain in an 1997. 45(5): p. 543–9.
23
CHAPTER
281
282 Chapter 23 Behavioral Approaches to Manage Stress
(Adapted from: The Stress Response and Development of Allostatic Load from McEwen(1998), New England Journal of
Medicine (2)).
23
Figure 23.2 Comparative Impact of the Acute Stress and Relaxation Responses: Central and Peripheral Nervous System
Activities from Dusek and Benson (2009).4
Resilience is built by decreasing the stress response, positivity longitudinally predicts trait resilience56 and is in
promoting the relaxation response, and fostering growth turn associated with a sixfold decreased risk of depressive
enhancement. This model is summarized in Figure 23.4. symptoms57 and reduced stress.58 This adaptive coping is
Mind-body therapies (MBTs) are essential in decreasing fortified with the regular practice of elicitation of the relax-
the stress response and activating the relaxation response. ation response, providing further contrast between its posi-
MBTs include practices from different cultural traditions. tive impact and the negative impact of individual stress.
They are believed to share the common physiology as This, in turn, leads to more resilience.
described by the relaxation response. MBTs have shown As patients become secure in their self-awareness of the
to produce measurable reductions in levels of perceived stress response, MBT practice, and positive coping strate-
stress,11,30–43 increase positive emotions, and decrease lev- gies, it is important to recognize the personal work the
els of anxiety and depression.10,13,19,39,51,44–54,55 Table 23.1 patient is doing. Growth enhancement should be praised
summarizes research using MBT in disease treatment. and reinforced by providers. This is a key component to
Helping build resilience through growth enhancement building resilience. 59
is another essential component to managing chronic stress,
As defined earlier in the chapter, we know that stress is
relative to individual experience and perception. Therefore, 23.3 MIND-BODY THERAPIES
helping patients develop specific stress appraisal tech-
niques to identify stress, as well as the associated negative Figure 23.5 describes various MBTs found across many
mood, can help lead to more personal awareness. With this cultures to elicit the relaxation response.15 Clinicians can
intentional awareness, patients can easily identify stress’ provide prescriptions for these MBTs. Patients should be
negative effect and counteract it with positive coping strat- encouraged to explore different MBTs to determine which
egies, positive perspectives, more pleasing emotional states, practice(s) is better for him or her. The patient should
and positive behaviors. Evidence suggests that higher also be encouraged to develop regular practice so that
Relaxation Methods
Single-Pointed
Focus Meditation
Breath
Imagery
Awareness
Metta Autogenic
MINIS
Meditation Training
Mindful Yoga/Mindful
Awareness Movement PROXIMAL OUTCOME
Guided
Imagery
R
Cognitive
Decreasing
Physical Behavior Stress
Reactivity
RESILIENCY
Emotion
Increasing
Connectedness
to Self & Others
Growth Enhancement
Positivity STATE
Acceptance Empathy
Appreciation
TREATMENT APPROACHES
they feel not only comfortable with eliciting the relax- improving sleep,62 and reducing anxiety and stress.63–66
ation response but confident in their new regular routine. The following are various techniques of meditation that
Figure 23.6 gives a general overview of tips to help your build resilience in patients by eliciting the relaxation
patients develop a regular practice. The following exam- response in the body.
ples are more detailed descriptions of selected MBTs.
23.3.1.1 Breath Awareness
23.3.1 Meditation Breath awareness is a single-pointed focus meditation. It
is the practice of maintaining focused awareness on the
Herbert Benson, MD, originally coined the term relax- breath. This is one of the easiest and most widely used
ation response and advised that it can be invoked by two meditation practices. This is exemplified in Figure 23.7.
steps:1 repetition of a word, sound, phrase, or movement,
and 2 disregarding other thoughts when they come while
practicing.6 This practice, common in many forms of 23.3.1.2 Body Scan
meditation, is nothing new. Meditation has been practiced Body Scan is a great tool to notice any areas of tension,
for millennia across many cultures. It has been shown to tightness, and discomfort within the physical body. It is
have health benefits such as decreasing blood pressure,60,61 used in many traditions, including Mindfulness Based
23.3 Mind-Body Therapies 287
23
Figure 23.6 Tips for Developing a Practice. Figure 23.7 Breath Awareness.
288 Chapter 23 Behavioral Approaches to Manage Stress
23.3.1.3 Guided Imagery
This MBT allows for the use of imagination. Patients who
use this while having surgery have shown higher pain tol-
erance, less pain, and lower pain medication use as well
as less anxiety and lower heart rates.68 The patient partic-
ipating in imagery can sustain focus on an experience but
change it in their imagination to reflect a more positive
perspective or experience. The patient’s own imagination
can be a stress management tool by transforming nega-
tive memories and mental images69 through visualizing
growth in personal and/or social domains.70 Imagery can
reframe emotional responses to visual depictions of stress
and help overcome negative memories of the past and
stressful situations in the present. It can also help patients
prepare for anticipated stressful events in the future.
A memory can be revised to reflect a more pleasant expe-
rience, which deactivates the stress response related to
the experience. Figure 23.10 provides a script for guided
imagery. Figure 23.9 Progressive Muscle Relaxation.
23.3.2.2 Tai Chi
Tai Chi is another moving meditation that connects
controlled movements of the body with the breathing of
Figure 23.11 Contemplation and Prayer. the practitioner. It is a Chinese martial art that is first
290 Chapter 23 Behavioral Approaches to Manage Stress
mentioned over 3,000 years ago in an ancient Chinese life.90–95 Reports indicate long-term efficacy of tai chi, with
philosophical text known as the I Ching, or Book of benefits persisting at three years follow-up,96 depending on
Changes.87 Like yoga, there are many styles of tai chi the persistence and duration of practice. Though it is well
that differ slightly in technique and methodology, but all suited for all ages, the low-impact, slow-paced qualities
draw upon 13 basic postures and eight martial stances, of tai chi make it an especially viable option for mobility-
referred to as gates. The eight gates have a correspond- impaired and elderly patients.
ing energy that falls on the spectrum of yin (subtle) to
yang (aggressive), and the practitioner focuses on the
balance of contrasting movements, the yin and yang, to
23.3.3 Gratitude
create physical and mental harmony. Yang-style tai chi is Gratitude is also shown to build resilience. It is a key strat-
the most commonly studied in research.88 Figure 23.12 egy for adaptation to stress and helps achieve progressive
describes the multicomponent structure of tai chi, illus- growth in the face of stress. It is the practice of showing
trating the integration of physical and mental aspects of appreciation for the present moment, people, experiences,
the practice.89 and opportunities that are a part of our lives. When a
The reported lifetime and 12-month prevalence rates patient is stressed, and in allostatic load, the foundation
for tai chi are 3.1% and 1.2%, respectively.90 It was found of appreciation is lost, and thoughts can become ruminat-
to have proportionally higher 12-month prevalence rates ing, worrisome, and negative.97–99
for individuals of Asian, African American, or other ethnic Gratitude has many physiological effects, including a
descent and for individuals 30 years or older, with great decreased heart rate.100 Gratitude practice has also shown
increases over the past decade in the number of partici- changes in the brain. MRI images of participants in one
pants from minority backgrounds relative to those from study found gratitude had manipulated the regions of the
non-minority backgrounds.90 Given that minorities tend brain associated with emotion self-regulation and self-
to be at higher risk for health complications, the increase motivation.100 Another study found that those who prac-
in MBT use among these groups may bring upon positive ticed gratitude had an increase in appreciative behavior, a
changes in health outcomes. decrease in anxiety and depression symptoms, and a last-
Tai chi may help to decrease blood triglycerides and ing neural sensitivity to gratitude even three months after
blood pressure, and to manage pain and arthritis, mental interventions.101 Therefore, gratitude not only has mitigat-
health, cardiovascular disease, and neurological condi- ing effects but also changes neural regulation in the brain
tions.73,74 Individuals with Parkinson’s disease, fibromy- with prolonged positive effects.101 Expressing gratitude
algia, rheumatoid arthritis, and osteoarthritis may find has the benefit of reducing levels of perceived stress, anger,
solace in practicing tai chi, as it been shown to ease symp- and burnout,46,97–99,102–111 and increasing feelings of well-
tom severity, disease-specific pain, and somatic complaints, being98 and happiness. Practicing gratitude has also been
while increasing balance, stability, and overall quality of observed to show an overall sense of gratefulness for loved
ones and for life and social supports.103,111 It also leads to suggests that positive emotions are essential for opti-
23
a more positive affect,112 positive reframing, acceptance, mal functioning, including building resilience, improv-
humor, and better coping.105 ing attention, fostering creativity, disengaging persistent
negativity, improving interpersonal relationships, becom-
ing more resourceful, increasing overall well-being, and
23.3.3.1 Practicing Gratitude ultimately allowing the person to move beyond survival
People who express gratitude regularly are more likely to and into a state of thriving. Positivity also helps with emo-
respond to stressors with appreciation instead of nega- tional regulation and the ability to be more adaptive when
tive emotions. It has also helped to build a more positive coping with negativity and stress.115
perspective in those who regularly practice gratitude.97–99 Humor is essential to building positive perspective
Some clinicians are using gratitude as a treatment for anx- and helping to combat and manage stress. Laughter and
iety, depression, and anger.102–106,108–110,113 humor are some of the most commonly used and easily
Building a practice of gratitude requires intentionally accessible self-care practices.116 Everyone can laugh! In
expressing appreciation on a consistent basis. The practice fact, individuals with a high sense of humor report less
can be done through gratitude journaling, writing letters anxiety, view stimuli as less stressful, and are more likely
of gratitude, talking to family and friends about grati- to use cognitive reappraisal and problem-solving coping
tude, and sharing gratitude on social media. The more strategies.117 Humor catalyzes the process of apprecia-
specific one is regarding the appreciation, the easier it is tion and acceptance, especially self-enhancing (laughing
to practice. See Figure 23.13 for tips to develop a Practice at oneself or making light of stress) and affiliative (mak-
of Gratitude. ing light of relatable experiences with others) humor. It is
important to understand both your own and the patient’s
style of humor. Encourage adaptive humor and reframe
23.3.4 Building a Positive Perspective any maladaptive humor, such as self-defeating and aggres-
sive/sarcastic styles.
Building a positive perspective is a critical process in the
management of stress and conditions caused or exac-
erbated by stress. This holds true for both patients and
healthcare providers. Individuals may better-manage stress
23.3.5 Adaptive Coping Strategies
in the moment and subsequently withstand stress in the Patients who experience stress often reach to maladaptive
long term by using positive coping strategies and enhanc- coping strategies that may be harmful to them. Helping
ing resilience—that is, building a positive perspective. patients develop more adaptive patterns will also help
Barbara Fredrickson (2004) developed the broaden- them secure high trait resilience, measured by self-effi-
and-build theory of positive emotions.114 That theory cacy, optimism, humor, and coherence. Adaptive copers
also have longer, happier, and less stressful lives.118
An important component to developing more posi-
tive and beneficial coping strategies involves cognitively
reframing the patient’s response to stress. Cognitive reap-
praisal is a stress-coping technique based on cognitive
behavioral therapy (CBT). CBT is a widely used form
of psychotherapy that helps patients identify negative
thought and behavior patterns and then change the related
thoughts and underlying beliefs to reflect more positivity
when dealing with emotional distress.119 CBT is highly
effective and has been used to treat anxiety, depression,
relationship issues, posttraumatic stress disorder, and
chronic pain.119 Cognitive reappraisal is adaptive and
aims to regulate emotions in times of stress by adjusting
thought, interpretations, and responses to the stimuli.120
It is a tool to help edit negative thoughts and shift think-
ing from stress reaction to adaptive coping (Table 23.2
gives a few examples of positive coping traits). Patients
who practice cognitive reappraisal, changing their percep-
tion of negative events, reduce their stress by reframing
psychological and physiological responses elicited by the
stress response.121
for use in clinical settings. However, healthcare provid- changes take time and that practicing these skills regularly
ers can introduce cognitive reappraisal skills to patients, will help them develop resilience over time. Tips to pre-
which the patients can use in their daily life. Patients who scribe cognitive reappraisal to your patients can be found
use cognitive reappraisal skills report improvements in in Figure 23.14.
well-being and reduced stress, and enjoy improved health
outcomes.122
The first step in using cognitive reappraisal is thinking 23.3.6 Other Lifestyle Modifications
of a situation or experience the patient deems as “stress-
ful.” Then help them identify the emotions that they feel Adjusting lifestyle behavior is the most basic method of
related to the stressor. Every negative emotion is linked making positive, lasting changes in stress levels. Healthy
to an underlying belief that the patient feels is true. For choices in nutrition, exercise, sleep, and habits not only
example, the underlying belief of anxiety is “I am not helps to manage stress but can also prevent and/or ease
safe, I am not in control.” Once the emotions and under- symptoms of chronic diseases.123 These modifications are
lying beliefs are identified, reappraisal of the stressor can discussed in depth in other chapters of this book, but it
begin by recognizing the maladaptive, negative emotions is important to recognize that perceived stress can affect
and beliefs and working to counteract them with a posi- a patient’s lifestyle choices. To help patients implement
tive emotion. An example could be helping a patient feel changes in habits and routines, it is important to recog-
acceptance, forgiveness, or surrender to the stressor. This nize that many people feel overwhelmed by the thought
helps them associate positive emotions with the stressor of change. To control a negative habit, first understand
and in turn reinforces the positive underlying belief of why the habit was formed, and second, find an adaptive
that emotion, releasing the negative emotion and thought replacement. Attaching new positive behaviors to preex-
patterns related to the belief. This allows the patient to isting daily structure can help to facilitate positive change.
move forward, reframing their thoughts to be more posi-
tive, beneficial, or motivational. Understanding this basic 23.3.6.1 Nutrition and Stress
structure can help providers to clearly explain this pro-
cess to patients and ensure its benefit (see examples in Proper nutrition is an important pillar of well-being; how-
Table 23.3). It is important to inform your patients that ever, stressful stimuli can cause healthy eating habits to
crumble. Stress impacts eating behaviors at physiologi-
cal and neurobiological levels inasmuch as it can trigger
TABLE 23.2 Protective Positive Coping Traits for Stress the body’s reward system to seek highly palatable foods
Management containing large amounts of sugar and fat, mirroring the
response of an addiction.124 This reward-seeking behavior
Positive Coping Traits for Stress Management
is accompanied by potentially harmful alterations in glu-
Self-efficacy Confidence that one can do what is required to cose metabolism and insulin sensitivity, and by changes in
cope and that one’s efforts will work other hormones related to energy balance.125
Optimism Having positive expectations about the future
23.3.6.1.1 Mindful Eating
Humor Being able to laugh at oneself or situations in a
good-natured, light-hearted way Eating mindfully can ease the stress-related effects on
eating behaviors. To eat mindfully is to fully engage the
Coherence Having a general orientation that sees life as
meaningful and manageable senses in the preparation and consumption of a meal or
snack.126 Taking the time to fully enjoy a meal reduces
TABLE 23.3 Management and Resiliency Training: Resilience Relaxation Response (SMART-3RP59) Coping Log
Identifying Negative Thoughts Building an Adaptive Response
Negative Emotion Cognitive Distortion Adaptive Feeling Cognitive Reappraisal
Anger My circumstances are unfair or Tolerance, Clarity, and I allow what is and make compromises
unjust Sacrifice
Hopelessness Nothing will help me, I am a lost Power and Perseverance I can have a positive influence
cause
Sadness I am experiencing a loss in my life Appreciation and I cherish and value what I have or will work
Detachment with what is
Guilt I am not living up to my own morals Newness and Process I value potential for growth and change, one
step at a time
Shame I’ve done something wrong or at Courage and Choice How can I act in the face of fear to fix the
risk of being found out problem and prevent it for next time?
Resentment They don’t deserve my forgiveness Forgiveness and Focus on healing my own suffering and
Compassion understanding others, not blaming them
23.4 The Role of Technology in Stress Management 293
23
temperature, a clear indication of the sympathetic nervous can become a useful tool in routine practice. Utilizing the
system relaxation response. 51 A systematic review of 8 techniques described in this chapter, building resilience,
clinical trials found considerable backing for the useful- and unleashing the mind’s capacity to affect health is
ness of online and virtual delivery of MBT in decreasing an essential treatment option for patients of all ages and
perceived stress.138 E-mail is another effective commu- health states. The more MBTs are integrated into prac-
nication tool studied for guided, self-help interventions. tice as the standard of treatment and prevention, the more
Subjects responded positively, and with significant ben- acceptable they will become and the more positive our
efit, to e-mail based gratitude intervention on increasing impact will be on our patients’ health. This will also lead
sleep and decreasing sleep worry.139 These models of care to more research, further confirming the benefits of MBM
delivery are useful, as demand for technology-based appli- and paving the way for new discoveries about the inter-
cations and education increases with modern advance- connectedness of the mind, brain, and body.
ments. These models also allow for increased touch points
between providers and patients, while being both practi-
cal and appealing to patients and clinicians, as they are CLINIC APPLICATIONS
often convenient to use, widely available and still show
significant effects on stress reduction. • Mind-Body Medicine and many MBTs are benefi-
cial on a physiological, biochemical, psychological,
and behavioral level to patients.
23.5 SUMMARY • Providers should use the tools provided in this chap-
ter as prescriptive for wellness promotion, disease
Mind Body Medicine (MBM) and many MBTs are ben- prevention, and illness management by prescribing
eficial on a physiological, a biochemical, and an immune MBT as routine practice.
response level to patients, and have many positive psycho- • Prescribing these essential skills to patients, as
logical and behavioral outcomes. There are many health well as developing a powerful self-practice, has
benefits, both preventative and managerial in nature. the potential to increase positive interactions and
Knowing this, providers should use the tools provided in interpersonal provider-patient relationships as well
this chapter as the norm for wellness promotion, disease as provide protective and adaptive resilience in
prevention, and illness management. Prescribing MBT everyone.
REFERENCES
1. Lazarus RS and Folkman S. Stress, forms of meditation. Int. J. Cardiol. 16. NIH. NIH Complementary and Integrative
Appraisal and Coping. New York, NY: 2004;95(1):19–27. Health Agency Gets New Name. Bethesda,
Springer Publishing Company, 1984. 10. Casey A, Chang B-H, Huddleston J, Virani MD: National Center for Complementary
2. McEwen BS. Protective and damaging N, Benson H, and Dusek JA. A model and Integrative Health, U.S. Department
effects of stress mediators. N. Engl. J. for integrating a mind/body approach of Health and Human Services. 2015.
Med. 1998 Jan 15;338(3):171–179. to cardiac rehabilitation: Outcomes and https://www.nih.gov/news-events/news-
3. MacArthur SES & Health Network | correlators. J. Cardiopulm. Rehabil. Prev. releases/nih-complementary-integrative-
Research [Internet]. [cited 2017 Oct 27]. 2009;29(4):230–238. health-agency-gets-new-name.
Available from: http://www.macses.uc 11. Arora S, Aggarwal R, Moran A, 17. Bouchard S, Bernier F, Boivin E, Morin
sf.edu /research /allostatic /allostatic.php Sirimanna P, Crochet P, Darzi A, et al. B, and Robillard G. Using biofeedback
4. Dusek JA and Benson H. Mind-body Mental practice: Effective stress manage- while immersed in a stressful videogame
medicine: A model of the compara- ment training for novice surgeons. J. Am. increases the effectiveness of stress
tive clinical impact of the acute stress Coll. Surg. 2011;212(2):225–233. management skills in soldiers. PloS One
and relaxation responses. Minn. Med. 12. Ballegaard S, Petersen PB, Harboe GS, 2012;7(4):e36169.
2009;92(5):47. Karpatschof B, Gyntelberg F, and Faber 18. Jung HY, Lee H, and Park J. Comparison
5. Sterling P. Allostasis: A new paradigm to J. The association between changes in of the effects of Korean mindfulness-
explain arousal pathology. Handbook of pressure pain sensitivity and changes based stress reduction, walking, and
Life Stress, Cognition and Health, New in cardiovascular physiological factors patient education in diabetes mellitus.
York: John Wiley & Sons, 1988. associated with persistent stress. Scand. J. Nurs. Health Sci. 2015;17(4):516–525.
6. Wallace RK, Benson H, and Wilson Clin. Lab. Invest. 2014;74(2):116–125. 19. Konsta A, Dikeos D, Bonakis A,
AF. A wakeful hypometabolic physi- 13. Chen Y, Yang X, Wang L, and Zhang Economou N, Chrousos G, and Darviri
ologic state. Am. J. Physiol. Content. X. A randomized controlled trial C. Stress management techniques in pri-
1971;221(3):795–799. of the effects of brief mindfulness mary insomnia: A randomized controlled
7. Sudsuang R, Chentanez V, and Veluvan meditation on anxiety symptoms and trial. Sleep Med. 2013;14:e173.
K. Effect of Buddhist meditation on systolic blood pressure in Chinese 20. Matvienko-Sikar K and Dockray S. Effects
serum cortisol and total protein levels, nursing students. Nurse Educ. Today of a novel positive psychological interven-
blood pressure, pulse rate, lung volume 2013;33(10):1166–1172. tion on prenatal stress and well-being: A
and reaction time. Physiol. Behav. 14. Katsarou AL, Vryonis MM, Protogerou pilot randomised controlled trial. Women
1991;50(3):543–548. AD, Alexopoulos EC, Achimastos A, Birth 2017;30(2):e111–e118.
8. Dusek JA, Hibberd PL, Buczynski B, Papadogiannis D, et al. Stress manage- 21. Phillips KM, Antoni MH, Lechner SC,
Chang B-H, Dusek KC, Johnston JM, ment and dietary counseling in hyperten- Blomberg BB, Llabre MM, Avisar E,
et al. Stress management versus lifestyle sive patients: A pilot study of additional et al. Stress management intervention
modification on systolic hypertension effect. Prim. Health Care Res. Dev. reduces serum cortisol and increases
and medication elimination: A random- 2014;15(1):38–45. relaxation during treatment for nonmeta-
ized trial. J. Altern. Complement. Med. 15. Chrousos GP and Gold PW. The static breast cancer. Psychosom. Med.
2008;14(2):129–138. concepts of stress and stress sys- 2008;70(9):1044–1049.
9. Peng C-K, Henry IC, Mietus JE, tem disorders: Overview of physical 22. Esch T and Stefano GB. The neurobiology
Hausdorff JM, Khalsa G, Benson H, and behavioral homeostasis. JAMA of stress management. Neuroendocrinol.
et al. Heart rate dynamics during three 1992;267(9):1244–1252. Lett. 2010;31(1):19–39.
References 295
23. McCain NL, Gray DP, Elswick Jr RK, 36. Coban AE and Hamamci Z. The anxiety disorder: Effects on anxiety
Robins JW, Tuck I, Walter JM, et al. A comparison of the effects of a didactic and stress reactivity. J. Clin. Psychiatry
randomized clinical trial of alternative
stress management interventions in per-
sons with HIV infection. J. Consult. Clin.
stress management program and group
counselling on the coping strategies of
school counsellors. J. Psychol. Couns.
49.
2013;74(8):786.
Kang YS, Choi SY, and Ryu E. The effec-
tiveness of a stress coping program based
23
Psychol. 2008;76(3):431. Sch. 2009;19(1):71–87. on mindfulness meditation on the stress,
24. Fang CY, Reibel DK, Longacre ML, 37. Ertekin Pinar S, Duran Aksoy O, Daglar anxiety, and depression experienced by
Rosenzweig S, Campbell DE, and G, Yurtsal ZB, and Cesur B. Effect of nursing students in Korea. Nurs. Educ.
Douglas SD. Enhanced psychosocial stress management training on depres- Today 2009;29(5):538–543.
well-being following participation in sion, stress and coping strategies in 50. Lee SH, Ahn SC, Lee YJ, Choi TK,
a mindfulness-based stress reduction pregnant women: A randomised controlled Yook KH, and Suh SY. Effectiveness of
program is associated with increased trial. J. Psychosom. Obstet. Gynecol. a meditation-based stress management
natural killer cell activity. J. Altern. 2017;39(3):1–8. program as an adjunct to pharmaco-
Complement. Med. 2010;16(5):531–538. 38. Greene C and Greene BA. Efficacy of therapy in patients with anxiety disorder.
25. Kang D-H, McArdle T, Park N-J, Weaver guided imagery to reduce stress via the J. Psychosom. Res. 2007;62(2):189–195.
MT, Smith B, and Carpenter J. Dose internet: A pilot study. Holist. Nurs. 51. Shah LBI, Torres S, Kannusamy P, Chng
effects of relaxation practice on immune Pract. 2012;26(3):150–163. CML, He H-G, and Klainin-Yobas P.
responses in women newly diagnosed 39. Greeson JM, Smoski MJ, Suarez EC, Efficacy of the virtual reality-based stress
with breast cancer: An exploratory Brantley JG, Ekblad AG, Lynch TR, et management program on stress-related
study. Oncol. Nurs. Forum 2011;38(3): al. Decreased symptoms of depression variables in people with mood disorders:
240–252. after mindfulness-based stress reduction: The feasibility study. Arch. Psychiatry
26. Lengacher CA, Kip KE, Post-White J, Potential moderating effects of religios- Nurs. 2015;29(1):6–13.
Fitzgerald S, Newton C, Barta M, et al. ity, spirituality, trait mindfulness, sex, 52. Smith B, Metzker K, Waite R, and
Lymphocyte recovery after breast cancer and age. J. Altern. Complement. Med. Gerrity P. Short-form mindfulness-based
treatment and mindfulness-based stress 2015;21(3):166–174. stress reduction reduces anxiety and
reduction (MBSR) therapy. Biol. Res. 40. Jallo N, Salyer J, Ruiz RJ, and French improves health-related quality of life in
Nurs. 2013;15(1):37–47. E. Perceptions of guided imagery for an inner-city population. Holist. Nurs.
27. Fan Y, Tang Y-Y, Ma Y, and Posner MI. stress management in pregnant African Pract. 2015;29(2):70–77.
Mucosal immunity modulated by inte- American women. Arch. Psychiatry Nurs. 53. Spadaro KC and Hunker DF. Exploring
grative meditation in a dose-dependent 2015;29(4):249–254. the effects of an online asynchronous
fashion. J. Altern. Complement. Med. 41. Koloverou E, Tentolouris N, Bakoula mindfulness meditation intervention
2010;16(2):151–155. C, Darviri C, and Chrousos G. with nursing students on stress, mood,
28. Baer RA. Measuring mindful- Implementation of a stress management and cognition: A descriptive study. Nurs.
ness. Contemp. Buddhism program in outpatients with type 2 dia- Educ. Today 2016;39:163–169.
2011;12(01):241–261. betes mellitus: A randomized controlled 54. Whitebird RR, Kreitzer M, Crain AL,
29. Southwick SM and Charney DS. The trial. Hormones 2014;13(4):509–518. Lewis BA, Hanson LR, and Enstad
science of resilience: Implications for the 42. Pipe TB, Bortz JJ, Dueck A, Pendergast CJ. Mindfulness-based stress reduc-
prevention and treatment of depression. D, Buchda V, and Summers J. Nurse tion for family caregivers: A random-
Science 2012 Oct 5;338(6103):79–82. leader mindfulness meditation program ized controlled trial. Gerontologist
30. Agee JD, Danoff-Burg S, and Grant for stress management: A random- 2012;53(4):676–686.
CA. Comparing brief stress manage- ized controlled trial. J. Nurs. Adm. 55. Boxleitner G, Jolie S, Shaffer D,
ment courses in a community sample: 2009;39(3):130–137. Pasacreta N, Bai M, and McCorkle R.
Mindfulness skills and progressive 43. Riley KE, Park CL, Wilson A, Sabo Comparison of two types of meditation
muscle relaxation. Explore J. Sci. Heal. AN, Antoni MH, Braun TD, et al. on patients’ psychosocial responses dur-
2009;5(2):104–109. Improving physical and mental health in ing radiation therapy for head and neck
31. Blom M, Georgiades A, Janszky I, frontline mental health care providers: cancer. J. Altern. Complement. Med.
Alinaghizadeh H, Lindvall B, and Ahnve Yoga-based stress management versus 2017;23(5):355–361.
S. Daily stress and social support among cognitive behavioral stress manage- 56. Galatzer-Levy IR, Brown AD, Henn-
women with CAD: Results from a 1-year ment. J. Workplace Behav. Health Haase C, Metzler TJ, Neylan TC, and
randomized controlled stress manage- 2017;32(1):26–48. Marmar CR. Positive and negative
ment intervention study. Int. J. Behav. 44. Abercrombie PD, Zamora A, and emotion prospectively predict trajec-
Med. 2009;16(3):227–235. Korn AP. Lessons learned: Providing a tories of resilience and distress among
32. Bormann JE, Hurst S, and Kelly A. mindfulness-based stress reduction pro- high-exposure police officers. Emotion
Responses to mantram repetition pro- gram for low-income multiethnic women 2013;13(3):545.
gram from veterans with posttraumatic with abnormal pap smears. Holist. Nurs. 57. Kleim B, Thörn HA, and Ehlert U.
stress disorder: A qualitative analysis. J. Pract. 2007;21(1):26–34. Positive interpretation bias predicts well-
Rehabil. Res. Dev. 2013;50(6):769–784. 45. Brennan J, McGrady A, Lynch DJ, being in medical interns. Front. Psychol.
33. Brady S, O’connor N, Burgermeister Schaefer P, and Whearty K. A stress 2014;5:640–646.
D, and Hanson P. The impact of management program for higher risk 58. Nezlek JB, Holas P, Rusanowska M, and
mindfulness meditation in promoting medical students: Preliminary find- Krejtz I. Being present in the moment:
a culture of safety on an acute psychi- ings. Appl. Psychophysiol. Biofeedback Event-level relationships between
atric unit. Perspect. Psychiatr. Care 2016;41(3):301–305. mindfulness and stress, positivity, and
2012;48(3):129–137. 46. Cutshall SM, Wentworth LJ, Wahner- importance. Personal. Individ. Differ.
34. Carlson L, Beattie T, Giese-Davis J, Roedler DL, Vincent A, Schmidt JE, 2016;93:1–5.
Faris P, Tamagawa R, Fick L, et al. Loehrer LL, et al. Evaluation of a 59. Park ER, Traeger L, Vranceanu A-M,
Mindfulness-Based Cancer Recovery biofeedback-assisted meditation program Scult M, Lerner JA, Benson H, et al. The
(MBCR) and Supportive Expressive as a stress management tool for hospital development of a patient-centered pro-
Therapy (SET) Maintain Telomere nurses: A pilot study. Explore J. Sci. gram based on the relaxation response:
Length (TL) and cortisol slopes relative Heal. 2011;7(2):110–112. The Relaxation Response Resiliency
to control in distressed breast cancer 47. Dziembowska I, Izdebski P, Rasmus A, Program (3RP). Psychosomatics
survivors. J. Altern. Complement. Med. Brudny J, Grzelczak M, and Cysewski P. 2013;54(2):165–174.
2014;20(5):A24–A25. Effects of heart rate variability biofeed- 60. Paul-Labrador M, Polk D, Dwyer JH,
35. Carlson LE, Doll R, Stephen J, Faris back on EEG alpha asymmetry and anxi- Velasquez I, Nidich S, Rainforth M, et al.
P, Tamagawa R, Drysdale E, et ety symptoms in male athletes: A pilot Effects of a randomized controlled trial
al. Randomized controlled trial of study. Appl. Psychophysiol. Biofeedback of transcendental meditation on compo-
mindfulness-based cancer recovery 2016;41(2):141–150. nents of the metabolic syndrome in sub-
versus supportive expressive group 48. Hoge EA, Bui E, Marques L, Metcalf jects with coronary heart disease. Arch.
therapy for distressed survivors of breast CA, Morris LK, Robinaugh DJ, et al. Intern. Med. 2006;166(11):1218–1224.
cancer (MINDSET). J. Clin. Oncol. Randomized controlled trial of mind- 61. Barnes VA, Treiber FA, and Davis H.
2013;31(25):3119–3126. fulness meditation for generalized Impact of Transcendental Meditation® on
296 Chapter 23 Behavioral Approaches to Manage Stress
cardiovascular function at rest and dur- 76. Wayne PM, Berkowitz DL, Litrownik Chi on four chronic conditions—Cancer,
ing acute stress in adolescents with high DE, Buring JE, and Yeh GY. What do we osteoarthritis, heart failure and chronic
normal blood pressure. J. Psychosom. really know about the safety of tai chi? A obstructive pulmonary disease: A sys-
Res. 2001;51(4):597–605. systematic review of adverse event reports tematic review and meta-analyses. Br. J.
62. Cohen L, Warneke C, Fouladi RT, in randomized trials. Arch. Phys. Med. Sports Med. 2015;50(7):397–407.
Rodriguez M, and Chaoul-Reich A. Rehabil. 2014;95(12):2470–2483. 94. Yang Y, Li X-Y, Gong L, Zhu Y-L, and Hao
Psychological adjustment and sleep 77. Patañjali. The Yoga Sutras of Patanjali: Y-L. Tai Chi for improvement of motor
quality in a randomized trial of the The Book of the Spiritual Man: An function, balance and gait in Parkinson’s
effects of a Tibetan yoga intervention Interpretation. London: Watkins, 1975. disease: A systematic review and meta-
in patients with lymphoma. Cancer 78. Jeter PE, Slutsky J, Singh N, and Khalsa analysis. PloS One 2014;9(7):e102942.
2004;100(10):2253–2260. SBS. Yoga as a therapeutic intervention: 95. Li F, Harmer P, Fitzgerald K, Eckstrom
63. Raskin M, Bali LR, and Peeke HV. Muscle A bibliometric analysis of published E, Stock R, Galver J, et al. Tai chi
biofeedback and transcendental medita- research studies from 1967 to 2013. J. and postural stability in patients with
tion: A controlled evaluation of efficacy Altern. Complement. Med. 2015 Jul Parkinson’s disease. N. Engl. J. Med.
in the treatment of chronic anxiety. Arch. 21;21(10):586–592. 2012;366(6):511–519.
Gen. Psychiatry 1980;37(1):93–97. 79. Yogendra J. The study of clinical-cum- 96. Grossman P, Tiefenthaler-Gilmer U,
64. Jin P. Efficacy of Tai Chi, brisk walking, medical research and yoga. J. Yoga Inst. Raysz A, and Kesper U. Mindfulness
meditation, and reading in reducing men- 1970;16:3–10. training as an intervention for fibro-
tal and emotional stress. J. Psychosom. 80. Cramer H, Ward L, Steel A, Lauche R, myalgia: Evidence of postinterven-
Res. 1992;36(4):361–370. Dobos G, and Zhang Y. Prevalence, pat- tion and 3-year follow-up benefits in
65. Astin JA. Stress reduction through terns, and predictors of yoga use; Results well-being. Psychother. Psychosom.
mindfulness meditation: Effects on of a U.S. nationally representative survey. 2007;76:226–233.
psychological symptomatology, sense Am. J. Prev. Med. 2016;50(2):230–235. 97. Krejtz I, Nezlek JB, Michnicka A, Holas P,
of control, and spiritual experiences. 81. Barner, JC, Bohman TM, Brown CM, and Rusanowska M. Counting one’s bless-
Year B Psychiatry Appl. Ment. Health and Richards KM. Use of complementary ings can reduce the impact of daily stress.
1998;1998(4):113–114. and alternative medicine for treatment J. Happiness Stud. 2016;17(1):25–39.
66. Speca M, Carlson LE, Goodey E, and among African-Americans: A multivari- 98. Millstein RA, Celano CM, Beale EE,
Angen M. A randomized, wait-list con- ate analysis. Res. Soc. Adm. Pharm. 2010 Beach SR, Suarez L, Belcher AM, et al.
trolled clinical trial: The effect of a mind- Sep;6(3):196–208. The effects of optimism and gratitude on
fulness meditation-based stress reduction 82. Abbott RA, Martin AE, Newlove- adherence, functioning and mental health
program on mood and symptoms of stress Delgado TV, Bethel A, Thompson-Coon following an acute coronary syndrome.
in cancer outpatients. Psychosom. Med. J, Whear R, et al. Psychosocial interven- Gen. Hosp. Psychiatry 2016;43:17–22.
2000;62(5):613–622. tions for recurrent abdominal pain in 99. O’Leary K and Dockray S. The effects
67. Ussher M, Spatz A, Copland C, Nicolaou childhood. Cochrane Libr. 2017;3:1–89. of two novel gratitude and mindfulness
A, Cargill A, Amini-Tabrizi N, et al. 83. Bauer BA, Tilburt JC, Sood A, Li G, interventions on well-being. J. Altern.
Immediate effects of a brief mindfulness- and Wang S. Complementary and Complement. Med. 2015;21(4):243–245.
based body scan on patients with chronic alternative medicine therapies for 100. Kyeong S, Kim J, Kim DJ, Kim HE, and
pain. J. Behav. Med. 2014;37(1):127–134. chronic pain. Chin. J. Integr. Med. Kim J-J. Effects of gratitude meditation
68. Barrows KA and Jacobs BP. Mind-body 2016;22(6):403–411. on neural network functional connectiv-
medicine: An introduction and review 84. Panebianco M, Sridharan K, and ity and brain-heart coupling. Sci. Rep.
of the literature. Med. Clin. North Am. Ramaratnam S. Yoga for epilepsy. 2017;7:5058–5071.
2002;86(1):11–31. Cochrane Database Syst. Rev. 101. Kini P, Wong J, McInnis S, Gabana
69. Huss E and Sarid O. Visually transform- 2015;(5):CD001524. N, and Brown JW. The effects of
ing artwork and guided imagery as a 85. Agarwal RP and Maroko-Afek A. gratitude expression on neural activity.
way to reduce work related stress: A Yoga into cancer care: A review of the NeuroImage 2016;128:1–10.
quantitative pilot study. Arts Psychother. evidence-based research. Int. J. Yoga 102. Cheng S-T, Tsui PK, and Lam JH.
2014;41(4):409–412. 2018;11(1):3. Improving mental health in health care
70. Bermudez D, Benjamin MT, Porter SE, 86. Khalsa SB. Yoga as a therapeutic inter- practitioners: Randomized controlled
Saunders PA, Myers NAL, and Dutton vention. Princ. Pract. Stress Manag. trial of a gratitude intervention. J.
MA. A qualitative analysis of beginning 2007;3:449–462. Consult. Clin. Psychol. 2015;83(1):177.
mindfulness experiences for women 87. Koh TC. Tai chi chuan. Am. J. Chin. 103. Greene N and McGovern K. Gratitude,
with post-traumatic stress disorder and Med. 1981;9(01):15–22. psychological well-being, and perceptions
a history of intimate partner vio- 88. Yang G-Y, Wang L-Q, Ren J, Zhang Y, of posttraumatic growth in adults who
lence. Complement. Ther. Clin. Pract. Li M-L, Zhu Y-T, et al. Evidence base of lost a parent in childhood. Death Stud.
2013;19(2):104–108. clinical studies on Tai Chi: A bibliometric 2017;41(7):436–446.
71. Breslin MJ and Lewis CA. Theoretical analysis. PloS One 2015;10(3):e0120655. 104. Kerr SL, O’Donovan A, and Pepping CA.
models of the nature of prayer and health: 89. Wayne PM, Manor B, Novak V, Costa Can gratitude and kindness interventions
A review. Ment. Health Relig. Cult. MD, Hausdorff JM, Goldberger AL, et enhance well-being in a clinical sample?
2008;11(1):9–21. al. A systems biology approach to study- J. Happiness Stud. 2015;16(1):17–36.
72. Fredrickson BL, Cohn MA, Coffey KA, ing Tai Chi, physiological complexity and 105. Lau BH-P and Cheng C. Gratitude and
Pek J, and Finkel SM. Open hearts build healthy aging: Design and rationale of a coping among familial caregivers of per-
lives: Positive emotions, induced through pragmatic randomized controlled trial. sons with dementia. Aging Ment. Health
loving-kindness meditation, build conse- Contemp. Clin. Trials 2013;34(1):21–34. 2017;21(4):445–453.
quential personal resources. J. Pers. Soc. 90. Lauche R, Wayne P, and Dobos G. 106. Ng M-Y and Wong W-S. The dif-
Psychol. 2008;95(5):1045. Prevalence, patterns, and predictors of ferential effects of gratitude and sleep
73. Sharma M. Yoga as an alternative and t’ai chi and qigong use in the United on psychological distress in patients
complementary approach for stress States: Results of a nationally representa- with chronic pain. J. Health Psychol.
management: A systematic review. J. tive survey. J. Altern. Complement. Med. 2013;18(2):263–271.
Evid. Based Complement. Altern. Med. 2016;22(4):336–342. 107. Petrocchi N and Couyoumdjian A. The
2014;19(1):59–67. 91. Del Rosso A and Maddali-Bongi S. impact of gratitude on depression and
74. Wang F, Lee E-KO, Wu T, Benson H, Mind body therapies in rehabilita- anxiety: The mediating role of criticizing,
Fricchione G, Wang W, et al. The effects tion of patients with rheumatic dis- attacking, and reassuring the self. Self
of tai chi on depression, anxiety, and eases. Complement. Ther. Clin. Pract. Identity 2016;15(2):191–205.
psychological well-being: A systematic 2016;22:80–86. 108. Southwell S and Gould E. A randomised
review and meta-analysis. Int. J. Behav. 92. Theadom A, Cropley M, Smith HE, wait list-controlled pre-post-follow-
Med. 2014;21(4):605–617. Feigin VL, and McPherson K. Mind and up trial of a gratitude diary with a
75. Cramer H. The efficacy and safety body therapy for fibromyalgia. Cochrane distressed sample. J. Posit. Psychol.
of yoga in managing hypertension. Database Syst. Rev. 2015;(4):CD001980. 2017;12(6):579–593.
Exp. Clin. Endocrinol. Diabetes 93. Chen Y-W, Hunt MA, Campbell KL, 109. Van Dusen JP, Tiamiyu MF, Kashdan
2016;124(02):65–70. Peill K, and Reid WD. The effect of Tai TB, and Elhai JD. Gratitude, depression
References 297
and PTSD: Assessment of struc- 127. Mason AE, Daubenmier J, Moran PJ, illness. Int. J. Environ. Res. Public Health
tural relationships. Psychiatry Res. Kristeller J, Dallman M, Lustig RH, et 2015;12:1928.
2015;230(3):867–870.
110. Vernon LL, Dillon JM, and Steiner
AR. Proactive coping, gratitude, and
al. Increases in mindful eating predict
reductions in consumption of sweets
and desserts: Data from the support-
140. Hoge EA, Bui E, Marques L, Metcalf
CA, Morris LK, Robinaugh DJ, et al.
Randomized controlled trial of mindfulness
23
posttraumatic stress disorder in col- ing health by integrating nutrition and meditation for generalized anxiety disor-
lege women. Anxiety Stress Coping exercise (SHINE) clinical trial. J. Altern. der: Effects on anxiety and stress reactivity.
2009;22(1):117–127. Complement. Med. 2014;20(5):A17–A17. J. Clin. Psychiatry 2013;74(8):786.
111. Wood AM, Maltby J, Gillett R, Linley 128. Jordan CH, Wang W, Donatoni L, and 141. Lakkireddy D, Atkins D, Pillarisetti J,
PA, and Joseph S. The role of gratitude in Meier BP. Mindful eating: Trait and Ryschon K, Bommana S, Drisko J, et al.
the development of social support, stress, state mindfulness predict healthier eat- Effect of yoga on arrhythmia burden,
and depression: Two longitudinal studies. ing behavior. Personal. Individ. Differ. anxiety, depression, and quality of life in
J. Res. Personal. 2008;42(4):854–871. 2014;68:107–111. paroxysmal atrial fibrillation: The YOGA
112. Shao D, Gao W, and Cao F-L. Brief psy- 129. Davies SK, Ang JE, Revell VL, Holmes my heart study. J. Am. Coll. Cardiol.
chological intervention in patients with B, Mann A, Robertson FP, et al. Effect 2013;61(11):1177–1182.
cervical cancer: A randomized controlled of sleep deprivation on the human 142. Cramer H, Lauche R, Klose P, Lange
trial. Health Psychol. 2016;35(12):1383. metabolome. Proc. Natl. Acad. Sci. S, Langhorst J, and Dobos G. Yoga
113. Baxter HJ, Johnson MH, and Bean D. 2014;111(29):10761–10766. for improving health‐related qual-
Efficacy of a character strengths and 130. Irwin MR, Olmstead R, and Carroll ity of life, mental health and cancer‐
gratitude intervention for people with JE. Sleep disturbance, sleep duration, related symptoms in women diagnosed
chronic back pain. Aust. J. Rehabil. and inflammation: A systematic review with breast cancer. Cochrane Libr.
Couns. 2012;18(2):135–147. and meta-analysis of cohort studies and 2017;(1):CD010802.
114. Fredrickson BL. The broaden-and-build experimental sleep deprivation. Biol. 143. Khobragade Y, Abas ABL, Ankur B, and
theory of positive emotions. Philos. Trans. Psychiatry 2016;80(1):40–52. Khobragade S. Meditation as primary
R. Soc. B Biol. Sci. 2004;359(1449):1367. 131. Sano A, Phillips AJ, Amy ZY, McHill intervention strategy in prevention of
115. Tugade MM and Fredrickson BL. AW, Taylor S, Jaques N, et al. cardiovascular diseases. Int. J. Res. Med.
Resilient individuals use positive emo- Recognizing academic performance, Sci. 2016;4(1):12–21.
tions to bounce back from negative emo- sleep quality, stress level, and mental 144. Streeter CC, Gerbarg PL, Whitfield TH,
tional experiences. J. Pers. Soc. Psychol. health using personality traits, wear- Owen L, Johnston J, Silveri MM, et al.
2004;86(2):320. able sensors and mobile phones. In: Treatment of major depressive disorder
116. Lubinska-Welch I, Pearson T, Comer L, Wearable and Implantable Body Sensor with Iyengar yoga and coherent breath-
and Metcalfe SE. Nurses as instruments Networks (BSN), 2015 IEEE 12th ing: A randomized controlled dosing
of healing: Self-care practices of nurses International Conference on Wearable study. J. Altern. Complement. Med.
in a rural hospital setting. J. Holist Nurs. and Implantable Body Sensor Networks 2017;23(3):201–207.
2016;34(3):221–228. (BSN), Cambridge, MA: IEEE, 2015. pp. 145. Gainey A, Himathongkam T, Tanaka
117. Abel MH. Humor, stress, and coping 1–6. doi: 10.1109/BSN.2015.7299420 H, and Suksom D. Effects of Buddhist
strategies. Humor Int. J. Humor Res. 132. Irish LA, Kline CE, Gunn HE, Buysse DJ, walking meditation on glycemic control
2002;15(4):365–381. and Hall MH. The role of sleep hygiene and vascular function in patients with
118. Arvidsdotter T, Marklund B, Taft C, and in promoting public health: A review type 2 diabetes. Complement. Ther. Med.
Kylén S. Quality of life, sense of coher- of empirical evidence. Sleep Med. Rev. 2016;26:92–97.
ence and experiences with three different 2015;22:23–36. 146. Pacanowski CR, Diers L, Crosby RD, and
treatments in patients with psychological 133. Paruthi S, Brooks LJ, D’Ambrosio C, Neumark-Sztainer D. Yoga in the treat-
distress in primary care: A mixed-meth- Hall WA, Kotagal S, Lloyd RM, et al. ment of eating disorders within a residen-
ods study. BMC Complement. Altern. Consensus statement of the American tial program: A randomized controlled
Med. 2015;15(1):132. Academy of sleep medicine on the recom- trial. Eat. Disord. 2017;25(1):37–51.
119. Butler AC, Chapman JE, Forman EM, mended amount of sleep for healthy 147. Kuo B, Bhasin M, Jacquart J, Scult MA,
and Beck AT. The empirical status of children: Methodology and discussion. J. Slipp L, Kagan Riklin EI, et al. Genomic
cognitive-behavioral therapy: A review Clin. Sleep. Med. 2016;12(11):1549–1561. and clinical effects associated with a
of meta-analyses. Clin. Psychol. Rev. 134. Panel CC, Watson NF, Badr MS, relaxation response mind-body interven-
2006;26(1):17–31. Belenky G, Bliwise DL, Buxton OM, et tion in patients with irritable bowel syn-
120. Gross JJ and Thompson RA. Emotion al. Recommended amount of sleep for drome and inflammatory bowel disease.
Regulation: Conceptual Foundations, New a healthy adult: A joint consensus state- PloS One 2015;10(4):1–26. doi:10.1371/
York, NY, US: The Guilford Press 2007. ment of the American Academy of sleep journal.pone.0123861
121. Jamieson JP, Mendes WB, and Nock MK. medicine and sleep research society. J. 148. Shallcross AJ and Visvanathan PD.
Improving acute stress responses: The Clin. Sleep. Med. 2015;11(6):591. Mindfulness-Based Cognitive Therapy
power of reappraisal. Curr. Dir. Psychol. 135. Billings DW, Cook RF, Hendrickson A, for Insomnia. In: Mindfulness-Based
Sci. 2013;22(1):51–56. and Dove DC. A web-based approach to Cognitive Therapy. [Internet]. Springer,
122. Troy AS, Shallcross AJ, Davis TS, and managing stress and mood disorders in 2016 [cited 2017 Jul 30]. p. 19–29.
Mauss IB. History of mindfulness-based the workforce. J. Occup. Environ. Med. Available from: http://link.spri nger.com/
cognitive therapy is associated with 2008;50(8):960. chapter/10.1007/978-3 -319-29866 -5_3
increased cognitive reappraisal ability. 136. Mani M. E-Mindful Health: Evaluation 149. Sharma V, Saito Y, and Amit S. Mind-
Mindful. J. 2013;4(3):213–222. of Mobile Apps for Mindfulness. body medicine and irritable bowel
123. American College of Lifestyle Medicine. Brisbane, Australia: Queensland syndrome: A randomized control trial
What Is Lifestyle Medicine? [Internet], University of Technology, 2017. using stress reduction and resiliency
2015. Available from: www.lifestyleme 137. Blodt S, Pach D, Roll S, and Witt CM. training. J. Altern. Complement. Med.
dicine.org / What-is-Lifestyle-Medicine Effectiveness of app-based relaxation 2014;20(5):A94–A94.
124. Masih T, Dimmock JA, Epel ES, and for patients with chronic low back pain 150. Morone NE, Greco CM, Moore CG,
Guelfi KJ. Stress-induced eating and the (relaxback) and chronic neck pain (relax- Rollman BL, Lane B, Morrow LA, et al.
relaxation response as a potential anti- neck): Study protocol for two randomized A mind-body program for older adults
dote: A review and hypothesis. Appetite pragmatic trials. Trials 2014;15(1):490. with chronic low back pain: A random-
2017;118:136–143. 138. Jayawardene WP, Lohrmann DK, Erbe ized clinical trial. JAMA Intern. Med.
125. Sinha R and Jastreboff AM. Stress RG, and Torabi MR. Effects of preven- 2016;176(3):329–337.
as a common risk factor for obe- tive online mindfulness interventions on 151. Deng GE, Rausch SM, Jones LW,
sity and addiction. Biol. Psychiatry stress and mindfulness: A meta-analysis Gulati A, Kumar NB, Greenlee H, et al.
2013;73(9):827–835. of randomized controlled trials. Prev. Complementary therapies and integrative
126. Framson C, Kristal AR, Schenk JM, Med. Rep. 2017;5:150–159. medicine in lung cancer: Diagnosis and
Littman AJ, Zeliadt S, and Benitez D. 139. Sahlin E, Ahlborg Jr G, Tenenbaum A, and management of lung cancer: American
Development and validation of the mind- Grahn P. Using nature-based rehabilitation College of chest physicians evidence-
ful eating questionnaire. J. Am. Diet. to restart a stalled process of rehabilitation based clinical practice guidelines. Chest J.
Assoc. 2009;109(8):1439–1444. in individuals with stress-related mental 2013;143(5):420–436.
298 Chapter 23 Behavioral Approaches to Manage Stress
152. Millstine D, Chen CY, and Bauer B. Chi versus physical therapy on mindful- Melow-Murchie M. Investigating
Complementary and integrative medicine ness in knee osteoarthritis. Mindful. J. impacts of incorporating an adjuvant
in the management of headache. BMJ 2017;8(5):1195–1205. mind–body intervention method into
2017 May 16;357:j1805. 155. Colgan DD, Christopher M, Michael P, treatment as usual at a community-
153. Burschka JM, Keune PM, Hofstadt- and Wahbeh H. The body scan and mind- based substance abuse treatment
van Oy U, Oschmann P, and Kuhn P. ful breathing among veterans with PTSD: facility: A pilot randomized controlled
Mindfulness-based interventions in Type of intervention moderates the rela- study. SAGE Open 2015;5(1). doi:
multiple sclerosis: Beneficial effects of Tai tionship between changes in mindfulness 2158244015572489.
Chi on balance, coordination, fatigue and and post-treatment depression. Mindful. 157. Rosen JE, Gardiner P, and Lee SL.
depression. BMC Neurol. 2014;14(1):165. J. 2016;7(2):372–383. Complementary and integrative treat-
154. Lee AC, Harvey WF, Wong JB, Price LL, 156. Nakamura Y, Lipschitz DL, Kanarowski ments: Thyroid disease. Otolaryngol.
Han X, Chung M, et al. Effects of Tai E, McCormick T, Sutherland D, and Clin. North Am. 2013;46(3):423–435.
24
CHAPTER
Key Points.................................................................................. 299 24.3.2 Visit Structures and Delivery Methods................... 305
24.1 Introduction...................................................................... 299 24.3.3 Health and Wellness Coaching Payment Models.......305
24.2 Health and Wellness Coaching (HWC)—as a Field and 24.4 Evaluation and Research in Health and Wellness
a Profession...................................................................... 300 Coaching.......................................................................... 306
24.2.1 Theoretical Platform and Historical Underpinnings..... 300 24.4.1 Current Evidence Base......................................... 306
24.2.2 Coaching versus Therapy..................................... 301 24.5 Health and Wellness Coaching—Practical Nuts and Bolts......307
24.2.3 Coaching versus Health Education and Case 24.5.1 Coaches Need Coaching....................................... 307
Management������������������������������������������������������� 302 24.5.2 Referral to Health and Wellness Coaches.............. 307
24.2.4 Standardizing the Field of Health and Wellness 24.5.3 Hiring Health and Wellness Coaches..................... 307
Coaching (HWC)�������������������������������������������������� 302 24.5.4 Assimilation of Health and Wellness Coaches........ 308
24.2.5 Health and Wellness Coach Training and 24.5.5 Protecting Client/Patient Privacy........................... 308
Education������������������������������������������������������������ 303 24.6 Health Coaching in the Future of Health Care—a
24.3 Health and Wellness Coaching—Best Practices in Vision of Hope................................................................... 308
Clinical Areas of Innovation............................................... 304 Clinical Applications................................................................... 308
24.3.1 Client and Patient Populations and Care Settings......304 References................................................................................ 309
frameworks within systems that allow neither time nor smoking in restaurants for example), innovative treat-
reimbursement for counseling for positive lifestyle change. ment approaches, and increased awareness of the hazards
This situation creates stories of disempowered, injured, or of smoking, led to this success. It seems readily apparent
ill persons being told what to do and when to do it while that while having accurate information about health and
only rarely being told why they need to make the changes health behaviors is critical, knowledge alone does not
or how they may achieve these changes given their own change behaviors. Indeed, in the field of management, it
unique life circumstances, values, and beliefs. had been established that knowledge alone does not lead to
Health and wellness coaches partner with clients to help action but that attitudes, subjective norms, and perceived
them recognize their own narratives of illness and healing; behavioral control were major determinants of behavior
reveal beliefs and choose those they wish to change; rein- change.6 These thoughts had not yet been extrapolated to
force their engagement and empowerment; identify their attempts in shifting health behaviors.
values and priorities; chart their plan for lifestyle changes
within reasonable time frames; recognize resources and
address barriers; set, track, and attain self-selected goals; 24.2.1 Theoretical Platform and
and establish accountability and social support. They hold
the vision of the wholeness within an individual—espe- Historical Underpinnings
cially when the patients are unable to see it for themselves. The roots of health and wellness coaching (HWC) emerge
While all healthcare providers would ideally provide some from multiple fields outside of healthcare. In particular,
of these services, it is not routinely done. Even in inte- different branches of psychology have contributed a great
grative practices aligned with a holistic model of healing, deal to the foundation, beginning a century ago with
practitioners are often still the experts being sought for the work of Adler and Jung. Adler described our need to
advice, information, or intervention rather than as sup- achieve personal goals that have value for society and how
porting the patient as the expert in their own life. Indeed, these goals stem from the creative and unique power of
the health and wellness coach has been the “missing pro- an individual (even if unconscious). He further noted that
vider” from our healthcare system. The recognition of adults use planning to create their future, and emphasized
that need, and the training and employment of health and how individuals, when feeling encouraged by others, feel
wellness coaches to fill this gap, increases our likelihood capable and appreciated, and act in connected and coop-
of success in improving overall health through individuals erative ways.7 Similarly, Jung proposed that individuals
achieving sustainable lifestyle changes and creating new continued learning throughout life as they moved toward
narratives for well-being. living authentically and “on purpose.” He emphasized
choosing the values by which they live rather than reflex-
ively conforming to social norms.8 Mid-century theorists
24.2 HEALTH AND WELLNESS added to these core tenets important findings on how
COACHING (HWC)—AS A humans are motivated to find personal meaning9 and meet
their basic needs in addition to striving toward self-actu-
FIELD AND A PROFESSION alization.10 Humanistic psychology added to the study
of motivation by emphasizing the role of interpersonal
Given the growing burden of chronic disease and con- connectedness and sense of purpose.11 More recent work
tributory health behaviors, the importance of adopting a further articulates the underpinnings of HWC through
Lifestyle Medicine approach to health and wellness has self-determination theory12 and subsequently, self-concor-
been well established elsewhere in this book. The largest dance theory.13,14 These theories explain that individuals
malleable factor in the development and course of many, if strive toward goal attainment when they perceive their
not all, chronic illnesses is lifestyle. In the 1990s, despite the goals as being determined by their core values and inter-
recognition of the importance of personal and community ests rather than by external forces. Later developmental
health behavior choices,1 the medical system was still not psychologists added a constructivist element15,16 and dis-
successfully impacting most individuals’ behavior choices. cerned the precedents for “vital engagement”16 in one’s
Early efforts in disease and case management, patient edu- life. Taken together, these theorists consider individuals
cation, and other population-based interventions showed as life-long learners whose individual values and sense
some benefit in utilization reduction3 and medication of purpose facilitate their potential for positive change.
compliance. It had been established decades earlier that HWC is founded on the framework that humans strive
successfully making positive lifestyle changes requires self- toward self-actualization, have strong intrinsic resources,
efficacy,4 an individual’s confidence in successfully engag- and best access their ability for positive change in a safe,
ing in a specific behaviors. However, self-efficacy was still confidential alliance wherein they are treated with deep
not readily discussed or applied in mainstream medical respect and unconditional positive regard.
care. Multiple educational initiatives were implemented At the same time that the above foundation was evolv-
both in public health forums and within physicians’ prac- ing in psychology and birthing the intervention of coaching,
tices, yet the statistics in health areas that are significantly further exploration in healthcare, in conjunction with the
impacted by lifestyle choices—such as prevalence of diabe- reemerging social phenomenon of wholeness, combined to
tes, obesity, and heart disease—continued to worsen. The give rise to Integrative HWC as a new field, one that was
only negative health behavior among Americans that has in alignment with the holistic and integrative movement
diminished has been smoking.5 A comprehensive approach within health and well-being. While HWC and Integrative
to tobacco usage, combining public health policies (no HWC share the theoretical and applied grounding in
24.2 Health and Wellness Coaching (HWC)—as a Field and a Profession 301
change theory, behavioral health principles, and techniques international group of researchers, theorists, and thera-
24
for coaching practice, integrative health coaching has pists to provide a more comprehensive model of change
deeper underpinnings from the holistic and complementary than was currently in use for the treatment of addictive
healthcare arenas. Apart from the following description behaviors. Popularized in Changing for Good, the model
of its evolution, and occasional differentiation in research posits that individuals undertaking an intentional change
studies, for the purposes of this chapter, we will use the term go non-linearly through particular stages in consider-
HWC to be inclusive of all health and wellness coaching ing, approaching, enacting, and maintaining change. The
practice, recognizing that integrative HWC has a deeper model has continued to evolve, and as of 2016, in Changing
commitment to a mind/body/spirit perspectives, and aware- to Thrive, 25 it provides increased focus on working with
ness of a broader range of available integrative healthcare individuals who are not yet ready to prepare or take action
practitioners and therapeutic approaches. Leaders in HWC and are in need of change in a health-related area.
and Integrative HWC have joined together to advance the In the 1990s, companies, beginning with IBM, began
commonality of minimal standards setting for knowledge, taking “coaching from being a personal development
skills competency, and educational requirements, acknowl- vehicle for individuals to a way of developing people in
edging that integrative HWC requires an additional level of business”. 26 Thomas Leonard in 1995 started the non-
skill and training above this minimum. profit International Coach Federation (ICF), which began
The first U.S. holistic retreat center was created by to define coaching competencies and offer standardized
Evarts Loomis, MD, in 1958, bringing the perspective of coach credentials. By 1999, ICF implemented coach-train-
whole-person healing through the application of lifestyle ing standards and began to accredit individual life coach
modification, including nutrition, exercise, mind/body training programs.
practices, and time in nature. In the 1970s, Dr. Loomis
went on to be a co-founder of the American Holistic
Medical Association. The emerging human potential
24.2.2 Coaching versus Therapy
movement, cultivating wellness and personal transforma- A significant proportion of patients/clients in healthcare
tion, laid the groundwork for coaching in the personal and community health settings are also dealing with men-
development area. Tim Gallwey brought the Inner Game tal health conditions, including depression, anxiety, and
approach to coaching17 emphasizing the process of how addiction. 27 The theoretical framework described above
to get out of your own way to let your best emerge. John has been further augmented with myriad techniques
Travis, MD, self-published The Wellness Inventory,18 derived from over five decades of outcomes data in psycho-
launching the wellness movement and introducing the therapy28 and the development of brief solution-focused
Illness-Wellness continuum, expanding our horizons therapies. 29,30 These techniques enable providers, espe-
beyond a treatment paradigm (Figure 24.1). cially coaches, to focus not on pathology but on behavior
In the 1980s, Thomas Leonard began life coaching as change. National standards in mental health literacy for
a practice and worked to codify, popularize, and globalize health and wellness coaches have not yet been established
the discipline of coaching outside of the sporting world.19 but are an important gap to fill in the future. While there
Anthony Grant’s work in coaching psychology are important areas of overlap between HWC and psycho-
advanced the legitimacy of life coaching as a platform for therapy, there are critical distinctions. One is that health
applying positive psychology for enhanced mental health, and wellness coaches do not diagnose or treat, and they
quality of life, and goal attainment. 20 William Miller focus not on the pathology or diagnosis of a problem but
introduced motivational interviewing 21 for use with prob- on a goal. HWC doesn’t seek to provide direction but to
lem drinkers. As a style of communication, it laid a foun- create opportunity through questions asked in a safe space
dation for health and wellness coaching. 22 It is now highly that allow clients to discover their own insights.31 Clarity
evidence-based and used with multiple health issues23 to on HWC scope-of-practice is important. At times, indi-
access clients’ present motivation to change behaviors that viduals experiencing a psychiatric disorder, for example,
are inconsistent with personal values or goals. In 1982, a major depressive disorder or severe anxiety, may seek
the Transtheoretical Model (TTM) was initially pro- HWC as their treatment. Health and wellness coaches are
posed 24 and then further developed collaboratively by an trained to know how and when to refer these individuals
WELLNESS PARADIGM
Pre- High-
Mature Level
Disability Symptoms Signs Awareness Education Growth
Death Wellness
TREATMENT PARADIGM
Neutral Point
(No discernible illness or wellness)
for appropriate treatment with licensed mental health 3. HWC Training programs varying widely in
professionals. HWC can be a safe portal into needed approach, content, skills training, format, assess-
mental health services, as some individuals may avoid ment, and length; and
seeking needed therapy because of fear or misperceptions. 4. Research studies with unclear or inconsistent inter-
In many situations, a client may benefit from receiving ventions, all entitled HWC.
therapy and coaching at the same time, as each addresses
different needs, with therapy working at elucidating past (See Evaluation and Research in Health and Wellness
events leading to current dysfunction and HWC focus- Coaching for more details.)
ing on present and future goals achievement and mind/ In order to nurture the professional advancement of
body skill acquisition for improved self-regulation. Clients HWC, national standards for the use of terms and mini-
with active addictions or eating disorders are also likely to mal criteria for basic training and education needed to
require connection to a mental health provider, although be established. Clear definitions and standards were
HWC may sometimes work synergistically (Figure 24.2). also needed in order to create a consistent basis for rig-
orous and meaningful evaluation studies. Therefore, in
2010, the National Consortium for Credentialing Health
24.2.3 Coaching versus Health Education and Wellness Coaching (NCCHWC) was born out of a
and Case Management national summit that brought together over 70 stakehold-
ers from widely diverse fields of healthcare (grant sup-
All educational approaches focus on conveying information, port generously provided by the Institute for Integrative
or perhaps the teaching of skills for managing health condi- Health; https://tiih.org/). Those stakeholders, donors, and
tions. While health and wellness coaches do at times provide advisors represented professional associations in health
information or resources, education is never their domi- promotion, coaching psychology, nursing, and medicine;
nant function. A “coaching approach” to teaching occurs researchers, experienced coaches, and subject matter
as “elicit, provide, elicit,” a technique from Motivational experts; and commercial training organizations and expe-
Interviewing that involves asking for permission to share rienced university educators in the field. With nonprofit
content, exploring what the client’s current knowledge or 501(c)(3) status gained in 2013, the NCCHWC’s goal was
understanding is, and then offering new information and to professionalize the expanding field of health and well-
asking how clients may implement or apply it.23 The second ness coaching with an evidence-informed foundation.
philosophical difference arises from the goal setting pro- Given the repeated calls in the literature to clarify
cess. The HWC agenda, unlike in the other approaches, is the heterogeneity of the term health and wellness coach-
client-driven—not dictated by the goals or priorities of the ing, and to use an evidence-based approach to iden-
disease management company, insurer, employer, or health- tify the conceptual and interventional components of
care provider—and confirms the “clients’ values, sense of HWC, Wolever, Simmons, Sforzo et al. 32 systemati-
purpose and personal vision for their lives”.31 cally reviewed the English and Spanish HWC literature
through January 2013, using the international guidelines
established by PRISMA (Preferred Reporting Items for
24.2.4 Standardizing the Field of Health Systematic Review and Meta-Analyses). The Pico-derived
and Wellness Coaching (HWC) primary research question was: “How are interven-
tions described as health or wellness coaching defined
In 2008, it became clear to leaders in this field that grow- and operationalized in the peer-reviewed medical lit-
ing numbers in four domains had created a climate of con- erature?” Specifically, the review sought to clarify what
fusion and erratic quality: approaches, practices, strategies, and methodologies con-
stitute HWC in the peer-reviewed literature. A standard-
1. Widely diverse practitioners self-identifying as ized definition of HWC would allow for a more rigorous
health and/or wellness coaches; evaluation of HWC. In addition, the professional skills
2. Organizations professing to offer health and/or needed to appropriately train HWC could be better iden-
wellness coaching as a service line; tified (Figure 24.3).
24
adequate detail to code
Patient Centered (Institute of 86% of 228 trials partially or completely
Medicine 2001) aligned
Patient-determined goals 71% of 217 trials
Figure 24.3 Full-text articles (284 total articles) were identified for the quantitative synthesis to define the key aspects of
HWC, as operationalized in the literature. Six particular definitional elements were evaluated using all articles that provided
adequate detail to code for each key element, of which 11 to 23% did not.
Overall, the literature described HWC as: 24.2.5 Health and Wellness Coach
A relationship-based (78%) “process that is fully or
Training and Education
partially patient-centered (86% of articles), included In 2016, the NCCHWC moved into a formal collaboration
patient-determined goals (71%), incorporated self- with the National Board of Medical Examiners (NBME)
discovery and active learning processes (63%) (vs. and in 2017 evolved into a 501(c)(6), the ICHWC—
more passive receipt of advice), encouraged account- the International Consortium for Health and Wellness
ability for behaviors (86%), and provided some type Coaching (www.ICHWC.org). Their work resulted in
of education to patients along with using coaching exacting processes for approval of educational programs
processes (91%). and national board certification of individual coaches.
The Wolever, Simmons, Sforzo et al.32 systematic review
The summative results of the first six years of of the HWC literature also examined the reported education
NCCHWC work were published in 201533 and proposed and training information. Of the 246 articles that provided
this working definition of HWC: adequate information about the professional background
of the health and wellness coaches, 95% employed human
Health and Wellness Coaches are professionals from coaches, while the remaining 5% employed technology-
diverse backgrounds and education who work with based coaching only. Of the programs that used human
individuals and groups in a client-centered process coaches, 93% used professionals and 7% (17 of 234) used
to facilitate and empower the client to achieve self- lay individuals (Figure 24.4).
determined goals related to health and wellness. Only 22% of the articles using human coaches
Successful coaching takes place when coaches apply described the amount of coach-specific training received
clearly defined knowledge and skills so that clients by those employing the coaching. Coach-specific training
mobilize internal strengths and external resources ranged from less than two hours to close to two years, with
for sustainable change.33 a median between six and 40 hours. Such wide variance
Other 0.8%
Medical
Professionals: Physicians 6%
demands professional attention in order to improve and levels); private sector; government (e.g., U.S. Department
standardize the field. of Veterans Affairs), and internal programs of large orga-
Historically, formal training in life coaching and in nizations, which include employee benefits vendors, well-
executive coaching began with ICF in the mid-1990s. As ness vendors, health systems, and health plans. Some
of 2016, more than 20,000 coaches held one of the ICF programs have a strong integrative health focus, 36,37 and
coach credentials: Associate Certified Coach, Professional others emphasize subspecialties such as nurse coaching. 38
Certified Coach, and Master Certified Coach. ICF has Program fees vary widely from approximately $2,000 for
accredited more than 200 coach-training programs world- a private sector training program to over $40,000 for the
wide (at least 125 hours of coaching competency training). cost of a Master’s Degree.
(ICF website accessed 8.18.17) The ICF core competencies Currently, both those from non-clinical and licensed
and ethical guidelines are widely applied and respected clinical backgrounds are eligible to become national
as the foundation for professional coaching in leadership, board certified health and wellness coaches (NBC-HWC).
business, and life.34 ICF standards are mostly focused on Future studies on the impact of a coach’s background and
the executive and business domains, not on health and training on the effectiveness of coaching may lead to fur-
wellness coaching, and do not yet include a robust base ther refinement of standards for the education of health
in coaching science, coaching psychology, or coaching and wellness coaches.
research.
In the 1990s, the first pioneering health, wellness,
and integrative health coaches began practicing. The first 24.3 HEALTH AND WELLNESS
independent health and wellness coach training and cer-
tification program launched in 2002, the first academic COACHING—BEST
program in 2005, and by 2017, more than 50 diverse U.S.
programs had been approved by the ICHWC. Program
PRACTICES IN CLINICAL
standards include synchronous training and mentoring AREAS OF INNOVATION
in health and wellness coaching competencies confirmed
by a pass/fail assessment of practical skills. Coach gradu- 24.3.1 Client and Patient Populations
ates of ICHWC transitionally approved training programs
are eligible to sit for the national board certification for
and Care Settings
health and wellness coaches, an exam of coaching knowl- HWC started out as an adjunct service, with most health
edge launched nationally in September 2017, and offered and wellness coaches working in a private practice, fee-
biannually as of 2018. The examination and process were for-service setting, separate from where patients received
developed jointly by ICHWC and NBME, the latter of other medical care. More recently, as HWC is becom-
which has implemented physician-credentialing examina- ing an increasingly recognized healthcare profession, it
tions since 1915. The national coaching competencies for is also integrating into the healthcare delivery systems, 39
health and wellness coaches emerged from a rigorous and wellness centers,40 recreation facilities,41 employee health
inclusive process designed by the NBME, building upon a programs,42,43 community centers,44 and educational envi-
best practice Job Task Analysis conducted by ICHWC35,33 ronments,45 and is being offered for special populations
While competencies overlap significantly with those of like the homeless and other underserved46,47 groups. New
ICF, additional knowledge of domains relevant to health integration into the healthcare delivery system increases
behavior change—including self-determination theory, the the potential for innovative HWC to become an impactful
transtheoretical model, motivational interviewing, social systemic change agent.
cognitive theory, and positive psychology—is required. Physician counseling for health behaviors can help
Twenty-six topical competencies are organized into four patients implement positive lifestyle changes.48 Therefore,
domains (coaching structure, coaching process, legal and one potential strategy to enhance HWC’s impact is to inte-
ethical standards, and health and wellness knowledge, as grate it into a person’s routine medical care. For example,
well as evidence-based healthy lifestyle standards). The in one study nearly 1,000 patients (average BMI 34.5)
training and education of health and wellness coaches is were referred to a telephonic health coaching program
supported by ten textbooks authored by thought leaders by their healthcare provider for assistance with weight
on coaching competencies, motivational interviewing, and management. The each, on average, received on average
the transtheoretical model, plus a growing current peer- 1.8 wellness coaching sessions, and demonstrated a one
reviewed literature base. In 2018, national HWC training unit reduction in their BMI over 12 months, compared to
and education program standards will advance to require a the approximately 19,000 control patients who remained
minimum of 60 hours of training in coaching competencies weight stable.49
(40 hours must be synchronous, interactive training), and One novel setting for health and wellness coaching is
15 hours of healthy lifestyle education, plus mentor coach within a worksite wellness center. It has been well doc-
feedback on three coaching sessions, and a pass/fail evalu- umented that stress is prevalent in the workplace and is
ation of a coach’s demonstrated practical skills. associated with negative health behaviors, and that high
Health and wellness coach training and education stress is associated with the increased presence of health
programs are currently diverse in setting, structure, and conditions in employees. 50 However, how to help employ-
cost, including academic non-degree; academic degree ees make lasting positive lifestyle changes is not yet clear.
(at bachelor’s degree, graduate certificate, and master’s A recent survey of 676 health system employees found
24.3 Health and Wellness Coaching—Best Practices in Clinical Areas of Innovation 305
that the relationship between having a high stress level effective for a specific domain of intervention and for any
24
and negative health behaviors remained consistent over specific individual who is entering into HWC.
five years. 51 Therefore, providing HWC to address stress One approach to help guide decision-making about
management is likely to positively impact health behav- the method of delivery for health and wellness coach-
iors, such as increasing physical activity, which in turn can ing is to examine the participants’ own perspectives on
save money42 and improve outcomes.40 their experience. Clark and colleagues conducted a small
but insightful qualitative study aimed at understand-
ing the perspectives of employees who had completed a
24.3.2 Visit Structures and three-month wellness coaching program.57 Twenty-seven
worksite participants reported that they appreciated the
Delivery Methods personal connection with their wellness coach, and they
Content and context both determine the optimal choice were surprised by the impact of the professional relation-
of structure and method for a HWC visit. In terms of the ship they developed with their coach. They rated humor,
content of HWC interventions, motivational interview- non-judgmental communications, and evocation as being
ing and goal setting appear to be consistent components positive aspects of wellness coaching. They enjoyed the
of the HWC interventions. 52 Contextually, in Wolever collaborative decision-making process but also reported
et al.32 systematic review of health coaching literature, 32 it being motivated by feeling accountable to their wellness
was noted that: coach. The participants attributed their positive changes
to feeling more confident in their abilities, being able to
78% of articles indicated that the coaching occurs reprioritize their wellness goals, and having a broader
in the context of a consistent, ongoing relationship definition of wellness.
with a human coach who is trained in specific behav- HWC has been most frequently provided in a one-to-
ior change, communication, and motivational skills. one setting. Given that many wellness centers have limited
staff and that groups can be a source of positive social sup-
The needs for direct connection and safe relationship port, group wellness coaching is a new, rapidly expanding
both appear to be requisite for HWC, as it is defined here; avenue of delivery. 58 The implementation of group coach-
therefore, synchronous, voice-to-voice connection (either ing as an option for clients increases access and decreases
in person or via phone or computer) with a consistent costs, while effectiveness will need to be demonstrated.
provider appears optimal for effective coaching. While
asynchronous interventions with healthcare providers are
utilized in other areas, these have been predominantly for 24.3.3 Health and Wellness Coaching
the purposes of education, not coaching. 53 New virtual
interventions (sometimes mistakenly called coaching) are
Payment Models
continually being explored, but their impacts on lasting In the employer wellness sector, employers typically pay
behavior change are not well established at this time.54 for coaching services as part of a broader offering of
While single-sessions with any particular health and well- health and wellness services intended to control the rise
ness coach may have some benefit, such an intervention of healthcare costs as well as improve productivity and
has been minimally examined. 55 These authors do not presenteeism. Many vendors offer HWC by phone or vid-
currently advocate such practices as asynchronous com- eoconferencing to employee populations59 at low or no
munication or isolated sessions with different health and cost. The health and wellness coaches who offer private
wellness coaches as preferred methods of HWC. practice services are predominantly working as fee-for-
As noted, synchronous health coaching sessions can be service, often combined with other services, such as yoga,
offered in person (most studied), telephonically, or online mindfulness training, personal training, cooking instruc-
(least studied). The format, length, frequency, and method tion, and therapy (from licensed mental health providers)
of delivery vary widely. 56 The number, frequency, length (Figure 24.5).
of HWC sessions, and the duration of engagement are not In the primary care setting, coaching services are
standardized for practice or research. The typical coach- offered on a small scale, as reimbursement of the nation-
ing “dose” was explored in the Wolever et al. review, 32 ally board certified health and wellness coaches is not yet
although published studies often did not report length of established for existing reimbursement codes that relate
session (75%), number of sessions (52%), and duration of to prevention, wellness, and engagement in healthy life-
a series of sessions (64%). Where data did exist, the aver- styles. It should be noted that health and wellness coaches
age duration of a coaching session was 36 minutes (rang- who are members of holistic care teams in primary care
ing from five minutes to 2.5 hours); the average number settings60,61 have been found to be impactful agents of
of sessions was 10.1 (median of six sessions with a range change in primary care. Dietitians, health educators, and
of 1–90 sessions); and the average contact hours reported nurses are currently eligible to deliver annual wellness vis-
was 6.2 hours (median of three hours, with a range of 15 its, and nurse practitioners and physician assistants are
minutes to 135 hours). HWC program duration for cli- eligible to deliver obesity counseling and chronic care
ents was quite varied. For example, 23% of the interven- sessions for individuals and groups. Capitated models,
tions were five weeks to three months; 25% were 3.5 to six where a provider is paid a monthly stipend to manage a
months; and 22% were ten to 12.5 months. Clearly, more patient’s care, open the opportunity for integration of the
needs to be learned about what format of delivery, length, health and wellness coach in supporting the patient to
number of sessions, and time frames of session are most engage fully in self-care and medical care. For example,
306 Chapter 24 Health Coaching and Behavior Change
40%
Self-employed or independent
35%
contractors
30%
Employed Medical outpatient
25%
5% Employed in Academic,
government, military and
community-based facilities
0%
Distribution of Practicing Health Coaches
there were 13 studies and hence there was the ability to and life improvement goals. For example, in the University
24
provide some information on HWC in this population. of Minnesota’s graduate programs in Integrative Health
A summary of the findings from the data based articles and Well-Being Coaching, all students receive three hours
reveal HWC as a promising intervention for chronic dis- a semester of HWC provided by an outside professional
eases, though further research is needed in most categories. coach who is not otherwise involved in their education
The above findings are strong enough to warrant fur- (http s ://w w w.cs h .umn . edu/ e duca t ion/ m aste r -art s -deg
ther investigation of HWC. Many studies demonstrated ree-integrative-health-and-wellbeing-coaching).
significant improvements in nutrition, physical activity,
weight management, or medication adherence; coaching
also appears to improve self-efficacy and self-empower- 24.5.2 Referral to Health and
ment, as well as goal attainment, self-reported adherence, Wellness Coaches
health status, and self-esteem. Reviews suggest that health
coaching improves management of chronic diseases, HWC calls clients to develop new health behaviors, a new
including diabetes, and has positive effects soon after the positive lifestyle, or even, and sometimes most impor-
intervention on patients’ physiological, behavioral, and tantly, to transform underlying cognitive and belief struc-
psychological conditions as well as on their social life. tures. Hence, the U.S. national standards include the
However, consistent in every single review was the lack of competency of assisting clients in assessing whether they
clarity in operational definitions of HWC and the signifi- are ready to effectively engage in a HWC program and are
cant lack of detailed description of the specific tools and ready to develop and sustain new health habits of mind
skill sets embedded in HWC. There is an identified need and body. While physician referrals are rarely required
for longer-term effectiveness, as well as cost-effectiveness, for HWC, and since validated instruments to assess suit-
studies. Additionally, there is need for effectiveness stud- ability for coaching don’t yet exist, healthcare providers
ies clearly differentiating between standard HWC and are best positioned to recognize patients best suited to the
integrative HWC, as comparisons between the approaches HWC process. The absolute best way for any healthcare
may prove to be significant as the field matures. 22,37 provider to understand HWC, and make optimal refer-
Resolving the heterogeneity in definitions of health and rals, is to receive HWC themselves, even if they do only an
wellness coaching was one impetus to form NCCHWC, isolated session.
and subsequently ICHWC, as discussed earlier. While it is
critical clinically to clarify HWC roles and methods, there
is an even greater imperative for researchers to clearly
24.5.3 Hiring Health and Wellness Coaches
define HWC; describe in detail the methods, frequency, To date, there is no research that compares the effective-
and dose used in their HWC interventions; and provide ness of HWC based upon coaches’ educational and/or
specific information on the background and coach-spe- professional backgrounds. Hence, commonsense princi-
cific training of the health and wellness coaches involved ples and evaluation of an individual’s demonstrated skills
in studies. It is essential to improve trial quality gener- are critical in employing health and wellness coaches.
ally, including the careful selection of control groups. For Ideally, a health and wellness coach has completed a repu-
a better understanding of issues relevant to selection of table accredited professional program that provides skills
appropriate control groups, see Freedland et al., 2011.69 training and integrated application of coaching-related
theories, and that requires demonstration of adequate
coaching skills. The health and wellness coach should
24.5 HEALTH AND WELLNESS demonstrate knowledge of HWC competencies, excellent
communication skills, curiosity, compassion, and empa-
COACHING—PRACTICAL thy; and should model their own commitment to optimiz-
NUTS AND BOLTS ing their personal health and well-being.
National Board certification became available for
Nurse coaches in 2013 through the American Holistic
24.5.1 Coaches Need Coaching Nurses Credentialing Corporation (www.ahncc.org).
It is widely accepted across all domains of professional National Board certification for all Health and Wellness
coaching—including executive or leadership, life, and Coaches began being offered through the International
health and wellness coaching—that competent coaches Consortium for Health and Wellness Coaching (www.
regularly employ their own coaches to support their per- ichwc.org) in collaboration with the National Board of
sonal and professional growth. It is also similarly valu- Medical Examiners (www.nbme.org) in 2017. Such cre-
able for other healthcare providers to work with health dentials do ensure a baseline level of educational back-
and wellness coaches on their personal health and well- ground, core knowledge, and demonstrated skills;
being so that they “walk the wellness walk,” and are bet- therefore, the hiring of board certified health and wellness
ter able to refer patients to coaches and support patient coaches is professionally recommended.
engagement in HWC. Walking the coaching walk enables Healthcare organizations recruiting health and well-
coaches to engage in a similar process as their clients and ness coaches often look for a combination of a credible
more fully engage in lifelong learning and growth. coaching credential and other health credentials. Nurses
During professional training and education programs, are often desired, as they bring considerable clinical and
health and wellness coaches are typically working with fel- patient management experience and understanding of
low students or professional coaches on their own health healthcare system issues, including scopes of practice,
308 Chapter 24 Health Coaching and Behavior Change
billing, and HIPAA. This is true of physician assistants based on the personal values and strengths of the individ-
and physicians as well, although their costs will be higher. ual and by inviting active participation and empowerment
Some may seek health and wellness coaches who are also through specific communication techniques. 23 The client’s
dietitians or exercise physiologists, who can contribute perceptions of the issue and generation of the solution are
healthy lifestyle expertise under reimbursement protocols. explored in the context of the client’s values. An empha-
Health and wellness coaches with formal mental health sis on strengths and continued learning allow the health
licensure may perform dual roles—delivering therapy ser- and wellness coach to support the clients’ own vision of
vices as well as coaching. their best selves. Borrowing from positive psychology70
and other strength-based approaches,71 the health and
wellness coach also trains clients both to recognize how
24.5.4 Assimilation of Health and they are continuing to learn and to see the impact of their
own positive behavior in bringing about their vision. This
Wellness Coaches process applies key lessons from health psychology on the
A challenge for health and wellness coaches in many importance of tracking behaviors.72 Effective self-man-
organizations is that the culture and leadership practices agement interventions that are central to care of chronic
in a particular setting may not align with key coaching disease73,74,75 are then provided using particular education
principles—such as fostering autonomy, intrinsic motiva- techniques that align with how adults best learn.76,77,78
tion, compassion, mindfulness, strengths, self-awareness, Finally, the health and wellness coach plays a key role
and an open, creative and collaborative change process. in helping the client to develop support networks and
Consequently, health and wellness coaches may feel iso- resources that access the client’s community and health-
lated and unsupported by their teams and leaders. Ideally, care system.
health and wellness coaches have managers and super- It is time for us to call in a new vision of health and
visors who have a deep understanding of coaching, and healthcare in America. Health coaching can play a piv-
teams that are well informed on the nature of health otal role in the creation of this new narrative. Innovative
and wellness coaching. Fortunately, there is an emerging models that partner education for self-efficacy with health
interest in developing coaching cultures within organiza- and wellness coaching, like the PACT program for chronic
tions, such that all leaders and team members learn basic pain,79 leverage our healthcare dollars and improve out-
coaching and communication skills. This will enhance the comes. Health and wellness coaches can provide critical
acceptance and support of professional coaches, and their skills to our evolving interprofessional healthcare teams
effectiveness in their roles. that place the client, or patient, at the center of their own
care. Nationally, the VA healthcare system—the largest
system in the United States—has been implementing early
24.5.5 Protecting Client/Patient Privacy initiatives along this line, bringing in a holistic philoso-
phy of care, empowering the patient in their own care,
A successful HWC engagement depends upon trust (e.g.,
and actively employing coaching techniques with their
the health and wellness coach is benevolent, authentic,
patients.80,81
honest, and competent) and privacy (the client’s personal
This new narrative will very much emerge from the
information is in secure hands). It is important for health
dreams, the pioneering initiatives, and the intentions
and wellness coaches to follow established practices to
we generate today. In systems theory, it is clear that the
protect the privacy and confidentiality of client/patient
most unstable systems are those most able to be suddenly
information, including following HIPAA requirements
and powerfully changed. Transformation arises through
for technology security and sharing of patient/client
chaos, which is an accurate descriptor of our current
information with other providers. It’s vital that clients/
system of medical care in the United States. Health
patients are informed of practices that protect their pri-
and wellness coaching has the potential, right now, to
vacy and require their permission for sharing of personal
change our stories of health and well-being, individu-
information.
ally and as a system. Health and wellness coaching can
be a transformative agent, helping to create a system of
care—nationally, if not globally—that empowers indi-
24.6 HEALTH COACHING IN viduals in their efforts not just to survive or recover
THE FUTURE OF HEALTH from disease but to create and sustain holistic health
and optimal well-being.
CARE—A VISION OF HOPE
An existing body of outcome studies suggests that the key CLINICAL APPLICATIONS
levers for achieving healthy change include the therapeu-
tic alliance, the client’s active participation, the client’s Consider connecting patients to individual or group
perception of the issues, the client’s guided generation of health and wellness coaching, especially in the following
the solution, and the client’s use of resources. HWC, as situations. A patient:
we propose it, embodies these aspects of a supportive and
creative relationship to elicit positive lifestyle change. The • Receives a new diagnosis of any illness for which
health and wellness coach is effective in supporting the lifestyle behaviors contribute significantly, either to
competence of the patient by eliciting intrinsic motivation the cause, or the course, of that illness. This could
References 309
include anything from cardiac disease and diabetes medication utilization, relationships, or perspectives
24
to cancer. on their challenges.
• Is living with a chronic disease and would function- • Wants to improve their overall health and well-being,
ally do better if able to make improvements in habits and decrease risks for future disease or disabilities.
around eating, exercise, sleep, stress management, They are asking for help in making real change.
REFERENCES
1. McGinnis, James and William H. Foege. 18. Travis, John. Wellness Inventory. 1975th, 33. Jordan, Meg. “National training and edu-
“Actual causes of death in the United 1981st, 1988th ed. Wellness Association cation standards for health and wellness
States”. JAMA, vol. 270, no. 18, Nov. Publications. coaching: The path to national certifica-
1993, pp. 2207–2212, doi:10.1001/ 19. Leonard, Thomas. Becoming a Coach: tion”. Global Advances in Health and
jama.1993.03510180077038 The Coach U Approach. First, Coach Medicine, vol. 4, no.3, 2015, pp. 46–45.
2. Khaw, Kay-Tee, et al. “Combined impact University, 1999. 34. Griffiths, Kerryn E. and Marilyn A.
of health behaviours and mortality in 20. Grant, Anthony M. “The impact of Campbell. “Regulating the regula-
men and women: The EPIC-Norfolk life coaching on goal attainment, tors: Paving the way for international,
prospective population study”. PLOS metacognition and mental health”. evidence-based coaching standards”.
Medicine, vol. 5, no. 1, Jan. 2008, p. e12, Social Behavior and Personality: An International Journal of Evidence Based
doi:10.1371/journal.pmed.0050012 International Journal, vol. 31, no. Coaching and Mentoring, vol. 6, no. 1,
3. Lorig, Kate R., et al. “Evidence sug- 3, 2003, pp. 253–263, doi:10.2224/ 2008, pp. 19–31.
gesting that a chronic disease self- sbp.2003.31.3.253 35. Wolever, Ruth Q., et al. “Advancing a
management program can improve 21. Miller, William R. “Motivational new evidence-based professional in health
health status while reducing hospital- interviewing with problem drink- care: Job task analysis for health and
ization: A randomized trial”. Medical ers”. Behavioural and Cognitive wellness coaches”. BMC Health Services
Care, vol. 37, no. 1, 1999, pp. 5–14, Psychotherapy, vol. 11, no. 2, 1983, pp. Research, vol. 16, no. 1, 2016, p. 205.
doi:10.1097/00005650-199901000-00003 147–172. 36. Kreitzer, Mary J., et al. “Health coach-
4. Bandura, Albert. Self-efficacy: Toward 22. Simmons, Leigh A. and Ruth Q. Wolever. ing: Innovative education and clinical
a unifying theory of behavioral change. “Integrative health coaching and programs emerging”. Explore: The
Advances in Behaviour Research and motivational interviewing: Synergistic Journal of Science and Healing, vol. 4,
Therapy, vol. 84, no. 2, 1977, pp. 191– approaches to behavior change in health- no. 2, 2008, pp. 154–155.
215, doi:10.1037/0033-295X.84.2.191 care”. Global Advances in Health and 37. Lawson, Karen. “The four pillars of
5. National Health Interview Survey, Medicine, vol. 2, no. 4, 2013, pp. 28–35. health coaching: preserving the heart of a
1965–2014. https: //www.cdc.gov/tobac 23. Rollnick, Stephen, et al. Motivational movement”. Global Adv Health Med, vol.
co/data_statistics/tables/trends/cig _smo Interviewing in Health Care: Helping 2, no. 3, 2013, 6–8.
king/i ndex.htm Patients Change Behavior. The Guilford 38. Southard, Mary E. “Nurse coaching:
6. Ajzen, Icek and Martin Fishbein. Press, 2008. Reaching new frontiers”. Beginnings, vol.
Understanding Attitudes and Predicting 24. Prochaska, James O. and Carlo C. 34, no. 3, 2014, pp. 28–29.
Social Behavior, 1st ed. Pearson, 1980. DiClemente. “Transtheoretical therapy: 39. Collins, David A., et al. “Evaluation of a
7. Adler, Alfred. Understanding Human Toward a more integrative model of health coaching course for providers and
Nature. Translated by C. Brett, Hazelden, change”. Psychotherapy: Theory, staff in Veterans health affairs medical
2010. Research & Practice, vol. 19, no. 3, 1982, facilities”. Journal of Primary Care &
8. Campbell, Joseph. The Portable Jung, Ed. p. 276. Community Health, vol. 6, no. 4, 2015,
Translated by R. Hull. Penguin Viking, 25. Prochaska, James O. and Janice M. pp. 250–255.
1976. Prochaska. Changing to Thrive: Using the 40. Clark, Matthew M., et al. The
9. Frankl, Viktor E. Man’s Search for Stages of Change to Overcome the Top Effectiveness of Wellness Coaching for
Meaning: Revised and Updated. Threats to Your Health and Happiness. Improving Quality of Life, Vol. 89.
Washington Square Press, 1984. Simon and Schuster, 2016. Elsevier, 2014. pp. 1537–1544.
10. Maslow, Abraham H. Toward a 26. O’Connor, Joseph and Andrea Lages. 41. Sforzo, Gary A., et al. “Delivering change
Psychology of Being. Van Nostrand, How Coaching Works: The Essential that lasts: Health and wellness coaching
1968. Guide to the History and Practice of competencies for exercise professionals”.
11. Rogers, Carl R. Client-Centered Therapy. Effective Coaching. A & C Black, 2007. ACSM’s Health & Fitness Journal, vol.
Boston, 1951. Google Scholar, 1973. 27. Grant, Anthony M. “A model of goal 19, no. 2, 2015, pp. 20–26.
12. Deci, Edward L. and Richard M. Ryan. striving and mental health for coaching 42. Borah, Bijan J., et al. “Association of
“Self-determination theory: When mind populations”. International Coaching worksite wellness center attendance with
mediates behavior”. The Journal of Mind Psychology Review, vol. 2, no. 3, Dec. weight loss and health care cost sav-
and Behavior, vol. 1, no. 1, 1980, pp. 2007, pp. 250–264. ings: Mayo clinic’s experience”. Journal
33–43. 28. Hubble, Mark A., et al. The Heart and of Occupational and Environmental
13. Sheldon, Kennon M. and Andrew J. Soul of Change: What Works in Therapy. Medicine, vol. 57, no. 3, 2015, pp.
Elliot. “Goal striving, need satisfac- American Psychological Association, 229–234.
tion, and longitudinal well-being: The 1999. 43. Butterworth, Susan, et al. “Effect
self-concordance model”. Journal of 29. De Shazer, Steve. Keys to Solution in of motivational interviewing-based
Personality and Social Psychology, vol. Brief Therapy. Ww Norton, 1985. health coaching on employees’ physical
76, no. 3, 1999, p. 482. 30. O’Hanlon, William H., et al. A Guide to and mental health status”. Journal of
14. Sheldon, Kennon M. “The self-concor- Possibility Land: Fifty-One Methods for Occupational Health Psychology, vol. 11,
dance model of healthy goal striving: Doing Brief, Respectful Therapy. WW no. 4, 2006, p. 358.
When personal goals correctly repre- Norton & Company, 1999. 44. Holland, Stephen K., et al. “Community-
sent the person”. Handbook of Self- 31. Wolever, Ruth Q., et al. “Integrative based health coaching, exercise, and
Determination Research. University of health coaching: An organizational case health service utilization”. Journal of
Rochester Press, 2004. pp. 65–86. study”. Explore (New York, N.Y.), vol. Aging and Health, vol. 17, no. 6, 2005,
15. Kegan, Robert. The Evolving Self. 7, no. 1, 2011, pp. 30–36, doi:10.1016/j. pp. 697–716.
Harvard University Press, 1982. explore.2010.10.003 45. Sforzo, Gary A. “The study of health
16. Nakamura, Jeanne and Mihaly 32. Wolever, Ruth Q., et al. “A systematic coaching: The Ithaca coaching project,
Csikzentmihalyi. The Construction of review of the literature on health and research design, and future direc-
Meaning through Vital Engagement, 2003. wellness coaching: Defining a key behav- tions”. Global Advances in Health and
17. Gallwey, Timothy W. The Inner Game of ioral intervention in healthcare”. Global Medicine, vol. 2, no. 3, 2013, pp. 58–64.
Tennis. New York, NY: Random House, Advances in Health and Medicine, vol. 2, 46. Jordan, Meg. “Health coaching for the
1974. no. 4, 2013, pp. 38–57. underserved”. Global Advances in Health
310 Chapter 24 Health Coaching and Behavior Change
and Medicine, vol. 2, no. 3, 2013, pp. Behavior and Policy Review, vol. 1, no. & Health, vol. 26, no. 11, 2011, pp.
75–82. 3, 2014, pp. 218–228. 1479–1498.
47. Baldwin, Sara A. “A neighborhood-cen- 58. Armstrong, Colin, et al. “Group health 69. Freedland, Kenneth E., et al. “Usual and
tered clinical project: Improving diabetes coaching: Strengths, challenges, and next unusual care: Existing practice control
and cardiovascular outcomes in Hispanic steps”. Global Advances in Health and groups in randomized controlled trials of
women”. Journal of Nursing Education, Medicine, vol. 2, no. 3, 2013, pp. 95–102. behavioral interventions”. Psychosomatic
vol. 54, no. 3, 2015, pp. 159–163. 59. Sherman, Ryan P., et al. “Primary Medicine, vol. 73, no. 4, 2011, p. 323.
48. Christian, James G., et al. “Clinic-based sup- care–based health coaching interven- 70. Kauffman, Carol. “Positive psychology:
port to help overweight patients with type 2 tion for weight loss in overweight/obese The science at the heart of coaching”.
diabetes increase physical activity and lose adults: A 2-year experience”. American Evidence Based Coaching Handbook:
weight”. Archives of Internal Medicine, vol. Journal of Lifestyle Medicine, June 2017, Putting Best Practices to Work for Your
168, no. 2, 2008, pp. 141–146. doi:10.1177/1559827617715218 Clients, 2006. pp. 219–253.
49. Schmittdiel, Julie A., et al. “The impact 60. Crawford, Chris. Iora Primary Care Gets 71. Dweck, Carol. Mindset: Changing the
of telephonic wellness coaching on Creative in Tackling Chronic Disease. Way You Think to Fulfil Your Potential.
weight loss: A ‘Natural Experiments for American Academy of Family Practice Hachette UK, 2017.
Translation in Diabetes (NEXT‐D)’ Study”. News, 19 July 2016. http://www.aafp 72. Michie, Susan, et al. “Effective tech-
Obesity, vol. 25, no. 2, 2017, pp. 352–356. .org/news/family-medicine-americas- niques in healthy eating and physical
50. Clark, Matthew M., et al. “Stress level, health /20160719f mah-chronic.htm l activity interventions: A meta-regres-
health behaviors, and quality of life in 61. Richards, Tessa. “Enlist the patients’ sion”. Health Psychology, vol. 28, no. 6,
employees joining a wellness center”. help”. BMJ: British Medical Journal, vol. 2009, p. 690.
American Journal of Health Promotion: 343, 2011. 73. Bodenheimer, Tom, et al. “Patient
AJHP, vol. 26, no. 1, 2011, pp. 21–25, 62. Albright, Ann L. and Edward W. Gregg. self-management of chronic disease in
doi:10.4278/ajhp.090821-QUAN-272 “Preventing type 2 diabetes in communi- primary care”. JAMA, vol. 288, no. 19,
51. Clark, Matthew M., et al. “High stress ties across the US: The National Diabetes Nov. 2002, pp. 2469–2475, doi:10.1001/
and negative health behaviors: A five- Prevention Program”. American Journal jama.288.19.2469
year wellness center member cohort of Preventive Medicine, vol. 44, no. 4, 74. Lorig, Kate, et al. “Online diabetes self-
study”. Journal of Occupational and 2013, pp. S346–S351. management program”. Diabetes Care,
Environmental Medicine, vol. 58, no. 9, 63. Lindner, Helen, et al. “Coaching for behav- vol. 33, no. 6, 2010, pp. 1275–1281.
2016, pp. 868–873. iour change in chronic disease: A review 75. Schulman‐Green, Dena, et al. “Processes
52. Sforzo, Gary A., et al. “Compendium of the literature and the implications for of self‐management in chronic illness”.
of the health and wellness coaching coaching as a self-management interven- Journal of Nursing Scholarship, vol. 44,
literature”. American Journal of Lifestyle tion”. Australian Journal of Primary no. 2, 2012, pp. 136–144.
Medicine, 2017, doi:1559827617708562 Health, vol. 9, no. 3, 2003, pp. 177–185. 76. Berger, John G. “Adult development
53. de Jong, Catharina C., et al. “The effects 64. Newnham-Kanas, Courtney, et al. theory and executive coaching prac-
on health behavior and health outcomes “Annotated bibliography of life coach- tice (Chapter 3)”. In: Evidence Based
of internet-based asynchronous com- ing and health research”. International Coaching Handbook: Putting Best
munication between health providers Journal of Evidence Based Coaching and Practices to Work for Your Clients,
and patients with a chronic condition: A Mentoring, vol. 7, no. 1, 2009, pp. 39–103. edited by D. R. Stober and A. M. Grant.
systematic review”. Journal of Medical 65. Kivelä, Kirsi, et al. “The effects of health John Wiley & Sons, 2006.
Internet Research, vol. 16, no. 1, 2014. coaching on adult patients with chronic 77. Drago-Severson, Eleanor. “How adults
54. Lehto, Tuomas, et al. “Virtual health diseases: A systematic review”. Patient learn”. Journal of Staff Development,
coaching for consumers: A persuasive sys- Education and Counseling, vol. 97, no. 2, vol. 32, no. 5, 2011, pp. 10–12.
tems design perspective”. International 2014, pp. 147–157. 78. Rollnick, Stephen, et al. “Competent
Journal of Networking and Virtual 66. Ammentorp, Jette, et al. “Can life coach- novice: Motivational interviewing”. BMJ:
Organisations, vol. 13, no. 1, 2013, pp. ing improve health outcomes?–A system- British Medical Journal, vol. 340, no.
24–41. atic review of intervention studies”. BMC 7758, 2010, pp. 1242–1245.
55. Brand, V. S., et al. “Impact of single‐ Health Services Research, vol. 13, no. 1, 79. Fricton, James, et al. “Transformative
session motivational interviewing on 2013, p. 428. care for chronic pain and addiction:
clinical outcomes following periodontal 67. Hill, Briony, et al. “Do we know how to Healing the patient and the health care
maintenance therapy”. International design effective health coaching interven- system through a health coaching model”.
Journal of Dental Hygiene, vol. 11, no. 2, tions: A systematic review of the state Practical Pain Management, vol. 17, no.
2013, pp. 134–141. of the literature”. American Journal 7, Sept. 2017, pp. 16–29.
56. Olsen, Jeanette M. and Bonnie J. Nesbitt. of Health Promotion, vol. 29, no. 5, 80. Atwood, Katharine A., et al. “Search fam-
“Health coaching to improve healthy life- May 2015, pp. e158–e168, doi:10.4278/ ily medicine share links”. Family Medicine,
style behaviors: An integrative review”. ajhp.130510-LIT-238 vol. 48, no. 9, 2016, pp. 711–719.
American Journal of Health Promotion, 68. Michie, Susan, et al. “A refined taxonomy 81. Krejci, Laura P., et al. “Whole health:
vol. 25, no. 1, 2010, pp. e1–e12. of behaviour change techniques to help The vision and implementation of person-
57. Ridgeway, Jennifer L., et al. people change their physical activity alized, proactive, patient-driven health
“Understanding participant perspectives and healthy eating behaviours: The care for veterans”. Medical Care, vol. 52,
of workplace wellness coaching”. Health CALO-RE taxonomy”. Psychology 2014, pp. S5–S8.
25
CHAPTER
diet, sleep, stress management, social connection, and chapter given their limited applicability to behavior
substance moderation/cessation. Many of the most prom- change. Electronic medical records (EMR) are now ubiq-
ising technologies are within the field of mHealth, which uitous in the United States, with nearly nine in ten office-
specifically focuses on the use of mobile communication based physicians18 and almost all hospitals (96%)19 using
devices, such as cellular phones, smartphones, and wear- an EMR system. While EMRs can play a role in improv-
able devices.15 While most computing technology was ing lifestyle, such as tracking important lifestyle data and
stationary in the early 2000s, the ability to consume and reminding clinicians to ask about patient behaviors, their
generate data from anywhere has produced a wide range primary purpose is to support clinical care rather than
of new opportunities to improve and monitor health in to promote behavior change. Similarly, telemedicine, the
diverse populations throughout the world.16,17 As of 2016, use of telecommunications technologies for the delivery of
the World Bank reports 98% penetration of cellular remote clinical services, 20 has become increasingly preva-
phones in high-income countries and approximately 80% lent within the healthcare system. While it may be used
penetration in the developing world. Even among the bot- in behavior change interventions, such as online health
tom fifth of the population worldwide, nearly 70% own a coaching or therapy sessions, it has been omitted from the
mobile phone, and the poorest households are more likely chapter given its primarily clinical focus.
to have access to mobile phones than to toilets or clean An effort has been made throughout the chapter to pro-
water.17 Other digital health technologies with the poten- vide practical considerations for implementation, as sum-
tial to promote behavior change include dedicated devices, marized in Figure 25.2. Whether designing an intervention
some mobile and some stationary, which can monitor and for a small practice or large organization, a repeated theme
encourage behaviors such as sleep, food intake, and physi- is the role of technology as a tool, not a complete solution.
cal activity. Additionally, social media will be discussed, Numerous studies have shown that simply adding a new
given its growing role in promoting social connection and technology will not significantly change patient behav-
spreading messages throughout communities. While each ior.21,22 Effective behavior change interventions require
of these technologies is valuable independently, digital instead a well-designed combination of people, processes,
therapeutics integrate multiple technologies into systems and technologies to achieve maximum impact. Intelligently
that aim to replace or augment traditional medication combining traditional programs with digital health tools is
treatments. Figure 25.1 provides an overview of current likely to be most effective in reaching the behavioral objec-
and emerging digital health technologies for behavior tive.23,24 Furthermore, factors such as design, ease of use,
change. financial incentives, training, staffing, and integration into
Some technologies may be considered within the existing workflows all play important roles in the success
realm digital health but have been omitted from this of a technology. Lastly, digital health interventions should
Figure 25.1 Current and Emerging Digital Health Technologies for Behavior Change Interventions.
25.2 Section 1: Text Messaging 313
25
Figure 25.2 Multiple Considerations May Determine the Success of Digital Health Technology Implementations.
be consistent with proven behavior change techniques, Nevertheless, compared with other areas of medical
such as self-monitoring, positive feedback, or barrier iden- research, this body of literature may be considered in its
tification,25 and may benefit from a basis in theoretical con- adolescence, with most studies of low-moderate quality
structs for behavior change.26 and many open questions about effective intervention
characteristics and cost-effectiveness.31
The benefits of using text messaging for behavior
25.2 SECTION 1: TEXT MESSAGING change are numerous. The technology is low-cost, instant,
easy to use, scalable, and can be personalized. 27,31,32
Text messaging is the most widely used data application in Information can be pushed directly to the intended
the world, used by over 78% of all mobile phone subscrib- audience, and it is less likely to be misplaced compared
ers as of 2012. 27,28 Furthermore, text messaging is effec- with print materials. Furthermore, text messages are
tive for reaching its audience, with estimates that 99% of considered less invasive than phone calls, and receiv-
received mobile text messages are opened, 90% within ing text messages for many people can even be a plea-
three minutes of being received. 29,30 surable experience associated with a small dopamine
The literature for text messaging applications is exten- release. 27,31 The messages can be timed precisely, rang-
sive compared with other digital health technologies. The ing from infrequent reminders to bursts throughout the
first study was published in 2002, the first systematic day to specific moments of decision making. Lastly, text
review in 2009, and the first systematic review of reviews messaging can mirror elements of in-person counseling,
in 2014.31 Today there are over 20 systematic reviews such as tailored advice, behavioral monitoring, goal set-
and meta-analyses assessing the use of the technology. ting, and feedback. 32 Adverse events associated with text
314 Chapter 25 Digital Health Technology for Behavior Change
messaging are uncommon, with potential issues such as with type 2 diabetes in high-, middle-, and low-income
traffic crashes or repetitive thumb injury rarely reported countries, and showed a 0.53% decrease in HgA1c across
in the literature. 13 trials.37
Text messaging interventions may be particularly use-
ful for low-income populations and in developing coun-
tries given the ubiquity of cellular phones and the low cost 25.2.2 Considerations for Implementation
of sending text messages. In the United States, text mes-
saging use is spread across diverse socioeconomic and eth- Despite the large number of text messaging studies, there is
nic populations, with higher use in Hispanic and African still limited evidence to determine the most efficacious inter-
American populations than among the White popula- vention characteristics, and most reviews and meta-analy-
tion, 33 and 80% of low-income Medicaid households ses have not been able to draw strong conclusions on which
use text messaging regularly. 27 In settings with a limited characteristics work better than others.31 Nevertheless,
healthcare workforce, limited financial resources, high various reviews on intervention design have been com-
burden of disease, or hard-to-reach populations, text mes- pleted which can serve as a guide for those developing a
saging has been found to be cost-effective and to produce text messaging intervention.27,32 Abroms et al. specified a
positive impact on clinical outcomes, quality of life, and multi-step process, starting with understanding the key
treatment adherence.34,35 behavior change mechanisms and goals for the population
of interest.32 Next, communication objectives, behavioral
techniques, and theoretical constructs for the intervention
should be determined.32 While few text messaging studies
25.2.1 Outcomes articulate explicit behavior change theories,31,37 examples
While a wide variety of text messaging interventions have of constructs used include the Transtheoretical Model
been used for different purposes, reviews of text messag- of Behavior Change, the Health Belief Model, Behavior
ing interventions have generally shown positive outcomes. Learning Theory, and the Information Motivation Behavior
A 2015 review of 15 systematic reviews and meta-analyses Model.32,37
incorporating 89 individual studies from 2009 to 2014 The design details of any intervention are critical.
found that the majority of text messaging interventions Extensive literature exists on user-centered design, with
had statistically significant positive effects on health out- guidelines such as consistency, simple error handling, and
comes and/or behaviors. 31 Multiple reviews have shown offering informative feedback for user actions.44 Specific
benefit in diabetes self-management, cardiovascular dis- areas of consideration include:
ease, weight loss, physical activity, smoking cessation, and
medication adherence.31,36–39 • Message Content – Content may include remind-
Feasibility and Acceptability: Text messaging inter- ers, motivational messages, educational material,
ventions have generally been found to be both feasible and goal setting, feedback, requests for users to track
acceptable to patients with a variety of conditions.37,40 As behavior, and so on. Other considerations include
discussed later, the acceptability of the interventions may the length of the message,45 sender of the message,
be strongly related to intervention design, such as mes- style of writing, cultural and linguistic appropriate-
sage content and frequency, which must be tailored to the ness, 27,41 literacy level of the population (generally
intended audience. 27,41 eighth-grade level is maximum used for adults), and
Behavior Change: Text messaging studies for behav- the need for translations.32 Messages may use text
ior change have primarily assessed improvements in only, images, videos, and/or links to websites. 31,46
diet, physical activity, and smoking cessation. Overall Standard libraries are increasingly available with
results have been mixed, but slightly positive. A 2015 empirically tested content. 27,41
meta-analysis of 38 randomized controlled trials with • Frequency and Timing – Frequency of messages var-
19,641 diverse participants in developed and developing ies widely in studied interventions, from multiple
countries showed a small, positive significant effect on times daily to weekly, and various recommendations
a broad range of behaviors.42 Another systematic review exist in the literature.38,46–49 Some studies provide
of chronic conditions reported three out of four studies more messages during key behavior change periods,
with improvements in self-management behaviors, and some only send messages when requested by a user,
two out of four studies with significant improvement in and others vary frequency based on the text hab-
health outcomes.43 With regard to smoking cessation, in its of their users or based on users’ adherence (e.g.,
particular, six of eight studies showed statistically sig- higher frequency when adherence is low).32 The
nificant effects on health outcomes or behaviors, and a time(s) when messages are sent should also be con-
separate Cochrane review of 12 studies assessing smok- sidered, since messages are received instantly.
ing cessation interventions showed beneficial impact on • Interactivity – A key consideration is whether the
six-month outcomes. 39 Extensive research has been done intervention should be unidirectional (provider
for diabetes management. Hall et al. found very positive to patient only) or bidirectional (patient also send
results in which 16 studies of diabetes patients all showed information to provider). Bidirectional systems are
significant improvement on health outcomes and/or health likely to be more complex and resource intensive.
behaviors despite a diversity of interventions.31 Another While some messaging systems allow for automated
systematic review and meta-analysis looked at 15 trials responses, others require a human to monitor.
targeted at improving diet and physical activity for people Special consideration must be given to managing
25.3 Section 2: Mobile (Smartphone and Tablet) Applications 315
smartphone application in addition to usual care was not variety of conditions, including heart disease, concussion,
associated with increased weight loss.72 Nevertheless, a melanoma, postpartum depression, and sleep health.84,85
subsequent review of 12 studies looking at the effective- Subsequent versions are attempting to study lifestyle inter-
ness of mobile phone applications to promote weight loss ventions. While mobile applications can be difficult and
and increase physical activity did find that mobile phone costly to build, many start-up companies provide coding
app-based interventions were associated with a 1.04 kg and technical support for clinicians who may not have
greater weight loss than conventional outreach.73 Further such expertise themselves.86–88
supporting this finding, a 2017 survey of 794 National Frameworks for analyzing the quality of mobile appli-
Weight Control Registry participants who maintained a cations have also been developed. The Mobile App Rating
13.6 kg weight loss for at least a year were more likely Scale was developed in 2015 for classifying and assessing
to own health tracking smartphone applications than the the quality of mobile health applications based on engage-
general population, suggesting the applications may have ment, functionality, aesthetics, and information quality.89
contributed to their success.74 Reviews are available assessing the quality of many life-
Physical Activity: Mobile applications are increasingly style intervention applications, including those for mind-
used to encourage physical activity. Most smartphones fulness90 and for improving diet, physical activity, and
are inherently embedded with tri-axial accelerometers, sedentary behavior in children.91 A framework has also
which can accurately track step counts,75 as well as GPS been developed to help application developers and users
for tracking location. As such, applications based on assess possible risks posed by health applications, includ-
these devices can serve as valuable feedback tools to help ing possible loss of reputation, loss of privacy, poor qual-
increase daily physical activity. A 2012 meta-analysis of ity patient data, poor lifestyle or clinical decisions, and
11 studies showed some benefit of these tools for increas- inappropriate clinical actions.92
ing physical activity,76 and applications have been theo- Good mobile application design is crucial. Two cen-
rized to be particularly of use in engaging and motivating tral themes emerge from a review of the research guiding
teenagers.77 In 2016, the Pokémon Go application led to application development—the need to build upon existing
a temporary “population-level” surge in step counts, as clinical guidelines, and the need to embrace proven behav-
discussed in the Virtual and Augmented Reality section. ior change techniques.
Nutrition: Preliminary trials show some efficacy of Existing clinical guidelines can delineate components
mobile applications to track and improve dietary intake. of interventions needed to improve outcomes, and app
Smartphone-based self-monitoring has been shown to be designers must not ignore effective interventional compo-
as usable as paper tracking,78 and smartphone apps may nents. For example, the UK National Institute for Health
increase adherence with dietary monitoring.79 A 2015 and Clinical Excellence and the American Diabetes
review found nine randomized studies demonstrating that Association both recommend education on good diet,
use of smartphone applications can be associated with proper glucose control, and the role of exercise. However,
better dietary compliance for low-calorie, low-fat, and in a review of 137 mobile applications focused on diabetes
high-fiber foods.80 Furthermore, a mobile-phone-based management, education was featured in less than 38% of
game has been shown to motivate children to practice the studies published.93
healthier eating habits.81 Researchers are investigating which behavioral change
Mindfulness and Mental Health: Many mobile appli- techniques work best within mobile applications. Stanford
cations have been developed to support mindfulness in University researchers have looked at three different
various forms, such as guided meditations, relaxation motivational frameworks for physical activity, including
techniques, resilience training, and so on. While these an analytical framework focused on personalized goal-
applications have become quite popular, there have not setting and self-monitoring, a social framework focused
been high-quality studies to date evaluating their health on social comparisons and support, and an “affective”
outcomes.82 Mobile apps have also been increasingly framework focused on reinforcing positive and negative
used to deliver personalized mental health interventions. behaviors using an avatar.94 Initial results indicated that
A 2013 retrospective review found five mental health applications utilizing any of the three frameworks can be
applications had demonstrated significant reductions in effective at improving regular moderate-to-vigorous inten-
depression, stress, or substance use, but the majority of sity physical activity. A subsequent randomized study of
commercially available apps lacked scientific evidence the three different applications amongst 95 underactive
about their efficacy.83 individuals found that the social framework was particu-
larly effective for increasing physical activity and reducing
sedentary behavior.95
25.3.2 Considerations for Implementation
Both the iOS and Android mobile operating systems have
platforms for building health tracking and research appli-
cations. Apple’s HealthKit is used for managing health
25.4 SECTION 3: WEARABLES,
and activity data, while ResearchKit is designed for SENSORS, AND DEVICES
research. Similarly, the Google Fit framework is used for
developing physical activity applications on the Android Wearable devices (aka “wearables”) and sensors are trans-
platform, while ResearchStack is used for research apps. forming the way behaviors are tracked. Wearables most
Clinician-led studies have recently utilized these research commonly provide heart rate tracking and physical activ-
platforms to perform large epidemiological studies on a ity monitoring, and frequently integrate with applications
25.4 Section 3: Wearables, Sensors, and Devices 317
and notifications. Other wearable devices are more task- weight loss intervention looked at 471 participants. 22 It
25
specific, including those that monitor sleep, track mood or found that adding a wearable device to monitor diet and
stress levels, or deliver workouts. While wearable owner- physical activity failed to increase physical activity, fit-
ship is tiny compared with that of smartphones,65 research ness, or improve body composition and diet at 24 months
shows that one in six consumers in the United States now compared with monitoring via a website alone.
use wearable technology,96 with the most popular being Glucose Monitoring: The continuous glucose moni-
smartwatches. Industry analysts forecast that wearable tor measures glucose levels in interstitial fluid, eliminat-
devices will become increasingly popular, reaching 240.1 ing the need for frequent blood stick checks. The first
million devices shipped annually by 2021.97 Given the device for adults was approved by the U.S. FDA in 2017
growing popularity of wearable devices with consumers, based on a clinical study of adults with diabetes,108 though
along with their wide array of useful sensors, they present the devices were previously adopted internationally and
useful opportunities to monitor and encourage behavior shown to be quite accurate.109 Studies have found that
change. real-time continuous glucose monitoring systems can be
Non-wearable sensors are contributing to the rise of clinically useful, including in the reduction of severe hypo-
the Internet of Things—a network of devices, appliances, glycemia in type 1 diabetes patients who may be unaware
and other items embedded with electronics and sensors of these episodes.110
able to connect to a network to exchange data. For exam- Mindfulness and Stress: Devices available to support
ple, digital scales can now detect not only weight and body mindfulness or stress reduction currently have limited evi-
fat measurements, but also streamline daily weigh-ins by dence to support their use. For example, one commercially
automatically sending measurements to a smartphone available device utilizes electrical stimulation to help the
application or an online database.98 Smart refrigerators body relax, and the company cites internal research that
can help track available groceries, create shopping lists, their device can improve mood and sleep safely with
and even help order food.99 Mattress covers connected substantially lower side effects than pharmaceuticals.111
to the Internet can monitor temperature, breathing, and Another device utilizes electroencephalography (EEG) to
heart rate to track sleep quality.100 Eventually these smart enhance mindfulness training,112 while others are utilizing
devices may be connected to allow seamless interactions electrodermal activity to monitor stress levels.113
between them to facilitate healthier behaviors. Freestanding Devices: Some technologies, such as
wireless-enabled scales, have shown efficacy as part of
digital therapeutic programs.114 Others, such as sleep
monitoring devices, often advertise claims with limited
25.4.1 Outcomes evidence. For example, one sleep system utilizes a mat-
Physical Activity: Physical activity trackers are the mostly tress sensor with a bedside light and speaker, and claims
commonly worn devices, and may be the most well stud- to adjust a program of light and sound to ease a person
ied. These devices are capable of measuring steps and gently into and out of sleep.115
heart rate, and built-in accelerometers allow for objective A wide variety of new sensor technologies are under
quantification of physical activity.101 Smartphone applica- development, both for wearable and stand-alone use.
tions today are accurate to within 6.7% of observed step Some of these are discussed later in the “Emerging
counts.75 Wearable wrist-worn devices can now offer heart Technologies” section.
rate and energy expenditure measurements, also, though
the accuracy of these devices can be improved, with mea-
surement errors of some devices currently above 20%.102
The tri-axial accelerometer sensors used in activity
25.4.2 Considerations for Implementation
monitors have been adapted to measure other attributes, As devices and sensors vary, it is hard to make general-
such as falls. Terroso and colleagues developed a wearable ized comments about how to best design, test, and uti-
sensor unit that can alert family members of an elder’s lize them. However, Patel and colleagues present a generic
fall.103 Others have shown that sensors can be used to outline for how to design and adapt devices to facilitate
measure frailty in a geriatric population.104 These accel- behavioral change.96 First, the device user needs to be
erometer-based sensors have also been described to help motivated to acquire and use the device. A survey of 6,223
monitor real-world physical activities,105 upper limb ges- individuals showed that more than half who purchased a
tures in post-stroke rehabilitation,106 and gait analysis.107 wearable device stopped using it, with one-third quitting
Further research is needed to further validate the use of before six months. Notably, many trackers require fre-
these sensors for such purposes. quent maintenance, must be worn every day, and need to
Weight Management: As wearable devices are often be charged every few days to every few weeks. However,
able to help track calorie intake, physical activity, and a more recent study of over 35,000 people who elected to
biometric measurements, they have been commercially use wearable activity trackers as part of a health insur-
advertised to help maintain weight and a healthy lifestyle. ance wellness program found that 80.0% of participants,
However, the evidence is still unclear. One study has found including 90.4% of elderly persons, were still using the
that the addition of an energy monitoring armband and a devices after six months, suggesting that self-motivation
website to monitor energy intake and expenditure can yield and inclusion in a comprehensive program are important
greater weight loss than a standard in-person behavioral factors for sustaining use.116
program at six months. 23 The largest randomized clini- Second, the device must be able to accurately track its
cal trial assessing at the effects of a technology-enhanced target behavior. A systematic review of wearable devices
318 Chapter 25 Digital Health Technology for Behavior Change
to monitor physical activity, energy expenditure, and sleep Social connections are also known to influence obe-
found that many physical activity monitors tend to under- sity patterns.131 A 2015 study evaluated a set of variables
estimate energy expenditure and overestimate total sleep that may contribute to weight loss in an online weight loss
time.117 The U.S. FDA has been more closely monitoring community, and found that greater embeddedness in the
continuously worn devices in which accuracy is critical to online network was the variable with the highest statisti-
patient health (e.g., continuous glucose monitors) and has cal significance for weight loss.132 In a survey of weight
indicated that they will be formalizing their regulatory loss forum members, the major social support themes were
oversight over digital health devices.14 encouragement and motivation, information, and shared
Last, and perhaps most important, the information experiences. Members reported that they valued conve-
must be displayed to the user in a way that motivates life- nience, anonymity, and the non-judgmental interactions
style changes for health. To foster real changes, wearable as unique characteristics of Internet-mediated support.133
devices must be used in conjunction with proven behavior Patient Knowledge Exchange: Online social networks
change techniques. For example, one product consists of are especially popular for patients with chronic health
an indoor bicycle that brings the experience of a cycling conditions as a place to become active participants in
studio class to the user. It leverages personalization (the managing their health.130,134,135 As patients share their
bike is able to track prior personal bests and use that infor- own experiences, medical and technical information is
mation to motivate users during workouts) and social net- translated into “patient knowledge” and useful guides to
working (users can stream live classes and compare speeds navigate day-to-day lives.129
with others in the class) to make “every workout addict- Decreased Reliance on Clinicians: Analysis of 16,492
ing”.118 While sales were strong in the first two years,119 no messages from a smoking cessation network showed users
objective studies have been published to validate whether took control of their cessation with a variety of tactics,
users do indeed engage in higher levels of physical activity such as virtual bonfires and pledges. None of the messages
with the use of the cycle. mentioned the role of a physician in their smoking cessa-
tion efforts, suggesting the behavior change effort in this
community was primarily self-propelled.136 Furthermore,
25.5 SECTION 4: SOCIAL MEDIA online network interventions can help to sustain behav-
ior change over time, as network members often maintain
Social media is defined as an online means of communi- relationships with fellow patients with minimal ongoing
cation used to share information and develop social con- support from healthcare providers.137,138
tacts.120 It includes online social networks, forums, and Data Collection: Patient-shared data can be collected
messaging boards. online to create research databases. For example, a social
Social media use has exploded from 5% of the U.S. network focused on ALS treatment compiled patient out-
population in 2005 to 69% in 2017,121 including 34% of comes on lithium and showed no clinical effect within the
those over 65 years old, with users spending an average first 12 months,139 highlighting the potential of patient-
1.7 hours per day on these activities.7 Patients are turn- shared data to accelerate clinical discovery.
ing to social media both for health information122,123 and
for social support through shared experiences,124 and
social media presents a convenient and popular medium 25.5.2 Considerations for Implementation
to facilitate connectedness. Though it does not replace
the need for in-person networks and connections, social Many accessible and affordable options are available for
media creates a new space for the dissemination of infor- implementing social media tools. Healthcare profession-
mation, collation and correction of information, emo- als can integrate a social component into preexisting web-
tional support, campaigning, fundraising, and network sites by adding a forum or messaging board. Alternatively,
formation.125 they may consider creating a stand-alone social media site,
which allows additional features like networks, blogs, mes-
saging, and member directories. There are numerous tools
for both add-on and stand-alone options.140,141 Lastly, if
25.5.1 Outcomes the target audience already spends time on a social media
Convenience: Social media provides instant information website, clinicians may simply consider creating a group
exchange, easy access, self-paced interactions, and lack of or application on that site to lower the barrier to entry.
restrictions regarding time and location.126 Social media guidelines specific to the medical com-
Social Support and Connection: Social connections munity are starting to emerge, but these guidelines remain
are critical for overall health and for healthy habits.127 a starting point, as they are general and lack specific guid-
With loneliness affecting 25%–60% of older adults,128 ance.142 Despite the growing popularity of social media,
online options may help fill an in-person void. Online few healthcare providers currently engage with their
social support is particularly valuable for chronically ill patients online.143,144 Among those who do, many describe
or immobile individuals, since illness-related concerns or using social media as a “megaphone” or mouthpiece, indi-
questions cannot always be shared with close friends and cating they are predominately sharing their own views.145
family without straining offline relationships.129 Social A key element of online networks, a two-way communica-
network use not only enhances online relationships but tion or group setting, appears to be underutilized.145
can alleviate strain in—and even strengthen—offline per- Research evaluating which social media features and
sonal relationships.130 components contribute to successful health outcomes
25.6 Section 5: Digital Therapeutics 319
is still limited. One recurring theme is the importance tests and sometimes seek regulatory approvals. The first
25
of integrating coaches into an online network.146,147 FDA approval was in 2013 for a prescription mobile dia-
Research on BecomeAnEx.org, an online social network betes program, and the second approval was in 2017 for
focused on smoking cessation, found that among smok- a cognitive behavioral therapy platform for substance
ers not using coaches, online community visitors were no abuse. Due in part to FDA approvals and successful indi-
more likely to quit than non-visitors. However, among vidual studies, some digital therapeutic programs for
those who used the coach, visitors were twice as likely diabetes and weight loss are now covered by employer-
to have quit at six months.146 Online coaches also play provided insurance, but reimbursement policies are still
a vital role in guiding lifestyle choices in chronic disease evolving, as evidenced by Medicare’s recent decision to
prevention programs,147 as discussed later in the “Digital cover in-person diabetes prevention programs (DPP), but
Therapeutics” section. not virtual DPP.155 Continued research will likely be the
More data is needed to determine who will benefit key to expanding insurance coverage under Medicare and
most from social media and who is prone to misuse it. The other insurance carriers.
AGES (Activating and Guiding the Engagement of Seniors Notably, digital therapeutics can collect a high volume
through Social Media) 2.0 project revealed that elderly of user data from a variety of sources, ranging from tra-
patients trained in the use of social media, as well as Skype ditional clinical biomarkers to personalized physiologic
and email, performed better cognitively and experienced parameters and social patterns.156 These data sets allow
improved mental health and physical well-being compared for big data analytics during active treatment periods,
to a control group receiving usual care.148 In contrast to the easy access to longitudinal data patterns, and insight into
elderly population, a survey of young adults aged 19–32 the effectiveness of specific lifestyle medicine program
found increased social media use was associated with social variations, all of which should contribute to research and
isolation.149 Participants who used social media more than lead to further program improvements.
two hours a day had twice the odds for perceived social
isolation than their peers who spent less than half an hour
on social media each day. In another study, researchers 25.6.1 Outcomes
used biomarkers to demonstrate that social media overuse
may lead to increased stress and higher cortisol levels.150 Though “digital therapeutics” was coined in 2013,
However, these negative effects may be explained by an research on digital treatment solutions began in 2000,157
emerging maladaptive use pattern known as problematic with a surge of activity since 2016. Thus far, studies have
social media use, characterized by addictive components. focused on COPD, asthma, substance abuse, depression,
Shensa et al. suggest that it may be how we use social arthritis, weight loss, and diabetes.158–162 A 2010 meta-
media, not how much, that poses a risk.151 analysis reviewed 85 studies on Internet-delivered pro-
grams from 2000 to 2008 and showed that a broader
use of behavior change techniques and modes of delivery
25.6 SECTION 5: DIGITAL (particularly regular notifications) improved the efficacy
of a given program. It also found that digital therapeutics
THERAPEUTICS have a “statistically small but significant effect on health-
related behavior”.153 However, digital therapeutics have
Online searches for illness-related information date back become more advanced since that time, and multiple stud-
to the early stages of the Internet.152 Nine of ten Americans ies have now shown clinically significant outcomes.
use the Internet,121 and its ubiquitous nature has paved An online diabetes prevention program comprised of
the way for the new field of “digital therapeutics,” evi- a weekly lifestyle medicine curriculum, health coaching,
dence-based digital health tools that are utilized to treat support groups, digital scales, and activity tracking114
or reverse disease.153 Digital therapeutic programs aim to saw participants lose an average of 4.7% of baseline body
replace or augment traditional treatments with behavioral weight and undergo a 0.38% reduction in HgA1c levels
change programs that can be prescribed by a clinician. after one year. Although the active intervention was 12
They can be delivered via Web browsers, smartphone/ months (16-week core curriculum and then a 32-week
tablet applications, and/or medical devices, and typically maintenance curriculum), participants were given con-
combine many of the technologies covered in this chapter tinued access to the program, allowing for proactive use.
to create a comprehensive treatment program. Programs Both HgA1c and weight loss results were maintained
track results using wearable sensors, leverage the power through year two, far beyond the active intervention
of social networking to bolster social support, and uti- period,163 which underscores digital therapeutics’ ability
lize smartphone/tablet applications or text messaging to to enable long-term maintenance of lifestyle changes with
display information or reminders. On the back end, they minimal ongoing treatment or cost.
may include clinical assessment tools, clinician moni- Multiple digital therapeutic programs are aimed at
tored dashboards and HIPAA-compliant data storage.154 reversing diabetes. For example, in one program, glucose
Many programs also incorporate remote human coach- meters and virtual health coaching via mobile devices
ing, which has emerged as an effective and scalable option were added to ongoing community primary care. The pro-
for providing intensive behavioral counseling, particularly gram identified trends and patterns in the patient’s glucose
when in-person programs are not accessible or convenient. and lifestyle, and shared this information with the user,
To distinguish digital therapeutics from health apps, healthcare team, and virtual coach, who could provide
digital therapeutics companies tend to carry out clinical personalized feedback in real time. The program’s two
320 Chapter 25 Digital Health Technology for Behavior Change
clinical trials demonstrated significant reduction in A1c of for energy homeostasis, which may affect weight loss or
1.9% and 2.03%, respectively.164,165 gain.169 Furthermore, the trillions of bacteria, archaea,
Outside of diabetes, a hypertension prevention plat- fungi, and viruses which make up the gut microbiome are
form found a significant average drop in both systolic known to affect food processing, metabolism, vitamin
and diastolic blood pressure (18.6 mmHg and 6.4 mmHg, synthesis, and weight regulation.175 Bacterial composition
respectively) during a 24-week study.166 Participants used changes in response to diet and weight loss,176 suggesting
a mobile program to log meals, record blood pressure that the microbiome may be used to monitor the effective-
and weight, and receive both phone calls and in-app sup- ness of lifestyle changes.
port from a human coach. Actions within the application Knowledge of one’s multiomic profile alone can poten-
that predicted changes in blood pressure and weight were tially influence behavior. This has been demonstrated
completion status, baseline weight, frequency of weigh- with genetic variations identifying serious disease risk
ins, and meal logging. This study highlighted the impor- (e.g., BRCA mutations leading to mastectomy), but studies
tance of frequent tracking in lifestyle interventions, which have shown mixed results for motivating lifestyle change.
can be done in a quick and integrated manner with digital A Cochrane review showed little to no effect of commu-
solutions. nicating DNA-based disease risk on smoking or physi-
Lastly, a 12-week app-based program, comprising cal activity, and only a small effect on diet or intention
sensor-guided physical exercises, weekly education, activ- to change behavior, though evidence was low quality.177
ity tracking, and psychosocial support, such as personal While some studies show that notification of genetic nutri-
coaching and cognitive behavioral therapy (CBT), has tion profiles leads to short-term improvements in motiva-
evaluated reductions in chronic knee pain. In a single-arm tion to change, none show long-term changes or significant
study, participants reported a 57% reduction in pain along effect on health outcomes.178–180
with reduced knee stiffness and improved knee function, Multiomic technology may be used to determine which
all of which were maintained at six-month follow-up.167 patients will respond to lifestyle interventions, which
The application tracked the execution of the exercises and markers should be used to monitor success,181 and/or how
provided real-time feedback to the user to ensure that the lifestyle recommendations should be tailored for individu-
exercises were performed correctly, and also allowed for als. Only small trials have demonstrated this potential to
precise tracking of participation, showing that on average date, such as the Pound Lost Trial in which individuals
participants performed exercise therapy three to four days with particular FTO gene variations were found to ben-
per week. efit from a high protein, calorie-restricted diet. The recent
Food4Me trial showed no benefit of a personalized weight
loss program, however, compared with those who received
25.7 SECTION 6: EMERGING more generalized recommendations.172 Despite the lack of
research to date, many start-up companies have in recent
TECHNOLOGIES years provided personalized nutrition recommendations
based on genomic or microbiomic profiles, and there is
25.7.1 Multiomics significant optimism that identification of individual mul-
tiomic variations will lead to more effective interventions.
Remarkable advancements in the speed and cost of
sequencing technology have occurred in recent years,168
leading to a rapid increase in knowledge of the human
genome, epigenome, transcriptome, proteome, metabo-
25.7.2 Virtual and Augmented Reality
lome, and microbiome,169 collectively known as mul- Both virtual and augmented reality have surged in popu-
tiomics. A significant amount of research is now dedicated larity in recent years. Virtual reality (VR) is an artificial,
to understanding how multiomics can guide healthy life- computer-generated simulation of a real-life environment.
style behaviors for disease prevention. Lifestyle genomics Users typically wear a headset, immersing themselves in
investigates lifestyle-gene interactions,170 while the field of an environment which makes them feel like they are in
nutritional genomics (also known as nutrigenomics) stud- a simulated reality. Augmented reality (AR) is a technol-
ies the relationship between genes and diet.171 ogy that layers computer-generated enhancements atop an
Nearly 150 genetic variants have already been associ- existing reality. AR is built into applications on mobile
ated with cross-sectional measures of obesity, and about devices to add digital components into the real world.182
half of the inter-individual variance in body size can be There is reason to believe that these technologies,
attributed to genetics.169 Furthermore, genes have been especially augmented reality, may be helpful for behav-
shown to influence metabolism, food preferences, and eat- ior change. On July 6, 2016, an augmented reality game
ing behaviors. Numerous studies now show the ability to called Pokémon Go (developed by Niantic, Inc.) was
lose or gain weight is in part genetically determined.172–174 developed for iOS and Android devices that led to a
Genetics may also play a role in physical activity, and a “population-level” surge in fitness tracker step counts.183
limited number of genes have been found that may affect The application was adopted by 40 million users world-
exercise adherence and/or tolerance.169 wide and had 500 million downloads.184 One study found
Other areas of multiomics may provide further insights that users with high interest in the game increased their
into lifestyle change. Epigenome-wide association stud- activity by 26% (1,479 steps/day) and were almost three
ies have shown physical activity and high-fat diets may times as likely to meet official physical activity guide-
alter the DNA methylation pattern in tissues important lines.184 Another study showed a 34.8% relative increase
25.8 Conclusion 321
in step counts, while the number of participants achiev- these sensors also promise novel physiological measure-
25
ing a goal of 10,000 steps per day increased from 15.3% ments, such as caloric intake or hydration. However, while
to 27.5%.185 Notably, both studies reported significant a large array of sensors has demonstrated sufficient capa-
improvements in sedentary, overweight/obese, and older bilities under laboratory conditions, very few such devices
users. Unfortunately, the results of the intervention were have become commercially viable, typically due to signal-
short-lived, and the number of daily steps returned to pre- to-noise ratios in real-world conditions and/or because the
installation levels by week six.186 technology to reliably and cheaply mass-produce these
Despite the short-lived nature of these improvements, sensors has not yet been invented. 202 While these novel
other augmented reality applications may emerge that sensors are likely to emerge in the future, in the near term
stimulate physical activity, diet, or other lifestyle behav- it may be more likely that miniaturization of existing
iors in creative ways. For example, a recent randomized sensors into wireless or disposable forms will impact the
trial showed that an augmented reality application on a practice of lifestyle medicine. For example, the recent FDA
tablet computer helped participants more accurately mea- approval of a patch containing a very-thin filament for
sure standard serving sizes compared with those who continuous glucose monitoring108 has potential to improve
received information only.187 There is also a possibility patient engagement in lifestyle change programs.
that VR applications may be useful for increasing lifestyle
behaviors, especially physical activity. A 2017 systematic
review and meta-analysis of 28 studies showed that vir- 25.7.5 Big Data and Machine Learning
tual reality games had positive effects on balance and fear
of falling in community-dwelling older adults,188 though The technologies described in the preceding sections will
previous reviews examining the use of virtual reality for generate massive amounts of data, requiring advanced
physical activity in older adults were inconclusive due to a analytics to make the data meaningful and actionable.
lack of high-quality evidence.189,190 Artificial intelligence (AI)—the ability for machines
to mimic facets of human cognition—is already being
applied to other fields of medicine, such as making diag-
noses in radiology and pathology. 203 The branch of AI
25.7.3 Assistive Mobility Devices that holds the most immediate-term relevance for lifestyle
To date, the use of advanced exoskeletons has largely been medicine is that of Machine Learning (ML). ML is an ana-
limited to patients with paraplegia or other severe neuro- lytical method that allows a computer to be trained on
logical disorders, and to specialized military or industrial massive quantities of data to make decisions about other
applications. While the technology has proven valuable data. 204 As the computer gains more experience via more
for rehabilitation and limited functional ambulation, it data, its ability to make decisions improves. ML can iden-
has faced many barriers to adoption, including high cost, tify certain patterns of physiological or behavioral data,
heavy components, and difficulty donning and doffing.191 sometimes referred to as digital biomarkers, which can be
However, new types of exoskeletons and exosuits that use used to predict the likelihood of future clinical outcomes.
soft materials, such as fabrics, and alternative actuator Such “predictive analytics” have potential to augment
systems, such as air compression, are significantly lighter, digital lifestyle medicine, as they could be embedded in
easier to use, more adaptable to body differences, and less behavioral feedback loops and population medicine strat-
expensive.192,193 While the technology is only starting to egies. 205 For example, a digital therapeutic could capture
be assessed in the literature,194–196 it has potential to be patient text messaging patterns to assess the need for men-
widely integrated into daily life. People with less severe tal health intervention 206 or monitor arm movements to
limitations than paraplegia, such as the elderly, those with determine abnormal eating patterns. 207
joint pains or muscle weakness,197,198 or even healthy users,
could wear these devices to assist with daily activity. The
technologies could be incorporated into clothing, braces, 25.8 CONCLUSION
or shoes to enable easier ambulation, running, hiking,199
jumping, or other physical activities. Digital health tools have developed rapidly in recent
years and have demonstrated the potential to signifi-
cantly enhance healthy behavior change interventions.
Mobile phones and tablets, wearable devices and sen-
25.7.4 Novel Sensors and Form Factors sors, social media, and many other emerging technologies
The progressive miniaturization of electronics, advances are now pervasive in daily life, and utilizing them adds
in wireless data transmission, improved optics, the steady many opportunities to influence patient behavior. While
growth of computing power, and the development of new the development of digital health technology is advancing
materials, including those created using nanotechnology, faster than the research evaluating it, there is sufficient
have driven great interest in the development of novel evidence to support the use of many current technologies
wearable or embeddable sensors. A common theme among in clinical practice.
these sensors is the capture of standard physiological data The use of digital health tools for behavior change
(e.g., pulse, blood pressure, electrocardiogram, blood glu- is likely to grow rapidly as digital health technologies
cose, temperature) via a miniaturized, continuous monitor advance and adoption increases. Furthermore, the shift
in a novel form factor, such as a stick-on tattoo, bandage, towards value-based reimbursement models in the United
microfiber, or minimally invasive implant. 200–202 Some of States will likely lead providers to focus more on reducing
322 Chapter 25 Digital Health Technology for Behavior Change
costs in a patient population, increasing demand for digi- and various emerging technologies for promoting
tal health tools that cost-effectively monitor and encour- healthy behavior change.
age healthy behaviors at scale. • Clinical applications of digital health tools include
However, this chapter emphasizes that the benefits of increased patient engagement (encouragement, goal
digital health tools can only be realized through careful setting, health coaching, education, reminders/
design and the use of proven behavior change approaches. notifications, and fostering social connection) and
Clinicians or organizations must first articulate their patient monitoring (activity, biochemical markers,
behavior change goals and understand the specific needs home behaviors, medication adherence, sleep, stress/
of their patient population before adopting technology. To mood, or vital signs).
achieve meaningful and lasting behavior change, digital • Digital health tools can be used either as stand-
health tools need to be chosen carefully, integrated within alone applications or complements to in-person
a larger system of people and processes, and ideally tested interventions, but effective clinical use requires a
in the target population. The most cost-effective behav- well-designed integration of people, processes, and
ior change interventions are likely to be those that intel- technology.
ligently combine traditional programs with appropriate • Whether developing a tool or using an existing one,
technology. Ultimately, healthcare providers must remem- implementation considerations include an appropri-
ber that digital health technologies are valuable only to ate behavior change framework, content and func-
the degree that they promote the simple, powerful, healthy tionality designed for the target audience, good
behaviors fundamental to lifestyle medicine. usability, sufficient user testing, and proper data
handling.
• Digital Therapeutics are an emerging category of
CLINICAL TAKEAWAYS evidence-based digital health programs that pre-
vent, treat, or reverse disease, and may be prescribed
• A growing body of evidence supports the use of text by a clinician. They typically combine many of the
messaging, mobile (smartphone or tablet) appli- technologies covered in this chapter, are studied in
cations, wearables/sensors/devices, social media, clinical trials, and may require regulatory approval.
REFERENCES
1. Diehl, H. A. 1998. “Coronary risk 8. Health, Center for Devices and 4300 | Main 202 419 4349 | Fax 202 419
reduction through intensive community- Radiological. n.d. Digital Health—US 4372 | Media Inquiries. 2017. “Mobile
based lifestyle intervention: The coronary FDA. WebContent. Accessed October 6, fact sheet.” Pew Research Center:
health improvement project (CHIP) 2017. https: //www.fda.gov/medicaldev Internet, Science & Tech (blog). January
experience.” The American Journal of ices/d igitalhealth/. 12, 2017. http://www.pewinternet.org /fac
Cardiology 82 (10B): 83T–87T. 9. Sonnier, Paul. n.d. “Definition of digital t-sheet/mobile/.
2. Knowler, William C., Elizabeth Barrett- health.” Paul Sonnier—Story of Digital 17. World Bank. 2016. World Development
Connor, Sarah E. Fowler, Richard F. Health (blog). Accessed October 6, 2017. Report—Digital Dividends. World Bank.
Hamman, John M. Lachin, Elizabeth A. http://stor yofdigital healt h.com /defi niti http://docu ments.worldbank.org/cura
Walker, David M. Nathan, and Diabetes on/. ted/en /896971468194972881/pdf/10272
Prevention Program Research Group. 10. Topol, Eric. 2016. The Patient Will See 5-PUB -Replacement-PU BLIC.pdf.
2002. “Reduction in the incidence of type You Now: The Future of Medicine Is 18. Office-Based Physician Electronic
2 diabetes with lifestyle intervention or in Your Hands. Reprint edition. Basic Health Record Adoption. n.d. Accessed
metformin.” The New England Journal Books. December 1, 2017./quickstats/pages/p
of Medicine 346 (6): 393–403. doi: 11. Topol, Eric. 2012. The Creative hysician-eh r-adoption-trends.php.
10.1056/NEJMoa012512. Destruction of Medicine: How the 19. Adoption of Electronic Health Record
3. D. Ornish et al., “Intensive lifestyle Digital Revolution Will Create Better Systems among U.S. Non-Federal
changes for reversal of coronary heart Health Care. Basic Books. Acute Care Hospitals: 2008–2015. n.d.
disease,” JAMA, vol. 280, no. 23, pp. 12. The Economist. 2016. Things Are Accessed December 1, 2017. http://eva
2001–2007, Dec. 1998. Looking App. March 10, 2016. https luations/data-briefs/non-federal-acute-c
4. D. Ornish et al., “Can lifestyle changes ://www.economist.com/news/ business/ are-hospital-ehr-adoption-2008-2015
reverse coronary heart disease? The life- 21694523-mobile-healt h-apps-are -bec .php.
style heart trial,” Lancet Lond. Engl., vol. oming-more- capable-and-potentially- 20. Health IT Playbook. n.d. Accessed
336, no. 8708, pp. 129–133, Jul. 1990. rather-usef ul-th ings-are-looking. December 1, 2017. https: //www.healthit
5. Mobile Matures as the Cross-Platform 13. 2016 Year End Funding Report: A .gov/playbook/patient-engagement/.
Era Emerges. n.d. ComScore, Inc. Reality Check for Digital Health. n.d. 21. Finkelstein, Eric A., Benjamin A.
Accessed October 9, 2017. http://www Rock Health. Accessed October 6, 2017. Haaland, Marcel Bilger, Aarti
.comscore.com/I nsights/Blog/Mobile- https: //rockhealth.com/reports / 2016 -year Sahasranaman, Robert A. Sloan, Ei Ei
Matures-as-the-Cross- Platform-E ra-E -end-f unding-report-a-reality- check-for- Khaing Nang, and Kelly R. Evenson.
merges. digital-health/. 2016. “Effectiveness of activity trackers
6. Winnick, Michael. n.d. Putting a Finger 14. Voice, F. D. A. n.d. Fostering Medical with and without incentives to increase
on Our Phone Obsession. Accessed Innovation: A Plan for Digital Health physical activity (TRIPPA): A randomised
October 5, 2017. https://blog.dscout.com/ Devices | FDA Voice. Accessed October controlled trial.” The Lancet. Diabetes
mobile-touches. 6, 2017. https: //blogs.fda.gov/fdavoice/ and Endocrinology 4 (12): 983–995. doi:
7. Bauer, Roxanne. 2017. #6 from 2016: index.php/ 2017/ 06/fosteri ng-medical-inn 10.1016/S2213-8587(16)30284-4.
Media (R)Evolutions: Time Spent Online ovation-a-plan-for-digital-health-devices /. 22. Jakicic, J. M., K. K. Davis, R. J. Rogers,
Continues to Rise. Text. People, Spaces, 15. Definitions of MHealth. 2012HIMSS. W. C. King, M. D. Marcus, D. Helsel,
Deliberation. January 3, 2017. https: // January 5, 2012. http://www.himss.org/ A. D. Rickman, A. S. Wahed, and S.
blogs.worldbank.org/publicsphere /6-20 defi n itions-mhealth. H. Belle. 2016. “Effect of wearable
16-med ia-revolutions-time- spent-onli ne-c 16. Street, 1615 L., NW, Suite 800 technology combined with a lifestyle
ontinues-rise. Washington, and DC 20036 202 419 intervention on long-term weight loss:
References 323
The IDEA randomized clinical trial.” of MHealth interventions in low- and 46. Head, K. J., S. M. Noar, N. T. Iannarino,
JAMA 316 (11): 1161–1171. doi: 10.1001/ middle-income countries—What has been and N. Grant Harrington. 2013.
23.
jama.2016.12858.
Pellegrini, Christine A., Steven D. Verba,
Amy D. Otto, Diane L. Helsel, Kelliann 36.
shown to work?” Global Health Action 7
(1): 25606. doi: 10.3402/gha.v7.25606.
Adler, A. J., N. Martin, J. Mariani, C.
“Efficacy of text messaging-based inter-
ventions for health promotion: A meta-
analysis.” Social Science and Medicine
25
K. Davis, and John M. Jakicic. 2012. D. Tajer, O. O. Owolabi, C. Free, N. C. 97 (November): 41–48. doi: 10.1016/j.
“The comparison of a technology-based Serrano, J. P. Casas, and P. Perel. 2017. socscimed.2013.08.003.
system and an in-person behavioral “Mobile phone text messaging to improve 47. Poorman, E., J. Gazmararian, R. M.
weight loss intervention.” Obesity (Silver medication adherence in secondary Parker, B. Yang, and L. Elon. 2015.
Spring, Md.) 20 (2): 356–363. doi: prevention of cardiovascular disease.” “Use of text messaging for maternal and
10.1038/oby.2011.13. Cochrane Database of Systematic infant health: A systematic review of the
24. Spring, Bonnie, Jennifer M. Duncan, E. Reviews 4 (April): Cd011851. doi: literature.” Maternal and Child Health
Amy Janke, Andrea T. Kozak, H. Gene 10.1002/14651858.CD011851.pub2. Journal 19 (5): 969–989. doi: 10.1007/
McFadden, Andrew DeMott, Alex Pictor, 37. Arambepola, C., I. Ricci-Cabello, P. s10995-014-1595-8.
et al. 2013. “Integrating technology into Manikavasagam, N. Roberts, D. P. 48. Shaw, R., and H. Bosworth. 2012.
standard weight loss treatment: A ran- French, and A. Farmer. 2016. “The “Short message service (SMS) text mes-
domized controlled trial.” JAMA Internal impact of automated brief messages saging as an intervention medium for
Medicine 173 (2): 105–111. doi: 10.1001/ promoting lifestyle changes delivered weight loss: A literature review.” Health
jamainternmed.2013.1221. via mobile devices to people with type 2 Informatics Journal 18 (4): 235–250. doi:
25. Abraham, Charles, and Susan Michie. diabetes: A systematic literature review 10.1177/1460458212442422.
2008. “A taxonomy of behavior change and meta-analysis of controlled trials.” 49. Siopis, G., T. Chey, and M. Allman-
techniques used in interventions.” Health Journal of Medicine Internet Research 18 Farinelli. 2015. “A systematic review
Psychology: Official Journal of the (4): e86. doi: 10.2196/jmir.5425. and meta-analysis of interventions for
Division of Health Psychology, American 38. Finitsis, D. J., J. A. Pellowski, and B. T. weight management using text messag-
Psychological Association 27 (3): 379– Johnson. 2014. “Text message interven- ing.” Journal of Human Nutrition and
387. doi: 10.1037/0278-6133.27.3.379. tion designs to promote adherence to Dietetics 28 Suppl 2 (February): 1–15.
26. Prestwich, A., F. F. Sniehotta, C. antiretroviral therapy (ART): A meta- doi: 10.1111/jhn.12207.
Whittington, S. U. Dombrowski, L. analysis of randomized controlled trials.” 50. Farmer, A. J., J. McSharry, S.
Rogers, and S. Michie. 2014. “Does the- PLoS One 9 (2): e88166. doi: 10.1371/ Rowbotham, L. McGowan, I. Ricci-
ory influence the effectiveness of health journal.pone.0088166. Cabello, and D. P. French. 2016. “Effects
behavior interventions? Meta-analysis.” 39. Whittaker, R., H. McRobbie, C. Bullen, of interventions promoting monitoring
Health Psychology 33 (5): 465–474. doi: A. Rodgers, and Y. Gu. 2016. “Mobile of medication use and brief messaging
10.1037/a0032853. phone-based interventions for smok- on medication adherence for people with
27. Fitts Willoughby, J., and R. Furberg. ing cessation.” Cochrane Database of type 2 diabetes: A systematic review of
2015. “Underdeveloped or underre- Systematic Reviews 4 (April): CD006611. randomized trials.” Diabetic Medicine 33
ported? Coverage of pretesting practices doi: 10.1002/14651858.CD006611.pub4. (5): 565–579. doi: 10.1111/dme.12987.
and recommendations for design of 40. Velthoven, M. H. van, S. Brusamento, 51. Fjeldsoe, B. S., A. L. Marshall, and Y. D.
text message-based health behavior A. Majeed, and J. Car. 2013. “Scope Miller. 2009. “Behavior change interven-
change interventions.” Journal of Health and effectiveness of mobile phone tions delivered by mobile telephone short-
Communication 20 (4): 472–478. doi: messaging for HIV/AIDS care: A sys- message service.” American Journal of
10.1080/10810730.2014.977468. tematic review.” Psychology, Health, Preventive Medicine 36 (2): 165–173. doi:
28. Kohut, A., R. Wilke, J. Menasce and Medicine 18 (2): 182–202. doi: 10.1016/j.amepre.2008.09.040.
Horowitz, K. Simmons, J. Poushter, C. 10.1080/13548506.2012.701310. 52. Kharbanda, E. O., M. S. Stockwell,
Barker, J. Bell, and E. M. Gross. 2011. 41. U.S. Department of Health and Human, H. W. Fox, and V. I. Rickert. 2009.
Global Digital Communication: Texting, and Services. Health Resources and “Text4Health: A qualitative evaluation
Social Networking Popular Worldwide. Services Administration. 2014. Using of parental readiness for text message
Pew Research Center. Health Text Messages to Improve immunization reminders.” American
29. Squared, Mobile. 2010. Conversational Consumer Health Knowledge, Behaviors, Journal of Public Health 99 (12): 2176–
Advertising (Commissioned by and Outcomes: An Environmental Scan. 2178. doi: 10.2105/AJPH.2009.161364.
Singlepoint). http://www.mobilesqua red. U.S. Department of Health and Human 53. Naughton, F., A. T. Prevost, H. Gilbert,
co.uk /media /27820/Conversational-Ad Services. https: //www.hrsa.gov/sites /def and S. Sutton. 2012. “Randomized con-
vertising_ SinglePoint _2010.pdf. ault/fi les /archive/healthit/tx t4tots /env trolled trial evaluation of a tailored leaflet
30. Tatango. 2013. SMS Open Rates Exceed ironmentalscan.pdf. and SMS text message self-help interven-
99%. https: //www.tatango.com/blog/s 42. Orr, J. A., and R. J. King. 2015. “Mobile tion for pregnant smokers (MiQuit).”
ms-open-rates-exceed-99/. phone SMS messages can enhance Nicotine and Tobacco Research 14 (5):
31. Hall, A. K., H. Cole-Lewis, and J. healthy behaviour: A meta-analysis of 569–577. doi: 10.1093/ntr/ntr254.
M. Bernhardt. 2015. “Mobile text randomised controlled trials.” Health 54. Park, L. G., J. Howie-Esquivel, and K.
messaging for health: A system- Psychology Review 9 (4): 397–416. doi: Dracup. 2014. “A quantitative system-
atic review of reviews.” Annual 10.1080/17437199.2015.1022847. atic review of the efficacy of mobile
Review of Public Health 36 43. Jongh, T. de, I. Gurol-Urganci, V. phone interventions to improve medica-
(March): 393–415. doi: 10.1146/ Vodopivec-Jamsek, J. Car, and R. Atun. tion adherence.” Journal of Advanced
annurev-publhealth-031914-122855. 2012. “Mobile phone messaging for Nursing 70 (9): 1932–1953. doi: 10.1111/
32. Abroms, L. C., R. Whittaker, C. Free, J. facilitating self-management of long- jan.12400.
Mendel Van Alstyne, and J. M. Schindler- term illnesses.” Cochrane Database of 55. National Cancer Institute, Public Health
Ruwisch. 2015. “Developing and pretest- Systematic Reviews 12 (December): Service, National Institutes of Health.
ing a text messaging program for health CD007459. doi: 10.1002/14651858. 2004. Making Health Communication
behavior change: Recommended steps.” CD007459.pub2. Programs Work: A Planner’s Guide, Pink
JMIR Mhealth Uhealth 3 (4): e107. doi: 44. Shneiderman’s Eight Golden Rules of Book. https: //pubs.cancer.gov/ncipl/detai
10.2196/mhealth.4917. Interface Design. n.d. Accessed October l.aspx?prod id=T068.
33. Zickuhr, K., and A. Smith. 2012. Digital 8, 2017. https: //faculty.washi ngton.edu/ 56. Street, 1615 L., NW, Suite 800
Differences. Pew Research Center. jtenenbg/courses/360 /f04/sessions/schne Washington, and DC 20036 USA 202
34. Beratarrechea, A., A. G. Lee, J. M. Willner, idermanGoldenRules.ht ml. 419 4300 | Main 202 419 4349 | Fax202
E. Jahangir, A. Ciapponi, and A. Rubinstein. 45. Horvath, T., H. Azman, G. E. Kennedy, 419 4372 | Media Inquiries. n.d. Internet
2014. “The impact of mobile health inter- and G. W. Rutherford. 2012. “Mobile & Technology - Pew Research Center.
ventions on chronic disease outcomes in phone text messaging for promoting Accessed October 8, 2017. http://www.
developing countries: A systematic review.” adherence to antiretroviral therapy in pewinternet.org/.
Telemedicine Journal and E Health 20 (1): patients with HIV infection.” Cochrane 57. Organization, World Health. n.d. Be
75–82. doi: 10.1089/tmj.2012.0328. Database of Systematic Reviews, (3): He@lthy, Be Mobile. http: //www.who.
35. Hall, C. S., E. Fottrell, S. Wilkinson, and CD009756. doi: 10.1002/14651858. int/ncds/prevent ion/ b e-hea lthy-be-m
P. Byass. 2014. “Assessing the impact CD009756. obile/en/.
324 Chapter 25 Digital Health Technology for Behavior Change
58. Bau, Ignatius. 2011. “HHS Text4Health 72. Laing, Brian Yoshio, Carol M. Mangione, “Mindfulness-based mobile applications:
task force recommendations.” Ignatius Chi-Hong Tseng, Mei Leng, Ekaterina Literature review and analysis of current
Bau (blog). October 4, 2011. https: //ig Vaisberg, Megha Mahida, Michelle features.” JMIR MHealth and UHealth 1
natiusbau.com/2011/10 /03/ h hs-text4h Bholat, Eve Glazier, Donald E. Morisky, (2). doi: 10.2196/mhealth.2733.
ealth-task-force -recommendations/. and Douglas S. Bell. 2014. “Effectiveness 83. Donker, Tara, Katherine Petrie, Judy
59. Jhumhealth. n.d. Jhumhealth. Accessed of a smartphone application for weight Proudfoot, Janine Clarke, Mary-Rose
October 8, 2017. https://www.jhum- loss compared to usual care in overweight Birch, and Helen Christensen. 2013.
health.org. primary care patients: A randomized “Smartphones for smarter delivery of
60. Schilling, L., G. Bennett, S. Bull, A. controlled trial.” Annals of Internal mental health programs: A systematic
Kempe, M. Wretling, and E. Staton. Medicine 161 (10 0): S5-12. doi: 10.7326/ review.” Journal of Medical Internet
2013. Text Messaging in Healthcare M13-3005. Research 15 (11). doi: 10.2196/jmir.2791.
Research Toolkit. http://www.ucdenver. 73. Flores Mateo, Gemma, Esther Granado- 84. McConnell, Michael V., Anna
edu/academics/colleges/med icalschool / Font, Carme Ferré-Grau, and Xavier Shcherbina, Aleksandra Pavlovic, Julian
prog rams/crisp/trai ning /toolk its/texti Montaña-Carreras. 2015. “Mobile phone R. Homburger, Rachel L. Goldfeder,
ngtool kit/Pages/defau lt.aspx. apps to promote weight loss and increase Daryl Waggot, Mildred K. Cho, et al.
61. Morio, M., H. Goertz, B. Taliesin, physical activity: A systematic review 2017. “Feasibility of obtaining measures
and K. Wilson. 2014. MHealth Mobile and meta-analysis.” Journal of Medical of lifestyle from a smartphone app: The
Messaging Toolkit: Considerations When Internet Research 17 (11). doi: 10.2196/ MyHeart counts cardiovascular health
Selecting a Mobile Messaging Platform jmir.4836. study.” JAMA Cardiology 2 (1): 67–76.
Vendor. http://www.path.org/publicatio 74. Goldstein, C. M., J. G. Thomas, R. R. doi: 10.1001/jamacardio.2016.4395.
ns/detail.php?i=2491. Wing, and D. S. Bond. 2017. “Successful 85. ResearchKit and CareKit. n.d. Apple.
62. Anglada-Martinez, H., M. Martin- weight loss maintainers use health- Accessed November 2, 2017. http://www.
Conde, M. Rovira-Illamola, J. M. Sotoca- tracking smartphone applications more apple.com/researchkit/.
Momblona, E. Sequeira, V. Aragunde, than a nationally representative sample: 86. Medable | The Best Platform For
and C. Codina-Jane. 2017. “An interac- Comparison of the national weight con- Healthcare Innovation. n.d. Accessed
tive mobile phone-website platform trol registry to pew tracking for health.” October 6, 2017. https://www.medable.
to facilitate real-time management of Obesity Science and Practice 3 (2): com/.
medication in chronically Ill patients.” 117–126. doi: 10.1002/osp4.102. 87. Home. n.d. THREAD. Accessed October
Journal of Medical Systems 41 (8): 122. 75. Case, Meredith A., Holland A. Burwick, 6, 2017. http://www.threadresearch.com/.
doi: 10.1007/s10916-017-0767-7. Kevin G. Volpp, and Mitesh S. Patel. 88. Vimcare - Launch a Custom Digital
63. CareMessage | Home. n.d. Accessed 2015. “Accuracy of smartphone applica- Health App. n.d. Accessed October 6,
October 8, 2017. https://caremessage. tions and wearable devices for tracking 2017. https://vimcare.com/.
org/. physical activity data.” JAMA 313 (6): 89. Stoyanov, Stoyan R., Leanne Hides,
64. Collins, Lauren, and Scott R. Ellis. 2015. 625–626. doi: 10.1001/jama.2014.17841. David J. Kavanagh, Oksana Zelenko,
Mobile Devices: Tools and Technologies. 76. Fanning, Jason, Sean P. Mullen, and Dian Tjondronegoro, and Madhavan
Taylor & Francis. Edward McAuley. 2012. “Increasing Mani. 2015. “Mobile app rating scale:
65. GlobalWebIndex. n.d. Device Trends physical activity with mobile devices: A new tool for assessing the quality of
2017 | Mobile Device Statistics & More | A meta-analysis.” Journal of Medical health mobile apps.” JMIR MHealth
GlobalWebIndex. Accessed December 1, Internet Research 14 (6). doi: 10.2196/ and UHealth 3 (1): e27. doi: 10.2196/
2017. jmir.2171. mhealth.3422.
66. Poushter, Jacob. 2016. “Smartphone 77. Arteaga, Sonia M., Mo Kudeki, Adrienne 90. Mani, Madhavan, David J. Kavanagh,
ownership and internet usage continues Woodworth, and Sri Kurniawan. 2010. Leanne Hides, and Stoyan R. Stoyanov.
to climb in emerging economies.” Pew “Mobile system to motivate teenag- 2015. “Review and evaluation of
Research Center’s Global Attitudes ers’ physical activity.” In Proceedings mindfulness-based IPhone apps.” JMIR
Project (blog). February 22, 2016. http: of the 9th International Conference MHealth and UHealth 3 (3): e82. doi:
//www.pewglobal.org/2016/02/22/smar on Interaction Design and Children 10.2196/mhealth.4328.
tphone -ownership -and-inter net-usage (IDC’10), ACM, New York, NY, 1–10. 91. Schoeppe, Stephanie, Stephanie Alley,
-conti nues-to-climb-i n-emerging-eco 78. Tsai, Christopher C., Gunny Lee, Fred Amanda L. Rebar, Melanie Hayman,
nomies /. Raab, Gregory J. Norman, Timothy Nicola A. Bray, Wendy Van Lippevelde,
67. Street, 1615 L., NW, Suite 800 Sohn, William G. Griswold, and Kevin Jens-Peter Gnam, Philip Bachert, Artur
Washington, and DC 20036 USA 202 419 Patrick. 2007. “Usability and feasibility Direito, and Corneel Vandelanotte. 2017.
4300 | Main 202 419 4349 | Fax202 419 of PmEB: A mobile phone application for “Apps to improve diet, physical activity
4372 | Media Inquiries. 2017. “Mobile monitoring real time caloric balance.” and sedentary behaviour in children and
fact sheet.” Pew Research Center: Mobile Networks and Applications adolescents: A review of quality, features
Internet, Science & Tech (blog). January 12 (2–3): 173–184. doi: 10.1007/ and behaviour change techniques.” The
12, 2017. http://www.pewinternet.org /fac s11036-007-0014-4. International Journal of Behavioral
t-sheet/mobile/. 79. Wharton, Christopher M., Carol S. Nutrition and Physical Activity 14 (1):
68. tax, * All products require an annual Johnston, Barbara K. Cunningham, 83. doi: 10.1186/s12966-017-0538-3.
contract Prices do not include sales. and Danielle Sterner. 2014. “Dietary 92. Lewis, Thomas Lorchan, and Jeremy
n.d. “Top health app preferences United self-monitoring, but not dietary quality, C. Wyatt. 2014. “MHealth and mobile
States 2012 | Statistic.” Statista. Accessed improves with use of smartphone app medical apps: A framework to assess
November 21, 2017. https: //www.statista technology in an 8-week weight loss risk and promote safer use.” Journal of
.com/statistics/348731/preferences-for-h trial.” Journal of Nutrition Education Medical Internet Research 16 (9). doi:
ealth-apps-by-ty pe-in-the-us/. and Behavior 46 (5): 440–444. doi: 10.2196/jmir.3133.
69. Krebs, Paul, and Dustin T. Duncan. 10.1016/j.jneb.2014.04.291. 93. Chomutare, Taridzo, Luis Fernandez-
2015. “Health app use among US mobile 80. Coughlin, Steven S., Mary Whitehead, Luque, Eirik Årsand, and Gunnar
phone owners: A national survey.” Joyce Q. Sheats, Jeff Mastromonico, Hartvigsen. 2011. “Features of mobile
JMIR MHealth and UHealth 3 (4). doi: and Selina Smith. 2016. “A review of diabetes applications: Review of the
10.2196/mhealth.4924. smartphone applications for promot- literature and analysis of current applica-
70. Ventola, C. Lee. 2014. “Mobile devices ing physical activity.” Jacobs Journal of tions compared against evidence-based
and apps for health care profession- Community Medicine 2 (1). guidelines.” Journal of Medical Internet
als: Uses and benefits.” Pharmacy and 81. Pollak, J., G. Gay, S. Byrne, E. Wagner, Research 13 (3). doi: 10.2196/jmir.1874.
Therapeutics 39 (5): 356–364. D. Retelny, and L. Humphreys. 2010. 94. King, Abby C., Eric B. Hekler, Lauren
71. Withrow, D., and D. A. Alter. 2011. “The “It’s time to eat! Using mobile games to A. Grieco, Sandra J. Winter, Jylana
economic burden of obesity worldwide: promote healthy eating.” IEEE Pervasive L. Sheats, Matthew P. Buman, Banny
A systematic review of the direct costs of Computing 9 (3): 21–27. doi: 10.1109/ Banerjee, Thomas N. Robinson, and
obesity.” Obesity Reviews: An Official MPRV.2010.41. Jesse Cirimele. 2013. “Harnessing dif-
Journal of the International Association 82. Plaza, Inmaculada, Marcelo Marcos ferent motivational frames via mobile
for the Study of Obesity 12 (2): 131–141. Piva Demarzo, Paola Herrera-Mercadal, phones to promote daily physical activity
doi: 10.1111/j.1467-789X.2009.00712.x. and Javier García-Campayo. 2013. and reduce sedentary behavior in aging
References 325
adults.” PLoS ONE 8 (4): e62613. doi: Mendez-Zorrilla. 2014. “Gait analysis On-Demand. n.d. Accessed July 28,
10.1371/journal.pone.0062613. methods: An overview of wearable and 2017. https://www.pelotoncycle.com/
95. King, Abby C., Eric B. Hekler, Lauren
A. Grieco, Sandra J. Winter, Jylana
L. Sheats, Matthew P. Buman, Banny
non-wearable systems, highlighting
clinical applications.” Sensors (Basel,
Switzerland) 14 (2): 3362–3394. doi:
company/.
119. This Cycling Startup Expects $150
Million in Sales This Year. n.d. Fortune.
25
Banerjee, Thomas N. Robinson, and Jesse 10.3390/s140203362. Accessed October 7, 2017. http://fortune.
Cirimele. 2016. “Effects of three motiva- 108. Commissioner, Office of the. n.d. Press com/2016/06/18/peloton/.
tionally targeted mobile device applica- Announcements - FDA Approves First 120. Social Media | Define Social Media
tions on initial physical activity and Continuous Glucose Monitoring System at Dictionary.Com. n.d. Accessed
sedentary behavior change in midlife and for Adults Not Requiring Blood Sample November 26, 2017. http://www.dict
older adults: A randomized trial.” PLOS Calibration. WebContent. Accessed ionary.com / browse/social-media.
ONE 11 (6): e0156370. doi: 10.1371/ October 8, 2017. https: //www.fda.gov/ 121. Street, 1615 L., NW, Suite 800
journal.pone.0156370. NewsEvents / Newsroom/ PressA nnou Washington, and DC 20036 USA202 419
96. Patel, Mitesh S., David A. Asch, and ncements/ucm577890.ht m. 4300 | Main 202 419 4349 | Fax202 419
Kevin G. Volpp. 2015. “Wearable 109. Christiansen, Mark, Timothy Bailey, 4372 | Media Inquiries. 2017. “Internet/
devices as facilitators, not drivers, of Elaine Watkins, David Liljenquist, David broadband fact sheet.” Pew Research
health behavior change.” JAMA 313 (5): Price, Katherine Nakamura, Robert Center: Internet, Science & Tech (blog).
459–460. doi: 10.1001/jama.2014.14781. Boock, and Thomas Peyser. 2013. “A January 12, 2017. http://www.pewintern
97. Lamkin, Paul. n.d. Wearable Tech new-generation continuous glucose et.org /fact-sheet/internet-broadband /.
Market To Double By 2021. Forbes. monitoring system: Improved accuracy 122. Sadasivam, Rajani S., Rebecca L.
Accessed October 7, 2017. https: //ww and reliability compared with a previous- Kinney, Stephenie C. Lemon, Stephanie
w.forbes.com/sites/paullam kin/2017/ generation system.” Diabetes Technology L. Shimada, Jeroan J. Allison, and
06/22/wearable-tech-market-to-doubl and Therapeutics 15 (10): 881–888. doi: Thomas K. Houston. 2013. “Internet
e-by-2021/. 10.1089/dia.2013.0077. health information seeking is a team
98. Fitbit Aria 2TM Wi-Fi Smart Scale. n.d. 110. Choudhary, Pratik, Sharmin Ramasamy, sport: Analysis of the pew internet
Accessed November 22, 2017. https:// Louisa Green, Geraldine Gallen, Siobhan survey.” International Journal of Medical
www.fitbit.com/aria2. Pender, Anna Brackenridge, Stephanie A. Informatics 82 (3): 193–200. doi:
99. Overview. n.d. Samsung Electronics Amiel, and John C. Pickup. 2013. “Real- 10.1016/j.ijmedinf.2012.09.008.
America. Accessed November 22, 2017./ time continuous glucose monitoring 123. Cutrona, Sarah L., Douglas W. Roblin,
us/explore/fam ily-hub-refrigerator/ove significantly reduces severe hypoglycemia Joann L. Wagner, Bridget Gaglio, Andrew
rview/. in hypoglycemia-unaware patients with E. Williams, Rosalie Torres Stone, Terry
100. Luna Mattress Protectors - Premium type 1 diabetes.” Diabetes Care 36 (12): S. Field, and Kathleen M. Mazor. 2013.
Mattress Protector Products. n.d. 4160–4162. doi: 10.2337/dc13-0939. “Adult willingness to use email and social
Accessed November 22, 2017. https:// 111. Thync. n.d. How It Works. Accessed media for peer-to-peer cancer screening
www.lunamattress.com/. October 7, 2017. http://www.thync.com/ communication: Quantitative interview
101. Sylvia, Louisa G., Emily E. Bernstein, how-it-works. study.” JMIR Research Protocols 2 (2):
Jane L. Hubbard, Leigh Keating, and 112. Bhayee, Sheffy, Patricia Tomaszewski, e52. doi: 10.2196/resprot.2886.
Ellen J. Anderson. 2014. “A practical Daniel H. Lee, Graeme Moffat, Lou 124. Ancker, Jessica S., Kristen M. Carpenter,
guide to measuring physical activity.” Pino, Sylvain Moreno, and Norman A. Paul Greene, Randi Hoffmann, Rita
Journal of the Academy of Nutrition S. Farb. 2016. “Attentional and affective Kukafka, Laura A. V. Marlow, Holly G.
and Dietetics 114 (2): 199–208. doi: consequences of technology supported Prigerson, and John M. Quillin. 2009.
10.1016/j.jand.2013.09.018. mindfulness training: A randomised, “Peer-to-peer communication, cancer
102. Shcherbina, Anna, C. Mikael Mattsson, active control, efficacy trial.” BMC prevention, and the internet.” Journal of
Daryl Waggott, Heidi Salisbury, Jeffrey Psychology 4 (November): 60. doi: Health Communication 14 (S1): 38–46.
W. Christle, Trevor Hastie, Matthew 10.1186/s40359-016-0168-6. doi: 10.1080/10810730902806760.
T. Wheeler, and Euan A. Ashley. 2017. 113. Poh, Ming-Zher, Nicholas C. Swenson, 125. Griffiths, Frances, Tim Dobermann,
“Accuracy in wrist-worn, sensor-based and Rosalind W. Picard. 2010. “A wear- Jonathan A. K. Cave, Margaret
measurements of heart rate and energy able sensor for unobtrusive, long-term Thorogood, Samantha Johnson, Kavé
expenditure in a diverse cohort.” Journal assessment of electrodermal activity.” Salamatian, Francis X. Gomez Olive,
of Personalized Medicine 7 (2). doi: IEEE Transactions on Bio-Medical and Jane Goudge. 2015. “The impact
10.3390/jpm7020003. Engineering 57 (5): 1243–1252. doi: of online social networks on health and
103. Terroso, M., R. Freitas, J. Gabriel, A. T. 10.1109/TBME.2009.2038487. health systems: A scoping review and
Marques, and R. Simoes. 2013. “Active 114. Health, Omada. n.d. Digital Therapeutics case studies.” Policy and Internet 7 (4):
assistance for senior healthcare: A for Chronic Disease | Omada Health. 473–496. doi: 10.1002/poi3.97.
wearable system for fall detection.” In Accessed November 18, 2017. https:// 126. Chung, Jae Eun. 2014. “Social net-
8th Iberian Conference on Information www.omadahealth.com. working in online support groups for
Systems and Technologies (CISTI), 1–6. 115. Withings Aura - Nokia. n.d. Accessed health: How online social networking
104. Schwenk, Michael, Jane Mohler, October 7, 2017. https: //support.heal benefits patients.” Journal of Health
Christopher Wendel, Karen D’Huyvetter, th.nok ia.com/hc /en-us /categories/20 Communication 19 (6): 639–659. doi:
Mindy Fain, Ruth Taylor-Piliae, and 0189426-Wit hings-Aura. 10.1080/10810730.2012.757396.
Bijan Najafi. 2015. “Wearable sensor- 116. Patel, Mitesh S., Luca Foschini, Gregory 127. Martino, Jessica, Jennifer Pegg, and
based in-home assessment of gait, W. Kurtzman, Jingsan Zhu, Wenli Wang, Elizabeth Frates. 2015. “The connec-
balance, and physical activity for Charles A. L. Rareshide, and Susan tion prescription: Using the power of
discrimination of frailty status: Baseline M. Zbikowski. 2017. “Using wearable social interactions and the deep desire
results of the Arizona frailty cohort devices and smartphones to track physical for connectedness to empower health
study.” Gerontology 61 (3): 258–267. doi: activity: Initial activation, sustained use, and wellness.” American Journal of
10.1159/000369095. and step counts across sociodemographic Lifestyle Medicine 11 (October). doi:
105. Dobkin, Bruce H. 2013. “Wearable characteristics in a national sample.” 10.1177/1559827615608788.
motion sensors to continuously measure Annals of Internal Medicine 167 (10): 128. Hawkins, Kevin, Shirley Musich, Sara
real-world physical activities.” Current 755. doi: 10.7326/M17-1495. Wang, and Charlotte Yeh. 2015. “The
Opinion in Neurology 26 (6): 602–608. 117. Evenson, Kelly R., Michelle M. Goto, and impact of loneliness on quality-of-life
doi: 10.1097/WCO.0000000000000026. Robert D. Furberg. 2015. “Systematic and patient satisfaction among sicker,
106. Wearable Kinesthetic System for review of the validity and reliability of older adults.” The American Journal of
Capturing and Classifying Upper Limb consumer-wearable activity trackers.” Geriatric Psychiatry 23 (3): S168–S169.
Gesture in Post-Stroke Rehabilitation | The International Journal of Behavioral doi: 10.1016/j.jagp.2014.12.176.
SpringerLink. n.d. Accessed October 7, Nutrition and Physical Activity 129. Pols, Jeannette. 2014. “Knowing
2017. https: //lin k.springer.com/article/1 12 (December): 159. doi: 10.1186/ patients: Turning patient knowledge
0.1186%2F1743-00 03-2- 8?LI=true. s12966-015-0314-1. into science.” Science, Technology,
107. Muro-de-la-Herran, Alvaro, Begonya 118. Peloton | Exercise Bike With Indoor and Human Values 39 (1): 73–97. doi:
Garcia-Zapirain, and Amaia Cycling Classes Streamed Live & 10.1177/0162243913504306.
326 Chapter 25 Digital Health Technology for Behavior Change
130. Kingod, Natasja, Bryan Cleal, Ayo .quertime.com/ar ticle /15-best-online -for use and depressive symptoms among U.S.
Wahlberg, and Gitte R. Husted. 2017. um-platforms-sof tware -free -and-paid/. young adults: A nationally-representative
“Online peer-to-peer communities in 142. Pillow, Malford T., Laura Hopson, study.” Social Science and Medicine
the daily lives of people with chronic Michael Bond, Daniel Cabrera, Leigh (1982) 182: 150–157. doi: 10.1016/j.
illness: A qualitative systematic review.” Patterson, David Pearson, Harsh Sule, et socscimed.2017.03.061.
Qualitative Health Research 27 (1): al. 2014. “Social media guidelines and 152. Jadad, A. R., and A. Gagliardi. 1998.
89–99. doi: 10.1177/1049732316680203. best practices: Recommendations from “Rating health information on the
131. Christakis, Nicholas A., and James H. the council of residency directors social internet: Navigating to knowledge or to
Fowler. 2007. “The spread of obesity in a media task force.” The Western Journal babel?” JAMA 279 (8): 611–614.
large social network over 32 years.” New of Emergency Medicine 15 (1): 26–30. 153. Webb, T. L., J. Joseph, L. Yardley, and
England Journal of Medicine 357 (4): doi: 10.5811/westjem.2013.7.14945. S. Michie. 2010. “Using the internet
370–379. doi: 10.1056/NEJMsa066082. 143. Brown, James, Christopher Ryan, and to promote health behavior change: A
132. Poncela-Casasnovas, Julia, Bonnie Anthony Harris. 2014. “How doctors systematic review and meta-analysis of
Spring, Daniel McClary, Arlen C. Moller, view and use social media: A national the impact of theoretical basis, use of
Rufaro Mukogo, Christine A. Pellegrini, survey.” Journal of Medical Internet behavior change techniques, and mode of
Michael J. Coons, Miriam Davidson, Research 16 (12). doi: 10.2196/jmir.3589. delivery on efficacy.” Journal of Medical
Satyam Mukherjee, and Luis A. Nunes 144. Moorhead, S. Anne, Diane E. Hazlett, Internet Research 12 (1).
Amaral. 2015. “Social embeddedness in Laura Harrison, Jennifer K. Carroll, 154. What We Do. n.d. Pear Therapeutics.
an online weight management pro- Anthea Irwin, and Ciska Hoving. Accessed November 13, 2017. https: //pe
gramme is linked to greater weight loss.” 2013. “A new dimension of health care: artherapeutics.com/what-we -do/.
Journal of the Royal Society Interface Systematic review of the uses, benefits, 155. Medicare Program; Revisions to
12 (104): 20140686. doi: 10.1098/ and limitations of social media for health Payment Policies Under the Physician
rsif.2014.0686. communication.” Journal of Medical Fee Schedule and Other Revisions to Part
133. Hwang, Kevin O., Allison J. Ottenbacher, Internet Research 15 (4): e85. doi: B for CY 2018; Medicare Shared Savings
Angela P. Green, M. Roseann Cannon- 10.2196/jmir.1933. Program Requirements; and Medicare
Diehl, Oneka Richardson, Elmer V. 145. Campbell, Lauren, Yolanda Evans, Diabetes Prevention Program. 2017.
Bernstam, and Eric J. Thomas. 2010. Megan Pumper, and Megan A. Moreno. Federal Register. July 21, 2017. https: //
“Social support in an internet weight loss 2016. “Social media use by physicians: ww w.federalregister.gov/docu ments /201
community.” International Journal of A qualitative study of the new frontier 7/07/21/2017-14639/medicare-program
Medical Informatics 79 (1): 5–13. doi: of medicine.” BMC Medical Informatics -revisions-to-payment-policies-under-the
10.1016/j.ijmedinf.2009.10.003. and Decision Making 16 (July). doi: -physician-fee-schedu le-and-other-revisi
134. Nielsen, A. J. and L. Grøn. 2012. 10.1186/s12911-016-0327-y. ons.
“Standardising the lay: Logics of change 146. Cutrona, Sarah L., Rajani S. Sadasivam, 156. Hird, Nick, Samik Ghosh, and Hiroaki
in programs of disease self-management.” Kathryn DeLaughter, Ariana Kamberi, Kitano. 2016. “Digital health revolution:
Culture Unbound 4: 425–442. Julie E. Volkman, Nathan Cobb, Gregg perfect storm or perfect opportunity
135. Eijk, Martijn van der, Marjan J. Faber, H. Gilbert, Midge N. Ray, and Thomas for pharmaceutical R&D?” Drug
Johanna W. M. Aarts, Jan A. M. Kremer, K. Houston. 2016. “Online tobacco web- Discovery Today 21 (6): 900–911. doi:
Marten Munneke, and Bastiaan R. sites and online communities—Who uses 10.1016/j.drudis.2016.01.010.
Bloem. 2013. “Using online health them and do users quit smoking? The 157. Ritterband, Lee M., and Deborah F. Tate.
communities to deliver patient-centered quit-primo and national dental practice- 2009. “The science of internet interven-
care to people with chronic conditions.” based research network Hi-Quit studies.” tions.” Annals of Behavioral Medicine 38
Journal of Medical Internet Research 15 Translational Behavioral Medicine 6 (4): (1): 1. doi: 10.1007/s12160-009-9132-5.
(6): e115. doi: 10.2196/jmir.2476. 546–557. 158. Merchant, Rajan, Rubina Inamdar, Kelly
136. Myneni, Sahiti, Nathan Cobb, and 147. Sepah, S. Cameron, Luohua Jiang, and Henderson, Meredith Barrett, and David
Trevor Cohen. 2016. “In pursuit of Anne L. Peters. 2014. “Translating Van Sickle. 2016. “Patient reported value
theoretical ground in behavior change the diabetes prevention program into and usability of a digital health interven-
support systems: Analysis of peer-to-peer an online social network: Validation tion for asthma.” Iproceedings 2 (1): e36.
communication in a health-related online against CDC standards.” The Diabetes doi: 10.2196/iproc.6242.
community.” Journal of Medical Internet Educator 40 (4): 435–443. doi: 159. Dahlberg, Leif, Daniel Grahn, Jakob
Research 18 (2): e28. doi: 10.2196/ 10.1177/0145721714531339. E. Dahlberg, and Carina Thorstensson.
jmir.4671. 148. Morton, Thomas A., Neil Wilson, 2016. “A web-based platform for patients
137. Latkin, Carl A., and Amy R. Knowlton. Catherine Haslam, Megan Birney, with osteoarthritis of the hip and knee: A
2015. “Social network assessments and Rosemary Kingston, and Lauren-Grace pilot study.” JMIR Research Protocols 5
interventions for health behavior change: McCloskey. 2016. “Activating and guid- (June): e115. doi: 10.2196/resprot.5665.
A critical review.” Behavioral Medicine ing the engagement of seniors with online 160. Chen, Jessica, Shelanda Jones-Ford,
(Washington, D.C.) 41 (3): 90–97. doi: social networking: Experimental findings Shannon Goeldi, Meredith A. Barrett,
10.1080/08964289.2015.1034645. from the AGES 2.0 project.” Journal and David Van Sickle. 2017. “Feasibility
138. Castro Sweet, Cynthia M., Vinay of Aging and Health 30 (1): 27–51. doi: and clinical impact of deploying a digital
Chiguluri, Rajiv Gumpina, Paul Abbott, 10.1177/0898264316664440. health intervention on a medicare popula-
Erica N. Madero, Mike Payne, Laura 149. Primack, Brian A., Ariel Shensa, Jaime E. tion with asthma or chronic obstructive
Happe, Roger Matanich, Andrew Renda, Sidani, Erin O. Whaite, Liu yi Lin, Daniel pulmonary disease (COPD).” In A48
and Todd Prewitt. 2017. “Outcomes of Rosen, Jason B. Colditz, Ana Radovic, COPD: Issues in Health Care Delivery.
a digital health program with human and Elizabeth Miller. 2017. “Social media American Thoracic Society International
coaching for diabetes risk reduction use and perceived social isolation among Conference Abstracts, American Thoracic
in a medicare population.” Journal of young adults in the U.S.” American Society, A1722–A1722.
Aging and Health 30 (5): 692–710. doi: Journal of Preventive Medicine 53 (1): 161. Campbell, Aimee N. C., Edward V.
10.1177/0898264316688791. 1–8. doi: 10.1016/j.amepre.2017.01.010. Nunes, Abigail G. Matthews, Maxine
139. Wicks, Paul, Timothy E. Vaughan, 150. Morin-Major, Julie Katia, Marie- Stitzer, Gloria M. Miele, Daniel Polsky,
Michael P. Massagli, and James France Marin, Nadia Durand, Nathalie Eva Turrigiano, et al. 2014. “Internet-
Heywood. 2011. “Accelerated clinical Wan, Robert-Paul Juster, and Sonia delivered treatment for substance abuse:
discovery using self-reported patient data J. Lupien. 2016. “Facebook behav- A multi-site randomized controlled
collected online and a patient-matching iors associated with diurnal cortisol clinical trial.” The American Journal
algorithm.” Nature Biotechnology 29 (5): in adolescents: Is befriending stress- of Psychiatry 171 (6): 683–690. doi:
nbt.1837. doi: 10.1038/nbt.1837. ful?” Psychoneuroendocrinology 63 10.1176/appi.ajp.2014.13081055.
140. Business Software Directory. n.d. CMS (Supplement C): 238–246. doi: 10.1016/j. 162. Pinto, Melissa D., Amy M. Greenblatt,
Critic. Accessed November 27, 2017. psyneuen.2015.10.005. Ronald L. Hickman, Heather M. Rice,
https://www.cmscritic.com/dir/. 151. Shensa, Ariel, César G. Escobar-Viera, Tami L. Thomas, and John M. Clochesy.
141. 15 Best Online Forum Platforms/ Jaime E. Sidani, Nicholas D. Bowman, 2016. “Assessing the critical parameters
Software (Free and Paid) - Quertime. n.d. Michael P. Marshal, and Brian A. of ESMART-MH: A promising avatar-
Accessed November 27, 2017. http://www Primack. 2017. “Problematic social media based digital therapeutic intervention
References 327
to reduce depressive symptoms.” Delahanty, Inga Peter, Bahar Erar, 184. Althoff, Tim, Ryen W. White, and Eric
Perspectives in Psychiatric Care 52 (3): Shafqat Ahmad, et al. 2015. “Genetic Horvitz. 2016. “Influence of Pokémon go
157–168. doi: 10.1111/ppc.12112.
163. Sepah, S. Cameron, Luohua Jiang, and
Anne L. Peters. 2015. “Long-term out-
predisposition to weight loss and regain
with lifestyle intervention: Analyses from
the diabetes prevention program and the
on physical activity: Study and impli-
cations.” Journal of Medical Internet
Research 18 (12): e315. doi: 10.2196/
25
comes of a web-based diabetes prevention look AHEAD randomized controlled jmir.6759.
program: 2-year results of a single-arm trials.” Diabetes 64 (12): 4312–4321. doi: 185. Xian, Ying, Hanzhang Xu, Haolin Xu,
longitudinal study.” Journal of Medical 10.2337/db15-0441. Li Liang, Adrian F. Hernandez, Tracy
Internet Research 17 (4): e92. doi: 174. Keski-Rahkonen, Anna, Benjamin Y. Wang, and Eric D. Peterson. 2017.
10.2196/jmir.4052. M. Neale, Cynthia M. Bulik, Kirsi H. “An initial evaluation of the impact
164. Quinn, Charlene C., Suzanne Sysko Pietiläinen, Richard J. Rose, Jaakko of Pokémon GO on physical activ-
Clough, James M. Minor, Dan Lender, Kaprio, and Aila Rissanen. 2005. ity.” Journal of the American Heart
Maria C. Okafor, and Ann Gruber- “Intentional weight loss in young adults: Association 6 (5): e005341. doi: 10.1161/
Baldini. 2008. “WellDoc mobile diabetes Sex-specific genetic and environmen- JAHA.116.005341.
management randomized controlled tal effects.” Obesity Research 13 (4): 186. Howe, Katherine B., Christian Suharlim,
trial: Change in clinical and behavioral 745–753. doi: 10.1038/oby.2005.84. Peter Ueda, Daniel Howe, Ichiro
outcomes and patient and physician 175. Reinehr, Thomas, and Christian L. Roth. Kawachi, and Eric B. Rimm. 2016.
satisfaction.” Diabetes Technology 2015. “The gut sensor as regulator of “Gotta Catch’em All! Pokémon GO and
and Therapeutics 10 (3): 160–168. doi: body weight.” Endocrine 49 (1): 35–50. physical activity among young adults:
10.1089/dia.2008.0283. doi: 10.1007/s12020-014-0518-1. Difference in differences study.” BMJ 355
165. Quinn, Charlene C., Michelle D. 176. Sweeney, Timothy E., and John M. (December): i6270. doi: 10.1136/bmj.
Shardell, Michael L. Terrin, Erik A. Barr, Morton. 2013. “The human gut microbi- i6270.
Shoshana H. Ballew, and Ann L. Gruber- ome: A review of the effect of obesity and 187. Rollo, Megan E., Tamara Bucher,
Baldini. 2011. “Cluster-randomized trial surgically induced weight loss.” JAMA Shamus P. Smith, and Clare E. Collins.
of a mobile phone personalized behav- Surgery 148 (6): 563–569. doi: 10.1001/ 2017. “ServAR: An augmented reality
ioral intervention for blood glucose con- jamasurg.2013.5. tool to guide the serving of food.” The
trol.” Diabetes Care 34 (9): 1934–1942. 177. Marteau, Theresa M., David P. French, International Journal of Behavioral
doi: 10.2337/dc11-0366. Simon J. Griffin, A. T. Prevost, Stephen Nutrition and Physical Activity 14 (1):
166. Toro-Ramos, T., Y. Kim, M. Wood, Sutton, Clare Watkinson, Sophie 65. doi: 10.1186/s12966-017-0516-9.
J. Rajda, K. Niejadlik, J. Honcz, D. Attwood, and Gareth J. Hollands. 2010. 188. Neri, Silvia Gr, Jefferson R. Cardoso,
Marrero, A. Fawer, and A. Michaelides. “Effects of communicating DNA-based Lorena Cruz, Ricardo M. Lima, Ricardo
2017. “Efficacy of a mobile hyperten- disease risk estimates on risk-reducing J. de Oliveira, Maura D. Iversen, and
sion prevention delivery platform with behaviours.” The Cochrane Database of Rodrigo L. Carregaro. 2017. “Do virtual
human coaching.” Journal of Human Systematic Reviews, (10): CD007275. reality games improve mobility skills
Hypertension 31 (12): jhh201769. doi: 178. Bloss, Cinnamon S., Nicholas J. Schork, and balance measurements in commu-
10.1038/jhh.2017.69. and Eric J. Topol. 2011. “Effect of direct- nity-dwelling older adults? Systematic
167. Smittenaar, Peter, Jennifer C. Erhart- to-consumer genomewide profiling to review and meta-analysis.” Clinical
Hledik, Rose Kinsella, Simon Hunter, assess disease risk.” The New England Rehabilitation 31 (10): 1292–1304. doi:
Gabriel Mecklenburg, and Daniel Perez. Journal of Medicine 364 (6): 524–534. 10.1177/0269215517694677.
2017. “Translating comprehensive doi: 10.1056/NEJMoa1011893. 189. Miller, Kimberly J., Brooke S. Adair,
conservative care for chronic knee pain 179. Grant, Richard W., Kelsey E. O’Brien, Alan J. Pearce, Catherine M. Said,
into a digital care pathway: 12-week Jessica L. Waxler, Jason L. Vassy, Linda Elizabeth Ozanne, and Meg M. Morris.
and 6-month outcomes for the hinge M. Delahanty, Laurie G. Bissett, Robert 2014. “Effectiveness and feasibility of
health program.” JMIR Rehabilitation C. Green, et al. 2013. “Personalized virtual reality and gaming system use
and Assistive Technologies 4 (1). doi: genetic risk counseling to motivate at home by older adults for enabling
10.2196/rehab.7258. diabetes prevention: A randomized physical activity to improve health-related
168. Mardis, Elaine R. 2011. “A decade/’s trial.” Diabetes Care 36 (1): 13–19. doi: domains: A systematic review.” Age and
perspective on DNA sequencing technol- 10.2337/dc12-0884. Ageing 43 (2): 188–195. doi: 10.1093/
ogy.” Nature 470 (7333): 198–203. doi: 180. Voils, Corrine I., Cynthia J. Coffman, ageing/aft194.
10.1038/nature09796. Janet M. Grubber, David Edelman, Azita 190. Molina, Karina Iglesia, Natalia
169. Bray, Molly S., Ruth J. F. Loos, Jeanne Sadeghpour, Matthew L. Maciejewski, Aquaroni Ricci, Suzana Albuquerque
M. McCaffery, Charlotte Ling, Paul W. Jamiyla Bolton, Alex Cho, Geoffrey S. de Moraes, and Monica Rodrigues
Franks, George M. Weinstock, Michael Ginsburg, and William S. Yancy. 2015. Perracini. 2014. “Virtual reality using
P. Snyder, Jason L. Vassy, Tanya Agurs- “Does type 2 diabetes genetic testing games for improving physical func-
Collins, and The Conference Working and counseling reduce modifiable risk tioning in older adults: A systematic
Group. 2016. “NIH working group factors? A randomized controlled trial of review.” Journal of NeuroEngineering
report—Using genomic information to veterans.” Journal of General Internal and Rehabilitation 11 (1): 156. doi:
guide weight management: From univer- Medicine 30 (11): 1591–1598. doi: 10.1186/1743-0003-11-156.
sal to precision treatment.” Obesity 24 10.1007/s11606-015-3315-5. 191. Esquenazi, Alberto, Mukul Talaty,
(1): 14–22. doi: 10.1002/oby.21381. 181. Tworoger, Shelley S., Jessica Chubak, and Arun Jayaraman. 2017. “Powered
170. Lifestyle Genomics | Karger Journal. n.d. Erin J. Aiello, Yutaka Yasui, Cornelia exoskeletons for walking assistance in
Accessed October 6, 2017. http://www M. Ulrich, Federico M. Farin, Patricia persons with central nervous system
.karger.com /Jour nal/ Home/275177. L. Stapleton, et al. 2004. “The effect of injuries: A narrative review.” PM &
171. Applying Genomics to Nutrition and CYP19 and COMT polymorphisms on R: The Journal of Injury, Function,
Lifestyle Modification. n.d. Medscape. exercise-induced fat loss in postmeno- and Rehabilitation 9 (1): 46–62. doi:
Accessed October 6, 2017. http://www pausal women.” Obesity Research 12 (6): 10.1016/j.pmrj.2016.07.534.
.medscape.com/viewarticle/ 771376. 972–981. doi: 10.1038/oby.2004.119. 192. Asbeck, Alan T., Robert J. Dyer, Arnar
172. Celis-Morales, Carlos, Cyril F. M. 182. Augment. 2015. “Virtual reality vs. aug- F. Larusson, and Conor J. Walsh. 2013.
Marsaux, Katherine M. Livingstone, mented reality.” Augment News (blog). “Biologically-inspired soft exosuit.” In
Santiago Navas-Carretero, Rodrigo October 6, 2015. http://www.augment.c Proceedings of the IEEE ... International
San-Cristobal, Rosalind Fallaize, Anna om/blog/vir tual-reality-vs-augmented-rea Conference on Rehabilitation Robotics,
L. Macready, et al. 2017. “Can genetic- lity/. 1–8.
based advice help you lose weight? 183. Silver, Kate. 2016. “Pokemon go leading 193. Lessard, Steven, Pattawong Pansodtee,
Findings from the Food4Me European to a `population-level’ surge in fitness Ash Robbins, Leya Breanna Baltaxe-
randomized controlled trial.” The tracker step counts.” Washington Post, Admony, James M. Trombadore, Mircea
American Journal of Clinical Nutrition July 15, 2016, sec. To Your Health. https Teodorescu, Adrian Agogino, and Sri
105 (5): 1204–1213. doi: 10.3945/ ://www.wash ingtonpost.com/news/to-y Kurniawan. 2017. “CRUX: A compliant
ajcn.116.145680. our-health/wp/2016/07/15/pokemon-go robotic upper-extremity exosuit for light-
173. Papandonatos, George D., Qing Pan, -leadi ng-to -a-population-level- surge -in- weight, portable, multi-joint muscular
Nicholas M. Pajewski, Linda M. fitness-tracker- step - counts/. augmentation.” In Proceedings of the
328 Chapter 25 Digital Health Technology for Behavior Change
IEEE ... International Conference on Kathryn Hendron, Lizeth H. Sloot, 316 (22): 2353–2354. doi: 10.1001/
Rehabilitation Robotics, 1633–1638. Pawel Kudzia, et al. 2017. “A soft robotic jama.2016.17438.
194. Dembia, Christopher L., Amy Silder, exosuit improves walking in patients after 204. Marr, Bernard. n.d. What Is The
Thomas K. Uchida, Jennifer L. Hicks, stroke.” Science Translational Medicine 9 Difference Between Deep Learning,
and Scott L. Delp. 2017. “Simulating (400). doi: 10.1126/scitranslmed.aai9084. Machine Learning and AI? Accessed
ideal assistive devices to reduce the meta- 199. Galle, Samuel, Philippe Malcolm, Wim November 20, 2017. https: //www.forbes.
bolic cost of walking with heavy loads.” Derave, and Dirk De Clercq. 2014. com/sites/bernard marr/ 2016/12/08/wha
PloS One 12 (7): e0180320. doi: 10.1371/ “Enhancing performance during inclined t-is-t he-difference-between-deep-lea rnin
journal.pone.0180320. loaded walking with a powered ankle- g-mach ine-learni ng-and-ai/#34b1604c
195. Ding, Ye, Ignacio Galiana, Alan T. foot exoskeleton.” European Journal of 26cf.
Asbeck, Stefano Marco Maria De Rossi, Applied Physiology 114 (11): 2341–2351. 205. Berman, Mark A., Kevin J. Appelbaum,
Jaehyun Bae, Thiago Ribeiro Teles doi: 10.1007/s00421-014-2955-1. Katherine L. Edwards, David M.
Santos, Vanessa Lara de Araujo, Sangjun 200. Webb, R. Chad, Andrew P. Bonifas, Alex Eisenberg, and David L. Katz, 2017.
Lee, Kenneth G. Holt, and Conor Walsh. Behnaz, Yihui Zhang, Ki Jun Yu, Huanyu “FareWell and the how of lifestyle
2017. “Biomechanical and physiologi- Cheng, Mingxing Shi, et al. 2013. medicine.” American Journal of Lifestyle
cal evaluation of multi-joint assistance “Ultrathin conformal devices for precise Medicine. Accessed November 20, 2017.
with soft exosuits.” IEEE Transactions and continuous thermal characterization http: //jou r nals.sagepub.com/doi /pdf /10.1
on Neural Systems and Rehabilitation of human skin.” Nature Materials 12 177/1559827617701411.
Engineering: A Publication of the IEEE (10): 938–944. doi: 10.1038/nmat3755. 206. Cook, Benjamin L., Ana M. Progovac,
Engineering in Medicine and Biology 201. Xi, Wang, Joo Chuan Yeo, Longteng Yu, Pei Chen, Brian Mullin, Sherry Hou,
Society 25 (2): 119–130. doi: 10.1109/ Shuai Zhang, and Chwee Teck Lim. 2017. and Enrique Baca-Garcia. 2016. “Novel
TNSRE.2016.2523250. “Ultrathin and wearable microtubular use of natural language processing
196. Panizzolo, Fausto A., Ignacio Galiana, epidermal sensor for real-time physi- (NLP) to predict suicidal ideation and
Alan T. Asbeck, Christopher Siviy, Kai ological pulse monitoring.” Advanced psychiatric symptoms in a text-based
Schmidt, Kenneth G. Holt, and Conor Materials Technologies 2 (5): n/a–n/a. mental health intervention in Madrid.”
J. Walsh. 2016. “A biologically-inspired doi: 10.1002/admt.201700016. Computational and Mathematical
multi-joint soft exosuit that can reduce 202. Thomas, Andreas, Lutz Heinemann, Methods in Medicine, Research article.
the energy cost of loaded walking.” Araceli Ramírez, and Alfred Zehe. doi: 10.1155/2016/8708434.
Journal of Neuroengineering and 2015. “Options for the development 207. Thomaz, Edison, Abdelkareem Bedri,
Rehabilitation 13 (1): 43. doi: 10.1186/ of noninvasive glucose monitor- Temiloluwa Prioleau, Irfan Essa, and
s12984-016-0150-9. ing.” Journal of Diabetes Science Gregory D. Abowd. 2017. “Exploring
197. Abbasi, Jennifer. 2017. “Lightweight and Technology 10 (3): 782–789. doi: symmetric and asymmetric bimanual
exosuit could help patients walk after 10.1177/1932296815616133. eating detection with inertial sensors
stroke.” JAMA 318 (10): 898. doi: 203. Jha, Saurabh, and Eric J. Topol. on the wrist.” In Proceedings of the
10.1001/jama.2017.13165. 2016. “Adapting to artificial intel- 1st Workshop on Digital Biomarkers
198. Awad, Louis N., Jaehyun Bae, Kathleen ligence: Radiologists and pathologists (DigitalBiomarkers’17), ACM, New
O’Donnell, Stefano M. M. De Rossi, as information specialists.” JAMA York, NY, 21–26.
V
PA RT
Women’ s Health
Paulette Chandler, MD, MPH
329
26
CHAPTER
26.1 INTRODUCTION 26.2 EPIDEMIOLOGY
Technological advances in the diagnosis and treatment Breast cancer is the leading cancer in women worldwide
of breast cancer have led to a decline in deaths from and the most common cause of cancer. In 2017, an esti-
breast cancer,1,2 but the disease prevalence is increasing. mated 252,7105 new cases of invasive breast cancer will
In the 1970s, the lifetime risk of being diagnosed with be diagnosed among U.S. women and 2,470 cases will
breast cancer was one in 11. Today, a woman living in be diagnosed in U.S. men. In addition, 63,410 cases of in
the United States has a 12.4%, or a 1-in-8, lifetime risk of situ breast carcinoma will be diagnosed among women.
being diagnosed with breast cancer. This increase in risk Approximately 40,610 women and 460 men are expected
over the past four decades is due to longer life expectancy, to die from breast cancer in 2017. (1) The risk of develop-
changes in reproductive patterns, menopausal hormone ing breast cancer is very dependent upon where a woman
331
332 Chapter 26 Breast Health
continue all its life functions.13 In Bruce Lipton, MD’s phase of the WHI follow-up study revealed that the can-
26
book, The Biology of Belief, he exposes a new model for a cers that occurred on the combined estrogen/progesterone
cell functioning independent of its DNA and applies it to hormone replacement therapy were diagnosed at higher
the human body.14 stage and have a worse prognosis with suggested higher
The science of epigenetics means “control above genet- mortality.40,41
ics.” Epigenetics has established that DNA blueprints Oral contraceptives have been associated with as
passed down through genes are not set in stone at birth. high as 44% increased risk of developing premenopausal
Lifestyle changes and environmental influences, such as breast cancer when they are taken prior to the comple-
nutrition and stress, can modify genes without chang- tion of a woman’s first pregnancy.15 An important study in
ing their basic blueprint. Evidence strongly suggests that 2017 concluded that women using oral contraceptives or
“when a gene product is needed, a signal from its environ- implanted intrauterine devices (IUDs) that contained the
ment, not an emergent property of the gene itself, activates hormone progestin overall experienced a 20% increase
expression of that gene.” In other words, when it comes to in the relative risk of breast cancer compared to nonus-
genetic control, “it’s the environment.” ers. The study also found that risk increased the longer
women used contraceptives with hormones, with age and
In the chromosome, the DNA forms the core, and varied by formulation.16 The use of exogenous estrogen
the proteins cover the DNA like a sleeve. When and progesterone has been clearly shown to increase a
the genes are covered, their information cannot be woman’s risk of developing breast cancer.17 We need to
“read.” Imagine your bare arm as a piece of DNA carefully consider the consequences to a woman’s overall
representing the gene that codes for blue eyes. In health and wellbeing before beginning exogenous estro-
the nucleus, this stretch of DNA is covered by gen regardless of its form.
bound regulatory proteins, which cover your blue-
eye gene like a shirtsleeve, making it impossible to
be read. How do you get that sleeve off? You need 26.7 SCREENING
an environmental signal to spur the “sleeve” pro-
tein to change shape, i.e., detach from the DNA’s Mammograms do not prevent breast cancer; they prevent
double helix, allowing the gene to be read. Once death from breast cancer. Population screening studies
the DNA is uncovered, the cell makes a copy of the have shown that with early detection we can experience
exposed gene. As a result, the activity of the gene is a 60% reduction in death from breast cancer.18 While we
“controlled” by the presence or absence of the en- work to create healthy lifestyle changes globally, we need
sleeving proteins, which are in turn controlled by to remain diligent about screening women for breast can-
environmental signals. The story of epigenetic con- cer to diagnose this disease as early as possible to affect
trol is the story of how environmental signals con- mortality. Density is now recognized as a risk factor for
trol the activity of genes. developing breast cancer; therefore, it needs to be assessed
in all women and, screening recommendations need to
include automated whole-breast ultrasound as an adjunct
26.6 HORMONE THERAPY to mammography.19–22
Digital mammography is the main means of early
Menopause is a normally occurring process in a woman’s detection, and as of February 11, 2011, the FDA
life cycle. After menopause, breasts are no longer under the approved 3-D tomosynthesis digital tomography as an
cyclic influence of the ovaries; however, they are influenced adjunct screening modality in dense-breasted 23 women.
by estrogen from other internal and external sources. Many It can more readily detect cancers in mammographi-
women fail to recognize that a woman’s largest source of cally dense women and also decrease the rate of recall
estrogen after menopause is her body fat, particularly that (false positives) for benign findings on screening mam-
fat that is found surrounding her waist and in her abdo- mography. 24 The addition of 3-D Automated Whole
men. This fat serves as a substrate to produce estrone and Breast Ultrasound (ABUS) to full field digital screen-
estradiol through multiple steps with the final being the ing mammography in women with American College of
conversion of fat via the enzyme aromatase which is pro- Radiology category 3 or 4 breast density significantly
duced in the adrenal gland. improved invasive breast cancer detection rate. MRI
Hormone replacement therapy has been used for is also used to screen high-risk populations, including
years to treat the “symptoms” of menopause. Hot flashes, BRCA-positive individuals and women with a cumula-
night sweats, irritability, vaginal dryness, and weight tive lifetime risk of >20% as calculated by the IBIS or
gain are considered symptoms of menstrual cessation. In GAIL Risk Model. 25
a ground-breaking study released in 2003, the Women’s Gamma imaging is also being used in dense-breasted
Health Initiative (WHI) findings brought to light that patients, but due to radiation exposure, it is not available
fact that breast cancer incidence was increased by taking as a routine screening tool. Thermography has received
estrogen and progesterone in combination. Many women significant interest as an alternative to mammography
quickly stopped taking their estrogen replacement in but has not been proven in clinical trials to have the
2003 and there was a decline in the incidence of breast sensitivity, specificity or biopsy directed capabilities as
cancer for a short period. In the fall of 2010, the second mammography.
334 Chapter 26 Breast Health
Screening mammography26 is recommended annually differentiation of the breast.33 The breast tissue is par-
for average-risk women over the age of 40, unless there is ticularly vulnerable prior to its complete maturation at
a significant family history of premenopausal breast can- the birth of a woman’s first child. The role of secondhand
cer; in which case, screening schedules should be individu- smoking and breast cancer is less clear, although there has
alized and may include MRI. 27,28 For women with dense been some suggestion for an increased risk for premeno-
breasts, whole-breast screening ultrasound should also be pausal breast cancer.32
considered.
26.9.1 Alcohol
26.8 PREVENTION Alcohol consumption, a modifiable risk factor for cancer,
has become rampant in our society. It is viewed as a nor-
There are pharmacological means of decreasing breast mal part of our social lives and few women or men know
cancer risk. First and foremost, avoid exogenous estrogen that 5.8% of all cancer deaths worldwide were estimated
in any form. Oral contraceptives, hormone replacement to be attributable to alcohol. Alcohol in any form is con-
therapy, and any form of estrogen should be prescribed sidered a carcinogen by the National Cancer Institute. 34
based upon severity of symptoms being treated and at the The amount of alcohol consumed is causal and directly
lowest dose to achieve relief of the symptom. proportional to the increased risk of breast cancer among
For women at high risk of developing breast cancer both pre- and postmenopausal women and for both
(>20% lifetime or >1.7% over 5 years), Exemestane, 29 ER-positive and ER-negative disease. 35
Tamoxifen, and Raloxifene have been shown to decrease Despite a consistent association between alcohol con-
the risk of developing breast cancer by ~ 48%. Raloxifene sumption and breast cancer risk, the underlying mecha-
and Exemestane can only be used in postmenopausal nisms remain unclear. The most-commonly investigated
women and are an excellent choice in high-risk women. pathways include the effect of alcohol on circulating estro-
Raloxifene has the added benefit of treating osteoporosis. gen levels and ER in mammary epithelial cells and the car-
Tamoxifen is approved for prevention in premenopausal cinogenic role of ethanol metabolites. Given the increased
women at high risk. Women need to be informed that susceptibility of breast tissue to tumorigenesis between
there is an associated risk of developing uterine cancer of menarche and first pregnancy and the high prevalence of
approximately 2.5% with Tamoxifen.30 alcohol use in adolescent girls and young women, under-
Surgical options for risk reduction in high-risk women, standing how alcohol intake before first pregnancy influ-
including women who carry the BRCA I and II, TP53, ences breast cancer development is important for breast
PTEN, CDH1 mutations, include prophylactic/risk-reduc- cancer prevention. Alcohol also may increase breast can-
tion mastectomies. Currently, prophylactic salpingo- cer risk by damaging DNA in cells.
oophorectomy is recommended in the carriers of BRCA I Women should understand the accumulation of risk
and II, HNPCC, BRIP1, RAD51C, and RAD51D genes. across the life course and the lifelong increase in risk of
In 67% of BRCA I carriers and 35% of BRCA II carriers, breast cancer from moderate and heavy consumptions in
the cancers that develop are ER-, PR-, HER-2/neu-; there- early adult years. The risks of breast cancer and prolif-
fore, estrogen reduction from oophorectomy will not help erative benign breast disease are increased by 11% and
to prevent these breast cancers.31 16% for one drink/day alcohol intake before first preg-
nancy when breast tissue is likely at its most vulnerable
stage. 36
26.9 RISK FACTORS In premenopausal adult women, alcohol intake has
been associated with higher circulating levels of estradiol
Cigarette smoking has been clearly linked to the devel- and estrone. Alcohol, regardless of what type, not only
opment of lung cancer and heart disease and has also increases empty caloric intake but also interferes with the
been shown to increase the incidence of breast cancer in degradation of estrogen. We know that estrogen does not
postmenopausal women in both current and past smok- cause breast cancer but can act as fuel on a fire that is
ers. In 2012, the International Agency for Research on already burning. Compared to women who don’t drink at
Cancer confirmed a positive association between tobacco all, women who had three alcoholic drinks per week had
smoking and breast cancer. The 2014 report of the U.S. a 15% higher risk of breast cancer. Experts estimate that
Surgeon General revised their 2004 statement, now to the risk of breast cancer goes up another 10% for each
report an estimated 10% increased breast cancer risk for additional drink women regularly have each day. Women
women with a history of smoking. Tobacco smoke con- who have a family history of breast cancer should consider
tains thousands of chemicals, many of which are known avoiding alcohol altogether or drink it sparingly. Women
to be mammary carcinogens.32 in general should limit their alcohol intake to less than one
The most-recent weight of the evidence has suggested a drink per day.37
potentially casual role for active smoking and breast can-
cer, particularly for long-term heavy smoking and smok-
ing initiation at an early age. Smoking appears to have 26.10 OBESITY
adverse effects if initiated during adolescence or early
adulthood before the first pregnancy because of height- Obesity is epidemic and is an established breast cancer risk
ened susceptibility to chemical carcinogens before full factor. There has been a three-fold increase in obesity in
26.10 Obesity 335
26
genetic changes to our DNA, such as increasing the activ-
ity of cancer-promoting genes or decreasing the activity
of cancer-suppressing genes.40 Exposure to pesticides
may cause the net production of reactive oxygen species
(ROS) in tissues when antioxidant defense mechanisms
are overwhelmed, and a consequence of their overpro-
duction is that they can cause extensive DNA and protein
damage in cells.
We know that certain fruits and vegetables are more
susceptible to the pesticides used in farming and there-
fore organically grown varieties are considered superior.
The Environmental Working Group aggregated and
analyzed data from the U.S. Department of Agriculture
found that nearly 70% of samples of 48 types of conven-
tionally grown produce were contaminated with pesticide
residues. The pesticides persisted on fruits and vegetables
even when they were washed and, in some cases, peeled.
The Environmental Working Group (EWG) breaks down
which fruits and vegetables have the highest and lowest
loads of pesticide residues and created the “Dirty Dozen”
and the “Clean 15” list. The lists are to help the con-
sumer decide when it is worth buying organic produce.
For the year 2017 the dirty list, meaning buy organic
Figure 26.1 National Institute on Alcohol Abuse and
Alcoholism. when possible, includes strawberries, spinach, nectarines,
apples, peaches, celery, grapes, pears, cherries, tomatoes,
Source: http://www.aicr.org/cancer-research-update/2016/11_ sweet bell peppers, and potatoes. If organic produce is
02/cru-women-drinking-increasing-amounts-of-alcohol- not affordable or available, consider the health benefits
more-cancer-risk.html. of fruits and vegetable outweighing the risks of pesticide
exposure.
Shapira recently published an extensive review of the
our fast-paced society over the last 30 years. Body compo- literature regarding dietary factors and breast cancer pre-
sition plays a significant role in several factors regarding vention. Recommendations include low-energy-density
breast cancer occurrence and recurrence. Postmenopausal foods, low-glycemic load, and nutritious, plant-based foods
breast cancer risk is about 1.5 times higher in overweight as the main source of nutrition. Minimal or no intake of
women and about 2 times higher in obese women than animal protein and minimal to no alcohol consumption are
in lean women.38 Women with a BMI >30% have a sig- also recommended. In addition, as previously discussed,
nificant risk of breast cancer recurrence once they have lifestyle recommendations include regular physical activ-
been diagnosed. This is likely related to higher estrogen ity, decreasing body/abdominal fatness, limit adult weight
levels because fat tissue is the largest source of estrogen in gain, and extended breastfeeding duration.41
postmenopausal women but may also be related to other
mechanisms, including the higher levels of insulin among
obese women. Obesity is a risk factor for type II diabetes,
which has also been linked to increased risk for postmeno- 26.10.2 Sleep
pausal breast cancer. A review of 40 studies concluded Sleep duration is a potentially modifiable lifestyle factor.
that breast cancer risk was 16% higher in women with Recently, results were presented from the first study to assess
type II diabetes independent of obesity.38 the association of sleep duration using Oncotype DX recur-
With lifestyle modification, a woman’s goal should be rence scores in breast cancer patients.42 They found a strong
to achieve a healthy weight and body composition and inverse correlation between average hours of sleep per night
then to maintain it throughout her lifetime.39 Obesity in and recurrence scores, specifically in postmenopausal breast
youth is associated with early menarche and the beginning cancer patients. The data suggest that lack of sufficient sleep
of lifelong poor eating habits. A BMI < 25% from child- may cause biologically more-aggressive tumors. The women
hood throughout adulthood is ideal. who reported six or fewer hours of sleep per night on average
had higher average recurrence scores compared with women
reporting between six and seven hours of sleep per night or
26.10.1 Clean Eating more than seven hours of sleep. One possible mechanism
Pesticide residues found in fruits and vegetables may for the observed association may be the increased estrogen
cause adverse health problems. The exposure to a mix- and altered estrogen-receptor activity in response to reduced
ture of pesticides with a possible additive or synergistic melatonin from lack of sleep.43,44
effect is still not completely understood. Many carcino- Working the night shift has been associated with ele-
genic pesticides are fat soluble and may be embedded vated risk of numerous cancers, including breast cancer.45– 48
in the adipose tissues for years. These chemicals may Not only shift work constitutes a risk, but there are also
336 Chapter 26 Breast Health
many other factors which are related to the disruption Exercise and physical activity have been documented
of the sleep–wake rhythm such as a lack of melatonin, to decrease a woman’s risk of developing breast cancer.
the disruption of the circadian rhythms of the body on a Three to five hours of physical exercise weekly decreases
molecular level, and disruptions of the circadian rhythm a woman’s risk of breast cancer by 18%. The more lean
of the release of stress hormones such as cortisol and of muscle mass you have the more fat you burn and the less
sex hormones such as estradiol. Likewise, increased stress fat remains to be a substrate for estrogen production.56
due to sleep deprivation, the coordination of shift work Recreational activity at any intensity level during the
with family life, irregular meals, a lack of physical exer- reproductive and postmenopausal years have the greatest
cise, and smoking contribute to a heightened risk. benefit for reducing breast cancer risk. Substantial post-
Several studies have looked at the addition of melato- menopausal weight gain may eliminate the benefits of
nin as a supplement at bedtime using 6–20 mg and show regular activity.57 Epidemiological evidence supports the
promising results from aromatase inhibition in advanced participation in physical activity before and after breast
cancers49 to improved sleep and decreased depression cancer diagnosis as a contributing factor in decreasing risk
symptoms. Since supplementation with melatonin does of breast cancer recurrence and mortality.58
not inhibit the body’s production, there is no adverse
effect to supplementation daily at bedtime. 50,51 26.10.6 Stress Reduction
It is essential to develop good sleep patterns prior to
undergoing cancer surgery, radiation, or chemotherapy. Stress is a major factor in the production of cortisol and
With practical strategies and information, women and inflammatory factors. It is well known that women with
men can correct imbalances and develop healthier sleep breast cancer have psychological distress during diagnosis
patterns for the rest of their lives. and treatment.59 Psychological symptoms in breast cancer
patients are depression, anxiety, and anger. To complicate
matters, prior to a cancer diagnosis, a patient may be suffering
26.10.3 Lifestyle Evaluation from chronic stress symptoms such as irritability, headaches,
and Modifications fatigue, anxiety, nervous stomach, and insomnia. Creating
opportunities to organize and manage stress before it takes
With 75% of breast cancers occurring in women who
its toll is essential.60 Mindfulness involves bringing attention
have no family history, we must make a change in how we
to one’s present moment experiences, including thoughts,
view our personal risk and make changes in our everyday
feelings, and physical sensations, with openness, curiosity,
lives to decrease our individual risk and our global risk. 52
and acceptance.61 Fifteen interventions have been developed
Personal accountability is needed to initiate this shift in
to cultivate mindfulness through formal meditation and
thinking and we need to empower our sisters, daughters,
granddaughters, friends, and colleagues to make con-
scious, healthier choices in their lives. How can we begin
to create a healthier lifestyle? First and foremost, we need
to modify the risk factors that are under our control.
26.10.4 Nutrition
A well-balanced diet is a key component of an overall
healthy lifestyle. Three cohort studies (5–7) have recently
investigated the association between high fruit and vegeta-
ble intake and decreased risk of breast cancer by receptor
status. All three studies found that women who consumed
higher levels of fruits and vegetables had a 32% to 50%
lower risk of ER-breast cancer compared with women who
consumed low levels of fruits and vegetables. In another
cohort study that evaluated only dietary patterns, women
consuming a high fruit or salad pattern were observed to
have a 45% lower risk of ER-breast cancer.53 Earlier studies
of fiber intake and breast cancer risk reduction have been
inconsistent and non-significant and were hypothesized to
reduce breast cancer incidence by inhibiting reabsorption of
estrogen. A study in 2016 revealed that there was a 13%-
lower breast cancer risk per 10 g/day fiber increment dur-
ing early adulthood and 14%-lower breast cancer risk per Figure 26.2 Plausible mechanisms mediating the impact of
10 g/day fiber increment during adolescence.54 diet and exercise on breast cancer recurrence.
26.10.5 Exercise and Recreational Activity Source: Dieli-Conwright CM, Lee K, Kiwata JL. Reducing the
Risk of Breast Cancer Recurrence: an Evaluation of the Effects
Promotion of physical activity is a key component for and Mechanisms of Diet and Exercise. Curr Breast Cancer
population-wide cancer prevention and control efforts.55 Rep. 2016;8(3):139–150.
26.10 Obesity 337
informal practice, and randomized controlled trials have Vitamin D may not directly lower the risk of breast cancer,
26
documented benefits of mindfulness-based interventions but it has substantial health benefits. A healthy level of 25
among breast cancer survivors, including improvements in hydroxy-vitamin D should be maintained above 40 ng/ml.
depressive symptoms, stress, and fatigue.62–68 Women should understand the significance of being defi-
In 2012, a randomized controlled trial at UCLA pro- cient and take supplemental Vitamin D3 to attain a nor-
vided the first evaluation of a brief mindfulness-based mal level. Antioxidants may play a role in risk reduction
intervention for younger breast cancer survivors designed by blocking the formation of free radicals and protecting
to reduce stress, depression, and inflammatory activ- cells from free radical damage.75
ity. In addition, the intervention led to improvements in
fatigue, sleep disturbance, menopausal symptoms, and
positive psychological processes. Mindfulness also led to 26.10.10 CoQ10
significant reductions in pro-inflammatory gene expres-
sion and bio-informatics indications of pro-inflammatory Coenzyme Q10 (CoQ10) is considered an important cel-
signaling.69 lular antioxidant as it is a component of the mitochon-
Techniques to relieve distress include guided imagery, drial electron transport chain. Low circulating levels of
visualization, meditation, progressive muscle relaxation, CoQ10 have been associated with an increased incidence
massage, breathing techniques, prayer, Tai Chi, Qigong, of several cancers as well as poor prognosis for many can-
and yoga. cer types. The effectiveness of CoQ10 administration to
improve the tolerability or prognosis of cancer treatments
has not been fully evaluated, but trends are favorable.76
26.10.7 Important Vitamins,
Antioxidants, and Minerals
26.10.11 Folate
There are several vitamins, antioxidants, and minerals
that can have a significant impact on breast cancer devel- Folate and other B vitamins play important roles in the
opment and risk. production and maintenance of new cells. They are also
needed to make DNA and RNA. The Shanghai Women’s
Study suggests that vitamins E and B supplements may
26.10.8 Vitamin A confer protection against breast cancer among women
who have low dietary intake of those vitamins.77 High
26.10.8.1 Retinol and β-Carotene folate intake in a prospective study of 62,000 French
Vitamin A plays an important role in immune surveillance, women was associated with decreased postmenopausal
cell differentiation, and cell division as well as many other breast cancer risk.78 In the women who had low folate
functions. The genetic expression of inflammatory media- intake and drank alcohol, an increased incidence of breast
tors in women with breast cancer was evaluated in a case- cancer was observed.79 Dietary sources are spinach, aspar-
control study looking at levels of α-tocopherol, retinol, and agus, Brussels sprouts, and fortified cereals.
β-carotene. The study shows that antioxidant nutrients
have a possible biological effect in preventing breast can-
cer. It also supports the belief that immune response is acti- 26.10.12 Vitamin E and Vitamin C
vated during breast cancer.70 Cells undergo many changes
before they become fully aggressive and metastatic. At Vitamins E and C are powerful antioxidants that also play
Thomas Jefferson University, they used a model of breast a role in immune surveillance.
cancer progression composed of four types of cells, each The University of Rochester looked at the role of
one representing a different stage of breast cancer: normal, alpha-tocopherol-associated protein. It is co-expressed
pre-cancerous, cancerous, and a fully aggressive model. with estrogen receptors in the luminal cells of normal/
When the researchers exposed the four breast cell types to benign breast tissue. They found alpha-tocopherol-asso-
different concentrations of retinoic acid – one of the chemi- ciated protein acting as an anti-proliferative factor in
cals that the body converts vitamin A into – they noticed a estrogen-receptor-positive luminal cells in normal/benign
strong change in the pre-cancerous cells. Not only did the breast tissue which serves as indirect evidence to support
pre-cancerous cells begin to look more like normal cells a role for vitamin E in breast cancer prevention.80 Results
in terms of their shape, they also changed their genetic from a meta-analysis suggest that post-diagnosis vitamin
signature back to normal.71 Daily vitamin A requirements C supplement use may be associated with a reduced risk of
should be obtained from a diet rich in Vitamin A. The best mortality. Dietary vitamin C intake was also statistically
food sources are sweet potatoes, carrots, spinach, kale, significantly associated with a reduced risk of total mor-
cantaloupes, apricots, papaya, and mango. tality and breast cancer-specific mortality. More research
is needed in the vitamin E and C breast cancer prevention
arena. Almonds, sunflower seeds, avocado, salmon, and
olive and wheat germ oils are the best dietary sources of
26.10.9 Vitamin D vitamin E. Good food sources for vitamin C include citrus
Vitamin D modulates cell growth, neuromuscular and fruits, red and green peppers, kiwifruit, broccoli, straw-
immune function, and reduction of inflammation.72–74 berries, brussels sprouts, and cantaloupe.
338 Chapter 26 Breast Health
REFERENCES
1. Tirona MT, Sehgal R, Ballester O. 7. Tamimi RM, Spiegelman D, Smith- 14. Lipton B. The Biology of Belief.
Prevention of breast cancer (part I): Warner SA, et al. Population attributable Carlsbad, California: Hay House Inc;
Epidemiology, risk factors, and risk risk of modifiable and nonmodifiable 2008. ISBN:1401923119.
assessment tools. Cancer Invest. 2010 breast cancer risk factors in postmeno- 15. Mørch LS, Skovlund CW, Hannaford
Aug;28(7):743–50. PubMed PMID: pausal breast cancer. Am. J. Epidemiol. PC, Iversen L, Fielding S, Lidegaard Ø.
20636109. 2016;184:884–93. Contemporary hormonal contracep-
2. Tirona MT, Sehgal R, Ballester O. 8. Buys SS, Sandbach JF, Gammon A, et al. tion and the risk of breast cancer. N.
Prevention of breast cancer (part II): Risk A study of over 35,000 women with Engl. J. Med. 2017 Dec 7;377:2228–39.
reduction strategies. Cancer Invest. 2010 breast cancer tested with a 25-gene panel doi:10.1056/NEJMoa1700732.
Dec;28(10):1070–7. ePub 2010 Oct 11. of hereditary cancer genes. Cancer. 2017 16. Soroush A, Farshchian N. The role of
Review. PubMed PMID: 20932221. May 15;123(10):1721–30. doi:10.1002/ oral contraceptive pills on increased
3. https: //www.cancer.org/content/dam/ cncr.30498. ePub 2017 Jan 13. PubMed risk of breast cancer in Iranian popula-
cancer-org /resea rch/cancer-facts-and-sta PMID: 28085182. tions: A meta-analysis. J. Cancer Prev.
tistics/breast- cancer-facts-and-figu res/ 9. http://ibis.ikonopedia.com/ 2016;21:294–301.
breast-cancer-facts-and-fi gures-2017-201 10. Martin RM, Middleton N, Gunnell D, 17. Beaber EF, Buist DS, Barlow WE, Malone
8.pdf Owen CG, Smith GD. Breast-feeding KE, Reed SD, Li CI. Recent oral contracep-
4. Li CI, Daling JR, Porter PL, Tang MT, and cancer: The Boyd Orr cohort tive use by formulation and breast cancer
Malone KE. Relationship between and a systematic review with meta- risk among women 20 to 49 years of age.
potentially modifiable lifestyle factors analysis. J. Natl. Cancer Inst. 2005 Oct Cancer Res. 2014 Aug 1;74(15):4078–89.
and risk of second primary contralateral 5;97(19):1446–57. Review. PubMed doi:10.1158/0008-5472.CAN-13-3400.
breast cancer among women diagnosed PMID: 16204694. 18. Tabár L, Yen MF, Vitak B, et al.
with estrogen receptor-positive invasive 11. Stuebe AM, Willett WC, Xue F, Michels Mammography service screening and
breast cancer. J. Clin. Oncol. 2009 Nov KB. Lactation and incidence of premeno- mortality in breast cancer patients:
10;27(32):5312–8. ePub 2009 Sep 8. pausal breast cancer, a longitudinal study. 20-year follow-up before and after intro-
PubMed PMID: 19738113; PubMed Arch. Intern. Med. 2009;169(15):1364– duction of screening. Lancet 26 April
Central PMCID: PMC2773216. 71. doi:10.1001/archinternmed.2009.231. 2003;361(9367):1405–10. doi:10.1016/
5. https://www.cancer.org/content/dam/ 12. Knox, R. Interview Dr. GESKE URSIN, S0140-6736(03)13143-1. www.
cancer-org/research/cancer-facts-and-sta University of Southern California Study: thelancet.com/journals/lancet/article/
tistics/breast-cancer-facts-and-figures/ Breast – Feeding Decrease Cancer Risk. PIIS0140-6736(03)13143-1/fulltext.
breast-cancer-facts-and-fi gures-2017-201 19 April 2007 NPR. 19. Melnikow J, Fenton JJ, Whitlock EP,
8.pdf 13. Sathyanarayana Rao TS, Jagannatha et al. Supplemental screening for breast
6. Jemal A, Bray F, Center MM, Ferlay J, Rao KS, Asha MR. Drooping cancer in women with dense breasts: A
Ward E, Forman D. Global cancer statis- genes v/s dancing genes. Indian systematic review for the U.S. Preventive
tics. CA Cancer J Clin. 2011;61(2):69–90. J. Psychiatry. 2009;51(3):167–8. Services Task Force. Ann. Intern. Med.
doi: 10.3322/caac.20107 doi:10.4103/0019-5545.55080. 2016;164(4):268–78.
References 339
20. National Comprehensive Cancer 36. Liu Y, Nguyen, Colditz GA. Links 51. Hansen MV, Andersen LT, Madsen MT,
Network (NCCN). NCCN Clinical between alcohol consumption and breast et al. Effect of melatonin on depres-
Practice Guidelines in Oncology: Breast
cancer screening and diagnosis, Version
2.2016. http://www.nccn.org, 2017.
cancer: A look at the evidence. Womens
Health 2015;11(1):65–77.
37. National Institute for Alcohol Abuse
sive symptoms and anxiety in patients
undergoing breast cancer surgery: a
randomized, double-blind, placebo-
26
21. Boyd NF, Guo H, Martin LJ, et al. and Alcoholism. http://www.aicr.org/ controlled trial. Breast Cancer Res.
Mammographic density and the risk and cancer-research-update/2016/11_02/cru- Treat. 2014;145:683. doi:10.1007/
detection of breast cancer. N. Engl. J. women-drinking-increasing-amounts-of- s10549-014-2962-2.
Med. 2007;356(3):227–36. alcohol-more-cancer-risk.html. 52. National Cancer Institute. 2019.
22. Yaghjyan L, Colditz GA, Collins LC, 38. La Vecchia C, Giordano SH, Hortobagyi www.cancer.gov/types/breast/hp/
et al. Mammographic breast density and GN, Chabner B. Overweight, obesity, breast-ovarian-genetics-pdq#link/_4
subsequent risk of breast cancer in post- diabetes, and risk of breast cancer: 53. Jung S, Spiegelman D, Baglietto L, et al.
menopausal women according to tumor Interlocking pieces of the puzzle. Fruit and vegetable intake and risk of
characteristics. J. Natl. Cancer Inst. Oncologist 2011;16:726–9. breast cancer by hormone receptor status.
2011;103(15):1179–89. 39. Petrelli JM, Calle EE, Rodriguez C, J. Natl. Cancer Inst. 2013;105(3):219–
23. Gilbert FJ, Tucker L, Young KC. Digital Thun MJ. Body mass index, height, 36. doi:10.1093/jnci/djs635.
breast tomosynthesis (DBT): A review of and postmenopausal breast cancer 54. Farvid MS, Eliassen AH, Cho E, Liao
the evidence for use as a screening tool. mortality in a prospective cohort of X, Chen WY, Willett WC. Dietary fiber
Clin. Radiol. 2016 Feb;71(2):141–50. U.S. women. Cancer Causes Control intake in young adults and breast cancer
doi:10.1016/j.crad.2015.11.008. ePub 2002;13(4):325–32. risk. Pediatrics. 2016;137(3):e20151226.
2015 Dec 23. Review. PubMed PMID: 40. Alavanja MCR, Ross MK, Bonner doi:10.1542/peds.2015–1226.
26707815. MR. Increased cancer burden among 55. Moore SC, Lee I, Weiderpass E, et al.
24. Wilczek B, Wilczek HE, Rasouliyan L, pesticide applicators and others due to Association of leisure-time physical
Leifland K. Adding 3D automated breast pesticide exposure. CA: Cancer J. Clin. activity with risk of 26 types of cancer
ultrasound to mammography screen- 2013;63:120–42. doi:10.3322/caac.2117. in 1.44 million adults. JAMA Intern.
ing in women with heterogeneously and 41. Shapira N. The potential contribu- Med. 2016;176(6):816–25. doi:10.1001/
extremely dense breasts: Report from tion of dietary factors to breast can- jamainternmed.2016.1548.
a hospital-based, high-volume, single- cer prevention. Eur. J. Cancer Prev. 56. McTiernen A, Kooperberg C, White E,
center breast cancer screening program. 2017 Sep;26(5):385–95. doi:10.1097/ et al. Recreational physical activity and
Eur. J. Radiol. 2016 Sep;85(9):1554–63. CEJ.0000000000000406. PubMed the risk of breast cancer in postmeno-
doi:10.1016/j.ejrad.2016.06.004. ePub PMID: 28746163; PubMed Central pausal women. JAMA. 2003;290:1331–6.
2016 Jun 7. PubMed PMID: 27501888. PMCID: PMC5553235. 57. McCullough LE, Eng SM, Bradshaw PT,
25. Wang X, Huang Y, Li L, Dai H, Song 42. Thompson CL, Li L. Association of sleep et al. Fat or fit: The joint effects of PA,
F, Chen K. Assessment of performance duration and breast cancer oncotypeDX weight gain, and body size on breast can-
of the Gail model for predicting breast recurrence score. Breast Cancer Res. cer risk. Cancer. 2012;118(19):4860–8.
cancer risk: A systematic review and Treat. 2012;134(3):1291–5. doi:10.1007/ doi:10.1002/cncr.27433.
meta-analysis with trial sequential analy- s10549-012-2144-z. 58. Dieli-Conwright CM, Lee K, Kiwata JL.
sis. Breast Cancer Res. 2018;20(1):18. 43. Blask DE. Melatonin, sleep distur- Reducing the risk of breast cancer recur-
26. Mainiero MB, Moy L, Baron P, et al. bance and cancer risk. Sleep Med. Rev. rence: An evaluation of the effects and
ACR Appropriateness Criteria® breast 2009;13(4):257–64. PubMed: 19095474. mechanisms of diet and exercise. Curr.
cancer screening. J. Am. Coll. Radiol. 44. Stevens RG. Circadian disruption and Breast Cancer Rep. 2016;8(3):139–50.
2017;14(11):S383–90. breast cancer: From melatonin to clock doi:10.1007/s12609-016-0218-3.
27. American Cancer Society. ACR genes. Epidemiology. 2005;16(2):254–8. 59. http://docplayer.net/59190294-T he-ef fect
Appropriateness Criteria® breast cancer PubMed: 15703542. -of-st ress-management-model-in- qual
screening. http://www.cancer.org /hea 45. Verkasalo PK, Lillberg K, Stevens RG, ity-of-life -in-breast-cancer-women.html
lthy/fi ndca ncerearly/cancerscreening guid et al. Sleep duration and breast cancer: 60. Garssen B. Psychological factors and
elines /american- cancer-society- guideline A prospective cohort study. Cancer cancer development: Evidence after 30
s-for-the- early- detec tion- of-cancer Res. 2005;65(20):9595–600. PubMed: years of research. Clin. Psychol. Rev.
28. American College of Surgeons. ACR 16230426. 2004;24:315–38.
Appropriateness Criteria® breast cancer 46. Wu AH, Wang R, Koh WP, et al. Sleep 61. https://www.ncbi.nlm.nih.gov/pmc/articles/
screening. http://www.facs.org/news/mam- duration, melatonin and breast cancer PMC4393338/pdf/nihms646659.pdf
mography1109.html among Chinese women in Singapore. 62. Saquib J, Madlensky L, Kealey S, et al.
29. Goss PE. Exemestane for breast-cancer Carcinogenesis. 2008;29(6):1244–8. Classification of CAM use and its
prevention in postmenopausal women. N. PubMed: 18448486. correlates in patients with early-stage
Engl. J. Med. 2011;364:2381–91. 47. Kakizaki M, Kuriyama S, Sone T, et al. breast cancer. Integr. Cancer Ther.
30. Tabár L, Dean PB. A new era Sleep duration and the risk of breast cancer: 2011;10:138–47. PubMed: 21382963.
in the diagnosis and treatment The Ohsaki Cohort Study. Br. J. Cancer. 63. Smalley SWD. Fully Present: The Science,
of breast cancer. 2 Nov 2010. 2008;99(9):1502–5. PubMed: 18813313. Art, and Practice of Mindfulness.
doi:10.1111/j.1524-4741.2010.00992.x. 48. Pinheiro SP, Schernhammer ES, Tworoger Philadelphia, PA: Da Capo Press; 2010.
31. Atchley DP, Albarracin CT, Lopez A, SS, Michels KB. A prospective study on 64. Wurtzen H, Dalton SO, Elsass P, et al.
Valero V, Amos CI, Gonzalez-Angulo habitual duration of sleep and incidence Mindfulness significantly reduces self-
AM, Hortobagyi GN, Arun BK. Clinical of breast cancer in a large cohort of reported levels of anxiety and depression:
and pathologic characteristics of women. Cancer Res. 2006;66(10):5521– Results of a randomised controlled trial
patients with BRCA-positive and BRCA- 5. PubMed: 16707482. among 336 Danish women treated for
negative breast cancer. J. Clin. Oncol. 49. Li Y, Li S, Zhou Y, Meng X, Zhang JJ, stage I–III breast cancer. Eur. J. Cancer.
2008;26(26):4282–8. Xu DP, Li HB. Melatonin for the preven- 2013;49:1365–73. PubMed: 23265707.
32. Dietericha M. Influence of lifestyle fac- tion and treatment of cancer. Oncotarget. 65. Lengacher CA, Johnson-Mallard
tors on breast cancer risk. Breast Care 2017 June 13;8(24):39896–921. V, Post-White J, et al. Randomized
2014;9:407–14. doi:10.1159/000369571. doi:10.18632/oncotarget.16379. Review. controlled trial of mindfulness-based
33. Reynolds P. Smoking and breast cancer. PubMed PMID: 28415828; PubMed stress reduction (MBSR) for survi-
J. Mammary Gland Biol. Neoplasia Central PMCID: PMC5503661. vors of breast cancer. Psychooncology
2013;18:15–23. 50. Innominato PF, Lim AS, Palesh O, 2009;18(12):1261–72. PubMed:
34. Luo J. Association of active and pas- Clemons M, Trudeau M, Eisen A, Wang 19235193.
sive smoking with risk of breast cancer C, Kiss A, Pritchard KI, Bjarnason GA. 66. Carlson LE, Doll R, Stephen J, et al.
among postmenopausal women: A The effect of melatonin on sleep and Randomized controlled trial of
prospective cohort study. BMJ 2011;342. quality of life in patients with advanced mindfulness-based cancer recovery
doi:10.1136/bmj.d101. breast cancer. Support Care Cancer. versus supportive expressive group
35. Harvie M. Can diet and lifestyle prevent 2016 Mar;24(3):1097–105. doi:10.1007/ therapy for distressed survivors of breast
breast cancer: What is the evidence? s00520-015-2883-6. Epub 2015 Aug 11. cancer (MINDSET). J. Clin. Oncol.
ASCO.org. p. 68. PubMed PMID: 26260726. 2013;31:3119–26. PubMed: 23918953.
340 Chapter 26 Breast Health
67. Henderson VP, Clemow L, Massion Evidence Report/Technology Assessment 80. Johnykutty S, Tang P, Zhao H, Hicks
AO, Hurley TG, Druker S, Hebert JR. No. 158 prepared by the University of DG, Yeh S, Wang X. Dual expression
The effects of mindfulness-based stress Ottawa Evidence-Based Practice Center of alpha-tocopherol-associated protein
reduction on psychosocial outcomes and under Contract No. 290-02.0021. AHRQ and estrogen receptor in normal/benign
quality of life in early-stage breast cancer Publication No. 07-E013. Rockville, MD: human breast luminal cells and the down-
patients: A randomized trial. Breast Agency for Healthcare Research and regulation of alpha-tocopherol-associated
Cancer Res. Treat. 2012;131:99–109. Quality; 2007. protein in estrogen-receptor-positive
PubMed: 21901389. 74. Holick MF. Vitamin D. In: Shils ME, breast carcinomas. Mod. Pathol. 2009
68. Hoffman CJ, Ersser SJ, Hopkinson JB, Shike M, Ross AC, Caballero B, Cousins Jun;22(6):770–5. ePub 2009 Mar 20.
Nicholls PG, Harrington JE, Thomas RJ, eds. Modern Nutrition in Health and PubMed PMID: 19305383.
PW. Effectiveness of mindfulness-based Disease, 10th ed. Philadelphia: Lippincott 81. Al-Saran N, Subash-Babu P, Al-Nouri
stress reduction in mood, breast- and Williams & Wilkins; 2006. DM, Alfawaz HA, Alshatwi AA. Zinc
endocrine-related quality of life, and 75. Holick, MF. Vitamin D deficiency. enhances CDKN2A, pRb1 expression
wellbeing in stage 0 to III breast cancer: NEJM. July 2007;357(3):226–81. and regulates functional apoptosis via
A randomized, controlled trial. J. Clin. 76. Aponte B, Carlos DJ, Hernández J, upregulation of p53 and p21 expres-
Oncol. 2012;30:1335–42. PubMed: Rivera Z, Winel SA. Role of coenzyme sion in human breast cancer MCF-7
22430268. Q10 in breast cancer. Pharm. Pharmacol. cell. Environ. Toxicol. Pharmacol.
69. Bower JE, Crosswell AD, Stanton AL, Int. J. 2015;3(2):00052. doi:10.15406/ 2016 Oct;47:19–27. doi:10.1016/j.
et al. Mindfulness meditation for younger ppij.2015.03.00052. etap.2016.08.002. ePub 2016 Aug 2.
breast cancer survivors: A random- 77. Dorjgochoo T, Shrubsole MJ, Shu XO, Lu PubMed PMID: 27567443.
ized controlled trial. Cancer 2015 W, Ruan Z, Zheng Y, Cai H, Dai Q, Gu K, 82. Ibs KH, Rink L. Zinc-altered immune
April 15;121(8):1231–40. doi:10.1002/ Gao YT, Zheng W. Vitamin supplement use function. J. Nutr. 2003 May;133(5 Suppl
cncr.29194. and risk for breast cancer: The Shanghai 1):1452 S–6 S. Review. PubMed PMID:
70. Abranches MV, Santos Mendes MC, Breast Cancer Study. Breast Cancer Res. 12730441.
Ribeiro SM, Franceschini SC, de Treat. 2008 Sep;111(2):269–78. Epub 83. Combs GF, Jr, Gray WP.
Paula SO, de Freitas RN, Peluzio MC. 2007 Oct 5. PubMed PMID: 17917808; Chemopreventive agents: Selenium.
Antioxidant vitamins and cytokines are PubMed Central PMCID: PMC2615487. Pharmacol. Ther. 1998;79:179–92.
altered in breast cancer. Eur. J. Cancer 78. Lajous M, Romieu I, Sabia S, Boutron- 84. McKenzie RC, Rafferty TS, Beckett
Prev. 2011 SEP 11;20(5):403–410. Ruault MC, Clavel-Chapelon F. Folate, GJ. Selenium: An essential element for
71. Thomas Jefferson University. Can vitamin vitamin B12 and postmenopausal breast immune function. Immunol. Today.
A turn back the clock on breast cancer? cancer in a prospective study of French 1998;19:342–5.
ScienceDaily. ScienceDaily. 2014 31 women. Cancer Causes Control. 2006 85. Hunter DJ, Morris JS, Stampfer MJ, Colditz
March. www.sciencedaily.com/releases/ Nov;17(9):1209–13. PubMed PMID: GA, Speizer FE, Willett WC. A prospective
2014/03/140331095550.htm. 17006726; PubMed Central PMCID: study of selenium status and breast cancer
72. Institute of Medicine, Food and PMC1925055. risk. JAMA. 1990 Sep 5;264(9):1128–31.
Nutrition Board. Dietary Reference 79. Kawai M, Minami Y, Kakizaki M, PubMed PMID: 2384937.
Intakes for Calcium and Vitamin D. Kakugawa Y, Nishino Y, Fukao A, Tsuji 86. McConnell KP, Jager RM, Bland KI,
Washington, DC: National Academy I, Ohuchi N. Alcohol consumption and Blotcky AJ. The relationship of dietary
Press; 2010. breast cancer risk in Japanese women: selenium and breast cancer. J. Surg.
73. Cranney C, Horsely T, O’Donnell S, et al. The Miyagi Cohort Study. Breast Cancer Oncol. 1980;15(1):67–70. PubMed
Effectiveness and Safety of Vitamin D. Res. Treat. 2011 Aug;128(3):817–25. PMID: 6252392.
27
CHAPTER
Key Take-Home Points............................................................... 341 27.4.2 Contraceptive Use in Active and Athletic Females......346
27.1 Introduction...................................................................... 341 27.4.3 Exercise During Pregnancy and the Post-Partum......347
27.2 Regular Physical Activity is Essential to the Health and 27.4.4 Hormone Replacement Therapy for Pre- and
Wellbeing of Girls.............................................................. 342 Menopausal Symptoms in Active and Athletic
27.2.1 Physical Activity Recommendations for Girls......... 342 Females�������������������������������������������������������������� 348
27.2.2 Epidemiology of Physical Activity in Girls.............. 342 27.5 The Role of Physical Activity in Chronic Disease
27.2.3 School-Based Physical Activity and Young Girls...... 342 Prevention and Management for Women........................... 348
27.2.4 Physical Literacy for Girls..................................... 343 27.5.1 Physical Activity as a Strategy to Prevent
27.2.5 Competitive Sports for Developing Females.......... 343 Overweight and Obesity in Women���������������������� 348
27.3 Benefits and Risks of Physical Activity and 27.5.2 Physical Activity and Bone Health in Women......... 348
Competitive Sports for Adolescent Females....................... 343 27.5.3 The Role of Regular Physical Activity and
27.3.1 Health Benefits of Regular Physical Activity........... 343 Diabetes Prevention and Management����������������� 348
27.3.2 Social and Emotional Benefits of Regular 27.5.4 The Role of Regular Physical Activity and High
Physical Activity and Sport����������������������������������� 343 Blood Pressure Prevention and Management������� 348
27.3.3 Early Sport Specialization and Risk of Injury......... 343 27.5.5 The Role of Regular Physical Activity in Breast
27.3.4 ACL Injuries in Female Athletes............................. 343 Cancer Prevention and Management������������������� 348
27.3.5 Eating Disorders and Disordered Eating in 27.5.6 The Role of Regular Physical Activity in the
Female Athletes��������������������������������������������������� 344 Prevention of Dementia��������������������������������������� 349
27.4 Reproductive Health in Active and Athletic Females........... 344 Key Clinical Messages............................................................... 349
27.4.1 The Female Athlete Triad....................................... 344 References................................................................................ 349
341
342 Chapter 27 Sports and Physical Activity for Women and Girls
and assist clinicians and care teams in advising patients on around the school day present the ideal opportunity to
physical activity, sports, and exercise for life. participate in recommended levels of physical activity.
This chapter will focus on physical activity, sport, and However, school-based physical education (PE) in the
exercise for women and girls. The chapter is organized United States has steadily declined over more than two
using a lifespan approach, starting with young girls and decades. Nearly 42% of high school students participated
concluding with the impact of regular physical activity in PE on five days of the week in 1991. The percentage
on chronic disease prevention and management in adult declined to 29.8% of high school students in 2015.5 The
females. Additional chapters will cover topics such as reasons for this decline are myriad and include U.S. legis-
exercise during pregnancy and post-partum and exercise lation such as President George W. Bush’s No Child Left
and healthy aging in greater detail. Behind law, which linked school funding with standardized
testing scores. This led many schools and school districts,
especially in disadvantaged communities, to eliminate
27.2 REGULAR PHYSICAL ACTIVITY physical education and recess to focus classroom time on
core subjects such as math, reading, science, and history.6
IS ESSENTIAL TO THE HEALTH The unintended consequence of this strategy was to figura-
AND WELLBEING OF GIRLS tively chain students to their classroom chairs, reducing or
eliminating the opportunity to run and play. An expanding
body of literature has demonstrated that students who are
27.2.1 Physical Activity physically active perform better in school, including bet-
Recommendations for Girls ter grades, school attendance, cognitive performance (e.g.,
The 2008 Physical Activity Guidelines for Americans rec- memory), and classroom behaviors (e.g., on-task behav-
ommends that girls (and boys) age 6–17 years participate in ior). Likewise, students with higher levels of physical fit-
60 minutes or more of moderate to vigorous physical activ- ness demonstrate improved cognitive performance (e.g.,
ity seven days per week. This should include a variety of concentration, memory) at multiple grade levels – elemen-
age-appropriate activities, including aerobic activities, mus- tary, junior high, and high school.7–9
cle strengthening, and bone strengthening (Table 27.1).1 A myriad of additional benefits associated with reg-
ular physical activity and sports participation by girls
include psychosocial benefits (lower rates of depression),10
27.2.2 Epidemiology of Physical lower rates of substance use,11 and lower rates of teen
Activity in Girls pregnancy.12 High school sport participation is indepen-
dently associated with higher rates of regular physical
Despite these recommendations, the 2016 U.S. Report activity participation in adulthood.13 Community-based
Card on Physical Activity for Children and Youth found afterschool programs such as Girls on the Run (GOTR)
that only 21.6% of 6- to 19-year-old children and ado- provide non-competitive opportunities for elementary
lescents in the United States attained 60 or more minutes school- and junior high-aged girls to participate in after-
of moderate-to-vigorous physical activity (MVPA) on at school physical activity, while learning lessons on resil-
least five days per week. 2 As children age, levels of physi- ience, teamwork, self-worth, and self-reliance:
cal activity generally decline, especially amongst girls.
Just over 70% of elementary school-aged girls achieve 60 [The Girls on the Run program teaches] life skills
minutes of MVPA seven days of the week.3 That number through dynamic, interactive lessons and running
declines to 22.5% for high school females.4 However, the games. The curriculum is taught by certified Girls
same paper found that nearly half (49.4%) of girls engaged on the Run coaches and includes three parts: under-
in some form of moderate-to-vigorous physical activity for standing ourselves, valuing relationships and team-
at least 60 minutes on five days or more each week.4 work and understanding how we connect with and
shape the world at large.
27.2.3 School-Based Physical Running is used to inspire and motivate girls,
encourage lifelong health and fitness, and build con-
Activity and Young Girls fidence through accomplishment. Important social,
As children and adolescents spend the majority of their psychological, and physical skills and abilities are
waking hours in school, time and environments in and developed and reinforced throughout the program.
At each season’s conclusion, the girls and their run- 12th grade. 5 Additionally, disparities exist in sports par-
27
ning buddies complete a 5 K running event which ticipation related to both race and socioeconomic status.
gives them a tangible sense of achievement as well Competitive sport participation by Caucasian students
as a framework for setting and achieving life goals.14 (62.4%) exceeds that of both Black (57.6%) and Hispanic
(48.5%) high school students. 5
Girls on the Run has served over one million girls in
all 50 states and the District of Columbia. A 2016 study
of GOTR sought to understand if program participants 27.3 BENEFITS AND RISKS OF
differed from nonparticipants on developmental outcomes
and life skills. Most notably, investigators found that com- PHYSICAL ACTIVITY AND
pared to a non-participating group, GOTR participants
were better able to manage emotions, resolve conflict, help
COMPETITIVE SPORTS FOR
others, and make intentional decisions.15 ADOLESCENT FEMALES
The benefits of participating in sports and physical activ-
27.2.4 Physical Literacy for Girls ity are broad and numerous, including health, cognitive,
social, and even economic. Benefits are accrued through-
An important outcome of regular physical activity, and
out the lifetime, improving quality of life, increasing lon-
especially school PE, is the development and mastery of
gevity, and decreasing premature mortality.
motor skills, such as kicking, throwing, and catching a
ball, referred to as physical literacy. Girls who lack the
opportunity to develop these skills are less confident in
their abilities and subsequently are less likely to partici-
27.3.1 Health Benefits of Regular
pate in sports and activities as children, adolescents, and Physical Activity
adults.16 Physical literacy extends beyond sports participa- The health benefits of regular physical activity start in
tion to include additional lifelong benefits such as lower childhood. The American Academy of Pediatrics recom-
rates of obesity, lower injury rates, and, specifically, less mends that children participate in age- and developmen-
lower back pain.17 This is especially beneficial when one tally appropriate physical activity starting in infancy.
considers that lower back and neck pain rank third to
diabetes and heart disease as the largest drivers of direct
healthcare costs in the United States.18 27.3.2 Social and Emotional Benefits of
The Aspen Institute’s Project Play has been a fore-
most advocate of physical literacy, which they define as Regular Physical Activity and Sport
the ability, confidence, and desire to be physically active While we are most likely to hear and read about the health
for life.19 But physical literacy requires more than just the benefits of sports and regular physical activity, some
development of motor skills – it’s also a matter of devel- would argue that the social and emotional benefits are
oping the mindset to use those skills. Providing oppor- even greater and more important to quality of life.
tunities for skill development AND confidence in using
those skills is key to developing physical literacy. Girls
are considered to be at high risk for low physical literacy, 27.3.3 Early Sport Specialization
given their lower participation rates in sports and physi-
cal activity. Joining them as high-risk groups are minority
and Risk of Injury
children, low-income children, and children with physical As girls start participating in competitive sports at younger
and developmental disabilities.19 Efforts to expand and ages, concerns about the impact of early sport specializa-
extend physical activity opportunities for these high-risk tion have arisen. Consequences of this include not only
groups need to be prioritized in schools and communities higher risk of injury but early burnout.
or these youth are at risk of insufficient physical activity
levels throughout life.
27.3.4 ACL Injuries in Female Athletes
27.2.5 Competitive Sports for It is well understood that female athletes participating
in sports such as soccer, basketball, and team handball
Developing Females have upwards of seven times greater risk of non-con-
Sports participation is increasingly available to children tact anterior cruciate ligament (ACL) injuries compared
and adolescents of all ages, and children are participating to male athletes participating in the same sports. 21 The
in organized competitive sports at younger and younger reasons for this difference are multiple and include both
ages. In the mid-1990s 9% of children six years of age modifiable and non-modifiable risk factors. Modifiable
or younger participated in competitive sports. By 2007, risk factors include environmental factors such as playing
the percentage of six-year-olds participating in competi- surface; footwear; anatomical risk factors such as higher
tive sport increased to 12%. 20 Fifty-three percent of high body mass index; and neuromuscular factors including
school girls participate in high school sports nationwide. muscle imbalances, core strength, neuromuscular con-
However, the percentage of high school students who trol, physical fitness, muscle fatigue, and sport skill level.
participate in sports steadily declines from 9th grade to Non-modifiable risk factors include anatomical factors
344 Chapter 27 Sports and Physical Activity for Women and Girls
such as generalized joint laxity/hypermobility, ACL notch differs from bulimia nervosa based on prolonged periods
size and geometry, and posterior tibial slope. 22 Other non- of dietary restriction typical of anorexia nervosa. Bulimia
modifiable risk factors include opponent behavior and nervosa, better known as binge–purge disease, is char-
unanticipated events during play, hormonal factors/men- acterized by recurrent episodes of binge eating followed
strual cycle phase, and demographic factors such as past by some compensatory behaviors such as self-induced
injury history, family history, and genetics. 23 vomiting, use of laxatives, diuretics, excessive exercise,
Some injury prevention programs have demonstrated or fasting. 25 Similar to those with anorexia nervosa, self-
significant reduction in non-contact ACL-injury rates. 24 evaluation is excessively based on body size, shape, and
These programs specifically address risk factors asso- weight. Binge eating disorder was added as a discrete
ciated with neuromuscular control and sport-specific eating disorder in the DSM5. The diagnostic criteria for
skills. 24 Screening for biomechanical risk factors associ- binge eating include eating rapidly until uncomfortably
ated with higher rates of ACL injury can be performed full, eating large amounts of food even when not hungry,
as part of the preparticipation physical evaluation (PPE), eating alone out of embarrassment, and feeling guilty or
especially for female athletes participating in pivoting and disgusted after eating excessively. 25
cutting sports such as soccer, basketball, and team hand-
ball. At-risk athletes identified through past history of
ACL injury or through the PPE screening process should
start an ACL-injury prevention program. In terms of pri- 27.4 REPRODUCTIVE HEALTH IN
mary prevention, coaches in higher-risk sports should
be encouraged to incorporate an ACL-injury prevention
ACTIVE AND ATHLETIC FEMALES
strategy into routine warm-ups for the team. 24
27.4.1 The Female Athlete Triad
The female athlete triad (Triad) is comprised of three dis-
27.3.5 Eating Disorders and Disordered tinct but related health conditions: low energy availability
(with or without an eating disorder), menstrual dysfunc-
Eating in Female Athletes tion, and low bone mineral density. The term was first
While eating disorders are oftentimes secretive disorders, coined in 1992 when a group of female clinicians and sci-
a study of elite Norwegian athletes identified that between entists met in Washington, DC to discuss their observa-
16% and 42% of female athletes met diagnostic criteria tions that thin, athletic women were more likely to lose
for an eating disorder, the lower number being seen in their menstrual periods and to suffer bone stress frac-
females participating in ball sports and the upper number tures. The American College of Sports Medicine (ACSM)
amongst females participating in aesthetic sports. 25 These published the first Female Athlete Triad Position Stand
shockingly high numbers underscore the importance of in 199726 and an updated Position Stand in 2007. 27 The
screening female athletes for disordered eating and eating updated position stand described a spectrum of patho-
disorders. The Diagnostic and Statistical Manual 5 (DSM5) physiology (Figure 27.1) ranging from health to disease.
identifies three main categories of eating disorders: Of note, low energy availability could occur in the set-
anorexia nervosa, bulimia nervosa, and binge eating dis- ting of intentional dietary restriction, such as an eating
order. Anorexia nervosa is characterized by the restriction disorder or disordered eating, or unintentionally in female
of dietary energy intake relative to requirements, resulting athletes not eating enough to support high levels of exer-
in low body weight for age and sex; and intense fear of cise energy expenditure.
becoming fat or gaining weight; and a mental distortion of The concept of energy availability was described
one’s body size, shape, and weight. 25 Two subtypes exist, by Anne Loucks, PhD, in 2003. 28 Energy availability is
a restricting type and a binge eating/purging type, which defined as the amount of dietary energy remaining after
subtraction of exercise energy expenditure, normalized to athlete’s compliance and follow through with a written
27
an athlete’s fat-free mass. The formula for which is. 5 contract. Athletes given limited clearance typically have
limitations placed on training and competition as a conse-
Average daily dietary energy intake (kcal) – quence of underlying health concerns. Those scoring 6 or
Energy availability Exercise energy expenditure (kcal) more points may be restricted from training and/or com-
(kcal/kg FFM) = Fat-free mass (FFM) (kg) petition depending on the severity of risk factors, and ath-
letes with active eating disorders should be restricted from
participation. Restriction should not be considered per-
Components of the energy availability formula can manent for the vast majority of individuals, in hopes that
be determined a number of ways. Smartphone applica- risk factors can be ameliorated sufficiently to allow for
tions like MyFitnessPal can be used to estimate dietary safe participation. It also bears mentioning that “past his-
energy intake. Exercise energy expenditure can be calcu- tory” risk factors may be non-modifiable (e.g. past history
lated using the Physical Activity Compendium, 29 and fat- of disordered eating (1 point), delayed menarche (up to 2
free mass can be estimated using bioelectrical impedance points), past history of stress fractures (up to 2 points),
scales or measured using a BodPod or whole-body, dual- previously low DXA Z-score (up to 2 points), resulting in
energy X-ray absorptiometry (DXA). a score greater than 6 in an athlete who is currently eat-
Energy availability of at least 30 kcal/kg FFM is ing healthfully, maintaining a normal body weight, and
considered sufficient to support normal reproductive regularly menstruating). In such cases, clinical judgment
function. 30 Energy availability less than 30 kcal/kg of by the sports medicine team physician, the athlete care
FFM is associated with disruption of normal menstrual team, and the athlete herself is warranted to determine
cycles. 30 However, an EA of 35 to 45 kcal/kg FFM or safe participation in sports.
likely greater than 45 kcal/kg FFM is desired for resump- Validation of the cumulative risk assessment stratifica-
tion of menses in females with either oligomenorrhea or tion tool revealed that athletes considered moderate risk
amenorrhea. 27,31–33 were two times as likely to suffer a bone stress injury,
Low energy availability results in menstrual dysfunc- and athletes at high risk, four times as likely to suffer a
tion by reducing the pulsatile release of gonadotropin- bone stress injury. The oligomenorrhea/amenorrhea score
releasing hormone (GnRH) from the hypothalamus. In and the prior stress fracture/reaction score were identi-
turn, this results in decreased production and release of fied as independent predictors for subsequent bone stress
follicle-stimulating hormone (FSH) and luteinizing hor- injuries.36
mone (LH) from the anterior pituitary gland. Absent In addition to recommendations on clearance and
this stimulation, ovarian production of estrogen and return to play, the Coalition Consensus paper provides
progesterone is significantly reduced, and menses either guidance to the sports medicine physician on pharmaco-
reduce in frequency (oligomenorrhea) or cease to occur logic interventions for amenorrhea and low bone mineral
(amenorrhea). density, as well as recommendations for diagnostic testing
The majority of females are dependent on estrogen for of menstrual dysfunction and low bone mineral density. 31
the development and maintenance of normal bone mineral It bears repeating that the primary treatment of
density (BMD).34 When estrogen levels are insufficient, in the female athlete triad is correcting low energy avail-
the case of either primary or secondary amenorrhea, or pro- ability through increases in dietary intake and, when
longed oligomenorrhea, BMD fails to develop sufficiently needed, decreases in exercise energy expenditure.
or is lost, leading to low bone mineral density for chrono- Multidisciplinary team treatment with a physician, sports
logical age amongst adolescents and osteopenia or even dietitian, and mental health professional is warranted
osteoporosis amongst adults. Females accrue 90% of their when athletes have clinical eating disorders, and often-
peak bone mass by age 18.35 In the setting of low energy times in those with disordered eating. Written contracts
availability and hypoestrogenemia during adolescence, should be considered for any athlete whose participa-
affected females risk significant reductions in lifetime total tion is provisional, limited, or restricted. The Coalition
BMD. Efforts to restore energy availability, appropriate Consensus paper contract can be accessed at: http://
body weight, and regular monthly menstrual periods are www.femaleathletetriad.org/important-documents/.
considered the recommended course of treatment. Evaluation and management of females affected by
In 2015, the Female Athlete Triad Coalition pub- the Triad are essential for sports medicine physicians.
lished its recommendations on clearance and return to Even better is primary prevention of the Triad, as well
play for those affected by the female athlete triad.31 The as secondary prevention or screening. Sports medicine
paper defines evidence-based risk factors associated with physicians should work closely with coaches, athletic
adverse health outcomes and stratifies risk from low to trainers, athletes and parents to educate them on the
high to guide clearance and return-to-play decision-mak- importance of fueling their bodies for health and per-
ing. (Figure 27.2) formance. Likewise, all involved need to understand
The risk-stratification tool can be used at the point of that the loss of regular menstruation is not a positive
care to guide clearance and return-to-play decisions with adaptation to training and increases the risk of bone
athletes in a transparent way. Athletes with a score of stress injuries. Finally, pharmacologic intervention for
2–5 points fall into the provisional or limited clearance menstrual dysfunction and low bone mineral density
category. Athletes with provisional clearance can typi- should be guided by the Coalition Consensus document
cally participate in full training/competition based on the recommendations. 31
346 Chapter 27 Sports and Physical Activity for Women and Girls
Figure 27.2 Female Athlete Triad: Cumulative Risk Assessment, Stratification, and Return to Play Guidelines.29
27.4.2 Contraceptive Use in Active study in more than 400 elite female athletes found that 70%
had used hormonal contraception at some point, with com-
and Athletic Females bined oral contraceptives being used most often (68.1%),
The medical literature is rather scarce on the topic of con- followed by progestin-only contraceptives (13.1%) and
traceptive use in active and athletic females. However, the intrauterine devices (2.8%). The study found that users of
impact of hormonal contraceptive agents on female health hormonal contraception experienced positive side effects
and athletic performance is likely more positive than it is related to their ability to predict and/or manipulate the tim-
negative.37 The use of combined oral contraceptives pro- ing, frequency, and amount of menstrual bleeding.38 There
vides athletes with the ability to manipulate their cycle is limited evidence suggesting that women taking combined
length, thereby avoiding menstrual bleeding or premen- oral contraceptive pills experience less delayed onset muscle
strual symptoms in and around key competitions. A recent soreness following vigorous intensity exercise.39
27.4 Reproductive Health in Active and Athletic Females 347
It’s important to remember that contraceptive agents also influences the rate of breakthrough bleeding. Users
27
are not benign, nor are they foolproof. Probably the most of pills containing only 20 micrograms of ethinyl estra-
important feature of birth control is its reliability. The diol have 2.5 times higher rates of breakthrough bleed-
effectiveness of contraceptive agents should be consid- ing compared to females taking pills with greater than 20
ered when counseling and prescribing contraception to micrograms of ethinyl estradiol.44
sexually active women. At the lower end of the effective-
ness spectrum is spermicide alone (71%), fertility aware-
ness methodology (76–88%), and withdrawal (78%). 27.4.3 Exercise During Pregnancy
Condoms alone have an estimated effectiveness of 85%. and the Post-Partum
Hormonal contraception, including injectable depot
medroxyprogesterone, combined oral contraceptive pills, According to the American College of Obstetrics and
the contraceptive patch, and the Nuva Ring, ranges in Gynecology (ACOG) and the Physical Activity Guidelines
effectiveness from 91–94%. Finally, implantable contra- for Americans, healthy women having healthy uncompli-
ceptive agents, including IUDs and hormone-secreting cated pregnancies should be encouraged to participate
rods, have a greater than 99% effectiveness in preventing in regular physical activity throughout pregnancy.1,45
pregnancy.40 Pregnancy is a condition or state of being and not a dis-
The effectiveness of birth control is oftentimes depen- ease. At nearly two full-term pregnancies per woman
dent on the end user (e.g. taking pills daily as prescribed, in the United States, avoidance of exercise during preg-
placing the intravaginal ring as prescribed, receiving nancy would result in more than 20 months without
injectables on time). Contraceptive agents not taken exercise! The vast majority of women can safely partici-
or used incorrectly translate into less-effective birth pate in regular physical activity, even sport, throughout
control. Additionally, birth control not taken as pre- pregnancy; however, a minority of women do so. Only
scribed can result in untoward side effects such as break- 18.8% of women in the United States report regular
through bleeding – which when not prepared, can impact physical activity (defined as 150 minutes or more per
competition. week of moderate-to-vigorous physical activity per week
Contraceptive agents are not without potential side and muscle strength training two times per week).46 An
effects. A significant concern with hormonal birth control even smaller percentage of pregnant women meet rec-
is blood clots. Athletes traveling long distances between ommended levels of physical activity, with only 12.7%
competition, combined with dehydration and/or injury, meeting aerobic exercise guidelines as defined by 150
are at even greater risk for deep vein thrombosis (DVT). minutes of leisure-time physical activity performed over
Amongst females aged 15–44 taking combined oral con- five or more days a week.47 Yet, only 18% of pregnant
traceptive pills, the risk of DVT is 5–10 events per 100,000 women report being counseled by their obstetric care
women each year. This risk of DVT increases 3–4 times provider to exercise during their pregnancy.48 Regular
amongst users of second-generation combined oral con- physical activity during pregnancy provides many bene-
traceptive pills and upwards of 6–8 times in those taking fits to the mom and to the developing fetus. Active preg-
third-generation pills.41 nant women report fewer pregnancy-related symptoms
Another common concern with regard to contraception such as nausea, fatigue, lower back pain, and impaired
is weight gain. Combined oral contraceptive pills are con- sleep.45 Likewise, women who remain active throughout
sidered weight neutral. However, the same cannot be said pregnancy are less likely to experience excessive gesta-
for injectable depot medroxyprogesterone, where, after tional weight gain.49
three years of use, users experience an average of 11 lbs. While the majority of pregnant women can safely par-
of weight gain and an increase in body fat of 3.4%.42 ticipate in moderate, even vigorous, exercise during preg-
As previously mentioned, unexpected breakthrough nancy, it’s important to take into consideration a number
bleeding related to contraceptive use can be embarrassing of variables. Both exercise and pregnancy variables play a
to an athlete in competition, and bleeding-related symp- role in safe, enjoyable participation and include:
toms such as cramping and bloating can negatively impact
performance. Breakthrough bleeding is common when • Pregnancy/Maternal Variables
initiating hormonal contraceptive therapy, most signifi- • Pre-pregnancy health and fitness
cantly with the use of combined oral contraceptive pills • Health conditions and medications
and depot medroxyprogesterone, and typically diminishes • Absolute and relative contraindications to exer-
after 3–4 cycles. Amongst pill users, lack of adherence to cise during pregnancy
the prescribed medication is the most common cause of • Stage of pregnancy
breakthrough bleeding – specifically, skipping pills, tak- • Energy needs to support exercise and pregnancy
ing pills late, taking other medications or using herbal • Exercise Variables
supplements, and smoking tobacco. Patients with irregu- • Risk of injury
lar bleeding are 60–70% more likely than those without • Desired level of exertion
bleeding to have missed two or more pills in a pill pack.43 • Environmental conditions
While most women want the lowest amount of hormone
possible to provide adequate protection from pregnancy, Decision-making regarding exercise and sport partici-
prescribers should also be aware that the amount of hor- pation throughout pregnancy should be made jointly by
mone contained within combined oral contraceptive pills the patient and her obstetric care provider.
348 Chapter 27 Sports and Physical Activity for Women and Girls
27.4.4 Hormone Replacement Therapy for better reaction time, the latter two resulting in fewer
falls. Given that 50% of hip fractures occur in people
Pre- and Menopausal Symptoms with a prior history of hip fracture, efforts to prevent
in Active and Athletic Females the first fracture through regular physical activity across
The decision to take peri- and postmenopausal hormone the lifespan are important from both a public health and
replacement therapy (HRT) is one that should be made clinical medicine perspective.
jointly by a woman and her healthcare provider, taking
into consideration risks and benefits, and likely does not
differ between active and athletic women and women 27.5.3 The Role of Regular Physical
who are sedentary. If anything, the latter group is likely at Activity and Diabetes
greater risk of adverse consequences related to HRT given
the health protective nature of exercise.
Prevention and Management
Diabetes mellitus is the costliest medical condition in
the United States, topping more than $100 million in
27.5 THE ROLE OF PHYSICAL ACTIVITY direct healthcare costs per year.18 Ninety-five percent of
IN CHRONIC DISEASE PREVENTION those with diabetes suffer from type 2 diabetes mellitus
(T2DM). The National Diabetes Prevention Program,
AND MANAGEMENT FOR WOMEN published back in 2002, found that adults enrolled in an
intensive lifestyle intervention (including 150 minutes per
27.5.1 Physical Activity as a Strategy week of moderate intensity physical activity)54 experienced
a 58% decrease in the cumulative incidence of T2DM at
to Prevent Overweight and two years compared to a usual care control group. 55
Obesity in Women A systematic review of examining physical activity and
Forty-one percent of adult women in the United States incident type 2 diabetes mellitus found a 26% risk reduc-
are considered obese. 50 Rates of obesity amongst adult tion amongst U.S. adults achieving 150 minutes per week
women have increased from 35.4% to 41.1% between of moderate-intensity physical activity, which increased to
2007 and 2017. 50 Significant racial disparities in obesity a 36% reduction for those participating in 300 minutes of
exist. Thirty-eight percent of Non-Hispanic white are activity. 56
considered obese, compared to 54.8% of Non-Hispanic
blacks and 50.6% of Hispanics. 50 Regular physical activ-
ity is an important component of energy balance and 27.5.4 The Role of Regular Physical
weight maintenance. Women who achieve recommended Activity and High Blood Pressure
levels of physical activity are more likely to maintain body Prevention and Management
weight within normal limits.1
Nearly one in two U.S. adults (46%) have elevated blood
pressure or high blood pressure according to new blood
27.5.2 Physical Activity and Bone pressure guidelines published in November 2017. 57 The
joint statement from the American Heart Association and
Health in Women American College of Cardiology defines normal blood
Weight-bearing physical activity is an important contribu- pressure as < 120/80 mm Hg, elevated blood pressure as
tor to adequate bone mineral density (BMD). Wolff’s Law systolic blood pressure (SBP) of 120–129 mm Hg, and
states that BMD increases in response to a load. Women diastolic blood pressure (DBP) <80 mm Hg, stage 1 high
who engage in regular weight-bearing activity such as run- blood pressure as SBP of 130–139 mm Hg, and DBP of
ning, and sports such as tennis, have higher BMD than 80–89 mm Hg, and stage 2 high blood pressure (HBP)
women who are sedentary.51 Women who suffered from as SBP of at least 140 mm Hg, and DBP of at least 90
the female athlete triad in adolescence may have clinically mm Hg. 57 The guidelines stress the importance of life-
significant reductions in BMD that continue to affect them style interventions (dietary changes, physical activity, and
well into adulthood. Trabecular bone in the hip and spine weight loss) to address elevated blood pressure and pre-
are most sensitive to changes in hormonal milieu. Adding vent the development of high blood pressure. 57 Amongst
to insufficient levels of estrogen, low dietary intake of overweight and obese adults, a 5 kg or greater weight loss
calcium and vitamin D contribute to low BMD. While from baseline is associated with a 4–8 mm Hg decrease
most BMD is accrued by the late teens, BMD continues in both SBP and DBP. 58 This represents a clinically signifi-
to increase into the late 20s and early 30s, giving women cant decrease in blood pressure.
affected by the Triad a few years to gain back lost bone.35
Active women, however, are at lower risk of sus-
taining a hip fracture. 52 In a large retrospective cohort 27.5.5 The Role of Regular Physical
study in Sweden, one hour a week of walking or bicy- Activity in Breast Cancer
cling was associated with a 13% lower risk of hip
fracture compared to adults with less than one hour a
Prevention and Management
week of exercise. 53 The mechanisms for this are many Regular physical activity is associated with lower rates of
and likely include healthier BMD, better balance, and 13 cancers.59 While lung cancer has the highest death rate
References 349
due to cancer in both men and women, rates are declining 27.5.6 The Role of Regular Physical Activity
27
as rates of tobacco use decline,60 breast cancer remains
one of the most common cancers in women, affecting one
in the Prevention of Dementia
in eight women in the United States.60 Regular physical Alzheimer’s disease is the sixth leading cause of death in the
activity is associated with lower risk of developing breast United States and is more common in women than in men
cancer as well as lower mortality from breast cancer.61 (28.3 vs. 20.6 deaths per 100,000 population).63 Advancing
Ongoing research is examining the exact mechanism age is the most predictive risk factor, but our understanding
physical activity exerts on breast cancer incidence and of the contributions of lifestyle behaviors, resultant biomet-
survival.61 Cancer wellness programs promoting healthy rics, and cardiovascular fitness to the likelihood of dementia
nutrition and physical activity are commonplace and show is expanding. Several observational studies have described a
promise in improving wellbeing post breast cancer diag- direct relationship between cardiovascular fitness and risk
nosis.62 However, the percentage of women with breast of dementia. Among a cohort of mid-life women followed
cancer who are referred to cancer wellness programs is for 44 years, high cardiovascular fitness was associated
unknown. with an 88% decrease in the likelihood of dementia com-
pared to women with moderate fitness, and a mean delay in
the diagnosis of dementia by 9.5 years.64
REFERENCES
1. US Department of Health and Human 8. Centers for Disease Control and in sports and physical fitness activities
Services. 2008 Physical Activity Prevention. The Association Between during young adulthood. Youth Society
Guidelines for Americans. https: //health. School-Based Physical Activity, 2004; 35(4):495–520.
gov/paguidelines /pdf /paguide.pd f. 2008. Including Physical Education, and 14. Girls on the Run. Who We Are. https: //
Accessed April 20, 2018. Academic Performance. Atlanta, ww w.girlsontherun.org/ W ho-We -Are.
2. National Physical Activity Plan Alliance. GA: Centers for Disease Control and Accessed April 21, 2018.
The 2016 US Report Card on Physical Prevention, US Department of Health and 15. Weiss MR. Girls on the Run: A
Activity for Children And Youth. http: Human Services; 2010. Longitudinal Study of Program Impact.
//www.physicalac tivit yplan.org /repo 9. Michael SL, Merlo C, Basch C, https: //www.girlsontherun.org/assets /
rtcard /2016 FINAL _USReportCard.pdf. et al. Critical connections: health img /uploads/media/G OTR%20Long itud
Accessed April 20, 2018. and academics. J School Health inal%20Study%20Summar y%20Repor
3. Fakhouri THI, Hughes JP, Brody DJ, 2015;85(11):740–758. t.pdf. Accessed April 21, 2018.
Kit BK, Ogden CL. Physical activity and 10. Wiles NJ, Haase AM, Lawlor DA, 16. Johnstone L, Millar S. Actively engag-
screen-time viewing among elementary Ness A, Lewis G. Physical activity and ing women and girls promising practices
school–aged children in the united states depression in adolescents: cross-sectional from the canadian sport and physical
from 2009 to 2010. JAMA Pediatr findings from the ALSPAC cohort. activity system. https://www.caaws.ca/
2013;167(3):223–229. Soc Psychiatry Psychiatr Epidemiol ActivelyEngaging/documents/2013/2013_
4. Laura K, McManus T, Harris WA, et al. 2012;47(7):1023–1033. CAAWS_CS4L.pdf. Accessed April 28,
Youth risk behavior surveillance—United 11. Kwan M, Bobko S, Faulkner G, Donnelly 2018.
States, 2015. MMWR 2016;65(6):1–174. P, Cairney J. Sport participation and 17. Harkness-Tomeldan L. Physical Literacy
5. Frieden TR, Jaffe HW, Cono J, Richards alcohol and illicit drug use in adolescents for Youth: Why Is It Important? http://
CL, Iademarco IA. Youth risk behavior and young adults: a systematic review blogs.bmj.com / bjsm / 2014/03/13/physical
surveillance — United States, 2015. of longitudinal studies. Addiction 2014; -literacy-for-youth-why-is-it-i mportant/.
MMWR Surveill Summ 2016;65(6). 24(3):497–506. 2014. Accessed April 21, 2018.
6. Schneider H, Zhang N. School account- 12. Sabo DF, Miller KE, Farrell MP, Melnick 18. Dieleman JL, Baral R, Birger M, et al.
ability and youth obesity: Can Physical MJ, Barnes GM. High school athletic US Spending on Personal Health Care
education mandates make a difference? participation, sexual behavior and and Public Health, 1996-2013. JAMA
Educ Res Int 2013; 2013:1–14. adolescent pregnancy: a regional study. J 2016;316(24):2627–2646.
7. Centers for Disease Control and Prevention. Adolesc Health 1999; 25(3):207–216. 19. The Aspen Institute. Sport for all: Play for
Phyciscal Activity Facts. https://www.cdc 13. Perkins DF, Jacobs JE, Barber BL, Eccles life. A Playbook to Get Every Kid in the
.gov/healthyschools/physicalactivity/facts.ht JS. Childhood and adolescent sports par- Game. The Aspen Institute Project Play.
m. 2018. Accessed April 21, 2018. ticipation as predictors of participation 2013. https://assets.aspeninstitute.org/c
350 Chapter 27 Sports and Physical Activity for Women and Girls
ontent/uploads/2015/01/Aspen-Institute-P intervention in two exercising women 49. Samura T, Steer J, Michelis LD, Carroll
roject-Play-Report.pdf. Accessed April 21, with amenorrhea of varying duration. J L, Holland E, Perkins R. Factors
2018. Int Soc Sport Nutr. 2013;10:34. Associated With Excessive Gestational
20. Malina RM. Early sport specialization: 34. Cauley JA. Estrogen and bone health in Weight Gain: review of Current
roots, effectiveness, risks. Curr Sport men and women. Steroids 2015;99(Pt Literature. Glob Adv Health Med
Med Rep 2010;9(6):364–371. A):11–15. 2016;5(1):87–93.
21. Jenkins WL, Killian CB, Williams DS III, 35. National Institutes of Health 50. Hales CM, Carroll MD, Fryar CD, Ogden
London J, Raedeke SG. Anterior cruci- Osteoporosis and Related Bone Diseases CL. Prevalence of Obesity Among Adults
ate ligament injury in female and male National Resource Center. Osteoporosis: and Youth: United States, 2015–2016.
athletes. The relationship between foot Peak Bone Mass in Women. https: //ww NCHS Data Brief No. 288, October 2017.
structure and injury. J Am Podiatr Med w.bones.nih.gov/ healt h-info/bone/os 51. Etherington J, Harris PA, Nandra
Assoc 2007;97(5):371–376. teoporosis/ bone-mass#a. 2015. Accessed D, Hart DJ, Wolman RL, Doyle DV,
22. Griffin JR, et.al. Effects of increasing tib- April 21, 2018. Spector. TD. The effect of weight‐bearing
ial slope on the biomechanics of the knee. 36. Tenforde AS, Carlson JL, Change A, exercise on bone mineral density: A
Am J Sports Med 2004;32:376–382. Sainani KL, Shultz R, Kim JH, Cutti P, study of female ex‐elite athletes and the
23. Cameron KL. Commentary: time for a Golden NH, Fredericson M. Association general population. J Bone Miner Res
paradigm shift in conceptualizing risk of the female athlete triad risk assessment 1996;11(9):1333–1338.
factors in sports injury research. J Athl stratification to the development of bone 52. Trolle Lagerros Y, Hantikainen E,
Train 2010;45(1):58–60. stress injuries in collegiate athletes. Am J Michaëlsson K, Ye W, Adami HO,
24. Donnell-Fink LA, Klara K, Collins Sports Med 2017;45(2):302–210. Bellocco R. Physical activity and the risk
JE, Yang HY, Goczalk MG, Katz JN, 37. Frankovich RJ, Lebrun CM. Menstrual of hip fracture in the elderly: a prospec-
et al. Effectiveness of knee injury and cycle, contraception, and performance. tive cohort study. Eur J Epidemiol
anterior cruciate ligament tear preven- Clin Sports Med 2000;19(2):251–271. 2017;32(11):983–991.
tion programs: a meta-analysis. PLoS 38. Martin D, Sale C, Cooper SB, Elliott-Sale 53. Stattin K, Michaëlsson K, Larsson SC,
ONE2015;10(12):1–17. KJ. Period prevalence and perceived side Wolk A, Byberg L. Leisure-time physical
25. American Psychiatric Association. (2013). effects of hormonal contraceptive use and activity and risk of fracture: a Cohort
Diagnostic and Statistical Manual of the menstrual cycle in elite athletes. Int J Study of 66,940 Men and Women. J Bone
Mental Disorders (5th ed.). Arlington, Sports Physiol Perform 2017 28:1–22. Miner Res 2017;32(8):1599–1606.
VA: American Psychiatric Publishing. 39. Thompson HS, Hyatt JP, De Souza MJ, 54. The Diabetes Prevention Program
26. Otis CL, Drinkwater B, Johnson M, Clarkson PM. The effects of oral contra- (DPP) Research Group. The Diabetes
Loucks A, Wilmore J. American College ceptives on delayed onset muscle soreness Prevention Program (DPP): Description
of Sports Medicine position stand. The following exercise. Contraception of lifestyle intervention. Diabetes Care
Female Athlete Triad. Med Sci Sports 1997;56(2):59–65. 2002;25(12):2165–2171.
Exerc 1997;29(5):i–ix. 40. Planned Parenthood: All About Birth 55. Diabetes Prevention Program Research
27. Nattiv A, Loucks AB, Manore MM, Control. https: //www.plan nedpa rent Group. Reduction in the Incidence
Sanborn CF, Sundgot-Borgen J, Warren hood.org/learn/birth- control. 2018. of Type 2 Diabetes with Lifestyle
MP; American College of Sports Accessed April 21, 2018. Intervention or Metformin. N Engl J Med
Medicine. American College of Sports 41. Piparva KG, Buch JG. Deep vein throm- 2002;346:393–403.
Medicine position stand. The female bosis in a woman taking oral com- 56. Smith AD, Crippa A, Woodcock J, Brage
athlete triad. Med Sci Sports Exerc bined contraceptive pills. J Pharmacol S. Physical activity and incident type 2
2007;39(10):1867–1882. Pharmacother 2011;2(3):185–186. diabetes mellitus: a systematic review
28. Loucks A. Energy availability, not body 42. Albright M, Rani S, Gavagan T. and dose-response meta-analysis of
fatness, regulates reproductive function HelpDesk answers: do hormonal contra- prospective cohort studies. Diabetologia
in women. Exerc Sport Sci Rev 2003; ceptives lead to weight gain? J Fam Pract 2016;59(12):2527–2545.
31(3):144–148. 2015;64(6):371–372. 57. Whelton PK, Carey RM, Aronow WS,
29. Ainsworth BE, Haskell WL, Herrmann SD, 43. Lohr PA, Creinin MD. Oral contracep- Casey DE Jr, Collins KJ, Dennison
Meckes N, Bassett Jr DR, Tudor-Locke tives and breakthrough bleeding: what Himmelfarb C, DePalma SM, Gidding S,
C, Greer JL, Vezina J, Whitt-Glover MC, patients need to know. J Fam Pract 2006; Jamerson KA, Jones DW, MacLaughlin
Leon AS. The Compendium of Physical 55(10):872–880. EJ, Muntner P, Ovbiagele B, Smith SC Jr,
Activities Tracking Guide. https://sites.g 44. Gallo MF, Nanda K, Grimes DA, Lopez Spencer CC, Stafford RS, Taler SJ, Thomas
oogle.com/site/compendiumofphysicalactiv LM, Schulz KF. 20 µg versus >20 µg RJ, Williams KA Sr, Williamson JD, Wright
ities/. Accessed April 21, 2018. estrogen combined oral contraceptives for JT Jr. 2017. ACC/AHA/AAPA/ABC/ACP
30. Loucks AB, Thuma JR. Luteinizing hor- contraception. Cochrane Database Syst M/AGS/APhA/ASH/ASPC/NMA/PCNA
mone pulsatility is disrupted at a thresh- Rev 2013 Aug 1;(8):CD003989. Guideline for the Prevention, Detection,
old of energy availability in regularly 45. Physical activity and exercise dur- Evaluation, and Management of High
menstruating women. J Clin Endocrinol ing pregnancy and the postpartum Blood Pressure in Adults: A Report of the
Metab 2003; 88: 297–311. period. Committee Opinion No. American College of Cardiology/American
31. De Souza MJ, Nattiv A, Joy E, Misra M, 650American College of Obstetricians Heart Association Task Force on Clinical
Williams NI, Mallinson RJ, Gibbs JC, and Gynecologists. Obstet Gynecol Practice Guidelines. J Am Coll Cardiol.
Olmsted M, Goolsby M, Matheson G, 2015;126:e135–42. 2018;71(19):e127–e248.
and Expert Panel. 2014 female athlete 46. Centers for Disease Control and 58. Neter JE, Stam BE, Kok FJ, Grobbee
triad coalition consensus statement on Prevention National Center for Health DE, Geleijnse JM. Influence of weight
treatment and return to play of the female Statistics. Exercise or Physical Activity. reduction on blood pressure: a meta-
athlete triad: 1 st international conference Adult Health Behavior Tables National analysis of randomized controlled trials.
held in San Francisco, California, May Health Interview Survey 2011-2014. Hypertension 2003;42:878–884.
2012 and 2nd international conference Table A-14. https: //www.cdc.gov/nchs/ 59. Moore, SC et al. Association of leisure-
held in Indianapolis, Indiana, May 2013. nhis/SHS/tables.htm. Accessed April 21, time physical activity with risk of 26
Br J Sports Med 2014;48(4): 289–309. 2018. types of cancer in 1.44 million adults.
32. Kopp-Woodroffe, SA, Manore MM, 47. Hesketh KR, Evenson KR. Prevalence JAMA Int Med, 2016;176(6): 816–825.
Dueck CA, Skinner JS, Matt, KS. Energy of U.S. Pregnant Women Meeting 2015 60. National Institutes of Health, National
and nutrient status of amenorrheic ath- ACOG Physical Activity Guidelines. Am J Cancer Institute. Annual Report to the
letes participating in a diet and exercise Prev Med 2016;51(3):e87–e89. Nation 2017: Mortality Summary. https
training intervention program. Int J Sport 48. Yamamoto A, McCormick MC, Burris ://seer.cancer.gov/report _ to_nation /mort
Nutr 1999:9:70–88. HH. US provider-reported diet and ality.htmlAccessed April 21, 2018.
33. Mallinson RJ, Williams, NI, Olmsted physical activity counseling to pregnant 61. Picon‐Ruiz M, Morata‐Tarifa C,
MP, Scheid JL, Riddle ES, De Souza, and non-pregnant women of childbearing Valle‐Goffin JJ, Friedman ER, Slingerland
MJ. A case report of recovery of men- age during preventive care visits. Matern JM. Obesity and adverse breast cancer risk
strual function following a nutritional Child Health J 2014;18(7):1610–1618. and outcome: mechanistic insights and
References 351
strategies for intervention. CA Cancer J complementary medicine. J Cancer Educ. 64. Hörder H, Johansson L, Guo X,
Clin 2017; 67(5): 378–397. 2016;31(1):47–54. Grimby G, Kern S, Östling S, Skoog
62. Stoutenberg M, Sogor A, Arheart K,
Cutrono SE, Kornfeld J. A wellness
program for cancer survivors and care-
63. Taylor CA, Greenlund SF, McGuire LC,
Lu H, Croft JB. Deaths from Alzheimer’s
Disease — United States, 1999–2014.
I. Midlife cardiovascular fitness and
dementia: a 44-year longitudinal
population study in women. Neurology.
27
givers: developing an integrative pilot MMWR Morb Mortal Wkly Rep 2018;90(15):e1298–e1305.
program with exercise, nutrition, and 2017;66:521–526.
VI
PA RT
353
28
CHAPTER
355
356 Chapter 28 Impact of Lifestyle Medicine on Dysglycemia-Based Chronic Disease
pathways that, when subverted, can lead to chronic dis- Smaller dietary polysaccharides and disaccharides,
28
ease. Allostasis (“stability through change”) is the physi- such as maltose, lactose (common in dairy products), and
ological process that adjusts homeostatic (“resistance to sucrose, are hydrolyzed to glucose and other monosaccha-
change”) set points to achieve successful adaptation. rides during digestion and metabolism. With the excep-
In fasting states, normal glycemic levels are maintained tion of fructose, dietary-derived monosaccharides are
by both hepatic gluconeogenesis and glycogenolysis, gov- converted to glucose for further metabolism.
erned by glucagon release and low circulating insulin Through digestion, both starch and simple sugar inges-
levels.16 During physical activity, these processes and tion produce glucose, which functions as a highly ener-
myocyte glycogen hydrolysis maintain energy utilization getic water-soluble monosaccharide. 20 Glucose is easily
and euglycemia. Lipid metabolism is also activated as an transported through blood and transits across cell mem-
energy source within periods of fasting or physical activ- branes through transmembrane channels, many of which
ity. During meal consumption, glucagon is suppressed, are highly regulated. Intracellular glucose enters one of
and insulin release is stimulated by glucose-sensing chan- several metabolic pathways such as glycolysis, the com-
nels on pancreatic β-cells, nerve stimulation of pancreatic mon pathway for energy derivation from dietary starches
β-cells, and incretin hormones (e.g., GLP1) stimulation of and sugars.
pancreatic β-cells.16 The total amount of carbohydrate consumed during a
With dysglycemia and insulin resistance, many of the meal may be considered the glycemic load. 21 In individuals
aspects of glucose metabolism are subverted, resulting in with insulin resistance, the consumption of high glycemic
elevated fasting insulin levels, elevated glucagon activ- load meals produces hyperglycemia, increased oxidative
ity, elevated prandial hepatic glucose production, and free radicals, and increased production of advanced gly-
pancreatic β-cell dysfunction.17 Early on in insulin resis- cosylated end products. Reduction of carbohydrate intake
tance, β-cells dysfunction may be demonstrated as loss represents the cornerstone of dietary intervention that
of early-phase insulin release with delayed and, in some mitigates the detrimental effects of DBCD.
cases, exaggerated late-phase insulin release. There is also The glycemic index is another important concept
a reduction in the number of β-cells through apoptosis or regarding dietary carbohydrate intake. Defined by both
transformation to inactive cells. The goal of preservation the rate and severity of the positive glycemic excursion
and possibly restoration of normal β-cell function along following consumption, the glycemic index of each food
the DBCD spectrum can potentially prevent the conver- depends on the rate of digestion and intestinal absorption
sion of prediabetes to T2D as well as dampen the evolu- to produce readily available glucose. High glycemic index
tion of cardiometabolic risks, frank atherosclerosis, and foods, such as white bread and sugar-containing bever-
cardiovascular disease. ages, rapidly raise blood glucose levels, placing undue
burden on glucose regulatory systems. In DBCD, foods
with relatively high glycemic indices should be curtailed
28.2.2 Dietary Carbohydrates – or avoided altogether. 21
Starch, Fiber, and Sugar
Starches and simple sugars constitute the bulk of dietary
carbohydrate in the majority of eating patterns. Starch
28.2.3 Fructose
molecules are large multimers of glucose that are hydro- Fructose exists within food as monosaccharides, (e.g.,
lyzed during digestion for absorption, distribution, and high-fructose corn syrup [HFCS]), products of hydrolyzed
utilization. As a result, only glucose is produced dur- sucrose, or less commonly, fructose multimers that are
ing starch hydrolysis. In contrast, hydrolysis of sucrose, hydrolyzed during digestion (e.g., agave nectar). Other
or cane sugar, yields 50% glucose and 50% fructose by “natural” sweeteners such as honey or maple syrup also
weight. The relatively small amount of glycogen that is contain relatively large amounts of fructose. Fructose is
present in meat is also hydrolyzed to glucose, though this also present within fruits, though generally at low quanti-
represents only a minor portion of dietary glucose. ties having near negligible metabolic effects. In contrast,
Fiber, which exists as modified polysaccharide mole- the high fructose content of industrially produced natural
cules, represents a class of dietary carbohydrates that can- sweeteners (e.g., HFCS, sucrose, and agave nectar), as well
not be easily hydrolyzed. Fiber molecules remain within as locally produced honey and maple syrup, can confer
the gastrointestinal lumen during digestive processes and relatively greater detriment.
function as a fuel source for entercolonic microflora as well Fructose enters carbohydrate metabolism downstream
as providing stool bulk.18 Short-chain fatty acids produced of the major regulatory step of glycolysis, bypassing a
by the entercolonic microflora may be absorbed and serve highly important point of hormonal- and substrate-level
as an energy source providing 5–10% of daily calories. control. Moreover, cellular uptake of fructose is not under
Dietary fiber also inhibits intestinal α-glucosidase activity, hormonal regulation and does not induce or respond to
which delays starch hydrolysis. This reduces the rate of insulin activity. 20 Nearly all ingested fructose is taken
glucose absorption during a meal, which benefits patients up by hepatocytes. 22 Metabolism of fructose increases
with insulin resistance syndromes. One example of this hepatic fatty acid synthesis, and either release of free fatty
phenomenon is observed when beans, which are high in acids into circulation or hepatic triglyceride storage, even-
fiber, are combined with rice, which is high in starch, pre- tually leading to hepatosteatosis. 22
venting the significant postprandial glycemic excursion Given these mechanisms, excessive dietary fructose
that occurs when rice is consumed alone.19 intake is associated with insulin resistance, obesity and
358 Chapter 28 Impact of Lifestyle Medicine on Dysglycemia-Based Chronic Disease
accumulation of visceral fat, cardiovascular disease, renal reduction, and atherosclerotic cardiovascular disease risk
disease, and neuropathy. 20 While some authors argue that reduction.34,35 Low carbohydrate or Ornish diets also
the immediate response to fructose consumption does not improve circulating cholesterol levels, though to a some-
further compromise impaired insulin-glucose regulation what lesser extent. 34,36 A low-fat diet has been classically
in DBCD, 23 the long-term effects of high fructose intake promoted to reduce circulating cholesterol, but in direct
pose a significant hazard. 20 Results of an ongoing ran- comparison trials, Mediterranean or low carbohydrate
domized trial will help to resolve this controversy. 24 dietary patterns demonstrate greater improvements.34
Strategies to minimize dietary fructose intake are
strongly recommended in DBCD. 25 This may be achieved
through the avoidance of industrially processed foods 28.2.5 Omega-3 Fatty Acids
and sweetened beverages. Honey and maple syrup should
be used judiciously. Foods that contain large amounts of Polyunsaturated fatty acids (PUFA) are classified based
sucrose should be used sparingly, including baked goods on the position of carbon-carbon double bonds, which
and desserts. Fast foods (and certain restaurant foods) dictates physical and chemical properties. Though other
often contain covert and high levels of added sucrose and dietary factors contribute, including low fiber, high refined
should really be scrutinized and then avoided. 26 In con- carbohydrate, and high fructose content, a relatively low
trast, fresh fruit consumption should not be limited: mul- n-3 PUFA intake is a hallmark of the Western diet, and
tiple studies demonstrate metabolic benefits of fruit in the is strongly associated with the incidence of dysglycemia
general population as well as in insulin resistance. High syndromes. Moreover, the inflammatory nature of the
amounts of fresh fruit consumption are associated with modern Western diet is partially attributable to the high
reduced incidence of T2D27 as well as reduced rates of car- content of n-6 PUFAs and low amounts of n-3 PUFAs.
diovascular disease and mortality. 28 The minimal content Of note, ancestral human dietary patterns contain a ratio
of fructose within fruit is overcome by health benefits con- of n-6:n-3 PUFA content of approximately 1:1, which is
ferred by multiple components of fruits, including fiber, contrasted with modern Western diets in which the ratio
antioxidants, polyphenols, and vitamins. is approximately 16–20:1.37
Dietary patterns that decrease the risk of dysglycemia
contain abundant amounts of n-3 PUFAs. These dietary
28.2.4 Lipid Metabolism patterns are generally high in fish, vegetables, fruits, and
nuts, and are associated with reduced insulin resistance,
Lipid metabolism is also highly affected in DBCD. risk of T2D, and risk of cardiovascular events.38
Increased circulating free fatty acids that result from insu- In contrast to dietary modification, consumption of
lin resistance contribute to pancreatic β-cell dysfunction, dietary supplements or nutraceuticals that contain n-3
reduced hepatic sensitivity to insulin, macrophage activa- PUFAs does not appear to affect most aspects of insulin
tion, and low-grade systemic inflammation. Additionally, resistance. In the largest published placebo-controlled
adipose tissue, which becomes highly resistant to insu- randomized trial, 12,536 subjects with either impaired
lin, is redistributed with increased visceral and relatively fasting glucose, impaired glucose tolerance, or T2D were
decreased subcutaneous adipose tissue. These abnormali- randomized to receive either 1000 mg of n-3 PUFAs ver-
ties in adiposity and adipocyte function affect adipokine sus olive oil daily.39 After six years of follow-up, no dif-
production and can generate a state of low adiponectin, ferences were observed in blood glucose levels, blood
high resistin, and high chemerin that further drives insulin pressure, cardiovascular events, or mortality rates. The
resistance. 29 The triad of abnormal adipose tissue mass, only observed improvement with n-3 PUFA supplemen-
distribution, and function contributing to metabolic risk tation was a modest reduction in serum triglyceride lev-
is termed adiposity based chronic disease and represents els by 14.5 mg/dl among the group receiving n-3 PUFAs.
an expanded view and working model of obesity, while Similarly, a recently published meta-analysis demonstrates
also highlighting interactions with dysglycemia based no effect of n-3 PUFA supplementation on insulin resis-
chronic disease.30 tance or on circulating androgen levels in women with
Insulin signaling also directly stimulates lipoprotein PCOS.40 However, studies of n-3 PUFA supplementation
lipase activity and gene expression. Reduced lipoprotein in patients with hepatosteatosis demonstrate reduction in
lipase activity leads to a reduced clearance rate of circulat- markers of hepatocyte injury and reduced fibrosis scores.41
ing triglycerides. 31 The state of elevated triglycerides, low These results suggest that supplementation with n-3
HDL, and small, dense LDL particles is commonly seen in PUFAs is insufficient to alter the course of DBCD, though
DBCD, especially in MetS where the hypertriglyceridemia potential benefits for the treatment of hypertriglyceri-
and low HDL are diagnostic criteria.32 demia, and possibly hepatosteatosis, may be considered
Dysfunctional lipid metabolism that is observed in when appropriate.
DBCD and insulin resistance is highly atherogenic and
inflammatory. Cardiovascular events and stroke are
reported at twice the rate of the general population.33
When considering risk stratification, T2D is equivalent to
28.2.6 Antioxidants
previous myocardial infarction or known coronary artery Dysglycemia yields a two- to fourfold increase in produc-
disease. tion of reactive oxygen species.42 Despite no differences
Lifestyle interventions such as the Mediterranean in dietary intake, circulating levels of antioxidant vita-
diet have the greatest impact on lipid metabolism, LDL mins are 30–50% lower in syndromes of dysglycemia
28.2 Metabolic Components of Dysglycemia 359
compared to the general population, suggesting increased systemic effects in DBCD. Whether these effects can be
28
utilization.43 Under this pretext, some authors argue that achieved through dietary modification alone or through
supplementation with antioxidant substances such as vita- dietary supplementation requires further study.
mins A, C, E, selenium, ubiquinone, and α-lipoic acid may
be beneficial.44
A number of studies support this assertion. In one
randomized trial of well-controlled patients with T2D,
28.2.7 Plant Polyphenols
supplementation with 1000 mg vitamin C daily for one Dietary patterns that successfully target and manage dys-
year improved insulin sensitivity by 21%, compared to pla- glycemia and insulin resistance are plant-based (i.e., pri-
cebo.45 In a population study, subjects in the highest tertile marily composed of fruits, vegetables, spices, and herbs,
of vitamin C intake demonstrated a 24% lower incidence but may also contain in smaller quantities foods derived
of T2D over four years.46 A randomized trial investigat- from animals based on individual preference). In addition
ing supplementation of vitamin E in T2D, given at 400 to macronutrients, vitamins, and minerals, plants produce
mg α-tocopherol daily for three months, demonstrated a a wide array of chemical compounds, known as poly-
reduction in fasting blood glucose by 11 mg/dl compared phenols, that function to protect the plant against envi-
to controls.47 In a 96-week randomized trial, vitamin E ronmental threats, such as ultraviolet damage from sun
supplementation has been shown to improve histologic exposure or infection. Generally speaking, many polyphe-
markers of steatohepatitis at twice the rate of controls.48 nols have antioxidant properties.
Several small trials investigating the use of selenium Each plant species produces a unique set of polyphe-
in states of insulin resistance have been published. In one nols, with overlap among closely related species. These
randomized study, subjects with obesity supplemented compounds contribute substantially to the flavor of each
with 200 mcg selenium daily resulted in a 10% reduc- food, as well as to satiety generated by food consump-
tion in fasting insulin levels.49 In another study, subjects tion. 53 Over 18,000 such compounds have been described
with gestational diabetes randomized to receive selenium and divided into classes based on molecular structure.
supplements showed reductions in fasting plasma glucose The role of dietary plant polyphenols in health and dis-
by 10 mg/dl, and fasting plasma insulin by 1.98 μIU/ml. 50 ease is a subject of controversy. These substances exhibit
Supplementing α-lipoic acid, known as “the univer- diverse biochemical properties, some of which may be ben-
sal antioxidant” for its ability to regenerate vitamin C, eficial in insulin resistance. A large number of polyphenols
vitamin E, and glutathione, can also improve dysglycemia exhibit biologic activity when ingested (e.g., coumarin
markers. One randomized trial of α-lipoic acid demon- and caffeine). A subset of plant polyphenols demonstrates
strated a significant reduction in fasting and postprandial activity in glucose allostasis (Table 28.2).
hyperglycemia and in insulin resistance among patients The high polyphenol content of the Mediterranean
with T2D. 51 In another study, a three-month randomized diets may be responsible for the majority of health ben-
trial investigating the use of a daily supplement containing efits observed.54 A review of data from the National
α-lipoic acid 600 mg, zinc, and B vitamins, demonstrated Health and Nutrition Examination Survey (NHANES)
reductions in hyperglycemia, insulin resistance, serum tri- from 2003 to 2006 demonstrates high dietary polyphe-
glycerides, serum cholesterol, and markers of inflamma- nol content associated with improved glycemic control
tion in patients with T2D. 52 and reduced prevalence of diabetic retinopathy among
Taken together, these results are suggestive of the individuals with T2D. 55 An analysis of the Nurses Health
important role of antioxidants in diminishing some of the Study demonstrates that low polyphenol intake, measured
* See reference.109
360 Chapter 28 Impact of Lifestyle Medicine on Dysglycemia-Based Chronic Disease
by urinary isoflavone levels, is associated with increased host of AGE compounds, each with a potential to interfere
risk of T2D. 56 with normal physiology and biochemistry.
Perhaps the plant polyphenol that has generated the The process of cooking uses heat to drive the Maillard
most scientific interest of late in glucose metabolism is res- reaction and many of the same subsequent reactions,
veratrol, which occurs naturally in grapes, grapeseed oil, yielding AGE compounds within foods that are ingested.71
and red wine. In animal models of dysglycemia, adminis- The method of cooking has a significant impact on the
tration of resveratrol results in weight loss and improved amount of AGE that are formed: grilling, sautéing, and
glucose, insulin, and lipid metabolic profiles. 57 However, baking yield high amounts of AGE; boiling or steaming
in human trials, resveratrol supplementation demonstrates produce very little AGE. Additionally, cooking foods in
mixed results. In one randomized study of 45 patients an acid environment, such as with vinegar or lemon juice,
with PCOS, resveratrol given at 1500 mg daily for three reduces AGE formation.
months significantly reduced circulating androgens by In patients with T2D, and to a lesser extent, in those
approximately 25% and improved insulin sensitivity by with insulin resistance, higher circulating levels of AGE
65%, though no weight loss was observed.58 In another are observed.72 This is partly due to elevated plasma glu-
randomized study of 66 men with MetS, supplementa- cose levels that are more readily available for participa-
tion with resveratrol 1000 mg daily for 16 weeks failed tion in the Maillard reaction. Reduced clearance of AGE
to demonstrate benefit of insulin sensitivity measures, is also observed in insulin resistance.
body composition, blood pressure, or triglyceride levels. 59 When considering the pathogenesis of complications
A systematic review of published trials in humans also of insulin resistance, accumulation of AGE in tissues is
failed to demonstrate consistent metabolic improvements a leading hypothesis. Microvascular disease associated
with resveratrol supplementation in patients with MetS.60 with T2D may directly result from AGE formation and
Other short trials in subjects with T2D failed to show an deposition.73
effect of resveratrol on insulin resistance.61,62 Current published guidelines do not address the prob-
Several other plant polyphenols exhibit activities that lem of dietary AGE ingestion. However, several small
would benefit syndromes of dysglycemia. Anthocyanins, studies demonstrate improvements in dysglycemia with
which are abundant in bilberry extract, and other fla- reduced AGE intake. In one trial, healthy adults given an
vonoids, such as naringin and hesperidin, found in cit- isocaloric, macronutrient-matched diet high in AGE con-
rus fruits, demonstrate reduction in blood glucose levels tent for two weeks demonstrated reduced insulin sensitiv-
in mouse models of T2D.63–65 Quercetin, which is pres- ity by approximately 30% when compared to the same
ent in onions, fennel, cilantro, capers, and dill, has been group given a low-AGE diet.74 In another trial, insulin
shown to reduce fasting glucose levels in animal mod- resistance declined by 12% in obese women while con-
els of diabetes, potentially through inhibition intesti- suming a low-AGE diet.75 A trial that investigated the use
nal α-glucosidase.66,67 Epigallocatechin gallate, found in of oral resins to bind prandial AGE in patients with T2D
grapes, tea, and legumes, demonstrates improved insulin demonstrated a modest reduction in blood glucose levels.76
secretion and mitochondrial activity in cell culture studies These results suggest that the use of cooking meth-
and improved glucose tolerance in animal models.68,69 ods such as steaming or boiling to minimize dietary AGE
These findings from cell culture, animal model, and intake may be beneficial in dysglycemia. However, it
epidemiologic studies suggest metabolic benefit for these remains unclear how these findings may be incorporated
few important polyphenol compounds. Further study is into everyday practice, especially when following specific
likely to identify other individual polyphenols that exhibit dietary patterns that clearly demonstrate improvement in
specific insulin-sensitizing activities. However, rather dysglycemia while employing high-AGE cooking methods.
than a single mechanism from a specific polyphenol com-
pound, the combined and concerted mechanisms of multi-
ple dietary polyphenols present naturally within a cuisine 28.2.9 Systemic Inflammation
may provide the greatest metabolic benefit.70 As with the
case of n-3 PUFAs, rather than supplementation, dietary The presence of low-grade systemic inflammation is asso-
patterns that are high in fruits, vegetables, spices, and ciated with dysglycemia and insulin resistance syndromes.
herbs, and thus high in polyphenols, may be among the Perhaps the most striking difference among patients with
best options for the treatment and prevention of specific obesity and T2D compared to patients with obesity but
DBCD stages. without insulin resistance is the presence of inflammation
in the former group, as demonstrated by elevated levels
of circulating cytokines, complement, C-reactive protein,
pro-inflammatory prostaglandins and leukotrienes, and
28.2.8 Advanced Glycated End Products activated macrophages.77 Multiple mechanisms of insulin
The spontaneous biochemical reactions of sugars and resistance lead to inflammation, including increased circu-
proteins that occur within living systems yield a series of lating free fatty acids, increased reactive oxygen species,
compounds that are referred to as advanced glycated end and endothelial dysfunction.3 For the treatment of insu-
products (AGE). The first step in this set of non-enzymatic lin resistance, the administration of anti-inflammatory
processes is the Maillard reaction, in which a nucleophilic agents such as salicylic acid demonstrates reduction in
rearrangement induced by amine groups of proteins forms hyperglycemia and in markers of systemic inflammation.78
covalent bonds with sugar moieties. After several steps, Nevertheless, the precise causes, direct and indirect, of
Midori bases are generated. These react further, yielding a inflammation in DBCD remain unclear. Hence, specific
28.3 Dietary Patterns 361
anti-inflammatory dietary and lifestyle recommendations substituted for sugar in common food items. These sub-
28
that are beyond current health promotion guidelines are stances are also considered as EDC: the stimulatory effect
lacking. on taste receptors that are located within the gastrointesti-
nal tract may induce excessive insulin release, causing the
individual to consume more food to prevent hypoglyce-
28.2.10 Endocrine Disruptors mia.84 It remains unclear how much of this effect contrib-
utes to weight gain and dysglycemia.
A subset of industrially produced chemicals, known as A second mechanism by which artificial sweeteners
endocrine disrupting compounds (EDC), exhibits proper- disrupt energy metabolism is through alteration of gastro-
ties of normal hormone signal interruption and can con- intestinal microflora. With the exception of Stevia rebau-
tribute to insulin resistant states. EDC can either act as diana extracts, the consumption of artificial sweeteners
hormones themselves, complete with hormones at receptor has been shown to affect microflora species diversity and
sites or within carrier proteins, or affect hormone synthe- gene expression in both humans and animal models.82 In
sis or metabolism. Any of these actions can greatly affect short, artificial sweeteners should be avoided or at least
the host. Several classes of EDC that may affect glucose minimized in patients with DBCD.
metabolism and insulin resistance have been identified
through animal or population studies (Table 28.3).79–82
These include insecticides, plasticizers, and preservatives.
Proper study and risk assessment of EDC is a for-
28.3 DIETARY PATTERNS
midable task: the enormous array and widespread use A conscious effort to adopt a dietary pattern that is both
of industrial chemicals, as well as the continuous intro- metabolically beneficial and sustainable is central to the
duction of novel industrial compounds, may be insur- concept of intensive lifestyle intervention. Rather than fol-
mountable barriers to a complete understanding of EDC lowing a “diet” that restricts or limits certain foods, or
pathophysiology. Limitations by study design also restrict regarding individual foods as “good” or “bad,” embrac-
definitive conclusions in most cases. A prudent and practi- ing an aggregate pattern of food intake that emphasizes
cal approach may be to limit exposure to EDC wherever healthy choices can lead to improved outcomes. While one
possible. Given the ubiquitous use of plastics and other of several dietary patterns may fit these criteria, the most
industrial chemicals, this task may be quite difficult. EDC suitable is the dietary pattern that generates the greatest
are widely distributed and have been detected in remote adherence for an individual patient.85
areas.83
Although studies to evaluate the efficacy of any recom-
mendation to reduce EDC exposure have not been con- 28.3.1 Mediterranean Diets
ducted, a series of pragmatic measures may be considered
to achieve this goal. These may include washing of fruits Mediterranean diets are defined by the culinary traditions
and vegetables thoroughly before cooking or ingestion, that have developed around the Mediterranean basin and
washing hands, choosing produce grown with minimal have long been recognized and promoted as a health-con-
pesticide/synthetic fertilizer utilization, choosing wild scious lifestyle.86 Components of these dietary patterns,
fish, free-range meats and poultry, use of glass containers which vary a little among the various Mediterranean
and cookware that does not release potential EDC, and regions, include a large amount of vegetables (at least three
avoiding food consumption when using industrial chemi- to four servings per day), fruits (at least three to four serv-
cals (e.g., when using paint). ings per day), nuts, olive oil, lean meats and fish, cheese,
wine (about one to two glasses per day) and whole grains.
Carbohydrates account for approximately 30–40% of the
calories. In direct comparison trials with over six years
28.2.11 Artificial Sweeteners of follow-up, Mediterranean diets demonstrated signifi-
A number of compounds have been utilized as artifi- cant amounts of sustained weight loss and reductions
cial sweeteners for their ability to stimulate sweet taste in fasting glucose, fasting insulin, LDL cholesterol, and
receptors while providing little to no calorie content and triglycerides. 34,87
In addition to these metabolic improvements, individu- longer-term follow-up is needed before these results can
als who follow Mediterranean diets demonstrate a 30% be recommended. Moreover, the increased carbohydrate
reduction in cardiovascular events and mortality over six load of the OD may make this dietary pattern less effec-
years compared to those who follow traditional low-fat tive than Mediterranean diets or the NND in DBCD.96
diets. 35 With regard to insulin resistance, the incidence of
T2D was reduced by 30% among those who were assigned
a Mediterranean diet, and among patients already diag- 28.4 PHYSICAL ACTIVITY
nosed with T2D, a 40% reduction in diabetic retinopathy
was noted in the Mediterranean diet group. 54,88 For nearly all of human history, Homo sapiens have
Though controversial as a recommendation, wine is survived as a network of hunter-gatherer tribes.
an important component of Mediterranean diets. A two- Notwithstanding genotypic changes that have occurred
year randomized trial in which 224 subjects with T2D since the first agricultural revolution approximately over
who were already following the Mediterranean diet were 10,000 years ago, the forces of natural selection that
provided either 150 ml of red wine, white wine, or water optimized human metabolism for the needs of a hunter-
daily and asked to abstain from other alcohol; there was a gatherer lifestyle persist today. Studies of modern-day
reduction in fasting insulin among those assigned to either hunter-gatherers demonstrate levels of physical activ-
the red or white wine consumption.89 A recent evaluation ity and fitness generally not achievable in contemporary
of the Danish Health Examination Survey that included a cultures.
population of 76,454 individuals demonstrated the low- Regular physical activity, strength training, and car-
est incidence of T2D among those with moderate alco- diovascular fitness exert a multitude of metabolic effects
hol intake that was mostly wine (i.e., 14 drinks per week extending well beyond physique and cosmetic good looks.
for men, 9 drinks per week for women).90 These results These include methylation and activation of genes that
are consistent with many other trials that associate insu- affect metabolic function within adipose and muscle tis-
lin resistance and reduced markers of inflammation with sues,97 release of irisin by skeletal muscle, a hormone that
moderate consumption of alcohol, mainly wine.91 induces formation of brown adipose tissue and inhibits
hepatic gluconeogenesis,98 and a controlled shift of calorie
utilization to pathways involved in metabolic health.99
28.3.2 The New Nordic Diet In general, the direct calorie consumption by exercise
is modest at best. Among those with overweight or obe-
The New Nordic Diet (NND), based on local Scandinavian
sity, exercise alone does not yield weight loss.100 However,
cuisine and tradition, also promotes healthy food choices.
regular exercise maintains and increases physiological
The NND is comprised of fruits (especially berries), veg-
function of muscle and lean body tissues, and reduces
etables (including cabbage, root vegetables, and legumes),
insulin resistance.101
fresh herbs, wild mushrooms, nuts, fish, seaweed, and
The question of how much physical activity is neces-
meats.92 A randomized trial evaluating consumption
sary can be answered simply by “as much as possible.”
of the NND compared to a typical Western diet for six
Within the Finnish Diabetes Prevention Study, overweight
months among subjects with obesity demonstrated reduc-
adults with impaired glucose tolerance were randomized
tions in weight by 2 kg, fasting plasma insulin by three
to an intensive lifestyle that included supervised exer-
μU/L, fasting plasma glucose by five mg/dl, and fasting
cise training sessions and encouraged regular endurance
triglyceride levels by 18 mg/dl.93
exercise such as jogging, swimming, ball games or ski-
ing, as well as dietary changes.102 The incidence of T2D
was reduced by 63%. Similar findings were noted in the
28.3.3 The Ornish Diet Diabetes Prevention Program trial, in which individuals at
The central principle of the Ornish diet (OD) is a signifi- risk for the development of T2D were able to significantly
cant reduction, or elimination of, ingested animal fat and prevent this metabolic fate in part by exercising during
products derived from animal fat. To achieve this, the OD five sessions per week, with approximately 30 minutes of
necessarily includes increased carbohydrates in the form cardiovascular exercise per session.103
of whole grains. Components of the OD include fruits, Current guidelines recommend this level of physi-
vegetables, nuts, whole grains, reduced fish, and minimal cal activity for reduced insulin resistance and improved
meats. Only 15% of calories are derived from fat, and overall health.100 Associated insulin resistance syndromes
10% of calories are derived from protein. The majority, show significant improvement. Among subjects with
approximately 75% of calories, are in the form of complex hepatosteatosis, a systematic review of randomized trials
carbohydrates. demonstrates significant reduction in insulin resistance
The OD demonstrates significant improvement in with dietary change and moderate physical activity per-
circulating LDL levels and is beneficial in the treatment formed three to seven times per week, 20–60 minutes
and prevention of atherosclerotic disease.94 However, the per session.104 Even among adults without demonstrable
effect of the OD on insulin resistance syndromes has not impairment of glucose tolerance, an intensive lifestyle
been well characterized. In one uncontrolled cohort study, intervention with this degree of physical activity has been
the subset of subjects with T2D showed a reduction in shown to reduce fasting plasma glucose and A1C.105
average fasting glucose of 16 mg/dl and a 0.4% reduction Several exceptions to the concept of beneficial life-
in A1C levels after three months of following the OD.95 style changes include trials that investigate the use of less
Though somewhat suggestive, controlled studies and intense physical activity such as walking, which do not
References 363
consistently show a clear health benefit,106 and trials of intensive lifestyle intervention can lead to the best health
28
increased physical activity during pregnancy, which fail outcomes in patients with insulin resistance, MetS, PCOS,
to demonstrate reduced rates of gestational diabetes mel- T2D, and most importantly, end-organ disease progres-
litus.107 Although exercise without a change in dietary sion and complications—all part of DBCD risk mitigation.
intake is not sufficient for weight loss, maintaining a phys-
ically active lifestyle with regular cardiovascular exercise
will promote wellness and prevent the onset or reduce CLINICAL APPLICATIONS
morbidity of DBCD.100
• Due to the relatively high prevalence of suspected
and diagnosed prediabetes, type 2 diabetes, and
28.5 CONCLUSION cardiovascular disease, all patients should undergo
screening or aggressive case finding for dysglycemia.
A healthy lifestyle is paramount to the management of • Available tools include a detailed family history;
DBCD (see “Clinical Applications” section). This includes anthropometrics on physical exam to detect abnor-
a dietary pattern that is anti-inflammatory, reduces hyper- mal adiposity; hemoglobin A1c levels; and fasting,
glycemia, promotes insulin sensitivity, and promotes pan- casual, and post-challenge plasma glucose levels.
creatic β-cell function. The characteristics of an idealized • All patients with dysglycemia should have for-
dietary pattern include reduction in total carbohydrate mal nutritional counseling by a healthcare profes-
intake with incorporation of reduced GI and glycemic sional, preferably a physician, Registered Dietitian
load dietary patterns, increased fiber intake, and mini- Nutritionist, or Advanced Practice Provider.
mization of fructose consumption. In addition, these • Nutritional counseling should include patient-cen-
healthy dietary patterns for patients with DBCD should tered information about healthy dietary patterns,
avoid processed foods and increase dietary n-3 PUFAs, specific Eating Plans directed to individualized dia-
antioxidants, and polyphenols, primarily as fruits, veg- betes complication and cardiometabolic risks, and
etables, herbs, and spices. Furthermore, AGE and EDC personal and culturally adapted food preferences.
consumption should be avoided. The Mediterranean diets, • Other structured lifestyle medicine interventions for
NND, and Ornish diet represent three distinct approaches dysglycemia include increasing physical activity as
that have potential to achieve these goals. In combination well as avoiding or minimizing advanced glycated
with a significant amount of physical activity, this type of end product and endocrine disruptor consumption.
REFERENCES
1. Katsiki N, Mikhailidis DP, Gotzamani- 8. Sperling LS, Mechanick JI, Neeland receptor substrate-1 Ser312 phosphoryla-
Psarrakou A, Yovos JG, and Karamitsos IJ, Herrick CJ, Despres JP, Ndumele tion following laparoscopic ovarian elec-
D. 2011. Effect of various treatments on CE, Vijayaraghavan K, Handelsman Y, trocautery. Hum. Reprod. 22:1003–1010.
leptin, adiponectin, ghrelin and neuro- Puckrein GA, Araneta MR, Blum QK, 13. Macut D, Bjekic-Macut J, Rahelic D, and
peptide Y in patients with type 2 diabetes Collins KK, Cook S, Dhurandhar NV, Doknic M. 2017. Insulin and the polycys-
mellitus. Expert. Opin. Ther. Targets Dixon DL, Egan BM, Ferdinand DP, tic ovary syndrome. Diabetes Res. Clin.
15:401–420. Herman LM, Hessen SE, Jacobson TA, Pract. 130:163–170.
2. Temma J, Matsuhisa M, Horie T, Kuroda Pate RR, Ratner RE, Brinton EA, Forker 14. Gregg EW, Jakicic JM, Blackburn G,
A, Mori H, Tamaki M, Endo I, Aihara AD, Ritzenthaler LL, and Grundy SM. Bloomquist P, Bray GA, Clark JM, Coday
K, Abe M, and Matsumoto T. 2015. Non- 2015. The cardiometabolic health alli- M, Curtis JM, Egan C, Evans M, Foreyt
invasive measurement of skin autofluo- ance: Working toward a new care model J, Foster G, Hazuda HP, Hill JO, Horton
rescence as a beneficial surrogate marker for the metabolic syndrome. J. Am. Coll. ES, Hubbard VS, Jeffery RW, Johnson KC,
for atherosclerosis in patients with type 2 Cardiol. 66:1050–1067. Kitabchi AE, Knowler WC, Kriska A, Lang
diabetes. J. Med. Invest. 62:126–129. 9. Grundy SM, Cleeman JI, Daniels SR, W, Lewis CE, Montez MG, Nathan DM,
3. Muniyappa R, Montagnani M, Koh KK, Donato KA, Eckel RH, Franklin BA, Neiberg RH, Patricio J, Peters A, Pi-Sunyer
and Quon MJ. 2007. Cardiovascular Gordon DJ, Krauss RM, Savage PJ, X, Pownall H, Redmon B, Regensteiner J,
actions of insulin. Endocr. Rev. Smith SC, Jr., Spertus JA, and Costa F. Rejeski J, Ribisl PM, Safford M, Stewart
28:463–491. 2006. Diagnosis and management of the K, Trence D, Wadden TA, Wing RR, and
4. Muniyappa R and Quon MJ. 2007. metabolic syndrome: An American heart Yanovski SZ. 2016. Association of the
Insulin action and insulin resistance in association/national heart, lung, and magnitude of weight loss and changes in
vascular endothelium. Curr. Opin. Clin. blood institute scientific statement. Curr. physical fitness with long-term cardio-
Nutr. Metab. Care 10:523–530. Opin. Cardiol. 21:1–6. vascular disease outcomes in overweight
5. Miller JM, Kaylor MB, Johannsson M, 10. Cassar S, Misso ML, Hopkins WG, or obese people with type 2 diabetes: A
Bay C, and Churilla JR. 2014. Prevalence Shaw CS, Teede HJ, and Stepto NK. post-hoc analysis of the Look AHEAD
of metabolic syndrome and individual 2016. Insulin resistance in polycystic randomised clinical trial. Lancet Diabetes
criterion in US adolescents: 2001–2010 ovary syndrome: A systematic review and Endocrinol. 4:913–921.
National Health and Nutrition meta-analysis of euglycaemic-hyperinsu- 15. Lam DW and LeRoith D. 2015.
Examination Survey. Metab. Syndr. linaemic clamp studies. Hum. Reprod. Metabolic Syndrome. South Dartmouth,
Relat. Disord. 12:527–532. 31:2619–2631. MA: MDText.com, Inc.
6. Franks S. 2008. Polycystic ovary 11. Dunaif A and Finegood DT. 1996. Beta- 16. Petersen MC, Vatner DF, and Shulman
syndrome in adolescents. Int. J. Obes. cell dysfunction independent of obesity GI. 2017. Regulation of hepatic glucose
(Lond.) 32:1035–1041. and glucose intolerance in the polycystic metabolism in health and disease. Nat.
7. Bellentani S, Saccoccio G, Masutti F, ovary syndrome. J. Clin. Endocrinol. Rev. Endocrinol. 10:572–587.
Croce LS, Brandi G, Sasso F, Cristanini Metab. 81:942–947. 17. Armani A, Berry A, Cirulli F, and
G, and Tiribelli C. 2000. Prevalence 12. Seow KM, Juan CC, Hsu YP, Hwang Caprio M. 2017. Molecular mechanisms
of and risk factors for hepatic steatosis JL, Huang LW, and Ho LT. 2007. underlying metabolic syndrome: The
in Northern Italy. Ann. Intern. Med. Amelioration of insulin resistance in expanding role of the adipocyte. FASEB J.
132:112–117. women with PCOS via reduced insulin 10:4240–4255.
364 Chapter 28 Impact of Lifestyle Medicine on Dysglycemia-Based Chronic Disease
18. Sawicki CM, Livingston KA, Obin M, diabetes. Arterioscler. Thromb. Vasc. syndrome: A case control study. Adv.
Roberts SB, Chung M, and McKeown Biol. 32:1039–1044. Clin. Exp. Med. 25:689–700.
NM. 2017. Dietary fiber and the human 32. Smith DO and LeRoith D. 2004. Insulin 44. Spahis S, Borys JM, and Levy E. 2017.
gut microbiota: Application of evidence resistance syndrome, pre-diabetes, and Metabolic syndrome as a multifaceted
mapping methodology. Nutrients 9:E125. the prevention of type 2 diabetes mellitus. risk factor for oxidative stress. Antioxid.
19. Thompson SV, Winham DM, and Clin. Cornerstone 6:7–6. Redox Signal. 26:445–461.
Hutchins AM. 2012. Bean and rice meals 33. Konstantinou DM, Chatzizisis YS, 45. Mason SA, Della Gatta PA, Snow RJ,
reduce postprandial glycemic response in Louridas GE, and Giannoglou GD. 2010. Russell AP, and Wadley GD. 2015.
adults with type 2 diabetes: A cross-over Metabolic syndrome and angiographic Ascorbic acid supplementation improves
study. Nutr. J. 11:23. coronary artery disease prevalence in skeletal muscle oxidative stress and
20. Bidwell AJ. 2017. Chronic fructose association with the Framingham risk insulin sensitivity in people with type
ingestion as a major health concern: Is score. Metab. Syndr. Relat. Disord. 2 diabetes: Findings of a randomized
a sedentary lifestyle making it worse? A 8:201–208. controlled study. Free. Radic. Biol. Med.
review. Nutrients 9:E549. 34. Shai I, Schwarzfuchs D, Henkin Y, Shahar 93:227–238.
21. Ludwig DS. 2002. The glycemic index: DR, Witkow S, Greenberg I, Golan R, 46. Zhou C, Na L, Shan R, Cheng Y, Li Y,
Physiological mechanisms relating to obe- Fraser D, Bolotin A, Vardi H, Tangi- Wu X, and Sun C. 2016. Dietary vitamin
sity, diabetes, and cardiovascular disease. Rozental O, Zuk-Ramot R, Sarusi B, C intake reduces the risk of type 2 dia-
JAMA 287:2414–2423. Brickner D, Schwartz Z, Sheiner E, Marko betes in Chinese adults: HOMA-IR and
22. Tappy L and Le KA. 2010. Metabolic R, Katorza E, Thiery J, Fiedler GM, Bluher T-AOC as potential mediators. PLoS One
effects of fructose and the worldwide M, Stumvoll M, and Stampfer MJ. 2008. 11:e0163571.
increase in obesity. Physiol. Rev. 90:23–46. Weight loss with a low-carbohydrate, 47. Rafraf M, Bazyun B, Sarabchian MA,
23. Raatz SK, Johnson LK, and Picklo MJ. Mediterranean, or low-fat diet. N. Engl. J. Safaeiyan A, and Gargari BP. 2016.
2015. Consumption of honey, sucrose, Med. 359:229–241. Vitamin E improves serum paraoxonase-1
and high-fructose corn syrup produces 35. Estruch R, Ros E, Salas-Salvado J, Covas activity and some metabolic factors in
similar metabolic effects in glucose-tol- MI, Corella D, Aros F, Gomez-Gracia patients with type 2 diabetes: No effects
erant and -intolerant individuals. J. Nutr. E, Ruiz-Gutierrez V, Fiol M, Lapetra J, on nitrite/nitrate levels. J. Am. Coll.
145:2265–2272. Lamuela-Raventos RM, Serra-Majem L, Nutr. 35:521–528.
24. Dominguez Coello S, Carrillo Fernandez Pinto X, Basora J, Munoz MA, Sorli JV, 48. Sanyal AJ, Chalasani N, Kowdley KV,
L, Gobierno Hernandez J, Mendez Abad Martinez JA, and Martinez-Gonzalez McCullough A, Diehl AM, Bass NM,
M, Borges Alamo C, Garcia Dopico JA, MA. 2013. Primary prevention of cardio- Neuschwander-Tetri BA, Lavine JE,
Aguirre Jaime A, and Cabrera de Leon A. vascular disease with a Mediterranean Tonascia J, Unalp A, Van Natta M, Clark
2017. Effectiveness of a low-fructose and/ diet. N. Engl. J. Med. 368:1279–1290. J, Brunt EM, Kleiner DE, Hoofnagle
or low-sucrose diet in decreasing insulin 36. Orlich MJ, Singh PN, Sabate J, Jaceldo- JH, and Robuck PR. 2010. Pioglitazone,
resistance (DISFRUTE study): Study pro- Siegl K, Fan J, Knutsen S, Beeson WL, vitamin E, or placebo for nonalco-
tocol for a randomized controlled trial. and Fraser GE. 2013. Vegetarian dietary holic steatohepatitis. N. Engl. J. Med.
Trials 18:369. patterns and mortality in Adventist 362:1675–1685.
25. Lustig RH. 2013. Fructose: It’s “alco- Health Study 2. JAMA Intern. Med. 49. Alizadeh M, Safaeiyan A, Ostadrahimi
hol without the buzz”. Adv. Nutr. 173:1230–1238. A, Estakhri R, Daneghian S, Ghaffari
4:226–235. 37. Simopoulos AP. 2008. The importance of A, and Gargari BP. 2012. Effect of
26. Martinez Steele E, Baraldi LG, Louzada the omega-6/omega-3 fatty acid ratio in L-arginine and selenium added to a
ML, Moubarac JC, Mozaffarian D, and cardiovascular disease and other chronic hypocaloric diet enriched with legumes
Monteiro CA. 2016. Ultra-processed diseases. Exp. Biol. Med. (Maywood) on cardiovascular disease risk factors in
foods and added sugars in the US diet: 233:674–688. women with central obesity: A random-
Evidence from a nationally representa- 38. Sotos-Prieto M, Bhupathiraju SN, Mattei ized, double-blind, placebo-controlled
tive cross-sectional study. BMJ Open J, Fung TT, Li Y, Pan A, Willett WC, trial. Ann. Nutr. Metab. 60:157–168.
6:e009892. Rimm EB, and Hu FB. 2017. Association 50. Asemi Z, Jamilian M, Mesdaghinia E,
27. Du H, Li L, Bennett D, Guo Y, Turnbull of changes in diet quality with total and and Esmaillzadeh A. 2015. Effects of sele-
I, Yang L, Bragg F, Bian Z, Chen Y, Chen cause-specific mortality. N. Engl. J. Med. nium supplementation on glucose homeo-
J, Millwood IY, Sansome S, Ma L, Huang 377:143–153. stasis, inflammation, and oxidative stress
Y, Zhang N, Zheng X, Sun Q, Key TJ, 39. Bosch J, Gerstein HC, Dagenais GR, in gestational diabetes: Randomized,
Collins R, Peto R, and Chen Z. 2017. Diaz R, Dyal L, Jung H, Maggiono AP, double-blind, placebo-controlled trial.
Fresh fruit consumption in relation to Probstfield J, Ramachandran A, Riddle Nutrition 31:1235–1242.
incident diabetes and diabetic vascular MC, Ryden LE, and Yusuf S. 2012. n-3 51. Ansar H, Mazloom Z, Kazemi F, and
complications: A 7-y prospective study of fatty acids and cardiovascular outcomes Hejazi N. 2011. Effect of alpha-lipoic
0.5 million Chinese adults. PLoS Med. in patients with dysglycemia. N. Engl. J. acid on blood glucose, insulin resistance
14:e1002279. Med. 367:309–318. and glutathione peroxidase of type 2 dia-
28. Du H, Li L, Bennett D, Guo Y, Key TJ, 40. Sadeghi A, Djafarian K, Mohammadi betic patients. Saudi Med. J. 32:584–588.
Bian Z, Sherliker P, Gao H, Chen Y, Yang H, and Shab-Bidar S. 2017. Effect of 52. Derosa G, D’Angelo A, Romano D, and
L, Chen J, Wang S, Du R, Su H, Collins omega-3 fatty acids supplementation Maffioli P. 2016. A clinical trial about
R, Peto R, and Chen Z. 2016. Fresh fruit on insulin resistance in women with a food supplement containing alpha-
consumption and major cardiovascu- polycystic ovary syndrome: Meta-analysis lipoic acid on oxidative stress markers in
lar disease in China. N. Engl. J. Med. of randomized controlled trials. Diabetes type 2 diabetic patients. Int. J. Mol. Sci.
374:1332–1343. Metab. Syndr. 11:157–162. 17:E1802
29. Deng Y and Scherer PE. 2010. 41. Jump DB, Lytle KA, Depner CM, and 53. Panickar KS and Jang S. 2013. Dietary
Adipokines as novel biomarkers and regu- Tripathy S. 2018. Omega-3 polyunsatu- and plant polyphenols exert neuropro-
lators of the metabolic syndrome. Ann. rated fatty acids as a treatment strategy tective effects and improve cognitive
N. Y. Acad. Sci. 1212:E1–E19. for nonalcoholic fatty liver disease. function in cerebral ischemia. Recent Pat.
30. Mechanick JI, Hurley DL, and Garvey Pharmacol. Ther. 181:108–125. Food Nutr. Agric. 5:128–143.
WT. 2017. Adiposity-based chronic 42. Chattopadhyay M, Khemka VK, 54. Diaz-Lopez A, Babio N, Martinez-
disease as a new diagnostic term: The Chatterjee G, Ganguly A, Mukhopadhyay Gonzalez MA, Corella D, Amor AJ, Fito
American Association of clinical endocri- S, and Chakrabarti S. 2015. Enhanced M, Estruch R, Aros F, Gomez-Gracia E,
nologists and American College of endo- ROS production and oxidative damage in Fiol M, Lapetra J, Serra-Majem L, Basora
crinology position statement. Endocr. subcutaneous white adipose tissue mito- J, Basterra-Gortari FJ, Zanon-Moreno V,
Pract. 23:372–378. chondria in obese and type 2 diabetes Munoz MA, and Salas-Salvado J. 2015.
31. Nogueira JP, Maraninchi M, Beliard subjects. Mol. Cell Biochem. 399:95–103. Mediterranean diet, retinopathy, nephropa-
S, Padilla N, Duvillard L, Mancini J, 43. Godala MM, Materek-Kusmierkiewicz thy, and microvascular diabetes complica-
Nicolay A, Xiao C, Vialettes B, Lewis I, Moczulski D, Rutkowski M, Szatko F, tions: A post hoc analysis of a randomized
GF, and Valero R. 2012. Absence of Gaszynska E, Tokarski S, and Kowalski trial. Diabetes Care 38:2134–2141.
acute inhibitory effect of insulin on J. 2016. Lower plasma levels of antioxi- 55. Mahoney SE and Loprinzi PD. 2014.
chylomicron production in type 2 dant vitamins in patients with metabolic Influence of flavonoid-rich fruit and
References 365
vegetable intake on diabetic retinopa- 68. Ortsater H, Grankvist N, Wolfram S, prospective birth cohort study. Environ.
thy and diabetes-related biomarkers. J. Kuehn N, and Sjoholm A. 2012. Diet Health Perspect. 120:451–457.
56.
Diabetes Complicat. 28:767–771.
Ding M, Franke AA, Rosner BA,
Giovannucci E, van Dam RM, Tworoger
supplementation with green tea extract
epigallocatechin gallate prevents progres-
sion to glucose intolerance in db/db mice.
81. Verhulst SL, Nelen V, Hond ED, Koppen
G, Beunckens C, Vael C, Schoeters
G, and Desager K. 2009. Intrauterine
28
SS, Hu FB, and Sun Q. 2015. Urinary Nutr. Metab. (Lond). 9:11. exposure to environmental pollutants
isoflavonoids and risk of type 2 diabetes: 69. Cai EP and Lin JK. 2009. and body mass index during the first 3
A prospective investigation in US women. Epigallocatechin gallate (EGCG) and years of life. Environ. Health Perspect.
Br. J. Nutr. 114:1694–1701. rutin suppress the glucotoxicity through 117:122–126.
57. Bertelli AA and Das DK. 2009. Grapes, activating IRS2 and AMPK signaling in 82. Suez J, Korem T, Zeevi D, Zilberman-
wines, resveratrol, and heart health. J. rat pancreatic beta cells. J. Agric. Food Schapira G, Thaiss CA, Maza O, Israeli
Cardiovasc. Pharmacol. 54:468–476. Chem. 57:9817–9827. D, Zmora N, Gilad S, Weinberger A,
58. Banaszewska B, Wrotynska-Barczynska 70. de Brito Alves JL, de Sousa VP, Kuperman Y, Harmelin A, Kolodkin-
J, Spaczynski RZ, Pawelczyk L, and Cavalcanti Neto MP, Magnani M, Gal I, Shapiro H, Halpern Z, Segal E,
Duleba AJ. 2016. Effects of resveratrol on Braga VA, da Costa-Silva JH, Leandro and Elinav E. 2014. Artificial sweeteners
polycystic ovary syndrome: A double- CG, Vidal H, and Pirola L. 2016. New induce glucose intolerance by altering the
blind, randomized, placebo-controlled insights on the use of dietary polyphenols gut microbiota. Nature 514:181–186.
trial. J. Clin. Endocrinol. Metab. or probiotics for the management of arte- 83. Fu P and Kawamura K. 2010. Ubiquity of
101:4322–4328. rial hypertension. Front. Physiol. 7:448. bisphenol A in the atmosphere. Environ.
59. Kjaer TN, Ornstrup MJ, Poulsen 71. Luevano-Contreras C, Gomez-Ojeda Pollut. 158:3138–3143.
MM, Stodkilde-Jorgensen H, Jessen A, Macias-Cervantes MH, and Garay- 84. O’Brien P and Corpe CP. 2016. Acute
N, Jorgensen JOL, Richelsen B, and Sevilla ME. 2017. Dietary advanced gly- effects of sugars and artificial sweeten-
Pedersen SB. 2017. No beneficial effects cation end products and cardiometabolic ers on small intestinal sugar transport:
of resveratrol on the metabolic syn- risk. Curr. Diabetes Rep. 17:63. A study using CaCo-2 cells as an in vitro
drome: A randomized placebo-controlled 72. Okura T, Ueta E, Nakamura R, Fujioka model of the human enterocyte. PLoS
clinical trial. J. Clin. Endocrinol. Metab. Y, Sumi K, Matsumoto K, Shoji K, One 11:e0167785.
102:1642–1651. Matsuzawa K, Izawa S, Nomi Y, Mihara 85. Dansinger ML, Gleason JA, Griffith
60. Christenson J, Whitby SJ, Mellor D, H, Otsuka Y, Kato M, Taniguchi SI, JL, Selker HP, and Schaefer EJ. 2005.
Thomas J, McKune A, Roach PD, and and Yamamoto K. 2017. High serum Comparison of the Atkins, Ornish,
Naumovski N. 2016. The effects of resve- advanced glycation end products are asso- Weight Watchers, and Zone diets for
ratrol supplementation in overweight and ciated with decreased insulin secretion weight loss and heart disease risk
obese humans: A systematic review of in patients with type 2 diabetes: A brief reduction: A randomized trial. JAMA
randomized trials. Metab. Syndr. Relat. report. J. Diabetes Res. 2017:5139750. 293:43–53.
Disord. 14:323–333. 73. Rajaobelina K, Farges B, Nov S, Maury 86. Nordmann AJ, Suter-Zimmermann K,
61. Bashmakov YK, Assaad-Khalil SH, E, Cephise-Velayoudom FL, Gin H, Bucher HC, Shai I, Tuttle KR, Estruch
Abou Seif M, Udumyan R, Megallaa M, Helmer C, and Rigalleau V. 2017. Skin R, and Briel M. 2011. Meta-analysis
Rohoma KH, Zeitoun M, and Petyaev autofluorescence and peripheral neuropa- comparing mediterranean to low-fat diets
IM. 2014. Resveratrol promotes foot thy four years later in type 1 diabetes. for modification of cardiovascular risk
ulcer size reduction in type 2 diabetes Diabetes Metab. Res. Rev. 33:e2832. factors. Am. J. Med. 124:841–851 e842.
patients. ISRN Endocrinol. 2014:816307. 74. de Courten B, de Courten MP, Soldatos 87. Schwarzfuchs D, Golan R, and Shai I.
62. Poulsen MM, Vestergaard PF, Clasen G, Dougherty SL, Straznicky N, Schlaich 2012. Four-year follow-up after two-year
BF, Radko Y, Christensen LP, Stodkilde- M, Sourris KC, Chand V, Scheijen JL, dietary interventions. N. Engl. J. Med.
Jorgensen H, Moller N, Jessen N, Kingwell BA, Cooper ME, Schalkwijk 367:1373–1374.
Pedersen SB, and Jorgensen JO. 2013. CG, Walker KZ, and Forbes JM. 2016. 88. Salas-Salvado J, Bullo M, Estruch R,
High-dose resveratrol supplementation Diet low in advanced glycation end Ros E, Covas MI, Ibarrola-Jurado N,
in obese men: An investigator-initiated, products increases insulin sensitivity in Corella D, Aros F, Gomez-Gracia E,
randomized, placebo-controlled clinical healthy overweight individuals: A double- Ruiz-Gutierrez V, Romaguera D, Lapetra
trial of substrate metabolism, insulin sen- blind, randomized, crossover trial. Am. J. J, Lamuela-Raventos RM, Serra-
sitivity, and body composition. Diabetes Clin. Nutr. 103:1426–1433. Majem L, Pinto X, Basora J, Munoz
62:1186–1195. 75. Mark AB, Poulsen MW, Andersen S, MA, Sorli JV, and Martinez-Gonzalez
63. Mahmoud AM, Ashour MB, Abdel- Andersen JM, Bak MJ, Ritz C, Holst JJ, MA. 2014. Prevention of diabetes with
Moneim A, and Ahmed OM. 2012. Nielsen J, de Courten B, Dragsted LO, and Mediterranean diets: A subgroup analysis
Hesperidin and naringin attenuate hyper- Bugel SG. 2014. Consumption of a diet of a randomized trial. Ann. Intern. Med.
glycemia-mediated oxidative stress and low in advanced glycation end products 160:1–10.
proinflammatory cytokine production in for 4 weeks improves insulin sensitiv- 89. Gepner Y, Golan R, Harman-Boehm
high fat fed/streptozotocin-induced type ity in overweight women. Diabetes Care I, Henkin Y, Schwarzfuchs D, Shelef I,
2 diabetic rats. J. Diabetes Complicat. 37:88–95. Durst R, Kovsan J, Bolotin A, Leitersdorf
26:483–490. 76. Vlassara H, Uribarri J, Cai W, Goodman E, Shpitzen S, Balag S, Shemesh E,
64. Zhang Y and Liu D. 2011. Flavonol S, Pyzik R, Post J, Grosjean F, Woodward Witkow S, Tangi-Rosental O, Chassidim
kaempferol improves chronic hyper- M, and Striker GE. 2012. Effects of Y, Liberty IF, Sarusi B, Ben-Avraham S,
glycemia-impaired pancreatic beta-cell sevelamer on HbA1c, inflammation, Helander A, Ceglarek U, Stumvoll M,
viability and insulin secretory function. and advanced glycation end products in Bluher M, Thiery J, Rudich A, Stampfer
Eur. J. Pharmacol. 670:325–332. diabetic kidney disease. Clin. J. Am. Soc. MJ, and Shai I. 2015. Effects of initiating
65. Takikawa M, Inoue S, Horio F, and Nephrol. 7:934–942. moderate alcohol intake on cardiometa-
Tsuda T. 2010. Dietary anthocyanin-rich 77. Nishida K and Otsu K. 2017. bolic risk in adults with type 2 diabetes:
bilberry extract ameliorates hyperglyce- Inflammation and metabolic cardiomy- A 2-year randomized, controlled trial.
mia and insulin sensitivity via activa- opathy. Cardiovasc. Res. 113:389–398. Ann. Intern. Med. 163:569–579.
tion of AMP-activated protein kinase in 78. Kaiser D and Oetjen E. 2014. Something 90. Holst C, Becker U, Jorgensen ME,
diabetic mice. J. Nutr. 140:527–533. old, something new and something very Gronbaek M, and Tolstrup JS. 2017.
66. Kobori M, Masumoto S, Akimoto Y, and old: Drugs for treating type 2 diabetes. Alcohol drinking patterns and risk of
Takahashi Y. 2009. Dietary quercetin Br. J. Pharmacol. 171:2940–2950. diabetes: A cohort study of 70,551 men
alleviates diabetic symptoms and reduces 79. Baillie-Hamilton PF. 2002. Chemical and women from the general Danish
streptozotocin-induced disturbance of toxins: A hypothesis to explain the global population. Diabetologia. 60:1941–1950.
hepatic gene expression in mice. Mol. obesity epidemic. J. Altern. Complement. 91. Brien SE, Ronksley PE, Turner BJ,
Nutr. Food Res. 53:859–868. Med. 8:185–192. Mukamal KJ, and Ghali WA. 2011.
67. Li YQ, Zhou FC, Gao F, Bian JS, and 80. Valvi D, Mendez MA, Martinez D, Effect of alcohol consumption on biologi-
Shan F. 2009. Comparative evaluation Grimalt JO, Torrent M, Sunyer J, and cal markers associated with risk of coro-
of quercetin, isoquercetin and rutin as Vrijheid M. 2012. Prenatal concentra- nary heart disease: Systematic review and
inhibitors of alpha-glucosidase. J. Agric. tions of polychlorinated biphenyls, DDE, meta-analysis of interventional studies.
Food Chem. 57:11463–11468. and DDT and overweight in children: A BMJ 342:d636.
366 Chapter 28 Impact of Lifestyle Medicine on Dysglycemia-Based Chronic Disease
92. Mithril C, Dragsted LO, Meyer C, Kang YM, and Zhu GQ. 2015. Irisin incidence of type 2 diabetes with lifestyle
Blauert E, Holt MK, and Astrup A. 2012. inhibits hepatic gluconeogenesis and intervention or metformin. N. Engl. J.
Guidelines for the New Nordic Diet. increases glycogen synthesis via the Med. 346:393–403.
Public Health Nutr. 15:1941–1947. PI3K/Akt pathway in type 2 diabetic 104. Paris T, George ES, Roberts SK, and
93. Fritzen AM, Lundsgaard AM, Jordy AB, mice and hepatocytes. Clin. Sci. (Lond). Tierney AC. 2017. The effects of diet and
Poulsen SK, Stender S, Pilegaard H, Astrup 129:839–850. lifestyle interventions on insulin resis-
A, Larsen TM, Wojtaszewski JF, Richter 99. Pontzer H, Raichlen DA, Wood BM, tance in patients with nonalcoholic fatty
EA, and Kiens B. 2015. New Nordic Diet- Emery Thompson M, Racette SB, liver disease: A systematic review. Eur. J.
induced weight loss is accompanied by Mabulla AZ, and Marlowe FW. 2015. Gastroenterol. Hepatol. 29:867–878.
changes in metabolism and AMPK signal- Energy expenditure and activity among 105. Zhang X, Imperatore G, Thomas W,
ing in adipose tissue. J. Clin. Endocrinol. Hadza hunter-gatherers. Am. J. Hum. Cheng YJ, Lobelo F, Norris K, Devlin
Metab. 100:3509–3519. Biol. 27:628–637. HM, Ali MK, Gruss S, Bardenheier B,
94. Ornish D, Scherwitz LW, Billings JH, 100. Gonzalez-Campoy JM, St Jeor ST, Cho P, Garcia de Quevedo I, Mudaliar
Brown SE, Gould KL, Merritt TA, Castorino K, Ebrahim A, Hurley D, U, Saaddine J, Geiss LS, and Gregg EW.
Sparler S, Armstrong WT, Ports TA, Jovanovic L, Mechanick JI, Petak SM, 2016. Effect of lifestyle interventions on
Kirkeeide RL, Hogeboom C, and Brand Yu YH, Harris KA, Kris-Etherton P, glucose regulation among adults without
RJ. 1998. Intensive lifestyle changes for Kushner R, Molini-Blandford M, Nguyen impaired glucose tolerance or diabetes:
reversal of coronary heart disease. JAMA QT, Plodkowski R, Sarwer DB, and A systematic review and meta-analysis.
280:2001–2007. Thomas KT. 2013. Clinical practice Diabetes Res. Clin. Pract. 123:149–164.
95. Chainani-Wu N, Weidner G, Purnell DM, guidelines for healthy eating for the pre- 106. Freak-Poli RL, Cumpston M, Peeters A,
Frenda S, Merritt-Worden T, Pischke vention and treatment of metabolic and and Clemes SA. 2013. Workplace pedom-
C, Campo R, Kemp C, Kersh ES, and endocrine diseases in adults: Cosponsored eter interventions for increasing physical
Ornish D. 2011. Changes in emerging by the American Association of clinical activity. Cochrane Database Syst. Rev.
cardiac biomarkers after an intensive endocrinologists/the American College of 4:CD009209.
lifestyle intervention. Am. J. Cardiol. Endocrinology and the Obesity Society. 107. Han S, Middleton P, and Crowther CA.
108:498–507. Endocr. Pract. 19(Suppl 3):1–82. 2012. Exercise for pregnant women for
96. Gadgil MD, Appel LJ, Yeung E, 101. Lavie CJ, Lee DC, Sui X, Arena R, preventing gestational diabetes mel-
Anderson CA, Sacks FM, and Miller ER, O’Keefe JH, Church TS, Milani RV, and litus. Cochrane Database Syst. Rev.
3rd. 2013. The effects of carbohydrate, Blair SN. 2015. Effects of running on 7:CD009021.
unsaturated fat, and protein intake on chronic diseases and cardiovascular and 108. Hannon TS, Kahn SE, Utzschneider KM,
measures of insulin sensitivity: Results all-cause mortality. Mayo Clin. Proc. Buchanan TA, Nadeau KJ, Zeitler PS,
from the OmniHeart trial. Diabetes Care 90:1541–1552. Ehrmann DA, Arslanian SA, Caprio S,
36:1132–1137. 102. Tuomilehto J, Lindstrom J, Eriksson JG, Edelstein SL, Savage PJ, and Mather KJ.
97. Marinho R, Ropelle ER, Cintra DE, Valle TT, Hamalainen H, Ilanne-Parikka 2017. Review of methods for measuring
De Souza CT, Da Silva AS, Bertoli FC, P, Keinanen-Kiukaanniemi S, Laakso beta-cell function: Design considerations
Colantonio E, D’Almeida V, and Pauli M, Louheranta A, Rastas M, Salminen from the Restoring Insulin Secretion
JR. 2012. Endurance exercise training V, and Uusitupa M. 2001. Prevention of (RISE) Consortium. Diabetes Obes.
increases APPL1 expression and improves type 2 diabetes mellitus by changes in Metab. 20:14–24.
insulin signaling in the hepatic tissue lifestyle among subjects with impaired 109. Dominguez Avila JA, Rodrigo Garcia J,
of diet-induced obese mice, indepen- glucose tolerance. N. Engl. J. Med. Gonzalez Aguilar GA, and de la Rosa
dently of weight loss. J. Cell Physiol. 344:1343–1350. LA. 2017. The antidiabetic mechanisms
227:2917–2926. 103. Knowler WC, Barrett-Connor E, Fowler of polyphenols related to increased
98. Liu TY, Shi CX, Gao R, Sun HJ, Xiong SE, Hamman RF, Lachin JM, Walker EA, Glucagon-Like Peptide-1 (GLP1) and
XQ, Ding L, Chen Q, Li YH, Wang JJ, and Nathan DM. 2002. Reduction in the insulin signaling. Molecules 22:E903.
29
CHAPTER
Figure 29.1 Levels of Glucose Tolerance. These definitions are based on recommendations from the American Diabetes
Association 2017.
label stigmatizes patients and therefore introduces prob- clinical end points, such as cardiovascular disease, cancer,
lems with self-image, insurance, employment, and eco- infectious diseases, and mental health problems in people
nomic burdens for healthcare systems. Finally, critics of with prediabetes. 21,22 Overall, T2D and cardiovascular
the prediabetes diagnosis and management argue that risks are higher when IGT and IFG coexist. 23
no studies have examined the effect of lifestyle or drug The International Diabetes Federation reports that the
interventions in different prediabetes subtypes.4 This global prevalence of prediabetes in adults reached 6.7%
view is challenged by evidence showing that prediabetes in 2015 and is expected to rise to 7.8% by 2040. 24 About
represents a high-risk state for type 2 diabetes (T2D) and 69.2% of the prediabetes cases are found in low- and
cardiovascular morbidity and mortality. 5–8 Further, pre- middle-income countries, and 50.1% of cases are among
diabetes represents a significant monetary cost to health- adults under the age of 50. 24 The highest prevalence of pre-
care systems,9 amplified by potential future increases in diabetes is observed in the North America and Caribbean
new T2D cases and associated burdens.10 A strong meta- region (13.9% age-adjusted), and the lowest prevalence
analytic evidence base shows lifestyle interventions and in the Europe region (4.1% age-adjusted). 24 Differences
some drug classes offered to people with prediabetes pro- in prediabetes prevalence among ethnic groups have also
mote regression to normal glucose levels and prevent or been observed, even among groups from the same coun-
delay progression to T2D.11–16 Finally, prominent organi- try, as observed in India and China. 25,26 Furthermore,
zations such as the American Diabetes Association and the prevalence of isolated IFG versus isolated IGT differs
the American Association of Clinical Endocrinologists across ethnic subgroups, gender, and age. 27 The global
recommend lifestyle modification intervention for those prevalence of prediabetes reported by the International
with prediabetes to prevent or delay T2D onsent.1,17 Diabetes Federation was slightly lower in 2015 (6.7% or
Individuals with prediabetes have moderate-to-severe 318 million people), than that reported in 2003 (8.2%
insulin resistance in muscle and/or liver and impaired or 314 million people). 28,29 However, these estimates are
β-cell function. Insulin resistance has been linked to obe- based on IGT and do account for IFG, which may under-
sity and unhealthy lifestyles,18 while the factors underly- estimate true prediabetes prevalence globally. 28
ing impaired β-cell function appear to involve both genetic In the United States, 33.9% of adults aged 18 years
and environmental contributions,19 including inadequate and 48.3% aged 65 years or older had prediabetes in
compensation for insulin resistance. 20 These abnormali- 2015.30 Age-adjusted data from 2011–2014 show pre-
ties in glucose regulation increase the risk for T2D and diabetes prevalence was higher in men (36.6%) than in
cardiovascular disease. Indeed, people with prediabetes women (29.3%).30 IFG appears to be more common than
have a 4–12 times higher T2D progression rate than nor- IGT, with a prevalence of 25.7%, compared to 13.8%.31
moglycemic individuals,7 and almost twofold higher risk IGT appears to be more common among women, while
for cardiovascular diseases and mortality. 5,6 The annual IFG appears be more common among men.32 Prediabetes
incidence of T2D is greater among people with IFG and prevalence is similar among racial and ethnic groups, 30
IGT (15–19%) than in people with isolated IFG (6–9%) although recent studies have reported differences in
or with isolated IGT (4–6%).7 Higher degrees of hyper- prediabetes prevalence and susceptibility in certain
glycemia confer higher risk given the linear relationships ethnic groups. For instance, African Americans have
observed between fasting/postprandial glycemia and shown higher prevalence of prediabetes than their white
29.2 The Role of Lifestyle Factors in the Development of Prediabetes 369
counterparts, 33 while Asian Indians seem to be particu- varied extent of impaired β-cell function and/or insulin
29
larly susceptible to develop prediabetes.34 resistance in the early natural history of disease. 39 In
The economic burden of prediabetes in the United the Multi-Ethnic Study of Atherosclerosis (MESA), U.S.
States is alarming, and it reached $44 billion in direct Asian American Indians (i.e., of South Asian descent)
healthcare costs in 2012.9 This, however, may be an were found to have the poorest β-cell function compared
underestimate given that it accounts for direct medical to non-Hispanic whites, non-Hispanic blacks, Hispanics,
costs (i.e., due to medical visits and prescriptions), and and Chinese Americans, all while having a low average
excludes indirect costs such as loss of productivity due BMI, second only to Chinese Americans.40
to prediabetes. Prediabetes represents a substantial eco- Regarding lifestyle behaviors, excessive caloric intake
nomic burden,10 but given that IFG and IGT are likely to and physical inactivity lead to overweight/obesity and
progress to T2D, 5,35 it also represents a potential future increases in insulin resistance, thereby increasing predia-
increase in T2D care costs. betes risk.41 Insulin resistance has been found to increase
with age, although this is mainly due to age-related obe-
sity and physical inactivity.42 Poor nutrition at critical win-
29.2 THE ROLE OF LIFESTYLE dows of development both in utero and during childhood
FACTORS IN THE DEVELOPMENT is associated with glucose metabolism problems later in
life.43 Exercise impacts glucose regulation by promoting
OF PREDIABETES non-insulin mediated glucose transport in skeletal muscle
and insulin-mediated glucose regulation, and improve-
Though prediabetes is a highly heterogeneous meta- ments in markers of inflammation, insulin resistance,
bolic state, common characteristics of this state include blood pressure, lipid profile, fitness, and lean-to-fat mass
impaired insulin secretion, insulin resistance, subclinical ratio.44 Poor sleep quality and short sleep duration are
inflammation, disproportionate body fat distribution, or a associated with a two- to threefold increased prediabetes
combination of any these factors.36 The presence of these risk among U.S. adults.45 Smoking has also been found
characteristics reflects genetics (an expansion of non- to be associated with a 78% increased risk of IGT and
white populations who have a predisposition to develop impaired glucose sensitivity and secretion.46 Similarly,
prediabetes), the environment (lifestyle-related factors), high alcohol consumption has been found to be associated
and overall population aging. For instance, normal weight with a 42% increased prediabetes risk in men, and with
South Asians have been shown to progress from predia- a 1.4-fold increased risk in women.47 Evidence around
betes to T2D more rapidly than individuals of European how poor sleep, smoking, and alcohol consumption affect
descent.37 The Whitehall II cohort study in the United prediabetes risk is still emerging, as is evidence around
Kingdom also found that South Asians have poorer β-cell interventions targeting these behaviors for preventing or
reserves relative to Europeans.38 Another study compar- managing prediabetes.
ing thin Asian Indians with Pima Indians, a population Across a range of insulin action, glucose homeosta-
with a high mean body mass index (BMI), suggests that sis can be maintained if insulin secretion is adequate.48
heterogeneity of the phenotypes of disease risk reflect a Figure 29.2 shows that when insulin action decreases (e.g.,
Figure 29.2 Early Susceptibility to Impaired β-Cell Function and Insulin Resistance Are Precursors of Prediabetes and
Diabetes. Genetics, obesity, insulin resistance, lifestyle factors, and β-cell health interact to determine an individual’s risk for
developing impaired glucose regulation and then diabetes.
due to weight gain and/or physical inactivity or during age- and BMI-matched women without PCOS.55 Though
periods of growth or pregnancy), as long as β-cells can the exact mechanism remains unclear, one theory suggests
compensate for insulin resistance by an increase in insulin this is related to a post-insulin receptor defect that affects
secretion, normal glucose regulation (NGR) is sustained. signal transduction, resulting in an increase in ovarian
In contrast, individuals with impaired β-cell function have and adrenal androgens.54
inadequate compensatory secretion of insulin. If individu- Reducing body weight and increasing exercise are key
als with underlying impairment of β-cell function become lifestyle factors to counter the effects of obesity on hyper-
insulin resistant, hyperglycemia ensues, potentially result- glycemia. Exercise decreases concentrations of fatty acid
ing in prediabetes. Abnormalities of insulin secretion metabolites (e.g., DAG) to improve fatty acid-induced
in persons with prediabetes include reduced or absent insulin resistance in humans.51,56 In addition, exercise also
first-phase responses to intravenous glucose, delayed stimulates the translocation of GLUT-4 to the plasma mem-
and blunted secretory responses to ingestion of a mixed brane, using signals that differ from the signals involved
meal, alterations in the patterns of insulin secretion, and in insulin-induced GLUT-4 translocation.18,57 Exercise
increases in the plasma concentrations of proinsulin rela- can increase glucose uptake by the working muscle 7–20
tive to those of insulin. 20,27 times above the basal rate, with improvements in insulin
Insulin resistance is increased via two mechanisms: sensitivity lasting up to three days.58 Furthermore, exercise
(i) nonphysiological deposition of fat in visceral, hepatic, seems to improve serum levels of adiponectin,59 a hormone
and intramyocellular sites, and (ii) intracellular seques- that promotes insulin sensitivity,60 and is reduced in the
tration of GLUT-4 glucose transporters in unexercised presence of obesity.61 Overall, exercise improves glucose
muscle, resulting in reduced glucose uptake.18 Free fatty uptake and provides its own therapeutic benefit for those
acids, produced more readily in visceral abdominal fat, experiencing insulin resistance.18,62
decrease insulin sensitivity, impair vascular reactivity, The development of hyperglycemia (inadequate β-cell
and also increase endothelial dysfunction. “Toxic mes- compensation for insulin resistance) reflects both impaired
sages” from the adipose organ, such as free fatty acids, pancreatic β-cell function and loss of β-cell mass. The loss
altered cytokines (e.g., an increase in tumor necrosis of β-cell mass is due to apoptosis, and estimates show
factor-alpha and a decrease in adiponectin), and oxida- β-cell mas is persons with prediabetes is about 60% than
tive stress impair insulin action to restrain glucose pro- that of normoglicemic individuals.63 The extent to which
duction in the liver and promote glucose disposal in lifestyle change reduces insulin resistance and restores
muscle.49 Increases in intracellular diacylglycerol (DAG) normoglycemia in prediabetes depends on the severity of
have been recently identified as an important mechanism the β-cell defect, which is reflected by the clinical pheno-
of free fatty acid-induced insulin resistance in muscle and type. As shown schematically in Figure 29.3, the highest
liver, 50,51 disproving the “Randle hypothesis” of action insulin concentrations are required to promote glucose
via inhibition of pyruvate dehydrogenase. 52,53 Polycystic disposal into fat and muscle, the next highest to restrain
ovary syndrome (PCOS) has also been linked to insulin glucose production in the liver, and the lowest to restrain
resistance in women of reproductive age. Between 65%– lipolysis and ketogenesis. Thus, a mild β-cell defect pres-
70% of women with PCOS have insulin resistance, 54 and ents as postprandial hyperglycemia, a moderate defect as
they have been found to be more insulin resistant than fasting hyperglycemia, and a severe defect as ketoacidosis.
Figure 29.3 Correlation Between Degree of Insulin Deficit and Clinical Phenotype.
If the β-cell defect is mild, as in patients with predia- larger effects on glycemic outcomes than physical activ-
29
betes, lifestyle change can often restore normoglycemia. ity interventions alone.66 Another meta-analysis com-
In cases where the β-cell defect is more severe, lifestyle paring the impact of lifestyle interventions against usual
change is important to help control glucose excursions but care among adults without IGT found that interventions
may not restore normoglycemia, and pharmacologic ther- resulted in significant improvements in systolic blood
apy will be needed. Lifestyle change also tends to improve pressure (-2.16 mmHg), diastolic blood pressure (-1.83
postprandial hyperglycemia more than fasting hypergly- mmHg), total cholesterol (-0.10 mmol/L), low-density
cemia for instance, exercise can reduce insulin resistance lipoprotein cholesterol (-0.09 mmol/L), high-density lipo-
in muscle (the major target of glucose disposal) but has protein cholesterol (0.03 mmol/L), and triglycerides (-0.08
less effect on the liver (the source of glucose produc- mmol/L). Intervention effects were similar between stud-
tion). The impact of lifestyle changes on β-cell mass and ies of participants with low- vs. high-range glucose levels,
function has not been fully understood, but preliminary except for total cholesterol and triglycerides. In this meta-
animal and human studies suggest that physical activity analysis, studies that used combined physical activity and
improves β-cell function by up-regulating insulin signal- dietary strategies had the strongest effect on improving
ing pathways and β-cell mass by stimulating proliferation cardiovascular risk factors, followed by studies using diet
and preventing apoptosis.64 interventions only. Studies that only employed a physical
Overall, development of prediabetes depends on both activity intervention strategy had the weakest effect.65
the degree of insulin resistance and the extent of β-cell Lifestyle interventions can also restore NGR among
reserve. Though everyone who develops insulin resistance people with prediabetes. The Community Guide, an
will not develop prediabetes promoting lifestyle changes evidence summary prepared by the U.S. Community
in these individuals will still be beneficial for their glucose Preventive Services Task Force, found diet and physical
metabolic health. Furthermore, as glucose levels increase activity interventions achieved regression to normoglyce-
over the natural history of prediabetes, β-cell mass and mia as early as one year from intervention start. The per-
function decrease, making it harder for the body to sus- centage of participants regressing to NGR across studies
tain normal glucose levels. Accordingly, it is particularly ranged between 20% at two years and 52% at six years
important to utilize lifestyle change to restore normo- from intervention start. A pooled analysis showed that
glycemia early in the natural history of prediabetes, via participants receiving, versus not receiving, the lifestyle
decreased insulin resistance and reduced β-cell challenge, intervention were 53% more likely to achieve normogly-
since lifestyle change alone is less likely to restore normo- cemia at three years. The median risk difference for NGR
glycemia later in the natural history of glucose intolerance. regression between intervention and control participants
across studies was 12 percentage points.15
In the U.S. Diabetes Prevention Program (DPP), over-
29.3 LIFESTYLE INTERVENTIONS FOR weight participants with both IGT and IFG were random-
PREDIABETES PREVENTION ized to a placebo arm, metformin (850 mg twice daily),
or an intensive lifestyle intervention. The lifestyle modi-
AND TREATMENT fication arm included 16 weekly educational sessions fol-
lowed by eight monthly sessions, all focused on reducing
Individuals with IGT and/or IFG are a priority target pop- body weight by 7% and increasing moderate-intensity
ulation for lifestyle modification studies given the high risk physical activity to ≥ 150 min per week.67 At the end of
for diabetes they face. However, populations without IGT/ the 2.8 year follow-up period, metformin and the lifestyle
IFG but with other cardiovascular risk factors may out- intervention were similarly effective in restoring normal
number those with prediabetes and have the same urgent FBG, but the lifestyle intervention was more effective in
needs for risk reduction.65 This has raised considerable restoring normal two-hour post-load glucose values.67
debate about whether structured lifestyle interventions Lower baseline FPG and two-hour post-challenge glu-
should be offered only to people with IGT/IFG or whether cose, younger age, greater insulin secretion, and weight
they could be implemented more broadly to populations at loss were important factors driving regression.68 Those
risk that do not have IGT/IFG.66 Some experts have rec- who attained normal glucose regulation at least once dur-
ommended that population-wide approaches to improve ing DPP had 56% lower risk for progressing to diabetes
diet and physical activity be used among the wider, non- than those who consistently had prediabetes, irrespective
IGT population, while structured lifestyle interventions of group assignemt.69
could be used for those with prediabetes.66 In the Tübingen Lifestyle Intervention Program
Lifestyle interventions including diet and physical (TULIP), participants with prediabetes underwent nine
activity modification can improve glucose regulation and months of lifestyle modification intervention that included
cardiovascular risk factors among people without IGT. up to ten sessions of dietary counseling from a dietitian
A meta-analysis comparing the impact of lifestyle inter- and advice to perform at least three hours of moderate-
ventions against usual care among people without IGT intensity sports per week. Authors identified participants
found interventions improved FPG (-0.14 mmol/L), A1C with a high-risk phenotype at baseline-consisting of low
(-0.06%), body weight (-3.9%), and markers of insulin disposition index or low insulin sensitivity plus nonalco-
resistance. The effect on FPG was similar across different holic fatty liver disease-and participants with a low-risk
levels of glucose tolerance and among all groups regard- phenotype consisting of all other traits. Overall, 67% of
less of follow-up length. Dietary interventions and those individuals with the low-risk phenotype, compared with
combining physical activity plus dietary strategies had only 31% of those with the high-risk phenotype, reached
372 Chapter 29 Lifestyle Medicine and the Management of Prediabetes
NGR status at the end of the intervention. Low-risk par- versus a high-carbohydrate diet over six months, all partic-
ticipants were four times more likely to reach NGR than ipants in the high-protein diet reverted to NGR, compared
high-risk participants.70 See Table 29.1. to 33% of the participants in the high-carbohydrate diet.73
In Japan, lifestyle modification in participants with Some studies have shown the effect of lifestyle inter-
IGT promoted remission to NGR. Male participants were ventions on glucose tolerance differs according to pre-
randomly assigned to either an intervention group that diabetes phenotype. In the Indian Diabetes Prevention
included detailed lifestyle modification instructions every Program-1 (IDPP-1) and Program-2 (IDPP-2), lifestyle
three to four months or to a control group. Both groups modification consisting of monthly in-person advice
were advised to maintain a normal weight (i.e., BMI ≤ 24 on physical activity and diet over three years promoted
kg/m 2). After four years, more participants in the inter- regression to NGR. In IDDP-1, participants were ran-
vention group (53.8%) than in the control group (33.9%) domly assigned to receive lifestyle modification, metfor-
reverted to NGR. Decreases in body weight were associ- min, lifestyle modification plus metformin, or to a control
ated with improvements in glucose tolerance.71 group.74 In IDPP-2, a different cohort of people with IGT
Diet and exercise tested separately in smaller, shorter were randomly assigned to lifestyle modification plus pio-
follow-up studies have also been shown to promote glitazone or to lifestyle plus placebo.75 A pooled analysis
regression to NGR. In a randomized control trial testing of both programs showed that, in people with isolated
resistance training, 34% of participants with prediabetes IGT, lifestyle modification achieved similar normoglyce-
performing resistance training twice a week regressed to mia regression rates (35.7%) than when combined with a
normoglycemia at three months, 32% at nine months, and medication (38.2%), and larger regression rates than the
30% at 15 months. Participants with isolated IFG or iso- control group (14.1%). In people with both IGT and IFG,
lated IGT had a greater likelihood of achieving normogly- regression rates did not significantly differ between con-
cemia than those with combined IFG and IGT.72 In another trol (15.4%), lifestyle modification (20.5%), and lifestyle
randomized controlled trial comparing a high-protein diet modification plus medication (5.3%).76
TABLE 29.1 Effect of Lifestyle Modification Interventions on Prediabetes Prevention and Management*
Author Lifestyle Intervention Outcomes Reported
Prevention interventions
Zhou et al., 201766 Meta-analysis of diet and physical activity Compared to usual care, intervention participants reduced FPG
modification interventions in people -0.14 mmol/L and A1C -0.06%
without impaired glucose tolerance
Zhou et al., 201765 Meta-analysis of diet and physical Compared to usual care, intervention participants reduced body
activity modification interventions in weight -3.9%, SBP -2.16 mmHg, DBP -1.83 mmHg, TC -0.10
people without impaired glucose mmol/L, LDL -0.09 mmol/L, HDL 0.03 mmol/L, and TG -0.08
tolerance mmol/L
Management Interventions
Balk et al., 201515 Meta-analysis of diet and physical • 20% of intervention participants regressed to NGR at two years
activity modification interventions • 52% of intervention participants regressed to NGR at six years
Perrault et al., 201269 Educational sessions focused on • NGR was attained once in 23% of lifestyle, 25% of metformin,
reducing body weight by 7% and and 23% of placebo participants
increasing MVPA to ≥ 150 min per week • NGR was attained twice in 18% of lifestyle, 11% of metformin,
and 9% of placebo participants.
• NGT was attained three times in 9% of lifestyle, 4% of
metformin, and 5% of placebo participants
Stefan et al., 201570 Dietary counseling from a dietitian and • 67% of the low-risk phenotype participants regressed to NGR
advice to perform at least three hours of • 31% of high-risk phenotype participants regressed to NGR
moderate-intensity sports per week
Kosaka et al., 200571 Detailed lifestyle modification instructions • 53.8% of participants in intervention group regressed to NGR
every three to four months • 33.9% of participants in control group regressed to NGR
Davy et al., 201772 Resistance training twice a week for • 34% of participants regressed to NGR
three months
Stentz et al., 201673 High-protein diet versus a high- • 100% of participants in the high-protein diet regressed to NGR
carbohydrate diet over six months • 33% of participants in the high-carbohydrate diet regressed to NGR
Ramachandran et al., Monthly in-person advice on physical • 35.7% of participants with isolated IGT regressed to NGR
201076 activity and diet over three years • 20.5% of participants with IGT and IFG regressed to NGR
• 14.1% of participants in control group regressed to NGR
* Abbreviations: MVPA = moderate to vigorous physical activity; A1C = hemoglobin A1c; FPG = fasting plasma glucose; SBP = systolic blood pressure; DBP = diastolic blood
pressure; LDL = low-density lipoprotein cholesterol; HDL = high-density lipoprotein cholesterol; TC = total cholesterol; TG = triglycerides; NGR = normal glucose regulation;
IGT = impaired glucose tolerance; IFG = impaired glucose regulation.
29.4 Components of Effective Lifestyle Interventions Programs 373
Other lifestyle modification interventions focused on physical activity modification) on glucose regulation in
29
reducing T2D risk have found small or null effects in people adults without IGT.66 Specifically, compared to control
with isolated IFG. For instance, the Diabetes Community participants, dietary interventions achieved the larg-
Lifestyle Improvement Program (D-CLIP) implemented est reductions in FPG (-0.17 mmol/L) and body weight
among South Asians found that T2D risk reduction was (-6.21%), followed by interventions combining dietary and
less than half in participants with isolated IFG of what physical activity modification strategies (-0.15 mmol/L
it was in participants with IFG and IGT or with isolated for FPG and -4.12% for body weight).66 Interventions
IGT.77 Similarly, a study from Japan showed individual employing physical activity modification alone achieved
instruction and follow-up support for lifestyle modifica- the smallest effects in FPG (-0.07 mmol/L) and body
tion among Japanese people had a null effect among par- weight (-1.55%).66 A similar pattern was observed for
ticipants with isolated IFG.78 These studies suggest that fasting insulin and for homeostasis model assessment-esti-
lifestyle modification strategies focusing on improving mated insulin resistance (HOMA-IR).66 The Community
insulin action may have limited effect in people whose Guide found that combined diet and physical activity
primary problem is insulin secretion, and that other types interventions increase the likelihood of achieving NGR
of interventions may be needed in these populations.79 and improving T2D and cardiovascular disease risk fac-
A recent review suggests that interventions favorably tors. The Community Guide also found more intensive
affecting adiposity provide the best evidence for slow- interventions achieved greater NGR regression rates than
ing the deterioration of β-cell function.80 Another study less intensive interventions.15 Overall, multicomponent
showed both moderate- and vigorous-intensity structured interventions, including elements of calorie restriction,
exercise training improve β-cell function, though they do physical activity, and behavioral support are most effec-
so through distinct mechanisms, and it is not clear which tive in improving glucose tolerance.66
mechanism is preferable.81 Perhaps more structured and
intensive lifestyle modification programs are needed for
people whose primary defect is insulin secretion. 29.4.2 Weight Loss
Studies testing lifestyle modification interventions suggest
29.4 COMPONENTS OF weight loss and changes in body composition improve glu-
cose regulation and promote regression to NGR. The U.S.
EFFECTIVE LIFESTYLE DPP and the Finnish Diabetes Prevention Study (DPS)
achieved a weight loss of 7% and 5%, respectively,67,82 and
INTERVENTIONS PROGRAMS found weight loss associated with improved insulin sensi-
tivity and β-cell function.83,84 Both studies found that life-
Lifestyle intervention studies suggest that modality, par- style modification interventions reduced T2D incidence by
ticipant behavioral changes, promotion of weight loss, 58%, and this was primarily due to weight loss.85,86 In the
and consequent changes in insulin secretion and action DPP, greater weight loss was also associated with a 34%
each contribute to restoring NGR among high BMI popu- greater likelihood of regressing to NGR, independent of
lations (Figure 29.4). age, gender, race, and baseline glucose levels.68 In another
lifestyle intervention study among Japanese males with
IGT, a two-kg weight loss was associated with a greater
29.4.1 Intervention Modality proportion of patients achieving normoglycemia at the
Meta-analysis data support the use of lifestyle interven- end of the study.71 Finally, progressive resistance train-
tions (diet modification alone and combined diet and ing in people with prediabetes has been found to improve
Figure 29.4 Components of Successful Lifestyle Modification Interventions for Prediabetes Prevention and Management
Converge and Improve Insulin Sensitivity and Secretion.
374 Chapter 29 Lifestyle Medicine and the Management of Prediabetes
participants’ muscle strength, fat-free mass, and meta- per day.82 In the DPP, the lifestyle intervention goals were
bolic status, where each percent point increase in fat-free to reduce body weight by 7% and increase moderate-
mass was associated with an 18% higher odds of being intensity physical activity to ≥ 150 min per week.67 In the
normoglycemic.72 IDPP-1, participants were advised to maintain or increase
Other studies have found no association between moderate-intensity physical activity to least 30 minutes
weight loss and improved glucose regulation. For instance, each day and to decrease total calorie intake, decrease
in a meta-analysis of lifestyle modification in people with- refined carbohydrates and fats intake, avoid consuming
out IGT and a mean BMI of 30.3 kg/m 2 , meta-regression sugar, and consume fiber-rich foods.74 Achieving these
analysis found no association between the magnitude of lifestyle goals was associated with improvements in glu-
percent body weight change and the magnitude of FPG cose regulation and lower T2D risk;85,86,88,89 thus, pro-
change.66 In the IDDP-1, T2D risk was reduced by 28.5% moting weight loss in high BMI populations, increasing
in the lifestyle intervention arm, but without significant physical activity, and improving dietary patterns should
weight reductions. Furthermore, weight loss was not be strategic targets of prediabetes prevention.
associated with reductions in plasma glucose in any of Physical activity involves any bodily movement pro-
the intervention groups.74 Normal weight Asian Indians duced by skeletal muscles that requires energy expenditure.
have been found to be at increased dysglycemia risk due This includes leisure-time physical activity, transportation
to β-cell dysfunction.37,40 This suggests that among low (e.g., walking or cycling), occupational (i.e., work), house-
BMI populations weight loss may not be the most effective hold chores, play, games, and sports or planned exercise
strategy for improving glucose regulation. (see Table 29.2).90 A range of physical activities and inten-
sities are associated with improvements in glucose regula-
tion markers. For instance, moderate-to-vigorous intensity
29.4.3 Changes in Insulin Secretion and physical activity has been linked to enhanced β-cell func-
tion and glucose regulation, independent of weight loss.91
Action Structured exercise training has been found to improve
Improving insulin sensitivity and β-cell function is also β-cell function and insulin sensitivity among people with
important for promoting regression to normoglycemia in prediabetes.81,92 These effects are comparable or superior
people with prediabetes. Large intervention studies such to those achieved with common anti-diabetic drugs.44,92
as the DPP, DPS, and IDPP-1 demonstrated that diet and To achieve these benefits, international guidelines recom-
physical activity modification can improve β-cell func- mend that adults 18 years and older engage in 150 minutes
tion and insulin sensitivity among those with prediabe- of moderate-intensity or 75 minutes of vigorous-intensity
tes.83,84,87 In the DPP, improved β-cell insulin secretion aerobic physical activity (or a combination of these) per
and tissue insulin sensitivity were associated with a 9% week, accumulated in bouts of at least 10 minutes dura-
and 7% greater likelihood of regressing to NGR, respec- tion, with muscle-strengthening activities involving major
tively.68 Participants who achieved normoglycemia during muscle groups performed on two or more days a week.90
DPP were also three times more likely to be normogly- A quarter of the world’s adult population do not meet
cemic during the 5.7-year observation period after inter- these physical activity recommendations,93 and given that
vention completion. This was partially explained by the 6.7% of the global population has prediabetes, 24 strate-
maintenance of improved β-cell function and insulin sensi- gies to increase physical activity are imperative. To pro-
tivity throughout the DPP and throughout the observation mote participation in physical activity or exercise, aiming
period that followed, in which all participants received for gradual increases in quantity and intensity will likely
a less intensive version of the lifestyle intervention.69 In improve adherence and acceptability,94 and programs that
IDPP-1, regression to NGR, which was higher in the life- include both aerobic and resistance exercises can promote
style intervention than in control participants, occurred adherence, probably because they allow participants to
only when insulin sensitivity improved and β-cell function do a variety of exercises.95 Simple tools, like pedometers,
remained normal.87 Although these trials targeted only can also be used to improve physical activity and glucose
individuals with existing prediabetes at baseline, similar levels, as demonstrated in the PREPARE (Pre-diabetes
lifestyle improvements could also imrpove insulin sensi- Risk Education and Physical Activity Recommendation
tivity and β-cell function among those with normal glu- and Encouragement) program.96 However, helping people
cose levels. engage in health-enhancing physical activity will require
approaches that go beyond the traditional individual
focus; it will require multilevel approaches97 that make it
29.4.4 Physical Activity and Diet easier for people to be physically active where they live,
learn, work, play, and pray. Examples of such strategies
Behavior Change include behavioral and social approaches, informational
The most successful lifestyle modification interventions, campaigns, and environmental and policy approaches
such as the DPP, DPS, and IDPP-1, implemented interven- that have been found to be effective at increasing physical
tions aimed at promoting weight loss, improving diet, and activity across various ages, social groups, communities,
increasing physical activity. In the DPS, intervention goals and countries.98
were to achieve a weight reduction of ≥ 5%, reduce total Evidence around the effects of dietary modification on
fat intake to < 30%, reduce saturated fat intake to < 10%, glucose regulation is mainly focused on populations with
increase fiber intake to ≥ 15 g per 1000 kcal, and engage in prediabetes or T2D. Generally, these studies show that
moderate-intensity physical activity for at least 30 minutes decreasing calorie intake and improving diet quality are
29.4 Components of Effective Lifestyle Interventions Programs 375
TABLE 29.2 Physical Activity Definitions According to the World Health Organization 2010
Definition 29
Exercise A physical activity that is planned, structured, repetitive, and purposeful in the sense that the improvement or
maintenance of one or more components of physical fitness is the objective.
Physical An absence of physical activity or exercise. Usually defined as not meeting the international physical activity
Inactivity recommendations.
Physical Activity Any bodily movement produced by skeletal muscles that requires energy expenditure.
Type The mode of participation in physical activity. The type of physical activity can take many forms: aerobic, strength,
flexibility, balance.
Frequency Number of times an exercise or activity is performed. Frequency is generally expressed in sessions, episodes, or
bouts per week.
Duration The length of time in which an activity or exercise is performed. Duration is generally expressed in minutes.
Intensity* Rate at which the activity is being performed or the magnitude of the effort required to perform an activity or
exercise.
• Light: On an absolute scale, light intensity refers to activity that is performed at less than 3.0 times the intensity
of rest. On a scale relative to an individual’s personal capacity, light physical activity is usually less than four on
a scale of 0–10 (e.g., light walking, cooking).
• Moderate: On an absolute scale, moderate intensity refers to activity that is performed at 3.0–5.9 times the
intensity of rest. On a scale relative to an individual’s personal capacity, moderate-intensity physical activity is
usually a five or six on a scale of 0–10 (e.g., brisk walking, bicycling, jogging).
• Vigorous: On an absolute scale, vigorous intensity refers to activity that is performed at 6.0 or more times the
intensity of rest for adults and typically 7.0 or more times for children and youth. On a scale relative to an
individual’s personal capacity, vigorous- intensity physical activity is usually a seven or eight on a scale of 0–10
(e.g., running, swimming, playing soccer).
* Absolute intensity can be determined by the rate of work being performed (e.g., milliliters per kilogram per minute of oxygen consumed), while relative intensity is a percent-
age of an individual’s maximum heart rate or aerobic capacity (VO2max). See reference 90.
important for prediabetes prevention and management. weight loss) results in improvements in glycemic control in
For instance, a prospective analysis of the Whitehall II obese T2D patients.106 Behavioral change is difficult and
cohort showed that the healthy diet, a low-fat diet rich should be supervised gradually over time, starting with
in fiber, reduced the 15-year risk of T2D and death small changes (e.g., eating fried foods only on occasion or
from a coronary event or nonfatal myocardial infarction switching from white to whole-grain breads). However,
compared with the unhealthy diet (full-fat dairy prod- even gradual changes can be difficult if individuals do
ucts, refined grains, processed meats, and fried foods).99 not have the tools to make lasting behavior changes. That
Similarly, the DASH dietary pattern (a low-fat, high fiber is why successful programs, like the DPP and the DPS,
diet rich in vegetables, fruit, and low-fat dairy products) employed proven behavior change techniques (e.g., goal
was inversely associated with T2D risk.100 In the DPS, setting, action planning, and problem solving)107 to equip
consuming a low-fat, high fiber diet had a dose-dependent participants with the self-regulatory skills needed to adopt
effect on sustained weight loss and was also associated and maintain healthy behaviors. In order to change behav-
with reduced T2D risk.101 ior, individuals must have confidence in their ability to
Diets low in saturated fat and high in unsaturated fat, succeed (i.e., self-efficacy), the ability to problem solve and
fruit, vegetable, and fiber intake (e.g., the Mediterranean adapt (i.e., self-regulation), and the tools to overcome bar-
Diet) have also been shown to be beneficial for glucose riers to behavior change. For promoting lifestyle behavior
control for patients with T2D compared to diets with change, helping participants set lifestyle goals, providing
higher contents of simple sugars and carbohydrates.102 information on the health consequences of current behav-
Furthermore, in the PREDIMED-Reus Nutrition interven- iors, and using follow-up prompts and plans have been
tion randomized trial,103 a Mediterranean-style diet (high shown to be effective behavior change techniques.108,109
intake of vegetables, beans, fruits, nuts, fish, and olive oils, Similarly, empathy, nonjudgmental interactions, and spe-
with a low consumption of meat, high-fat dairy products, cific personalized recommendations have been identified
and processed foods) supplemented with extra-virgin olive as essential components of weight loss counseling.110
oil or mixed nuts was associated with a 51–52% lower Social support, such as that provided in group-based
T2D risk than that of a low-fat diet.103 Participants in the weight loss programs or walking groups, is also an effec-
Mediterranean diet groups achieved significant decreases tive tool to help people succeed in changing their behav-
in the prevalence of high FBG.104 In addition, diets ior111 and could be used to help individuals at greatest risk
reduced in glycemic index and glycemic load may also of failing in their attempts at lifestyle change. Research
be useful in helping prevent the development of T2D,105 has indicated that patients with higher BMI, anxiety,
and decreasing intake of simple sugars alone (without depression, or stress might require extra support and
376 Chapter 29 Lifestyle Medicine and the Management of Prediabetes
encouragement to make and sustain behavior changes.112 that better resemble those that could be achieved in the
Finally, lifestyle messages should be culturally appropriate real world. Effectiveness studies can provide evidence of
to improve acceptability and adherence. When people are which lifestyle interventions work, for whom, and under
approached in a culturally sensitive way, they are more which conditions.120
receptive to health messages.113,114 In addition, culturally With this goal in mind, researchers have adapted
appropriate advice can be easier to utilize immediately, proven lifestyle interventions to reduce cost, improve
as participants do not have to modify the advice on their feasibility of delivery, and facilitate implementation in a
own to account for common food and physical activity variety of community settings where heterogeneous pop-
choices in their community. ulations can be reached. For instance, the original DPP
Finally, technology can be used to promote behavior curriculum has been adapted for group-based delivery,
change. For instance, a meta-analysis of mobile health has been offered in YMCAs, churches, primary care clin-
interventions found that smartphone applications can be ics, and other community settings, and has been delivered
used to deliver proven behavior change techniques such by trained staff, physicians, lay community members,
as reminders, remote monitoring, and coaching, achieving and trhough technology-assisted devices (e.g., Internet
moderate improvements in A1C levels in people with dia- and text-messages).121–133 These DPP adapted interven-
betes.115 Another meta-analysis showed that technology- tions have achieved body weight reductions ranging from
delivered interventions (e.g., videos, Web-based resources, -1.9 to -8.7 kg122,123,125,126,128–132,134 and improvements in
telephone-based counseling, and text messaging) can pro- FPG ranging from -2.1 to -9 mm/dL.123,125,129,131,135–137
mote clinically meaningful weight loss and improvements Numerous translational T2D prevention programs
in glycemia in people with prediabetes.116 Internet-based have been tested worldwide, and evidence summaries sup-
strategies and smartphone applications can also be used to port their effectiveness. A meta-analysis of 26 DPP trans-
connect hard-to-reach populations with available preven- lation studies implemented in the United States found that
tion resources.117 Though promising, the expanded use of lifestyle interventions achieved a pooled weight reduction
health technologies to effectively support lifestyle behav- of 4%, regardless of whether the intervention was deliv-
ior change while securely sharing data and protecting pri- ered by healthcare professionals or lay community educa-
vacy is still a work in progress.118 tors.138 Another meta-analysis summarizing the effects of
Overall, lifestyle interventions can improve glucose 22 translation T2D prevention programs from 11 coun-
regulation in people without IGT and can promote regres- tries showed that lifestyle interventions achieved a pooled
sion to NGR among those with prediabetes. Also, lifestyle weight reduction of 2.3 kg, albeit effects varied widely
interventions are likely to have important benefits across across studies.139 Factors associated with heterogeneity in
the full distribution of A1C and fasting glucose and insu- effects included intervention dose (e.g., number of sessions
lin levels.66 However, such interventions may not prevent delivered and adherence to guidelines), intervention deliv-
the development of prediabetes among those with a more ery agent (e.g., healthcare provider, community member),
severe β-cell defect. Therefore, it is vital that these individ- the study design employed, and the length of the follow-up
uals be monitored closely. Furthermore, for these individ- period.138,139 The pooled effect of real-world lifestyle inter-
uals and in those who begin lifestyle change later in their vention studies on prediabetes prevention or regression to
natural history of glucose intolerance, glucose-lowering NGR has not yet been explored.
drugs might be needed earlier to complement the lifestyle Though available evidence comes from T2D preven-
interventions. The American Diabetes Association recom- tion studies, this evidence sheds light on intervention
mends that individuals with prediabetes, especially those strategies that have the potential to prevent or manage
with BMI ≥ 35 kg/m 2 , those aged < 60 years, women with prediabetes and can be implemented across clinical and
prior gestational diabetes mellitus, and/or those with ris- community settings. Indeed several translation studies
ing A1C despite lifestyle intervention, be considered for have adapted T2D prevention strategies in different clini-
treatment with metformin.1 cal settings, demonstrating feasibility and effectiveness
for improving patient lifestyle behaviors.123,130,136,140 –142
Furthermore, a meta-analysis showed that dietary and
29.5 PREVENTING AND MANAGING physical activity counseling for T2D prevention in routine
PREDIABETES IN THE REAL clinical practice is feasible and promotes weight and waist
circumference reductions in patients at risk for prediabe-
WORLD tes or T2D.143 Overall, the evidence supports the effective-
ness and feasibility of T2D prevention programs using
The lifestyle intervention studies discussed above are a variety of delivery formats (e.g., group or individual),
resource intensive and have generally been evaluated in across different implementers (e.g., healthcare profession-
homogeneous populations, implemented in highly con- als and community members), in diverse settings (e.g.,
trolled settings, and often delivered by healthcare profes- clinics, churches, and fitness centers), different interven-
sionals. Effects from these intervention studies are derived tion doses (e.g., number of intervention sessions), and in
from research conducted in optimal conditions (efficacy diverse populations.15,138,139
studies) and may overestimate the actual effects that would Environmental and policy approaches aimed at pro-
be accrued from application of interventions in real-world moting healthy lifestyles have also been implemented on
conditions (effectiveness).119 Effectiveness studies are con- community-wide, state, and national scales. A prominent
ducted in clinical and community settings as part of rou- example is the soda tax introduced in several countries to
tine practice and provide estimates of intervention effects discourage consumption of sugar-sweetened beverages.144
References 377
In the United States, Philadelphia and California have glucose tolerance and to promote regression to normal
29
introduced soda taxes and several cities are currently glucose regulation among those with prediabetes (see the
implementing or planning implementation of similar mea- “Clinical Applications” section). More studies are needed
sures. A 20-year longitudinal U.S. study found that a $1.00 to better understand the effect of lifestyle interventions in
increase in soda price was associated with lower daily different prediabetes phenotypes (i.e. isolated IFG vs iso-
energy intake, lower weight, and lower insulin resistance lated IGT). Interventions that are focused on helping par-
among adults.145 While the impact of the soda tax is still ticipants increase their physical activity and improve their
being evaluated, such policy strategies may represent prom- diets, that promote weight loss (among high BMI indi-
ising approaches to address overconsumption, help reduce viduals), and that achieve improvements in insulin secre-
energy intake, and potentially aid weight loss efforts. tion and action are the most promising. Available evidence
Improving food and physical activity environments is supports the effectiveness of lifestyle modification inter-
another example of real-world community-wide approaches ventions across clinical and community settings, delivery
to promote healthy eating and physical activity. For formats, implementers, and populations. Environmental
instance, availability of good-quality recreational facilities and policy approaches aimed to promote healthy lifestyles
or parks, sidewalks, walking trails, and bike paths can pro- have also been implemented at a community-wide, state,
mote physical activity in adults.146 Indeed, changes in the and national scale, achieving promising results. There
physical environment such as construction of rail-trails and are numerous opportunities for healthcare professionals,
policy accommodating pedestrians and bicyclists in streets communities, and healthcare systems to work together
was found to promote active transportation in a U.S. city.147 and provide individuals with the education, support, and
Efforts aimed at changing the food environment have also opportunities they need to maintain healthy lives, sustain
been tested. For instance, interventions in prepared-food normal glucose metabolism, promote regression from pre-
sources (e.g., introducing labeling and healthy menus) and diabetes to normal glucose metabolism, and prevent or
in small neighborhood stores (e.g., increasing the availability delay progression from prediabetes to T2D.
of healthy foods and point-of-purchase promotions) show
promising results in awareness and diet behavior.148,149
Finally, proven T2D prevention programs have been CLINICAL APPLICATIONS
implemented to scale in the United States. For instance,
the U.S. DPP has been rolled out as a national program • Prediabetes awareness on the part of patients and
and is being offered in different community settings such healthcare professionals should be improved to
as YMCAs. The program is based on the proven DPP cur- decrease downstream economic costs, morbidity,
riculum and includes 16 group educational sessions with and decreased quality of life; mortality from dysgly-
monthly follow-up delivered by trained lifestyle coaches.150 cemia-based chronic disease; and diabetes-related
Medicare also joined these efforts and now offers struc- complications, especially cardiovascular disease.
tured lifestyle modification intervention among Medicare • Prediabetes screening and aggressive case finding, as
beneficiaries diagnosed with prediabetes.151 Similarly, the part of routine clinical practice, should be performed
Veterans Health Administration healthcare system intro- as early as possible. This can be done through tar-
duced MOVE!, the largest T2D prevention program imple- geted screening: that is, using risk scores to identity
mented in a U.S. healthcare system. The program consists those who should undergo formal glucose testing.
of interactive educational sessions on nutrition, physical • Diagnostic criteria for prediabetes include fasting
activity, self-management, and goal setting, and is offered plasma glucose 100–125 mg/dl, two-hour post-chal-
to patients with overweight/obesity and a weight-related lenge plasma glucose 140–199 mg/dl, and hemoglo-
disorder. Participation in this program is associated with bin A1c 5.7–6.4%.
weight loss and reduced T2D incidence.152 • Lifestyle modification interventions that employ
proven behavior change techniques for improving
dietary and physical activity behaviors, and pro-
29.6 CONCLUSIONS mote weight loss in high BMI populations, are effec-
tive for reversing and managing prediabetes.
Prediabetes is an economically costly health problem and a • As recommended in diabetes care guidelines, cli-
major contributor to morbidity and mortality worldwide. nicians should identify patients with prediabetes
Lifestyle intervention programs are promising strategies and refer them to trusted lifestyle programs in the
to improve glucose regulation among people with normal community.
REFERENCES
1. American Diabetes Association. Standards 3. Nathan DM, Davidson MB, DeFronzo medicine and the politics. BMJ 2014;349.
of medical care in diabetes – 2017. Diabetes RA, Heine RJ, Henry RR, Pratley R, PMC4707710. https://www.bmj.com/
Care 2017;40(Supplement 1):S4–S132. Zinman B, and American Diabetes content/349/bmj.g4485.long
2. World Health Organization. About Association. Impaired fasting glu- 5. Levitan EB, Song Y, Ford ES, and Liu
Diabetes: Intermediate States of cose and impaired glucose tolerance: S. Is nondiabetic hyperglycemia a risk
Hyperglycemia, 1999. Available at http:// Implications for care. Diabetes Care factor for cardiovascular disease? A
www.who.i nt/diabetes/action_ online /bas 2007;30(3):753–759. meta-analysis of prospective stud-
ics/en /index2.ht ml. Accessed on October 4. Yudkin JS and Montori VM. The ies. Archives of Internal Medicine
6, 2017. epidemic of pre-diabetes: The 2004;164(19):2147–2155.
378 Chapter 29 Lifestyle Medicine and the Management of Prediabetes
6. Brunner EJ, Shipley MJ, Witte DR, Fuller D, Fonseca VA, Garber JR, Garvey WT, www.idf.org/diabetesatlas/5e/previous-
JH, and Marmot MG. Relation between Grunberger G, Handelsman Y, Hirsch editions
blood glucose and coronary mortality IB, Jellinger PS, McGill JB, Mechanick 30. Centers for Disease Control and
over 33 years in the Whitehall study. JI, Rosenblit PD, and Umpierrez GE. Prevention. National Diabetes Statistics
Diabetes Care 2006;29(1):26–31. Consensus statement by the American Report, 2017. Atlanta, GA: Centers for
7. Gerstein HC, Santaguida P, Raina P, Association of clinical endocrinolo- Disease Control and Prevention, U.S. Dept
Morrison KM, Balion C, Hunt D, Yazdi gists and American College of endo- of Health and Human Services, 2017.
H, and Booker L. Annual incidence and crinology on the comprehensive type 2 31. Cowie CC, Rust KF, Ford ES, Eberhardt
relative risk of diabetes in people with diabetes management algorithm – 2017 MS, Byrd-Holt DD, Li C, Williams DE,
various categories of dysglycemia: A Executive summary. Endocrine Practice Gregg EW, Bainbridge KE, Saydah SH,
systematic overview and meta-analysis of 2017;23(2):207–238. and Geiss LS. Full accounting of diabetes
prospective studies. Diabetes Research 18. Shepherd PR and Kahn BB. Glucose and pre-diabetes in the U.S. population
and Clinical Practice 2007;78(3):305– transporters and insulin action – in 1988–1994 and 2005–2006. Diabetes
312. PMID: 17601626. Implications for insulin resistance and Care 2009;32(2):287–294.
8. Tabák AG, Herder C, Rathmann diabetes mellitus. New England Journal 32. DECODE Study Group. Age- and
W, Brunner EJ, Kivimäki M, and of Medicine 1999;341(4):248–257. sex-specific prevalences of diabetes
Prediabetes: A high-risk state for 19. Schulz LO, Bennett PH, Ravussin E, and impaired glucose regulation in
developing diabetes. The Lancet Kidd JR, Kidd KK, Esparza J, and 13 European cohorts. Diabetes Care
2012;379(9833):2279–2290. Valencia ME. Effects of traditional and 2003;26(1):61–69.
9. Dall TM, Yang W, Halder P, Pang B, western environments on prevalence 33. Lee LT, Alexandrov AW, Howard VJ,
Massoudi M, Wintfeld N, Semilla AP, of type 2 diabetes in Pima Indians in Kabagambe EK, Hess MA, McLain
Franz J, and Hogan PF. The economic Mexico and the U.S. Diabetes Care RM, Safford MM, and Howard G.
burden of elevated blood glucose levels 2006;29(8):1866–1871. Race, regionality and pre-diabetes in
in 2012: Diagnosed and undiagnosed 20. Abdul-Ghani MA and DeFronzo RA. the Reasons for Geographic and Racial
diabetes, gestational diabetes mel- Pathophysiology of prediabetes. Current Differences in Stroke (REGARDS) study.
litus, and prediabetes. Diabetes Care Diabetes Reports 2009;9:193–199. Preventive Medicine 2014;63:43–47.
2014;37(12):3172–3179. 21. The Emerging Risk Factors 34. Gujral UP, Narayan KMV, Kahn SE,
10. Cefalu WT, Petersen MP, and Ratner Collaboration. Glycated hemoglo- and Kanaya AM. The relative asso-
RE. The alarming and rising costs of dia- bin measurement and prediction ciations of β-cell function and insulin
betes and prediabetes: A call for action! of cardiovascular disease. JAMA sensitivity with glycemic status and
Diabetes Care 2014;37(12):3137–3138. 2014;311(12):1225–1233. incident glycemic progression in migrant
11. Stevens JW, Khunti K, Harvey R, 22. The Emerging Risk Factors Asian Indians in the United States: The
Johnson M, Preston L, Woods HB, Collaboration. Diabetes mellitus, fast- MASALA study. Journal of Diabetes and
Davies M, and Goyder E. Preventing the ing glucose, and risk of cause-specific its Complications 2014;28(1):45–50.
progression to type 2 diabetes mellitus in death. New England Journal of Medicine 35. Edelstein SL, Knowler WC, Bain RP,
adults at high risk: A systematic review 2011;364(9):829–841. Andres R, Barrett-Connor EL, Dowse
and network meta-analysis of lifestyle, 23. Unwin N, Shaw J, Zimmet P, and Alberti GK, Haffner SM, Pettitt DJ, Sorkin JD,
pharmacological and surgical interven- KG. Impaired glucose tolerance and Muller DC, Collins VR, and Hamman
tions. Diabetes Research and Clinical impaired fasting glycaemia: The current RF. Predictors of progression from
Practice 2015;107(3):320–331. status on definition and intervention. impaired glucose tolerance to NIDDM:
12. Yuen A, Sugeng Y, Weiland TJ, and Diabetic Medicine 2002;19(9):708–723. An analysis of six prospective studies.
Jelinek GA. Lifestyle and medication 24. International Diabetes Federation. Diabetes 1997;46(4):701–710. 2517225.
interventions for the prevention or delay IDF Diabetes Atlas, 7th edition, 2015. 36. Stefan N, Fritsche A, Schick F, and
of type 2 diabetes mellitus in prediabe- Available at http://www.idf.org/diabetes- Häring H-U. Phenotypes of prediabetes
tes: A systematic review of randomised atlas. Accessed on September 25, 2017. and stratification of cardiometabolic risk.
controlled trials. Australian and New 25. Anjana RM, Pradeepa R, Deepa M, The Lancet Diabetes and Endocrinology
Zealand Journal of Public Health Datta M, Sudha V, Unnikrishnan R, 2016;4(9):789–798.
2010;34(2):172–178. Bhansali A, Joshi SR, Joshi PP, Yajnik 37. Sattar N and Gill JM. Type 2 diabetes
13. Merlotti C, Morabito A, and Pontiroli CS, Dhandhania VK, Nath LM, Das in migrant south Asians: Mechanisms,
AE. Prevention of type 2 diabetes: A AK, Rao PV, Madhu SV, Shukla DK, mitigation, and management. The
systematic review and meta-analysis Kaur T, Priya M, Nirmal E, Parvathi SJ, Lancet Diabetes and Endocrinology
of different intervention strategies. Subhashini S, Subashini R, Ali MK, and 2015;3(12):1004–1016.
Diabetes, Obesesity and Metabolism Mohan V. Prevalence of diabetes and 38. Ikehara S, Tabák AG, Akbaraly TN,
2014;16(8):719–727. prediabetes (impaired fasting glucose Hulmán A, Kivimäki M, Forouhi NG,
14. Haw JS, Galaviz KI, Straus AN, Magee and/or impaired glucose tolerance) in Iso H, and Brunner EJ. Age trajecto-
MJ, Weber MB, Wei J, Kowalski AJ, urban and rural India: Phase I results of ries of glycaemic traits in non-diabetic
Narayan KMV, and Ali MK. Long-term the Indian Council of Medical Research – south Asian and white individuals: The
sustainability of diabetes prevention INdia DIABetes (ICMR–INDIAB) study. whitehall II cohort study. Diabetologia
approaches: A meta-analysis of random- Diabetologia 2011;54(12):3022–3027. 2015;58:534–542.
ized controlled trials. JAMA Internal 26. Yang W, Lu J, Weng J, Jia W, Ji L, Xiao 39. Staimez LR, Deepa M, Ali MK, Mohan
Medicine 2017;177(12):1808–1817. J, Shan Z, Liu J, Tian H, Ji Q, Zhu D, Ge V, Narayan KM, and Hanson RL. The
doi: 10.1001/jamainternmed.2017.6040 J, Lin L, Chen L, Guo X, Zhao Z, Li Q, tale of two Indians: A comparison of
15. Balk EM, Earley A, Raman G, Avendano Zhou Z, Shan G, and He J. Prevalence beta-cell function and insulin resistance
EA, Pittas AG, and Remington PL. of diabetes among men and women in between Pima Indians and Asian Indians
Combined diet and physical activity China. New England Journal of Medicine [Abstract]. Diabetes 2014;63(Suppl.
promotion programs to prevent type 2 2010;362(12):1090–1101. 1):A400.
diabetes among persons at increased risk: 27. Abdul-Ghani MA, Tripathy D, and 40. Kanaya AM, Herrington D, Vittinghoff
A systematic review for the community Defronzo RA. Contributions of B-cell E, Ewing SK, Liu K, Blaha MJ, Dave
preventive services task force. Annals of dysfunction and insulin resistance to SS, Qureshi F, and Kandula NR.
Internal Medicine 2015;163(6):437–451. the pathogenesis of impaired glucose Understanding the high prevalence of dia-
PMC4692590 tolerance and impaired fasting glucose. betes in U.S. south Asians compared with
16. Phung OJ, Baker WL, Tongbram V, Diabetes Care 2006;29:1130–1139. four racial/ethnic groups: The MASALA
Bhardwaj A, and Coleman CI. Oral 28. Jaacks LM, Siegel KR, Gujral UP, and and MESA studies. Diabetes Care
antidiabetic drugs and regression from Narayan KM. Type 2 diabetes: A 21st 2014;37(6):1621–1628. PMC4030091.
prediabetes to normoglycemia: A meta- century epidemic. Best Practice & 41. Ferrannini E, Gastaldelli A, and Iozzo
analysis. Annals of Pharmacotherapy Research Clinical Endocrinology & P. Pathophysiology of prediabetes.
2012;46(4):469–476. Metabolism 2016;30(3):331–343. Medical Clinics of North America
17. Garber AJ, Abrahamson MJ, Barzilay JI, 29. International Diabetes Federation. 2011;95(2):327–339.
Blonde L, Bloomgarden ZT, Bush MA, Diabetes Atlas, 2nd, 3rd, 4th editions. 42. Amati F, Dube JJ, Coen PM, Stefanovic-
Dagogo-Jack S, DeFronzo RA, Einhorn 2003, 2006, 2009. Available at http:// Racic M, Toledo FG, and Goodpaster
References 379
BH. Physical inactivity and obesity 58. Sato Y, Nagasaki M, Nakai N, and intervention: A Japanese trial in IGT
underlie the insulin resistance of aging. Fushimi T. Physical exercise improves males. Diabetes Research and Clinical
43.
Diabetes Care 2009;32(8):1547–1549.
Barres R and Zierath JR. The role of
diet and exercise in the transgenera-
glucose metabolism in lifestyle-related
diseases. Experimental Biology and
Medicine 2003;228(10):1208–1212.
72.
Practice 2005;67(2):152–162.
Davy BM, Winett RA, Savla J, Marinik
EL, Baugh ME, Flack KD, Halliday TM,
29
tional epigenetic landscape of T2DM. 59. Simpson KA and Singh MA. Effects of Kelleher SA, Winett SG, Williams DM,
Nature Reviews Endocrinology exercise on adiponectin: A systematic and Boshra S. Resist diabetes: A random-
2016;12(8):441–451. review. Obesity 2008;16(2):241–256. ized clinical trial for resistance training
44. Fiuza-Luces C, Garatachea N, Berger 60. Berg AH and Scherer PE. Adipose maintenance in adults with prediabetes.
NA, and Lucia A. Exercise is the real tissue, inflammation, and cardiovas- PLoS One 2017;12(2):e0172610.
polypill. Physiology 2013;28(5):330–358. cular disease. Circulation Research 73. Stentz FB, Brewer A, Wan J, Garber C,
45. Engeda J, Mezuk B, Ratliff S, and Ning 2005;96(9):939–949. Daniels B, Sands C, and Kitabchi AE.
Y. Association between duration and 61. Kawano J and Arora R. The role Remission of pre-diabetes to normal
quality of sleep and the risk of pre-diabe- of adiponectin in obesity, diabetes, glucose tolerance in obese adults with
tes: Evidence from NHANES. Diabetic and cardiovascular disease. Journal high protein versus high carbohy-
Medicine 2013;30(6):676–680. of the CardioMetabolic Syndrome drate diet: Randomized control trial.
46. Piatti P, Setola E, Galluccio E, Costa 2009;4(1):44–49. BMJ Open Diabetes Research care
S, Fontana B, Stuccillo M, Crippa V, 62. Goodyear LJ and Kahn BB. Exercise, 2016;4(1):e000258.
Cappelletti A, Margonato A, Bosi E, glucose transport, and insulin sensi- 74. Ramachandran A, Snehalatha C, Mary
and Monti LD. Smoking is associated tivity. Annual Review of Medicine S, Mukesh B, Bhaskar AD, Vijay V, and
with impaired glucose regulation and 1998;49:235–261. Indian Diabetes Prevention Programme.
a decrease in insulin sensitivity and the 63. Butler AE, Janson J, Bonner-Weir S, The Indian diabetes prevention pro-
disposition index in first-degree relatives Ritzel R, Rizza RA, and Butler PC. gramme shows that lifestyle modification
of type 2 diabetes subjects independently Beta-cell deficit and increased beta-cell and metformin prevent type 2 diabetes
of the presence of metabolic syndrome. apoptosis in humans with type 2 diabetes. in Asian Indian subjects with impaired
Acta Diabetologica 2014;51(5):793–799. Diabetes 2003;52(1):102–110. glucose tolerance (IDPP-1). Diabetologia
47. Cullmann M, Hilding A, and Ostenson 64. Beaudry JL and Riddell MC. Effects of 2006;49(2):289–297.
CG. Alcohol consumption and risk of glucocorticoids and exercise on pancre- 75. Ramachandran A, Snehalatha C, Mary
pre-diabetes and type 2 diabetes develop- atic beta-cell function and diabetes devel- S, Selvam S, Kumar CK, Seeli AC, and
ment in a Swedish population. Diabetic opment. Diabetes Metabolism Research Shetty AS. Pioglitazone does not enhance
Medicine 2012;29(4):441–452. Reviews 2012;28(7):560–573. the effectiveness of lifestyle modification
48. Kahn SE, Hull RL, and Utzschneider 65. Zhang X, Devlin HM, Smith B, in preventing conversion of impaired
KM. Mechanisms linking obesity to insu- Imperatore G, Thomas W, Lobelo F, Ali glucose tolerance to diabetes in Asian
lin resistance and type 2 diabetes. Nature MK, Norris K, Gruss S, Bardenheier B, Indians: Results of the Indian Diabetes
2006;444(7121):840–846. Cho P, Garcia de Quevedo I, Mudaliar Prevention Programme-2 (IDPP-2).
49. Furukawa S, Fujita T, Shimabukuro U, Jones CD, Durthaler JM, Saaddine J, Diabetologia 2009;52(6):1019–1026.
M, Iwaki M, Yamada Y, Nakajima Y, Geiss LS, and Gregg EW. Effect of life- 76. Ramachandran A, Arun N, Shetty AS, and
Nakayama O, Makishima M, Matsuda style interventions on cardiovascular risk Snehalatha C. Efficacy of primary preven-
M, and Shimomura I. Increased oxidative factors among adults without impaired tion interventions when fasting and post-
stress in obesity and its impact on metabolic glucose tolerance or diabetes: A system- glucose dysglycemia coexist: Analysis of the
syndrome. Journal of Clinical Investigation atic review and meta-analysis. PLoS One Indian Diabetes Prevention Programmes
2004;114(12):1752–1761. 535065. 2017;12(5):e0176436. (IDPP-1 and IDPP-2). Diabetes Care
50. Erion DM and Shulman GI. 66. Zhang X, Imperatore G, Thomas W, 2010;33(10):2164–2168. PMC2945153.
Diacylglycerol-mediated insu- Cheng YJ, Lobelo F, Norris K, Devlin 77. Weber MB, Ranjani H, Staimez LR,
lin resistance. Nature Medicine HM, Ali MK, Gruss S, Bardenheier B, Anjana RM, Ali MK, Narayan KM,
2010;16(4):400–402. Cho P, Garcia de Quevedo I, Mudaliar and Mohan V. The stepwise approach
51. Samuel VT, Petersen KF, and Shulman U, Saaddine J, Geiss LS, and Gregg to diabetes prevention: Results from the
GI. Lipid-induced insulin resistance: EW. Effect of lifestyle interventions on D-CLIP randomized controlled trial.
Unravelling the mechanism. Lancet glucose regulation among adults without Diabetes Care 2016;39(10):1760–1767.
2010;375(9733):2267–2277. 2995547. impaired glucose tolerance or diabetes: PMC5033082.
52. Boden G. Role of fatty acids in the patho- A systematic review and meta-analysis. 78. Saito T, Watanabe M, Nishida J, Izumi
genesis of insulin resistance and NIDDM. Diabetes Research and Clinical Practice T, Omura M, Takagi T, Fukunaga R,
Diabetes 1997;46(1):3–10. 2017;123:149–164. Bandai Y, Tajima N, Nakamura Y, Ito M,
53. Randle PJ, Garland PB, Hales CN, and 67. Diabetes Prevention Program Research and Zensharen Study for Prevention of
Newsholme EA. The glucose fatty-acid Group. Reduction in the incidence of Lifestyle Diseases Group. Lifestyle modi-
cycle. Its role in insulin sensitivity and the type 2 diabetes with lifestyle intervention fication and prevention of type 2 diabetes
metabolic disturbances of diabetes mel- or metformin. New England Journal of in overweight Japanese with impaired
litus. Lancet 1963;1(7285):785–789. Medicine 2002;346(6):393–403. fasting glucose levels: A randomized
54. Trolice MP. Defining prediabetes in poly- 68. Perreault L, Kahn SE, Christophi controlled trial. Archives of Internal
cystic ovarian syndrome. Open Journal of CA, Knowler WC, and Hamman RF, Medicine 2011;171(15):1352–1360.
Obstetrics and Gynecology 2011;1:36–41. Diabetes prevention program research 79. Narayan KMV. Type 2 diabetes: Why
55. Dunaif A, Segal KR, Shelley DR, group. Regression from pre-diabetes to we are winning the battle but losing the
Green G, Dobrjansky A, and Licholai normal glucose regulation in the diabetes war? 2015 Kelly West Award Lecture.
T. Evidence for distinctive and intrin- prevention program. Diabetes Care Diabetes Care 2016;39:653–663.
sic defects in insulin action in poly- 2009;32(9):1583–1588. PMC2732165. 80. Page KA and Reisman T. Interventions
cystic ovary syndrome. Diabetes 69. Perreault L, Pan Q, Mather KJ, Watson to preserve beta-cell function in the
1992;41(10):1257–1266. KE, Hamman RF, and Kahn SE. Effect management and prevention of type
56. Schenk S and Horowitz JF. Acute exercise of regression from prediabetes to normal 2 diabetes. Current Diabetes Reports
increases triglyceride synthesis in skeletal glucose regulation on long-term reduction 2013;13(2):252–260.
muscle and prevents fatty acid-induced in diabetes risk: Results from the diabetes 81. Slentz CA, Tanner CJ, Bateman LA,
insulin resistance. Journal of Clinical prevention program outcomes study. The Durheim MT, Huffman KM, Houmard
Investigation 2007;117(6):1690–1698. Lancet 2012;379(9833):2243–2251. JA, and Kraus WE. Effects of exer-
1866251. 70. Stefan N, Staiger H, Wagner R, Machann cise training intensity on pancreatic
57. Lund S, Holman GD, Schmitz O, and J, Schick F, Haring HU, and Fritsche A. beta-cell function. Diabetes Care
Pedersen O. Contraction stimulates trans- A high-risk phenotype associates with 2009;32(10):1807–1811. 2752909.
location of glucose transporter GLUT4 reduced improvement in glycaemia during 82. Tuomilehto J, Lindström J, Eriksson
in skeletal muscle through a mechanism a lifestyle intervention in prediabetes. JG, Valle TT, Hämäläinen H, Ilanne-
distinct from that of insulin. Proceedings Diabetologia 2015;58(12):2877–2884. Parikka P, Keinänen-Kiukaanniemi
of the National Academy of Sciences 71. Kosaka K, Noda M, and Kuzuya T. S, Laakso M, Louheranta A, Rastas
USA 1995;92(13):5817–5821. 41592. Prevention of type 2 diabetes by lifestyle M, Salminen V, Aunola S, Cepaitis Z,
380 Chapter 29 Lifestyle Medicine and the Management of Prediabetes
Moltchanov V, Hakumäki M, Mannelin metformin on insulin sensitivity in indi- Lamuela-Raventos RM, Serra-Majem L,
M, Martikkala V, Sundvall J, and viduals with prediabetes. Diabetes Care Pintó X, Basora J, Sorlí JV, Salas-Salvadó
Uusitupa M. Prevention of type 2 diabe- 2012;35(1):131–136. 3241331. J, and Investigators ftPS. Mediterranean
tes mellitus by changes in lifestyle among 93. World Health Organization. Global diets and metabolic syndrome status
subjects with impaired glucose toler- Health Observatory (GHO) Data. in the PREDIMED randomized trial.
ance. New England Journal of Medicine Prevalence of Insufficient Physical Canadian Medical Association Journal
2001;344(18):1343–1350. Activity. Available at http://www.who. 2014;186(17):E649–57. doi: 10.1503/
83. The Diabetes Prevention Program int/gho/ncd /risk _factors/physical_ac tivi cmaj.140764
Research Group. Role of insulin ty_tex t/en/. Accessed on October 4, 2017. 105. Willett W, Manson J, and Liu S.
secretion and sensitivity in the evolu- 2010. Glycemic index, glycemic load, and
tion of type 2 diabetes in the diabetes 94. Praet SF, van Rooij ES, Wijtvliet A, risk of type 2 diabetes. The American
prevention program: Effects of lifestyle Boonman-de Winter LJ, Enneking T, Journal of Clinical Nutrition
intervention and metformin. Diabetes Kuipers H, Stehouwer CD, and van Loon 2002;76(1):274S–280S.
2005;54(8):2404–2414. LJ. Brisk walking compared with an 106. Ziemer DC, Berkowitz KJ, Panayioto
84. de Mello VD, Lindstrom J, Eriksson individualised medical fitness programme RM, El-Kebbi IM, Musey VC, Anderson
J, Ilanne-Parikka P, Keinanen- for patients with type 2 diabetes: A LA, Wanko NS, Fowke ML, Brazier
Kiukaanniemi S, Sundvall J, Laakso randomised controlled trial. Diabetologia CW, Dunbar VG, Slocum W, Bacha
M, Tuomilehto J, and Uusitupa M. 2008;51(5):736–746. GM, Gallina DL, Cook CB, and Phillips
Insulin secretion and its determinants 95. Praet SF and van Loon LJ. Exercise: LS. A simple meal plan emphasizing
in the progression of impaired glucose The brittle cornerstone of type 2 healthy food choices is as effective as
tolerance to type 2 diabetes in impaired diabetes treatment. Diabetologia an exchange-based meal plan for urban
glucose-tolerant individuals: The finnish 2008;51(3):398–401. African Americans with type 2 diabetes.
diabetes prevention study. Diabetes Care 96. Yates T, Davies M, Gorely T, Bull F, and Diabetes Care 2003;26(6):1719–1724.
2012;35(2):211–217. PMC3263888. Khunti K. Effectiveness of a pragmatic 107. Michie S, Ashford S, Sniehotta FF,
85. Fujimoto WY, Jablonski KA, Bray GA, education program designed to promote Dombrowski SU, Bishop A, and French
Kriska A, Barrett-Connor E, Haffner S, walking activity in individuals with DP. A refined taxonomy of behaviour
Hanson R, Hill JO, Hubbard V, Stamm impaired glucose tolerance: A random- change techniques to help people change
E, and Pi-Sunyer FX. Body size and shape ized controlled trial. Diabetes Care their physical activity and healthy
changes and the risk of diabetes in the 2009;32(8):1404–1410. eating behaviours: The CALO-RE
diabetes prevention program. Diabetes 97. Pratt M, Perez LG, Goenka S, Brownson taxonomy. Psychology & Health
2007;56(6):1680–1685. RC, Bauman A, Sarmiento OL, and 2011;26(11):1479–1498.
86. Laaksonen DE, Lindstrom J, Lakka TA, Hallal PC. Can population levels of 108. Sanchez A, Bully P, Martinez C, and
Eriksson JG, Niskanen L, Wikstrom K, physical activity be increased? Global Grandes G. Effectiveness of physi-
Aunola S, Keinanen-Kiukaanniemi S, evidence and experience. Progress in cal activity promotion interventions
Laakso M, Valle TT, Ilanne-Parikka P, Cardiovascular Diseases 2015;57(4):356– in primary care: A review of reviews.
Louheranta A, Hamalainen H, Rastas M, 367. PMC4749397. Preventive Medicine 2015;76:S56–67.
Salminen V, Cepaitis Z, Hakumaki M, 98. Heath GW, Parra DC, Sarmiento OL, doi: 10.1016/j.ypmed.2014.09.012
Kaikkonen H, Harkonen P, Sundvall J, Andersen LB, Owen N, Goenka S, 109. Artinian NT, Fletcher GF, Mozaffarian
Tuomilehto J, and Uusitupa M. Physical Montes F, and Brownson RC. Evidence- D, Kris-Etherton P, Van Horn L,
activity in the prevention of type 2 based intervention in physical activity: Lichtenstein AH, Kumanyika S, Kraus
diabetes: The Finnish diabetes prevention Lessons from around the world. The WE, Fleg JL, Redeker NS, Meininger JC,
study. Diabetes 2005;54(1):158–165. Lancet 2012;380(9838):272–281. Banks J, Stuart-Shor EM, Fletcher BJ,
87. Snehalatha C, Mary S, Selvam S, Sathish 99. Brunner EJ, Mosdol A, Witte DR, Miller TD, Hughes S, Braun LT, Kopin
Kumar CK, Shetty SB, Nanditha A, Martikainen P, Stafford M, Shipley LA, Berra K, Hayman LL, Ewing LJ,
and Ramachandran A. Changes in MJ, and Marmot MG. Dietary pat- Ades PA, Durstine JL, Houston-Miller N,
insulin secretion and insulin sensitivity terns and 15-y risks of major coronary and Burke LE. Interventions to promote
in relation to the glycemic outcomes in events, diabetes, and mortality. The physical activity and dietary lifestyle
subjects with impaired glucose toler- American Journal of Clinical Nutrition changes for cardiovascular risk factor
ance in the Indian Diabetes Prevention 2008;87(5):1414–1421. reduction in adults: A scientific statement
Programme-1 (IDPP-1). Diabetes Care 100. Liese AD, Nichols M, Sun X, D’Agostino from the American Heart Association.
2009;32(10):1796–1801. PMC2752907. RB, Jr, and Haffner SM. Adherence to the Circulation 2010;122(4):406–441.
88. Roumen C, Blaak EE, and Corpeleijn DASH diet is inversely associated with 110. Rao G, Burke LE, Spring BJ, Ewing LJ,
E. Lifestyle intervention for prevention incidence of type 2 diabetes: The insulin Turk M, Lichtenstein AH, Cornier M-A,
of diabetes: Determinants of success resistance atherosclerosis study. Diabetes Spence JD, and Coons M. New and
for future implementation. Nutrition Care 2009;32(8):1434–1436. emerging weight management strategies
Reviews 2009;67(3):132–146. 101. Lindstrom J, Peltonen M, Eriksson JG, for busy ambulatory settings: A scientific
89. Lindstrom J, Louheranta A, Mannelin Louheranta A, Fogelholm M, Uusitupa statement from the American Heart
M, Rastas M, Salminen V, Eriksson M, and Tuomilehto J. High-fibre, Association endorsed by the society
J, Uusitupa M, and Tuomilehto J. The low-fat diet predicts long-term weight of behavioral medicine. Circulation
Finnish Diabetes Prevention Study (DPS): loss and decreased type 2 diabetes risk: 2011;124(10):1182–1203.
Lifestyle intervention and 3-year results The Finnish diabetes prevention study. 111. Jonnalagadda SS and Diwan S. Health
on diet and physical activity. Diabetes Diabetologia 2006;49(5):912–920. behaviors, chronic disease prevalence
Care 2003;26(12):3230–3236. 102. Garg A. High-monounsaturated-fat and self-rated health of older Asian
90. World Health Organization. Global diets for patients with diabetes mel- Indian immigrants in the U.S. Journal
Recommendations on Physical Activity litus: A meta-analysis. The American of Immigrant and Minority Health
for Health, 2010. Available at http:// Journal of Clinical Nutrition 1998;67(3 2005;7(2):75–83.
whqlibdoc.who.int/publications/2010/97 Suppl):577S–582S. 112. Delahanty LM, Conroy MB, and Nathan
89241599979_eng.pdf?ua=1. Accessed on 103. Estruch R, Ros E, Salas-Salvadó J, Covas DM. Psychological predictors of physical
October 4, 2017. MI, Corella D, Arós F, Gómez-Gracia activity in the diabetes prevention pro-
91. Chen Z, Black MH, Watanabe RM, E, Ruiz-Gutiérrez V, Fiol M, Lapetra J, gram. Journal of the American Dietetic
Trigo E, Takayanagi M, Lawrence JM, and Lamuela-Raventos RM. Primary Association 2006;106(5):698–705.
Buchanan TA, and Xiang AH. Self- prevention of cardiovascular disease with 113. Bhopal RS. The inter-relationship of folk,
reported physical activity is associ- a mediterranean diet supplemented with traditional and western medicine within
ated with b-cell function in Mexican extra-virgin olive oil or nuts. New England an Asian community in Britain. Social
American adults. Diabetes Care Journal of Medicine 2018;378:e34. Science & Medicine 1986;22(1):99–105.
2013;36:638–644. 104. Babio N, Toledo E, Estruch R, Ros E, 114. Pardhan S and Mahomed I. Knowledge,
92. Malin SK, Gerber R, Chipkin SR, Martínez-González MA, Castañer O, self-help and socioeconomic factors in
and Braun B. Independent and com- Bulló M, Corella D, Arós F, Gómez-Gracia South Asian and Caucasian diabetic
bined effects of exercise training and E, Ruiz-Gutiérrez V, Fiol M, Lapetra J, patients. Eye 2004;18(5):509–513.
References 381
115. Cui M, Wu X, Mao J, Wang X, and churches. Health Education Research 139. Dunkley AJ, Bodicoat DH, Greaves
Nie M. T2DM self-management via 2010;25(2):306–315. CJ, Russell C, Yates T, Davies MJ, and
smartphone applications: A systematic
review and meta-analysis. PLoS One
2016;11(11):e0166718.
128. Islam NS, Zanowiak JM, Wyatt LC,
Kavathe R, Singh H, Kwon SC, and
Trinh-Shevrin C. Diabetes prevention
Khunti K. Diabetes prevention in the real
world: Effectiveness of pragmatic lifestyle
interventions for the prevention of type 2
29
116. Bian RR, Piatt GA, Sen A, Plegue MA, De in the New York City Sikh Asian Indian diabetes and of the impact of adherence
Michele ML, Hafez D, Czuhajewski CM, community: A pilot study. International to guideline recommendations: A system-
Buis LR, Kaufman N, and Richardson CR. Journal of Environmental Research and atic review and meta-analysis. Diabetes
The effect of technology-mediated diabetes Public Health 2014;11(5):5462–5486. Care 2014;37(4):922–933.
prevention interventions on weight: A PMC4053907. 140. Ma J, Yank V, Xiao L, Lavori PW, Wilson
meta-analysis. Journal of Medical Internet 129. Ma J, Yank V, Xiao L, Lavori PW, SR, Rosas LG, and Stafford RS. Translating
Research 2017;19(3):e76. PMC5387112. Wilson SR, Rosas LG, and Stafford the diabetes prevention program lifestyle
117. Hunt CW. Technology and diabe- RS. Translating the diabetes prevention intervention for weight loss into primary
tes self-management: An integrative program lifestyle intervention for weight care: A randomized trial. JAMA Internal
review. World Journal of Diabetes loss into primary care: A random- Medicine 2013;173(2):113–121.
2015;6(2):225–233. ized trial. JAMA Internal Medicine 141. Endevelt R, Peled R, Azrad A, Kowen G,
118. Singh K, Drouin K, Newmark LP, 2013;173(2):113–121. Valinsky L, and Heymann AD. Diabetes
Lee J, Faxvaag A, Rozenblum R, 130. Piatt GA, Seidel MC, Powell RO, and prevention program in a mediterra-
Pabo EA, Landman A, Klinger E, and Zgibor JC. Comparative effectiveness of nean environment: Individual or group
Bates DW. Many mobile health apps lifestyle intervention efforts in the com- therapy? An effectiveness evaluation.
target high-need, high-cost popula- munity: Results of the Rethinking Eating Primary Care Diabetes 2015;9(2):89–95.
tions, but gaps remain. Health Affairs and ACTivity (REACT) study. Diabetes 142. Saaristo T, Moilanen L, Korpi-Hyovalti
2016;35(12):2310–2318. Care 2013;36(2):202–209. E, Vanhala M, Saltevo J, Niskanen L,
119. Flay BR. Efficacy and effectiveness 131. Vadheim LM, McPherson C, Kassner Jokelainen J, Peltonen M, Oksa H,
trials (and other phases of research) DR, Vanderwood KK, Hall TO, Butcher Tuomilehto J, Uusitupa M, and Keinanen-
in the development of health promo- MK, Helgerson SD, and Harwell TS. Kiukaanniemi S. Lifestyle intervention for
tion programs. Preventive Medicine Adapted diabetes prevention program prevention of type 2 diabetes in primary
1986;15(5):451–474. lifestyle intervention can be effectively health care: One-year follow-up of the
120. Glasgow RE, Lichtenstein E, and Marcus delivered through telehealth. The Finnish National Diabetes Prevention
AC. Why don’t we see more translation Diabetes Educator 2010;36(4):651–656. Program (FIN-D2D). Diabetes Care
of health promotion research to practice? 132. Whittemore R, Melkus G, Wagner J, 2010;33(10):2146–2151. 2945150.
Rethinking the efficacy-to-effectiveness Dziura J, Northrup V, and Grey M. 143. Cardona-Morrell M, Rychetnik L,
transition. American Journal of Public Translating the diabetes prevention Morrell SL, Espinel PT, and Bauman
Health 2003;93(8):1261–1267. program to primary care: A pilot study. A. Reduction of diabetes risk in routine
121. Ackermann RT, Finch EA, Brizendine E, Nursing Research 2009;58(1):2–12. clinical practice: Are physical activ-
Zhou H, and Marrero DG. Translating PMC2689783. ity and nutrition interventions feasible
the diabetes prevention program into the 133. Sattin R, Williams L, Dias J, Garvin and are the outcomes from reference
community: The DEPLOY pilot study. J, Marion L, Joshua T, Kriska A, trials replicable? A systematic review
American Journal of Preventive Medicine Kramer MK, and Venkat Narayan and meta-analysis. BMC Public Health
2008;35(4):357–363. KM. Community trial of a faith-based 2010;10:653. 2989959.
122. Ackermann RT, Finch EA, Caffrey lifestyle intervention to prevent diabetes 144. Katz MH and Bhatia R. Food surcharges
HM, Lipscomb ER, Hays LM, and among African-Americans. Journal of and subsidies: Putting your money where
Saha C. Long-term effects of a com- Community Health 2016;41(1):87–96. your mouth is. Archives of Internal
munity-based lifestyle intervention to doi: 10.1007/s10900-015-0071-8 Medicine 2010;170(5):405–406.
prevent type 2 diabetes: The DEPLOY 134. Benyshek DC, Chino M, Dodge-Francis 145. Duffey KJ, Gordon-Larsen P, Shikany
extension pilot study. Chronic Illness C, Begay TO, Jin H, and Giordano C. JM, Guilkey D, Jacobs DR, and Popkin
2011;7(4):279–290. Prevention of type 2 diabetes in urban BM. Food price and diet and health
123. Vanderwood KK, Hall TO, Harwell American Indian/Alaskan native com- outcomes: 20 Years of The CARDIA
TS, Butcher MK, and Helgerson SD. munities: The Life in BALANCE pilot Study. Archives of Internal Medicine
Implementing a state-based car- study. Journal of Diabetes Mellitus 2010;170(5):420–426.
diovascular disease and diabetes 2013;3(4):184–191. 146. Sallis JF, Floyd MF, Rodriguez DA, and
prevention program. Diabetes Care 135. Davis-Smith YM, Boltri JM, Seale JP, Saelens BE. The role of built environ-
2010;33(12):2543–2545. PMC2992185. Shellenberger S, Blalock T, and Tobin ments in physical activity, obesity, and
124. Benyshek DC, Chino M, Dodge-Francis B. Implementing a diabetes prevention cardiovascular disease. Circulation
C, Begay TO, Jin H, and Giordano C. program in a rural African-American 2012;125:729–737.
Prevention of type 2 diabetes in urban church. Journal of the National Medical 147. TenBrink DS, McMunn R, and Panken
American Indian/Alaskan native com- Association 2007;99(4):440–446. S. Project U-turn: Increasing active
munities: The Life in BALANCE pilot PMC2569663. transportation in Jackson, Michigan. The
study. Journal of Diabetes Mellitus 136. Katula JA, Vitolins MZ, Morgan TM, American Journal of Preventive Medicine
2013;3(4):184–191. PMC3952556. Lawlor MS, Blackwell CS, Isom SP, 2009;37(6 Suppl 2):S329–S335.
125. Boltri JM, Davis-Smith M, Okosun Pedley CF, and Goff DC, Jr. The healthy 148. Gittelsohn J, Lee-Kwan SH, and Batorsky
IS, Seale JP, and Foster B. Translation living partnerships to prevent diabetes B. Community-based interventions in
of the national institutes of health study: 2-Year outcomes of a randomized prepared-food sources: A systematic
diabetes prevention program in controlled trial. The American Journal review. Preventing Chronic Disease
African American churches. Journal of Preventive Medicine 2013;44(4 Suppl 2013;10:E180. PMC3816610.
of the National Medical Association 4):S324–332. 3731757. 149. Gittelsohn J, Rowan M, and Gadhoke
2011;103(3):194–202. 137. Kramer MK, Vanderwood KK, P. Interventions in small food stores to
126. Dallam GM and Foust CP. A comparative Eaglehouse YL, Miller RG, Arena VC, change the food environment, improve
approach to using the diabetes preven- Venditti EM, and Kriska AM. Diabetes diet, and reduce risk of chronic disease.
tion program to reduce diabetes risk in prevention efforts in the community Preventing Chronic Disease 2012;9:E59.
a worksite setting. Health Promotion are effective for older, at-risk adults. PMC3359101.
Practice 2013;14(2):199–204. Diabetes 2014;63:A3. 150. Vojta D, Koehler TB, Longjohn M,
127. Faridi Z, Shuval K, Njike VY, Katz JA, 138. Ali MK, Echouffo-Tcheugui JB, and Lever JA, and Caputo NF. A coor-
Jennings G, Williams M, and Katz DL. Williamson DF. How effective were dinated national model for diabetes
Partners reducing effects of diabetes lifestyle interventions in real-world set- prevention: Linking health systems to an
(PREDICT): A diabetes prevention tings that were modeled on the diabetes evidence-based community program. The
physical activity and dietary inter- prevention program? Health Affairs American Journal of Preventive Medicine
vention through African-American 2012;31(1):67–75. 2013;44(4 Suppl 4):S301–S306.
382 Chapter 29 Lifestyle Medicine and the Management of Prediabetes
151. Centers for Medicare and Medicaid 152. Jackson SL, Long Q, Rhee MK, Olson study. Lancet Diabetes Endocrinology
Services. Medicare Diabetes Prevention DE, Tomolo AM, Cunningham SA, 2015;3(3):173–180. PMC4401476.
Program (MDPP) Expanded Model. Ramakrishnan U, Narayan KM, and 153. Weber MB, Twombly JG, Narayan KMV,
Available at https://innovation.cms.go Phillips LS. Weight loss and incidence and Phillips LS. Lifestyle interventions
v/initiatives/medicare-diabetes-preventi of diabetes with the Veterans Health and the prevention and treatment of type
on-program/. Accessed on October 30, Administration MOVE! lifestyle 2 diabetes. American Journal of Lifestyle
2017. change programme: An observational Medicine 2010;4:468–480.
30
CHAPTER
383
384 Chapter 30 Lifestyle Therapies for the Management of Diabetes
Preventing obesity and increasing physical activity are tolerance test (OGTT), or a random plasma glucose), or
high priorities in the prevention of prediabetes and other hemoglobin A1c (A1C) criteria (Table 30.1).8,12
chronic diseases. Identifying individuals with prediabetes Blood glucose testing rather than A1C is recom-
and implementing prevention interventions is essential. mended to diagnose the acute onset of T1D in individu-
To assist in the management of T1D and to slow the pro- als with symptoms of hyperglycemia.8 A random plasma
gression of T2D, lifestyle therapies must continue over glucose ≥ 200 mg/dL [11.1 mmol/L] in the presence of
the continuum of the disease. In this chapter, lifestyle symptoms, but not under catabolic stress from another
therapies for T1D, T2D, and gestational diabetes mellitus condition, is sufficient to make the diagnosis of diabetes.
(GDM) are reviewed and summarized. Although all life- Health care professionals (HCP) also want to know the
style therapies are important, MNT will be a major focus. A1C to assist in determining how long a patient has had
The goals of MNT for diabetes are to support a healthy hyperglycemia.8
eating pattern to attain individualized glycemic, blood Testing for T2D in asymptomatic persons should be
pressure, and lipid goals. As diabetes progresses, the goal considered in adults of any age who are overweight or
of MNT is to delay/prevent and assist in the management obese (defined as body mass index [BMI] ≥ 25 kg/m 2
of complications. in Caucasians and other non-Asians, or ≥ 23 kg/m 2 in
MNT recommendations for people with diabetes must Asians, Asian Indians, or Asian Americans) and who have
be evidence-based and must promote and support healthy one or more additional risk factors for diabetes. For all
eating patterns, emphasizing a variety of nutrient-dense people, testing should begin at age 45 years and all tests
food in appropriate portion sizes. An individualized nutri- are equally appropriate. Unfortunately, in the last decade
tion therapy assessment, done in collaboration with the the incidence and prevalence of T2D in adolescents has
person, must address individual needs based on personal increased dramatically, especially in racial and ethnic
and cultural preferences, health literacy and numeracy, minority populations. Therefore, screening for T2D in
access to healthful food choices, and the willingness and asymptomatic youth who are overweight and have an
ability of the person to make behavioral changes.8 additional two risk factors is recommended.8
Reviewed in the following sections are lifestyle thera-
pies from the Academy of Nutrition and Dietetics (AND)
Nutrition Practice Guideline for Type 1 and Type 2 30.3 TYPE 1 DIABETES
Diabetes5,9 and Gestational Diabetes10 and from the
American Diabetes Association Diabetes (ADA).8,11 For Type 1 diabetes accounts for approximately 5% of diag-
the AND’ s systematic review used to develop the nutrition nosed diabetes and is due to cellular-mediated autoimmune
practice guideline (NPG) for T1D and T2D, a total of 60 destruction of the pancreatic beta-cells, usually leading to
studies met study inclusion criteria. Twenty-two of the stud- absolute insulin deficiency.1 The rate of beta-cell destruc-
ies provided the evidence for MNT effectiveness.5 For the tion is quite variable, being rapid in some individuals
nutrition intervention recommendations, 38 studies were (mainly infants and children) and slow in others (mainly
reviewed, and 30 conclusion statements and 19 nutrition adults). Immune-mediated diabetes commonly occurs in
interventions were written.9 Five additional recommenda- childhood and adolescence, but it can occur at any age,
tions were written based on the ADA evidence review.11 even in the eighth and ninth decades of life.8 Children
and adolescents may present with ketoacidosis as the first
symptom of the disease. Adults may retain sufficient beta-
30.2 DIAGNOSIS OF DIABETES cell function to prevent ketoacidosis for many years; how-
ever, such individuals eventually become dependent on
Diabetes may be diagnosed based on plasma glucose cri- insulin for survival and are at risk for ketoacidosis. This
teria (either the fasting plasma glucose (FPG), or the 2-h later-onset type 1 diabetes picture is referred to as Latent
plasma glucose (2-h PG) value after a 75-g oral glucose Autoimmune Diabetes of Adults (LADA).
* See references.8,12
In the absence of unequivocal hyperglycemia, results should be confirmed by repeat testing.
a
30.3 Type 1 Diabetes 385
30
tamic acid decarboxylase - 65 (GAD), islet cells, insulin, the decreases in A1C of 1.0% to 1.9% and significant improve-
tyrosine phosphatases 1A-2 and 1A-2β , and ZnT8. T1D is ments in quality of life (satisfaction with treatment and
currently defined by the presence of one or more of these improved psychological well-being). With continued sup-
autoimmune markers. The disease has strong HLA asso- port, improved glycemic control was maintained with no
ciation, with linkage to the DQA and DQB genes. These significant changes in weight. 5 Factors contributing to
HLA-DR/DQ alleles can be either predisposing or protective. successful effectiveness of MNT were initial and contin-
ued encounters with RDNS, as well as patient use of car-
bohydrate counting to guide mealtime insulin dosing.
30.3.1 Treatment of Type 1 Diabetes: Insulin The first priority for persons with T1D on MDI or CSII
and Blood Glucose Monitoring is to integrate an insulin regimen into their lifestyle. In
determining an insulin regimen, approximately half of the
Persons with T1D must be treated with multiple daily
insulin needs are for basal and half for prandial require-
subcutaneous injections (MDI) of a basal insulin and
ments. The Eating Plan is developed before the insulin reg-
rapid-acting prandial insulin, or a continuous subcuta-
imen and is based on the individual’ s appetite, preferred
neous insulin infusion (CSII; insulin pump therapy).8,13
foods, and usual schedule of meals and physical activity.
Individuals (or family members) and their HCP need to
An insulin regimen can then be integrated into the usual
decide which form of insulin therapy will be best for the
food/eating and physical activity schedules. Carbohydrate
individual. The Diabetes Control and Complications Trial
counting using insulin-to-carbohydrate ratios is used to
(DCCT) clearly showed that intensive therapy with MDI
adjust prandial bolus insulin doses based on planned car-
or CSII delivered by multidisciplinary teams of physicians,
bohydrate intake, premeal glucose levels, and anticipated
registered dietitian nutritionists (RDNs), nurses, and
physical activity.9,13 Individuals need to be reminded that
behavioral scientists, among others, improved glycemia,
all three macronutrients— carbohydrate, protein, and
complication risks, and long-term outcomes.14
fat— require insulin at some point for their metabolism.
Persons with T1D (or family members) must perform
Carbohydrate intake is the primary determinant of bolus
self-monitoring of blood glucose (SMBG) to guide treat-
insulin needs, as protein and fat intake tends to be rela-
ment decisions. Blood glucose goals must be individual-
tively consistent in many individuals. However, if meals
ized based on clinical priorities, logistical challenges, and
containing more protein and fat than usual are consumed,
resources; suggested recommendations for adults and
adjustments in bolus insulin doses to compensate for
youth are listed in Table 30.2.8,12 HCP achieve target gly-
delayed postprandial glucose excursion may be needed.15
cemic control using appropriate blood glucose monitor-
For individuals who are unable to learn and implement
ing, regular A1C testing, synchronization of insulin and
carbohydrate counting and insulin adjustments, a con-
nutritional therapies, aggressive case finding for potential
sistent carbohydrate intake and fixed insulin dosing will
diabetes-related complications, and durable lifestyle medi-
need to be used. Other MNT interventions that apply to
cine counseling and interventions.
T1D and T2D adults are reviewed in Table 30.3.
30.3.2 Lifestyle Interventions
for Type 1 Diabetes 30.3.2.2 Physical Activity/Exercise
All youth with T1D are encouraged to engage in 60 min-
30.3.2.1 Medical Nutrition Therapy (MNT) utes/day or more of moderate or vigorous aerobic activity,
There is strong evidence from clinical trials in subjects with vigorous muscle and bone strengthening activities
with T1D that MNT using carbohydrate counting and at least three days/week.16 Most adults with T1D are
TABLE 30.2 Summary of glycemic recommendations for many nonpregnant adults and youth with diabetes*
Peak postprandial capillary
A1C Preprandial capillary PGa PG Bedtime/overnight
Adults
ADA: < 7.0% (53 mmol/mol)b 80– 130 mg/dL (4.4– 7.2 mmol/L)b < 180 mg/dL (10.0 mmol/L)b,d
AACE/ACE: ≤ 6.5%c
Children and Adolescents with Type 1 Diabetes b,e
< 7.5% (58 mmol/mol) 90– 130 mg/dL (5.0– 7.2 mmol/L) 90– 150 mg/dL (5.0– 8.3 mmol/L)
* See references.8,12
Plasma glucose.
a
b More or less stringent glycemic goals may be appropriate for individual persons. Blood glucose goals should be modified in children with frequent hypoglycemia or hypo-
glycemia unawareness.
Goal if it can be achieved safely.
c
d Postprandial PG may be used if A1C goals are not met despite reaching preprandial PG goals.
e In children and adolescents, postprandial PG values should be measured when there is a discrepancy between preprandial PG values and A1C levels and to assess pre-
prandial insulin doses in those on basal-bolus or CSII regimens.
386 Chapter 30 Lifestyle Therapies for the Management of Diabetes
TABLE 30.3 Academy of nutrition and dietetics evidence-based nutrition therapy intervention recommendations for
type 1 and type 2 diabetes in adults*
Topic Recommendations Rating
Nutrition Individualize in collaboration with the adult; a variety of eating patterns are acceptable based on the Fair
prescription individual’ s preferences.
Energy intake • For overweight or obese adult: a reduced energy, healthful eating plan with goal of weight loss, Strong
weight maintenance, and/or prevention of weight gain.
• For appropriate-weight adults: a healthful eating plan with goal of weight maintenance and/or Consensus
prevention of weight gain.
Macronutrient An individualized, healthful eating plan within appropriate energy intake. Differing amounts of Fair
composition carbohydrate (39% to 57%) and fat (27% to 40%) report no significant effects on A1C or insulin levels,
independent of weight loss.
Carbohydrate • Adults on MDI or CSII: educate on carbohydrate counting using insulin-to-carbohydrate ratios. Strong
management • Adults on fixed insulin doses or on insulin secretagogues: educate on carbohydrate consistency Fair
strategies (timing and amount).
• Adults on MNT alone or on diabetes medication (other than insulin secretagogues): educate on Fair
carbohydrate management strategy.
• All recommendations are based on the individual’ s abilities, preferences, and management goals. Fair
Monitoring carbohydrate intake is a key strategy for achieving glycemic goals.
Fiber intake Encourage consumption of dietary fiber from foods such as fruits, vegetables, whole grains, and Fait
legumes at the levels recommended by the Dietary Reference Intakes of U.S. Department of
Agriculture due to the overall health benefits of dietary fiber.
Glycemic index Lowering GI or GL may or may not have a significant effect on glycemic control. Studies longer than Fair
(GI) and glycemic 12 weeks report no significant influence of GI or GL, independent of weight loss, on A1C levels.
load (GL)
Nutritive • Nutritive sweeteners when substituted isocalorically for other carbohydrates, will not have a Fair
sweeteners significant effect on A1C or insulin levels.
• Advise against excessive intake of nutritive sweeteners to avoid excessive calorie and Fair
carbohydrate intake.
Nonnutritive • Intake of FDA-approved NNS within the recommended daily intake levels established by the FDA Weak
sweeteners (NNS) does not have a significant influence on glycemic control.
• Substituting foods and beverages containing FDA-approved NNS within the recommended daily Fair
intake can reduce overall calorie and carbohydrate intake; however, the other sources of calories
and carbohydrates in these foods and beverages need to be considered.
Protein intake • Adding protein to meals and/or snacks does not prevent or assist in the treatment of Fair
hypoglycemia. Ingested protein appears to increase the insulin response without increasing plasma
glucose concentrations; therefore, protein should not be used to treat or prevent hypoglycemia.
• Adults with diabetes and diabetic kidney disease do not need protein restriction; there is no Strong
significant influence of protein intake.
• Type of protein (vegetable-based vs. animal-based) does not have a significant effect on Weak
glomerular filtration rate.
Cardioprotective • Encourage consumption of a cardioprotective eating pattern within the recommended energy intake. Strong
eating patterns • Encourage an individualized reduction in sodium intake. Less than 2,000 mg sodium per day is Fair
appropriate; for adults with both diabetes and hypertension, further reduction in sodium should
be individualized.
Nutrient adequacy: If proposed as a diabetes management strategy, advise that there is no clear benefit from Fair
vitamin, mineral, supplementation in people who do not have deficiencies.
and/or herbal
supplements
Alcohol When adults choose to drink alcohol, they should do so in moderation (up to one drink/day for women Weak
and up to two drinks/day for men). Alcohol consumption may place adults using insulin or insulin
secretagogues at increased risk for delayed hypoglycemia.
Physical activity Encourage an individualized physical activity plan, unless medically contraindicated, to gradually Strong
achieve the following:
• accumulating 150 minutes or more of physical activity per week;
• moderate-intensity aerobic exercise spread over at least three days/week with no more than two
consecutive days without exercise;
• resistance training at least twice per week; and
• reduce sedentary time by breaking up extended amounts of time (more than 90 minutes) spent sitting.
Glucose monitoring Ensure that adults are educated about glucose monitoring and using data to adjust therapy. Fair
* See references.5,9
30.4 Type 2 Diabetes 387
encouraged to engage in 150 minutes or more of mod- cells. Endogenous insulin levels may be normal, low, or
30
erate-to-vigorous intensity physical activity per week, elevated, but in any case, they are inadequate to overcome
spread over at least three days/week, with no more than the concomitant insulin resistance. In other words, insu-
two consecutive days without activity. They should also lin production rates become insufficient relative to glucose
engage in two to three sessions/week of resistance exercise levels and glucose production rates when frank hypergly-
on nonconsecutive days. cemia and T2D develop.
Prevention of hypoglycemia is a major concern. Hyperglycemia is usually first exhibited as an eleva-
Individuals may need to ingest some added carbohydrate if tion of postprandial blood glucose caused by insulin resis-
pre-exercise glucose levels are < 100 mg/dL (5.6 mmol/L), tance at the cellular level; however, as insulin secretion
whether they can lower exogenous insulin levels during decreases, hepatic glucose production increases, causing
the workout (such as with CSII or reduced pre-exercise the elevation in fasting glucose concentrations. Insulin
insulin dosage), the timing during the day when exercise resistance also is demonstrated at the adipocyte level, lead-
is done, and the intensity and duration of the specific ing to lipolysis and an elevation in circulating free fatty
activity.16 acids, also contributing to an increase in insulin resistance.
Increased free fatty acids also cause a further decrease in
insulin sensitivity at the cellular level, impair pancreatic
30.3.2.3 Education/Counseling and Support insulin secretion, and augment hepatic glucose produc-
It is essential that individuals with diabetes and their family tion. The progressive loss of ß - cell secretory function
receive Diabetes Self-Management Education and Support means persons with T2D will require more medication(s)
(DSMES). Education and counseling focus on supporting over time, and for many, eventually exogenous insulin.
the individual’ s empowerment by providing tools for the This is not a “ diet failure” but rather a “ beta-cell failure.”
individual or family member to make informed self-man- Two consensus statements on comprehensive approaches
agement decisions. Ongoing education and support are to management of T2D have been published. One by
needed to maintain effective self-management throughout the ADA and the European Association for the Study of
a lifetime of diabetes, especially as new challenges emerge Diabetes18 and the second by the American Association
and as advances in treatment become available.8 of Clinical Endocrinologists and the American College of
Endocrinology (AACE/ACE).19
Atherosclerotic cardiovascular disease (ASCVD) is
30.3.2.4 Psychosocial Care the leading cause of morbidity and mortality for indi-
The prevalence of clinically significant psychosocial/emo- viduals with diabetes and is the largest contributor to the
tional disorders, anxiety disorders, depression, and dis- direct and indirect costs of diabetes.8 Hypertension and
ordered eating behaviors in people with diabetes require dyslipidemia, common conditions associated with T2D,
screening and referrals for treatment. Disordered eat- are clear risk factors for ASCVD, and diabetes itself
ing behaviors should be considered when hyperglycemia confers independent risk. In all persons with diabetes,
and weight loss are unexplained based on self-reported cardiovascular risk factors should be assessed at least
behaviors related to medication dosing, the Eating Plan, annually. Abnormal risk factors should, in addition to
and physical activity.8 Deliberate insulin omission caus- lifestyle therapy, be treated with appropriate medications.
ing glycosuria in order to lose weight (often referred to The good news is that with treatment, ASCVD morbidity
as “ diabulima” ) is the most common reported disordered and mortality have decreased significantly over the past
eating behavior for individuals with T1D.17 Other eating 10-years. 20
disorders in people with diabetes include anorexia ner-
vosa, bulimia nervosa, and binge eating disorders. The
management of these conditions requires a multidisci- 30.4.1 Lifestyle Interventions
plinary team, which may consist of an endocrinologist/ for Type 2 Diabetes
diabetologist, RDN, nurse educator, psychologist, and
frequently, a psychiatrist. 30.4.1.1 Medical Nutrition Therapy
Strong evidence from 18 studies in the AND’ s review of
effectiveness reported MNT lowered A1C 0.3% to 2.0%
30.4 TYPE 2 DIABETES at three months and was continued to 0.6% to 1.8% in
studies longer than 12 months. Usual care study arms
T2D accounts for 90– 95% of all diabetes and is a pro- reported 0 to + 0.2% changes in A1C. Although MNT was
gressive disease.1,8 Many persons with T2D are obese, effective throughout the disease process, decreases in A1C
and obesity itself causes some degree of insulin resistance. were largest (0.5% to 2.0%) in newly diagnosed persons
Persons who are not obese by commonly used weight cri- and/or persons with baseline A1C > 8.0%.5 Significant
teria may have an increased percentage of body fat distrib- improvements in quality of life (improved self-perception
uted primarily in the abdominal region. However, many of health status, increased knowledge and motivation,
obese persons never develop T2D. Therefore, obesity com- and decreased emotional stress), and decreases in doses
bined with a genetic predisposition may be necessary for or number of glucose-lowering medications were also
T2D to occur. reported. Mixed effects on lipids and blood pressure
T2D is characterized by a combination of insulin (50– 70% of participants were already on lipid-lowering
resistance and ß -cell failure. Insulin resistance is pres- or anti-hypertensive medications) and body weight out-
ent in target tissues, mainly muscle, liver, and adipose comes were reported. A minimum of three encounters
388 Chapter 30 Lifestyle Therapies for the Management of Diabetes
with an RDN with continued follow-up visits were impor- from weight loss (the goal of MNT for the prevention of
tant. A variety of nutrition therapy interventions were diabetes) to achieving glycemic, lipid, and blood pressure
implemented and were effective. All interventions resulted targets. 24
in a reduced energy intake. An interesting report of one research center’ s five-year
The Academy’ s Nutrition Practice Guideline for T1D review of an intensive weight loss intervention in persons
and T2D in Adults (5,9) recommends that RDNs should with T2D documented the effect of weight regain on
educate adults with T2D receiving MNT alone or taking metabolic outcomes. 25 Approximately 50% of the 129
diabetes medication (other than insulin secretagogues), patients maintained a weight loss of 3.5% and ~50% of
based on his or her abilities, preferences, and management 9.0%. This could be predicted by a patient’ s ability to
goals, on one of the following carbohydrate management maintain ≥ 7% weight loss at one year. Both groups main-
strategies: (1) carbohydrate counting alone; plate method, tained improvements in low-density and high-density lipo-
portion control, and simplified meal plan, or (2) food lists protein cholesterol. However, the A1C in the first group
and carbohydrate choices.9 A simple diabetes healthy eat- increased from 7.5% at baseline to 8.0% at five years; the
ing pattern approach is often better suited to individuals A1C in the second group was 7.4% at baseline and 7.3%
with T2D who have numeracy concerns or low health lit- at five years. Therefore, the researchers concluded that a
eracy. However, as noted above, the focus is on a reduced weight loss of ≥ 7% was required to achieve benefits in
energy intake. For some persons, a reduced energy intake the majority of metabolic outcomes. Nevertheless, and as
may lead to weight loss, for some it may maintain weight noted above, this appears difficult for many persons with
loss, and for others it may prevent weight gain. Table 30.3 T2D to achieve, especially in clinical practice as opposed
provides a summary of nutrition therapy interventions for to research centers.
adults with diabetes. Various biological factors and pathways make weight
As individuals move from prediabetes and being insu- loss maintenance difficult. 26 Hormonal adaptations
lin resistant to T2D and insulin deficiency, one of the pri- (decreases in leptin, peptide YY, cholecystokinin, and
mary goals of therapy is to achieve near-euglycemia in insulin; increases in ghrelin, glucagon-like peptide 1, gas-
the hope of slowing ß - cell exhaustion. Moderate weight tric inhibitory polypeptide, and pancreatic polypeptide)
loss may be beneficial for some individuals, primarily encourage weight gain after diet-induced weight loss and
those who are still insulin resistant, but for many it is continue for at least one year after initial weight reduc-
too late for weight loss to improve hyperglycemia. At tion. Weight loss also results in adaptive thermogenesis
later stages of the disease when medication(s)— including (decreased resting metabolic rate), which is also main-
insulin— need to be combined with MNT, weight gain tained in the long term. Neural factors, such as dopamine,
often occurs, and preventing this becomes important. also signal the need to respond to an increased desire for
Furthermore, any beneficial effects on glycemia begin to fatty foods after weight loss.
occur early, before much weight is lost, 21 suggesting the Persons receiving either MNT alone or combined
benefits are from the reduced energy intake rather than with glucose-lowering medications or fixed insulin doses
from the actual weight loss. generally do better if carbohydrate intake is consistently
A systematic review and meta-analysis of weight loss distributed throughout the day on a day-to-day basis.
interventions (WLI) in adults with obesity and T2D and Diets too low in carbohydrate eliminate too many foods
with a minimum 12-month study duration was con- that are important sources of fiber, vitamins, and min-
ducted. 22 At 12 months in 11 trials (19 WLI where eight erals.9 Furthermore, they often become higher in fats,
compared two WLIs and three compared one WLI to a which in the long term is reported to contribute to insulin
usual care control group), 17 WLI groups reported weight resistance. 27
losses less than 5% of initial weight (~3.2 kg), resulting Many individuals with T2D also have dyslipidemia
in nonsignificant improvements in A1C, lipids, or blood and hypertension, so decreasing the intake of saturated
pressure. 22 Only two trials (a Mediterranean-style diet in fats, trans -fats, and sodium is a priority. A Mediterranean-
newly diagnosed adults and an intensive WLI in the Look style eating pattern (~50% of energy from carbohydrate
AHEAD Trial) reported weight losses ≥ 5% and benefi- and ≥ 30% fat, primarily from olive oil or mixed nuts) has
cial outcomes. Both included regular physical activity and been shown in persons with T2D to reduce the incidence
very frequent contact with HCPs. Additionally, compared of major cardiovascular events, likely by reducing inflam-
to people without diabetes, it appears more difficult for matory activity. 28,29
those with T2D to lose weight. In a systematic review of The recommendation for the general public to reduce
WLIs in subjects primarily without diabetes, weight loss sodium to < 2,300 mg/day is also appropriate for adults
also plateaued at six months, and the mean weight loss with diabetes; for adults with both diabetes and hyper-
at 12 months was 4.5– 7.5 kg (5– 8%), 23 whereas in 17 of tension, further reduction in sodium intake should be
the 19 WLI groups in people with T2D, mean weight loss individualized.9
at 12 months was 1.9– 4.8 kg (3.2%). 22 Weight loss > 5%
appears necessary for beneficial effects on A1C, lipids, and
blood pressure. Achieving this level of weight loss appears 30.4.1.2 Physical Activity
to be difficult because it requires intense interventions, For youth and adults with T2D, regular physical activity
including energy restriction, regular physical activity, and is strongly encouraged, primarily for the benefits associ-
very frequent contact with HCP. Since these modalities of ated with enhanced cardiorespiratory fitness that are inde-
intervention are difficult to implement in clinical practice, pendent of weight loss. However, physical activity must
the goals of MNT in the context of T2D treatment shift be undertaken regularly to have continued benefits.16 See
30.5 Gestational Diabetes 389
Table 30.3 for physical activity recommendations, which two methods: (1) “ one-step” 75-g oral glucose tolerance
30
are similar to the recommendations for T1D. test (OGTT), or (2) the “ t wo-step” method with a 50-g
(nonfasting) screen followed by a 100-g OGTT for those
who screen positive.8
30.4.1.3 Education/Counseling and Support Women with GDM are at increased risk for babies
Each person with diabetes needs to be actively involved who have macrosomia or other birth complications and
in education, self-management, and management plan- increased risk of T2D after pregnancy. Risks increase with
ning with his or her healthcare team, including the col- progressive hyperglycemia. After diagnosis, management
laborative development of an individualized Eating Plan. involves MNT, physical activity, weight management
The ADA recommends that all individuals with diabe- depending on pre-gestational weight, and glucose moni-
tes receive individualized MNT, preferably provided by toring. Glucose goals of therapy are listed in Table 30.4.8
an RDN. However, it is also important that each mem- Many women may achieve goals with lifestyle changes
ber of the healthcare team be knowledgeable and sup- alone. However, medications need to be added if goals are
portive of MNT implementation.8 For T2D, emphasis not met. Insulin is the preferred medication, as it does not
is on a healthy eating pattern containing nutrient-dense cross the placenta to a measurable extent. Metformin and
foods with a reduced energy intake. The Mediterranean, glyburide may be used, but both cross the placenta to the
Dietary Approaches to Stop Hypertension (DASH), and fetus. All oral agents lack long-term safety data in the con-
plant-based diets are all examples of healthy eating pat- text of GDM management.8
terns. It is also important to monitor metabolic outcomes Blood glucose levels during pregnancy are reported to
to determine if medications need to be added or adjusted. be approximately 84 mg/dL (4.7 mmol/L), preprandial
The overall objectives of education are to support 78 mg/dL (4.3 mmol/L), and peak postprandial 110 mg/
informed patient decision making, self-care behaviors, dL (6.1 mmol/L) at 70 minutes. 34 These values are lower
problem solving, and active collaboration with the health- than the normal fasting glucose level of < 100 mg/dL and
care team to improve clinical outcomes, health status, the normal two-hour glucose values of < 140 mg/dL.
and quality of life in a cost-effective manner. A joint posi- Women during pregnancy with too-low average blood
tion statement on DSMES in T2D from the ADA, the glucose levels are reported to have a higher incidence
American Association of Diabetes Educators, and the rate of small-for-gestational-age infants, whereas women
Academy includes a diabetes education algorithm that who had elevated glucose levels have a higher incidence of
defines when, what, and how DSMES should be provided large-for-gestational-age infants. Therefore, it is strongly
to adults with T2D.30 Healthcare teams should also be recommended that women with GDM perform self-mon-
provided with a clear understanding of how to integrate itoring of blood glucose (SMBG).35 Because postpran-
DSMES into routine clinical care. dial glucose monitoring is important during pregnancy,
the recommended SMBG protocol is four tests per day:
fasting and 1 or 2 hours postprandial. The rationale for
30.4.1.4 Psychosocial Care choosing either one or two hours postprandial has not yet
Among persons with obesity and T2D, expectations of been clarified.
weight loss benefits not realized may cause stress and There has been a significant increase in the number
avoidance of care, mistrust of doctors and other HCPs, of women of childbearing age who are overweight or
and poor adherences to diabetes care recommendations. 31 obese. In 2006, more than 50% of women ages 20 to 39
Unfortunately, many HCP still hold strong negative atti- were reported to have a BMI of 25 kg/m 2 or higher. 36
tudes and stereotypes about people with obesity, 32 further Beginning a pregnancy with excessive adiposity increases
compounding the problem. Educating HCP on the genetic, both maternal and fetal risks, including gestational hyper-
environmental, biological, psychological, and social con- tension, pre-eclampsia, fetal macrosomia, surgical or trau-
tributors to weight gain and weight loss is suggested. 31 matic delivery, and increased risk for maternal GDM.37
HCPs who understand this complex web of causality have Excessive gestational weight gain is associated with fat-
more positive attitudes about patients with obesity. 33 ter babies and higher postpartum weight retention. A key
concern for HCPs is to identify women at risk for exces-
sive weight gain early in pregnancy and then intervene
30.5 GESTATIONAL DIABETES to control subsequent weight gain. Unfortunately, little
research has been conducted in this important area, and
Previously GDM was defined as any degree of intolerance therefore, evidence-based practice recommendations are
that was first recognized during pregnancy, regardless of not available.
whether the condition may have predated the pregnancy
or persisted after the pregnancy. This has now changed.8
Because of the number of pregnant women with undiag- TABLE 30.4 Glucose goals for women with gestational
nosed T2D, the recommendation is to test women with risk diabetes*
factors for T2D at the initial prenatal visit, using standard
diagnostic criteria (Table 30.1). Women diagnosed with Fasting ≤ 95 mg/dL (5.3 mmol/L) and either
diabetes in the first trimester are now classified as having • One-hour postprandial ≤ 140 mg/dL (7.8 mmol/L)
T2D (or very rarely T1D). GDM is diabetes diagnosed in
• Two-hour postprandial ≤ 120 mg/dL (6.7 mmol/L)
the second or third trimester that is not clearly preexisting
T1D or T2D. A GDM diagnosis can be done with either of * See reference.8
390 Chapter 30 Lifestyle Therapies for the Management of Diabetes
Breastfeeding is strongly recommended for all women, and deaths, premature births, and rates of shoulder dysto-
including those with diabetes. Breastfeeding promotion cia, bone fractures, and nerve palsy.
by HCP is needed to increase the important role of breast- During pregnancy with GDM, MNT has three impor-
feeding in improving health and reducing health care tant goals: (1) minimize blood glucose excursion and
costs.38 Women with GDM should be tested for persistent maintenance of glucose values within target goal ranges
diabetes or prediabetes at 4– 12 weeks postpartum with pre- and postmeal, (2) ensure an appropriate energy intake
a 75-g OGTT using non-pregnancy criteria (Table 30.1). to achieve adequate gestational weight gain and avoidance
They should also be tested every 1– 3 years thereafter if of excess weight gain, and (3) provide safe and adequate
the 4– 12 week 75-g OGTT is normal, with frequency nutrients for maternal and fetal health.10 Regular and
depending on other risk factors.8 Women with a history of frequent MNT encounters are essential. Assessing blood
GDM have a greatly increased risk of conversion to T2D glucose levels, appetite, and weight gain guide in the
over time. Both intensive lifestyle and metformin inter- development of an individualized Eating Plan and in mak-
ventions can prevent or delay progression to diabetes in ing adjustments in the Eating Plan throughout pregnancy.
women with prediabetes and a history of GDM.4 Nutrition therapy intervention recommendations for
GDM are summarized in Table 30.5.10 It is the balance
between carbohydrate intake and available insulin that
30.5.1 Lifestyle Interventions for determines postprandial glucose levels. The challenge is for
Gestational Diabetes women to consume an adequate amount of carbohydrate
without raising postmeal glucose levels above the target of
30.5.1.1 Medical Nutrition Therapy 140 mg/dL [7.8 mmol/L] at one hour and/or 120 mg/dL
Comprehensive nutrition therapy interventions imple- [6.7 mmol/L] at two hours. Glucose monitoring provides
mented in women with GDM that included individual- critical data regarding the eating plan, specifically the car-
ized MNT compared to usual care have been shown to be bohydrate intake. The typical amount of carbohydrate
effective in improving blood glucose levels and neonatal at meal times is 45 to 60 grams or three to four carbo-
and maternal outcomes.10 Improved outcomes included hydrate choices and 15 to 30 grams of carbohydrate for
lower birth weight and reductions in the incidence of mac- each snack. It is usually more difficult to manage glucose
rosomia, need for insulin therapy, maternal hypertension, excursions after the breakfast meal due to the release of
hospitalizations, neonatal intensive care unit admissions placental hormones during the early morning hours which
TABLE 30.5 Academy of nutrition and dietetics evidence-based nutrition therapy interventions for women with
gestational diabetes
Topic Recommendations Rating
Calorie prescription Based on individualized nutrition assessment and on Dietary Reference Intake (DRI), Fair
encourage adequate caloric intake to promote fetal/neonatal and maternal health, achieve
glucose goals, and appropriate gestational weight gain. No research suggests an optimal
calorie intake. In obese women, reduced calorie intake does not lead to adverse outcomes.
Macronutrient requirements Adequate amounts of macronutrients to support pregnancy, based on nutrition assessment, Consensus
with guidance from the DRI, which recommends a minimum of 175 g carbohydrate and 71 g
protein (or 1.1 g/kg/day protein) per day.
Carbohydrate prescription Individualize the amount and type of carbohydrate to achieve postmeal glucose goals; Fair
research does not confirm an ideal amount or type of carbohydrate.
Carbohydrate and postmeal Individualize the amount and type of carbohydrate at breakfast based on nutrition Fair
breakfast glycemia assessment, treatment goals, and glucose response.
Meal and snack distribution Distribute total calories and carbohydrate into smaller meals and multiple snacks (three Consensus
meals and two or more snacks) based on glucose levels, physical activity, and medications.
Dietary vitamin and mineral Encourage healthy food choices and a variety of foods to meet the nutrient needs of Consensus
intake pregnancy.
Vitamin and mineral Recommend dietary supplementation within the DRI for pregnancy with a prenatal Consensus
supplementation multivitamin/mineral or specific vitamin or mineral supplement(s) to address inadequate
vitamin and mineral intake (e.g., iron, folate, calcium, vitamin D, choline, and iodine) or
documented micronutrient deficiency.
Nonnutritive sweeteners Select only FDA-approved NNS and limit amount to the FDA-acceptable daily intake. Consensus
(NNS)
Alcohol Reinforce abstinence from alcohol during pregnancy. Consensus
Physical activity Encourage a goal to achieve daily moderate physical activity of 30 minutes or more per day. Strong
Source: Adapted from the Academy of Nutrition and Dietetics “ Gestational Diabetes Mellitus (GDM) Evidence-Based Nutrition Practice Guideline 2016.” Available at: www.
andeal.org/topic.cfm?menu5288&cat=5539.10
Clinical Applications 391
create insulin resistance. As a result, typically reducing car- of outcomes. It is essential that HCPs understand and are
30
bohydrate at breakfast to 30 grams is recommended. knowledgeable about evidence-based lifestyle therapy rec-
Older research studies suggested that a low glycemic ommendations for diabetes and have the tools to guide
index diet could provide favorable outcomes39 ; however, and support implementation efforts.
more recent studies have shown that a higher-complex
carbohydrate/lower-fat diet also achieves glycemia below
therapy goals.40 Research on the glycemic index indicates CLINICAL APPLICATIONS
that there is a large person-to-person variable response
indicating that the prandial curve for each individual • The effectiveness of MNT provided by a registered
varies greatly.41 Since protein ingestion does not gen- dietitian nutritionist (RDN) to persons with diabe-
erally increase postprandial glucose levels, one or two tes is supported by strong evidence in the Academy
ounces of a protein food may be consumed with break- of Nutrition and Dietetics (Academy) Nutrition
fast or snacks as a way to add calories without affecting Practice Guideline for T1D and T2D.
glucose levels. • For persons with T1D, an insulin regimen
should be integrated into their usual food and
physical activity schedules. Carbohydrate count-
30.5.1.2 Physical Activity ing based on insulin-to-carbohydrate ratios is
Unless contraindicated, women with GDM are encour- used to adjust bolus (prandial) doses for planned
aged to participate in regular physical activity for 30 min- carbohydrate intake.
utes per day for a minimum of three times per week. In • For persons with T2D, a variety of nutrition
addition to improving glycemic control in women with therapy interventions are effective for glucose
GDM, regular physical activity during pregnancy reduces management; of importance is a reduced energy
the common discomforts of pregnancy without a negative intake. For some individuals, it may lead to
effect on maternal or neonatal outcomes.10 weight loss, for some it may maintain weight
loss, and for others it may prevent weight gain.
• There are no ideal percentages of calories from mac-
30.5.1.3 Education/Counseling and Support ronutrients that apply to all persons with diabetes.
Women diagnosed with GDM need to learn all aspects Of importance is an individualized healthy Eating
of diabetes management. Due to the relatively short dura- Plan, emphasizing a variety of nutrient-dense foods
tion of GDM, women should be seen within one week in appropriate portion sizes, developed in collabora-
of diagnosis for self-management education.10 First and tion with the person with diabetes that they are able
foremost, women must understand and accept that man- and willing to implement.
agement of GDM is important and achievable. Secondly, • Most adults with T1D and T2D are encouraged
women must understand that having GDM is a risk factor to engage in 150 minutes or more of moderate-to-
for developing T2D after delivery and for GDM in future vigorous intensity physical activity per week, spread
pregnancies. Therefore, guidelines and skills for the pre- over at least three days per week and with no more
vention of future diabetes are essential. than two consecutive days without activity. Two-
to-three sessions per week of resistance exercise on
nonconsecutive days is recommended. Youth with
30.5.1.4 Psychosocial Care T1D or T2D should engage in 60 minutes per day
Despite the short duration of GDM, making lifestyle or more of moderate-to-vigorous intensity aerobic
changes during pregnancy can be stressful and emotional. activity, with vigorous muscle-strengthening activi-
Encouraging women to talk about their concerns and feel- ties at least three days per week.
ings and assuring them that many women experience the • All persons with diabetes are encouraged to partici-
same feelings during their pregnancies can be helpful. pate in DSMES to obtain the knowledge, skills, and
ability necessary for diabetes self-care and contin-
ued self-management support.
30.6 SUMMARY • Psychosocial care should be integrated with a col-
laborative, patient-centered approach and provided
Education and counseling for lifestyle therapies for both to all persons with diabetes.
prediabetes and diabetes begins by developing a good • For women with GDM, lifestyle change is gener-
rapport with the patient. Nutrition therapy, whether pro- ally needed, and in many, lifestyle change alone
vided individually or in groups, involves a common pro- may suffice. The typical amount of carbohydrate at
cess: (1) assessment and determination of what lifestyle meal times is 45 to 60 grams (three to four carbohy-
changes the person is willing and able to make, (2) diag- drate choices) and 15 to 30 grams of carbohydrate
nosis of nutrition therapy-related problems and then devel- for each snack. However, reducing carbohydrate at
opment of appropriate interventions, (3) implementation breakfast to 30 grams may be needed. Regular phys-
of nutritional interventions using self-management educa- ical activity of 30 minutes per day for a minimum of
tion and counseling, and (4) monitoring and evaluation three times per week is recommended.
392 Chapter 30 Lifestyle Therapies for the Management of Diabetes
REFERENCES
1. Centers for Disease Control and Interventions and Complications (EDIC) Role of intramuscular accumulation
Prevention. National Diabetes Statistics Study Research Group. Mortality in type of lipid metabolites. J. Appl. Physiol .
Report, 2017 . Atlanta, GA: Centers 1 diabetes in the DCCT/EDIC versus 2006;100:1467– 1474.
for Disease Control and Prevention, the general population. Diabetes Care 28. Esposito K, Maiorino MI, Petrizzo M,
U.S. Department of Health and Human 2016;39:1378– 1383. et al. The effects of Mediterranean diet
Services, 2017. 15. Bell KJ, Smat CE, Steil GM, et al. Impact on the need for diabetes drugs and remis-
2. Gregg EW, Li Y, Wang J, et al. Changes of fat and protein in type 1 diabetes: sion of newly diagnosed type 2 diabe-
in diabetes-related complications in the Application of a model-based approach tes: Follow-up of a randomized trial.
United States, 1990– 2010. N. Eng. J. to derive insulin doses for open-loop Diabetes Care 2014;37:1874– 1880.
Med . 2014;370:1514– 1523. diabetes management. Diabetes Care 29. Maiorino MI, Bellastella G, Petrizzo
3. NCD Risk Factor Collaboration (NCD- 2016;39:1631– 1634. M, et al. Anti-inflammatory effect of
RisC). Worldwide trends in diabetes since 16. Colberg SR, Sigal RJ, Yardley JE, et al. Mediterranean diet in type 2 diabetes is
1980: A pooled analysis of 751 popula- Physical activity/exercise and diabetes: durable: 8-Year follow-up of a controlled
tion-based studies with 4.4 million par- A position statement of the American trial. Diabetes Care 2016;39:e44– e 45.
ticipants. Lancet 2016;387:1513– 1530. Diabetes Association. Diabetes Care 30. Powers MA, Bardsley J, Cypress M, et al.
4. Knowler WC, Fowler SE, Hamman 2016;39:2065– 2079. Diabetes self-management education and
RF, et al. 10-Year follow-up of diabetes 17. Larrañ aga A, Docet MF, and Garcia- support in type 2 diabetes: A joint posi-
incidence and weight loss in the diabetes Mayor RV. Disordered eating behaviors tion statement of the American Diabetes
prevention program outcomes study. in type 1 diabetic patients. World J. Association, the American Association
Lancet 2009;374:1677– 1686. Diabetes 2011;2:189– 195. of Diabetes Educators, and the Academy
5. Franz MJ, MacLeod J, Evert A, et al. 18. Inzucchi SE, Bergenstal RM, Buse JB, of Nutrition and Dietetics. J. Acad. Nutr.
Academy of nutrition and dietetics et al. Management of hyperglycemia in Diet . 2015;115:1323– 1334.
nutrition practice guideline for type 1 type 2 diabetes, 2015: A patient-centered 31. Phelan SM, Burgess DJ, Yeazel MW, et al.
and type 2 diabetes in adults: Systematic approach: Update to a position paper Impact of weight bias and stigma on qual-
review of evidence for medical nutrition of the American Diabetes Association ity of care and outcomes for patients with
therapy effectiveness and recommen- and the European Association for obesity. Obes. Rev . 2015;16:319– 326.
dations for integration into the nutri- the study of diabetes. Diabetes Care 32. Ochner CN, Tsai AG, Kushner RF,
tion care process. J. Acad. Nutr. Diet . 2015;38:140– 149. et al. Treating obesity seriously: When
2017;117:1659– 1679. 19. Garber AJ, Abrahamson MJ, Barzilary recommendations for lifestyle confront
6. Holman RR, Paul SK, Bethel MA, et al. JI, et al. Consensus statement by the biological adaptations. Lancet Diabetes
10-Year follow-up of intensive glucose American Association of Clinical Endocrinol . 2015;3:232– 234.
control in type 2 diabetes. N. Eng. J. Endocrinologists and American College 33. O’ Brien KS, Puhl RM, Latner JD,
Med . 2008;359:1577– 1589. of Endocrinology on the comprehensive et al. Reducing anti-fat prejudice in
7. Franz MJ. Lifestyle interventions across type 2 diabetes management algorithm – preservice health students: A random-
the continuum of type 2 diabetes: 2016 executive summary. Endocr. Pract . ized trial. Obesity (Silver Spring )
Reducing the risks of diabetes. Am. J. 2016;22:84– 113. 2010;18:2138– 2144.
Lifestyle Med . 2007;1:327– 334. 20. Ali MK, Bullard KM, Saaddine JB, et al. 34. Hod M and Ygeve Y. Goals of
8. American Diabetes Association. Achievement of goals in U.S. diabe- metabolic management of gesta-
Standards of medical care in dia- tes care, 1999– 2010. N. Eng. J. Med . tional diabetes. Diabetes Care
betes— 2017. Diabetes Care 2013;368:1613– 1624. 2007;20(Suppl 2):S180– S187.
2017;40(Suppl 1):S1– S127. 21. U.K. Prospective Diabetes Study Group. 35. American College of Obstetrics and
9. MacLeod J, Franz MJ, Handu D, et al. Response of fasting plasma glucose Gynecologists. ACOG Practice Bulletin
Academy of nutrition and dietetics to diet therapy in newly presenting 180Gestational diabetes mellitus. Obstet.
nutrition practice guideline for type 1 type II diabetic patients. Metabolism Gynecol . 2017;130:e17– e31.
and type 2 diabetes in adults: Nutrition 1990;39:905– 912. 36. Ogden CL, Carroll MD, Curtin LR, et al.
intervention evidence reviews and 22. Franz MJ, Boucher JL, Ruten-Ramos Prevalence of overweight and obesity in
recommendations. J. Acad. Nutr. Diet . D, et al. Lifestyle weight-loss interven- the United States, 1999– 2004. JAMA
2017;117:1637– 1658. tion outcomes in overweight and obese 2006;295:1549– 1555.
10. Academy of Nutrition and Dietetics adults with type 2 diabetes: A systematic 37. Institute of Medicine (IOM). Weight
Gestational Diabetes Mellitus (GDM ) review and meta-analysis of randomized Gain during Pregnancy: Reexamining
Guideline , 2016. Available at: www.a controlled trials. J. Acad. Nutr. Diet . the Guidelines . Washington, DC: The
ndeal.org/topic.cfm?menu5288&cat=55 2007;107:1755– 1767. National Academies Press, 2009.
38. Accessed July 2017. 23. Franz MJ, VanWormer JJ, Crain AL, 38. Academy of Nutrition and Dietetics.
11. Evert AB, Boucher JL, Cypress et al. Weight-loss outcomes: A systematic Position of the Academy of Nutrition
M, et al. Nutrition therapy recom- review and meta-analysis of weight- and Dietetics: Promoting and support-
mendations for the management of loss clinical trials with a minimum of ing breastfeeding. J. Acad. Nutr. Diet .
adults with diabetes. Diabetes Care 1-year follow-up. J. Acad. Nutr. Diet . 2015;115:444– 4 49.
2014;37(Suppl 1):S120–S143. 2007;107:1755– 1767. 39. Moses RG, Barker M, Winter M, et al.
12. Handelsman Y, Bloomgarden ZT, 24. Franz MJ. Weight management: Can a low-glycemic index diet reduce the
Grunberger G, et al. American Obesity to diabetes. Diabetes Spectr . need for insulin in gestational diabetes?
Association of Clinical Endocrinologists 2017;30:149– 153. Diabetes Care 2009;32:996– 1000.
and American College of Endocrinology 25. Hamdy O, Mottalib A, Morsi A, et al. 40. Hernandez TL, Van Pelt RE, Anderson
– Clinical practice guidelines for Long-term effect of intensive lifestyle MA, et al. A high-complex carbo-
developing a diabetes mellitus compre- intervention on cardiovascular risk hydrate diet in gestational diabetes
hensive care plan – 2015. Endocr. Pract . factors in patients with diabetes in mellitus achieves glucose targets and
2015;21(Suppl 1):1– 87. real-world clinical practice: A 5-year lowers postprandial lipids: A random-
13. Chamberlain JJ, Kalyani RR, Leal S, longitudinal study. BMJ Open Diabetes ized crossover study. Diabetes Care
et al. Treatment of type 1 diabetes: Res. Care 2017;5:e000259. 2014;37:1254– 1262.
Synopsis of the 2017 American Diabetes 26. Evert AB and Franz MJ. Why weight loss 41. Zeevi D, Korem T, Zmora N, et al.
Association standards of medical maintenance is difficult. Diabetes Spectr . Personalized nutrition by predic-
care in diabetes. Ann. Intern. Med . 2017;30:153– 156. tion of glycemic responses. Cell
2017;167:493– 498. 27. Lee JS, Pinnamaneni SK, Eo DJ, et al. 2015;163:1079– 1094.
14. Diabetes Control and Complications Saturated, but not n-6 polyunsaturated
Trial (DCCT)/Epidemiology of Diabetes fatty acids induce insulin resistance:
31
CHAPTER
393
394 Chapter 31 Implementing Nutritional Lifestyle Treatment Programs in Type 2 Diabetes
Purpose: to assess the effectiveness of the Pritikin program in patients with T2D.
Methods: retrospective review of data from 60 patients completing the 26-day residential
program.
Results: 21 of 23 patients on oral hypoglycemic agents at study entry were able to stop these
medications: 13 of 17 patients on insulin at study entry were able to stop their insulin: 2 of the 4
patients remaining on insulin had their dose reduced by 50%. Fasting blood glucose decreased
from 194.9 +/– 10.1 to 144.6 +/– 7.1 mg/dl. Serum cholesterol decreased from 225.4 +/– 5.7 to
181.7 +/– 4.9 mg/dl. Serum triglycerides decreased from 283.7 +/– 28.8 to 186.2 +/– 11.6 mg/dl.
In aggregate, the group lost 4.3 kg/body weight and achieved 40.5% of their desired weight loss
on average. Maximum work capacity increased from 5.6 +/– 0.3 to 7.9 +/– 0.4 metabolic
equivalent of task (MET), and daily walking increased from 11.7 +/– 2.4 to 102.8 +/– 4.8
minutes/day. There was no correlation between the decrease in fasting blood glucose and weight
loss (r = 0.24), increase in walking time (r = 0.00), or increase in MET capacity (r = 0.05).
Conclusion: the Pritikin program of diet and exercise is an effective means for treating patients
with T2D.
* See reference.134
Figure 31.1 Response of Patients with Type 2 Diabetes to the Pritikin Program.*
Throughout the 1980s, insulin receptor and glu- The discovery of multiple genetic associations instead
cose transport protein physiology was being clarified. of a single causative genetic mutations for insulin resis-
Specifically, Jerrold Olevsky and the team at UCSD, as tance, MetS and T2D, has refocused attention away from
well as others, began to untangle the biology of insulin using only specific pharmaceutical interventions to the
resistance.4 They demonstrated at the mechanistic level incorporation of bona fide and evidence-based structured
that reversal of hyperglycemia with weight reduction led lifestyle changes for these dysglycemic states.
to the normalization of insulin receptor kinase function, 5
a participant in one of the key pathophysiological path-
ways in T2D. 31.2 PRIMARY PREVENTION
In the Banting Award Lecture of 1987, Gerald Reaven
of Stanford University provided for many clinicians a Prevention strategies for dysglycemia are considered as:
broadening in the understanding of T2D.6 He linked
a high insulin level and insulin resistance with what he • Primordial: usually population-based and to prevent
termed “Syndrome X,” but which would later be referred the emergence of modifiable risk factors (e.g. insulin
to as the “metabolic syndrome” (MetS) or “insulin resis- resistance, unhealthy eating patterns, physical inac-
tance syndrome.” The problem with T2D was no longer tivity, or overweight/obesity);
understood as involving just a high glucose level, but • Primary: applicable to patients with risk factors (e.g.
rather incorporating the pathophysiology of insulin resis- prediabetes, insulin resistance syndrome, or MetS)
tance and hyperinsulinemia. and to prevent the emergence of disease (e.g. T2D
At this point, the mingling and plausible causal associ- and cardiovascular disease [CVD]);
ations of insulin resistance, abdominal obesity, hyperten- • Secondary: applicable to patients with early disease
sion, and hyperlipidemia/atherosclerosis raised important (e.g. T2D without symptoms or complications) and
questions about reversibility. Significantly, Dean Ornish to prevent the emergence of symptomatic disease or
demonstrated the possibility that heart disease could be disease-related complications (e.g. diabetic nephrop-
reversed in at least some people.7 Only later would evi- athy or CVD);
dence clarify the biological underpinnings of this process,8 • Tertiary: applicable to patients with late disease (e.g.
as well as demonstrate its application in clinical practice.9 T2D with symptoms and/or complications) and to
It was then generally recognized that lifestyle change is prevent disease progression and mortality; and
the dominant basis for population-based hypertension • Quaternary: applicable to all patients and to prevent
control10 and that lowering weight will also lower blood overmedicalization.
pressure.11 Obesity, and in particular the abdominal obe-
sity associated with caloric excess, is a central pathophysi- Multiple studies have addressed this behavioral per-
ological state in both MetS and T2D, so caloric deficit spective from a primary prevention standpoint: the
and weight loss were recognized as key strategic targets in Bedford Survey (1962–72) and its 10-year follow-up,12 the
managing these conditions. These advances in basic sci- six-year Malmo Feasibility study,13 Diabetes Prevention
ence, enriched by clinical trial data, and coupled with new Program (DPP),14 Finnish Diabetes Prevention Study,15
epidemiological information, led to revisions in biochemi- Indian DPP,16 Da Quing,17 and others (Table 31.1). The
cal classifiers (e.g. fasting blood glucose) for prediabetes DPP tested the effectiveness of medication (metfor-
and T2D. min) vs. intensive lifestyle intervention in preventing the
31.3 Secondary and Tertiary Prevention: Can Pathology be Reversed? 395
TABLE 31.1 Major primary prevention studies on Type 2 31.3 SECONDARY AND TERTIARY
diabetes*
PREVENTION: CAN 31
Study Goals
RR
reduction
AR
reduction NNT PATHOLOGY BE REVERSED?
Da BMI > 25 – WT loss Diet Type 2 diabetes is generally regarded as preventable, with
Quing17 0.5-1 kg/mo to < 23
31% 23.5% 4.25 T2D-related pathophysiology and complications being
(China) BMI < 25
reversible to varying degrees in a significant number of
Exercise
patients by appropriately implementing accessible and
46% 26.6% 3.75 affordable lifestyle interventions. 27 With respect to sec-
Diet and Exercise
ondary prevention, once diagnostic biochemical thresh-
olds have been crossed, the question arises whether the
42% 21.7% 4.60 key underlying pathophysiological process can be stopped
FDPS138 WT loss > 5% Lifestyle or reversed. The answer appears to be “yes” for at least
(Finland) (–4.2kg) some patients, but the concept of “reversibility” can also
Total fat < 30% 58% 12% 8.33
be viewed in a relative sense (i.e. different amounts of
SFA < 10% At +3 years improvement in specific markers) and need not necessarily
Fiber > 15gm/1000
43% & 15% 6.6
require a “cure” (complete absence of disease), and, there-
kcal
Exercise>30 minutes/ 36% fore, reversibility is a realistic deliverable for those in need
day of secondary or tertiary prevention.
The concept of the reversal of T2D has been one that
DPP14 WT loss > 7% (–5.6 Lifestyle
has generated significant emotion in the past with many
(United kg)
States) Total fat < 25% 58% 14.5% 6.9 well-intentioned clinicians firmly believing that using the
Exercise >150 Metformin
word “diabetes” and “reversal” together would give those
minutes/week with the disease process a false sense of hope. To whatever
31% 7.2% 13.9 extent primary and secondary prevention can demonstra-
Indian Balanced calories & Lifestyle bly achieve reversibility, it is unfortunate that tertiary pre-
DPP16 activity for vention fails to achieve this same level of success. Tertiary
28.5% 15.7% 6.4
(India) appropriate weight prevention targets T2D-related complications but cannot
Avoid simple sugars Metformin completely reverse end-stage diseases, such as blindness,
& refined CHO
26.4% 14.5% 6.9
chronic kidney disease on renal replacement therapy,
Total Fat < 30 gms/day
Restrict SFA
advanced heart failure, stroke, and amputation.
Lifestyle and Metformin On the other hand, and in many instances, aspects
Increase fiber foods
– e.g., whole grains, 28.2% 15.5% 6.5 of T2D pathophysiology and less severe T2D complica-
legumes, vegetables tions are indeed reversible with lifestyle interventions.
& fruits For example, diabetic neuropathy measures can improve
* Abbreviations: AR – absolute risk; BMI – body mass index in kg/m2; CHO – carbo-
in some patients with certain dietary supplements, 28
hydrates; DPP – Diabetes Prevention Program; FDPS – Finish Diabetes Prevention dietary changes, 29 or external electrical stimulation.30
Study; NNT – number needed to treat; RR – relative risk; SFA – saturated fatty Atherosclerosis is also reversible7 and there is significant
acids; WT – weight.
evidence that there may be a regeneration of cardiac mus-
cle after a significant ischemia cardiac event. 31 As far back
progression of prediabetes to T2D.14 The finding that as 1958, Kempner et al.32 demonstrated a rather dramatic
modest weight loss (median 7% of body weight) and exer- reversal of retinal damage in patients treated with his
cise were approximately twice as effective as metformin “rice diet,” publishing a series of eight before-and-after
(RR reduction 58% for lifestyle vs. 31% for metformin) retinographs. Arguably, the best evidence of reversibility
was noteworthy. The effectiveness was even more dra- pertains to MetS pathophysiological markers33,34 and is
matic in those over 65 years of age.18 supported by lifestyle, pharmaceutical, and surgical inter-
The application of the DPP program, which focused on vention studies.4
weight loss, diet, and exercise, has been applied multiple Motivation and hope are tools that can optimize the
times in multiple populations showing similar benefits: chances for success of T2D preventive programs. Taylor35
latinas,19 low income, 20 educated, 21 and others. 22 The identifies early adopters of lifestyle change as the “Health
evidence is sufficiently conclusive and so widely accepted Motivated” and suggests that, at the time of diagnosis,
that these programmatic DPP lifestyle recommendations they will benefit from being advised that they are likely
have been included in various guidelines from professional to be able to reverse their diabetes completely by achiev-
organizations such as the American Diabetes Association ing weight loss equivalent to 15–20% of body weight.
(ADA)23 and the American Association of Clinical In those who are not adequately motivated to make the
Endocrinologists/American College of Endocrinology. 24 necessary changes, current clinical practice guidelines for
The work of the NextD group in applying these lifestyle managing T2D play a more prominent role. The caregiver
medicine principles into real-world policies and practices should recognize and address the presenting level of readi-
is likely to accelerate the practical application process25 ness to change, being astute enough to intervene appropri-
and soon reach a significant cultural “tipping point” in ately while recognizing when the person becomes ready to
diabetes prevention. 26 make more intensive lifestyle interventions. It should also
396 Chapter 31 Implementing Nutritional Lifestyle Treatment Programs in Type 2 Diabetes
be kept in mind that health care professionals’ personal β-cells, and hepatocytes.35 A better understanding of the
lifestyle practices play a significant role in both the recom- negative role of caloric excess and the beneficial effects of
mendations given and the effectiveness of lifestyle treat- caloric restriction reveals that it is important to minimize
ment instructions. 36,37 fat calories (9 kcal/g) for volume-based satiety at lower
calorie levels; this improves real-world acceptance of this
dietary pattern, especially when the majority of the foods
are high in fiber and water, which adds minimally to the
31.4 LIFESTYLE PROGRAMS caloric burden.41,42
FOR TYPE 2 DIABETES Roy Taylor’s reversal program of 600+ kcal/day
focused on approximately 15–20% of calories from fat,
Programs that address the lifestyle dimensions of T2D may derived from a combination of Optifast™ liquid meal
occur in a variety of settings, the most expensive being the and non-starch vegetables for eight weeks.35 A significant
live-in programs and the least expensive being the self-help degree of caloric deficit and weight loss is paramount to
books. In between are hospital-, clinic-, home-, coaching-, decrease ectopic pancreatic and hepatic fat stores, and
and web-based, among others. Each modality has specific foods with higher fat content generally have higher caloric
strengths and weaknesses. Programs must contextualize density. However, despite a sound physiological rationale,
individual behaviors using social, environmental, emo- there are little data guiding optimal amounts of fat intake
tional, and psychological variables. Individual life situa- to control or reverse the T2D process.
tions influence program selection, and behavioral research There is significant evidence that saturated fats (espe-
will need to clarify this selection process (Table 31.2). cially palmitic acid) are more likely to be pathologic with
During encounters with patients with T2D and over- respect to lipid and vascular systems. The ADA places the
weight/obesity, it is helpful to focus on active discus- reduction of saturated fat, trans-fats, and cholesterol as
sions on insulin levels. This can be communicated more primary fat-related dietary goals with the strongest evi-
effectively, not to mention guiding therapy, when fasting dence.43 There is good evidence that dietary patterns capi-
and/or stimulated insulin or C-peptide levels, or HOMA talizing on unsaturated fats have a more beneficial effect
(Figure 31.2) can be reliably measured and reported. on glucose tolerance and are the preferred dietary fats.44 – 48
Discussing the glycemic indices and load of specific foods, At the same time, supplements of omega-3 fatty acids
beverages, and meals can also be presented in the con- have not been shown to be of benefit for those with heart
text of pancreatic health and helps move messaging about disease or diabetes.49–51 This agrees with previous expe-
T2D from technical remarks about biochemical markers riences with a variety of supplements and supports the
(glucose and A1C) to more individualized, relevant, and concept that whole food-based healthy dietary patterns
understandable food-based remarks about eating. Hence, are likely more important than manipulating individual
various dietary strategies require specific tactics in life- macro- or micronutrients.
style programs for T2D.
In addition to standard diabetes resources (glucose
meters, certified diabetes educators, diabetes technolo-
gies, a variety of diagnostics for diabetes-related complica-
31.4.2 100% Plant-Based Eating Patterns
tion aggressive case finding, etc.), lifestyle program design The 100% whole food and plant-based diet has been
will need to incorporate nutritional expertise (physicians, explored in the treatment of T2D. Those promoting it have
registered dietitians, and advanced practice providers), as focused on both the beneficial effects of plant micro- and
well as tools for the visual impact of food, educational macronutrients as well as the benefits to global CO2 and
materials for nutrient content of foods, body composition methane production. In the late 1970s, Nathan Pritikin
analysis (e.g. bioelectrical impedance), and a network of served minimally processed, whole, plant foods, and while
consultants at the ready for expedited referrals. others have used this approach since then,52 the 100%
Specific evidence-based tools and concepts about nutri- plant-based diet was studied in a randomized control trial
tion from lifestyle programs are discussed below. by Neal Barnard and reported in 2008.53 The original
22-week trial compared the standard 2003 ADA diet with
a low fat, 100% plant-based diet in 100 randomly assigned
participants. Adherents were then followed up post-trial to
31.4.1 Low Fat Eating Patterns 74 weeks.54 Statistical analyses were complicated by efforts
The effectiveness of low fat eating patterns has been to account for medication adjustments as glycemic control
reported since the 1950s. Singh’s low fat38 and Kemper’s improved. In the vegan group, A1C fell 0.96% points (P <
rice diet39 fueled what many regarded as a counterintui- 0.0001), and in the ADA group, A1C fell by 0.56% points
tive perspective on diabetes treatment. Restricting carbo- (P < 0.0009). The baseline-adjusted between-group p-value
hydrates in some manner seemed to be the logical way was 0.091. However, in those with unchanged diabetes
to treat T2D. However, advances in the understanding of medications (N = 24 vegan; N = 33 ADA), there was an
insulin receptor signaling, glucose transport, and intra- A1C drop by 1.23% points and 0.38% points, respectively,
cellular metabolism have shed light on the pathological with a baseline-adjusted p-value of 0.007. Improvements
effects of ectopic fat in the liver and pancreas in T2D.35 in A1C were maintained at the end of the 74 weeks in those
Circulating fatty acids also play an important role in the on the 100% plant-based diet but returned to baseline in
development of insulin resistance in muscle,40 pancreatic those on the ADA diet.
TABLE 31.2 Behavioral programs for Type 2 diabetes
Program Type Description Strengths Weaknesses Examples
• Live-in • Individual pays to go to a “resort” for • Intensive care - experience dramatic • Cost of personnel for first class • NEWSTART. Weimar, California,
intensive lifestyle change changes in short time individualized experience Web: http://www.newstart.com
• Continuous vs. scheduled • A new start in a new place • Cost for purchase and • Pritikin Longevity Program, Miami,
programming • Physician supervised maintenance of facilities Florida, https://www.pritikin.com
• Customized care for the individual • No home community support
• May bill for some services • Hurdles for attendance – cost,
distance, time
• Hotel-based • Separates room rates from program • Uses existing structures and equipment • Depends on individual with • John McDougall, Santa Rosa,
and board charges. Trains hotel staff in • Can be done with 2-3 full time staff and strong public exposure California, https://www.drmcdougall.
appropriate food preparation hire contract speakers • Marketing com
• Resort services individualized • Minimal home community
• Win-win for hotel/resort support
• Easily scalable schedule – can start with
one a year and adjust for market demand
with minimal financial risk
• Hospital- • Uses existing hospital facilities and • Credibility • Medical staff resistance can • Saint Helena Center of Health
based personnel • Variety of staff pulled from different occur – James Peters, California, https://
• May be inpatient or outpatient centers decreases cost • Decreased procedural revenue www.adventisthealthtaketen.org
• Closeness to life-changing crisis that • Staff with acute care mentality or • Lee Health, Fort Meyers, Florida,
motivates change lack of understanding may http://www.leehealth.org/healthsolu
• Captive and focused marketing at time of counteract the message tion/CHIP.asp
crisis
• In-hospital lifestyle medicine consults
• Local health care system-based support
• Clinic-based • Physician-coordinated • Professional perception • Professional resistance and/or • Diabetes Undone, http://
• Conjunction with usual medical care • Increases practice with patients who want inertia diabetesundone.com
• May use Shared Medical Appointments to get better • Offices without classroom space
• Practice enjoyment • May need to hire individuals with
• Bill for services new skills
• Improved outcomes • Copays and deductibles may be
• Power of group process engages slow excessive for many patients
adopters • Market saturation
• Home community support • Privacy issues
• Business- • Employee focused lifestyle change • Employer is likely the strongest • Employer averse to decreasing • Cummins Livewell Center, http://
based • Financial incentives as motivators incentivizer of healthy lifestyle change health-care product use www.cumminslivewell.com
• Increased employee productivity, job
satisfaction, and quality of life
• Decreased health care costs due to less
chronic disease
• Group support and culture change
Continued
31.4 Lifestyle Programs for Type 2 Diabetes 397
31
TABLE 31.2 Behavioral programs for Type 2 diabetes (Continued)
Program Type Description Strengths Weaknesses Examples
• Community- • Prepared program run in community • Less expensive • Less professionalism when • Complete Health Improvement
based setting • Gets “graduates” involved in programs done without physician Program, https://www.chiphealth.
• Church • Creates community and cultural support support com
• YMCA • Minimal overhead • Volunteer based • Young Men’s Christian
• Public hall • Ease of access • Liability Association, http://www.ymca.net/
• Personal out-of- pocket diabetes-prevention/
expense may limit
participation.
• Community marketing
challenges
• Often run without subsidies
• Coaching- • Individual coaches • Individualized • Out-of-pocket expense Wellcoaches lifestyle coaches, http://
based • Directed personal choices are powerful • Coaches often experts in wellcoachesschool.com
for changing behavior making change but may not
know the best behaviors to
encourage
• Web-based • Program materials • Inexpensive and convenient • Less group support, • Diabetes Undone – linear and
• App or internet connections • Readily available community, engagement, and disease focused, http://
• May be incorporated into other accountability diabetesundone.com
programs • Hard to tell truth from
• Effectiveness of healthy behavior charlatan
tracking
• Self-help • Person reads or watches the • Inexpensive and convenient • No group support, • Forks Over Knives, https://www.
material, and then adopts the new • Readily available engagement, or accountability forksoverknives.com
lifestyle • Individualistic • Hard to tell truth from • NutritionFacts.org – review of
• Personal discovery charlatan latest nutritional research https://
• May be temporary lifestyle nutritionfacts.org
change
398 Chapter 31 Implementing Nutritional Lifestyle Treatment Programs in Type 2 Diabetes
31.4 Lifestyle Programs for Type 2 Diabetes 399
The homeostatic model assessment (HOMA) calculator is available from the United Kingdom
Prospective Diabetes Study (UKPDS) web site (https://ww w.dtu.ox.ac.uk/homacalculator/) and
can give a reasonable estimation of pancreatic beta-cell function and the combination of liver and
31
peripheral insulin resistance. The HOMA correlation coefficient with the gold standard glucose
clamp is reported as high as r = 0.82.135 HOMA calculations can identify those patients with
decreased pancreatic beta-cell function provided that there is an associated measure of insulin
resistance.136 Further understanding of HOMA may be found at www.familypracticepearls.com.
The evidence favors considering, offering, and even A 2009 review identified two intervention studies that
implementing a whole plant-based diet in patients with showed that fruit intake reduced body weight, while five
T2D, based on thorough discussions with the patient. One prospective observational studies showed that fruit con-
cannot say that the complete elimination of all animal sumption reduced the risk of developing overweight and
products is required, so it is preferred to avoid the explicit obesity, and four cross-sectional studies found an inverse
terms “vegan” or “vegetarian” in these discussions with association between fruit intake and body weight.61 There
patients. Rather, these evidence-based recommendations were no studies that identified a negative effect.61
may better be referred to as “healthy eating” patterns. More recent studies seek to identify the mechanisms
The term “diet” is oftentimes interpreted by patients as underlying the association of increased fruit intake with
restrictive or punitive and should, therefore, be used judi- improved weight in T2D. A recent review by Coe and
ciously. The term “plan” is typically used in the context Ryan reported that the glycemic and insulin responses
of a specific therapeutic endpoint, e.g. “diabetes eating to polyphenol-carbohydrate combinations varied accord-
plan.” It should be noted that a “cracker-cheese” vegetar- ing to their composition and that the polyphenol sources
ian or even a vegan that focuses on refined plant-based demonstrated the ability to reduce the peak and early-
food may not be choosing a healthy therapeutic option. phase glycemic response while maintaining the glycemic
Furthermore, foods that are refined or processed should response later in the digestion process.62 Interestingly,
be minimized. polyphenol sources were also shown to reduce peak insu-
lin response and sustain the insulin response, especially
when consumed with bread. A meta-analysis suggests that
31.4.3 Increased Fruit there may be a “priming effect” of small amounts of fruc-
tose (≤36 grams/day) that improves glycemic control with-
Standard T2D dietary advice often seeks to limit intake out negatively affecting body weight or insulin.63
of some plant products because of high glycemic load
issues. Fruit is commonly restricted in dietary instruction
because of its short-term effect on blood glucose despite
well-documented anti-inflammatory and health-promot- 31.4.4 Increased Vegetable Intake
ing effects. The beneficial effects of fruit are derived from Diets high in non-starchy vegetables have been associ-
many sources, including macronutrients, micronutrients, ated with reversal of some T2D parameters.57 In addition,
polyphenols, and even oligosaccharides. 55 There is inten- epidemiologic evidence has pointed to populations with
tion-to-treat RCT evidence that encouragement to take at higher starchy vegetable intake having lower T2D preva-
least two pieces vs. no more than two pieces of fruit daily lence rates.64 Yet, there are also reports of increased risk
did not have an adverse effect on A1C, weight, or abdomi- from staple starch sources. For example, epidemiologic evi-
nal circumference. 56 dence links potato intake with increased risk for developing
The weight of evidence does not support the general T2D.65 White (polished) rice is associated with higher T2D
practice of significantly reducing fruit intake in patients risks than brown rice.66,67 This may be due to the effect of
with MetS or T2D. 57 Rodriguez et al. 58 demonstrated that degermination and/or increased amylose in brown rice.68
a high fruit intake study group had a significant reduction
in waist circumference compared to a low fruit group (5.5
vs. 2.4 cm; p = 0.048) with weight loss being similar in
the two groups (6.1 vs. 6.4 kg; p = 0.78). De Oliveira et
31.4.5 Grain Intake
al. 59 reported an intervention study in which 49 women In 2016, Aune et al.69 published a systematic review and
with obesity and matched total energy and fiber dietary dose-response meta-analysis of cohort studies on whole
content were randomized to add either three apples, three and refined grains and the risk of T2D. Relative risk was
pears, or three oat cookies to their usual diet for 10 weeks. calculated using a random effects model of 16 cohort
The group with oat cookies lost less weight than the two studies. Three servings a day of whole grain showed a RR
groups with additional fruit (−0.9 vs. −0.8 vs. 0.2 kg, of 0.68 (95% CI 0.58–0.81, I 2 = 82%, N = 10) and for
respectively). Madero et al.60 demonstrated that a moder- refined grains, only 0.95 (95% CI 0.88–1.04, I 2 = 53%,
ate intake of natural fructose-containing foods reduced N = 6). They reported inverse associations for subtypes
body weight more than the low-fructose intake group (4.1 of whole grains including whole grain bread, whole grain
vs. 2.9 kg; p = 0.02). cereals, wheat bran, and brown rice. Again, white rice
400 Chapter 31 Implementing Nutritional Lifestyle Treatment Programs in Type 2 Diabetes
was associated with increased risk. In 2010, Carter et al.70 reported that in a “healthy” population, the substitution
analyzed prospective cohort studies of diet on diabetes of 3% of energy to plant protein from any animal pro-
risk in a meta-analysis. In the six studies that met inclu- tein (e.g. processed meat, red meat, eggs, dairy, poultry,
sion criteria, there were no significant benefits or harms or fish) led to a 10% decrease in all-cause mortality and a
of increasing the consumption of vegetables, fruit, or the 12% decrease in cardiovascular mortality.
combination, but in those that reported green leafy veg- There is also evidence that animal protein acceler-
etable consumption, there was a 14% risk reduction for ates nephropathy in those with diabetes. In 2016, Chen
T2D (hazard ratio of 0.86, 95% CI 0.77–0.97; p = 0.01). et al.85 reported that individuals in the National Health
Grains also affect appetite and energy intake through ben- and Nutrition Examination Survey (NHANES)-3 with
eficial effects on the microbiome, via increased prebiotic chronic kidney disease (estimated glomerular filtration
delivery71 and various humoral modulators, such as adipo- rate [eGFR] < 60 cc/min) had 23% lower mortality for
nectin.72 Grains have other benefits in the prevention and every 33% increase in the plant/total protein ratio. Micro-
treatment of T2D, as reviewed recently.73,74 albuminuria in T2D has been associated with high intake
from animal sources.86 Crossover trial testing has dem-
onstrated that the protein source can affect the degree of
micro-albuminuria with plant and chicken protein being
31.4.6 High Fiber Diet less harmful than red meat.87 In a four year RCT of adults
In the late 1970s, James Anderson of University of with T2D and micro-albuminuria, there was a significant
Kentucky, Lexington reported significant improvement improvement in proteinuria in those who had half of their
in glucose management when focusing on fiber intake, animal protein replaced with soy protein.88 There were
approximately 40–50 grams/day.75 At that time, the major also significant improvements in total cholesterol, LDL
debate for nutrition and T2D concerned low carbohydrate cholesterol, and fasting glucose. Potential mechanisms for
vs. low fat eating patterns. Since animal products have no these effects include decreased renal blood flow, decreased
fiber, this healthy eating pattern was tantamount to a diet GFR, and increased acid load of the animal proteins.89
rich in minimally processed plants. There is even evidence that removing animal protein (and
Dietary fiber modulates the postprandial glucose thereby creating a plant-based diet) can help improve neu-
response by acting as a physical barrier to glucose absorp- ropathy. The original report by Crane et al.29 was recently
tion and blunting prandial glycemic excursions.42,76,77 reproduced in a small, randomized control trial with com-
Fiber is metabolized by intestinal bacteria into short-chain munity-dwelling patients with T2D on a plant-based diet,
fatty acids, which improve glucose sensitivity and insulin demonstrating decreased neuropathy pain scores in 20
signaling.78 High fiber foods also have lower energy den- weeks when compared with those on the control diet.90
sity, promote satiety, and reduce insulin resistance, assist- Another interesting line of evidence for minimizing or
ing with weight loss.42 Specific prebiotic dietary fibers eliminating animal proteins is the effect of high amounts
such as galactooligosaccharides, inulins, and their fruc- of leucine on the mechanistic target of rapamycin com-
tooligosaccharide derivatives have been shown to improve plex 1 (mTORC1) signaling as identified by Melnik91 of
the species composition of the colonic microbiota.79 the University of Osnabrück, Germany. Dairy and meat
Beneficial changes in the gut microbiota increase short- protein independently stimulate insulin and insulin-like
chain fatty acids, particularly propionate, butyrate, and growth factor 1 (IGF-1) signaling effects on mTORC1 acti-
acetate, which have health-promoting properties, includ- vation.92 Added to this effect is the additional stimulus of
ing improved lipid metabolism and immunomodulatory a high concentration of leucine, itself a primary and inde-
effects.78 Certain fibers also enhance mineral absorption pendent stimulus of mTORC1 activation.93,94 The down-
of magnesium and other elements, which may be benefi- stream target of mTORC1, the serine/threonine-regulated
cial to MetS pathophysiology.80 kinase (S6K)-1, induces insulin resistance thereby increas-
ing the metabolic burden on β-cells.95 Leucine-mediated
mTORC1-S6K1 signaling plays an important role in adi-
pogenesis, increasing the likelihood of obesity-mediated
31.4.7 Low Protein Diet insulin resistance.96,97 Leucine-rich protein ingestion
Even though the 2015 Dietary Guidelines for Americans (muscle actin-myosin) leads to an exaggerated mTORC1-
support lean protein consumption81 for the general pop- dependent insulin secretion, increased β-cell growth, and
ulation, the evidence does not support the routine con- β-cell proliferation promoting an acceleration of replicative
sumption of animal proteins for people with T2D. A 2015 β-cell senescence and eventual apoptosis.98 Interestingly,
meta-analysis of 13 randomized controlled trials exam- Melnic99 also points out that metformin antagonizes leu-
ined the effect of transitioning from dietary animal to cine-mediated mTORC1 signaling and that plant-derived
plant protein (approximately 35% of calories in both polyphenols and flavonoids such as Reservatrol100 (from
groups) on glycemic control and found improvements in grapes), curcumin101 (from turmeric), epigallocatechin
A1C, fasting insulin, and fasting insulin.82 Also in 2015, gallate102 (EGCG; from green tea), genistein103 (soy-based
a large European study demonstrated that replacing 10 phytoestrogen), and 3,3ʹ-diindolylmethane (DIM; from
grams of dietary carbohydrate with animal protein in cruciferous vegetables) have all been identified as inhibi-
subjects with T2D led to significant weight gain while tory modulators of mTORC1 and demonstrate both anti-
replacing with plant proteins did not.83 More importantly, diabetic and anti-obesity effects.
those subjects that transitioned to the plant protein had a In short, an effective nutritional lifestyle intervention
21% decrease in all-cause mortality. In 2016, Song et al.84 that minimizes or eliminates animal proteins will generally
31.4 Lifestyle Programs for Type 2 Diabetes 401
lead to better outcomes.73 For office patients in transition decreased lipid or glucose osmotic pressures, decreased
31
programs, it is reasonable (even if not ideal) to recommend inflammatory cytokines from intra-abdominal fat,123
focusing on minimally refined plants and using animal prod- decreased Krebs cycle-driven endothelial inflammation,124
ucts as condiments (flavoring), with the intent of eventually and increased kidney function.125 With these observations
removing the animal products altogether or limiting them in mind, when the blood pressure begins to normalize with
only to 1–2 times a year for holiday celebrations. In more aggressive lifestyle treatment of MetS, the first medication
intensive lifestyle interventions, motivated patients can rea- that may be safely removed is commonly the diuretic while
sonably be taught through experience the benefits of remov- the last blood pressure medications removed are the ACE
ing all animal products from the diet for maximum effect. inhibitor or angiotensin receptor blocker.
While more research is needed regarding the impor-
tance of hydration in MetS and T2D, it seems reason-
able to avoid behaviors known to increase the activity of
31.4.8 Hydration and Sodium Intake angiotensin II and vasopressin, namely, dehydration and
Water intake has been recognized as a potential tool in low sodium intake. While over-hydration has its poten-
weight loss. Some investigators report that water-drinking tial negative effects, adequate hydration is clearly superior
enhances thermogenesis and increases metabolic rate.104 to dehydration and has both low risk and low monetary
Enhanced water intake contributes to reducing the sensa- expense. Since many, if not most, patients with T2D and
tion of hunger and increasing satiety.105 In a study that obesity tend to be dehydrated, it is reasonable to encour-
assessed pre-meal water consumption in patients on a age the free use of water.
hypo-caloric diet, the investigators found consuming 500 The best level of water intake remains unknown. It is
ml of water prior to each meal led to a larger weight loss not rare to find a person embracing an aggressive lifestyle
than the hypo-caloric diet alone.106 There is evidence that change to present with hyponatremia from excessive water
increased hydration decreases food intake and increases intake along with diuretic use. A variety of recommenda-
lipolysis.107 In addition, self-reported low hydration has tions have been made, but evidence is lacking regarding
been associated with higher blood sugars.108 optimal amounts of water to advise. Until more is known,
There is a growing evidence that elevated vasopressin it seems prudent to eat a diet high in minimally processed
(antidiuretic hormone) is a risk factor for hyperglycemia plants while aiming for clear (colored) urine output and
and T2D.109,110 Angiotensin II also correlates well with avoiding a severe sodium restriction.
body weight and MetS, and levels tend to decrease as
weight is reduced.111 Also of interest is the positive cor-
relation between angiotensin and leptin, and their nega- 31.4.9 Meal Timing and
tive correlations with lipoprotein lipase.109 Multiple other
signal processes are likely involved in this process as vaso-
Intermittent Fasting
pressin stimulates the release of glucocorticoids, which in It has been dogma in nutrition education for some time
turn up-regulates S6K1.112 that 3500 kcal is equivalent to one pound, either added
Sodium intake should be limited to reduce hyperten- or subtracted. However, evidence has mounted that this is
sion, cardiovascular morbidity, and mortality.113 Increased not the general case. Different types of calories are treated
hydration increases natriuresis and improves CVD risk. On differently. For example, it is commonly understood
the other hand, there is evidence that low sodium intake that carbohydrates (especially glucose) are preferentially
can increase angiotensin II, worsen insulin resistance, and burned or turned to heat while (excess) fat calories are
increase mortality114 –116 Overall, adequate hydration and a more likely to be stored.
moderate sodium intake is a safe strategy.117 The timing of caloric consumption can also make a sig-
Salt sensitivity is not practical to measure in the clini- nificant difference in how those calories are utilized. As
cal setting but has similar effects in longitudinal studies early as 1975, chronobiologist Franz Halberg and fellow
to hypertension on mortality; when salt sensitivity and researchers examined weight loss in a metabolic ward with
hypertension are both present, the effects are less than a valid crossover design and demonstrated greater weight
additive.118 There is evidence that salt sensitivity can loss in those taking the 2000 calories as a single daily
be reversed with adequate amounts of potassium in the meal in the morning, compared with the evening when
diet.119,120 The Institute of Medicine reports that 96% there was minimal weight loss or even weight gain.126 The
of Americans are not getting the Recommended Dietary dietary intake pattern of a single (larger) meal a day occur-
Allowance (RDA) of potassium presumably from inade- ring later in the day has resulted in worsening glucose tol-
quate intake of plants.121 These observations seem to indi- erance and fasting blood sugars when compared with the
cate that in the presence of adequate whole food and plant same hypocaloric intake taken in six meals.127 In contrast,
intake, a severe sodium restriction is not necessary and a a two-meals-a-day pattern with the leaving off of the eve-
moderate sodium intake is reasonable. ning meal seems to bring superior results with the added
Diuretics cause loss of sodium, potassium, and often evidence of a significant decrease in hepatic fat as well,
magnesium, all of which can potentially cause or complicate when compared with the same hypocaloric intake taken in
pathophysiology. Some patients adopting low-calorie diets six meals.127 Fasting plasma glucose, C-peptide, and gluca-
have observed an accelerated initial loss of weight, which gon decreased, while there was an increase in oral glucose
they have associated with diuresis.122 This water-weight insulin stimulation, compared with those with the same
loss likely occurs from a combination of factors, includ- caloric restriction split into six meals. These results suggest
ing the increased efficacy of atrial natriuretic peptide,122 that, for patients with T2D on a therapeutic hypoenergetic
402 Chapter 31 Implementing Nutritional Lifestyle Treatment Programs in Type 2 Diabetes
diet, eating larger breakfasts and lunches may be more There is also evidence that daily intermittent fasting (16
beneficial than six smaller meals during the day.128 hours with no intake of calories) increases adiponectin up
There is also RCT evidence that moving the majority to 37%.131 This correlates well with improved insulin sen-
of the calories to earlier in the day and minimizing the sitivity and adipose tissue lipolysis seen in other intermit-
evening meal is beneficial for adults with T2D.129 This tent fasting studies.132 For additional benefit, there is
makes sense with the added understanding that when the evidence that a longer time in the fasting state reduces
breakfast is a larger meal with significant carbohydrate the IFG-1/protein kinase A (PKA) ratio and seems to
and protein intake there is a corresponding decrease in the promote stem cell regeneration.133 See Figure 31.3 for
induced compensatory adjustments of hunger cravings, as a description of a successful lifestyle program for T2D
well as suppression of ghrelin.130 using intermittent fasting.
The advantages of fasting in patients with T2D are illustrated from the experiences of a live-in program active in
the early 2000’s at the Lifestyle Center of America in south-central Oklahoma (Sulphur, Oklahoma, USA). The team
used a three-day fast to “jumpstart” the physiological process. Patients were assessed for pancreatic reserve by both
stimulated C-peptide and HOMA-Beta testing. A stimulated C-peptide137 over 2 ng/ml (with a blood sugar of at least
170 mg/dl) and/or a HOMA-Beta136 above 35% (in the present of increased insulin resistance) reasonably predicted
the ability of the individual with T2D to discontinue insulin during the fast. Those with lower levels remained on low
basal insulin (around 8-20 units of insulin glargine; 0.1 unit/kg) during the fasting state. Lab testing was performed
for baseline electrolyte measures and patients were observed for sodium, potassium, and magnesium deficiency. These
were replaced with magnesium or potassium supplementation and/or bullion tea as needed. During the three-day
fast, patients were allowed to have bullion and herbal teas without added calories as well as a mixture of flavored non-
caloric guar gum and psillium (as soluble fibers). This provided something to ingest at mealtime social events and
served to decrease complaints of stomach irritation associated with medication ingestion.
During the fast, patients were also taken off all diabetes medications except metformin and any appropriate basal
insulin (around 0.1 u/kg). Hypertensive medications were left unchanged until the blood pressure was under 110
mmHg systolic or symptoms of orthostatic hypotension began to occur. Patients monitored their own blood sugars
with their personal glucometers and reported any problems. Most patients were surprised at how much better they
felt and it was common for them to request to fast a day longer as they saw their blood sugars decreasing. It was
observed that those with T2D do not experience the intense hunger during a fast that is experienced by those with
normal insulin levels and sensitivities.
The exercise program included a heavy reliance on intermittent training with target heart rates beginning around
50% of capacity (halfway between resting heart rate and theoretical maximum) which was well tolerated by those
who were fasting. Cardiac stress testing was done on every participant within the first day or two to ensure there
was no evidence of ischemia or arrhythmia at recommended exertion levels. It was common for fasting sugars to
have normalized by the end of the third day and, on day 4, breakfast consisted of steamed above-ground vegetables.
Prolonged fasting not only affected physiology but also dietary taste. Nearly all patients reported that these were the
best vegetables they had ever tasted, enabling them to start a new dietary pattern with significantly modified taste bud
perception. Other simply prepared, whole plant foods were then added and a more “normal” whole food plant-based
eating pattern ensued. Patients were told of the benefits to eliminating the evening meal and those who chose to do
so generally lost more weight and came off more medication without suffering untoward events. Some used the guar
gum/psyllium mixture as the evening meal, while others used the time to add more exercise.
During the fast, it was not uncommon for those with adequate insulin production (as demonstrated by HOMA Beta
calculation and stimulated C-peptide testing) to normalize sugars on just metformin. Blood pressures usually began
to drop at the end of the second week and medication dosages were cut back appropriately. At the end of the usual
18-day program there were commonly reports of decreasing GERD symptoms, less joint pain, better sleep, clearer
minds, less depression, improving neuropathy (generally after 7-10 days), and a general improvement in the sense of
well-being.
A one-year phone follow up data collection ascertained the success of the inpatient program at changing behaviors
and effecting outcomes. The easiest measure to collect was self-reported weight. Out of around 150 patients, only
two weighed more than when they left the program at one year. Everyone else had either stayed the same or lost more
weight. In comparing the top quintile (lost up to 60 pounds) with the lowest quintile, the largest predictor of weight
loss was the number of days in the last week on a 100% plant based diet. While other target behaviors were not found
to be predictive of the difference between the two groups, it was surprising how many patients were still continuing
with the program recommendations.
Figure 31.3 Intermittent Fasting in a Live-in Program for Type 2 Diabetes – Personal Observations.
Clinical Applications 403
31
eating pattern commonly recommended for those with
The evidence is growing that the expression of T2D is T2D. However, more research is needed to identify which
significantly influenced by lifestyle practices. Addressing patient subset best responds to various fasting strategies.
and improving lifestyle choices can often prevent T2D Besides nutritional services, other lifestyle modalities that
from occurring. There is now evidence that patients with are incorporated in T2D programs or part of an expe-
T2D adopting healthy lifestyle practices may experience dited referral network include exercise physiology con-
a reversal of the disease expression process as well. The sultations and classes, formal sleep hygiene assessments,
critical point here is that lifestyle medicine strategies behavioral medicine, and diabetes education programs. In
require actualization: a comprehensive, programmatic, sum, the use of implementation-science principles, as well
yet individualized approach to implementation tactics to as research efforts to improve lifestyle medicine program
best realize success. A review of clinical applications of development, are required to optimize T2D care.
this approach is summarized at the end of this chapter.
It is no longer appropriate to categorically tell patients
that T2D is not reversible. While some endpoint patholo- CLINICAL APPLICATIONS
gies are irreversible, many others may be at least improved
and possibly even reversed with aggressive lifestyle change. 1. Clinical evidence supports lifestyle choices as a
This aspect of health messaging is central to motivational driver of T2D disease expression and therefore these
interviewing and inducing the behavioral changes needed lifestyle variables need to be effectively addressed to
to actualize lifestyle medicine recommendations. More prevent or reverse disease progression.
specifically, there is the most evidence for the reversibility 2. Reversal of T2D may include complete or partial
of insulin resistance and coronary heart disease. There is reversal of primary or secondary effects. While some
an actionable amount of evidence supporting the improve- pathology is clearly not reversible (e.g. amputations
ment of β-cell function, neuropathy, and retinal pathology and end-stage kidney disease), there is evidence that
with appropriate lifestyle changes. There is less evidence other, less severe features are reversible at varying
for observed improvement in other associated patholo- degrees. These features include MetS components,
gies such as nephropathy, gastroparesis, gastroesophageal muscle, and liver insulin resistance, pancreatic β-cell
reflux disease, erectile dysfunction, and depression. function, atherosclerosis, abdominal obesity, and,
Effective lifestyle treatment for those with T2D should to some degree, both neuropathy and retinopathy.
incorporate identification of the patient’s insulin status. 3. Clinicians have an ethical responsibility to inform
When available, doing so with tools such as the HOMA cal- patients with T2D about the potential for and
culation and/or the insulin/C-peptide stimulation test will nature of reversibility, particularly in the context of
identify those who have inadequate insulin reserve due to motivational interviewing.
β-cell failure. This cognitive step helps the physician, health 4. Effective evidence-based lifestyle programs should
care professional, and patient to set appropriate expectations focus on low fat, plant-based eating patterns that
for the response to intensive lifestyle interventions, as well as include minimally processed fruit, vegetables, whole
furthering motivational discussions on disease mechanisms. grains, and high fiber foods as well as being low in
Programmatic interventions apply various lifestyle animal protein.
modalities that can be individually tailored in the treat- 5. Adequate hydration decreases inflammation
ment of T2D. Health care professionals should have expe- and improves insulin sensitivity, and should be
rience and expertise with a range of these modalities so encouraged.
that they are poised to fashion approaches having the 6. Meal timing is another diet-related strategy for
greatest likelihood for success. Achievement and mainte- improving the pathophysiology of T2D. There is evi-
nance of healthy body weight with calorically restricted dence that eating earlier in the day and either elimi-
eating patterns, as needed, form the foundation of success- nating or significantly minimizing the evening meal
ful lifestyle treatment programs. This approach focuses on in certain instances is beneficial. More research is
whole, minimally processed, and plant foods and tends to needed regarding meal timing strategies and tactics
be high in fiber, have less harmful proteins, and be low in T2D.
in fat. Other dietary modalities include adequate hydra- 7. Intermittent fasting has physiological effects favor-
tion and appropriate sodium intake. With caloric excess ing T2D reversal and can be accomplished by skip-
as a significant driver for T2D expression, it is not sur- ping the evening meal (short) or avoiding calorie
prising to find that caloric restriction and certain types intake for longer periods (e.g. 24 hours). However,
of fasting strategies can be advantageous as well. For more data is required in order to provide specific,
example, intermittent fasting induced by an elimination individualized patient recommendations regarding
or significant minimization of the evening meal can have intermittent fasting.
404 Chapter 31 Implementing Nutritional Lifestyle Treatment Programs in Type 2 Diabetes
REFERENCES
1. Barnard RJ. Effects of life-style modifica- 18. Brokaw SM, Carpenedo D, Campbell P, 32. Kempner W, Lohmann R, Schlayer C.
tion on serum lipids. Arch Intern Med et al. and the Montana Cardiovascular Effect of rice diet on diabetes mel-
1991;151:1389–1394. Disease and Diabetes Prevention litus associated with vascular disease.
2. Barnard RJ, Jung T, Inkeles SB. Diet and Workgroup. Effectiveness of an adapted Postgrad Med 1958;24(4):359–371.
exercise in the treatment of NIDDM. The diabetes prevention program lifestyle 33. Grundy SM. Metabolic syndrome update.
need for early emphasis. Diabetes Care intervention in older and younger adults. Trends Cardiovasc Med 2016;26(4):364–
1994;17:1469–1472. J Am Geriatr Soc 2015;63:1067–1074. 373. doi: 10.1016/j.tcm.2015.10.004.
3. Barnard RJ. Research at the Pritikin 19. O'Brien MJ, Perez A, Scanlan AB, Epub 2015 Oct 31. Review. PMID:
Longevity Center. Appl Physiol et al. PREVENT-DM comparative 26654259.
1985;13:8–13. effectiveness trial of lifestyle interven- 34. Sperling LS, Mechanick JI, Neeland IJ, et
4. Olefsky IM. Pathogenesis of non- tion and metformin. Am J Prev Med al. The cardio metabolic health alliance:
insulin dependent diabetes (Type II). In: 2017;52(6):788–797. doi:10.1016/j. Working toward a new care model for the
DeGroot U, Besser GM, Cahill JC, eds. amepre.2017.01.008. metabolic syndrome. J Am Coll Cardiol
Endocrinology. 2nd ed. Philadelphia: WB 20. Ackermann RT, Liss DT, Finch EA, et al. 2015;66(9):1050–1067. doi: 10.1016/j.
Saunders Co., 1989: 1369–1388. A randomized comparative effectiveness jacc.2015.06.1328. Review.
5. Olefsky JM, Nolan JJ. Insulin resis- trial for preventing type 2 diabetes. Am J 35. Taylor R. Pathogenesis of type 2 diabetes:
tance and non-insulin-dependent Public Health 2015;105(11):2328–2334. Tracing the reverse route from cure to
diabetes mellitus: Cellular and molecu- doi: 10.2105/AJPH.2015.302641. cause. Diabetologia 2008;51:1781–1789.
lar mechanisms. Am J Clin Nutr 21. O'Brien MJ, Whitaker RC, Yu D, et al. 36. Frank E, Segura C, Shen H, et al.
1995;61(supple):980S–986S. The comparative efficacy of lifestyle inter- Predictors of Canadian physicians’
6. Reaven GM. Banting Lecture 1988. Role vention and metformin by educational prevention counseling practices. Can J
of insulin resistance in human disease. attainment in the Diabetes Prevention Public Health 2010;101:390–395.
Diabetes 1988;37(12):1595–1607. PMID: Program. Prev Med 2015;77:125–130. 37. Oberg EB, Frank E. Physicians’ health
3056758. doi:10.1016/j.ypmed.2015.05.017. Epub practices strongly influence patient health
7. Ornish D, Scherwitz LW, Billings JH, 2015 May 27. practices. J R Coll Physicians Edinb
et al. Intensive lifestyle changes for 22. Ackermann RT. Working with the 2009;39(4):290–291.
reversal of coronary heart disease. JAMA YMCA to implement the diabetes preven- 38. Singh I. Low-fat diet and therapeutic
1998;280:2001–2007. doi: 10.1001. tion program. Am J Prev Med 2013;44(4 doses of insulin in diabetes mellitus.
8. Singh IM, Shishehbor MH Ansell BJ. Suppl 4):S352–S356. doi: 10.1016/j. Lancet 1955;268:422–425.
High-density lipopritein as a therapeu- amepre.2012.12.010. 39. Kempner W, Peschel RL, Schlayer C.
tic target. A systemic review. JAMA 23. Standards of Medical Care in Effect of rice diet on diabetes mel-
2007;298(7):786–798. Diabetes—2017. Diabetes Care Volume litus associated with vascular disease.
9. Esselstyn CB Jr, Gendy G, Doyle J, et 40, Supplement 1, January 2017. Postgrad Med 1958;24:359–371.
al. A way to reverse CAD? J Fam Pract 24. Consensus statement by the American 40. Martins AR, Nachbar RT, Gorjao R,
2014;63:356–364. Association of Clinical Endocrinologists et al. Mechanisms underlying skeletal
10. Ferdinand KC, Nasser SA. Management and American College of Endocrinology muscle insulin resistance induced by fatty
of essential hypertension. Cardiol Clin on the Comprehensive Type 2 Diabetes acids: Importance of the mitochondrial
2017;35(2):231–246. doi: 10.1016/j. Management Algorithm – 2017 Executive function. Lipids Health Dis 2012;11:30.
ccl.2016.12.005. Summary. Endocr Pract 2017;23(2):207– doi: 10.1186/1476-511X-11-30.
11. Stevens VJ, Obarzanek E, Cook NR, et al. 238. doi: 10.4158/EP161682.CS. 41. Lisle, DJ, Goldhamer DC. The Pleasure
for the Trials of Hypertension Prevention 25. Ackermann RT, Kenrik Duru O, Trap: Mastering the Hidden Force that
Research Group. Long-term weight loss Albu JB, et al. NEXT-D Study Group. Undermines Health & Happiness.
and changes in blood pressure: Results Evaluating diabetes health policies using Summertown, TN: Book Publishing
of the trials of hypertension prevention, natural experiments: The natural experi- Company, 2006.
Phase II. Ann Intern Med 2001;134:1–11. ments for translation in diabetes study. 42. Lattimer JM, Haub MD. Effects of
12. Keen H, Jarrett RJ, McCartney P. The Am J Prev Med 2015;48(6):747–754. doi: dietary fiber and its components on meta-
ten-year follow-up of the Bedford survey 10.1016/j.amepre.2014.12.010. bolic health. Nutrients 2010;2:1266–
(1962–1972): Glucose tolerance and 26. Ackermann RT. Diabetes prevention at 1289; doi: 10.3390/nu2121266.
diabetes. Diabetologia 1982;22:73–78. the tipping point: Aligning clinical and 43. American Diabetes Association. Lifestyle
13. Eriksson KF, Lindgarde F. Prevention of public health recommendations. Ann management. Sec. 4. In standards of
Type 2 (non-insulin-dependent) diabetes Intern Med 2015;163(6):475–476. doi: medical care in diabetes 2017. Diabetes
mellitus by diet and physical exercise. 10.7326/M15-1563. Care 2017;40(Suppl. 1):S33–S43.
Diabetologia 1991;34:891–898. 27. Herman WH, Edelstein SL, Ratner RE, 44. Estruch R, Ros E, Salas-Salvado ́ J, et al.;
14. Knowler WC, Barrett-Connor E, Fowler et al.; Diabetes Prevention Program PREDIMED Study Investigators. Primary
SE, et al.; Diabetes Prevention Program Research Group. Effectiveness and prevention of cardiovascular disease
Research Group. Reduction in the cost-effectiveness of diabetes preven- with a Mediterranean diet. N Engl J Med
incidence of type 2 diabetes with lifestyle tion among adherent participants. Am J 2013;368:1279–1290.
intervention or metformin. N Engl J Med Manage Care 2013;19(3):194–202. 45. Brehm BJ, Lattin BL, Summer SS, et al.
2002;346:393–403. 28. Ziegler D, Nowak H, Kempler P, et al. One- year comparison of a high-mono-
15. Uusitupa M, Lindi V, Louheranta A, et Low PA: Treatment of symptomatic unsaturated fat diet with a high-carbo-
al. Long-term improvement in insulin diabetic polyneuropathy with the antioxi- hydrate diet in type 2 diabetes. Diabetes
sensitivity by changing lifestyles of people dant alpha-lipoic acid: A meta-analysis. Care 2009;32:215–220.
with impaired glucose tolerance 4-year Diabet Med 2004;21:114–121. 46. Shai I, Schwarzfuchs D, Henkin Y, et
results from the Finnish diabetes preven- 29. Crane MG, Sample C. Regression al.; Dietary Intervention Randomized
tion study. Diabetes 2003;52:2532–2538. of diabetic neuropathy with total Controlled Trial (DIRECT) Group.
16. Teufel-Shone NI, Jiang L, Beals J, et al. vegetarian (vegan) diet. J Nutr Med Weight loss with a low-carbohydrate,
Changes in food choices of participants 1994;4:431–439. Mediterranean, or low-fat diet. N Engl J
in the special diabetes program for 30. Bosi E. Conti M, Vermigli C, et al. Med 2008;359:229–241.
Indians-diabetes prevention demonstra- Effectiveness of frequency-modulated 47. Brunerova L, Smejkalova V, Potockova
tion project, 2006–2019. Prev Chronic electromagnetic neural stimulation in the J, et al. A comparison of the influence of
Dis 2015;12;12:E193. doi: 10.5888/ treatment of painful diabetic neuropathy. a high-fat diet enriched in monounsatu-
pcd12.150266. Diabetologia 2005;48:817–823. rated fatty acids and conventional diet on
17. Pan XR, Li GW, Hu YH, et al. Effects 31. Dueñas A, Aranega AE, Franco D. More weight loss and metabolic parameters in
of diet and exercise in preventing than just a simple cardiac envelope; obese non-diabetic and type 2 diabetic
NIDDM in people with impaired cellular contributions of the epicardium. patients. Diabet Med 2007;24:533–540.
glucose tolerance. The Da Qing IGT Front Cell Dev Biol 2017;5:44. doi: 48. Bloomfield HE, Koeller E, Greer N,
and Diabetes Study. Diabetes Care 10.3389/fcell.2017.00044. PMCID: et al. Effects on health outcomes of a
1997;20(4):537–544. PMC5410615. Mediterranean diet with no restriction
References 405
on fat in- take: A systematic review 63. Sievenpiper JL, Chiavaroli L, de Souza 77. Li D, Kirsop J, Tang WH. Listening
and meta-analysis. Ann Intern Med RJ, et al. Systematic Review with Meta- to our gut: Contribution of gut micro-
49.
2016;165:491–500.
Wheeler ML, Dunbar SA, Jaacks LM, et
al. Macronutrients, food groups, and eat-
Analysis: ’Catalytic’ doses of fructose may
benefit glycaemic control without harm-
ing cardiometabolic risk factors: A small
biota and cardiovascular risk in
diabetes pathogenesis. Curr Diab Rep
2015;15:63.
31
ing patterns in the management of diabe- meta-analysis of randomised controlled 78. Baothman OA, Zamzami MA, Taher I,
tes: A systematic review of the literature, feeding trials. Br J Nutr 2012;108(3):418– et al. The role of gut microbiota in the
2010. Diabetes Care 2012;35:434–445. 423. doi: 10.1017/S000711451200013X. development of obesity and diabetes.
50. Crochemore ICC, Souza AFP, de Souza Epub 2012 Feb 21. Lipids Health Dis 2016;15:108.
ACF, et al. v-3 polyunsaturated fatty 64. Diet, nutrition and the prevention of 79. Macfarlane GT, Macfarlane S.
acid supplementation does not influence chronic diseases: Report of a joint WHO/ Fermentation in the human large
body composition, insulin resistance, FAO expert consultation. World Health intestine: Its physiologic consequences
and lipemia in women with type 2 Organ Tech Rep Ser 2003;916:i-viii, and the potential contribution of
diabetes and obesity. Nutr Clin Pract 1–149. prebiotics. J Clin Gstroenterol 2011;45
2012;27:553–560. 65. Muraki I, Rimm EB, Willett WC, et Suppl:S120–S127. doi: 10.1097/
51. Bosch J, Gerstein HC, Dagenais GR, et al. Potato consumption and risk of MCG.0b013e31822fecfe.
al.; ORIGIN Trial Investigators. n-3 fatty type 2 diabetes: results from three 80. Legette LL, Lee W, Martin BR, et al.
acids and cardiovascular outcomes in prospective cohort studies. Diabetes Prebiotics enhance magnesium absorp-
patients with dysglycemia. N Engl J Med Care 2016;39:376–384. doi: 10.2337/ tion and inulin-based fibers exert chronic
2012;367:309–318. dc15-0547. effects on calcium utilization in a
52. Barnard ND, Katcher HI, Jenkins 66. Hu EA, Pan A, Malik V, et al. White rice postmenopausal rodent model. J Food Sci
DJA, et al. Vegetarian and vegan consumption and risk of type 2 diabetes: 2012;77(4):H88–H94. doi: 10.1111/j.1750-
diets in type 2 diabetes management. Meta-analysis and systematic review. 3841.2011.02612.x. Epub 2012 Mar 6.
Nutr Rev 2009;67(5):255–263. doi: BMJ 2012;344:e1454 doi: 10.1136/bmj. 81. Dietary Guidelines for Americans
10.1111/j.1753-4887.2009.00198.x. e1454. 2015–2020. Chapter 1: Key elements of
53. Barnard ND, Cohen J, Jenkins DJ, et al. 67. Sun Q, Spiegelman D, van Dam RM, et healthy eating patterns. https://health.
A low-fat vegan diet improves glycemic al. White rice, brown rice, and risk of gov/ dietar yguidelines/2015/guidelines/c
control and cardiovascular risk factors in type 2 diabetes in US men and women. hapter-1/ accessed?
a randomized clinical trial in individu- Arch Intern Med 2010;170:961–969. doi: 82. Viguiliouk E, Stewart SE, Jayalath VH,
als with type 2 diabetes. Diabetes Care 10.1001/archinternmed.2010.109. et al. Effect of replacing animal protein
2006;29:1777–1783. 68. Abubakar B, Zawawi N, Omar AR, et with plant protein on glycemic control in
54. Barnard ND, Cohen J, Jenkins DJA, et al. al. Predisposition to insulin resistance diabetes: A systematic review and meta-
A low-fat vegan diet and a conventional and obesity due to staple consumption of analysis of 13 randomized controlled
diabetes diet in the treatment of type rice: Amylose content versus germination trials. Nutrients 2015;7:9804–9824.
2 diabetes: A randomized, controlled, status. PLoS One 2017;12(7):e0181309. 83. Campmans-Kuijpers MJ, Sluijs I,
74-wk clinical trial. Am J Clin Nutr doi: 10.1371/journal.pone.0181309. Nothlings U, et al. Iso-caloric substitu-
2009;89(suppl):1588S–1596S. eCollection 2017. tion of carbohydrates with protein: The
55. Sun J, Liu W, Ma H, et al. Effect of 69. Aune D, Norat T, Romundstad P, et al. association with weight change and
cranberry (Vaccinium macrocarpon) Whole grain and refined grain consump- mortality among patients with type 2 dia-
oligosaccharides on the formation of tion and the risk of type 2 diabetes: A betes. Cardiovasc Diabetol 2015;14:39.
advanced glycation end-products. J Berry systematic review and dose-response 84. Song M, Fung TT, Hu FB, et al.
Res 2016;16;6(2):149–158. doi: 10.3233/ meta-analysis of cohort studies. Eur J Association of animal and plant protein
JBR-160126. Epidemiol 2013;28(11):845–858. doi: intake with all-cause and cause-
56. Christensen AS, Viggers L, Hasselström 10.1007/s10654-013-9852-5. Epub 2013 specific mortality. JAMA Intern Med
K, et al. Effect of fruit restric- Oct 25. 2016;176:1453–1463.
tion on glycemic control in patients 70. Carter P, Gray LJ, Troughton J, et al. 85. Chen X, Wei G, Jalili T, et al. The
with type 2 diabetes—A random- Fruit and vegetable intake and incidence associations of plant protein intake with
ized trial. Nutr J 2013;12:29. doi: of type 2 diabetes mellitus: Systematic all-cause mortality in CKD. Am J Kidney
10.1186/1475-2891-12–29. review and meta-analysis. BMJ 2010, Dis 2016;67(3):423–430. doi: 10.1053/j.
57. Wang PY, Fang JC, Gao ZH, et al. 341:c4229. ajkd.2015.10.018. Epub 2015 Dec 10.
Higher intake of fruits, vegetables or 71. Barengolts E. Gut Microbiota, prebiotics, 86. Almeida JC, Zelmanovitz T, Vaz JS, et al.
their fiber reduces the risk of type 2 probiotics, and synbiotics in manage- Sources of protein and polyunsaturated
diabetes: A meta-analysis. J Diabetes ment of obestiy and prediabetes: Review fatty acids of the diet and microalbumin-
Investig 2016;7(1):56–69. doi: 10.1111/ of randomized controlled trials. Endocr uria in type 2 diabetes mellitus. J Am
jdi.12376. Epub 2015 Jun 22. Pract 2016;22(10):1224–1234. Epub Coll Nutr 2008;27:528–537.
58. Rodriguez MC, Parra MD, Marques- 2016 Jul 13. 87. de Mello VD, Zelmanovitz T, Perassolo
Lopes I, et al. Effects of two energy- 72. Rühl R, Landrier JF. Dietary regulation MS, et al. Withdrawal of red meat
restricted diets containing different of adiponectin by direct and indirect lipid from the usual diet reduces albumin-
fruit amounts on body weight loss and activators of nuclear hormone receptors. uria and improves serum fatty acid
macronutrient oxidation. Plant Foods Mol Nutr Food Res 2016;60(1):175–184. profile in type 2 diabetes patients with
Hum Nutr 2005;60:219–224. doi: 10.1002/mnfr.201500619. Epub macroalbuminuria. Am J Clin Nutr
59. de Oliveira MC, Sichieri R, Venturim 2015 Dec 10. 2006;83:1032–1038.
Mozzer R: A low-energy-dense diet add- 73. McMacken M, Shah S. A plant-based 88. Azadbakht L, Atabak S, Esmaillzadeh A.
ing fruit reduces weight and energy intake diet for the prevention and treatment Soy protein intake, cardiorenal indices,
in women. Appetite 2008;51:291–295. of type 2 diabetes. J Geriatr Cardiol and C-reactive protein in type 2 diabetes
60. Madero M, Arriaga JC, Jalal D, et al. 2017;14(5):342–354. doi: 10.11909/j. with nephropathy: A longitudinal
The effect of two energy-restricted diets, issn.1671-5411.2017.05.009. randomized clinical trial. Diabetes Care
a low-fructose diet versus a moderate 74. Beidokhti MN, Jäger AK. Review of 2008;31:648–654.
natural fructose diet, on weight loss antidiabetic fruits, vegetables, beverages, 89. Hariharan D, Vellanki K, Kramer H. The
and metabolic syndrome parameters: A oils and spices commonly consumed in Western diet and chronic kidney disease.
randomized controlled trial. Metabolism the diet. J Ethnopharmacol 2017;201:26– Curr Hypertens Rep 2015;17(3):16. doi:
2011;60:1551–1559. 41. doi: 10.1016/j.jep.2017.02.031. Epub 10.1007/s11906-014-0529-6.
61. Alinia S, Hels O, Tetens I. The poten- 2017 Mar 1. 90. Bunner AE, Wells CL, Gonzales J,
tial association between fruit intake 75. Anderson JW, Ward K. High- et al. A dietary intervention for chronic
and body weight—A review. Obes Rev carbohydrate, high-fiber diets for insulin- diabetic neuropathy pain: A randomized
2009;10:639–647. treated men with diabetes mellitus. Am J controlled pilot study. Nutr Diabetes
62. Coe S, Ryan L. Impact of polyphenol-rich Clin Nutr 1979;32:2312–2321. 2015;5:e158.
sources on acute postprandial glycae- 76. Bach Knudsen KE. Microbial degradation 91. Melnik BC. Leucine signaling in the
mia: A systematic review. J Nutr Sci of whole-grain complex carbohydrates pathogenesis of type 2 diabetes and obe-
2016;5:e24. doi: 10.1017/jns.2016.11. and impact on short-chain fatty acids and sity. World J Diabetes 2012;3(3):38–53.
eCollection 2016. health. Adv Nutr 2015;6:206–213. doi: 10.4239/wjd.v3.i3.38.
406 Chapter 31 Implementing Nutritional Lifestyle Treatment Programs in Type 2 Diabetes
92. Avruch J, Long X, Ortiz-Vega S, et al. 109. Saiki A1, Ohira M, Endo K, et al. 125. Goraya N1, Simoni J, Jo C, et al. Dietary
Amino acid regulation of TOR com- Circulating angiotensin II is associ- acid reduction with fruits and vegetables
plex 1. Am J Physiol Endocrinol Metab ated with body fat accumulation and or bicarbonate attenuates kidney injury in
2009;296:E592–E602. insulin resistance in obese subjects with patients with a moderately reduced glo-
93. Duran A, Amanchy R, Linares JF, et al. type 2 diabetes mellitus. Metabolism merular filtration rate due to hypertensive
p62 is a key regulator of nutrient sens- 2009;58(5):708–713. doi: 10.1016/j. nephropathy. Kidney Int 2012;81(1):86–
ing in the mTORC1 pathway. Mol Cell metabol.2009.01.013. 93. doi: 10.1038/ki.2011.313. Epub 2011
2011;44:134–146. 110. Enhörning S, Wang TJ, Nilsson PM, Aug 31.
94. Hara K, Yonezawa K, Weng QP, et al. et al. Plasma copeptin and the risk 126. Hirsch EE, Halberg F, Goetz FC, et al.
Amino acid sufciency and mTOR regulate of diabetes mellitus. Circulation Body weight change during 1 week on a
p70 S6 kinase and eIF-4E BP1 through 2010;121:2102–2108. single daily 2,000-calorie meal con-
a common effector mechanism. J Biol 111. Thornton SN. Angiotensin, the hypo- sumed as breakfast (B) or dinner (D).
Chem 1998;273:14484–14494. volaemia hormone, aggravates hyper- Chronobiologia 1975;2(suppl. 1):31–32.
95. Kwon G, Marshall CA, Pappan KL, et al. tension, obesity, diabetes and cancer. 127. Carlson O, Martin B, Stote KS, et al.
Signaling elements involved in the meta- J Intern Med 2009;265:616–617. doi: Impact of reduced meal frequency
bolic regulation of mTOR by nutrients, 10.1111/j.1365-2796.2008.02037.x. without caloric restriction on glucose
incretins, and growth factors in islets. 112. Lang F, Guelinckx I, Lemetais G, et al. regulation in healthy, normal weight mid-
Diabetes 2004;53 Suppl 3: S225–S232. Two liters a day keep the doctor away? dle-aged men and women. Metabolism
96. Lynch CJ, Fox HL, Vary TC, et al. Considerations on the pathophysiol- 2007;56(12):1729–1734.
Regulation of amino acid-sensitive TOR ogy of suboptimal fluid intake in the 128. Kahleova H, Belinova L, Malinska H,
signaling by leucine analogues in adipo- common population. Kidney Blood et al. Eating two larger meals a day
cytes. J Cell Biochem 2000;77:234–251. Press Res 2017;42(3):483–494. doi: (breakfast and lunch) is more effective
97. Lynch CJ. Role of leucine in the 10.1159/000479640. than six smaller meals in a reduced-
regulation of mTOR by amino acids: 113. Paul K. Whelton sodium, potassium, energy regimen for patients with type 2
Revelations from structure-activity stud- blood pressure, and cardiovascular diabetes: A randomised crossover study.
ies. J Nutr 2001;131:861S-865S. disease in humans. Curr Hypertens Diabetologia 2014;57(8):1552–1560. doi:
98. Karunakaran U, Kim HJ, Kim JY, et al. Rep 2014;16:465. doi: 10.1007/ 10.1007/s00125-014-3253-5.
Guards and culprits in the endoplasmic s11906-014-0465-5. 129. Jakubowicz D, Wainstein J, Ahrén
reticulum: Glucolipotoxicity and β-cell 114. Alderman, MH: Evidence relating dietary B, et al. High-energy breakfast with
failure in type II diabetes. Exp Diabetes sodium to cardiovascular disease. J Am low-energy dinner decreases overall
Res 2012;2012:639762. Col Nutr 2006;25(3):256S–261S. daily hyperglycaemia in type 2 diabetic
99. Kalender A, Selvaraj A, Kim SY, et al. 115. O’Donnell M, Mente A, Rangarajan S, patients: A randomised clinical trial.
Metformin, independent of AMPK, et al. Urinary sodium and potassium Diabetologia 2015;58(5):912–919.
inhibits mTORC1 in a rag GTPase- excretion, mortality, and cardiovascular 130. Jakubowicz D, Fray O, Wainstein J, et al.
dependent manner. Cell Metab events. N Engl J Med 2014;371:612–623. Meal timing and composition influence
2010;11:390–401. doi: 10.1056/NEJMoa1311889. ghrelin levels, appetite scores and weight
100. Fröjdö S, Cozzone D, Vidal H, et al. 116. Graudal N, Jürgens G, Baslund B, et al. loss maintenance in overweight and obese
Resveratrol is a class IA phosphoinosit- Compared with usual sodium intake, low adults. Steroids 2012;77(4):323–331. doi:
ide 3-kinase inhibitor. Biochem J and excessive sodium diets are associated 10.1016/j.steroids.2011.12.006.
2007;406:511–518. with increased mortality: A meta-anal- 131. Halberg N, Henriksen M, Soderhamn N,
101. Beevers CS, Chen L, Liu L, et al. ysis. Am J Hypertens 2014;27(9):1129– et al. Effect of intermittent fasting and
Curcumin disrupts the mammalian target 1137. doi: 10.1093/ajh/hpu028. Epub refeeding on insulin action in healthy
of rapamycin- raptor complex. Cancer 2014 Mar 20. men. J Appl Physiol 2005;99:2128–2136.
Res 2009;69:1000–1008. 117. Ekinci EI, Moran JL, Thomas MC, 132. Fernemark H, Jaredsson C, Bunjaku
102. Van Aller GS, Carson JD, Tang W, et et al. Relationship between urinary B, et al. A randomized cross-over trial
al. Epigallocatechin gallate (EGCG), sodium excretion over time and mortal- of the postprandial effects of three
a major component of green tea, is a ity in type 2 diabetes. Diabetes Care different diets in patients with type 2
dual phos-phoinositide-3-kinase/mTOR 2014;37:e62–e63. diabetes. PLoS One 2013;8:e79324. doi:
inhibitor. Biochem Biophys Res Commun 118. Weinberger MH, Fineberg NS, Fineberg 10.1371/journal. pone.0079324. PMID:
2011;406:194–199. SE, et al. Salt sensitivity, pulse pressure, and 24312178.
103. Anastasius N, Boston S, Lacey M, et death in normal and hypertensive humans. 133. Cheng C, Adams GB, Perin L, et al.
al. Evidence that low-dose, long-term Hypertension 2001;37[part 2]:429–432. Prolonged fasting reduces IGF-1/PKA to
genistein treatment in- hibits oestradiol- 119. Morris RC, Schmidlin O, Frassetto LA, et promote hematopoietic-stem-cell-based
stimulated growth in MCF-7 cells by al. Relationship and interaction between regeneration and reverse immunosuppres-
down- regulation of the PI3-kinase/Akt sodium and potassium. J Am College sion. Cell Stem Cell 2014;14:810–823.
signalling pathway. J Steroid Biochem Nutr 2006;25(3):262S–270S. doi: 10.1016/j.stem.2014.04.014.
Mol Biol 2009;116:50–55. 120. Morris RC Jr, Sebastian A, Forman 134. Barnard RJ, Lattimore L, Holly RG, et
104. Boschmann M, Steiniger J, Franke G, A, et al. Normotensive salt-sensitivity: al. Response of non-insulin-dependent
et al. Drinking induces thermogenesis Effects of race and dietary potassium. diabetic patients to an intensive program
through osmosensitive mechanisms. J Clin Hypertension 1999;33:18–23. of diet and exercise. Diabetes Care
Endocrinol Metab 2007;92(8):3334–3337. 121. Whelton PK. Sodium, Potassium, 1982;5(4):370–374.
105. Dennis EA, Dengo AL, Comber DL, et al. blood pressure, and cardiovascular 135. Bonora E, Targher G, Alberiche M, et al.
Water consumption increases weight loss disease in humans. Curr Hypertens Homeostasis model assessment closely
during a hypocaloric diet intervention in Rep 2014;16:465. doi: 10.1007/ mirrors the glucose clamp technique
middle-aged and older adults. Obesity s11906-014-0465-5. in the assessment of insulin sensitivity.
2010;18(2):300–307. 122. Dessì-Fulgheri P, Sarzani R, Serenelli M, Diabetes Care 2000;23:57–63.
106. Stookey JD, Constant F, Popkin BM, et al. Low calorie diet enhances renal, 136. Wallace TM, Levy, JC, Matthews DR.
et al. Drinking water is associated with hemodynamic, and humoral effects of Use and abuse of HOMA modeling.
weight loss in overweight dieting women exogenous atrial natriuretic peptide Diabetes Care 2004;27:1487–1495.
independent of diet and activity. Obesity in obese hypertensives. Hypertension 137. Leighton E, Sainsbury CAR, Jones GC.
2008;16(11):2481–2488. 1999;33(2):658–662. A practical review of c-peptide testing in
107. Thornton SN. Increased hydration 123. Hall JE, Granger JP, do Carmo JM, et al. diabetes. Diabetes Ther 2017;8:475–487.
can be associated with weight loss. Hypertension: Physiology and pathophys- doi: 10.1007/s13300-017-0265-4.
Front Nutr 2016;3:18. doi: 10.3389/ iology. Compr Physiol 2012;2(4):2393– 138. Matti Uusitupa, et al. Long-term
fnut.2016.00018. eCollection 2016. 2442. doi: 10.1002/cphy.c110058. improvement in insulin sensitivity
108. Roussel R, Fezeu L, Bouby N, et al. Low 124. Brownlee M. Banting Lecture 2004 by changing lifestyles of people with
water intake and risk for new-onset hyper- The pathobiology of diabetic complica- impaired glucose tolerance 4-year results
glycemia. Diabetes Care 2011;34:2551– tions: A unifying mechanism. Diabetes from the finnish diabetes prevention
2554. doi: 10.2337/dc11-0652. 2005;54(6):1615–1625. study. Diabetes 2003;52:2532–2538.
VII
PA RT
407
32
CHAPTER
409
410 Chapter 32 Diet and Cancer Prevention
for consumption tend to exclude starchy vegetables such eat at least five portions/servings (at least 400 g or 14 oz.)
as potato, yam, sweet potato, and cassava. Examples of of a variety of non-starchy vegetables and or fruits every
non-starchy vegetables include broccoli, cabbage, spin- day of different colors including red, green, yellow, white,
ach, kale, cauliflower, carrots, lettuce, cucumber, tomato, purple, and orange, and including tomato-based products
leek, rutabaga, and turnip. Non-starchy vegetables prob- and allium vegetables such as garlic. People who consume
ably protect against cancers of the mouth, pharynx, and starchy roots or tubers as staples also need to ensure suf-
larynx, and those of the esophagus and stomach.5 Limited ficient intake of non-starchy vegetables and fruits. At the
evidence also suggests that they may protect against can- population level, average consumption of non-starchy veg-
cers of the nasopharynx, lung, colorectum, ovary, and etables and fruits should be at least 600 g (21 oz.) daily.10
endometrium. 5 Fruits probably protect against cancers of
the mouth, pharynx, and larynx, and those of the esopha-
gus, lung, and stomach. 5 The possibility that fruits may 32.3 SPECIFIC MICRONUTRIENTS
also protect against cancers of the nasopharynx, pancreas,
liver, and colorectum has also surfaced. 5 Meta-analysis of AND PHYTOCHEMICALS
fruit and/or vegetable intake and lung cancer risk con-
Both the micronutrients and phytochemicals present in
ducted as part of the CUP found that there was a protec-
fruits and vegetables can bring about a plethora of bio-
tive role of fruits and vegetables on lung cancer risk, but
logical responses that may be important in modifying
this effect was only significant in current smokers but not
carcinogenesis. Examples of phytochemicals include allyl
in former- or never–smokers.7 Two recent meta-analyses8,
9 reached conflicting conclusions about the relationship
sulfur compounds (from allium foods including garlic and
onions), terpenes (from citrus fruits), plant phenols (from
between fruit and vegetable intake and breast cancer sur-
grapes, strawberries, apples), polyphenols (from green tea
vival. Although these relationships are based upon the epi-
and chocolate), indoles and isothiocyanates (from cruci-
demiologic literature, there are several shortcomings that
ferous vegetables), and phytoestrogens (from soy and soy
are specific to the analysis of dietary intake of fruits and
products). Since a comprehensive review of the interac-
vegetables. These include: most studies of consumption of
tions between micronutrients, phytochemicals, and cancer
dietary fruits and vegetables have been conducted in pop-
is beyond the scope of this chapter and has been published
ulations with relatively homogeneous diets, smokers con-
elsewhere,11,12 only a couple of examples are included
sume fewer fruits and vegetables than non-smokers, fat
below to highlight the assumption that these food compo-
intake inversely correlates with fruit and vegetable intake
nents are capable of altering a variety of cancer processes.
in the United States, and studies using self-reporting tend
These examples reveal the vastness and complexity of the
to over-report vegetable and fruit consumption. Thus, it
potential interactions. It is clear that several factors influ-
is not surprising that many uncertainties exist about the
ence the response to these dietary components, including
relationship between total fruit and/or vegetable con-
the timing of exposure, the quantity, and duration of con-
sumption and cancer prevention.
sumption, interactions among food components, and the
Fruits and vegetables contain as many as 100,000
genetic background of the consumer.
unique bioactive food components including both essen-
tial micronutrients (e.g. vitamins C, D, E, and folic acid
and the minerals selenium, zinc, iodine, and calcium)
and phytochemicals. The term phytochemicals is a gen-
32.3.1 Garlic and Allium Vegetables
eral name for an assortment of plant constituents that Food is generally complex, as illustrated by the allium
often perform important functions in the plant, such as family which contains about 500 species including garlic,
providing color, flavor, or protection. Phytochemicals are onion, leeks, chives, and scallions. Allium vegetables are
classified according to their chemical structure and func- used throughout the world for their sensory characteris-
tional characteristics and include salicylates, phytosterols, tics, as well as their apparent health benefits. Health bene-
saponins, glucosinolates, polyphenols, protease inhibi- fits of allium vegetables are attributed to sulfur-containing
tors, monoterpenes, phytoestrogens, sulfides, terpenes, compounds, which are generated upon processing (cutting
lectins, etc. The phytochemical composition of fruits and or chewing). However, it is also clear that they contain
vegetables depends on a combination of genetics (species many other constituents that may provide protection,
and subtype) and environmental factors including culti- including amino acids, carbohydrates, and flavonoids.
vation, growing, harvesting, and storage conditions. It is Similarly, other foods contain a multitude of phytochemi-
likely that many of the health benefits of diets enriched cals that make it impossible to draw conclusions about the
with fruits and vegetables, including cancer prevention, health benefits of a single component.
are partly due to the presence of multiple bioactive food Epidemiologic findings and preclinical (animal and cell
components. Moreover, the magnitude of the response to culture) studies provide evidence that garlic and related
fruit and vegetables, as well as other dietary components, sulfur constituents can suppress cancer risk and alter the
is likely influenced by many factors, including the person's biological behavior of tumors.13 The strongest evidence
genetic background and a host of environmental factors, points to protective effects of garlic and/or onions against
as well as the type, quantity, and duration of consumption cancers of the digestive tract. The WCRF/AICR report
of these foods, and interactions among food components. indicated that garlic probably protects against colorectal
The WCRF has made a number of personal and public cancer. 5 A total of 2 cohort studies, 27 case-control stud-
health recommendations regarding the consumption of fruits ies, and 2 ecological studies investigated the relationship
and vegetables for cancer prevention.10 Individuals should between allium vegetables and cancer. 5 Meta-analysis of
32.3 Specific Micronutrients and Phytochemicals 411
this data showed a 23% decreased risk per 50 g allium that folate deficiency is associated with DNA strand
32
vegetables/day and a 59% decreased risk per serving of breaks, impaired DNA repair, and increased mutations,
garlic/day. 5 Some recent meta-analyses confirm a protec- and that folate supplementation can correct some of these
tive effect of allium vegetables, particularly garlic, against defects induced by folate deficiency.
gastric,14 colorectal15 and upper aerodigestive tract16 can- A very recent meta-analysis suggests that high dietary
cers. However, the evidence is derived mainly from case- folate is protective against upper gastrointestinal cancers
control studies. While one randomized controlled trial including esophageal, gastric, and pancreatic cancers. 21
reported a statistically significant 29% reduction in both Moreover, linearity dose-response analysis indicated
size and number of colon adenomas in colorectal patients that with 100 µg/day increase in dietary folate intake,
taking aged garlic extract,17 in prospective studies, the use the risk of esophageal, gastric, and pancreatic cancers
of garlic supplements was associated with a significant would decrease by 9%, 1.5%, and 6%, respectively. 21
18% increased risk of colorectal cancer.18 This disparity In contrast, high serum folate levels are associated with
between epidemiologic studies of dietary garlic vs. garlic an increased risk of prostate cancer and a dose-response
supplements may be because of altered chemical composi- was evident, 22 suggesting that the same nutrient can have
tion, such as the lack of allicin. This is the major biologi- different effects in different tissues.
cally active component in crushed fresh garlic, but dietary Genetic polymorphisms may also influence the
supplements lack alliinase to convert allinin to allicin.19 response to dietary folate and cancer risk. For example,
These findings are in line with the WCRF/AICR recom- a common polymorphism in methylenetetrahydrolate
mendation that dietary supplements are not recommended reductase (MTHFR), a key protein that controls whether
for cancer prevention. folate is partitioned towards DNA precursor synthesis or
There is considerable preclinical evidence with many DNA methylation, can potentially modify the relation-
different model carcinogens and transplantable tumors ship between folate status and cancer. The most common
that supports a cancer-protective effect of garlic and some variant in the MTHFR gene, C677T, causes a valine for
of its allyl sulfur components. Animal studies have shown alanine substitution in the protein and reduced enzyme
that garlic and/or its related organosulfur compounds activity in the heterozygotes (CT; 35%) and homozygotes
suppress mammary, colon, skin, uterine, esophagus, lung, (TT; 70%). 23 Studies suggest that there was no clear rela-
rental, forestomach, and liver cancer incidence.11 tionship between plasma folate and colorectal adenomas
Similar to other foods, garlic and its sulfur-contain- among those with the CC or CT genotype for MTHFR;
ing constituents appear to exert their cancer protective thus, only a subset of the population (i.e. those with
effects through multiple mechanisms including inhibition the TT genotype) may benefit from an increased folate
of carcinogen metabolism, inhibition of DNA adduct for- intake. 24 These results demonstrate that not all respond
mation, upregulation of antioxidant defenses and DNA identically to bioactive food components. Furthermore,
repair, suppression of cell proliferation, induction of mutations in another folate metabolizing enzymes, thy-
apoptosis, decreased inflammation, and blocked angio- midylate synthase, appear to modulate folate intake
genesis. 20 It is likely that many of these processes are mod- and colon cancer risk. 25 Possibly 50–100 genes, either
ified simultaneously. directly or indirectly, are involved with folate metabo-
lism; including receptors, binding proteins, enzymes,
tissue-specific gene products, and downstream factors
that rely upon folate-derived metabolites may determine
32.3.2 Folate if this vitamin is an important dietary variable. The vari-
Folate is a water-soluble B vitamin, so called because it ability within the human genome means that there are
is abundant in foliage (green leafy vegetables). Folic acid, thousands of polymorphisms that may determine the
the synthetic form of folate, is used to fortify manufac- biological response to folate.
tured cereal products, flours, grains, and spreads. The Folate also serves as an excellent example that a
relationship between dietary folate and cancer serves as dietary component may have different biological effects
an important example of the significance of the timing of when given as a normal dietary constituent (folate) or as
exposure and diet-gene interactions. The mechanisms by a supplement (folic acid) and that the effect may be dif-
which dietary folate can influence cancer development are ferent in normal compared to transformed cells. Animal
related to the sole biochemical function for folate—medi- studies and clinical observations suggest that folate pos-
ating the transfer of one-carbon units. In this role, folate sesses dual modulatory effects on carcinogenesis depend-
is an important factor in DNA synthesis, stability, integ- ing on the timing and dose of folate intervention. 26 Folate
rity, and repair. If dietary folate is limited, the balance deficiency in normal epithelial tissues appears to predis-
of purine and pyrimidine DNA precursors is altered, and pose them to neoplastic transformation, and modest lev-
normal DNA repair is inhibited. Moreover, uracil, which els of folate supplementation suppress the development of
is not normally present in DNA, is mis-incorporated into tumors in normal tissues. 26 In contrast, data from ani-
the DNA molecule in place of thymidine, resulting in mal models, human intervention studies, and analyses of
DNA strand breakage, chromosomal damage, and malig- cancer incidence data suggest that supplementation with
nant transformation. Furthermore, cytosine methylation synthetic folic acid may promote the growth of initiated
is altered, leading to global DNA hypomethylation and/ cells. 27, 28 Rodent studies report a reduction in early mark-
or changes in gene-specific methylation and inappropri- ers of colon cancer, such as aberrant crypt foci when folic
ate protooncogene activation. A growing body of evidence acid is given prior to initiation of lesions, 29 but cancer
from cell culture, animal, and human studies indicates development is accelerated if folic acid is given after the
412 Chapter 32 Diet and Cancer Prevention
emergence of lesions; presumably through the provision safety and efficacy is required for individual fruit and veg-
of DNA precursors for cancer cell growth.30 Recent find- etable constituents before dietary guidelines beyond sim-
ings from several large-scale human observational or pla- ply greater consumption can be proposed. These results
cebo-controlled trials indicate that supplemental folic acid also highlight that consumption of supplements for cancer
increases the risk of cancer at several sites, including the prevention might have unexpected adverse effects and that
breast, 31 lung, 32 and prostate. 27 Combined high-dose folic consumption of the relevant nutrients through the diet is
acid and vitamin B12 supplementation (5 mg and 1.25 mg preferred.
daily for 6 months, respectively) had detrimental effects
on biomarkers of genomic stability including increased
uracil mis-incorporation and tumor suppressor gene 32.4 DIETARY FIBER
promoter methylation in rectal biopsies from colorectal
adenoma patients. 33 Overall, these types of observations The term “dietary fiber” encompasses a complex mix of
suggest that the optimal timing, dose, and form of a nutri- mostly non-digestible plant cell compounds with vari-
ent intervention need to be established for safe and effec- able effects on gut physiology. Fiber is either soluble,
tive cancer prevention in humans. which means that it dissolves in water, or insoluble, which
means that it doesn’t. Dietary fiber from different sources
varies in composition, and it is unlikely that all will be
equally protective against cancer. Soluble fiber is found
32.3.3 Carotenoids in oats, barley, beans, and various fruits and vegetables.
Folate is not the only nutrient where high dose supplemen- Insoluble fiber is found in whole grains, legumes, seeds,
tation may potentially have adverse effects on cancer risk. nuts and dark-green, leafy vegetables. Fiber exerts sev-
Common green, yellow/red, and yellow/orange vegetables eral biological effects including slowing digestion so that
and fruits contain a host of carotenoids. These include you feel full longer, helping lower blood sugar levels and
lutein, zeaxanthin, cryptoxanthin, lycopene, β-carotene, possibly aiding insulin sensitivity, lowering blood choles-
and α-carotene. Epidemiological studies have reported terol concentrations, diluting harmful substances in the
that high intakes of β-carotene-rich fruits and vegetables colon and preventing constipation, and protecting the
or high plasma concentrations of the nutrient usually lining of the colon, and therefore preventing the develop-
have a significant inverse association with lung cancer ment of cancerous cells. Fermentation products, especially
risk. 5 Moreover, an updated meta-analysis of prospective short-chain fatty acids, are produced by the gut micro-
studies of blood concentrations of carotenoids and reti- flora from a wide range of dietary fibers. Short-chain fatty
nol and lung cancer risk found that blood concentrations acids, such as butyrate, induce apoptosis, cell-cycle arrest,
of α-carotene, β-carotene, total carotenoids, and retinol and differentiation of cancer cells. In contrast, butyrate
were significantly inversely associated with lung cancer is a growth factor and nutrient toward non-transformed
risk; however, in stratified analysis by sex, the signifi- colon cells. An important mechanism by which butyrate
cant inverse associations for β-carotene and retinol were causes biological effects in colon cancer cells is through
observed only in men, not in women. 34 The epidemiologi- inhibition of histone deacetylase activity, which leads to
cal data linking high intakes of β-carotene-rich fruits and hyperacetylation of histones resulting in transcriptional
vegetables to reduced lung cancer risk, along with animal dysregulation and silencing of genes that are involved in
data demonstrating that β-carotene modifies many path- the control of cell-cycle progression, differentiation, apop-
ways associated with carcinogenesis, provided strong tosis, and cancer development.
support for testing the effect of β-carotene supplements Health experts recommend eating at least 25 grams of
on lung cancer in randomized intervention trials, as was fiber each day.38 Fiber intake should be divided through-
done in the α-Tocopherol β-Carotene Study (ATBC), 35 the out the day, and whole grains and beans should be con-
Physician’s Health Study, 36 and the Beta-Carotene and sumed with most meals. Moreover, fiber intake should
Retinol Efficacy Trial (CARET). 37 Unexpectedly, results be increased slowly, as suddenly adding large amounts
from the ATBC and CARET studies showed adverse treat- of fiber to your diet may cause gastrointestinal pain.
ment effects in terms of increased lung cancer incidence in Drinking plenty of water can be helpful. Moreover, fiber
high-risk (heavy smokers) subjects. The different results supplements are not recommended as they do not provide
obtained in supplementation trials compared to cohort the vitamin, minerals, antioxidants, and phytochemicals
studies may reflect that fruits and vegetables contain, in that work together to prevent cancer.38
addition to β-carotene, numerous other compounds that Twenty-three studies were included in the WCRF/
may be protective against cancer. In fact, β-carotene may AICR continuous update project analysis for foods con-
simply be a marker for the actual protective nutrients taining dietary fiber and colorectal cancer. 39 The over-
and phytochemicals in fruit and vegetables. Alternately, all evidence was consistent, showing a decreased risk of
β-carotene may have different effects when consumed as colorectal cancer with the consumption of dietary fiber.
a supplement rather than via the food supply. It is pos- Similarly, a 9% decreased risk of developing colorec-
sible that a protective association present at dietary-intake tal adenomas was observed per 10 g/day increase of
amounts of carotenoids is lost or reversed by the pharmaco- intake of dietary fiber.40 The WCRF/AICR continuous
logical levels present in supplementation trials. Moreover, update project concluded that the evidence is probable
it may be that a heavy smoker subgroup is particularly that foods containing dietary fiber are protective against
vulnerable to excess β-carotene. The ATBC, CARET, colorectal cancer. This recommendation was based
and PHS studies illustrate that definitive evidence of both on consistent evidence from cohort studies as well as
32.5 Meat Intake 413
plausible biological mechanisms. In contrast, the pro- processed meat as a definite cause of cancer.49 After an
32
tective effect of dietary fiber against colon cancer has analysis of more than 800 studies, experts found that eat-
not been observed in randomized intervention trials. ing 50 grams of processed meat (the equivalent of about
Adopting a diet that is low in fat and high in fiber, fruits, four strips of bacon or one hot dog) every day increased
and vegetables did not affect the risk of recurrence of the risk of colorectal cancer by 18% and eating 100 g por-
colorectal adenomas41 and did not alter rectal mucosal tion of red meat increased the risk of colorectal cancer by
cell proliferation rates.42 A Cochrane meta-analysis of 17%.49 However, it is important to put these results into
five randomized controlled trials of increased dietary perspective. Overall, the lifetime risk that an individual
fiber found no difference between intervention and con- will develop colon cancer is 5%, and the increased risk
trol groups for the development of adenomas.43 The dif- from eating the amount of processed meat or red meat in
ferent results obtained between the observational and the IARC report would raise the average lifetime risk to
intervention studies may reflect the fact that the inter- almost 6%. 50 While the strongest evidence is for colorectal
vention studies utilized high-risk individuals, did not use cancer, there is also evidence that red meat and processed
a sufficiently large intake range to detect a response, or meat consumption may increase the risk for other types
that the duration of exposure was insufficient to detect of cancer. Consumption of 100 g/d red meat increased
a difference. Nevertheless, study results linking dietary the risk of advanced prostate cancer by 19%, and the
fiber and colon cancer remain inconclusive. consumption of 50 g/day of processed meat increases
The effect of dietary fiber on mammary and prostate the risk of total prostate cancer (4%), cancer mortality
cancer risk has also been inconsistent. Whereas a high (8%), breast cancer (9%), colorectal cancer (18%), and
intake of fiber was protective against breast cancer in the pancreatic cancer (19%). 51 Similarly, each 65 g/d increase
Malmo Diet and Cancer Cohort,44 dietary fiber and fiber in total red meat intake was associated with a risk of 1.36
fractions did not affect breast cancer risk in the Nurses' for endometrial cancer, 1.25 for esophageal cancer, and
Health Study.45 The WCRF/AICR continuous update 1.22 for lung cancer incidences. 51 It is also important to
project identified three studies that investigated the rela- realize that increased meat intake likely will not affect
tionship between consumption of foods containing fiber all individuals the same. Evidence exists that a combina-
before a diagnosis of primary breast cancer and subse- tion of multiple SNPs in four cytochrome P-450 enzymes,
quent all-cause mortality; there was a statistically signifi- which is present in almost 5% of the population, may pre-
cant 32% decreased risk per 10 g increased intake/day.46 dispose risk. Over a 40-fold increased risk of colorectal
A large case-control study conducted in Italy found a cancer was found in these individuals who consumed a
moderate but significant inverse association between high red meat consumption (>5 times/week) and had the
selected types of dietary fiber and prostate cancer risk; combination of polymorphisms compared to those who
the association was strongest for cellulose and for sol- did not. 52
uble and vegetable fibers.47 However, a recent meta- There is evidence that an increased cancer risk may
analysis found that for the highest group compared with not be a function of meat per se, but may reflect high fat
the lowest dietary fiber intake, a significantly decreased intake, and/or carcinogens generated through various
risk with prostate cancer was observed in case-control meat cooking or processing methods. The high energy
studies but not in cohort studies.48 The assessment of a density of meat increases the likelihood of obesity, itself a
cancer-protective effect for dietary fiber can be compli- major risk factor for cancer. In fact, total meat consump-
cated by correlations among dietary fiber, dietary fat, tion is positively associated with weight gain in a cohort
and caloric intakes (i.e. high fiber diets may be relatively of almost 275,000 men and women. 53 After adjustment
low in fat and calories). A further confounding factor for estimated energy intake, an increase in meat intake
in examining the association between cancer risk and (250 g/d) led to a 2-kg higher weight gain after 5 years. 53
high-fiber diets is the possible effect on risk caused by Moreover, the amount of excess body weight or the degree
micronutrients, particularly folate, and phytochemicals of adiposity may mediate the relationship between dietary
in high-fiber foods. red meat and processed meat intake and serum biomark-
ers associated with obesity and inflammation, which are
risk factors for colorectal cancer.54 Cooking methods may
32.5 MEAT INTAKE foster the formation of carcinogens including polycyclic
aromatic hydrocarbons (PAH) and heterocyclic amines
Meat, including all animal flesh apart from fish and sea- (HCA). 5 Carcinogenic nitroso-compounds may occur in
food, can be further classified as either red (beef, pork, some processed meats.
lamb, and goat) or poultry, which usually has more Over 100 distinct PAH are formed when organic sub-
white than red muscle fibers. The term “processed meat” stances like meat are burnt. These compounds are formed
refers to meats preserved by smoking, curing, or salt- from the pyrolysis of fats that occurs when fat drips from
ing, or addition of chemical preservatives. 5 Examples of meat onto hot coal, forming smoke that is redeposited on
processed meat include ham, bacon, pastrami, salami, the meat surface. Eleven PAH compounds have been clas-
hot dogs, and sausages. The WCRF/AICR report sug- sified as carcinogenic to laboratory animals and as suspect
gests that there is probable evidence that red meats and carcinogens in humans. 55 The second class of compounds
convincing evidence that processed meats are related to found in cooked meats are the HCA. These are formed
increased risk of colorectal cancer. 39 More recently the during high-temperature cooking by pyrolysis of proteins,
International Agency for Research on Cancer (IARC) amino acids, or creatinine. The amount in the diet can
has classified red meat as a probable cause of cancer and be substantial and is influenced by cooking habits such
414 Chapter 32 Diet and Cancer Prevention
TABLE 32.1 Clinical recommendations by professional societies make similar recommendations for diet and cancer
prevention
American Cancer Society guidelines on nutrition for cancer prevention75
32
• Consume a healthy diet, with an emphasis on plant foods
• Choose foods and beverages in amounts that help achieve and maintain a healthy weight
• Limit consumption of processed meat and red meat
• Eat at least 2.5 cups of vegetables and fruits each day
• Choose whole grains instead of refined grains
• If you drink alcoholic beverages, limit consumption. Drink no more than 1 drink per day for women or 2 per day for men
American Institute for Cancer Research/World Cancer Research Fund Guidelines76
• Eat more of a variety of vegetables, fruits, whole grains and legumes such as beans
• Avoid sugary drinks. Limit consumption of energy-dense foods.
• Limit consumption of red meats (such as beef, pork and lamb) and avoid processed meats.
• If consumed at all, limit alcoholic drinks to 2 for men and 1 for women a day.
• Limit consumption of salty foods and foods processed with salt (sodium).
• Don't rely on supplements to protect against cancer.
no detectable activity causes acetaldehyde accumulation In fact, professional societies have made similar recom-
after alcohol drinking; individuals experience facial flush- mendations for diet and cancer prevention (Table 32.1).
ing, tachycardia, nausea, and hypotension.72 This variant The overall response is likely dependent on literally thou-
is prevalent in Asians, with a frequency of up to 40%, sands of bioactive components that occur in the foods
whereas it does not exceed 5% in European and African consumed. The research highlighted in this chapter is only
populations.73 Prospective studies in cancer-free alcohol- a small part of the large body of evidence linking diet
ics have shown that the hazard ratio for future aerodiges- and cancer risk. Previous research has generally utilized
tive tract cancers in individuals with the inactive protein a reductionist approach which consisted of looking at the
is approximately 12 times higher than in individuals with effects of an isolated compound, a mixture of compounds,
the active protein.74 A true understanding of the effect of or specific foods of interest on disease risk. However,
dietary alcohol may be clouded because of the compounds nowadays, studies are using integrated approaches that
found in alcoholic beverages including flavonoids, such as consider the complexity of the diet and the different
resveratrol, which can potentially suppress tumorigenesis. dietary patterns, as well as the interaction between dif-
While alcohol use has been linked to several types of ferent active molecules and the role played by the food
cancer, recommendations are complicated by the fact that matrix.77 While a wealth of epidemiological and preclini-
low-to-moderate alcohol intake has been linked with a cal (animal and cell culture) investigations exist, more
lower risk of heart disease. According to recommenda- randomized prevention trials are needed. Variation in the
tions by the WCRF/AICR, it is best not to drink alcohol response among individuals likely depends on individual
to prevent a substantial proportion of cancer. However, if genetic polymorphisms or interactions among dietary
alcoholic drinks are to be consumed, it is recommended to components that influence absorption, metabolism, or
limit consumption to no more than two drinks a day for site of action. These effects, which may be stimulatory or
men and one drink a day for women (one drink contains inhibitory depending on the specific bioactive food com-
about 10–15 g of ethanol). ponent, are mediated through diverse biological mecha-
nisms. The identification and elucidation of the specific
molecular sites for food components are critical for iden-
32.7 SUMMARY AND CONCLUSION tifying those who will benefit maximally or placed at risk
from excess exposures. Until this information is available,
Accumulating evidence continues to suggest that the foods it remains prudent to eat a variety of foods, particularly
people eat can influence cancer risk and tumor behavior. fruits, vegetables, whole grains, and pulses.
REFERENCES
1. National Cancer Institute-Cancer 5. World Cancer Research Fund/ 8. Peng C, Luo WP, Zhang CX. Fruit
Statistics. www.cancer.gov/about- cancer/ American Institute for Cancer and vegetable intake and breast cancer
understanding /statistics (accessed July 13, Research. Food, Nutrition, Physical prognosis: A meta-analysis of pro-
2017). Activity, and the Prevention of Cancer: spective cohort studies. Br J Nutr
2. World Health Organization: Cancer. A Global Perspective, Washington, 2017;117:737–749.
www.who.int /mediacent re/factsheets/ DC, 2007. 9. He J, Gu Y, Zhang S. Consumption of
fs297/cn/ (accessed July 13, 2017) 6. Continuous update project American vegetables and fruits and breast cancer
3. Hanahan D, Weinberg RA. The hall- Institute for Cancer Research (AICR). survival: A systematic review and meta-
marks of cancer. Cell 2000;100:57–70. www.aicr/org/continuous-update-project/ analysis. Sci Rep 2017;7:599.
4. Doll R, Peto R. The causes of can- (accessed July 13, 2017). 10. World Cancer Research Fund
cer: Quantitative estimates of avoid- 7. Veira AR, Abar L, Vingeliene S, et al. International. Plant Foods. http://www
able risk of cancer in the United Fruits, vegetables and lung cancer risk: A .wcrf.org/i nt/research-we-fund /cancer-pr
States today. J Natl Cancer Inst systematic review and meta-analysis. Ann evention-recommendations/plant-foods
1981;66:1191–1308. Oncol 2016;27:81–96. (accessed July 13, 2017).
416 Chapter 32 Diet and Cancer Prevention
11. Davis CD. Mechanisms for the cancer- 27. Mason JB, Dickstein A, Jacques PF, fruit and vegetable intervention on
protective effects of bioactive dietary et al. A temporal association between rectal mucosal proliferation. Cancer
components in fruits and vegetables. In: folic acid fortification and an increase in 2003;98:1161–1168.
Handbook of Nutrition and Food, 2nd colorectal cancer rates may be illuminat- 43. Asano TK, McLeod RS. Dietary fibre for
edition. Berdanier CD, Dwyer J, Feldman ing important biological principles: A the prevention of colorectal adenomas
EB, eds. CRC Press, Boca Raton, FL, hypothesis. Cancer Epidemiol Biomark and carcinomas (Cochrane Review). In:
2007, pp. 1187–1210. Prev 2007;16:1325–1329. The Cochrane Library. John Wiley &
12. Wildman REC, ed. Handbook of 28. Figueiredo JC, Grau MV, Haile RW, et al. Sons, London, 2004.
Nutraceuticals and Functional Foods. Folic acid and risk of prostate cancer: 44. Mattison I, Wirfalt E, Johansson U,
CRC Press LLC, Boca Raton, FL, 2004. Results from a randomized clinical trial. J Bullberg B, Olsson H, Berglund G.
13. Nicastro HL, Ross SA, Milner JA. Natl Cancer Inst 2009;101:432–435. Intakes of plant foods, fibre and fat and
Garlic and onions: Their cancer pre- 29. Kim YI. Folate and colorectal cancer: An risk of breast cancer—A prospective
vention properties. Cancer Prev Res evidence-based critical review. Mol Nutr study in the Malmo Diet and Cancer
2015;8:181–189. Food Res 2007;51:267–292. cohort. Br J Cancer 2004;90:122–127.
14. Turati F, Pelucchi C, Guercio V, La 30. Song J, Sohn K-J, Medline A, Ash C, 45. Holmes MD, Liu S, Hankinson SE,
Vecchia C, Galeone C. Allium vegetable Gallinger S, Kim Y-I. Chemopreventive Coldizt GA, Hunter DJ, Willett WC.
intake and gastric cancer: A case-control effects of dietary folate on intestinal Dietary carbohydrates, fiber and
study and meta-analysis. Mol Nutr Food polyps in Apc+/MSH-/-mice. Cancer Res breast cancer risk. Am J Epidemiol
Res 2015;59:171–179. 2000;6:3191–3199. 2004;159:732–739.
15. Turati F, Guercio V, Pelucchi C, La 31. Stolzenberf-Solomon RZ, Chang SC, 46. World Cancer Research Fund Continuous
Vecchia C, Galeone C. Colorectal cancer Leitzmann MF, et al. Folate intake, alco- Update Project. Diet, Nutrition, Physical
and adenomatous polyps in relation to hol use and postmenopausal breast cancer Activity and Breast Cancer Survivors.
allium vegetables intake: A meta-analysis risk in the prostate lung colorectal and http://www.wcrf.org/sites/defau lt/fi les/
of observational studies. Mol Nutr Food ovarian screening trial. Am J Clin Nutr Breast-Cancer-Su rvivors-2014-Report
Res 2014;58:1907–1914. 2006;83:895–904. .pdf (accessed on August 24, 2017).
16. Guercio V, Turati F, La Vecchia C, 32. Ebbing M, Bonaa KH, Nygard O, et al. 47. Pelucchi C, Talamini R, Galeone C, et al.
Galeone C, Tavani A. Allium veg- Cancer incidence and mortality after Fibre intake and prostate cancer risk. Int
etables and upper aerodigestive tract treatment with folic acid and vitamin B12 . J Cancer 2004;109:278–280.
cancers: A meta-analysis of observa- JAMA 2009;302:2119–2126. 48. Sheng T, Shen RL, Shao H, Ma TH. No
tional studies. Mol Nutr Food Cancer 33. van den Donk M, Pellis L, Crott JW, association between fiber intake and
2016;60:212–222. et al. Folic acid and vitamin B12 supple- prostate cancer risk: A meta-analysis of
17. Shukla Y, Kaira N. Cancer chemopre- mentation does not favorably influence epidemiological studies. World J Surg
vention with garlic and its constituents. uracil minsincorporation and promoter Oncol 2015;13:264.
Cancer Lett 2007;247:167–181. methylation in rectal mucosa DNA of 49. Bourvard V, Loomis D, Guyton KZ,
18. Zhu B, Zou L, Qi L, Zhong R, Miao X. subjects with previous colorectal adeno- et al. Carcinogenicity of consumption of
Allium vegetables and garlic supple- mas. J Nutr 2007;137:2114–2120. red and processed meat. Lancet Oncol
ments do not reduce risk of colorectal 34. Abar L, Veira AR, Aune D, et al. Blood 2105;16:1599–600.
cancer, based on meta-analysis of concentrations of carotenoids and retinol 50. American Cancer Society. World Health
prospective studies. Clin Gastro Hepatol and lung cancer risk: An update of the Organization Says Processed Meat
2014;12:1991–2001. WCRF-AICR systematic review of pub- Causes Cancer. https: //www.cancer.org/
19. Lawson LD, Wang ZJ. Low allicin lished prospective studies. Cancer Med latest-news/world-healt h-organization
release from garlic supplements: A 2016;5:2069–2083. -says-processed-meat- causes-cancer.html
major problem due to the sensitivies of 35. Heinonen OP, Huttunen IK, Albanes (accessed on August 25, 2017).
allinase activity. J Agric Food Chem D et al. for the Alpha Tocopherol 51. Wolk A. Potential health hazards
2001;49:2592–2599. BetaCarotene Cancer Prevention Study of eating red meat. J Intern Med
20. Nagini S. Cancer chemoprevention by Group. The effect of vitamin E and beta 2017;281:106–122.
garlic and its organosulfur compounds- carotene on the incidence of lung cancer 52. Kury S, Buecher B, Robiou-du-Pont S,
panacea or promise? Anticancer Agents and other cancers in male smokers. N et al. Combinations of cytochrome P450
Med Chem 2008;8:313–321. Engl J Med 1994;330:1029–1035. gene polymorphisms enhancing the risk
21. Liu W, Zhou H, Zhu Y, Tie C. 36. Hennekens CH, Buring IE, Manson for sporadic colorectal cancer related to
Associations between dietary folate IE, et al. Lack of effect of long-term red meat consumption. Cancer Epidemiol
intake and risks of esophageal, gastric supplementation with beta carotene on Biomarkers Prev 2007;16:1460–1467.
and pancreatic cancers: An overall and the incidence of malignant neoplasms 53. Vergnaud A-C, Norat T, Romaguera D,
dose-response meta-analysis. Oncotarget and cardiovascular disease. N Engl J Med et al. Meat consumption and prospec-
2017;8:18775. 1996;334:1145–1149. tive weight change in participants of the
22. Wang R, Zheng Y, Huang JY, et al. 37. Omenn OS, Goodman GE, Thomquist EPIC-PANACEA study. Am J Clin Nutr
Folate intake, serum folate levels and MD, et al. Effects of a combination of 2010;92:398–407.
prostate cancer risk: A meta-analysis of beta carotene and vitamin A on lung 54. Chai W, Morimoto Y, Cooney RV, et al.
prospective studies: BMC Public Health cancer and cardiovascular disease. N Eng Dietary red and processed meat intake
2014;14:1326. J Med 1996;334:1150–1155. and markers of adiposity and inflamma-
23. Frosst P, Blom HJ, Milos R, et al. 38. American Institute for Cancer Research tion: The multiethnic cohort study. J Am
Candidate genetic risk factor for vas- fact sheet on fiber. http://www.aicr.org/ Coll Nutr 2017;36:378–385.
cular disease: A common mutation in assets/docs/pdf/fact-sheets/factsheet-about-f 55. Goldamn R, Shields PG. Food mutagens.
methylenetetrahydrofolate reductase. Nat iber.pdf (accessed on August 24, 2017). J Nutr 2003;133:965S973S.
Genet 1995;10:111–113. 39. World Cancer Research Fund/American 56. Snyderwine EG, Sinha R, Felton JS,
24. Marugame T, Tsuji E, Kiyohara C, et al. Institute for Cancer Research Diet, nutrition, Ferguson LR. Highlights of the eighth
Relation of plasma folate and methyl- physical activity and colorectal cancer 2017 international conference on carcinogenic/
tetrahydrofolate reductase C677T poly- Report. http://wcrf.org/sites/default/files/ mutagenic Nsubstituted aryl compounds.
morphism to colorectal adenomas. Int J CUP%20Colorectal%20Report_2017_Dig Mutation Res 2002;506–507:1–8.
Epidemiol 2003;32:64–66. ital.pdf (accessed on September 21, 2017). 57. Murtaugh MA, Ma K, Sweeney C, Caan
25. Ulrich CM, Curtin K, Potter JD, 40. Ben Q, Sun Y, Chai R, Qian A, Xu B, BJ, Slattery ML. Meat consumption pat-
Bigler J, Caan B, Slattery ML. Yuan Y. Dietary fiber intake reduces risk terns and preparation, genetic variants of
Polymorphisms in the reduced folate car- for colorectal adenoma: A meta-analysis. metabolic enzymes, and their association
rier, thymidylate synthase, or methio- Gastroenterology 2014;146:689–699. with rectal cancer in men and women.
nine synthase and risk of colon cancer. 41. Schatzkin A, Lanza E, Corle D, et al. J Nutr 2004;134:776–784.
Cancer Epidemiol Biomarkers Prev Lack of effect of a lowfat, highfiber diet 58. Ferguson LR. Natural and human-made
2005;14:2509–2516. on the recurrence of colorectal adenomas. mutagens and carcinogens in the human
26. Kim YI. Role of folate in colon cancer N Eng J Med 2000;342:1149–1155. diet. Toxicology 2002;181–182:79–82.
development and progression. J Nutr 42. Pfeiffer R, McShane L, Wargovich M, 59. Joosen AM, Lecommandeur E, Kuhnle
2003;133:3731s–3739s. et al. The effect of a lowfat, high fiber, GG, Aspinall SM, Kap L, Rodwell SA.
References 417
Effect of dietary meat and fish on endog- 66. Shield KD, Micallef CM, Hill C, et al. alcohol consumption. PLoS Med
enous nitrosation, inflammation and New cancer cases in France in 2015 2009;3:258–263.
60.
genotoxicity of faecal water. Mutagenesis
2010;25:243–247.
Sutandyo N. Nutritional carcinogenesis.
attributable to different levels of alcohol
consumption. Addiction 2018;113:247–
256. doi: 10.1111/add.14009.
73. Brennan P, Lewis S, Hashibe M, et al.
Pooled analysis of alcohol dehydro-
genase genotypes and head and neck
32
Arch Med Indones 2010;42:36–42. 67. Xi B, Veeranki SP, Zhao M, Ma C, Yan cancer: A HuGE review. Am J Epidemiol
61. Sesnick AL, Termont DS, Kleibeuker JH, Y, Mi J. Relationship of alcohol consump- 2004;159:1–16.
Van der Meer R. Red meat and colon tion to all-cause, cardiovascular, and 74. Yokoyama A, Omori T, Yokoyama T, et
cancer: The cytotoxic and hyperprolifera- cancer related mortality in U.S. adults. J al. Risk of squamous cell carcinoma of the
tive effects of dietary heme. Cancer Res Am Coll Cardiol 2017;70:913–922. upper aerodigestive tract in cancer-free
1999;59:5704–5709. 68. Bellocco R, Pasqualli E, Rota M, et al. alcoholic Japanese men: An endoscopic
62. Tappel A. Heme of consumed ret meat Alcohol drinking and risk of renal cell follow-up study. Cancer Epidemiol
can act as a catalyst of oxidative damage carcinoma: Results of a meta-analysis. Biomarkers Prev 2006;15:2209–221.
and could initiate colon, breast and pros- Ann Oncol 2012;23:2235–2244. 75. Kushi LH, Coyle C, McCullough M,
tate cancers, heart disease and other dis- 69. Tramacere I, Pelucchi C, Bonifazi M, et al. American Cancer Society guide-
eases. Med Hypothesis 2007;68:562–564. et al. A meta-analysis on alcohol drinking lines on nutrition and physical activity
63. Mole DR. Iron homeostasis and its inter- and risk of Hodgkin lymphoma. Eur J for cancer prevention: Reducing the
action with prolyl hydroxylases. Antioxid Cancer Prev 2012;21:268–273. risk of cancer with healthy food choices
Redox Signal 2010;12:445–458. 70. Seitz, HK, Becker P. alcohol metabolism and physical activity. CA Cancer J Clin
64. Cross AJ, Ferrucci LM, Risch A, et al. and cancer risk. Alcohol Res Health 2012;62:30–67.
A large prospective study of meat con- 2007;30:44–47. 76. American Institute for Cancer
sumption and colorectal cancer risk: an 71. Kanda J, Matsuo K, Suzuki T, et al. Impact Research Cancer Prevention
investigation of potential mechanisms of alcohol consumption with polymor- Recommendations. http://www.aicr.org/
underlying this association. Cancer Res phisms in alcohol-metabolizing enzymes can-prevent/what-you-can-do/10-reco
2010;70:2406–2414. on pancreatic cancer risk in Japanese. mmendations.html?referrer=https://www.go
65. World Cancer Research Fund Cancer Sci 2009;100:296–302. ogle.com/ (assessed on September 21, 2017).
International. Animal Foods. http://www 72. Brooks PJ, Enoch M-E, Goldman D, 77. Sebedio JL, Metabolomics, nutrition and
.wcrf.org/i nt/research-we-fund /cancer-pr Li T-K, Yokoyama A. The alcohol potential biomarkers of food quality,
evention-recommendations/animal-foods flushing response: An unrecognized intake and health status. Adv Food Nutr
(accessed on August 25, 2017). risk factor for esophageal cancer from Res 2017;82:83–116.
33
CHAPTER
419
420 Chapter 33 Lifestyle Approaches Targeting Obesity to Reduce Cancer Risk, Progression, and Recurrence
nutritional deficiencies.8–10 Individuals with a BMI of 18.5 and hematopoietic cells, is intensely metabolic with mul-
to 24.9 are considered normal and usually serve as the ref- tiple physiologic functions including appetite regulation,
erence range for conditions associated with elevated BMI. inflammation, modulation of insulin sensitivity, nutri-
Individuals with a BMI of 25–29.9 are considered over- ent uptake and storage, and other processes as well.19–22
weight and those with a BMI of 30 or over are considered Obesity-associated aberrations in these physiologic func-
obese. Obesity is sometimes further divided into 30.0–34.9 tions result in multiple and overlapping pathophysiologic
kg/m2, known as type 1 obesity, and BMI 35–39.9, known mechanisms by which obesity promotes cancer.23,24
as type 2 obesity, while BMI greater than 40 is considered
severe or morbid obesity.
Prior to 1962, only 14.3% of the U.S. adult popula-
tion was estimated to be obese.11 More recent U.S. data
33.2 MECHANISMS OF OBESITY
indicates the prevalence of obesity to be 36% in adults and IMPACT ON CANCER
17% in those under 20, with higher rates, 38.3%, in adult
women and lower rates, 34.3%, in men.12 Obesity rates When considering the multiple mechanisms by which
show a regional distribution with higher prevalence in the obesity affects cancer, it is important to note that obesity
eastern United States and even higher rates in the South, is not considered to initiate the carcinogenic process but
reaching greater than 35% in the Mississippi Delta states rather to promote cancer progression.24 As adipose tissue
of Louisiana and Alabama. Obesity likewise has an ethnic expands in association with overweight and obesity, adi-
distribution with the highest prevalence in Non-Hispanic pocytes, the fat containing cells, enlarge; some undergo
Black Americans, 48.1%, followed by Hispanics, 42.5%, cell death and become surrounded by pro-inflammatory
Non-Hispanic Whites, 34.5%, and is lowest among Non- macrophages to form crown-like structures (CLS), which
Hispanic Asians, 11.7%. generate cellular and humoral pro-inflammatory factors,
Although the United States is in the unenviable posi- including lipids, cytokines, IL-6, IL-1, and TNFα.25 These,
tion of leading the world in the prevalence of overweight in turn, further act to provide cellular and humoral growth
and obesity, similar trends occur in countries throughout promoting microenvironments that lead to insulin resis-
Europe, Australia, and the Middle East. In contrast, the tance.20,21 In addition, adipose tissue is responsible for syn-
prevalence of obesity in sub-Saharan Africa, India, and thesis and secretion of a number of adipokines, proteins
China is significantly lower; however, these countries are that under normal conditions have a variety of physiologic
now showing marked increases in the incidence of obesity, functions.22,26 These include leptin, which under normal
especially in urban areas where residents acquire western conditions increases in proportion to fat cell mass and
lifestyles.4 has an anorexigenic effect, that is, it down regulates appe-
The public is aware of the impact of obesity on heart tite;27 adiponectin, which increases in response to calorie
disease, stroke, and diabetes and engaged in multiple strate- restriction and has an orexigenic or appetite-stimulating
gies to reduce these comorbidities. However, a 2017 report function,28 and retinol binding protein 4 (RBP4) which
from the American Institute of Cancer Research (AICR) facilitates vitamin A uptake and transport.29 Increased
indicated that only 50% of Americans were aware that levels of these adipokines, such as leptin and RBP4, pro-
obesity stimulates cancer growth.13 After extensive review mote tumor cell growth by stimulating cell proliferation,
of epidemiologic data, the International Agency for Cancer survival, and invasion.30,31 In contrast, adiponectin, which
Research (IACR) recently concluded that there is sufficient suppresses cell proliferation and stimulates apoptotic cell
evidence to link 13 human malignancies to excess body fat- death, is decreased in obesity.28
ness.14 The obesity-linked malignancies are gastrointestinal Levels of insulin and insulin-like growth factor (IGF-1)
tract tumors including esophageal adenocarcinoma, gastric are usually increased in obesity where they may contrib-
cardia cancer, colon and rectal cancer, liver cancer, gall- ute to tumor growth. 21,22 While the normal physiologic
bladder and pancreatic cancer. The obesity-linked malig- function of insulin is to stimulate cellular glucose uptake
nancies also include post-menopausal breast, corpus uteri, and utilization, insulin can also stimulate cell growth.32,33
ovarian, renal cell, and thyroid cancers, meningioma, and Thus, elevated levels of insulin secreted by the pancreas in
multiple myeloma.14 In addition, there is suggestive but response to insulin resistance may have the pathophysi-
not conclusive evidence that other malignancies, including ologic effect of promoting tumor cell growth and cancer
some hematologic malignancies, prostate cancer, and even progression.32,33 IGF-1, synthesized mostly by the liver,
possibly lung cancer may be associated with obesity.15–18 has a structure similar to insulin, and commonly func-
Improved awareness and understanding of how excess tions to stimulate normal tissue growth. 33 Elevated levels
fat, overweight, and obesity, as well as high-fat diets, pro- of IGF-1 may likewise contribute to the pathophysiologic
mote cancer development and progression should contrib- mechanism by which obesity promotes tumor cell growth
ute to improved lifestyle efforts to control obesity, reduce and cancer progression.33
cancer risk, and mitigate some of its effects on prognosis. Aromatase, the enzyme responsible for convert-
Adipose tissue was once considered a storage depot where ing androstenedione to estrone and estrogen, is found
reserve energy was maintained in the form of fats (triglyc- in many organs including adipose tissue. Because of the
erides) to be released and utilized by peripheral tissues in increased adipose tissue associated with obesity, increased
times of energy demand or periods of restricted food avail- aromatase produces increased estrogen, which promotes
ability. However, it was shown that adipose tissue, com- the growth of breast cancer.34,35 Another process by
posed of adipocytes, stromal fibroblasts, vascular, immune which obesity promotes tumor growth is mediated by
33.2 Mechanisms of Obesity Impact on Cancer 421
the intestinal microbiome, which harbors a great num- has the same metabolic, hormonal, or pro-inflammatory
33
ber and extensive variety of bacteria whose concentration activity, and likewise, not all adipose tissue has the same
and metabolic products are highly dependent on both the tumor-promoting activities. Visceral fat, consisting of the
composition and quantity of our dietary intake and nutri- fat in and around abdominal organs, is more intensely met-
tional status. Shifts in these populations, such as increases abolic and pro-inflammatory, produces more pro-inflam-
in bacteroidetes or decreases in firmicutes, promoted by matory cytokines such as TNFα and IL-6, and is more
high-fat diets, may lead to metabolic changes and circu- likely to stimulate insulin resistance, diabetes, and cardio-
lating toxins that promote cancer growth. 36 Obesity may vascular disease than subcutaneous fat, which lies directly
also predispose to cancer by mechanical factors such as under the skin.50–52 Visceral fat has been epidemiologi-
stretching of diaphragmatic muscles leading to a hia- cally linked to tumor promotion in humans. 53,54 In mouse
tal hernia and gastro-esophageal reflux disease thereby models, surgery to remove visceral fat depots has been
predisposing to esophageal adenocarcinoma.37–39 It has shown to reduce the development of intestinal tumors55
recently been shown that adipocytes (fat cells) can take up and ultraviolet light-induced skin carcinogenesis. 56
and metabolize cancer chemotherapeutic agents, thereby However, this surgery is not practical in humans. Although
reducing available chemotherapy in the tumor microen- liposuction removes subcutaneous fat, it has been used
vironment. Thus, the increase in adipocyte number and primarily for cosmetic body contouring57 but has not been
size associated with obesity, along with their ability to shown to produce sustained body weight loss or to reduce
reduce tumor exposure to chemotherapeutic agents, pro- risk for many of the pathophysiologic consequences of
vides a mechanism for tumor cells to escape and survive obesity. Caloric restriction, on the other hand, is likely
chemotherapy.40 to reduce both subcutaneous and visceral adipose mass
Many of the effects just described are the result of alter- and to reduce risk of obesity-associated comorbidities. In
ations in metabolic, hormonal, or pro-inflammatory sig- preclinical animal model studies, the prevention of obesity
naling pathways associated with obesity. These pathways by calorie control or weight loss after calorie restriction,
may be regulated in relatively rapid response to changes following diet-induced obesity, has been shown to reduce
in nutritional status. Obesity may also alter cellular mes- or delay the incidence of tumors. 58
saging by more stable epigenetic processes in which modi- Other studies demonstrate that the tumor-promoting
fication of the DNA or its supporting chromatin proteins effects of obesity can be reduced by pharmacologic inter-
change the genetic readout without altering the genetic ference with obesity-mediated growth promotion and
sequence.41–43 Such alterations include chemical modifi- pro-inflammatory pathways. For example, the blockade
cations like methylation of DNA or methylation, acety- of insulin or IGF-1 receptors59 and molecular interfer-
lation, or other changes in chromosomal proteins that ence with leptin receptor60 counteract obesity promotion
alter their structure and function.41–43 These epigenetic of breast cancer. Likewise, both genetic and pharmaco-
changes may persist after nutritional status changes.44,45 logic interference with the pro-inflammatory activity of
They may become heritable, through multiple generations the complement system counteracts the obesity-mediated
of cell division, and may even become transgenerational, progression of colorectal tumors.61
passing from parent to offspring.44–46 It is now becoming While obesity itself is associated with an increased
apparent that lifestyle phenomena such as starvation, obe- risk for cancer, it is also clear that different dietary fats
sity, and physical activity may alter epigenetic factors that may have different effects on cancer development. Murine
affect individuals and pathophysiology of chronic condi- models and human epidemiologic studies indicate that
tions like obesity, diabetes, and cancer.42,47,48 For example, not all dietary fat is equal in influencing obesity and can-
obesity has been shown to induce epigenetic, structural cer risk. For example, saturated coconut oil and corn oil
changes in organization and structure of chromatin in promote tumor growth, while equal amounts of olive oil
colon epithelium that alters binding of transcription fac- promote obesity but not tumor growth.61 Further, high-fat
tors promoting colon development and growth.49 While lard-based diets fed to obesity-resistant BALB/C mice pro-
these changes did not directly promote tumor growth, they moted growth and metastasis of mammary carcinoma.62
induced chromatin structural remodeling that enhanced In general, tumor-promoting fatty acids include medium-
cell signaling pathways driving cancer progression.49 The chain saturated fatty acids such as lauric and myristic
sustainability of these epigenetic changes suggests the pos- acids; long-chain saturated fatty acids including palmitic
sibility that the tumor-promoting effects of obesity, at any and stearic acid, and ω6 polyunsaturated fatty acids, lin-
stage of life, may contribute to cancer progression at later oleic and arachidonic acids. In contrast, unsaturated fatty
ages leading to the need for epigenetic-targeted therapy.43 acids including oleic and conjugated linoleic acid and ω3
The importance of considering both the metabolic, hor- polyunsaturated fatty acids, including eicosapentaenoic,
monal, and pro-inflammatory effects of obesity and the docosahexaenoic, and α-linolenic acid, have anti-inflam-
epigenetic effects is that the former may be largely elimi- matory properties that function as tumor suppressors.63
nated or reversed with weight loss, whereas the latter may Studies with animal models indicating that different
be more durable. Thus, while elimination of obesity and types of dietary fat may impact tumor growth have been
restoration of normal body weight is desirable at any time shown to be clinically relevant. For example, the consump-
of life, it may not always reverse all cancer-promoting the tion of high quantities of olive oil was associated with a
consequences of obesity. decreased risk of upper aerodigestive and breast cancer.64
In studies on the effects of obesity on adverse health Increasing ω-3 PUFAs has been shown to alter the risk
outcomes, it is noteworthy that not all adipose tissue of several malignancies including breast, colon, lung, and
422 Chapter 33 Lifestyle Approaches Targeting Obesity to Reduce Cancer Risk, Progression, and Recurrence
prostate cancer.65,66 Additionally, a high fat, walnut-based The beneficial consequences of intentional weight loss
diet decreased the risk of pancreatic cancer and cancer have been most successfully demonstrated by bariatric sur-
metastasis.67,68 gery in which obese patients undergo one of several surgi-
High carbohydrate diets leading to hyperglycemia cal procedures to reduce and/or bypass gastric function and
and insulin resistance, especially in obese and/or diabetic capacity.83 With appropriate post-surgical management,
individuals, have been shown in model, epidemiologic, these procedures are among the most successful in achieving
and clinical studies to contribute to cancer progression sustained weight loss and reduction of comorbidities associ-
and its adverse effects. 69–71 While obesity is associated ated with obesity84–87. In the Swedish Obese Subject (SOS)
with the increasing incidence of esophageal adenocar- prospective study, comparing the outcomes in 2010 bariatric
cinoma, increased carbohydrate consumption appears surgery-treated patients to 2036 controls, bariatric surgery
to be a contributing factor.70 At the clinical level, in was associated with a 40% reduction in cancer incidence
patients with stage III colon cancer and elevated BMI after 10.9 years follow-up.84,85 In a retrospective single-prac-
and who had failed adjuvant chemotherapy, increased tice study from Utah of 7,925 patients who underwent gas-
glycemic and carbohydrate loads led to shorter overall tric bypass surgery, the surgical intervention showed a 60%
survival.71 decrease in cancer mortality compared to 7,955 controls.88
In one of the longest follow-up periods, 16 years, the
overall mortality in the SOS study was reduced in patients
33.3 STRATEGIES TO DISRUPT THE undergoing surgery compared to medically managed obese
patients. Cancer was noted to be the most common cause of
OBESITY–CANCER LINKAGE death with 47 cancer deaths in the control group compared
to 29 in the surgery group. The number of first-time cancer
From a clinical perspective, the most effective way to pre- diagnoses, 117 in the surgery group, was lower than in the
vent the increased cancer risk associated with obesity is controls 169.85 Bariatric surgery has been shown to reduce
by maintaining a lean body mass throughout life, using the risk of endometrial cancer in severely obese patients.89
prudent lifestyle practices of dietary regulation, and per- In a recent retrospective study of 22,198 subjects who had
forming regular physical activity. For individuals who are bariatric surgery for severe obesity compared to 66,427
overweight or obese, reducing the excess obesity asso- matched controls, surgically treated patients had a 33%
ciated with comorbid risk factors should primarily be lower incidence of new cancers over a three-year follow-
addressed by lifestyle modifications to lose weight and up period compared to controls.90 The risk reduction was
restore normal body mass. Studies to demonstrate the greater for obesity-associated cancers including post-meno-
clinical effectiveness of this approach are limited; how- pausal breast, colon, endometrial, and pancreatic cancer.90
ever, they do indicate that intentional weight reduction Bariatric surgery has also been successful in achieving
by lifestyle modification, in morbidly obese patients, is weight loss in cancer survivors91 following primary treat-
associated with normalization of circulating cancer risk ment of malignancy, but long-term effects on recurrence
factors including estrogens, insulins, IGF-1, inflammatory and on overall or disease-related survival have not yet
markers such as IL-6, TNFα, and others.72–74 It is note- been reported. Bariatric surgery to reduce weight during
worthy that these effects occurred with sustained weight the active treatment of malignancy has not been reported
loss. Weight cycling, repeated cycles of loss followed by in enough numbers to evaluate its potential for mitigating
regaining of the excess weight, has not effectively been adverse prognostic effects in patients with cancer.
shown to reduce obesity-associated cancer risk. It may in In summary, dietary interventions have resulted in
fact have the opposite effect of increasing risk for breast modest weight loss, improvement in cancer biomarkers,
cancer, renal cell cancer, and non-Hodgkin Lymphoma in decrease in incidence of several cancers, and extended
post-menopausal women.75 overall survival. Importantly, these beneficial effects
While studies indicate that intentional weight loss can appear to be associated with weight loss and are unlikely
reduce obesity-associated biomarkers that are potential to occur with weight cycling. In contrast, bariatric surgery
promoters of cancer progression, there have been limited has produced greater and more sustained weight loss and
randomized controlled studies to evaluate whether dietary greater reduction in cancer risk. The limited benefits of
interventions can improve cancer risks or outcomes. In dietary interventions compared to bariatric surgery serve
general, studies to alter dietary composition have not been to emphasize the importance of significant and sustained
effective at primary prevention of breast cancer occur- weight loss and restoration of lean body mass to reduce
rence or secondary prevention of tumor recurrence except cancer incidence among overweight and obese patients.
when interventions were accompanied by weight loss.76–82 Persistence of some degree of elevated risk after weight loss
Despite not yielding risk reduction, reduced fat diets and may be associated with lasting epigenetic consequences
resultant weight reduction did, however, result in sur- of obesity and may require specific targeted therapy to
vival benefits for post-menopausal women with hormone reverse. While those possibilities are in development, the
receptor-negative tumors.81,82 Importantly, however, there overweight/obesity-increased risk is most effectively pre-
were no adverse effects associated with the dietary inter- vented by maintaining lean body mass throughout life
ventions, and it is possible that a more rigorous dietary and by emphasizing the necessity for adopting prudent
intervention with greater adherence could still have more lifestyle practices, including diet modulation, avoidance
significant beneficial effects. of pro-inflammatory foods, and regular physical activity.
33.4 Lifestyle Recommendations to Disrupt the Obesity–Cancer Linkage 423
33
litus, hypertension, coronary artery disease, strokes,
TO DISRUPT THE OBESITY– and, of course, many cancers.4– 6 As previously noted,
individuals should strive to achieve and keep a lean body
CANCER LINKAGE weight throughout life, including throughout childhood
and old age, since increased weight at any time of life
33.4.1 Recommendations for may result in obesity at later stages and may also have
Lifestyle Modifications for long-lasting epigenetic effects. In a recent meta-analysis
Primary Cancer Prevention of 50 prospective studies, adult weight gain was sig-
nificantly associated with increased risk for post-meno-
As previously discussed, maintaining a healthy BMI (18.5 pausal breast cancer, endometrial and ovarian cancers,
to 24.9) throughout life is as important to prevent certain as well as colon cancer in men.92 In adolescents, over-
common types of cancer as is avoidance of tobacco con- weight and obesity have been associated with increased
sumption. While there are multiple guidelines and recom- risk for colon cancer93 and colon cancer-related death.94
mendations on what constitutes a healthy approach to And even though the incidence of colon cancer has
weight management, the most important behaviors focus decreased overall since the late 1990s, colon and rectal
on diet and physical activity. As any excessive energy con- cancer rates have actually increased by 90% and 124%
sumption will be stored as fat, it is fundamental for success- respectively for patients ages 20 to 34.95
ful weight loss to decrease the number of calories ingested In adolescents and children over two years old, a BMI
while increasing physical activity. For persons striving to between the 5th and the 85th percentiles is considered
keep current weight, expenditure and consumption of calo- healthy. BMIs between the 85th and 95th percentiles are
ries should be relatively balanced. Provided that endocrine considered overweight and above the 95th percentile qual-
disorders affecting basal metabolic rate do not play a role ifies as obese. Childhood obesity predicts not only adult-
in one’s health (i.e. hypothyroidism), the simple math of hood obesity but also type 2 diabetes mellitus (DM) and
keeping energy expenditure greater than energy consump- abdominal obesity.96 For the overweight or obese, contro-
tion should suffice as a rough guide. versy exists as to which is more effective, rapid or gradual
A number of guidelines on physical activity and diet for weight loss; however, whichever approach is taken, it is
cancer prevention are accessible to the general public and quite clear that long-term management is essential for
health practitioners (Table 33.1). The majority of recom- maintenance.97,98
mendations focus on maintaining a lean body weight and Since 1 pound is equal to 3500 calories, in order to
avoiding obesity and were created using the best currently lose 1–2 pounds in 1 week, one must decrease the inges-
available data and a multitude of studies of mostly obser- tion of calories by 500–1000 calories per day, on average.
vational nature have supported the benefits of adhering to Making lifelong lifestyle changes is recommended by all
such guidelines for cancer prevention. In this section, we national guidelines and leading experts to modify energy
provide a compilation of current guidelines while adding balance and maintain a healthy weight.
personal recommendations on nutrition and physical activ-
ity to decrease cancer risk.
33.4.1.2 Avoid High-calorie Foods and Sugary Drinks
33.4.1.1 Achieve and Maintain a Lean A major contributor to the obesity epidemic is the avail-
Weight Across Life Span ability and appeal of energy-dense foods, which are
defined as having an energy content of at least 225 Kcal
A body mass index between 18.5 and 24.9 is consid-
per 100 grams. The densest micronutrient is fat, as each
ered healthy as it is associated with decreased risk for
gram of fat equals nine calories. Each gram of protein
or carbohydrate, on the other hand, corresponds to four
TABLE 33.1 Obesity cancer guidelines calories.99 Naturally, for the same number of calories, a
person can consume a much larger portion of food with
American Cancer Society http://www.cancer.org/healthy/ lower energy density than a food higher in energy density.
Guidelines for Nutrition eat-healthy-get-active/acs-guidelin As an example, one orange has 1/4 of the energy density
and Physical Activity es-nutrition-physical-activity-canc
er-prevention/guidelines .html
of one fried egg. In general, foods with the lowest energy
density tend to be high in water and fiber content and
American Institute for http://aicr.org/can-prevent/need-to very low in fat (fruits and vegetables). The consumption
Cancer Research -know/index.html of energy-dense foods should be done sparingly.100 Sugary
– Cancer Prevention
Recommendation
drinks should be avoided completely and so should fast
foods. Fruit juices should also be limited. Fruits are best
National Heart, Lung and https://www.nhlbi.nih.gov/health-to eaten whole.100
Blood Institute pics/topics/obe
U.S. Department of http://www.gov/fitness/eat-healthy/
Health and Human dietary -guidelines-for-americans/ 33.4.1.3 Prioritize Healthy Eating Patterns—Rich
Services: President’s index.html in Whole Foods, Plant-based Elements
Council of Fitness,
Sports and Nutrition
Because vegetables, legumes, whole grains, and fruits are
very high in fiber and water and overall low in fat, they
424 Chapter 33 Lifestyle Approaches Targeting Obesity to Reduce Cancer Risk, Progression, and Recurrence
are the perfect example of low energy-dense foods that meaningful weight loss can boost energy levels, improve
promote healthy weight loss or weight maintenance. They mobility, self-esteem, and mood, leading to greater adher-
should be consumed mostly whole, with minimal if any ence to lifestyle modifications.
processing, including juicing. Processing, such as juicing,
reduces the fiber content that promotes gastric stretching 33.4.1.6.1 Weight Management Programs
and feeling of satisfaction after eating while concentrat-
ing carbohydrates and calories. For a detailed discussion Typically focusing on behavioral treatment, weight
on this topic, refer to the chapter on Diet and Cancer management programs offer a comprehensive approach
Prevention. to obesity and overweight, including a large element of
coaching. Following individualized assessment, subjects
commonly engage in both individual and group sessions
33.4.1.4 Physical Activity aiming to educate and develop strategies to overcome bar-
riers to lifestyle modifications. Patients are encouraged
Physical activity has many health benefits. Not only does
to establish weight-loss goals, develop a plan for reduced
it “burn calories,” but exercise can also enhance muscle
caloric intake and increased physical activity, as well as
mass leading to increased baseline metabolic rate, aiding
self-monitoring strategies. Individuals are encouraged to
in weight loss maintenance. It can also decrease levels of
engage in a steady and slow weight-loss process of 1–2
growth factor hormones such as insulin and insulin growth
pounds per week, as very rapid weight loss (more than 3
factor 1 (IGF-1), improve lipid profile, and increase bone
pounds per week) can be associated with health hazards
mineral density. Many studies have supported a protective
such as gallstones.
effect of exercise in breast cancer101 even more so with vig-
orous activity.102 Similar associations have been reported
for colon103 and endometrial cancers.104 For more infor- 33.4.1.6.2 Bariatric Surgery
mation, see the chapter on Physical Activity and Cancer. Morbidly obese individuals (BMI ≥ 40 Kg/m 2) or obese
subjects (BMI ≥ 35 Kg/m 2) who also have comorbidities
(type 2 DM, for instance) and despite behavioral treat-
33.4.1.5 Maintain Good Sleep Hygiene
ment cannot achieve target health outcomes are typically
Sleep may play a more important role in weight manage- referred for a consultation with a bariatric surgeon.116
ment than it is given credit for. For natural, successful Compared to lifestyle modifications, bariatric surgery
sleep to occur, a highly structured circadian interplay of leads to greater weight loss and higher rates of successful
biological mechanisms, for example, melatonin release in control of metabolic syndrome indicators, such as glucose
response to environmental cues requires dimming of lights/ intolerance/type 2 DM.117 On average, patients undergo-
darkening. Lack of adequate sleep has been associated ing bariatric surgery lose 60% of excess body weight, with
with many diseases, including obesity. Recently it has been more than 80% of patients achieving either complete reso-
demonstrated that sleep restriction can, in fact, activate lution or improvement of type 2 DM.118
the endocannabinoid system, which modulates appetite There are different types of operations, with different
and food intake,105 as well as other appetite-stimulating technical challenges, complications, and morbidity. The
hormones such as ghrelin,106 leading to an increase in roux-en-y gastric bypass (RYGB) and the sleeve gastrec-
body mass index.107 Sleep deprivation also worsens insu- tomy procedures typically have higher success rates when
lin sensitivity and is a risk factor for type 2 DM.108 Short compared to gastric banding.119,120 As with any medical
sleep duration has been associated with colorectal adeno- intervention, failures can also occur, and re-operation
mas109 and cancer.110 In breast cancer patients with hor- may be required. For individuals undergoing operations
mone receptor-positive tumors, shorter sleep is correlated leading to significant anatomical changes, such as with
with a higher likelihood for systemic relapse.111 The initial the RYGB surgery, vitamin deficiencies can develop121 and
recommended approach to chronic insomnia is cognitive monitoring and replacement for life (vitamin B12 , iron,
behavioral therapy, which mostly addresses healthy sleep vitamin D) may be indicated.
practices and relaxation training.112 It can lead to signifi- Existing data is still conflicting regarding whether
cant and durable symptom control.113 It may be necessary bariatric surgery affects cancer-related mortality, in part
to address an existing psychiatric disorder, and pharmaco- due to the limitations of the studies reported, which are
therapy when cognitive behavioral therapy alone does not mostly of cohort nature and with short follow-ups. Some
effectively control insomnia.114 studies have demonstrated at least a 60% reduction in
cancer-related deaths88,122,123 while others have found no
effect.124 In contrast, two Swedish studies suggest that
33.4.1.6 Lose Weight If You Are Overweight or Obese bariatric surgery patients may have a higher incidence of
As previously discussed, weight loss is achieved if a caloric colon cancer, especially at 10 years following surgery.125,126
deficit is created by restricting the intake of calories with Thus, although bariatric surgery provides proof of the
or without increasing the energy expenditure with exer- principle that significant weight loss can reduce cancer
cise. Clinicians should screen all adults for overweight and risk, because of the unresolved controversy about the
obesity and counsel on weight loss, referring patients to late increase in colon cancer and the radical nature of the
weight management programs if needed. It is important procedure, we conclude that there is insufficient evidence
to stress that even a 5–10% weight loss is already asso- to recommend for or against bariatric surgery for cancer
ciated with substantial health benefits.115 Also, small but risk reduction, though it clearly constitutes an option for
33.4 Lifestyle Recommendations to Disrupt the Obesity–Cancer Linkage 425
treatment of severe and refractory obesity and metabolic hormonal therapy, and radiotherapy) that decreases
33
comorbidities.86,87 physical mobility and ability to exercise
• Development of side effects such as neuropathy,
myalgia, and arthralgia that can make regular forms
33.4.1.7 Follow Cancer Screening Guidelines of exercise a painful and challenging endeavor
While people who are overweight or obese have a tendency • Use of hormonal manipulation (especially in the case
to avoid cancer screening, it is important to remember of breast and prostate cancers) leading to decrease in
that obesity increases risk for cancer occurrence and that muscle mass leading to sarcopenic obesity (obesity
early detection increases the chance of cure and decreases with depleted muscle mass)
the need for more extensive therapies that can cause • Gastrointestinal side effects, such as dysgeusia (taste
unwanted side effects and complications. Accordingly, it bud changes), nausea, diarrhea, and constipation,
is important that all individuals, especially those who are that lead to perversion of natural food choices and
overweight or obese, follow the recommended screening may skew food intake towards unhealthy food groups
guidelines for breast, colorectal, lung, and gynecologic • Sleep dysfunction is a common manifestation of
cancers.127–133 cancer and/or side effect from treatment and, as pre-
viously discussed, can contribute to weight gain
TABLE 33.2 Recommendations for lifestyle modifications for primary cancer prevention
Achieve and maintain a lean weight across life span Healthy BMI for adults: 18.5–24.9
Adolescents and children over age 2: BMI between 5th and 85th percentile
for the age
If overweight or obese, lose weight gradually Weight loss goal: 1–2 pounds per week
Avoid calorie-dense foods and sugary drinks Drink more water and avoid high glycemic foods such as desserts, sodas,
white breads
Prioritize healthy eating patterns, eating plant-based Consume at least 5 portions of vegetables and fruits of different colors (dark
whole foods that are not calorie- but nutrient-dense leafy greens, orange, red, yellow and purple) daily. Use legumes (beans) as a
(high in vitamins and minerals) and high in fiber content major source of protein.
Limit the amount of certain animal-derived foods Red meat (beef, pork, lamb, goat) should be limited to <500 grams/week. If
consuming animal protein, prioritize fish and poultry
Consider adopting a well-balanced vegetarian or vegan Whole foods, plant-based diet aid in weight loss and maintenance of healthy
(whole foods, completely plant-based) diet weight through avoidance of calorie-dense foods while providing ample
amounts of protein, minerals, and vitamins
Engage in physical exercise Aim for at least 150 minutes of moderate exercise (brisk walk, biking, yoga)
or 75 minutes of vigorous exercise (swimming, running/jogging) per week
Avoid completely the use of tobacco and if drinking Men should limit alcohol intake to up to 2 drinks per day and women to less
alcohol, use moderation than 1 drink per day. One standard drink = 5-oz glass of wine, 1.5 oz hard liquor,
12 oz beer. Alcohol is a calorie-dense drink and can lead to weight gain.
Prioritize sleep Aim for 7–8 hours of sleep every night
Avoid dietary supplements unless prescribed by a Obtain all vitamins and minerals from your diet. People following a strict
physician plant-based diet (vegan diet) require oral B12 supplementation
If unable to lose weight by making all aforementioned Achieving and keeping a healthy BMI should be a priority. Discuss with
recommendations, consider joining a weight primary care provider bariatric surgery evaluation if behavior modifications
management program fail to promote meaningful weight loss
increasing the consumption of fruits and vegetables and 33.4.2.6 Invest in Sleep Hygiene
decreasing the consumption of dietary fat. In this cohort
Insomnia is an often non-recognized symptom in cancer
of pre- and post-menopausal women, there were no dif-
survivors. While many patients are insomniacs by the
ferences in outcomes between the intervention and the
time of cancer diagnosis, many develop this symptom as
control group79 in terms of weight loss, progression-free
a consequence of adjusting to the diagnosis, side effects
survival, or overall mortality. It is noteworthy, however,
from therapy, or cancer-related symptoms. As such,
that the WHEL study was not designed to achieve weight
insomnia should be addressed in every cancer survivor
loss. In contrast, the Women’s Initiative in Nutrition
and treated.
Study (WINS) addressed the impact of decreasing all
dietary fat to 15% of total energy intake and found a
24% lower risk of breast cancer recurrence; however, this
was not statistically significant. Nonetheless, a secondary 33.4.3 Type 2 Diabetes Mellitus
analysis found a 42% lower recurrence risk in the hor-
monal receptor-negative breast cancer patients. Of note, and Cancer Risk
even though the study did not target weight reduction, Obesity is a major risk factor for the development of
there was nonetheless a mean weight loss of six pounds in type 2 DM. Type 2 DM is a condition defined by resis-
the intervention group.81 These studies suggest that while tance to insulin, leading to sustained hyperinsulinemia
dietary change alone was not sufficient to reduce the risk and hyperglycemia. It has been associated with an
for breast cancer, risk may be reduced when diet change increased risk for different types of malignancies, includ-
was accompanied with weight loss. The contrasting ing pancreatic, colon, endometrial, breast, and hepatobi-
results in WINS and WHEL studies may also be attrib- liary cancers.154 One of the working hypotheses for the
utable, in part, to the fact that WINS focused on post- increased cancer risk seen in diabetics is the cancer-pro-
menopausal women while WHEL studied both pre- and moting effect of insulin and IGF-1, the levels of which are
post-menopausal women, along with other differences.77 typically elevated in this population. These hormones can
An ongoing initiative, Breast Cancer Weight Loss (BWEL activate mitogenic pathways, affecting tumor microenvi-
Study) is a randomized controlled study to specifically ronment and cell signaling pathways that lead to tumor
evaluate a portion control and calorie restriction weight growth and progression.155 Type 2 DM is associated with
loss intervention on breast cancer recurrence and survival excess mortality in a multitude of cancer types, including
in overweight or obese, pre- and post-menopausal women colorectal, breast, pancreatic, gastric, liver, endometrial,
with early stage breast cancer.153 and even lung cancers.156–158
References 427
Metformin is commonly the first drug used for the the weight and height of the individual. Deviating from
33
treatment of type 2 DM. Through activation of the standard dosing and dose-intensity can compromise long-
AMP-activated protein kinase (AMPK) pathway,159 it term outcomes and survival of cancer patients, particu-
can decrease the production of glucose in the liver. It also larly when treating with curative intent. In that regard,
increases insulin sensitivity and lowers its circulating levels. the American Society of Clinical Oncology (ASCO) has
AMPK regulates cell metabolism and becomes activated issued guidelines for treating oncologists on how to dose
when there is shortage of energy and also acts as a tumor chemotherapy agents in the ever-growing obese popula-
suppressor.160 Through AMPK activation, metformin may tion. ASCO recommends that chemotherapy agents are
exert cancer prevention properties and has been impli- full weight-based dosed, and that ideal body weight or
cated in reducing the incidence of certain types of cancers adjusted body weight are not used for dosing.167 Obese
in diabetics, including pancreatic, breast, and liver can- cancer patients should be aware of this recommendation
cers.161,162 Many prospective studies are underway explor- and ensure that treating oncologists are knowledgeable in
ing the chemopreventive properties of this drug. In the this regard.
meantime, we recommend this as the therapy of choice
when treating type 2 DM in cancer survivors.
There is much controversy regarding an association 33.5 CONCLUSIONS
between insulin use in patients with type 2 DM and
increased risk of cancer and poorer survival.163–166 It is Obesity is a risk factor for many types of malignancies,
possible that some of the positive association is biased including the highly prevalent post-menopausal breast
by the chronicity of type 2 DM diagnosis and its severity and colorectal cancers. Excessive adipose tissue can pro-
requiring insulin use. Accordingly, patients with both can- mote tumor progression through a variety of mechanisms,
cer and type 2 DM should be sure that their DM is man- including inflammatory, hormonal, and epigenetic altera-
aged by a physician knowledgeable about these effects. tions. Therefore, maintaining a healthy BMI across the
lifespan is essential for cancer prevention. This can be
achieved by adherence to national guidelines on diet and
physical exercise. Since even after an initial cancer diagno-
33.4.4 Special Considerations sis obesity may impact cancer-related outcomes, achieving
The doses of most antineoplastic agents are traditionally and keeping a healthy weight constitutes a key priority in
calculated based on the body surface area (BSA), using cancer survivorship.
REFERENCES
1. Bassett MT, Perl S. Obesity: The public 9. Coin A, Sergi G, Beninca P, et al. 17. Hidayat K, Du X, Chen G, Shi M, Shi
health challenge of our time. Am J Public Bone mineral density and body B. Abdominal obesity and lung cancer
Health. 2004;94(9):1477. composition in underweight and risk: Systematic review and meta-anal-
2. Hurt RT, Kulisek C, Buchanan normal elderly subjects. Osteoporosis. ysis of prospective studies. Nutrients.
LA, McClave SA. The obesity 2000;11(12):1043–50. 2016;8(12):810.
epidemic: Challenges, health ini- 10. Muller O, Krawinkel M. Malnutrition 18. Carreras-Torres R, Johansson M,
tiatives, and implications for gastro- and health in developing countries. Can Haycock PC, et al. Obesity, metabolic
enterologists. Gastroenterol Hepatol. Med Assoc J. 2005;173(3):279–86. factors and risk of different histologi-
2010;6(12):780–92. 11. Ogden CL, Carroll MD. Prevalence of cal types of lung cancer: A Mendelian
3. Ezzati MN-RC. Trends in adult body- overweight, obesity, and extreme obesity randomization study. PloS One.
mass index in 200 countries from 1975 among adults: united states, trends 2017;12(6):e0177875.
to 2014: A pooled analysis of 1698 1960–1962 through 2007–2008: NCHS 19. Hotamisligil GS, Arner P, Caro JF,
population-based measurement studies - Health E-Stats, 2010; www.cdc.gov/nch Atkinson RL, Spiegelman BM. Increased
with 19.2 million participants. Lancet. s/data /hestat/overweight/overweight _ adul adipose tissue expression of tumor
2016;387(10026):1377–96. t.htm(accessed on November 1, 2017) necrosis factor-alpha in human obesity
4. Afshin A, Forouzanfar MH, Reitsma 12. Flegal KM, Kruszon-Moran D, and insulin resistance. J Clin Invest.
MB, et al. Health effects of overweight Carroll MD, Fryar CD, Ogden CL. 1995;95(5):2409–15.
and obesity in 195 countries over 25 Trends in obesity among adults in the 20. Hotamisligil GS. Inflammation
years. N Engl J Med. 2017;377(1):13–27. United States, 2005 to 2014. JAMA. and metabolic disorders. Nature.
5. Massetti GM, Dietz WH, Richardson 2016;315(21):2284–91. 2006;444(7121):860–7.
LC. Excessive weight gain, obesity, and 13. American Institute for Cancer Research. 21. Reilly SM, Saltiel AR. Adapting to
cancer: opportunities for clinical inter- Cancer Risk Awareness Infographic obesity with adipose tissue inflammation.
vention. JAMA. 2017;318:1975–6. 2017. http://www.aicr.org/learn-more Nat Rev Endocrin. 2017;13(11):633–43.
6. Finkelstein EA, Trogdon JG, Cohen -about-cancer/in fographics /infograph ic-c 22. Ouchi N, Parker JL, Lugus JJ, Walsh
JW, Dietz W. Annual medical spending ancer-risk-awareness.html (accessed on K. Adipokines in inflammation and
attributable to obesity: Payer-and service- November 1, 2017). metabolic disease. Nat Rev Immun.
specific estimates. Health Affairs (Project 14. Lauby-Secretan B, Scoccianti C, et al. 2011;11(2):85–97.
Hope). 2009;28(5):w822–31. Body Fatness and Cancer—Viewpoint of 23. Hursting SD, Digiovanni J, Dannenberg
7. National Heart L, Blood Institute the IARC Working Group. N Engl J Med. AJ, et al. Obesity, energy balance,
(NHLBI). Aim for a Healthy Weight: 2016;375(8):794–8. and cancer: New opportunities
NIH. http://www.nhlbi.nih.gov/health / 15. Snowdon DA, Phillips RL, Choi W. Diet, for prevention. Cancer Prev Res.
educational/lose_wt /BMI / bmicalc.ht m obesity, and risk of fatal prostate cancer. 2012;5(11):1260–72.
(accessed on November 1, 2017). Am J Epidemiol. 1984;120(2):244–50. 24. Berger NA. Obesity and cancer
8. Roh L, Braun J, Chiolero A, et al. 16. Poynter JN, Richardson M, Blair CK, et pathogenesis. Ann N Y Acad Sci.
Mortality risk associated with under- al. Obesity over the life course and risk 2014;1311:57–76.
weight: A census-linked cohort of 31,578 of acute myeloid leukemia and myelodys- 25. Park EJ, Lee JH, Yu GY, et al. Dietary
individuals with up to 32 years of follow- plastic syndromes. Cancer Epidemiol. and genetic obesity promote liver
up. BMC Public Health. 2014;14:371. 2016;40:134–40. inflammation and tumorigenesis by
428 Chapter 33 Lifestyle Approaches Targeting Obesity to Reduce Cancer Risk, Progression, and Recurrence
enhancing IL-6 and TNF expression. 45. Choi SW, Friso S. Epigenetics: A new carcinoma cells and mortality in obesity-
Cell. 2010;140(2):197–208. bridge between nutrition and health. Adv resistant BALB/c mice. Breast Cancer
26. Riondino S, Roselli M, Palmirotta R, Nutr. 2010;1(1):8–16. Res. 2011;13(4):R78.
et al. Obesity and colorectal cancer: 46. Heard E, Martienssen RA. 63. Doerner S, Berger NA. Dietary fats as
Role of adipokines in tumor initia- Transgenerational epigenetic inheri- mediators of obesity, inflammation and
tion and progression. World J Gastro. tance: Myths and mechanisms. Cell. colon cancer. In: Dannenberg AJ, Berger
2014;20(18):5177–90. 2014;157(1):95–109. NA, editors. Obesity, Inflammation and
27. Zhang Y, Proenca R, Maffei M, et al. 47. Dunn GA, Morgan CP, Bale TL. Cancer. Energy Balance and Cancer.
Positional cloning of the mouse obese Sex-specificity in transgenerational New York: Springer; 2013, pp. 99–132.
gene and its human homologue. Nature. epigenetic programming. Horm Behav. 64. Pelucchi C, Bosetti C, Negri E, et al.
1994;372(6505):425–32. 2011;59(3):290–5. Olive oil and cancer risk: An update
28. O’Leary VB, Kirwan JP. Adiponectin, 48. Ahmed F. Epigenetics: Tales of adversity. of epidemiological findings through
obesity, and cancer. In: Reizes O, Berger Nature. 2010;468(7327):S20. 2010. Curr Pharmaceut Des.
NA, editors. Adipocytokines, En ergy 49. Li R, Grimm SA, Chrysovergis K, et al. 2011;17(8):805–12.
Balance, and Cancer. Cham: Springer Obesity, rather than diet, drives epig- 65. Iyengar NM, Hudis CA, Gucalp A.
International Publishing; 2017, p. 21–38. enomic alterations in colonic epithelium Omega-3 fatty acids for the prevention
29. Noy N, Li L, Abola MV, Berger NA. Is resembling cancer progression. Cell of breast cancer: An update and state
retinol binding protein 4 a link between Metab. 2014;19(4):702–11. of the science. Curr Breast Cancer Rep.
adiposity and cancer? Hormone Mol Biol 50. Qiang G, Kong HW, Fang D, et al. 2013;5(3):247–54.
Clin Invest. 2015;23(2):39–46. The obesity-induced transcriptional 66. Azrad M, Turgeon C, Demark-
30. Zheng Q, Banaszak L, Fracci S, et al. regulator TRIP-Br2 mediates visceral Wahnefried W. Current evidence linking
Leptin receptor maintains cancer fat endoplasmic reticulum stress- polyunsaturated Fatty acids with cancer
stem-like properties in triple negative induced inflammation. Nat Commun. risk and progression. Front Oncol.
breast cancer cells. Endocr-Rel Cancer. 2016;7:11378. 2013;3:224.
2013;20(6):797–808. 51. Lee MJ, Wu Y, Fried SK. Adipose 67. Bao Y, Hu FB, Giovannucci EL, et al.
31. Karunanithi S, Levi L, DeVecchio J, et al. tissue heterogeneity: Implication of Nut consumption and risk of pancre-
RBP4-STRA6 pathway drives cancer depot differences in adipose tissue for atic cancer in women. Br J Cancer.
stem cell maintenance and mediates high- obesity complications. Mol Aspects Med. 2013;109(11):2911–6.
fat diet-induced colon carcinogenesis. 2013;34(1):1–11. 68. Bao Y, Han J, Hu FB, et al. Association
Stem Cell Rep. 2017;9(2):438–50. 52. Tchkonia T, Thomou T, Zhu Y, et al. of nut consumption with total and
32. Boyd DB. Insulin and cancer. Integrative Mechanisms and metabolic implications cause-specific mortality. N Engl J Med.
Cancer Therapies. 2003;2(4):315–29. of regional differences among fat depots. 2013;369(21):2001–11.
33. Yu H, Rohan T. Role of the insulin-like Cell Metab. 2013;17(5):644–56. 69. Healy ME, Lahiri S, Hargett SR, et al.
growth factor family in cancer develop- 53. Stoll BA. Upper abdominal obesity, Dietary sugar intake increases liver
ment and progression. J Natl Cancer Inst. insulin resistance and breast cancer risk. tumor incidence in female mice. Sci Rep.
2000;92(18):1472–89. Int J Obes Rel Metab Disord: J Int Assoc 2016;6:22292.
34. Zahid H, Simpson ER, Brown KA. Study Obes. 2002;26(6):747–53. 70. Thompson CL, Khiani V, Chak A, et al.
Inflammation, dysregulated metabo- 54. Donohoe CL, Doyle SL, Reynolds JV. Carbohydrate consumption and esopha-
lism and aromatase in obesity and Visceral adiposity, insulin resistance geal cancer:an ecological assessment. Am
breast cancer. Curr Opin Pharmacol. and cancer risk. Diabetol Metab Syndr. J Gastroenterol. 2008;103(3):555–61.
2016;31:90–6. 2011;3:12. 71. Meyerhardt JA, Sato K, Niedzwiecki D,
35. Iyengar NM, Brown KA, Zhou XK, et al. 55. Huffman DM, Augenlicht LH, Zhang et al. Dietary glycemic load and cancer
Metabolic obesity, adipose inflammation X, et al. Abdominal obesity, indepen- recurrence and survival in patients with
and elevated breast aromatase in women dent from caloric intake, accounts for stage III colon cancer: Findings from
with normal body mass index. Cancer the development of intestinal tumors in CALGB 89803. J Natl Cancer Inst.
Prev Res. 2017;10(4);235–43. Apc(1638N/+) female mice. Cancer Prev 2012;104(22):1702–11.
36. Zhang YJ, Li S, Gan RY, et al. Impacts Res. 2013;6(3):177–87. 72. Linkov F, Maxwell GL, Felix AS, et al.
of gut bacteria on human health and dis- 56. Lu YP, Lou YR, Bernard JJ, et al. Longitudinal evaluation of cancer-
eases. Int J Mol Sci. 2015;16(4):7493–519. Surgical removal of the parametrial fat associated biomarkers before and
37. Veugelers PJ, Porter GA, Guernsey DL, pads stimulates apoptosis and inhibits after weight loss in RENEW study
Casson AG. Obesity and lifestyle risk fac- UVB-induced carcinogenesis in mice fed participants: Implications for can-
tors for gastroesophageal reflux disease, a high-fat diet. Proc Natl Acad Sci U S A. cer risk reduction. Gynecol Oncol.
Barrett esophagus and esophageal adeno- 2012;109(23):9065–70. 2012;125(1):114–9.
carcinoma. Dis Esophagus: Off J Int Soc 57. Sarwer DB, Polonsky HM. Body image 73. Parker ED, Folsom AR. Intentional
Dis Esophagus. 2006;19(5):321–8. and body contouring procedures. weight loss and incidence of obesity-
38. Pohl H, Wrobel K, Bojarski C, et al. Risk Aesthetic Surg J. 2016;36(9):1039–47. related cancers: The Iowa Women’s
factors in the development of esopha- 58. Hill-Baskin AE, Markiewski MM, Health Study. Int J Obes Rel Metab
geal adenocarcinoma. Am J Gastro. Buchner DA, et al. Diet-induced Disord: J Int Assoc Study Obes.
2013;108(2):200–7. hepatocellular carcinoma in genetically 2003;27(12):1447–52.
39. Hampel H, Abraham NS, El-Serag HB. predisposed mice. Hum Mol Genet. 74. Byers T, Sedjo RL. Does intentional
Meta-analysis: Obesity and the risk for 2009;18(16):2975–88. weight loss reduce cancer risk? Diabetes
gastroesophageal reflux disease and 59. Novosyadlyy R, Leroith D. Insulin-like Obes Metab. 2011;13(12):1063–72.
its complications. Ann Intern Med. growth factors and insulin: At the cross- 75. Thompson HJ, McTiernan A. Weight
2005;143(3):199–211. road between tumor development and cycling and cancer: Weighing the
40. Sheng X, Parmentier JH, Tucci J, et al. longevity. J Gerontol Ser A, Biol Sci Med evidence of intermittent caloric restric-
Adipocytes sequester and metabolize the Sci. 2012;67(6):640–51. tion and cancer risk. Cancer Prev Res.
chemotherapeutic daunorubicin. Mol 60. Zheng Q, Dunlap SM, Zhu J, et al. 2011;4(11):1736–42.
Cancer Res. 2017;15(12);1704–13. Leptin deficiency suppresses MMTV- 76. Prentice RL, Caan B, Chlebowski RT,
41. Jones PA. Epigenetics in carcinogenesis Wnt-1 mammary tumor growth in obese et al. Low-fat dietary pattern and risk
and cancer prevention. Ann N Y Acad mice and abrogates tumor initiat- of invasive breast cancer: The Women’s
Sci. 2003;983:213–9. ing cell survival. Endocr-Rel Cancer. Health Initiative Randomized Controlled
42. Issa JP. Cancer prevention: Epigenetics 2011;18(4):491–503. Dietary Modification Trial. JAMA.
steps up to the plate. Cancer Prev Res. 61. Doerner SK, Reis ES, Leung ES, et al. 2006;295(6):629–42.
2008;1(4):219–22. High-fat diet-induced complement activa- 77. Thomson CA, Van Horn L, Caan BJ,
43. Jones PA, Issa JP, Baylin S. Targeting the tion mediates intestinal inflammation and et al. Cancer incidence and mortality
cancer epigenome for therapy. Nat Rev neoplasia, independent of obesity. Mol during the intervention and postinter-
Genet. 2016;17(10):630–41. Cancer Res. 2016;14(10):953–65. vention periods of the Women’s Health
44. Jang H, Serra C. Nutrition, epi- 62. Kim EJ, Choi MR, Park H, et al. Dietary Initiative dietary modification trial.
genetics, and diseases. Clin Nutr Res. fat increases solid tumor growth and Cancer Epidemiol Biomarkers Prev.
2014;3(1):1–8. metastasis of 4T1 murine mammary 2014;23(12):2924–35.
References 429
78. Chlebowski RT, Aragaki AK, Anderson adolescence and the incidence of colorec- 109. Thompson CL, Larkin EK, Patel S, et al.
GL, et al. Low-Fat Dietary Pattern tal cancer in a cohort of 1.1 million Short duration of sleep increases
and Breast Cancer Mortality in the
Women’s Health Initiative Randomized
Controlled Trial. J Clin Oncol.
males. Cancer Epidemiol Biomarkers
Prev. 2011;20(12):2524–31.
94. Bjorge T, Engeland A, Tverdal A,
risk of colorectal adenoma. Cancer.
2011;117(4):841–7.
110. Jiao L, Duan Z, Sangi-Haghpeykar
33
2017;35(25):2919–26. Smith GD. Body mass index in ado- H, et al. Sleep duration and inci-
79. Pierce JP, Natarajan L, Caan BJ, et al. lescence in relation to cause-specific dence of colorectal cancer in post-
Influence of a diet very high in veg- mortality: A follow-up of 230,000 menopausal women. Br J Cancer.
etables, fruit, and fiber and low in fat on Norwegian adolescents. Am J Epidemiol. 2013;108(1):213–21.
prognosis following treatment for breast 2008;168(1):30–7. 111. Thompson CL, Li L. Association of sleep
cancer: The Women’s Healthy Eating and 95. Bailey CE, Hu CY, You YN, et al. duration and breast cancer OncotypeDX
Living (WHEL) randomized trial. JAMA. Increasing disparities in the age-related recurrence score. Breast Cancer Res
2007;298(3):289–98. incidences of colon and rectal cancers Treat. 2012;134(3):1291–5.
80. Pierce JP. Diet and breast cancer prog- in the United States, 1975–2010. JAMA 112. Qaseem A, Kansagara D, Forciea MA,
nosis: Making sense of the Women’s Surg. 2015;150(1):17–22. et al. Clinical Guidelines Committee of
Healthy Eating and Living and Women’s 96. Liang Y, Hou D, Zhao X, et al. the American College of P. Management
Intervention Nutrition Study trials. Curr Childhood obesity affects adult metabolic of Chronic Insomnia Disorder in Adults:
Opin Obstet Gynecol. 2009;21(1):86–91. syndrome and diabetes. Endocrine. A clinical practice guideline from the
81. Chlebowski RT, Blackburn GL, Thomson 2015;50(1):87–92. American College of Physicians. Ann
CA, et al. Dietary fat reduction and 97. Nackers LM, Ross KM, Perri MG. The Intern Med. 2016;165(2):125–33.
breast cancer outcome: Interim efficacy association between rate of initial weight 113. Trauer JM, Qian MY, Doyle JS, et al.
results from the Women’s Intervention loss and long-term success in obesity Cognitive behavioral therapy for
Nutrition Study. J Natl Cancer Inst. treatment: Does slow and steady win the chronic insomnia: A systematic review
2006;98(24):1767–76. race? Int J Behav Med. 2010;17(3):161–7. and meta-analysis. Ann Intern Med.
82. Chlebowski RT, Blackburn GL. 98. Montesi L, El Ghoch M, Brodosi L, et al. 2015;163(3):191–204.
Women’s Intervention Nutrition Study Long-term weight loss maintenance for 114. Buysse DJ, Rush AJ, Reynolds CF, 3rd.
Investigators: Final Survival Analyses obesity: A multidisciplinary approach. Clinical management of insomnia disor-
from the Women’s Intervention Nutrition Diabetes, Metab Syndr Obes: Targets der. JAMA. 2017;318(20):1973–1974.
Study (WINS) evaluating dietary fat Ther. 2016;9:37–46. 115. Kushner RF, Ryan DH. Assessment
reduction as adjuvant breast cancer 99. Hendrickson K. How to Calculate and lifestyle management of patients
therapy. San Antonio Breast Cancer Energy From Foods Livestrong.com2017 with obesity: Clinical recommenda-
Symposium; 2014 [10/31/2017]. ASCO [cited 2017 11/21/2017]. https: //www.liv tions from systematic reviews. JAMA.
Post 1/25/2015 issue:[Abstract S5–08]. estrong.com /article/312047-how-to-c 2014;312(9):943–52.
83. Buchwald H. The evolution of meta- alculate-energy-from-foods /. 116. Jensen MD, Ryan DH, Apovian CM,
bolic/bariatric surgery. Obes Surg. 100. CDC. Low-Energy-Dense Foods and et al. 2013 AHA/ACC/TOS guideline
2014;24(8):1126–35. Weight Management: Cutting Calories for the management of overweight
84. Sjostrom L, Gummesson A, Sjostrom While Controlling Hunger [cited 2017 and obesity in adults: A report of
CD, et al. Effects of bariatric surgery 11/21/2017]. https: //www.cdc.gov/nccdp the American College of Cardiology/
on cancer incidence in obese patients in hp/dnpa/nut rition/pdf /r2p_ energ y_de American Heart Association Task Force
Sweden (Swedish Obese Subjects Study): nsity.pd. on Practice Guidelines and the Obesity
A prospective, controlled intervention 101. McTiernan A, Kooperberg C, White E, Society. J Am Coll Cardiol. 2014;63(25
trial. Lancet Oncol. 2009;10(7):653–62. et al. Recreational physical activity Pt B):2985–3023.
85. Sjostrom L. Review of the key results and the risk of breast cancer in post- 117. Gloy VL, Briel M, Bhatt DL, et al.
from the Swedish Obese Subjects (SOS) menopausal women: The Women’s Bariatric surgery versus non-surgical
trial - a prospective controlled interven- Health Initiative Cohort Study. JAMA. treatment for obesity: A systematic
tion study of bariatric surgery. J Intern 2003;290(10):1331–6. review and meta-analysis of randomised
Med. 2013;273(3):219–34. 102. Tehard B, Friedenreich CM, Oppert controlled trials. BMJ. 2013;347:f5934.
86. Schauer PR, Kashyap SR, Wolski K, et al. JM, Clavel-Chapelon F. Effect of 118. Buchwald H, Estok R, Fahrbach K, et al.
Bariatric surgery versus intensive medical physical activity on women at increased Weight and type 2 diabetes after bariatric
therapy in obese patients with diabetes. N risk of breast cancer: Results from the surgery: Systematic review and meta-
Engl J Med. 2012;366(17):1567–76. E3N cohort study. Cancer Epidemiol analysis. Am J Med. 2009;122(3):248–56
87. Schauer PR, Bhatt DL, Kirwan JP, et al. Biomarkers Prev. 2006;15(1):57–64. e5.
Bariatric surgery versus intensive medical 103. Boyle T, Keegel T, Bull F, et al. Physical 119. Chang SH, Stoll CR, Song J, et al. The
therapy for diabetes - 5-year outcomes. N activity and risks of proximal and distal effectiveness and risks of bariatric sur-
Engl J Med. 2017;376(7):641–51. colon cancers: A systematic review gery: An updated systematic review and
88. Adams TD, Gress RE, Smith SC, et al. and meta-analysis. J Natl Cancer Inst. meta-analysis, 2003–2012. JAMA Surg.
Long-term mortality after gas- 2012;104(20):1548–61. 2014;149(3):275–87.
tric bypass surgery. N Engl J Med. 104. Moore SC, Gierach GL, Schatzkin 120. Colquitt JL, Pickett K, Loveman E,
2007;357(8):753–61. A, Matthews CE. Physical activity, Frampton GK. Surgery for weight loss
89. Ward KK, Roncancio AM, Shah NR, sedentary behaviours, and the preven- in adults. Cochrane Database Syst Rev.
et al. Bariatric surgery decreases the risk tion of endometrial cancer. Br J Cancer. 2014(8):CD003641.
of uterine malignancy. Gynecol Oncol. 2010;103(7):933–8. 121. Weng TC, Chang CH, Dong YH, et al.
2014;133(1):63–6. 105. Hanlon EC, Tasali E, Leproult R, et al. Anaemia and related nutrient deficiencies
90. Schauer DP, Feigelson HS, Koebnick C, Sleep restriction enhances the daily after Roux-en-Y gastric bypass surgery: A
et al. Bariatric surgery and the risk of rhythm of circulating levels of endocan- systematic review and meta-analysis. BMJ
cancer in a large multisite cohort. Ann nabinoid 2-arachidonoylglycerol. Sleep. Open. 2015;5(7):e006964.
Surg. 2017;XX:1–7. 2016;39(3):653–64. 122. Adams TD, Stroup AM, Gress RE, et al.
91. Philip EJ, Torghabeh MH, Strain GW. 106. Taheri S, Lin L, Austin D, et al. Short Cancer incidence and mortality after
Bariatric surgery in cancer survivor- sleep duration is associated with gastric bypass surgery. Obesity (Silver
ship: Does a history of cancer affect reduced leptin, elevated ghrelin, and Spring). 2009;17(4):796–802.
weight loss outcomes? Surg Obes Rel increased body mass index. PLoS Med. 123. Tee MC, Cao Y, Warnock GL, et al.
Diseases: Off J Am Soc Bariatric Surg. 2004;1(3):e62. Effect of bariatric surgery on onco-
2015;11(5):1105–8. 107. Mozaffarian D, Hao T, Rimm EB, et al. logic outcomes: A systematic review
92. Keum N, Greenwood DC, Lee DH, et al. Changes in diet and lifestyle and long- and meta-analysis. Surg Endoscopy.
Adult weight gain and adiposity-related term weight gain in women and men. N 2013;27(12):4449–56.
cancers: A dose-response meta-analysis of Engl J Med. 2011;364(25):2392–404. 124. Douglas IJ, Bhaskaran K, Batterham RL,
prospective observational studies. J Natl 108. Spiegel K, Knutson K, Leproult R, et al. Smeeth L. Bariatric surgery in the United
Cancer Inst. 2015;107(2). Sleep loss: A novel risk factor for insulin Kingdom: A cohort study of weight loss
93. Levi Z, Kark JD, Barchana M, et resistance and Type 2 diabetes. J Appl and clinical outcomes in routine clinical
al. Measured body mass index in Physiol (1985). 2005;99(5):2008–19. care. PLoS Med. 2015;12(12):e1001925.
430 Chapter 33 Lifestyle Approaches Targeting Obesity to Reduce Cancer Risk, Progression, and Recurrence
125. Derogar M, Hull MA, Kant P, et al. surgery--an institutional study and sys- 153. Ligibel JA, Barry WT, Alfano C, et al.
Increased risk of colorectal can- tematic review of the literature. Gynecol Randomized phase III trial evaluating the
cer after obesity surgery. Ann Surg. Oncol. 2015;139(2):369–76. role of weight loss in adjuvant treatment
2013;258(6):983–8. 141. Park SM, Lim MK, Jung KW, et al. of overweight and obese women with
126. Ostlund MP, Lu Y, Lagergren J. Risk of Prediagnosis smoking, obesity, insulin early breast cancer (Alliance A011401):
obesity-related cancer after obesity sur- resistance, and second primary cancer Study design. NPJ Breast Cancer.
gery in a population-based cohort study. risk in male cancer survivors: National 2017;3:37.
Ann Surg. 2010;252(6):972–6. Health Insurance Corporation Study. 154. Tsilidis KK, Kasimis JC, Lopez DS, et al.
127. Oeffinger KC, Fontham ET, Etzioni R, J Clin Oncol. 2007;25(30):4835–43. Type 2 diabetes and cancer: Umbrella
et al. Breast cancer screening for women 142. Mustian KM, Sprod LK, Janelsins M, review of meta-analyses of observational
at average risk: 2015 guideline update et al. Exercise recommendations for can- studies. BMJ. 2015;350:g7607.
from the American Cancer Society. cer-related fatigue, cognitive impairment, 155. Shlomai G, Neel B, LeRoith D, Gallagher
JAMA. 2015;314(15):1599–614. sleep problems, depression, pain, anxiety, EJ. Type 2 diabetes mellitus and cancer:
128. Siu AL. Screening for breast cancer: U.S. and physical dysfunction: A review. The role of pharmacotherapy. J Clin
Preventive services task force recom- Oncol Hematol Rev. 2012;8(2):81–8. Oncol. 2016;34(35):4261–9.
mendation statement. Ann Intern Med. 143. Knols R, Aaronson NK, Uebelhart D, 156. Park SM, Lim MK, Shin SA, Yun YH.
2016;164(4):279–96. et al. Physical exercise in cancer patients Impact of prediagnosis smoking, alcohol,
129. Aberle DR, Adams AM, Berg CD, et al. during and after medical treatment: A obesity, and insulin resistance on survival
Reduced lung-cancer mortality with low- systematic review of randomized and in male cancer patients: National Health
dose computed tomographic screening. N controlled clinical trials. J Clin Oncol. Insurance Corporation Study. J Clin
Engl J Med. 2011;365(5):395–409. 2005;23(16):3830–42. Oncol. 2006;24(31):5017–24.
130. Winawer SJ, Zauber AG, Ho MN, et al. 144. Meneses-Echavez JF, Gonzalez-Jimenez 157. Barone BB, Yeh HC, Snyder CF,
Prevention of colorectal cancer by E, Ramirez-Velez R. Effects of super- et al. Long-term all-cause mortal-
colonoscopic polypectomy. The National vised exercise on cancer-related fatigue ity in cancer patients with preexist-
Polyp Study Workgroup. N Engl J Med. in breast cancer survivors: A systematic ing diabetes mellitus: A systematic
1993;329(27):1977–81. review and meta-analysis. BMC Cancer. review and meta-analysis. JAMA.
131. Imperiale TF, Ransohoff DF, Itzkowitz 2015;15:77. 2008;300(23):2754–64.
SH, et al. Fecal DNA versus fecal occult 145. Gardner JR, Livingston PM, Fraser SF. 158. Hu FB, Manson JE, Liu S, et al.
blood for colorectal-cancer screening Effects of exercise on treatment-related Prospective study of adult onset diabetes
in an average-risk population. N Engl J adverse effects for patients with prostate mellitus (type 2) and risk of colorectal
Med. 2004;351(26):2704–14. cancer receiving androgen-deprivation cancer in women. J Natl Cancer Inst.
132. Lin JS, Piper MA, Perdue LA, et al. therapy: A systematic review. J Clin 1999;91(6):542–7.
Screening for colorectal cancer: Updated Oncol. 2014;32(4):335–46. 159. Zhou G, Myers R, Li Y, et al. Role of
evidence report and systematic review 146. Kampshoff CS, Chinapaw MJ, Brug J, AMP-activated protein kinase in mecha-
for the US preventive services task force. et al. Randomized controlled trial of the nism of metformin action. J Clin Invest.
JAMA. 2016;315(23):2576–94. effects of high intensity and low-to-mod- 2001;108(8):1167–74.
133. Saslow D, Solomon D, Lawson HW, et al. erate intensity exercise on physical fitness 160. Kuhajda FP. AMP-activated protein
American Cancer Society, American Society and fatigue in cancer survivors: Results kinase and human cancer: Cancer
for Colposcopy and Cervical Pathology, of the Resistance and Endurance exercise metabolism revisited. Int J Obes (Lond).
and American Society for Clinical After ChemoTherapy (REACT) study. 2008;32 Suppl 4:S36–41.
Pathology screening guidelines for the pre- BMC Med. 2015;13:275. 161. Decensi A, Puntoni M, Goodwin P,
vention and early detection of cervical can- 147. Mock V, Pickett M, Ropka ME, et al. et al. Metformin and cancer risk in
cer. CA: Cancer J Clin. 2012;62(3):147–72. Fatigue and quality of life outcomes of diabetic patients: A systematic review
134. American Cancer Society. Cancer Facts exercise during cancer treatment. Cancer and meta-analysis. Cancer Prev Res.
and Figures 2017. Atlanta, GA: The Pract. 2001;9(3):119–27. 2010;3(11):1451–61.
American Cancer Society; 2017. 148. Butt Z, Rosenbloom SK, Abernethy AP, 162. Chlebowski RT, McTiernan A,
135. Chan DS, Vieira AR, Aune D, et al. Body et al. Fatigue is the most important symp- Wactawski-Wende J, et al. Diabetes,
mass index and survival in women with tom for advanced cancer patients who metformin, and breast cancer in
breast cancer-systematic literature review have had chemotherapy. J Natl Compr postmenopausal women. J Clin Oncol.
and meta-analysis of 82 follow-up stud- Canc Netw. 2008;6(5):448–55. 2012;30(23):2844–52.
ies. Ann Oncol. 2014;25(10):1901–14. 149. Mishra SI, Scherer RW, Snyder C, et al. 163. Wu JW, Azoulay L, Majdan A, et al.
136. Meyerhardt JA, Catalano PJ, Haller DG, Exercise interventions on health-related Long-term use of long-acting insulin
et al. Influence of body mass index on quality of life for people with cancer dur- analogs and breast cancer incidence
outcomes and treatment-related toxicity ing active treatment. Cochrane Database in women with type 2 diabetes. J Clin
in patients with colon carcinoma. Cancer. Syst Rev. 2012(8):CD008465. Oncol. 2017;35(32):3647–3653.
2003;98(3):484–95. 150. Fairey AS, Courneya KS, Field CJ, et al. 164. Onitilo AA, Stankowski RV, Berg RL,
137. Efstathiou JA, Bae K, Shipley WU, Effects of exercise training on fasting et al. Type 2 diabetes mellitus, glycemic
et al. Obesity and mortality in men insulin, insulin resistance, insulin-like control, and cancer risk. Eur J Cancer
with locally advanced prostate cancer: growth factors, and insulin-like growth Prev. 2014;23(2):134–40.
Analysis of RTOG 85–31. Cancer. factor binding proteins in postmenopausal 165. Dehal AN, Newton CC, Jacobs EJ,
2007;110(12):2691–9. breast cancer survivors: A random- et al. Impact of diabetes mellitus and
138. Paskett ED, Dean JA, Oliveri JM, ized controlled trial. Cancer Epidemiol insulin use on survival after colorectal
Harrop JP. Cancer-related lymphedema Biomarkers Prev. 2003;12(8):721–7. cancer diagnosis: The Cancer Prevention
risk factors, diagnosis, treatment, 151. Ligibel JA, Campbell N, Partridge A, Study-II Nutrition Cohort. J Clin Oncol.
and impact: A review. J Clin Oncol. et al. Impact of a mixed strength and 2012;30(1):53–9.
2012;30(30):3726–33. endurance exercise intervention on insu- 166. Tang X, Yang L, He Z, Liu J. Insulin
139. Meyerhardt JA, Tepper JE, Niedzwiecki lin levels in breast cancer survivors. J Clin glargine and cancer risk in patients with
D, et al. Impact of body mass index on Oncol. 2008;26(6):907–12. diabetes: A meta-analysis. PLoS One.
outcomes and treatment-related toxicity 152. Friedenreich CM, Woolcott CG, 2012;7(12):e51814.
in patients with stage II and III rectal McTiernan A, et al. Alberta physical 167. Griggs JJ, Mangu PB, Anderson H, et al.
cancer: Findings from Intergroup Trial activity and breast cancer preven- Appropriate chemotherapy dosing
0114. J Clin Oncol. 2004;22(4):648–57. tion trial: Sex hormone changes in a for obese adult patients with cancer:
140. Bouwman F, Smits A, Lopes A, et al. The year-long exercise intervention among American Society of Clinical Oncology
impact of BMI on surgical complications postmenopausal women. J Clin Oncol. clinical practice guideline. J Clin Oncol.
and outcomes in endometrial cancer 2010;28(9):1458–66. 2012;30(13):1553–61.
34
CHAPTER
cancer risk reduction remain unknown, there is growing 40,610 women will die from breast cancer in 2017 in the
evidence supporting the role of physical inactivity in vari- United States alone.11 Inactivity has been identified with
ous cancer diagnoses. heightened breast cancer risk for over three decades.
When thinking about physical activity and cancer A 1985 study demonstrated that former college athletes
relationship, it is important to consider the cancer contin- experienced lower breast cancer prevalence relative to
uum and levels of disease prevention. Primary prevention their non-athlete counterparts.12 Since that study, the body
comprises health promotion and risk reduction in healthy of evidence linking physical activity to cancer risk reduc-
populations. Secondary prevention involves screening, tion has grown. Physical activity may be a more effica-
detecting, diagnosing, and treating early-stage or pre- cious breast cancer prevention method in postmenopausal
malignant cancers. Lastly, tertiary prevention revolves women;13 research has consistently supported an inverse
around symptom management, rehabilitation, and end-of- correlation between postmenopausal physical activity and
life care.7 Physical activity can and should be included at breast cancer risk reduction,13– 16 Although studies have
all three prevention levels; however, the mechanistic influ- also suggested a relationship between inactivity and breast
ence and health impact of physical activity on cancer risk cancer in premenopausal women, the evidence is limited.17
reduction, cancer recurrence risk reduction, and symp- Mechanistically, physical activity may decrease breast
toms management differ across the cancer continuum. cancer risk by reducing levels of sex hormones and
increasing concentrations of sex hormone-binding glob-
ulin proteins.18 Androgens housed in peripheral adipose
34.2.2 The Role of Physical Activity in tissue serve as the primary source of endogenous circu-
lating estrogen.19 Exercise can decrease adiposity, thereby
Primary Cancer Prevention inhibiting overexpression of estrogen and preventing
Most physical activity and cancer research have revolved adverse alterations to metabolic hormones such as insulin
around a small subset of cancer types.8 Researchers have and insulin-like growth factor (IGF) 1. 20 These hormones
frequently explored the relationship between physical activ- can increase estrogen levels and decrease sex hormone-
ity and colon cancer, breast cancer, and/or endometrial can- binding globulin concentrations. 20 While the intricacies of
cer.8 Nonetheless, more cancers are being linked to inactivity. these bio-mechanisms remain poorly understood, physical
According to World Cancer Research Fund International, activity-mediated reduction of biologically available sex
20% of cancer cases in the United States can be prevented hormones appears to play a significant role in decreasing
through physical activity, weight control, and consumption the risk of breast, endometrial, ovarian, prostate, and tes-
of a healthy diet.9 Furthermore, a pooled analysis of twelve ticular cancers. 21
prospective cohort studies and 1.44 million participants from The relationship between exercise and endometrial
the United States and Europe demonstrated an association cancer risk bears some similarities to that of physical
between higher levels of leisure-time physical activity and activity and breast cancer. High physical activity strongly
risk reduction of 13 different cancer types.10 Although more correlates with endometrial cancer risk reduction, but
cancers are being linked to inactivity, breast, endometrial, this inverse relationship is attenuated somewhat in pre-
and colon cancers remain some of the most well-researched. menopausal women. 22 Nonetheless, even low-intensity
Figure 34.1 illustrates these findings in further detail. physical activity and walking decrease one’ s predisposi-
Twelve percent of American women will develop inva- tion to endometrial cancer. 22 Similar to the mechanisms of
sive breast cancer during their lifetimes, and an estimated breast cancer risk reduction, physical activity may reduce
Figure 34.1 Increased Physical Activity Is Associated with Risk Reduction of Various Cancers (based on10 ).
34.3 Defining “ Health-Enhancing” Physical Activity 433
endometrial cancer risk via regulation of metabolites and 34.2.4 The Role of Physical Activity in
34
endogenous sex hormones. 23
Inactivity also positively correlates with colon cancer
Tertiary Cancer Prevention
risk.24 A recent study of nondiabetic patients revealed that While sustaining an active lifestyle can contribute to primary
physical activity was associated with a 20% reduced risk and secondary cancer prevention, it can also serve as a valu-
of colon cancer.25 The mechanisms of physical activity- able tool during rehabilitation and chronic disease manage-
influenced colon cancer risk reduction differ from the ment. An analysis of 26 prospective cohort studies of breast,
processes involved in breast and endometrial cancer pre- colorectal, and prostate cancers revealed a 37% pooled risk
vention. Researchers have posited that immune function reduction for cancer-specific mortality when comparing the
modulation and reductions in intestinal transit time, IGF most active to least active patients.33 While activity serves
concentrations, hyperinsulinemia, and inflammation are as an important tertiary prevention tool for a host of can-
the central ways in which physical activity decreases colon cers, its role has been most examined with respect to breast
cancer risk.24,25 Nonetheless, the biological link between cancer. Compared to other modifiable lifestyle factors such
inactivity and heightened colon cancer risk is poorly under- as smoking, diet, and alcohol intake, physical activity has
stood.26 Limited empirical evidence of proposed mecha- been shown to have the strongest effect on attenuating the
nisms, compounded by the existence of unknown physical risk of breast cancer recurrence and reducing mortality.34,35
activity-induced processes, highlights the uncertainty sur- Research continues to show that physical activity can have a
rounding how physical activity reduces colon cancer risk.24 profound influence on disease management, helping patients
increase longevity and quality of life.
Long-term cancer survivors should also incorpo-
rate regular activity and exercise into their daily regime.
34.2.3 The Role of Physical Activity in Up to 52% of adult survivors of childhood cancer are sed-
Secondary Cancer Prevention entary, 36 which suggests that clinicians may not be plac-
In addition to its merit as a primary cancer prevention ing sufficient emphasis on physical activity in previously
strategy, physical activity may also have a role in second- diagnosed, cancer-free populations.
ary cancer prevention. Animal models have been used to As with primary prevention, researchers’ understand-
demonstrate the potential for physical activity to inhibit ing of the complex mechanisms involved with physi-
tumor initiation and tumor multiplicity and to change the cal activity-mediated tertiary prevention is evolving.
intratumoral microenvironment.27 Physical activity aids as Regulation of IGF concentrations and signaling, natural
a post-diagnosis prescription as new cancer patients begin killer cell function, and inflammation have been frequently
to undergo treatment and various side effects manifest. identified as key cancer biomarkers affected by physi-
Physical activity and exercise training have been shown to cal activity and exercise, 37,38 Nonetheless, various other
mitigate some of these effects,28 including fatigue, anxiety, mechanisms have been studied, with some likely related to
depression, and reduced sexual activity.29 A major 2012 multiple cancer types and others restricted to specific can-
review by Brown et al. asserted that “ there is a growing cers. For example, researchers have suggested that activity
base of evidence that suggests engaging in exercise, such as may induce downstream gene suppression and oxidative
brisk walking, yields fewer symptoms and side effects dur- stress reduction as tertiary prevention mechanisms for
ing treatment and retards the rate at which physiological gastric and colorectal cancers, respectively.38 As research-
systems are effected”30 Fatigue is one of the most common ers gain a more comprehensive and conclusive understand-
ancillary effects associated with taxing cancer therapies. ing of these relationships at the molecular level, clinicians
However, many patients receiving treatment identify exer- will become better equipped to prescribe physical activity
cise as one of the most effective deterrents to fatigue.31 more strategically.
Patients engaging in physical activity can alleviate side Perhaps the biggest factors distinguishing physi-
effects of cancer treatment, and they can improve their cal activity from other cancer therapies are the lack of
health status and long-term health outcomes. A study treatment-specific sequelae. No studies have shown that
of breast cancer patients demonstrated the efficacy of physical activity adversely affects cancer outcomes.33 That
post-diagnosis physical activity: disease-specific mortal- being said, the side effects of protracted cancer treatment
ity decreased by 39% and overall mortality declined by may hamper physical function, and clinicians should take
46% when comparing the most- vs. least-physically active such limitations into account when prescribing activity for
women after diagnosis.32 These results exemplify the cancer survivors. 30 Furthermore, in order to personalize
potential of physical activity for newly diagnosed cancer physical activity and exercise prescriptions for cancer and
populations. non-cancer patients, clinicians must understand exactly
Despite the positive impact of physical activity as a treat- what “ health-enhancing” activity entails.
ment mechanism, not enough cancer patients are active
consistently. One study suggested that breast carcinoma
patients decreased total physical activity by two hours per
week between pre- and post-diagnosis.31 Inactivity can
34.3 DEFINING “ HEALTH-ENHANCING”
have deleterious disease-specific and nonspecific effects on PHYSICAL ACTIVITY
cancer and non-cancer populations. Therefore, clinicians
should leverage physical activity as a secondary treatment Definitions of “ health-enhancing” physical activity
tool while being conscientious of patients’ physical and have evolved over decades. In the 1960s and 1970s, the
psychological wellbeing post-diagnosis. physical activity discussion revolved around how specific
434 Chapter 34 Physical Activity and the Prevention and Treatment of Cancer
exercise programs could promote fitness. 39 The 1978 and preferably exercise is evenly distributed throughout
American College of Sports Medicine (ACSM) position the week. For children, one hour of moderate or vigorous
statement provided recommendations and guidelines on activity is suggested each day, and vigorous activity should
how physical activity could promote cardiorespiratory occur at least three times per week.43 According to the
endurance, but more people wanted to understand how guidelines, moderate intensity activities include walking,
physical activity could affect health. 39 This provided leisurely bicycling, golfing, general yard maintenance, and
the impetus for a new definition of physical activity occupation-related walking and lifting activities. The ACS
that encompassed lifestyle physical activity rather than considers vigorous intensity activities to be ones that acti-
merely exercise for fitness. In 1985, physical activity was vate large muscle groups, increase heart rate, and acceler-
defined as “ a ny bodily movement produced by skeletal ate breathing and sweating.43 For example, jogging, fast
muscles that results in energy expenditure.” 40 The 1993 bicycling, basketball, digging, and heavy manual occupa-
International Consensus Conference on Physical Activity tional labor would be considered vigorous intensity physi-
Guidelines for Adolescents helped propel the physi- cal activities. In addition to these recommendations, the
cal activity paradigm shift further: instead of focusing ACS also recommends reducing the amount of time spent
exclusively on exercise for fitness, people were to include sitting at home and at the workplace. While the ACS sug-
physical activity as a core component of daily lifestyle gests that using the stairs, walking or biking to work, and
activities. 39 Just three years prior, the ACSM had also wearing pedometers may reduce sitting time,43 clinicians
restructured its definition to distinguish health-related should cater to their patients to find solutions that are easy
physical activity from fitness-related physical activity. 39 and enjoyable.
These events were pivotal for shaping the recommenda-
tions that are in existence today, as health professionals
now know that low levels of physical activity can still be 34.3.2 Physical Activity Guidelines
beneficial to one’ s health even if they do not sufficiently
improve fitness. 39
for Cancer Populations
Due to the abundance of evidence affirming the value While exercise can help prevent cancer, it can also be har-
of physical activity in cancer risk reduction and symptom nessed as a treatment tool for cancer populations. Safety
management, more clinicians now consider exercise an would appear to be the most fundamental concern sur-
integral strategy across the cancer prevention spectrum. rounding activity and exercise among cancer survivors.
Various cancer-specific physical activity guidelines have However, studies have demonstrated that physical activity
been released in recent years to identify the ideal exercise promotion programs among cancer survivors are simul-
type, amount, and frequency for cancer survivors and taneously safe and efficacious.44– 47 The ACS organized
individuals proactively preventing cancer. This section a team of experts on physical activity and cancer survi-
highlights current physical activity recommendations for vorship to evaluate the role exercise should play during
healthy populations and cancer populations. treatment, recovery, and protracted disease-free living
or stable disease.48 They found that physical activity is
safe for individuals undergoing treatment and can reduce
34.3.1 Physical Activity Guidelines fatigue while improving physical functioning and overall
quality of life.48 Similarly, the ACS panel found exercise
for Healthy Populations to be an integral component of recovery post-treatment.48
Many current recommendations have been framed around Individuals in remission or with stable disease status
guidelines published by the ACSM. Currently, the ACSM should engage in regular physical activity for 150 min-
advises that adults perform 30 minutes of moderate to vig- utes per week while including strength training exercises
orous physical activity five times a week, supplemented at least twice weekly.48
by two or more days of muscle-strengthening activities.40 The AICR offers a set of recommendations for cancer
According to ACSM designations, moderate activity is survivors that utilize daily, rather than weekly, physical
performed at a level that allows a person to talk but not activity thresholds. Aiming for 30 minutes of moderate
sustain notes in song. Vigorous activity comprises signifi- intensity activity per day, which translates to 210 min-
cantly elevated heart rate and an inability to hold a con- utes per week, is suggested for minimizing risk of cancer
versation while exercising.41 recurrence.49 AICR also encourages cancer survivors to
Cancer-focused organizations have also issued physi- increase the intensity, duration, and number of exercise
cal activity recommendations for the prevention of can- sessions after four to six weeks, while also incorporating
cer. The American Institute for Cancer Research (AICR) strength training exercises at least two days per week.49
recommends 30 minutes or more of moderate physical The Oncology Nursing Society also offers general physi-
activity every day and to limit sedentary behaviors (e.g. cal activity guidelines for cancer survivors. These recom-
watching television).42 The American Cancer Society mendations advise 150 minutes of moderate intensity or
(ACS) Guidelines for Nutrition and Physical Activity for 75 minutes of vigorous intensity aerobic activity in con-
Cancer Prevention suggest that adults engage in at least junction with two days of strength training exercises every
150 minutes of moderate intensity or 75 minutes of vigor- week. 50
ous intensity activity each week.43 Given these recommen- The National Comprehensive Cancer Network pro-
dations, two minutes of moderate activity can replace one vides guidelines for individuals undergoing cancer treat-
minute of vigorous activity and vice versa. A combination ment, proposing 30 minutes of aerobic exercise at least
of moderate and vigorous activity can also be completed, five times per week. 51 This exercise regimen is aimed at
34.4 Physical Activity Behavior Change 435
Organization
Target
Population
Stage in Cancer
Care Continuum Recommendation
34
American Cancer Society Adults Prevention 150 mins. moderate intensity, 75 mins. vigorous intensity,
or equivalent combination of the two each week43
American Cancer Society Children Prevention 60 mins. moderate or vigorous intensity each day; at least
three days with vigorous intensity activity43
American Cancer Society Non-Specific Survivorship 150 mins. exercise with strength training activities at least
twice per week48
American College of Sports Adults Prevention 30 mins. moderate to vigorous activity five times per week;
Medicine at least two days of strength training each week41
American Institute for Cancer Non-Specific Prevention 30 mins. moderate activity every day; limit sedentary
Research habits42
American Institute for Cancer Non-Specific Survivorship 30 mins. moderate intensity activity each day; at least two
Research days of strength training each week49
Oncology Nursing Society Non-Specific Survivorship 150 mins. moderate intensity or 75 mins. vigorous intensity
aerobic activity50
National Comprehensive Non-Specific Treatment 30 mins. aerobic activity at least five times per week51
Cancer Network
mitigating cancer-related fatigue, and can be segmented by must appreciate the barriers to, and strategies for, espous-
patients undergoing physically taxing cancer therapies.51 ing behavior change.
The guidelines across the survivorship spectrum reinforce
the merit of physical activity for treating and preventing
the reoccurrence of cancer. All of the aforementioned rec-
ommendations are summarized in Table 34.1.
34.4 PHYSICAL ACTIVITY BEHAVIOR
CHANGE
34.3.3 Summary of Physical Activity The success of physical activity interventions is contingent
upon fostering sustained behavior change in the target
Guidelines Adherence population of interest. Health programs must help par-
Most healthy individuals and cancer survivors do not ticipants replace unhealthy or risky health behaviors with
meet recommended physical activity levels. 52,53 Results health-promoting or risk-averse ones. While approaches
from the National Health Interview Survey suggest that to behavior change differ, public health interventions
only 49% of adults aged 18 and over met the CDC’ s must empower individuals to adopt and sustain healthy
Physical Activity Guidelines for aerobic physical activ- lifestyles. 55
ity. 52 Moreover, only 20.9% of Americans in this same Behavior change plays a significant role in cancer
age cohort met requirements for both aerobic and muscle- prevention and treatment programs. Although behavior
strengthening activity. 52 change alone may not preclude cancer diagnosis or allevi-
Alarmingly low levels of exercise reinforce the exist- ate symptoms, it can prove beneficial to patients across the
ing concerns pertaining to the cancer-inactivity nexus. cancer continuum. Persistently low levels of physical activ-
Augmenting rates of physical activity is particularly ity adherence among healthy persons and survivors make
important due to the profound effect of inactivity on all- it even more important for clinicians and public health
cause mortality. A 2015 cohort study of over 334,000 professionals to promote behavior change as a means of
European men and women revealed that inactivity was increasing activity and improving cancer-related health
a larger contributor than obesity to all-cause mortal- outcomes.
ity. 54 Moreover, the study suggested that even marginal
increases in physical activity among inactive individuals
could prove beneficial for general health and wellbeing.54 34.4.1 Barriers to Physical Activity
Physical activity should be a central tenet of any cancer
prevention or treatment strategy. While there is a degree
for Healthy Populations
of heterogeneity between the physical activity guidelines Various obstacles may inhibit or prevent an individual
for cancer prevention, survivorship, and treatment, the from practicing and maintaining a physically active life-
fundamental message is the same: consistent moderate- style. Time constraints, social influences, travel distance,
to-vigorous lifestyle physical activity is a vital prevention and adverse weather can prevent individuals from getting
and treatment tool at all stages of the cancer continuum. active at home or exercising at a gym.56 Additionally, the
In order to help patients become more active, clinicians lack of energy, motivation, skills, or resources to perform
436 Chapter 34 Physical Activity and the Prevention and Treatment of Cancer
physical activity are significant barriers healthy individu- of behavioral theory present possible solutions for this
als frequently face.56 Physical activity levels also vary by problem. Personal beliefs, knowledge, and awareness are
race and ethnicity, socioeconomic status, education level, vital to consider when designing physical activity interven-
employment status, and income level. For example, blacks, tions for cancer patients. For example, self-efficacy levels
Hispanics and other non-white racial groups, individuals serve as a major factor in individual adherence to physi-
with low levels of education, and unemployed persons cal activity guidelines. Recent studies examining physical
report lower levels of leisure-time physical activity.57 Since activity and cancer have shown that self-efficacy is among
these populations often face significant impediments to the best predictors of intention to exercise compared to
performing physical activity consistently, it is vital that other cognitive constructs.67– 72 One of these studies ana-
healthcare professionals equip them with the tools to get lyzed cognitive and effective physical activity predictors
active. for outpatient cancer patients. The results showed that
self-efficacy explained 38.4% of participants’ physical
activity practices, while physical activity enjoyment also
34.4.2 Barriers to Physical Activity served as a major predictor of physical activity.64
Engendering self-efficacy and intertwining exercises
for Cancer Populations that excite and motivate patients are simple strategies that
As with many chronic conditions, cancer can compromise can help patients meet recommended physical activity
quality of life and restrict physical capabilities. Aggressive levels. Nevertheless, interventions centered around exer-
treatments such as chemotherapy can compound the cise pose a unique challenge: physical activity can only be
problem, inadvertently inhibiting physical activity among self-administered.33 and as such, fostering patient buy-in
patients. Fatigue, or pervasive tiredness related to cancer is especially critical. Therefore, clinicians should not only
and/or cancer treatment may impede physical function- encourage maintenance of a physical activity regimen but
ing. 58 This fatigue can arise prior to treatment, in congru- also enable patient self-efficacy and enjoyment.67 Educating
ence with treatment, or during remission. 59– 63 patients about specific exercises and demonstrating how to
Several factors can predict exercise adherence among perform corresponding movements will allow patients to
patients undergoing active cancer treatment. Baseline get active on their own. Similarly, incorporating fun, safe,
physical activity levels, pretreatment fatigue, emotional and appropriate exercises into a physical activity plan may
disturbances or trauma from treatment, and marital sta- motivate patients to adopt more active lifestyles.
tus have all been shown to influence patients’ adherence Although clinicians have a key role in triggering life-
to physical activity regimens.64 While physiological barri- style changes in patients, they do not have to provide
ers manifest as pain, fatigue, and malaise from symptoms rigorous exercise counseling to instigate physical activ-
and/or treatment, other obstacles also restrict patients’ ity adherence. At a minimum, clinicians must convey the
ability to exercise. vital importance of physical activity to their patients, refer
Psychological and logistical restraints can prevent phys- them to certified physical trainers with expertise in cancer
ical activity among cancer survivors. Time restrictions due supportive care, and/or provide culturally competent self-
to medical examinations and school commitments and help resources to support patients.48
spatial limitations within hospitals can attenuate physi- With respect to cancer survivors, many interventions
cal activity levels in child and adolescent cancer patients.65 have prescribed structured, gym-based exercise pro-
A study of adult cancer patients between the ages of 42 grams.73 As mentioned previously, barriers such as time,
and 88 also supported that time constraints were a pri- money, and transportation availability can hinder the
mary barrier to exercise, with poor health cited as the only effectiveness of initiatives requiring gym visitation and
impediment more significant than time.66 Additionally, utilization. Tailored, self-guided programs that offer read-
isolation and lack of motivation present unique chal- ily accessible educational resources and consultation may
lenges. Many patients believe that exercising around other be more effective at fostering physical activity adherence.73
severely ill patients makes them feel sicker,65 and others These interventions provide the patient with information
believe that maximizing sleep is the best way to assuage regarding physical activity-related benefits, goal-setting,
the side effects of chemotherapy or similar treatments.65 self-monitoring, and how and when to increase physical
In order to augment physical activity in cancer and non- activity.73 While counseling can motivate patients to initi-
cancer populations, clinicians can employ various strate- ate and sustain a regimen, patients are also often highly
gies to overcome some of these challenges. receptive to counseling from their healthcare providers.
A study of cancer survivors aged 20– 4 4 years old revealed
that 78% were interested in participating in a physi-
cal activity program, and approximately 50% wanted
34.5 STRATEGIES FOR PHYSICAL to receive counseling from fitness experts at their cancer
ACTIVITY INTERVENTIONS center.74 Patients preparing for or undergoing treatment
should also receive physical activity counseling. Nurse
Many cancer patients do not meet recommended activ- counseling has been shown to increase physical activity
ity levels due to the perceived barriers and costs associ- among patients preparing to undergo intensive cancer
ated with exercising. While failure to reach these physical treatment.75 In addition to patient consultation and advis-
activity thresholds can undermine treatment and symptom ing, other innovative strategies should also be explored.
management efforts, it may also contribute to the manifes- Mounting rates of Internet accessibility and smart-
tation of other chronic comorbidities. Some components phone ownership have made e-health a powerful
References 437
TABLE 34.2 Key topics and questions for future research related to physical activity and cancer (based on8 )
• Causality: Does physical inactivity cause cancer and/or does engaging in physical activity prevent cancer?
• Dose – response: What is the optimal intensity and duration of physical activity to reduce cancer risk? Are certain exercise types,
34
conducted at certain times in a person’ s life, more beneficial?
• Biological Mechanisms: What biological mechanisms and biomarkers are at play with respect to the PA-cancer relationship?
• Confounding: How do confounding factors such as nutrition and BMI attenuate or amplify the effects of PA on cancer risk
reduction?
• Genetic Implications: Does PA benefit individuals genetically susceptible to cancer, and if so, to what extent?
disease prevention and management technology. One weight could mediate or confound results from physi-
study showed that 80% of older cancer survivors were cal activity and breast or endometrial cancer studies. 23
willing to participate in an online physical activity pro- Moreover, controlling for potential confounding fac-
gram.76 Online resources and mobile applications can tors, such as body mass index (BMI) and dietary intake,
allow cancer survivors to set goals, network with one is particularly difficult but vitally important in order to
another, receive exercise tips, and find health information distinguish effects of physical activity from effects driven
in one convenient location.76 As with any intervention, by other intervening variables. Lastly, dose– response
these programs must be catered to patients’ needs. Use of relationships between physical activity and cancer risk
adequate message tones and clarity, provision of appropri- reduction are not well understood. For instance, it is
ate physical activity prescriptions, physical activity regi- unclear whether shorter, segmented daily exercise yields
men personalization, and presence of resources for goal more benefits than exercise completed in one sequence.43
attainment have all been identified by cancer survivors as Future research should target these limitations in order to
essential features of online physical activity programs.77 better guide clinical oncology practice. Table 34.2 high-
Devising user-friendly mobile technologies designated lights the key limitations hindering this field of inquiry,
specifically for individuals at specific stages along the can- all of which make clinical research in physical activity
cer continuum can stimulate activity levels among seden- and cancer costly and difficult to implement.
tary patients.
34.7 CONCLUSION
34.6 LIMITATIONS OF
PHYSICAL ACTIVITY AND For many noncancerous chronic conditions such as car-
diovascular disease, stroke, and diabetes, exercise is
CANCER RESEARCH ubiquitously prescribed as both a preventive and symp-
tom-alleviating treatment. However, there is now substan-
Various limitations currently hinder this field of research tial observational evidence in the oncological community
and application in clinical medicine. Observational evi- to support that inactivity is a major risk factor for multi-
dence supporting physical activity as a cancer preven- ple cancers as well. As such, clinicians should incorporate
tion and mitigation tool continues to mount. However, physical activity regimens into health and wellness pro-
research investigating the correlation between physical grams for at-risk patients, individuals battling cancer, and
activity and cancer risk and survivorship is still ham- cancer survivors. Physical activity interventions are essen-
pered by fundamental uncertainty regarding the underly- tial for two underlying reasons. Most obviously, exercise
ing biological mechanisms involved. Various studies have is an entirely safe prescription that does not increase can-
hypothesized the biochemical underpinnings of physi- cer risk or exacerbate cancer status. But most importantly,
cal activity-mediated cancer risk reduction or survivor- physical activity adherence is among the cheapest and
ship promotion.15,27,78–81 Yet, many of these mechanisms most effective prevention strategies for cancer while also
remain abstract or inconclusive. The multifactorial etiol- serving as one of the best deterrents against stroke and
ogy of cancers that are linked with inactivity also makes heart disease. Just by recommending exercise to patients,
it difficult to separate the effects of physical activity from clinicians can help reduce risk for three of the five leading
other healthy behaviors. 21 For example, physical activity causes of death in the United States.82 Moving forward,
influences weight control and the effects of these two life- physical activity should serve as a central tenet of cancer
style factors are difficult to dissociate. As a result, body prevention and treatment strategies.
REFERENCES
1. World Health Organization: The top 10 3. American Cancer Society: Cancer facts and sus.gov/quickfac ts/table/P ST045216/0 0
causes of death. http://www.who.i nt/m figures 2017. https://www.cancer.org/co (accessed April 7, 2017).
ediacentre /factsheets /fs310/en / (accessed ntent/dam/cancer-org/research/cancer-fac 5. Global Burden of Disease Cancer
April 7, 2017). ts-and-statistics/annual-cancer-facts-an Collaboration. Global, regional, and
2. World Health Organization: Cancer: Key d-figures/2017/cancer-facts-and-figures- national cancer incidence, mortality,
facts. http://www.who.int/mediacentre/ 2017.pdf (accessed December 11, 2017). years of life lost, years lived with dis-
factsheets/fs297/en/(accessed December 11, 4. United States Census Bureau: QuickFacts: ability, and disability-adjusted life-years
2017). United States 2016. https: //www.cen for 32 cancer groups, 1990 to 2015:
438 Chapter 34 Physical Activity and the Prevention and Treatment of Cancer
A systematic analysis for the global bur- 21. Friedenreich CM, Orenstein MR. and their guardians. Cancer 2005;
den of disease study. JAMA Oncol 2017; Physical activity and cancer preven- 103(10):2171– 2180.
3(4):524– 548. tion: Etiologic evidence and biologi- 37. Winzer BM, Whiteman DC, Reeves MM,
6. National Cancer Institute: Cancer cal mechanisms. J Nutr 2002; 132(11 Paratz JD. Physical activity and cancer
prevalence and cost of care projections, Suppl):3456S– 3464S. prevention: A systematic review of clini-
2011. https://costprojections.cancer. 22. Schmid D, Behrens G, Keimling M, cal trials. Cancer Causes Control 2011;
gov/(accessed April 7, 2017). Jochem C, Ricci C, Leitzmann M. A sys- 22(6):811– 826.
7. Al-Amri AM. Prevention of breast tematic review and meta-analysis of phys- 38. Steindorf K, Clauss D, Wiskemann J,
cancer. J Family Commun Med 2005; ical activity and endometrial cancer risk. Schmidt ME. Physical activity and gastro-
12(2):71– 74. Eur J Epidemiol 2015; 30(5):397– 412. intestinal cancers: Primary and tertiary
8. National Cancer Institute: About Cancer: 23. Borch KB, Weiderpass E, Braaten T, preventive effects and possible biological
Physical Activity and Cancer. https: //ww Jareid M, Gavrilyuk OA, Licaj I. Physical mechanisms. Sports 2015; 3:145– 158.
w.cancer.gov/about-cancer/causes-prevent activity and risk of endometrial cancer 39. United States Department of Health and
ion/risk/obesit y/physical-activity-fact- in the Norwegian Women and Cancer Human Services. Physical Activity and
sheet(accessed April 13, 2017). (NOWAC) study. Int J Cancer 2017; Health: A Report of the Surgeon General.
9. World Cancer Research Fund 140(8):1809– 1818. 1996, Centers for Disease Control
International: Cancer preventability 24. Wolin KY, Yan Y, Colditz GA, Lee IM. and Prevention, National Center for
estimates for diet, nutrition, body fatness, Physical activity and colon cancer preven- Chronic Disease Prevention and Health
and physical activity. http://wcrf.org/int/ tion: A meta-analysis. Br J Cancer 2009; Promotion, Atlanta, GA, p. 292.
cancer-facts-fig ures/preventability- esti 100(4):611– 616. 40. Caspersen CJ, Powell KE, Christenson
mates /cancer-preventabilit y-estimates-di 25. Schmid D, Behrens G, Matthews CE, GM. Physical activity, exercise, and
et-nut rition (accessed May 17, 2017). Leitzmann MF. Physical activity and risk physical fitness: Definitions and distinc-
10. Moore SC, Lee IM, Weiderpass E, et al. of colon cancer in diabetic and nondia- tions for health-related research. Public
Association of leisure-time physical activ- betic US adults. Mayo Clin Proc 2016; Health Rep 1985; 100(2):126– 131.
ity with risk of 26 types of cancer in 1.44 91(12):1693– 1705. 41. Speck RM, Schmitz KH: Cancer
million adults. JAMA Intern Med 2016; 26. Nilsen TIL, Romundstad PR, Petersen H, Prevention. http: //www.acsm.org/publi
176(6):816– 825. Gnnell D, Vatten LJ. Recreational physi- c-information/ar ticles/2016/10/07/cancer
11. Breastcancer.org: US Breast Cancer cal activity and cancer risk in subsites of -prevention-lifestyle -changes (accessed
Statistics, 2017. http://www.breastcancer. the colon (the Nord-Trondelag Health May 18, 2017).
org/symptoms /understand_bc/statistics Study). Cancer Epidem Biomar 2008; 42. American Institute for Cancer Research:
(accessed May 4, 2017). 17(1):183– 188. Recommendations for Cancer Prevention.
12. Frisch RE, Wyshak G, Albright NL, et al. 27. Ashcraft KA, Peace RM, Betof AS, http://www.aicr.org/reduce -your-cancer-r
Lower prevalence of breast cancer and Dewhirst MW, Jones LW. Efficacy and isk/recommendations-for-cancer-prev
cancers of the reproductive system mechanisms of aerobic exercise on cancer ention /recommendations_02 _ activity.
among former college athletes compared initiation, progression,and metastasis: html (accessed December 12, 2017).
to non-athletes. Br J Cancer 1985; A critical systematice review of in vivo 43. American Cancer Society: ACS
52(6):885– 891. preclinical data. Cancer Res 2016; Guidelinse for Nutrition and Physical
13. Goncalves AK, Dantas Florencio GL, 76(14):4032– 4050. Activity. https: //www.cancer.org/healthy
Maisonnette de Atayde Silva MJ, Cobucci 28. Jones LW, Peppercorn J, Scott JM, /eat-healthy-get-active/acs-guidelines-n
RN, Giraldo PC, Cote NM. Effects of Battaglini C. Exercise therapy in the utrition-physical-activit y-cancer-preven
physical activity on breast cancer preven- management of solid tumors. Curr Treat tion/g uidelines.html (accessed May 17,
tion: A systematic review. J Phys Act Option Oncol 2010; 11(0):45– 58. 2017).
Health 2014; 11(2):445– 454. 29. Hunter EG. Gibson RW, Arbesman 44. Rajotte EJ, Yi JC, Baker KS, Gregerson L,
14. Monninkhof EM, Elias SG, Vlems FA, M, D’ A mico M. Systematic review of Leiserowitz A, Syrjala KL. Community-
et al. Physical activity and breast cancer: occupational therapy and adult cancer based exercise program effectiveness
A systematic review. Epidemiology 2007; rehabilitation: Part 1. Impact of physi- and safety for cancer survivors. J Cancer
18(1):137– 157. cal activity and symptom management Surviv 2012; 6(2):219– 2 28.
15. McTiernan A. Mechanisms linking physi- interventions. Am J Occup Ther 2017; 45. Pekmezi DW, Demark-Wahnefried W.
cal activity with cancer. Nat Rev Cancer 71(2):1– 11. Updated evidence in support of diet an
2008; 8(3):205– 211. 30. Brown JC, Winters-Stone K, Lee A, exercise interventions in cancer survivors.
16. Patel AV, Callel EE, Bernstein L, Wu AH, Schmitz KH. Cancer, physical activ- Acta Oncol 2011; 50(2):167– 178.
Thun MJ. Recreational physical activity ity, and exercise. Compr Physiol 2012; 46. Speck RM, Courneya KS, Masse LC,
and risk of postmenopausal breast cancer 2(4):2775– 2809. Duval S, Schmitz KH. An update of
in a large cohort of US women. Cancer 31. Graydon JE, Bubela N, Irvine D, Vincent controlled physical activity trials in
Causes Control 2003; 14(6)519– 529. L. Fatigue-reducing strategies used by cancer survivors: A systematic review
17. Steindorf K, Ritte R, Eomois PP, et al. patients receiving treatment for cancer. and meta-analysis. J Cancer Surviv 2010;
Physical activity and risk of breast cancer Cancer Nurs 1995; 18(1):23– 28. 4(2):87– 100.
overall and by hormone receptor status: 32. Irwin ML, McTiernan A, Manson JE, 47. Haines TP, Sinnamon P, Wetzig NG, et al.
The European prospective investigation et al. Physical activity and survival in Multimodal exercise improves quality
into cancer and nutrition. Int J Cancer postmenopausal women with breast of life of women being treated for breast
2013; 132(7):1667– 1678. cancer: Results from the women’ s cancer, but at what cost? Randomized
18. Friedenreich CM, Woolcott CG, health initiative. Cancer Prev Res 2011; trial with economic evaluation. Breast
McTiernan A, et al. Alberta physical 4(4):522– 529. Cancer Res Treat 2010; 124(1):163– 175.
activity and breast cancer prevention 33. Friedenreich CM, Neilson HK, Farris 48. Rock CL, Doyle C, Demark-Wahnefried
trial: Sex hormone changes in a year-long MS, Courneya KS. Physical activity and W, et al. Nutrition and physical activ-
exercise intervention among postmeno- cancer outcomes: A precision medi- ity guidelines for cancer survivors. CA
pausal women. J Clin Oncol 2010; cine approach. Clin Cancer Res 2016; Cancer J Clin 2012; 62(4):243– 274.
28(9):1458– 1466. 22(19):4766– 4775. 49. American Institute for Cancer Research:
19. Mullooly M, Yang HP, Falk RT, et al. 34. Hamer J, Warner E. Lifestyle modifica- AICR’ s Guidelinse for Caner Survivors.
Relationship between crown-like tions for patients with breast cancer http://www.aicr.org/patients-su rvivors/a
structures and sex-steroid hormones in to improve prognosis and optimize icrs-g uidelines-for-cancer.html (accessed
breast adipose tissue and serum among overall health. Can Med Assoc J 2017; May 17, 2017).
postmenopausal breast cancer patients. 189(7):E268– E 274. 50. Jankowski CM, Matthews EE: General
Breast Cancer Res 2017; 19:8. 35. Dieli-Conwright CM, Orozco BZ. Exercise Guidelines for Cancer Survivors.
20. Dieli-Conwright CM, Lee K, Kiwata JL. Exercise after breast cancer treatment: https: //ww w.ons.org/sites/defau lt/fi les/
Reducing the risk of breast cancer recur- Current perspectives. Breast Cancer Cancer_patient_ general_exercise _bro
rence: An evaluation of the effects and 2015; 7:353– 362. chure.pdf (accessed May 17, 2017).
mechanisms of diet and exercise. Curr 36. Demark-Wahnefried W, Werner C, Clipp 51. National Comprehensive Cancer
Breast Cancer Rep 2016; 8(3):139– 150. EC, et al. Survivors of childhood cancer Network: Exercising During Cancer
References 439
Treatment. https: //www.nccn.org/pati 63. Meyerowitz BE, Sparks FC, Spears IK. to physical exercise after completion of
ents/resources/ life_w ith_ cancer/exercise Adjuvant chemotherapy for breast carci- primary cancer treatment. Int J Behav
52.
.aspx(accessed May 17, 2017).
Centers for Disease Control and
Prevention: Exercise or Physical Activity.
noma: Psychosocial implications. Cancer
1979; 43(5):1613– 1618.
64. Shang J, Wenzel J, Krumm S, Griffith K,
73.
Nutr Phys 2016; 13:100.
Basen-Engquist K, Taylor CL, Rosenblum
C, et al. Randomized pilot test of a
34
https: //ww w.cdc.gov/nchs/fastats/exercis Stewart K. Who will drop out and who lifestyle physical activity intervention
e.htm(accessed April 21, 2017). will drop in: Exercise adherence in a for breast cancer survivors. Patient Educ
53. Brunet J, Wur A, O’ R ielly C, Howell D, randomized clinical trial among patients Couns 2006; 64(1– 2):225– 235.
Belanger M, Sussman J. Th effectiveness receiving active cancer treatment. Cancer 74. Belanger LJ, Plotnikoff RC, Clark A,
of health care provider physical activity Nurs 2012; 35(4):312– 322. Courneya KS. A survey of physical activ-
recommedations in cancer survivors: 65. Gotte M, Kesting S, Winter C, ity programming and counseling prefer-
A systematic review and meta-analysis Rosenbaum D, Boos J. Experience of ences in young-adult cancer survivors.
protocol. Syst Rev 2017; 6:66. barriers and motivations for physical Cancer Nurs 2012; 35(1):48– 54.
54. Ekelund U, Ward HA, Norat T, et al. activities and exercise during treatment 75. Komatsu H, Watanuki S, Koyama Y, et al.
Physical activity and all-cause mortality of pediatric patients with cancer. Pediatr Nurse counseling for physical activity
across levels of overall and abdominal Blood Cancer 2014; 61(9):1632– 1637. in patients undergoing esophagectomy.
adiposity in European men and women: 66. Yang DD, Hausien O, Ageel M, et al. Gastroenterol Nurs 2018; 41(3):233.
The European Prospective Investigation Physical activity levels and barriers to 76. Hong Y, Vollmer Dahlke D, Ory M, et al.
into Cancer and Nutrition Study (EPIC). exercise referral among patients with Designing iCanFit: A mobile-enabled web
Am J Clin Nutr 2015; 101(3):613– 621. cancer. Patient Educ Couns 2017; application to promote physical activity
55. Gray E. In Practice: Behaviour change 100(7):1402– 1407. in older cancer survivors. JMIR Res
and public health interventions. Perspect 67. Ungar N, Wiskemann J, Sieverding M. Protoc 2013; 2(1):e12.
Public Health 2013; 133(5):239. Physical activity enjoyment and self- 77. Robertson MC, Tsai E, Lyons EJ, et al.
56. Centers for Disease Control and efficacy as predictors of cancer patients’ Mobile health physical activity interven-
Prevention: Overcoming Barriers to physical activity level. Front Psychol tion preferences in cancer survivors: A
Physical Activity. https: //www.cdc.gov/ 2016; 7:898. qualitative study. JMIR mHealth uHealth
physicalactivit y/basics/adding-pa/ba rrie 68. Karvinen KH, Courneya KS, Campbell 2017; 5(1):e3.
rs.htm l (accessed June 1, 2017). KL, et al. Correlates of exercise motiva- 78. Friedenreich CM. Physical activity and
57. Saffer H, Dhaval D, Grossman M, Leung tion and behavior in a population-based breast cancer: Review of the epidemio-
LA. Racial, ethnic, and gender differ- sample of endometrial cancer survivors: logic evidence and biologic mechanisms.
ences in physical activity. J Human Cap An application of the theory of planned Recent Results Cancer Res 2011;
2013; 7(4):378– 410. behavior. Int J Behav Nutr Phy 2007; 188:125– 139.
58. Mock V, Atkinson A, Barsevick A, 4:21. 79. Shephard RJ. Cancers of the esophagus
et al. NCCN practice guidelines for 69. Keats MR, Culos-Reed SN, Courneya and stomach: Potential mechanisms
cancer-related fatigue. Oncology 2000; KS, McBride M. Understanding physical behind the beneficial influence of
14(11A):151– 161. activity in adolescent cancer survivors: physical activity. Clin J Sport Med 2017;
59. Gerber LH. Cancer-related fatigue: An application of the theory of planned 27(4):415– 421.
Persistent, pervasive, and problem- behavior. Psychooncology 2007; 80. Hayes BD, Brady L, Pollak M, Finn SP.
atic. Phys Med Rehabhil Clin N 2017; 16(5):448– 457. Exercise and prostate cancer: Evidence
28(1):65– 88. 70. Trinh L, Plotnikoff RC, Rhodes RE, and proposed mechanisms for dis-
60. Haylock PJ, Hart LK. Fatigue in patients North S, Courneya KS. Correlates of ease modification. Cancer Epidemiol
receiving localized radiation. Cancer physical activity in a population-based Biomarkers Prev 2016; 25(9):1281– 1288.
Nurs 1979; 2(6)461– 467. sample of kidney cancer survivors: An 81. Wekesa A, Harrison M, Watson
61. Pertl MM, Hevey D, Collier S, Lambe application of the theory of planned RW. Physical activity and its mecha-
K, O’ D wyer AM. Predictors of fatigue behavior. Int J Behav Nutr Phys 2012; nistic effects on prostate cancer.
in cancer patients before and after 9:96. Prostate Cancer Prostatic Dis 2015;
chemotherapy. J Health Psychol 2013; 71. Speed-Andrews AE, Rhodes RE, 18(3):197– 207.
19(6):699– 710. Blanchard CM, et al. Medical, demo- 82. Centers for Disease Control and
62. Cassileth BR, Lusk EJ, Bodenheimer BJ, graphic and social cognitive correlates of Prevention: Up to 40 Percent of Annual
Farber JM, Jochimsen P, Morrin-Taylor physical activity in a population-based Deaths from Each of Five Leading US
B. Chemotherapeutic toxicity— T he rela- sample of colorectal cancer survivors. Eur Causes are Preventable. https: //www.cdc
tionship between patients’ pretreatment J Cancer Care 2012; 21(2):187– 196. .gov/media /releases/2014/p 0501-prev
expectations and posttreatment results. 72. Kampshoff CS, van Mechelen W, Shep entable-deaths.html (accessed December
Am J Clin Oncol 1985; 8(5):419– 425. G, et al. Participation in and adherence 11, 2017).
35
CHAPTER
441
442 Chapter 35 Nutrition Therapy for the Cancer Patient
observed unintentional lipolysis due to increased levels of aspects of QOL highlights the importance of nutrition
35
adipose triglyceride lipase (ATGL) and hormone-sensitive intervention with cancer patients.
lipase (HLS) enzymes seen in cancer patients. Lipolysis in Poor nutrition status impacts the cancer treatment
cancer associated cachexia is also induced by hormones plan and is associated with a decreased tolerance of che-
such as glucocorticoids and catecholamines along with motherapy and radiation, higher rates of hospital admis-
cytokines.44 sions, and increased length of hospital stay (LOS). 50–53
A phenomenon known as white adipose tissue brown- Screening for malnutrition can facilitate the early iden-
ing is thought to occur in the initial stages of cachexia tification of patients who are malnourished or who are
and is associated with increased energy expenditure in at risk for malnutrition and can lead to improved out-
animals.16 Brown adipose tissue (BAT) differs from white comes. 54 There are several screening tools validated
adipose tissue (WAT) because rather than storing energy for use with oncology patients, including the Patient
it is responsible for the dissipation of energy as heat. BAT Generated-Subjective Global Assessment (PG-SGA), the
produces a “non-shivering” interscapular thermogenesis Malnutrition Screening Tool (MST), 55 the Malnutrition
in response to extended exposure to cold temperatures.16,27 Screening Tool for Cancer Patients (MSTC), 56 and the
Mouse models of cancer cachexia have shown increased Malnutrition Universal Screening Tool (MUST). 50 These
thermogenic activity of adipose tissue, which may contrib- tools are simple to use, can either be completed by the
ute to accelerated energy expenditure and points to the patient or a healthcare professional, and determines
atrophy of both muscle and fat. 33 The mouse tumor whether a patient is at risk for malnutrition and requires
transplant model suggests that the thermogenesis of inter- further nutritional evaluation.
scapular BAT contributes to the hypermetabolic state of The Nutrition Care Process is a systematic approach
cachexia.45 to providing high-quality nutrition care and consists of
Morphology changes with WAT have been described nutritional assessment, nutritional diagnosis, interven-
as the phenomenon of “WAT browning”27 Pre-clinical tion that will be directed to the root cause of the nutri-
models show the “browning” of adipocytes in WAT cells tion problem, and monitoring and evaluation. Medical
to “beige” cells16 that increase energy expenditure.46 Nutrition Therapy (MNT) is a specific application of the
WAT browning is associated with increased expression Nutrition Care Process in clinical settings that is focused
of UCP1, which uncouples mitochondrial respiration on the management of diseases. MNT involves in-depth
toward thermogenesis instead of ATP synthesis.16 While individualized nutrition assessment and a duration and
this energy expenditure is useful in obesity, it is detri- frequency of care to manage the disease.
mental for cachectic cancer patients who cannot afford In 11 studies examining patients with a variety of high-
further weight loss. Petruzzelli and colleagues16 observed risk cancers, including head and neck and GI and prior to
WAT browning took place in the initial stages of can- receiving radiotherapy or combined radiotherapy in ambu-
cer cachexia, even before skeletal muscle atrophy and latory and inpatient oncology centers, MNT was found
contributed to increased energy expenditure and lipid effective in improving multiple treatment outcomes. 57–67
mobilization. In these studies, the most common frequency for nutrition
Chronic inflammation and cytokines also play a care during treatment was weekly. Interventions utilizing
critical role in the pathogenesis of WAT browning, in multiple sessions over extended time periods ranged from
particular, IL-6, which increases UCP1 expression in eight weeks to 12 months. Nutrition intervention posi-
WAT, along with the tumor-derived hormone parathy- tively impacted: calorie and protein intake; anthropomet-
roid-related peptide (PTHrP).16 Animal studies indicate ric measurements, including weight; body composition
that other mediators, such as the activation of macro- measurements, including preservation of fat-free mass;
phages47 and β-adrenergic fibers,48 also play a role in nutritional status and degree of deterioration in nutri-
stimulating WAT browning and induce thermogenesis tional status, including wasting; QOL; symptoms, such
in adipose tissue, either alone or in combination with as fatigue, pain, nausea/vomiting, and appetite; radiother-
cytokines.16 The inhibition of WAT browning through a apy-induced toxicities; physical and functional status; and
β-adrenergic blockade is a promising approach to mini- hospital LOS. 58–68
mizing cachexia.16 Additionally, in five studies examining ambulatory
and inpatient patients with a variety of cancers (and
prior to receiving chemotherapy), MNT was effective in
35.4 NUTRITION SCREENING improving multiple treatment outcomes. 57,68–72 Outcomes
that were positively impacted by nutrition intervention
An individual’s nutrition status greatly impacts QOL included: weight status; nutritional status; dietary intake;
and how cancer treatments are tolerated. In an observa- QOL; decrease in reported symptoms; functional status,
tional study of cancer patients, Nourissat and colleagues49 endurance, and strength.68–72
assessed nutritional status and different aspects of QOL, A key benefit to MNT is identifying malnutrition and
including physical, functional, social, cognitive, and symp- cachexia early in cancer patients and offering nutrition
tom management. Approximately 30% of the patients support via enteral feeding, parenteral feeding, and/or
lost more than 10% of their weight since diagnosis and managing nutrition impact symptoms. Nutrition interven-
reported a significantly lower global QOL score of 49% tion is most successful when cancer patients’ nutritional
compared to those individuals with less than 10% weight needs are met by considering the increased energy expen-
loss since diagnosis, who rated their QOL at 63%.49 This diture resulting from the tumor itself, or the individual’s
significant association with weight loss and the different response to the tumor, along with factors such as stress,
444 Chapter 35 Nutrition Therapy for the Cancer Patient
anxiety, or depression, all of which gravely impact nutri- Although, the cause of muscle wasting is still not fully
tion and often minimize a cancer patient’s food intake.73,74 understood, there is a clinical need to have appropriate
Adequate nutrition status is seen when a cancer patient is early nutrition intervention and to distinguish between
consuming, digesting, and absorbing their required nutri- the inevitable muscle mass loss seen with aging and can-
ents. MNT has been shown to improve an individual’s cer cachexia’s muscle wasting due to molecular mecha-
performance status, recovery from surgery, decrease post- nisms.87 Precise protein signatures for diagnosing cancer
operative complications, enhance weight status, improve cachexia are being studied and hold promise for early and
cancer treatment tolerance, and decrease treatment toxic- clear detection of cancer cachexia.87
ity to chemoradiation. 51,52,75
Continued
446 Chapter 35 Nutrition Therapy for the Cancer Patient
35.6 COMPLEMENTARY AND Several motivators for CAM use were reported from
breast and prostate cancer patients undergoing treat-
RESTORATIVE THERAPEUTIC ment, including the prevention of cancer recurrence,
participating in recovery, improving immune system,
TREATMENT OF CANCER managing stress, and hope.91 Common psychological
symptoms that cause cancer patients and survivors to
CAM is not traditionally included in allopathic medi-
be more prone to using CAM include depression and
cine. Complementary refers to modalities incorporated
anxiety, 92 which often persist even after an encouraging
into conventional medicine while alternative modalities
prognosis or treatment, 93 cancer-related fatigue, sleep
replace conventional treatment. The National Institutes
disturbances, cognitive dysfunction, and peripheral
of Health’s National Center for Complementary and
neuropathy.94
Integrative Health classifies CAM into two main cat-
Although in European cancer centers and hospi-
egories: biological products, which encompasses dietary
tals the top CAM modalities reflect a broader interest
supplements, including nonvitamin, nonmineral dietary
in MBIs,95 U.S. cancer patients and long-term survivors
supplements, i.e. herbs along with special diets; and mind-
prefer biological-based CAM modalities such as vitamin
body interventions (MBIs), which include modalities such
or mineral supplements (64% to 81%, respectively) and
as meditation, yoga, deep breathing, tai chi, and qi gong.90
35.6 Complementary and Restorative Therapeutic Treatment of Cancer 447
multivitamin/mineral supplements (26% to 77%, respec- accompanied by feelings of vulnerability and loss. Patients
35
tively).96 National Health Interview Survey data on CAM seek ways to manage the behavior-related symptoms of
practices in the U.S. ranks special diets in the top ten a cancer diagnosis, including anxiety, stress, and cancer-
CAM practices.90 fatigue.93,97,98 The possibility of cancer reoccurrence and
pending death often augments an individual’s inclination
to try novel and often unproven choices such as alterna-
35.6.1 Special and Alternative tive diets.99
Diets—Metabolic Therapy Select popular special diets used in cancer patients are
shown in Table 35.3. Anecdotal accounts of remission
vs. Dietary Approaches using popular alternative special diets, such as the Gerson
Cancer patients are often looking to take an active role and Gonzalez diets, are appealing as a potential cure,
in their lifestyle and nutrition choices. Patients often feel despite the limited evidence.97,100,101 The topmost cancer
a loss of control after a cancer diagnosis, which is often diets reported are the alkaline, fasting, Gerson, ketogenic
(carbohydrate restricted), macrobiotic, raw food, and adapt to glycolysis to generate ATP.107,109,111,112 This effect
vegan.102 Other popular anti-cancer diets include the is a primary metabolic alteration common to the majority
Budwig, the Gonzalez regimen, and the no sugar diet.97 of cancer cells despite cancer being a heterogeneous dis-
Although health professionals generally do not endorse ease with distinct genotypes.109
the use of certain diets that lack evidence, some cancer The Warburg effect has been the basis of dietary
patients may elect to use them,102,103 and in extreme cases manipulations such as the Ketogenic Diet (KD) and calo-
may go so far as to replace anti-cancer treatment with a rie restriction as an adjuvant therapeutic approach to can-
special cancer diet. cer treatment.107,113
the development and growth of cancers, including insulin, KD limits fruits and vegetables, as well as other nutrient-
35
IGF-1, leptin, adiponectin, cytokines, and inflammation- dense foods, such as enriched grains and calcium-rich
related molecules.121 The limited data on IER and IF show foods. The International Ketogenic Diet Study Group
some beneficial effects, however, are not yet conclusive.121 recommends short-term multivitamin, trace miner-
als, vitamin D, and calcium supplementation while on
the KD.129–131 The length of KD intervention should be
35.6.4 The Ketogenic Diet a minimum of three weeks in order to deplete glycogen
stores and allow for keto-adaptation.107 Reported short
The KD is a high fat, moderate to low protein, and very and long-term side effects of the KD include but are not
low carbohydrate intake diet. Health interest with the KD limited to GI issues such as constipation, renal damage,
began several decades ago when Dr. R. M. Wilder studied and potential hyperlipidemia.124,132 Patient adherence can
the KD for patients with epilepsy. Since then, there has be challenging due to the poor palatability of the diet.
been extensive research for the KD as a potential treat-
ment for epileptic seizures, other neurologic diseases,122
and other conditions, such as obesity, diabetes, cardio-
vascular disease, and cancer.107 In the late 1980’s, the 35.7 CONCLUSION
KD gained interest as a possible adjuvant cancer treat-
ment when mice with colon adenocarcinoma xenografts Malnutrition, which affects a large percentage of can-
showed improved cachexia and decreased tumor weight cer patients, often goes unnoticed, especially in the
when consuming a KD.123 early stages, and can have detrimental consequences
It is theorized that diets low in glucose and other car- on health outcomes and QOL. Identifying malnutrition
bohydrates and high in fat selectively cause metabolic early through validated screening tools and intervening
oxidative stress in cancer cells.124 Cancer cells have high with Medical Nutrition Therapy may lead to improved
levels of mitochondrial-derived reactive oxygen species outcomes. Given the simplicity of incorporating these
(ROS) and require increased glucose and hydroperoxide tools into routine practice, it seems shortsighted that
metabolism to compensate for the increased ROS. The they are underutilized in cancer centers in the U.S.
rationale of the KD is based on the lower carbohydrate More sophisticated tools, such as CT images, may pro-
uptake and simultaneous increase in the levels of ketone vide more insight into a patient’s body composition and
bodies resulting in biochemical changes that mimic that often they have been performed as part of a patient’s
of fasting. Fat metabolism occurs via oxidation of fatty medical workup, thereby not requiring additional
acids in the liver and creates a state of ketosis with the testing.
overproduction of the ketone bodies acetoacetate, beta- CAM therapies are popular in the U.S, and particularly
hydroxybutyrate, and acetone in the blood118,124 and in cancer patients and, depending on the modality, may
further resulting in decreased glucose levels, decreased positively impact a cancer patient’s QOL. Practitioners
insulin levels, and maintenance of blood pH levels.124,125 should be aware of the popular cancer diets that are not
Purportedly, since cancer cells have downregulated oxi- evidence-based because some of these diets can cause seri-
dative phosphorylation and are unable to use ketone ous harm.
bodies for fuel, apoptosis occurs.126 Schroeder and col- Despite the pervasiveness of the Warburg effect across
leagues127 reported lower levels of lactate in tumor tissue a wide range of human cancers, limited systematic clinical
after five days of a KD, indicating an influence on cancer investigations with metabolic and dietary therapies such
cell metabolism. as fasting, caloric restriction, KDs and cancer have been
The classic KD is 90% fat, 2% carbohydrates, and 8% conducted. Nonetheless, these dietary metabolic therapies
protein, providing a 4:1 fat to carbohydrate and protein offer promise as an adjunct therapy with cancer treatment.
ratio by weight.124 Over the years, modified versions of More human clinical trials are being investigated, and
the KD have emerged to replace most of the carbohydrate several trials using various forms of therapeutic metabolic
sources, besides non-starchy vegetable carbohydrates, with therapies such as fasting and KD are underway. More con-
low to moderate amounts of proteins and high amounts of sistent evidence is needed to make clinical recommenda-
monounsaturated and polyunsaturated fats.126 The Low tions for cancer patients.133 Future RCTs will provide a
Glycemic Index Treatment (LGIT) is one such modified better understanding of the impact on nutritional status,
version, and aims to maintain low, stable insulin levels by the potential side effects, and the cancer types that are
eating foods with a low glycemic index. It includes most most receptive to metabolic therapies as an adjuvant can-
fruits, green vegetables, beans, legumes, and peas, and cer treatment.111
restricts high glycemic index foods such as refined grains,
juice, sugar-sweetened beverages, and some fruits. The
Atkins diet is another version of the KD popularized by ACKNOWLEDGMENTS
Dr. Robert Atkins as a treatment for obesity that provides
a 3:1 ratio of fat to carbohydrates and has 30% of calories The authors would like to thank Alicia A. Livinski, the
from protein.128 NIH Library, and the National Institute of Health for
The American Cancer Society recommends a mini- conducting the literature review and assisting with the
mum of 2.5 cups of vegetables and fruits per day, yet the bibliography.
450 Chapter 35 Nutrition Therapy for the Cancer Patient
REFERENCES
1. Dewys, W.D., C. Begg, P.T. Lavin, et al. 18. Muscaritoli, M., S.D. Anker, J. Argilés, 33. Kir, S. and B. Spiegelman. Cachexia and
Prognostic effect of weight loss prior to et al. Consensus definition of sarco- brown fat: A burning issue in cancer.
chemotherapy in cancer patients. Eastern penia, cachexia and pre-cachexia: Trends Cancer 2016;2:461–463.
Cooperative Oncology Group. Am J Med Joint document elaborated by Special 34. Plata-Salamán, C., Y. Oomura, and Y.
1980;69:491–497. Interest Groups (SIG) “cachexia- Kai. Tumor necrosis factor and interleu-
2. Academy of Nutrition and Dietetics anorexia in chronic wasting diseases” kin-1 beta: Suppression of food intake
Evidence Analysis Library. Oncology and “nutrition in geriatrics”. Clin Nutr by direct action in the central nervous
(ONC) Guidelines (2013). https: //ww 2010;29:154–159. system. Brain Res 1988;448:106–114.
w.andeal.org/topic.cf m?menu=5291&ca 19. White, J.V., P. Guenter, G. Jensen, et al. 35. Fearon, K., A. Voss, D. Hustead, et al.
t=5066 (accessed October 4, 2017). Academy of Nutrition and Dietetics Definition of cancer cachexia: Effect of
3. Fearon, K., F. Strasser, S.D. Anker, et al. Malnutrition Work Group; A.S.P.E.N. weight loss, reduced food intake, and
Definition and classification of cancer Malnutrition Task Force; A.S.P.E.N. systemic inflammation on functional
cachexia: An international consensus. Board of Directors. J Acad Nutr Diet status and prognosis. Am J Clin Nutr
Lancet Oncol 2011;12:489–495. 2012;112:730–738. 2006;83:1345–1350.
4. Schcolnik-Cabrera, A., A. Chávez- 20. Tan, B.H., L.A. Birdsell, L. Martin, et al. 36. Jensen, G., P. Hsiao, and D. Wheeler.
Blanco, G. Domínguez-Gómez, et Sarcopenia in an overweight or obese Adult nutrition assessment tutorial. J
al. Understanding tumor anabolism patient is an adverse prognostic factor Parenter Enteral Nutr 2012;36:267–274.
and patient catabolism in cancer- in pancreatic cancer. Clin Cancer Res 37. Cori, C. and G. Cori. The carbohydrate
associated cachexia. Am J Cancer Res 2009;15:6973–6979. metaoblism of tumors: II. Changes in
2017;7:1107–1135. 21. O’Connor, A., W. Fischbach, J.P. Gisbert, sugar, lactic acid, and CO2-combining
5. Morley, J., D. Thomas, and M. et al. Treatment of Helicobacter pylori power of blood passing through a tumor.
Wilson. Cachexia: Pathophysiology infection 2016. Helicobacter 2016;21 J Biol Chem 1925;65:397–405.
and clinical relevance. Am J Clin Nutr Suppl 1:55–61. 38. Bing, C. and P. Trayhurn. Regulation
2006;83:735–743. 22. Trujillo, E.B., S.L. Bergerson, J. Graf, of adipose tissue metabolism in cancer
6. Loumaye, A. and J. Thissen. Biomarkers et al. Cancer. In A.S.P.E.N. Nutrition cachexia. Curr Opin Clin Nutr Metab
of cancer cachexia. Clin Biochem 2017. Support Practice Manual, 2nd edition, Care 2008;11:201–207.
7. Andreyev, H.J., A.R. Norman, J. Oates, 2005, pp. 150–164. 39. Holroyde, C.P., C.L. Skutches, G. Boden,
et al. Why do patients with weight loss 23. Prado, C.M., J.R. Lieffers, L.J. et al. Glucose metabolism in cachectic
have a worse outcome when undergoing McCargar, et al. Prevalence and clini- patients with colorectal cancer. Cancer
chemotherapy for gastrointestinal malig- cal implications of sarcopenic obesity Res 1984;44:5910–5913.
nancies? Eur J Cancer 1998;34:503–509. in patients with solid tumours of the 40. Figueroa-Clarevega, A. and D. Bilder.
8. Wang, X., A.M. Pickrell, T.A. Zimmers, respiratory and gastrointestinal tracts: A Malignant Drosophila tumors interrupt
et al. Increase in muscle mitochondrial population-based study. Lancet Oncol insulin signaling to induce cachexia-like
biogenesis does not prevent muscle loss 2008;9:629–635. wasting. Dev Cell 2015;33:47–55.
but increased tumor size in a mouse 24. Prado, C.M., Y.L. Maia, M. Ormsbee, 41. Kwon, Y., W. Song, I.A. Droujinine,
model of acute cancer-induced cachexia. et al. Assessment of nutritional status et al. Systemic organ wasting induced
PLoS One 2012;7:e33426. in cancer--the relationship between by localized expression of the secreted
9. Solheim, T.S., D. Blum, P.M. Fayers, et al. body composition and pharmacoki- insulin/IGF antagonist ImpL2. Dev Cell
Weight loss, appetite loss and food intake netics. Anticancer Agents Med Chem 2015;33:36–46.
in cancer patients with cancer cachexia: 2013;13:1197–1203. 42. Wagner, E. and M. Petruzzelli. Cancer
Three peas in a pod? - analysis from a 25. Dodson, S., V.E. Baracos, A. Jatoi, et al. metabolism: A waste of insulin interfer-
multicenter cross sectional study. Acta Muscle wasting in cancer cachexia: ence. Nature 2015;521:430–431.
Oncol 2014;53:539–546. Clinical implications, diagnosis, and 43. Das, S.K., S. Eder, S. Schauer, et al.
10. Fearon, K., D. Glass, and D. Guttridge. emerging treatment strategies. Annu Rev Adipose triglyceride lipase contributes
Cancer cachexia: Mediators, signaling, Med 2011;62:265–279. to cancer-associated cachexia. Science
and metabolic pathways. Cell Metab 26. Tisdale, M.J. Mechanisms of cancer 2011;333:233–238.
2012;16:153–166. cachexia. Physiol Rev 2009;89:381–410. 44. Tisdale, M.J. Are tumoral factors respon-
11. Iwata, Y., N. Suzuki, H. Ohtake, et al. 27. Petruzzelli, M. and E. Wagner. sible for host tissue wasting in cancer
Cancer cachexia causes skeletal muscle Mechanisms of metabolic dysfunction in cachexia? Future Oncol 2010;6:503–513.
damage via transient receptor potential cancer-associated cachexia. Genes Dev 45. Tsoli, M., M. Moore, D. Burg, et al.
vanilloid 2-independent mechanisms, 2016;30:489–501. Activation of thermogenesis in brown adi-
unlike muscular dystrophy. J Cachexia 28. Fredrix, E.W., P.B. Soeters, E.F. Wouters, pose tissue and dysregulated lipid metab-
Sarcopenia Muscle 2016;7:366–376. et al. Effect of different tumor types on olism associated with cancer cachexia in
12. Aoyagi, T., K.P. Terracina, A. Raza, resting energy expenditure. Cancer Res mice. Cancer Res 2012;72:4372–4382.
et al. Cancer cachexia, mechanism and 1991;51:6138–6141. 46. Shabalina, I.G., N. Petrovic, J.M. de
treatment. World J Gastrointest Oncol 29. Moses, A.W., C. Slater, T. Preston, et al. Jong, et al. UCP1 in brite/beige adipose
2015;7:17–29. Reduced total energy expenditure and tissue mitochondria is functionally ther-
13. Fearon, K., J. Arends, and V. Baracos. physical activity in cachectic patients mogenic. Cell Rep 2013;5:1196–1203.
Understanding the mechanisms and treat- with pancreatic cancer can be modulated 47. Mauer, J., B. Chaurasia, J. Goldau, et al.
ment options in cancer cachexia. Nat Rev by an energy and protein dense oral Signaling by IL-6 promotes alterna-
Clin Oncol 2013;10:90–99. supplement enriched with n-3 fatty acids. tive activation of macrophages to limit
14. Tan, B. and K. Fearon. Cachexia: Br J Cancer 2004;90:996–1002. endotoxemia and obesity-associated
Prevalence and impact in medicine. 30. Kumar, N.B., A. Kazi, T. Smith, et al. resistance to insulin. Nat Immunol
Curr Opin Clin Nutr Metab Care Cancer cachexia: Traditional therapies 2014;15:423–430.
2008;11:400–407. and novel molecular mechanism-based 48. Nguyen, K.D., Y. Qiu, X. Cui, et al.
15. Argilés, J., S. Busquets, B. Stemmler, approaches to treatment. Curr Treat Alternatively activated macrophages
et al. Cancer cachexia: Understanding Options Oncol 2010;11:107–117. produce catecholamines to sustain
the molecular basis. Nat Rev Cancer 31. Pepys, M.B., G.M. Hirschfield, G.A. adaptive thermogenesis. Nature
2014;14:754–762. Tennent, et al. Targeting C-reactive 2011;480:104–108.
16. Petruzzelli, M., M. Schweiger, R. protein for the treatment of car- 49. Nourissat, A., M.P. Vasson, Y.
Schreiber, et al. A switch from white to diovascular disease. Nature Merrouche, et al. Relationship between
brown fat increases energy expenditure in 2006;440:1217–1221. nutritional status and quality of life
cancer-associated cachexia. Cell Metab 32. Fearon, K.C., M.D. Barber, J.S. Falconer, in patients with cancer. Eur J Cancer
2014;20:433–447. et al. Pancreatic cancer as a model: 2008;44:1238–1242.
17. Johns, N., N. Stephens, and K. Fearon. Inflammatory mediators, acute-phase 50. Amaral, T.F., A. Antunes, S. Cabral,
Muscle wasting in cancer. Int J Biochem response, and cancer cachexia. World J et al. An evaluation of three nutri-
Cell Biol 2013;45:2215–2229. Surg 1999;23:584–588. tional screening tools in a Portuguese
References 451
oncology centre. J Hum Nutr Diet 65. Ravasco, P., I. Monteiro-Grillo, P.M. considerations. J Parenter Enteral Nutr
2008;21:575–583. Vidal, et al. Dietary counseling improves 2009;33:548–562.
51. Antoun, S., A. Rey, J. Beal, et al.
Nutritional risk factors in planned onco-
logic surgery: What clinical and biologi-
patient outcomes: A prospective, random-
ized, controlled trial in colorectal cancer
patients undergoing radiotherapy. J Clin
79. Forchielli, M. and S. Miller. Nutritional
goals and requirements. In A.S.P.E.N
Nutrition Support Practice Manual., R.
35
cal parameters should be routinely used? Oncol 2005;23:1431–1438. Merrit, editor. Silver Spring, MD: ASPEN
World J Surg 2009;33:1633–1640. 66. Ravasco, P., I. Monteiro-Grillo, P. Publishing, 2005, pp. 50–51.
52. Capuano, G., A. Grosso, P.C. Gentile, Marques Vidal, et al. Impact of nutrition 80. Rock, C.L., C. Doyle, W. Denmark-
et al. Influence of weight loss on outcomes on outcome: A prospective randomized Wahnefried, et al. Nutrition and physical
in patients with head and neck cancer controlled trial in patients with head and activity guidelines for cancer survivors.
undergoing concomitant chemoradio- neck cancer undergoing radiotherapy. CA Cancer J Clin 2012;62:243–274.
therapy. Head Neck 2008;30:503–508. Head Neck 2005;27:659–668. 81. Song, G.M., X. Tian, L. Zhang, et al.
53. Eriksson, K.M., T. Cederholm, and J.E. 67. van den Berg, M.G., E.L. Rasmussen- Immunonutrition support for patients
Palmblad. Nutrition and acute leukemia Conrad, K.H. Wei, et al. Comparison of undergoing surgery for gastrointestinal
in adults: Relation between nutritional the effect of individual dietary counsel- malignancy: Preoperative, postop-
status and infectious complications ling and of standard nutritional care on erative, or perioperative? A bayesian
during remission induction. Cancer weight loss in patients with head and network meta-analysis of randomized
1998;82:1071–1077. neck cancer undergoing radiotherapy. Br controlled trials. Medicine (Baltimore)
54. Kruizenga, H.M., M.W. Van Tulder, J.C. J Nutr 2010;104:872–877. 2015;94:e1225.
Seidell, et al. Effectiveness and cost-effec- 68. Glare, P., W. Jongs, and B. Zafiropoulos. 82. Fearon, K.C., M.D. Barber, A.G.
tiveness of early screening and treatment Establishing a cancer nutrition reha- Moses, et al. Double-blind, placebo-
of malnourished patients. Am J Clin Nutr bilitation program (CNRP) for ambula- controlled, randomized study of
2005;82:1082–1089. tory patients attending an Australian eicosapentaenoic acid diester in patients
55. Ferguson, M., S. Capra, J. Bauer, et al. cancer center. Support Care Cancer with cancer cachexia. J Clin Oncol
Development of a valid and reliable 2011;19:445–454. 2006;24:3401–3407.
malnutrition screening tool for adult 69. Dintinjana, R.D., T. Guina, Z. Krznaric, 83. Murphy, R.A., M. Mourtzakis, Q.S.
acute hospital patients. Nutrition et al. Effects of nutritional support in Chu, et al. Nutritional intervention with
1999;15:458–464. patients with colorectal cancer dur- fish oil provides a benefit over standard
56. Kim, J.Y., G.A. Wie, Y.A. Cho, et al. ing chemotherapy. Coll Antropol of care for weight and skeletal muscle
Development and validation of a nutrition 2008;32:737–740. mass in patients with nonsmall cell lung
screening tool for hospitalized cancer 70. Glimelius, B., G. Birgegard, K. Hoffman, cancer receiving chemotherapy. Cancer
patients. Clin Nutr 2011;30:724–729. et al. Improved care of patients with 2011;117:1775–1782.
57. Chlebowski, R.T., G.L. Blackburn, I.M. small cell lung cancer. Nutritional and 84. Taylor, L.A., L. Pletschen, J. Arends, et al.
Buzzard, et al. Adherence to a dietary quality of life aspects. Acta Oncol Marine phospholipids--a promising new
fat intake reduction program in post- 1992;31:823–831. dietary approach to tumor-associated
menopausal women receiving therapy 71. Ollenschlager, G., W. Thomas, K. weight loss. Support Care Cancer
for early breast cancer. The Women’s Konkol, et al. Nutritional behaviour and 2010;18:159–170.
Intervention Nutrition Study. J Clin quality of life during oncological polyche- 85. Wigmore, S.J., M.D. Barber, J.A.
Oncol 1993;11:2072–2080. motherapy: Results of a prospective study Ross, et al. Effect of oral eicosapen-
58. Goncalves Dias, M.C., M. de Fatima on the efficacy of oral nutrition therapy in taenoic acid on weight loss in patients
Nunes Marucci, W. Nadalin, et al. patients with acute leukaemia. Eur J Clin with pancreatic cancer. Nutr Cancer
Nutritional intervention improves the Invest 1992;22:546–553. 2000;36:177–184.
caloric and proteic ingestion of head and 72. Ovesen, L., L. Allingstrup, J. Hannibal, 86. Wigmore, S.J., J.A. Ross, J.S. Falconer,
neck cancer patients under radiotherapy. et al. Effect of dietary counseling on et al. The effect of polyunsaturated fatty
Nutr Hosp 2005;20:320–325. food intake, body weight, response rate, acids on the progress of cachexia in
59. Isenring, E.A., J.D. Bauer, and S. Capra. survival, and quality of life in cancer patients with pancreatic cancer. Nutrition
Nutrition support using the American patients undergoing chemotherapy: A 1996;12:S27–S30.
Dietetic Association medical nutrition prospective, randomized study. J Clin 87. Ebhardt, H., S. Degen, V. Tadini, et al.
therapy protocol for radiation oncology Oncol 1993;11:2043–2049. Comprehensive proteome analysis of
patients improves dietary intake com- 73. Hamilton, K. Nutritional needs of the human skeletal muscle in cachexia and
pared with standard practice. J Am Diet adult oncology patient. In Oncology sarcopenia: A pilot study. J Cachexia
Assoc 2007;107:404–412. Nutrition for Clinical Practice, M. Leser, Sarcopenia Muscle 2017;8:567–582.
60. Isenring, E., S. Capra, J. Bauer, et al. et al., editors. Academy of Nutrition and 88. Grant, B. Nutritional effects of cancer
The impact of nutrition support on body Dietetics, Oncology Nutrition Dietetic treatment: Chemotherapy, biotherapy,
composition in cancer outpatients receiv- Practice Group, 2013, pp. 33–39. hormone therapy, and radiation therapy.
ing radiotherapy. Acta Diabetol 2003;40 74. National Academies of Sciences, In Oncology Nutrition for Clinical
Suppl 1:S162–164. Engineering, and Medicine. Examining Practice, E. Trujillo, editor. 2013.
61. Isenring, E., S. Capra, and J. Bauer. Acess to Nutrition Care in Outpatient 89. Hill, A., N. Kiss, B. Hodgson, et al.
Patient satisfaction is rated higher by Cancer Centers: Proceedings of a Associations between nutritional status,
radiation oncology outpatients receiv- Workshop. Washington, DC: The weight loss, radiotherapy treatment
ing nutrition intervention compared National Academies Press, 2016. toxicity and treatment outcomes in gas-
with usual care. J Hum Nutr Diet 75. Kathiresan, A.S., K.F. Brookfield, S.I. trointestinal cancer patients. Clin Nutr
2004;17:145–152. Schuman, et al. Malnutrition as a pre- 2011;30:92–98.
62. Isenring, E.A., S. Capra, and J.D. Bauer. dictor of poor postoperative outcomes 90. Clarke, T.C., L.I. Black, B.J. Stussman,
Nutrition intervention is beneficial in in gynecologic cancer patients. Arch et al. Trends in the Use of Complementary
oncology outpatients receiving radiother- Gynecol Obstet 2011;284:445–451. Health Approaches Among Adults: United
apy to the gastrointestinal or head and 76. Bozzetti, F. Nutritional support of States, 2002–2012. National Health
neck area. Br J Cancer 2004;91:447–452. the oncology patient. Crit Rev Oncol Statistics Reports; no 79. Hyattsville, MD:
63. Odelli, C., D. Burgess, L. Bateman, Hematol 2013;87:172–200. National Center for Health Statistics,
et al. Nutrition support improves patient 77. Fearon, K.C., M.F. Von Meyenfeldt, 2015.
outcomes, treatment tolerance and A.G. Moses, et al. Effect of a protein 91. Hann, D.M., F. Baker, C.S. Roberts,
admission characteristics in oesopha- and energy dense N-3 fatty acid enriched et al. Use of complementary therapies
geal cancer. Clin Oncol (R Coll Radiol) oral supplement on loss of weight among breast and prostate cancer patients
2005;17:639–645. and lean tissue in cancer cachexia: A during treatment: A multisite study.
64. Ravasco, P., I. Monteiro-Grillo, and randomised double blind trial. Gut Integr Cancer Ther 2005;4:294–300.
M.E. Camilo. Does nutrition influence 2003;52:1479–1486. 92. Cramer, H., S. Lange, P. Klose, et al.
quality of life in cancer patients undergo- 78. Sriram, K. and V.A. Lonchyna. Yoga for breast cancer patients and
ing radiotherapy? Radiother Oncol Micronutrient supplementation in survivors: A systematic review and meta-
2003;67:213–220. adult nutrition therapy: Practical analysis. BMC Cancer 2012;12:412.
452 Chapter 35 Nutrition Therapy for the Cancer Patient
93. Carlson, L.E. Mindfulness-based inter- 106. George, S.M., S.T. Mayne, M.F. 124. Allen, B., S. Bhatia, C. Anderson, et al.
ventions for coping with cancer. Ann N Y Leitzmann, et al. Dietary glycemic index, Ketogenic diets as an adjuvant cancer
Acad Sci 2016;1373:5–12. glycemic load, and risk of cancer: A therapy: History and potential mecha-
94. Bower, J.E. and D.M. Lamkin. prospective cohort study. Am J Epidemiol nism. Redox Biol 2014;2:963–970.
Inflammation and cancer-related fatigue: 2009;169:462–472. 125. Paoli, A., A. Rubini, J.S. Volek, et al.
Mechanisms, contributing factors, and 107. Oliveira, C.L., S. Mattingly, R. Beyond weight loss: A review of the
treatment implications. Brain Behav Schirrmacher, et al. A nutritional therapeutic uses of very-low-carbohy-
Immun 2013;30 Suppl:S48–57. perspective of ketogenic diet in cancer: drate (ketogenic) diets. Eur J Clin Nutr
95. Rossi, E., A. Vita, S. Baccetti, et al. A narrative review. J Acad Nutr Diet 2013;67:789–796.
Complementary and alternative medi- 2018;118:668–688. 126. Vergati, M., E. Krasniqi, G.D. Monte,
cine for cancer patients: Results of the 108. Warburg, O., F. Wind, and E. Negelein. et al. Ketogenic diet and other dietary
EPAAC survey on integrative oncology The Metabolism of tumors in the body. J intervention strategies in the treat-
centres in Europe. Support Care Cancer Gen Physiol 1927;8:519–530. ment of cancer. Curr Med Chem
2015;23:1795–1806. 109. Pelicano, H., D.S. Martin, R.H. Xu, et al. 2017;24:1170–1185.
96. Velicer, C.M. and C.M. Ulrich. Glycolysis inhibition for anticancer treat- 127. Schroeder, U., B. Himpe, R. Pries, et al.
Vitamin and mineral supplement use ment. Oncogene 2006;25:4633–4646. Decline of lactate in tumor tissue after
among US adults after cancer diagno- 110. Warburg, O. On the origin of cancer ketogenic diet: In vivo microdialysis study
sis: A systematic review. J Clin Oncol cells. Science 1956;123:309–314. in patients with head and neck cancer.
2008;26:665–673. 111. Klement, R.J. Beneficial effects of Nutr Cancer 2013;65:843–849.
97. O’Brien, S., M. Leser, and N. Ledesma. ketogenic diets for cancer patients: A 128. de Souza, R.J., J.F. Swain, L.J. Appel,
Diets, functional foods and dietary realist review with focus on evidence and et al. Alternatives for macronutrient
supplements for cancer prevention and confirmation. Med Oncol 2017;34:132. intake and chronic disease: A comparison
survival. In Integrative Oncology: The 112. Gatenby, R.A. and R.J. Gillies. Why do of the OmniHeart diets with popular
Role of Nutrition, M. Leser, et al., edi- cancers have high aerobic glycolysis? Nat diets and with dietary recommendations.
tors. Oncology Nutrition Dietetic Practice Rev Cancer 2004;4:891–899. Am J Clin Nutr 2008;88:1–11.
Group of the Academy of Nutrition and 113. Lv, M., X. Zhu, H. Wang, et al. Roles 129. Kossoff, E.H., B.A. Zupec-Kania,
Dietetics, 2013, pp. 61–78. of caloric restriction, ketogenic diet and P.E. Amark, et al. Optimal clinical
98. Abrams, D. Integrative oncology: The intermittent fasting during initiation, management of children receiving the
role of nutrition. In Oncology Nutrition progression and metastasis of cancer in ketogenic diet: Recommendations of
for Clinical Practice, M. Leser, et al., edi- animal models: A systematic review and the International Ketogenic Diet Study
tors. Oncology Nutrition Dietetic Practice meta-analysis. PLoS One 2014;9:e115147. Group. Epilepsia 2009;50:304–317.
Group of the Academy of Nutrition and 114. Michalsen, A. and C. Li. Fasting therapy 130. Slavin, J. Fiber and prebiotics:
Dietetics, 2013, pp. 53–60. for treating and preventing disease— Mechanisms and health benefits.
99. Rouleau, C.R., S.N. Garland, and L.E. Current state of evidence. Forsch Nutrients 2013;5:1417–1435.
Carlson. The impact of mindfulness- Komplementmed 2013;20:444–453. 131. Schoeler, N.E. and J.H. Cross. Ketogenic
based interventions on symptom burden, 115. Cava, E. and L. Fontana. Will calorie dietary therapies in adults with epi-
positive psychological outcomes, and restriction work in humans? Aging lepsy: A practical guide. Pract Neurol
biomarkers in cancer patients. Cancer (Albany NY) 2013;5:507–514. 2016;16:208–214.
Manage Res 2015;7:121–131. 116. Rous, P. The influence of diet on trans- 132. Klement, R.J. and U. Kammerer. Is there
100. PDQ Integrative Alternative planted and spontaneous mouse tumors. J a role for carbohydrate restriction in the
Complementary Therapies Editorial Exp Med 1914;20:433–451. treatment and prevention of cancer? Nutr
Board. Gerson therapy (PDQ(R)): 117. Lee, C., L. Raffaghello, S. Brandhorst, et al. Metab (Lond) 2011;8:75.
Health professional version. In PDQ Fasting cycles retard growth of tumors 133. Erickson, N., A. Boscheri, B. Linke, et al.
Cancer Information Summaries. and sensitize a range of cancer cell types to Systematic review: Isocaloric ketogenic
Bethesda, MD: National Cancer chemotherapy. Sci Transl Med 2012;4. dietary regimes for cancer patients. Med
Institute, National Institutes of 118. Bozzetti, F. and B. Zupec-Kania. Oncol 2017;34:72.
Health, 2002. Toward a cancer-specific diet. Clin Nutr 134. Elliott, L. Symptom management of can-
101. PDQ Integrative Alternative 2016;35:1188–1195. cer therapies. In Oncology Nutrition for
Complementary Therapies Editorial 119. O’Flanagan, C.H., L.A. Smith, S.B. Clinical Practice, M. Lesser, et al., edi-
Board. Gonzalez regimen (PDQ(R)): McDonell, et al. When less may be more: tors. Academy of Nutrition and Dietetics,
Health professional version. In PDQ Calorie restriction and response to cancer Oncology Nutrition Dietetics Practice
Cancer Information Summaries. therapy. BMC Med 2017;15:106. Grooup, 2013, pp. 115–121.
Bethesda, MD: National Cancer Institute, 120. Safdie, F.M., T. Dorff, D. Quinn, et al. 135. Katz, R. and M. Edelson. The Cancer
National Insitutes of Health, 2002. Fasting and cancer treatment in Fighting Kitchen. New York: Crown
102. Huebner, J., S. Marienfeld, C. humans: A case series report. Aging Publishing Group, 2009, p. 217.
Abbenhardt, et al. Counseling patients 2009;1:988–1007. 136. Kaur, S., E. Trujillo, and H. Seifried.
on cancer diets: A review of the literature 121. Harvie, M.N. and T. Howell. Could Dietary/supplemental interventions
and recommendations for clinical prac- intermittent energy restriction and and personal dietary preferences for
tice. Anticancer Res 2014;34:39–48. intermittent fasting reduce rates of cancer cancer. In Translational Toxicology
103. Ornish, D., G. Weidner, W.R. Fair, et al. in obese, overweight, and normal-weight and Therapeutics: Windows of
‑Intensive lifestyle changes may affect subjects? A summary of evidence. Adv Developmental Susceptibility in
the progression of prostate cancer. J Nutr 2016;7:690–705. Reproduction and Cancer, M. Waters
Urol 2005;174:1065–1069; discussion 122. Branco, A.F., A. Ferreira, R.F. Simoes, and C. Hughes, editors. Somerset, NJ:
1069–1070. et al. Ketogenic diets: From cancer to Wiley & Sons Inc., 2017.
104. Deng, T., C.J. Lyon, S. Bergin, et al. mitochondrial diseases and beyond. Eur J 137. Ebadi, M. and V.C. Mazurak. Evidence
Obesity, inflammation, and cancer. Annu Clin Invest 2016;46:285–298. and mechanisms of fat depletion in can-
Rev Pathol 2016;11:421–449. 123. Tisdale, M., R. Brennan, and K. Fearon. cer. Nutrients 2014;6:5280–5297.
105. Gallagher, E.J. and D. LeRoith. Insulin, Reduction of weight loss and tumour size 138. Fearon, K.C. Cancer cachexia and
insulin resistance, obesity, and cancer. in a cachexia model by a high fat diet. Br fat-muscle physiology. N Engl J Med
Curr Diab Rep 2010;10:93–100. J Cancer 1987;56:39–43. 2011;365:565–567.
VIII
PA RT
453
36
CHAPTER
36.2 MEASUREMENT OF ADIPOSITY than the other, making conclusions difficult. The absolute
differences between the Bod Pod, the commercially avail-
There are numerous accepted adiposity measurement able method of air-displacement plethysmography, and
systems used for directly and indirectly measuring total UWW were about 1% body fat and were not consistent in
body fat and for screening nutritional and health sta- any direction. 20 Studies have demonstrated high agreement
tus. Those measurements include hydrodensitometry, (0.91–0.94)20–22 between the Bod Pod, which uses a 2-C
dual-energy X-ray absorptiometry (DEXA), anthropom- model, and dual-energy X-ray absorptiometry for estimat-
etry, bioelectrical impedance analysis (BIA), computed ing body fat. In one study of 160 men the mean difference
tomography (CT), magnetic resonance imaging (MRI), in body fatness (2.2%) between methods was significant
and ultrasonic technique. Often more than one method and increased as body fat increased. 20 Advantages of the
of body fat measurement is used to assess body compo- air-displacement plethysmography technique include less
sition in order to address the clinical or research goal stress for the individual because there is no immersion in
appropriate for the individual and population. All meth- water, ease of operation, and low cost for testing.19,23 The
ods which estimate body fat are interpreted using the technique, however, may be a problem for those who are
same cut point for obesity (% body fat > 25.0 for men claustrophobic.
and >30.0 for women).6
36.2.2 Dual-Energy X-Ray
36.2.1 Densitometry Absorptiometry (DEXA)
Hydrodensitometry or underwater weighing (UWW)
DEXA was developed to assess body composition and
has long been considered one of the gold standards for
improve the accuracy over the 2-C model. It uses four
measuring body composition and estimating body fat.7 It
compartment (4-C) models examining regional and
is one of the classic two-compartment (2-C) models. In
whole-body composition, including body fat, lean soft tis-
the 2-C model, the body is divided into two components,
sue, water volume, and bone mineral mass.9,24 This tech-
fat mass and fat-free mass (water, protein, and mineral).
nique requires participants to remove all metal accessories
Therefore, by subtracting fat-free mass from body weight,
and lay in a supine position on a bed while the collimated
fat mass can be defined. The UWW applies Archimedes’
low-intensity X-ray source passes below the bed, synchro-
principle to determine total body volume or body density
nized with the movement of a detector array above the
by measuring the difference of the body’s weight in water
body. 25,26 DEXA is quick and easy to perform on most
and in air after correction for the volume of air in the
individuals, regardless of their disability, and often is used
respiratory system and in the gastrointestinal tract.8 In
as the gold standard reference method for body composi-
this model, it assumes that fat-free mass contents are fixed
tion analysis in clinical settings. 25 Limitations include its
for all ages.7, 9 Using Siri’s formula,10 fat mass can be deter-
expense and moderate validity. 24,27 DEXA’s accuracy is
mined, and percent body fat can be indirectly estimated
affected by varying fat distributions, but it is superior to
using Equation 36.1.
UWW weighing because it lacks sensitivity to a person’s
residual volume of unexpelled air or hydration status. 24,28
% body fat = (495 / body density ) − 450 (36.1) DEXA measures of central adiposity also correlate well
with measures of intra-abdominal fat measured by mag-
Although UWW has been widely accepted and frequently netic resonance imaging (MRI) in non-obese women
referred to as a gold standard for body density measure- (r = 0.88) and men (r = 0.87). 29
ment, there are several limitations associated with this
method. It is time and labor-consuming, requires special
training, and often creates individual discomfort.9,11,12 In 36.2.3 Anthropometric Measurements
addition, the fat-free mass component normally varies by
individuals due to gender, ethnicity, age, and/or physical 36.2.3.1 Body Mass index (BMI)
activity;13–15 hence, estimates must be corrected for varia- BMI is the most popular and practical indicator for over-
tion from these factors. Furthermore, this technique is weight and obesity classification because it is inexpensive,
particularly challenging with heterogeneous populations simple to calculate, and easy to gather weight and height
such as children, pregnant women, and elderly or disabled via measurements or self-report.30,31 Equation 36.2 indi-
individuals. cates the calculation of BMI.
An air-displacement plethysmography was developed
to be an alternative to hydrodensitometry. This method has
BMI = body weight ( kg ) / height ( m ) (36.2)
2
a similar principle to underwater weighing, but it deter-
mines body volume by measuring the changes of chamber
volume caused by placing an individual in a closed, air- Although BMI is the most frequently used measure of
filled chamber.11,16 Adequate corrections for temperature adiposity, it does not directly assess fat mass; instead, it
and gas composition, as well as lung volume, are required is a measure of weight controlling for height. BMI cor-
before calculating body volume. Several studies reported relates with percent body fat for the majority of the
the plethysmographic method demonstrated good agree- population. The use of BMI in adults allows for the cat-
ment with the UWW techniques.17–19 However, since both egorization of adiposity estimates independent of gender
of these methods are 2-C models neither is more accurate and age. Therefore, agencies such as the World Health
36.2 Measurement of Adiposity 457
non-central fat distribution with WHtR ≤ 0.5; classifica- measures use multiple body segments, its results are likely
tion for central fat distribution with WHtR > 0.5; and to be influenced by a number of factors such as hydration
central obesity with WHtR > 0.6.59,60 Prospective studies and fat fraction.76 In addition, as Lukaski and Scheltinga79
have shown WHtR is an effective indicator for abdominal noted, the trunk, which contains a large volume of con-
obesity and for predicting cardiovascular diseases com- ductors, only contributes a small amount to whole body
pared to BMI, WC, and WHR.61,62 resistance which might be a problem in overweight and
obese individuals.80,81 Therefore, segmental BIA has been
developed to minimize this effect. Segmental BIA focuses
36.2.3.5 Skinfolds on body segment measurements of resistance derived by
Skinfold thickness measurement has been used as a body applying either two additional electrodes on the wrist
composition measurement to estimate percentage of body and foot on the opposite side, the wrist, shoulder, upper
fat (%BF) since the 1970s.63 It is still considered the most iliac spine, and ankle, or the forearm, lower leg, and
practical method used to estimate body fat and fat-free trunk.82–84 Fat-free mass, fat mass, and total body water
mass. This technique is simple, quick, and inexpensive, are estimated using predictive equations including imped-
but does require training.64 According to Durnin and ance or resistance values.76 BIA in elderly Finnish women
Womersley63 skinfold thickness is measured to the nearest had an agreement with DEXA for fat-free mass of r = 0.7
0.1 mm on the right side of the body, at the biceps, triceps, and fat mass of r = 0.93 as compared to skinfold measures
subscapular, and supra-iliac areas, using a Harpenden with DEXA, which were r = 0.62 and 0.89, respectively.85
caliper (British Indicators Ltd, Luton, UK). The sum of Results by gender indicate BIA estimates of %BF in males
skinfold thickness at these four sites is used to predict had less error (6.8%) than those among females (8.8%)
%BF. The correlation between body fat measures from when compared to DEXA estimates of body fat.65 General
skinfolds and DEXA was r = 0.74 and for fat-free mass consensus suggests the equations used to calculate %BF
was r = 0.85 among 50 chronic kidney disease patients. 27 from BIA can explain some variation between studies.65,85
Studies have shown agreement between skinfold mea-
sures and DEXA measures of body fat decline as body fat
percentage increases, and the measures are lower among 36.2.5 Computed Tomography (CT)
females vs. males. Women consistently have a low agree- CT is an imaging technique widely used for body compo-
ment with the gold standard possibly due to their ratio sition measurement. This technique uses X-ray as a source
of subcutaneous and visceral fat and the difficulty of the to detect body fat distribution. During CT scanning the
skinfold measures to assess these parameters.65 X-ray rotates around the body or body segments cover-
ing 360˚ while the photodetectors send the information
regarding visceral and subcutaneous adipose tissue at
36.2.3.6 Sagitta Abdominal Diameter (SAD)
each degree of rotation to yield CT images.86,87 The main
SAD is measured at the highest point of the abdomen advantage of CT is the images can be used to identify and
with the subject lying flat in the supine position using a visualize body adipose tissue mass, providing highly accu-
sliding-beam abdominal caliper. Although SAD is less rate body fat estimation.88,89 Limitations of CT scanning
well-known and less likely to be used in epidemiological include high costs and the need for radiation for imag-
studies, it has been described as a strong predictor for car- ing, which cannot be applied outside clinical or laboratory
diovascular disease compared to WC.66–68 SAD also has settings.90
a strong correlation to visceral adipose tissue in various
ethnic groups69–71 and is strongly associated with insulin
resistance.72 The correlation between total abdominal 36.2.6 Ultrasound Technique (UT)
and abdominal visceral fat measures from SAD and a
CT image was r = 0.88 and r = 0.94 for men and women, Ultrasonography was proposed by Armellini and
respectively.73 colleagues91 to be an alternative method to CT for visceral
adiposity estimation. It is clinically accepted as the best
technique for quantifying intra-abdominal fat because it
directly measures fat thickness between the muscle and
36.2.4 Bioelectrical Impedance (BIA) the skin.91,92 The UT uses an ultrasound wave as a source
Compared to anthropometry methods, BIA is a more to determine the thickness of subcutaneous fat.93 The use
sophisticated technique to assess body fatness and %BF. of UT in intra-abdominal fat assessment was shown to be
It is non-invasive, simple to use, and has reproducible strongly correlated with %BF measured by DEXA 93 and
results. BIA is based on the principle that electrical current CT.90 UT is considered a non-invasive and accurate tech-
is more impeded through fat mass than fat-free mass or nique of body fat measurement and, also, is cheaper and
lean tissue (mostly water and electrolytes), resulting in dif- more convenient to use than CT.94
ferences in electrical resistance between fat mass and fat-
free mass.74,75 Two BIA measurements, whole body BIA
and segmental BIA, have been developed for body compo- 36.3 PREVALENCE OF OBESITY
sition assessment. For whole body BIA, surface electrodes
are placed on a hand and a foot, or foot-to-foot or hand- BMI remains the most popular proxy measurement for
to-hand, sending single or multiple frequencies measur- obesity surveillance and monitoring due to its afford-
ing whole body resistance.76–78 Because whole body BIA ability and simplicity. Despite its limitations, BMI allows
36.3 Prevalence of Obesity 459
for the standardized tracking and comparison of obesity groups experienced a statistically significant increase in
36
within and among populations. obesity prevalence from 1960 to 1991.97 Over a ten-year
period, 2005–2014, (Figures 36.1 and 36.2) the preva-
lence of obesity among both men and women increased,
though only significantly for women.100 In 2013–2014, all
36.3.1 U.S. Obesity Trends gender and ethnic groups had age-adjusted obesity preva-
The prevalence of obesity has been increasing for almost lence estimates exceeding 30%100.
100 years in the United States.95 Since the 1960s, the More men than women were considered overweight
National Health and Nutrition Examination Survey or obese, 73.9% vs. 63.7%, respectively, in 2009–2010.98
(NHANES) has taken an active role in tracking the Among men, obesity prevalence remained constant from
prevalence of obesity in the United States. The preva- 2009 to 2014, 35.5% to 35.2%, but increased for women,
lence of obesity remained fairly constant between 1960 36.3% to 40.5%.98,100 Obesity prevalence has increased
and 1980.96 However, in each interval from 1976 to 1980 significantly from 1999 to 2014 for females and males
and 1988 to 1994, the overall prevalence of adult obe- in all age groups.98–100,102 Minority populations generally
sity increased by 8 percentage points.97 Recent data sug- have higher rates of obesity compared to non-Hispanic
gests obesity trends plateaued with no significant increase whites.100,101 Additionally, gender differences in the preva-
in prevalence in the interval from 2003 to 2010,98 but lence of obesity often exist within ethnic groups; however,
increased again in the intervals from 2005–2006 and the direction and magnitude of the disparity depends on
2013–2014.99,100 The current prevalence of obesity is the population of interest.101 From 2009 to 2014 the prev-
more than double that of 1970 with 37.7 percent99 of the alence of obesity increased among non-Hispanic white
population considered obese and 68.8 percent considered women, 32.2% to 38.2%, but not among men, 36.2% to
overweight or obese.33,98,101 All gender, age, and ethnicity 34.7%.98,100 As well, non-Hispanic black and Hispanic
45
40
35
30
25
20
15
10 20-39 y
40-59 y
5
≥ 60 y
0
1999-2000 2001-2002 2003-2004 2005-2006 2007-2008 2009-2010 2011-2012 2013-2014
Figure 36.1 Trends in Male Prevalence (%) of Obesity (BMI > 30 kg/m2) by Age. Data from National Health and Nutrition
Examination Survey (NHANES).
50
45
40
35
30
25
20
15
20-39 y
10
40-59 y
5
≥ 60 y
0
1999-2000 2001-2002 2003-2004 2005-2006 2007-2008 2009-2010 2011-2012 2013-2014
Figure 36.2 Trends in Female Prevalence (%) of Obesity (BMI > 30 kg/m2) by Age. Data from National Health and Nutrition
Examination Survey (NHANES).
460 Chapter 36 Epidemiology of Adult Obesity
men had almost no change in prevalence, 38.8% to 38.0% participants indicate the mean worldwide BMI increased
and 37.0% to 37.9%, respectively.98,100 Similarly, non-His- 0.4 kg/m 2 per decade for men and 0.5 kg/m 2 for women
panic black women had little change in prevalence, 58.5% since 1980.106 Obesity has indeed reached the pandemic
to 57.2%, but obesity increased among Hispanic women level. It is no longer a crisis only for developed coun-
from 41.4% to 46.9%.98,100 tries as it is increasingly being seen in developing coun-
Significant variations exist in the geographic and demo- tries. 31,106–108 The onset of a rise in obesity began almost
graphic distribution of obesity. Geographically, the states of simultaneously in developed countries in the 1970s and
the southeastern and midwestern United States have the high- 1980s.31,106–108 Worldwide, the prevalence of obesity
est rates of obesity; although, the prevalence has increased among adults has increased by 27.5% from 1980 to 2013.
in every state over the last 30 years.103 Demographically, More women than men were obese in both developed
the distribution of obesity varies across gender, age, ethnic, and developing nations from 1980 to 2013. The rate of
and socioeconomic groups. Additionally, the prevalence of increase of overweight and obesity has plateaued in the
obesity is 50 percent higher among women of low socio- past decade, though prevalence remains high. In 1980,
economic status (SES) compared to women of higher SES, 28.8% of men and 29.8% of women were overweight or
whereas the prevalence of obesity is approximately equal obese and in 2013 those numbers had increased to 36.9%
among men regardless of SES.104 and 38.0%, respectively.1
Every age, sex, race, and smoking status group is expe- While comprehensive data are not available from
riencing the obesity epidemic, thus distributional changes in every country; evidence gathered by the Global Burden
these factors cannot fully explain the rapid changes seen in the of Disease Study supports the notion that the epidemic
last three decades. The increasing positive skew of the obesity has spread globally1. Figure 36.3 rank orders a selection
distribution is worrisome because it indicates the most obese of developed and developing countries by the prevalence
are even more obese than those in previous years.105 of obesity among males. Worldwide male prevalence
of obesity ranges from 1.3% in Cambodia to 52.4% in
Tonga. The females in Figure 36.4 are in the male ranked
order. Comparison of these two figures clearly indicates
36.3.2 Global Obesity Trends the gender discrepancies in prevalence of obesity within
Obesogenic environments currently exist in most countries.1 The range of obesity prevalence is wider
every country. Meta-analyses of data from 9.1 million among females than males ranging from 1.7% in East
Tonga
Samoa
Qatar
Kuwait
Kiriba
Bahrain
Saudi Arabia
New Zealand
Australia
UAE
Iceland
Egypt
USA
United Kingdom
Ireland
Chile
Canada
Oman
Mexico
Spain
France
Norway
Italy
Austria
Poland
Barbados
Russia
Fiji
Pakistan
South Africa
Venezuela
Nigeria
Brazil
Uzbekistan
Algeria
Panama
Angua and Barbuda
Congo
Thailand
Kenya
Japan
Ethiopia
China
India
East Timor
Cambodia
0 10 20 30 40 50 60
Figure 36.3 Adult Male Prevalence (%) of Obesity (BMI > 30 kg/m2). Data from the Global Burden of Disease Study 2013.
36.4 Potential Causes of Obesity 461
Tonga
Samoa
Qatar
Kuwait
Kiriba
Bahrain
36
Saudi Arabia
New Zealand
Australia
United Arab Emirates
Iceland
Egypt
United Kingdom
United States of…
Ireland
Chile
Canada
Oman
Mexico
Spain
France
Norway
Italy
Austria
Poland
Barbados
Russia
Fiji
Pakistan
South Africa
Venezuela
Nigeria
Brazil
Uzbekistan
Algeria
Panama
Angua and Barbuda
Congo
Thailand
Kenya
Japan
Ethiopia
China
India
East Timor
Cambodia
0 10 20 30 40 50 60 70 80
Figure 36.4 Adult Female Prevalence (%) of Obesity (BMI > 30 kg/m2). Data from the Global Burden of Disease Study 2013.
Timor to 69.1% in Samoa. Several large gender differ- epidemic is evident.111 However, the distal factors affect-
ences in the prevalence of obesity among both developed ing energy consumption, energy expenditure, and meta-
and developing countries are evident in Tonga, Samoa, bolic performance are complicated, and their roles are
Kuwait, Kiribati, Bahrain, Saudi Arabia, Oman, Mexico, not well understood. The influence of other risk factors
Barbados, Russia, Fiji, South Africa, and Algeria. Obesity for obesity has remained in the shadows of the two big
is most common in the low SES groups and in rural areas factors: over-consumption and inactivity. This section
in countries with a low gross domestic product. On the provides a brief overview of energy imbalance issues
other hand, the high socioeconomic groups in urban areas as well as numerous other risk factors for obesity and
have been the first to have increased obesity prevalence in describes how each could affect weight gain. Future
low- to middle-income countries.107 Evaluation of women obesity researchers will benefit from a systems approach
in 37 developing countries suggests lower SES women utilizing all identifiable risk factors to decipher the pan-
have had a faster increase in overweight than those among demic etiology.
higher SES women.109
36.4.1 Energy Imbalance
36.4 POTENTIAL CAUSES Weight change is associated with an imbalance between
OF OBESITY energy intake and energy expenditure. When energy
intake exceeds energy expenditure, the excess is stored as
Determining the causes of obesity is not a straightfor- fat, leading to increased adiposity. The effect of energy
ward issue. Many believe it is largely a problem of energy imbalance on body weight has been quantified and models
imbalance, and the solution is to reduce energy intake indicate gaining weight is indeed easier to do than los-
and increase physical activity. Body weight is determined ing weight.112,113 Simply reducing energy intake to tip the
by a combination of metabolic, genetic, environmental, balance in favor of weight loss may not result in steady
behavioral, cultural, and socioeconomic factors. 33 These weight loss because of physiologic adaptations of meta-
factors affect energy balance asymmetrically.107,110 The bolic rate and energy burn from physical activity.6,112,114,115
proximal role energy imbalance plays in the obesity This phenomenon is frequently seen in practice and helps
462 Chapter 36 Epidemiology of Adult Obesity
explain results from interventions to reduce obesity show- 1984 to 2015 indicates the prevalence of leisure time phys-
ing mixed effects and low sustainability.113 ical activity varies across states and has generally declined
Energy intake changes to support the rise in obesity are during the period in a majority of the states.120 In 2008,
attributed to portion size increases116 and increased avail- 25.4% of the U.S. population did not engage in any lei-
ability of inexpensive, energy-dense, nutrient-poor foods sure time physical activity.121 The prevalence of inactivity
and beverages. Portion sizes of many foods did increase reported in the BRFSS data has shown some states with
from 1977 to 1996.116 The portion sizes of salty snacks, over 30% of leisure time inactivity.120 Data to support the
desserts, soft drinks, fruit drinks, french fries, hamburg- impact of reductions in physical activity are scant; thus,
ers, cheeseburgers, and Mexican foods increased regard- the impact of changes in these behaviors is difficult to
less of whether they were consumed in the home or not. quantify. However, available data suggest this component
Increased portions resulted in energy increases ranging of energy balance has indeed declined, which could exac-
from 49 to 133 kcal per food.116 Between 1977 and 2006 erbate increased weight.95,107,112,113,115,120
changes in portion size accounted for an average 10 kcal
per day increase in energy intake.117
Energy density per eating occasion increased steadily 36.4.2 Genetics and Epigenetics
over the last 30 years according to nationally representa-
Although obesity is often considered a consequence of
tive data.117 Inexpensive, convenient, energy-dense food
prolonged energy imbalance, increasing evidence sug-
is readily available throughout the day for most people.
gests inherited factors contribute to obesity susceptibility.
Much of our food preparation is now done at a mass pro-
Enormous efforts have provided extensive information
duction level and not by individuals. The available food is
about the genetic component of obesity.122 Most nota-
inexpensive, highly processed, and contains added sugar
bly, variation of the fat mass and obesity-associated gene
(or high fructose corn syrup, fat, salt, and flavor enhanc-
(FTO) has been linked to increased energy intake and
ers enhancing the taste of food and encouraging con-
adiposity,123 with each additional copy of the risk allele
sumption.107,118 Examination of trends in energy intake
conferring an average increase in body mass of 1.5 kg. An
in U.S. adults from NHANES study periods 1971–1975
estimated 30–50% of the phenotypic variation in obesity
to 2009–2010 indicate there was a shift upward since the
can be explained by inherited genetic variation;124 how-
study period 1976–1980, peaking in 2003–2004.111,119
ever, obesity is a highly polygenic trait arising from the
However, in the subsequent years, energy intake has been
joint contributions of many genetic variants with relatively
decreasing, marking an important change with possible
small effects. To date, approximately 100 genetic loci in
ramifications to the U.S. obesity epidemic.119 The increases
genes implicated in insulin secretion, neuronal signaling,
in energy intake have not been as steep as the rise in obe-
lipid homeostasis, and adipogenesis have been associated
sity.111 An area of active investigation focuses on the mac-
with variation in body mass index, body fat percentage,
ronutrient mix of the energy component of diet. Weight
body fat mass, waist-to-hip ratio, or other indices of obe-
change can differ by the macronutrient content of the diet
sity.125–128 Collectively, these variants account for less
even if energy levels remain constant. The energy stored
than 5% of the total estimated heritability.129 Most of the
from equal amounts of protein, fat, and carbohydrate dif-
remaining heritability is likely attributed to genetic poly-
fers markedly. In addition, the body employs a complex
morphisms that explain less than 0.01% of the observed
regulation of fuel sources, which varies by macronutri-
variation in adiposity.130
ent. And, although short term energy restricted diets of
In addition to genetic sequence variation, epigenetic
all macronutrient combinations can lead to weight loss,
mechanisms, including DNA methylation and histone
little is known about the long-term efficacy of diets by
modification, may regulate important molecular pro-
macronutrient content.112,113,115 Changes over time in the
cesses involved in energy homeostasis. Animal models
energy sources of the diet may be an important aspect of
have illustrated that parental high fat diets can propa-
understanding the obesity epidemic.
gate obesity in offspring via epigenetic modification.131
Energy expenditure occurs from metabolism, ther-
Accordingly, large epidemiologic studies of adult popu-
moregulation, and daily physical activity. Metabolism
lations have identified obesity-associated DNA methyla-
and thermoregulation account for 60–70% of energy
tion at more than 200 cytosine-guanine dinucleotides
expenditure and daily physical activity among pre-
(CpG sites) linked to genes involved in inflammation,
dominately sedentary individuals about 20–30%.111 The
insulin signaling, and lipid metabolism.132–134 Although
energy expenditure concepts thought to influence the
many of the identified methylation profiles appear to be a
rise in obesity include reduced physical activity result-
consequence of obesity,133 methylation of CpG sites near
ing from the “built environment” and reduced physical
NFATC2IP, RNF145, CPT1A, Ly6G6E, and PRR5L
activity in schools. Technologic conveniences and labor-
genes has been prospectively associated with weight
saving devices continually make life easier diminishing the
gain.132,133
energy required for completion of previously labor-inten-
sive tasks. Sedentary jobs are prevalent and energy expen-
diture from transportation decreased. Television, videos,
and computers occupy increasingly more of peoples’ time.
36.4.3 Infections
Television viewing has increased steadily from 10.4 hours The etiologic role of infections in the development of
per week in 1965 to 15.1 hours in 1985, and 25.2 hours obesity is novel. There are possibly interactions between
per week in 1992–1994.111 Analysis of data from the the similar function of the immune system and adipose
Behavioral Risk Factor Surveillance System (BRFSS) from tissue. There are 10 microbes reported to cause obesity
36.6 Economic Costs of Obesity in the U.S. 463
osteoarthritis, etc.) and the indirect costs, which are studies, the authors found the economic burden of obesity
comprised of different indicators of lost productivity and for all costing methods in relative values averaged 1.39
include presenteeism, absenteeism, disability and worker’s and in absolute values averaged $49 billion. The database
compensation claims, and premature mortality. Multiple studies had the highest costs compared to the other two
systematic reviews have been conducted examining the costing methods. Grieve et al. conducted the only sys-
direct and indirect costs of obesity.176–178 The two main tematic review focusing solely on severe obesity.178 They
approaches to estimate economic costs are top-down and reviewed 15 studies (14 U.S. and 1 U.K.) examining the
bottom-up. Comparability and inference from these sys- economic burden of the severely obese, Class III and IV
tematic reviews are difficult because included studies had (BMI ≥ 40kg/m 2). They found that, compared with nor-
differences in the top-down and bottom-up approaches mal weight individuals, the severely obese had 1.5–3.9
and other methodological differences. times higher direct costs.
While the estimates vary based on how the study was
conducted and what obesity comorbid conditions were
included, it is clear that obesity results in significant indi-
36.6.1 Direct costs vidual and societal direct health care costs, diminish-
Obesity direct costs are defined typically as the expenses ing the resources of national economies and employers.
(both out-of-pocket and insurance-covered) related to Furthermore, as the obesity prevalence increases, the asso-
treatment or services provided by a healthcare provider ciated costs have and will continue to increase.
(e.g. physician, nurse practitioner, etc.) for office-based,
outpatient, inpatient hospital, or emergency room care
and pharmaceuticals or procedures.179 However, because 36.6.2 Indirect costs
obesity as a condition is usually not treated directly, the
direct costs of obesity usually are estimated based on the Indirect costs are those non-direct medical expenditures
costs associated with treating related comorbid condi- representing lost productivity in the workforce. They
tions, such as hypertension, diabetes, heart and other car- include presenteeism, absenteeism, disability and worker’s
diovascular-related diseases, osteoarthritis, sleep apnea, compensation claims, and premature mortality.179 No sys-
etc., all conditions for which obesity has been demon- tematic review has been conducted on only indirect costs
strated to substantially increase risk. Thus, the propor- of obesity, but reviews have looked at both direct and
tion for each disease condition that can be attributed to indirect costs of obesity.
obesity, as well as the prevalence of that condition and the Dee et al. reviewed five studies examining both the
medical expenditures associated with each condition, are direct and indirect costs of both overweight and obe-
used to estimate the direct costs of obesity with aggregate sity from 2001 to 2011.177 The authors concluded that
data.180,181 If individual data is available, then actual medi- increased BMI is associated with increased healthcare
cal expenditures for comorbid conditions can be compared costs, reduced productivity, and early mortality, and the
for obese and non-obese individuals.180,181 A number of risk of comorbidity is greatest in the obese population.
studies calculated the direct medical and health care costs They also found indirect costs were higher than direct
attributable to obesity, but their estimates vary based on costs and accounted for 54–59% of the estimated total
a number of factors including how many comorbid con- costs of obesity.
ditions were included that are linked to obesity.179 Thus, In the Grieve et al. systematic review focusing solely on
there is no definitive estimate of health care costs associ- those Class III and IV obese, the researchers found that,
ated with obesity. compared with normal weight individuals, the severely
However, the following review articles provide insight obese had 1.7–8.0 times higher indirect costs.178 They
into the economic burden of obesity. Tremmel and col- highlight Finkelstein,183 discussed below, who reported
leagues reviewed 23 studies across developed and devel- those in Class III obesity represent 3% of the employed
oping countries from January 2011 to September 2016.176 population but 21% of the costs due to obesity from
They concluded obesity was responsible for a large pro- absenteeism and medical expenditures.
portion of costs to the medical system and society, and if The Tremmel systematic review is the most recent
the prevalence of obesity continues on the projected trend, review to include indirect costs.176 The review included
the costs of obesity will increase. Unfortunately, the het- articles from 2011 to September 2016 with only two stud-
erogeneity across the studies hindered the comparability ies focusing solely on indirect costs. Obesity was reported
due to very different methodological approaches, inclu- to result in significant economic costs due to loss in pro-
sion of comorbidities, and populations. The authors high- ductivity. The review included six studies examining both
light two studies conducted in Germany as an example of direct and indirect costs. Overall, these studies showed
the rising costs of obesity. The societal cost of obesity in indirect costs were slightly higher than direct costs.
Germany increased from €9.8 million in 2002 to €12.2
million in 2008. The studies serve as an example of a valid
and structured way to examine the obesity trend given the 36.6.2.1 Presenteeism and Absenteeism
same methods and population were used to measure the Presenteeism is defined as time and productivity lost due
cost of obesity. to workers who are at work but are unable to perform
Bierl et al. conducted a review comparing the different at their full capacity as a result of obesity-related health
costing methods for obesity (database, patient-attribut- problems.179,184 Absenteeism refers to the loss of produc-
able fraction, and modelling).182 In an analysis of 16 U.S. tivity associated with missed work days or sick leave.179,184
36.6 Economic Costs of Obesity in the U.S. 465
A number of studies have examined the relationship obese, and Class II and III obese combined were estimated
36
between obesity and the primary indicators of lost pro- to be $74.41, $254.00, and $1,682.90 per firefighter,
ductivity in the U.S. workplace.184 For example, Tucker respectively.191
and Friedman185 found that obese workers were 70% more Finkelstein et al.192 evaluated the costs associated with
likely to experience absenteeism categorized as “high- presenteeism and absenteeism, both at the level of the indi-
level” (i.e. seven or more absences due to illness in the past vidual worker and then extrapolated to aggregate costs for
six months) than lean employees. Pronk and associates186 all workers in a sample of over 32,000 full-time workers.
found that obesity was associated with more work loss Average incremental annual costs per worker for absentee-
days and greater difficulty getting along with coworkers ism and presenteeism associated with obesity were esti-
while greater levels of physical activity and cardiorespira- mated to be $1,960 and $5,193 for obese male workers
tory fitness were associated with better work quality, job and $1,736 and $5,393 for obese female workers, respec-
performance, and greater work quantity and effort in a tively. Extrapolated to all workers, obesity was estimated
diverse sample of workers. to cost employers $12.8 and $30.0 billion for productivity
In addition to documenting an association between losses associated with absenteeism and presenteeism.192
obesity and losses in work productivity, several studies
estimated the economic losses to employers. In a very early
study on this topic, Robbins et al.187 found male military 36.6.2.2 Disability and Premature Mortality
service personnel who exceeded their maximum allowable Disability costs, for both short- and long-term, result from
weights accrued 17,117 lost work days over 12 months salary continuation benefits, insurance policies, and gov-
totaling $2.2 million annually, resulting in excess weight ernment programs (e.g. workers’ compensation claims)
attributable costs of approximately $2,809 per male ser- allowing employees time away from work due to illness
vice member. Ricci and Chee188 conducted a national or injury for periods of time longer than allowed for typi-
telephone survey of 7,472 adult workers in the U. S., cal sick leave.179,184 Premature mortality refers to the lower
estimating obesity-attributable costs for both presentee- projected life expectancy experienced by obese workers
ism and absenteeism combined totaling $42.3 billion (in when compared to non-obese individuals, leading to lost
2002 dollars). productivity during working years and increased life
In a large study of more than 50,000 American work- insurance premiums and payouts.179,184
ers in a variety of job classifications (e.g. professional, Several studies have focused on estimating costs asso-
managers, sales, service, office, and equipment and trans- ciated with disability and premature mortality. Disability
portation operators), workers who were obese were found studies usually focus on evaluating costs associated with
to experience a significantly higher probability of missing time away from work that involved disability claims or
any work when compared to workers in the normal weight payments while premature mortality studies estimate the
range.189 In addition, their absences were associated with value of years of life lost related to obesity.179,184 For exam-
greater incremental per worker costs when compared to ple, both Dor et al.179,184 and Trogdon et al.179,184 reviewed
normal weight employees, and their aggregated costs to several studies and concluded that obesity was consistently
employers were estimated to be nearly $4.3 billion (in a significant predictor of disability, and for studies in the
2004 dollars). United States, the costs associated with disability for obese
Gates and colleagues190 evaluated lost productivity individuals were substantial. For example, Soteriades
in a sample of manufacturing employees and found that et al.193 prospectively evaluated risk of any type of short-
workers who were Class II (35–39 kg/m 2) and III obese term or permanent disability in a group of male firefight-
reported more work limitations with regard to time ers over more than six years. They found that obesity
needed to complete work tasks and ability to perform predicted which firefighters would receive disability; each
physical job demands. They also found both Class I (20– BMI unit increase was associated with a 5% increase in
34.9 kg/m 2) and Class II and III obese workers had signifi- the likelihood that a firefighter would be disabled. Annual
cantly higher absenteeism than normal weight workers. costs of short-term disability for a number of studies were
The resultant loss in overall productivity was estimated to computed by Dor and colleagues,179,184 and they estimated
cost the employer $506.00 for presenteeism and $433.00 that, when compared to normal weight employees, obese
for absenteeism per each Class II and III obese worker employees’ disability costs were $349 per employee.
annually.190 Other investigators examined the relationship between
Poston et al.191 examined the relationship between obe- obesity and workers’ compensation claims and found that
sity and missed work days due to injury in a large group there was significant association between increasing BMI
of male, career firefighters in the midwestern U.S. Obese and number of claims.194 For example, Class I, II, and
firefighters missed between 2.7 and 5 times more (depend- III obese individuals had 8.8, 10.8, and 11.7 claims per
ing on obesity Class) the number of days due to injury 100 full time equivalents (FTEs) compared to only 5.8
when compared to normal weight firefighters, even after for normal weight workers, respectively. Not surprisingly,
adjustments for potential confounders. They also com- this greater number of claims resulted in greater medical
puted the economic costs of absenteeism for firefighters and indemnity (i.e. income replacement) claims costs. For
who were at increasing levels of overweight and obesity example, the total estimated medical and indemnity claims
compared to normal weight firefighters. When compared costs for obese workers totaled $94,125 and $117,107 per
to normal weight firefighters, the additional costs to fire 100 FTEs, respectively. The same claims costs for normal
departments because of the greater missed days of work weight workers were only $7,503 and $5,396; thus, the
after injury in firefighters who were overweight, Class I excess costs due to obesity were substantial.
466 Chapter 36 Epidemiology of Adult Obesity
Premature mortality, has been quantified by Fontaine implications of a continued rise in this obesity epidemic
et al. as years of life lost195 using national data, which are staggering. An immediate global effort is needed with
was then converted into cost estimates by Dor and col- systematic approaches involving governments, businesses,
leagues.179,184 For example, they estimated that obesity and individuals.
resulted in a total loss of income of $468,333 and $376,667
for non-Hispanic white men and women, respectively, and
that the gender difference is partly a function of the fact CLINICAL APPLICATIONS
that obese men have a lower life expectancy than obese
women. Other studies estimate that the costs of lost earn- • More than one method of body fat measurement
ings in the United States due to obesity to be approxi- will more accurately describe body composition.
mately $30 billion dollars.184 • All ethnic, gender, and age groups have an age
adjusted obesity prevalence exceeding 30%.
• Minority populations are at greater risk of obesity
36.7 SUMMARY compared to non-Hispanic whites.
• Those severely obese are even more obese than those
The prevalence of obesity is alarmingly high and is in previous years.
described as a global pandemic107 with an uncertain tra- • There is no singular cause of obesity—it is a multi-
jectory. The drivers of the proposed causal factors are factorial health issue.
complicated; thus, proven, successful interventions to curb • Obesity is positively associated with mortality and
this epidemic are not in place. The economic and health increases risk of multiple comorbidities.
REFERENCES
1. Ng, M., Fleming, T., Robinson, M., et estimating percent body fat. Journal of Rehabilitation Clinics of North America
al. 2014. Global, regional, and national Applied Physiology (Bethesda, Md.: 9(1):127–143.
prevalence of overweight and obesity in 1985) 88(4):1175–1180. 18. Holmes, J. C., Gibson, A. L., Cremades,
children and adults during 1980–2013: A 10. Siri, W. E. 1961. Body composition from J. G., et al. 2011. Body-density mea-
systematic analysis for the global burden fluid spaces and density: Analysis of surement in children: The BOD POD
of disease study 2013. Lancet (London, methods. In Techniques for Measuring versus hydrodensitometry. International
England) 384(9945):766–781. Body Composition, eds. J. Brozek, A. Journal of Sport Nutrition and Exercise
2. Anonymous. 1998. Clinical guidelines Henschel, 223–244. Washington, D.C.: Metabolism 21(3):240–247.
on the identification, evaluation, and National Academy of Sciences. 19. Fields, D. A., Goran, M. I., McCrory, M.
treatment of overweight and obesity in 11. Dempster, P., Aitkens, S. 1995. A new air A. 2002. Body-composition assessment
adults—The evidence report. national displacement method for the determi- via air-displacement plethysmography
institutes of health. Obesity Research nation of human body composition. in adults and children: A review. The
6(Suppl 2):51S–209S. Medicine and Science in Sports and American Journal of Clinical Nutrition
3. Allison, D. B., Fontaine, K. R., Manson, Exercise 27(12):1692–1697. 75(3):453–467.
J. E., et al. 1999. Annual deaths attrib- 12. Williams, C. A., Bale, P. 1998. Bias and 20. Ball, S. D., Altena, T. S. 2004.
utable to obesity in the united states. limits of agreement between hydroden- Comparison of the bod pod and
The Journal of the American Medical sitometry, bioelectrical impedance and dual energy x-ray absorptiometry
Association 282(16):1530–1538. skinfold calipers measures of percentage in men. Physiological Measurement
4. Flegal, K. M., Graubard, B. I., body fat. European Journal of Applied 25(3):671–678.
Williamson, D. F., et al. 2005. Excess Physiology and Occupational Physiology 21. Maddalozzo, G. F., Cardinal, B. J., Snow,
deaths associated with underweight, 77(3):271–277. C. A. 2002. Concurrent validity of the
overweight, and obesity. The Journal 13. Cote, K. D., Adams, W. C. 1993. Effect BOD POD and dual energy x-ray absorp-
of the American Medical Association of bone density on body composition tiometry techniques for assessing body
293(15):1861–1867. estimates in young adult black and white composition in young women. Journal
5. Ellulu, M., Abed, Y., Rahmat, A., et al. women. Medicine and Science in Sports of the American Dietetic Association
2014. Epidemiology of obesity in develop- 25:290–296. 102(11):1677–1679.
ing countries: Challenges and prevention. 14. Deurenberg, P., Weststrate, J. A., van 22. Hames, K. C., Anthony, S. J., Thornton,
Global Epidemic Obesity 2(1):2. doi: der Kooy, K. 1989. Is an adaptation of J. C., et al. 2014. Body composition
10.7243/2052-5966-2-2. siri’s formula for the calculation of body analysis by air displacement plethys-
6. National Institute of Health, National fat percentage from body density in the mography in normal weight to extremely
Heart, Lung, and Blood Institute, Joint elderly necessary? European Journal of obese adults. Obesity (Silver Spring, Md.)
National Committee on Prevention, Clinical Nutrition 43(8):559–567. 22(4):1078–1084.
Detection, Evaluation, and Treatment 15. Schutz, Y., Kyle, U. U., Pichard, C. 23. Lowry, D. W., Tomiyama, A. J. 2015.
of High Blood Pressure. 2000. North 2002. Fat-free mass index and fat Air displacement plethysmography
American Association for the Study mass index percentiles in caucasians versus dual-energy x-ray absorptiometry
of Obesity. The Practical Guide: aged 18–98 y. International Journal in underweight, normal-weight, and
Identification, Evaluation, and of Obesity and Related Metabolic overweight/obese individuals. PloS One
Treatment of Overweight and Obesity in Disorders: Journal of the International 10(1):e0115086.
Adults. Bethesda, MD: NIH. Association for the Study of Obesity 24. Van Der Ploeg, G. E., Withers, R. T.,
7. Ellis, K. J. 2000. Human body composi- 26(7):953–960. Laforgia, J. 2003. Percent body fat
tion: In vivo methods. Physiological 16. McCrory, M. A., Gomez, T. D., Bernauer, via DEXA: Comparison with a four-
Reviews 80:649–680. E. M., et al. 1995. Evaluation of a new air compartment model. Journal of Applied
8. Behnke, A. R., Feen, B. G., Welham, W. displacement plethysmograph for measur- Physiology (Bethesda, Md.: 1985)
C. 1942. Specific gravity of healthy man. ing human body composition. Medicine 94(2):499–506.
The Journal of the American Medical and Science in Sports and Exercise 25. Kelly, T. L., Wilson, K. E., Heymsfield,
Association 118:498–501. 27(12):1686–1691. S. B. 2009. Dual energy X-ray absorp-
9. van der Ploeg, G. E., Gunn, S. M., 17. McCrory, M. A., Wright, N. C., Kilmer, tiometry body composition reference
Withers, R. T., et al. 2000. Comparison D. D. 1998. Nutritional aspects of neuro- values from NHANES. PloS One
of two hydrodensitometric methods for muscular diseases. Physical Medicine and 4(9):e7038.
References 467
26. Kelly, T. L., Berger, N., Richardson, T. 39. Poston, W. S. C., Foreyt, J. P. 2002. Body obesity: An update. Physiological
L. 1998. DXA body composition: Theory mass index: Uses and limitations. Journal Reviews 93(1):359–404.
and practice. Applied Radiation and
Isotopes 49(5/6):511–513.
27. Avesani, C. M., Draibe, S. A., Kamimura,
of Strength and Conditioning Research
24:15–17.
40. Witt, K. A., Bush, E. A. 2005. College
52. International Diabetes Federation (IDF).
2006. The IDF Consensus Worldwide
Definition of the Metabolic Syndrome
36
M. A., et al. 2004. Assessment of athletes with an elevated body mass [cited July 1, 2011]. Available from http:
body composition by dual energy index often have a high upper arm //www.idf.org/webdata /docs /IDF_ Meta
X-ray absorptiometry, skinfold thick- muscle area, but not elevated triceps _def_ fi nal.pdf.
ness and creatinine kinetics in chronic and subscapular skinfolds. Journal 53. Lohman, T., Roache, A. F., Martorell, R.
kidney disease patients. Nephrology, of the American Dietetic Association 1988. Anthropometric Standardization
Dialysis, Transplantation: Official 105(4):599–602. Reference Manual. Champaign, IL:
Publication of the European Dialysis and 41. Rothman, K. J. 2008. BMI-related Human Kinetics.
Transplant Association - European Renal errors in the measurement of obesity. 54. Expert Panel on Detection, Evaluation,
Association 19:2289–2295. International Journal of Obesity (2005) and Treatment of High Blood Cholesterol
28. Nord RH, Rayne RK. 1995. Dual-energy 32(Suppl 3):S56–S59. in Adults (Adult Treatment Panel III).
X-ray absorptiometry vs underwater 42. Heymsfield, S. B., Peterson, C. M., 2001. Expert panel on detection, evalua-
weighing comparison of strengths and Thomas, D. M., et al. 2016. Why are tion, and treatment of high cholesterol in
weaknesses. Asia Pacific Journal of there race/ethnic differences in adult adults (2001) executive summary of the
Clinical Nutrition 4:173–175. body mass index-adiposity relationships? third report of the national cholesterol
29. Kamel, E. G., McNeill, G., Han, T. S., A quantitative critical review. Obesity education program (NCEP). Journal
et al. 1999. Measurement of abdominal Reviews: An Official Journal of the of the American Medical Association
fat by magnetic resonance imaging, International Association for the Study 285:2486–2497.
dual-energy X-ray absorptiometry of Obesity 17(3):262–275. 55. National Institutes of Health, National
and anthropometry in non-obese men 43. Aloia, J. F., Vaswani, A., Mikhail, Heart Lung & Blood Institute. 1998.
and women. International Journal M., et al. 1999. Body composition by Clinical Guidelines on the Identification,
of Obesity and Related Metabolic dual-energy X-ray absorptiometry in Evaluation, and Treatment of
Disorders: Journal of the International black compared with white women. Overweight and Obesity: The Evidence
Association for the Study of Obesity Osteoporosis International: A Journal Report. Washington, DC: U.S.
23(7):686–692. Established as Result of Cooperation Government Press.
30. World Health Organization. 1995. between the European Foundation 56. Flegal, K. M., Shepherd, J. A., Looker, A.
Physical Status: The Use and for Osteoporosis and the National C., et al. 2009. Comparisons of percent-
Interpretation of Anthropometry. Report Osteoporosis Foundation of the USA age body fat, body mass index, waist
of a WHO Consultation. Geneva: World 10(2):114–119. circumference, and waist-stature ratio in
Health Organization, 894. 44. Rush, E. C., Goedecke, J. H., Jennings, adults. The American Journal of Clinical
31. World Health Organization. 2000. C., et al. 2007. BMI, fat and muscle Nutrition 89(2):500–508.
Obesity: Preventing and managing the differences in urban women of five 57. Heitmann, B. L., Frederiksen, P.,
global epidemic. Report of a WHO ethnicities from two countries. Lissner, L. 2004. Hip circumference and
consultation. World Health Organization International Journal of Obesity (2005) cardiovascular morbidity and mortality
Technical Report Series 894: i–xii, 31(8):1232–1239. in men and women. Obesity Research
1–253. 45. Calle, E. E., Thun, M. J., Petrelli, J. M., 12(3):482–487.
32. WHO Consultation on Obesity. 1997. et al. 1999. Body-mass index and mortal- 58. de Koning, L., Merchant, A. T., Pogue,
Obesity: Preventing and Managing the ity in a prospective cohort of U.S. adults. J., et al. 2007. Waist circumference and
Global Epidemic. Geneva: World Health The New England Journal of Medicine waist-to-hip ratio as predictors of cardio-
Organization. 341(15):1097–1105. vascular events: Meta-regression analysis
33. Office of the Surgeon General (US), 46. Ashwell, M., Cole, T. J., Dixon, A. K. of prospective studies. European Heart
Office of Disease Prevention and Health 1996. Ratio of waist circumference Journal 28(7):850–856.
Promotion (US), Centers for Disease to hip is a strong predictor of intra- 59. Ashwell, M. 2009. Obesity risk:
Control and Prevention (US), et al. 2001. abdominal fat. British Medical Journal Importance of the waist-to-height
The Surgeon General’s Call to Action 313:559–560. ratio. Nursing Standard (Royal College
to Prevent & Decrease Overweight 47. Han, T. S., Lean, M. E. 1998. Self- of Nursing (Great Britain): 1987)
and Obesity. Rockville, MD: National reported waist circumference compared 23(41):49–54; quiz 55.
Institute of Health. with the ‘waist watcher’ tape-measure to 60. Ashwell, M., Gibson, S. 2009. Waist
34. World Health Organization. 2011. identify individuals at increased health to height ratio is a simple and effective
Obesity and Overweight. Geneva, risk through intra-abdominal fat accumu- obesity screening tool for cardiovascular
Switzerland: World Health Organization lation. The British Journal of Nutrition risk factors: Analysis of data from the
[database online]. Available from http:// 80(1):81–88. british national diet and nutrition survey
www.who.i nt/mediacentre /factsheets /fs3 48. Turcato, E., Bosello, O., Di Francesco, of adults aged 19–64 years. Obesity Facts
11/en/index.html. V., et al. 2000. Waist circumference and 2(2):97–103.
35. Cole, T. J., Bellizzi, M. C., Flegal, K. abdominal sagittal diameter as sur- 61. Ashwell, M., Gunn, P., Gibson, S.
M., et al. 2000. Establishing a stan- rogates of body fat distribution in the 2012. Waist-to-height ratio is a better
dard definition for child overweight elderly: Their relation with cardiovas- screening tool than waist circumfer-
and obesity worldwide: International cular risk factors. International Journal ence and BMI for adult cardiometabolic
survey. BMJ (Clinical Research Ed.) of Obesity and Related Metabolic risk factors: Systematic review and
320(7244):1240–1243. Disorders: Journal of the International meta-analysis. Obesity Reviews: An
36. WHO Expert Consultation. 2004. Association for the Study of Obesity Official Journal of the International
Appropriate body-mass index for asian 24(8):1005–1010. Association for the Study of Obesity
populations and its implications for 49. Smith, S. C., Jr, Haslam, D. 2007. 13(3):275–286.
policy and intervention strategies. Lancet Abdominal obesity, waist circumference 62. Browning, L. M., Hsieh, S. D., Ashwell,
363(9403):157–163. and cardio-metabolic risk: Awareness M. 2010. A systematic review of waist-
37. Gallagher, D., Heymsfield, S. B., Heo, among primary care physicians, the to-height ratio as a screening tool for the
M., et al. 2000. Healthy percentage body general population and patients at prediction of cardiovascular disease and
fat ranges: An approach for developing risk—The shape of the nations survey. diabetes: 0.5 could be a suitable global
guidelines based on body mass index. The Current Medical Research and Opinion boundary value. Nutrition Research
American Journal of Clinical Nutrition 23(1):29–47. Reviews 23(2):247–269.
72(3):694–701. 50. Hu, F. B. 2007. Obesity and mortal- 63. Durnin, J. V., Womersley, J. 1974. Body
38. Prentice, A. M., Jebb, S. A. 2001. Beyond ity: Watch your waist, not just your fat assessed from total body density and
body mass index. Obesity Reviews: An weight. Archives of Internal Medicine its estimation from skinfold thickness:
Official Journal of the International 167:875–876. Measurements on 481 men and women
Association for the Study of Obesity 51. Tchernof, A., Despres, J. P. 2013. aged from 16 to 72 years. The British
2(3):141–147. Pathophysiology of human visceral Journal of Nutrition 32(1):77–97.
468 Chapter 36 Epidemiology of Adult Obesity
64. Moreno, L. A., Joyanes, M., Mesana, M. 77. Jebb, S. A., Cole, T. J., Doman, D., et 90. Ribeiro-Filho, F. F., Faria, A. N.,
I., et al. 2003. Harmonization of anthro- al. 2000. Evaluation of the novel tanita Azjen, S., et al. 2003. Methods of
pometric measurements for a multi center body-fat analyser to measure body estimation of visceral fat: Advantages
nutrition survey I Spanish adolescent. composition by comparison with a four- of ultrasonography. Obesity Research
Nutrition 19:481–486. compartment model. British Journal of 11(12):1488–1494.
65. Wattanapenpaiboon, N., Lukito, W., Nutrition 83:115–122. 91. Armellini, F., Zamboni, M., Rigo, L., et
Strauss, B. J., et al. 1998. Agreement of 78. Utter, A. C., Nieman, D. C., Ward, al. 1990. The contribution of sonography
skinfold measurement and bioelectri- A. N., et al. 1999. Use of the leg-to- to the measurement of intra-abdominal
cal impedance analysis (BIA) methods leg bioelectrical impedance method in fat. Journal of Clinical Ultrasound
with dual energy X-ray absorptiometry assessing body-composition change in 18(7):563–567.
(DEXA) in estimating total body fat in obese women. The American Journal of 92. Abe, T., Kawakami, Y., Sugita, M.,
anglo-celtic Australians. International Clinical Nutrition 69(4):603–607. et al. 1995. Use of B-mod ultrasound
Journal of Obesity and Related 79. Lukaski, H. C., Scheltinga, M. R. M. for visceral fat mass evaluation:
Metabolic Disorders: Journal of the 1994. Improved sensitivity of the tetrapo- Comparisons with magnetic resonance
International Association for the Study lar bioelectrical impedance method to imaging. Applied Human Science:
of Obesity 22(9):854–860. assess fluid status and body composition: Journal of Physiological Anthropology
66. Kahn, H. S., Austin, H., Williamson, D. Use of proximal electrode placement. Age 14:133–139.
F., et al. 1996. Simple anthropometric and Nutrition 5:123–129. 93. Pineau, J. C., Lalys, L., Bocquet, M.,
indices associated with ischemic heart 80. Deurenberg, P. 1996. Limitations of the et al. 2010. Ultrasound measurement
disease. Journal of Clinical Epidemiology bioelectrical impedance method for the of total body fat in obese adolescents.
49(9):1017–1024. assessment of body fat in severe obesity. Annals of Nutrition and Metabolism
67. Kahn, H. S., Simoes, E. J., Koponen, The American Journal of Clinical 56(1):36–44.
M., et al. 1996. The abdominal diameter Nutrition 64(3 Suppl):449S–452S. 94. Pineau, J. C., Guihard-Costa, A. M.,
index and sudden coronary death in men. 81. Waki, M., Kral, J. G., Mazariegos, M., Bocquet, M. 2007. Validation of ultra-
The American Journal of Cardiology et al. 1991. Relative expansion of extra sound techniques applied to body fat
78(8):961–964. cellular water in obese versus nonobese measurement. A comparison between
68. Riserus, U., Arnlov, J., Brismar, K., et women. American Journal of Physiology. ultrasound techniques, air displacement
al. 2004. Sagittal abdominal diameter Endocrinology and Metabolism plethysmography and bioelectrical imped-
is a strong anthropometric marker of 261:E199–E203. ance vs. dual-energy X-ray absorptiome-
insulin resistance and hyperproinsu- 82. Organ, L. W., Bradham, G. B., Gore, try. Annals of Nutrition and Metabolism
linemia in obese men. Diabetes Care D. T., et al. 1994. Segmental bioelectri- 51(5):421–427.
27(8):2041–2046. cal impedance analysis: Theory and 95. Heimburger, D. C., Allison, D. B.,
69. Bosy-Westphal, A., Booke, C. A., application of a new technique. Journal Goran, M. I., et al. 2003. A festschrift for
Blocker, T., et al. 2010. Measurement of Applied Physiology (Bethesda, Md.: Roland L. weinsier: Nutrition scientist,
site for waist circumference affects its 1985) 77(1):98–112. educator, and clinician. Obesity Research
accuracy as an index of visceral and 83. Zhu, F., Schneditz, D., Levin, N. W. 11(10):1246–1262.
abdominal subcutaneous fat in a cauca- 1999. Sum of segmental bioimpedence 96. Flegal, K. M., Carroll, M. D.,
sian population. The Journal of Nutrition analysis during ultrafiltration and hemo- Kuczmarski, R. J., et al. 1998.
140(5):954–961. dialysis reduces sensitivity to changes Overweight and obesity in the united
70. Vasques, A. C., Rosado, L. E., Rosado, in body position. Kidney International states: Prevalence and trends, 1960–1994.
G. P., et al. 2009. Different measure- 56:692–699. International Journal of Obesity and
ments of the sagittal abdominal diameter 84. Scheltinga, M. R., Jacobs, D. O., Related Metabolic Disorders: Journal
and waist perimeter in the prediction Kimbrough, T. D., et al. 1992. Identifying of the International Association for the
of HOMA-IR. Arquivos Brasileiros De body fluid distribution by measuring elec- Study of Obesity 22(1):39–47.
Cardiologia 93(5):511–518. trical impedance. The Journal of Trauma 97. Kuczmarski, R. J., Flegal, K. M.,
71. Yim, J. Y., Kim, D., Lim, S. H., et al. 33(5):665–670. Campbell, S. M., et al. 1994. Increasing
2010. Sagittal abdominal diameter is 85. Haapala, I., Hirvonen, A., Niskanen, L., prevalence of overweight among US
a strong anthropometric measure of et al. 2002. Anthropometry, bioelectri- adults. the national health and nutri-
visceral adipose tissue in the Asian cal impedance and dual-energy X-ray tion examination surveys, 1960 to 1991.
general population. Diabetes Care absorptiometry in the assessment of body The Journal of the American Medical
33(12):2665–2670. composition in elderly Finnish women. Association 272(3):205–211.
72. Montague, C. T., O’Rahilly, S. 2000. Clinical Physiology and Functional 98. Flegal, K. M., Carroll, M. D., Kit, B. K.,
The perils of portliness: Causes and con- Imaging 22(6):383–391. et al. 2012. Prevalence of obesity and
sequences of visceral adiposity. Diabetes 86. Heymsfield, S. B., Gallagher, D., Visser, trends in the distribution of body mass
49(6):883–888. M., et al. 1995. Measurement of skeletal index among US adults, 1999–2010.
73. Clasey, J. L., Bouchard, C., Teates, C. D., muscle: Laboratory and epidemiological The Journal of the American Medical
et al. 1999. The use of anthropometric methods. The Journals of Gerontology. Association 307(5):491–497.
and dual-energy X-ray absorptiom- Series A, Biological Sciences and Medical 99. Ogden, C. L., Carroll, M. D., Fryar, C.
etry (DXA) measures to estimate total Sciences 50(Special issue):23–29. D., et al. 2015. Prevalence of obe-
abdominal and abdominal visceral fat 87. Rogalla, P., Meiri, N., Hoksch, B., et sity among adults and youth: United
in men and women. Obesity Research al. 1998. Low-dose spiral computer states, 2011–2014. NCHS Data Brief
7(3):256–264. tomography for measuring abdominal (219):1–8.
74. Lukaski, H. C., Bolonchuk, W. W., Hall, fat volume and distribution in a clinical 100. Flegal, K. M., Kruszon-Moran, D.,
C. B., et al. 1986. Validation of tetrapolar setting. European Journal of Clinical Carroll, M. D., et al. 2016. Trends in
bioelectrical impedance method to assess Nutrition 52:597–602. obesity among adults in the united
human body composition. Journal of 88. Cortet, B., Bourel, P., Dubois, P., et al. states, 2005 to 2014. The Journal of
Applied Physiology (Bethesda, Md.: 1998. CT scan texture analysis of the the American Medical Association
1985) 60(4):1327–1332. distal radius: Influence of age and meno- 315(21):2284–2291.
75. Nakadomo, F., Tanaka, K., Hazama, T., pausal status. Revue Du Rhumatisme 101. Flegal, K. M., Carroll, M. D., Ogden, C.
et al. 1990. Validation of body composi- (English Edition) 65(2):109–118. L., et al. 2010. Prevalence and trends in
tion assessed by bioelectrical impedance 89. Link, T. M., Majumdar, S., Lin, J. C., obesity among US adults, 1999–2008.
analysis. Japanese Journal of Applied et al. 1998. A comparative study of tra- The Journal of the American Medical
Physiology 20:321–330. becular bone properties in the spine and Association 303(3):235–241.
76. Kyle, U. G., Bosaeus, I., De Lorenzo, A. femur using high resolution MRI and CT. 102. Ogden, C. L., Carroll, M. D., Kit, B.
D., et al. 2004. Bioelectrical impedance Journal of Bone and Mineral Research: K., et al. 2014. Prevalence of childhood
analysis—Part I: Review of principles and The Official Journal of the American and adult obesity in the united states,
methods. Clinical Nutrition (Edinburgh, Society for Bone and Mineral Research 2011–2012. The Journal of the American
Scotland) 23(5):1226–1243. 13(1):122–132. Medical Association 311(8):806–814.
References 469
103. Mokdad, A. H., Serdula, M. K., Dietz, W. 119. Ford, E. S., Dietz, W. H. 2013. Trends in 134. Aslibekyan, S., Demerath, E. W.,
H., et al. 1999. The spread of the obesity energy intake among adults in the united Mendelson, M., et al. 2015. Epigenome-
epidemic in the united states, 1991–1998.
The Journal of the American Medical
Association 282(16):1519–1522.
states: Findings from NHANES. The
American Journal of Clinical Nutrition
97(4):848–853.
wide study identifies novel methylation
loci associated with body mass index
and waist circumference. Obesity (Silver
36
104. Department of Health and Human 120. An, R., Xiang, X., Yang, Y., et al. 2016. Spring, Md.) 23(7):1493–1501.
Services. 2000. Healthy People 2010: Mapping the prevalence of physical 135. McAllister, E. J., Dhurandhar, N. V.,
Understanding and Improving Health. inactivity in U.S. states, 1984–2015. PloS Keith, S. W., et al. 2009. Ten putative
Washington, DC: HHS. One 11(12):e0168175. contributors to the obesity epidemic.
105. Keith, S. W., Redden, D. T., Katzmarzyk, 121. Centers for Disease Control and Critical Reviews in Food Science and
P. T., et al. 2006. Putative contribu- Prevention (CDC). 2010. U.S. Physical Nutrition 49(10):868–913.
tors to the secular increase in obesity: Activity Statistics. CDC, Centers for 136. Pasarica, M., Shin, A. C., Yu, M., et al.
Exploring the roads less traveled. Disease Control and Prevention [cited 2006. Human adenovirus 36 induces
International Journal of Obesity (2005) October 24 2011] [database online]. adiposity, increases insulin sensitivity,
30(11):1585–1594. Available from http://www.cdc.gov/n and alters hypothalamic monoamines
106. Finucane, M. M., Stevens, G. A., Cowan, ccdphp/dnpa /physical/stats. in rats. Obesity (Silver Spring, Md.)
M. J., et al. 2011. National, regional, 122. Rankinen, T., Zuberi, A., Chagnon, Y. 14(11):1905–1913.
and global trends in body-mass index C., et al. 2006. The human obesity gene 137. Rogers, P. M., Fusinski, K. A., Rathod,
since 1980: Systematic analysis of health map: The 2005 update. Obesity (Silver M. A., et al. 2008. Human adenovirus
examination surveys and epidemio- Spring, Md.) 14(4):529–644. ad-36 induces adipogenesis via its E4
logical studies with 960 country-years 123. Speakman, J. R., Rance, K. A., orf-1 gene. International Journal of
and 9.1 million participants. Lancet Johnstone, A. M. 2008. Polymorphisms Obesity (2005) 32(3):397–406.
377(9765):557–567. of the FTO gene are associated with 138. Vangipuram, S. D., Sheele, J., Atkinson,
107. Swinburn, B. A., Sacks, G., Hall, K. D., variation in energy intake, but not energy R. L., et al. 2004. A human adenovirus
et al. 2011. The global obesity pandemic: expenditure. Obesity (Silver Spring, Md.) enhances preadipocyte differentiation.
Shaped by global drivers and local envi- 16(8):1961–1965. Obesity Research 12(5):770–777.
ronments. Lancet 378(9793):804–814. 124. Frayling, T. M., Timpson, N. J., Weedon, 139. Vangipuram, S. D., Yu, M., Tian, J., et al.
108. International Association for the Study M. N., et al. 2007. A common variant 2007. Adipogenic human adenovirus-36
of Obesity. 2011. Global Prevalence of in the FTO gene is associated with body reduces leptin expression and secretion
Adult Obesity. International Association mass index and predisposes to childhood and increases glucose uptake by fat cells.
for the Study of Obesity [cited October and adult obesity. Science (New York, International Journal of Obesity (2005)
20 2011] [database online]. N.Y.) 316(5826):889–894. 31(1):87–96.
109. Jones-Smith, J. C., Gordon-Larsen, P., 125. K ilpelainen, T. O., Zillikens, M. C., 140. Yamada, T., Hara, K., Kadowaki, T.
Siddiqi, A., et al. 2011. Cross-national Stancakova, A., et al. 2011. Genetic 2012. Association of adenovirus 36 infec-
comparisons of time trends in overweight variation near IRS1 associates with tion with obesity and metabolic markers
inequality by socioeconomic status reduced adiposity and an impaired in humans: A meta-analysis of observa-
among women using repeated cross- metabolic profile. Nature Genetics tional studies. PloS One 7(7):e42031.
sectional surveys from 37 developing 43(8):753–760. 141. Shang, Q., Wang, H., Song, Y., et al.
countries, 1989–2007. American Journal 126. Lu, Y., Day, F. R., Gustafsson, S., et al. 2014. Serological data analyses show that
of Epidemiology 173(6):667–675. 2016. New loci for body fat percent- adenovirus 36 infection is associated with
110. Rutter, H. 2011. Where next for obesity? age reveal link between adiposity and obesity: A meta-analysis involving 5739
Lancet 378(9793):746–747. cardiometabolic disease risk. Nature subjects. Obesity (Silver Spring, Md.)
111. Crawford, D., Jeffery, R. W., eds. 2005. Communications 7:10495. 22(3):895–900.
Obesity Prevention and Public Health. 127. Shungin, D., Winkler, T. W., Croteau- 142. Xu, M. Y., Cao, B., Wang, D. F., et al.
Oxford, UK: Oxford University Press. Chonka, D. C., et al. 2015. New genetic 2015. Human adenovirus 36 infection
112. Hall, K. D., Sacks, G., Chandramohan, loci link adipose and insulin biol- increased the risk of obesity: A meta-
D., et al. 2011. Quantification of the ogy to body fat distribution. Nature analysis update. Medicine 94(51):e2357.
effect of energy imbalance on body- 518(7538):187–196. 143. Chappell, C. L., Dickerson, M., Day, R.
weight. Lancet 378(9793):826–837. 128. Pei, Y. F., Ren, H. G., Liu, L., et al. 2017. S., et al. 2017. Adenovirus 36 antibody
113. Hall, K. D., Chow, C. C. 2010. Genomic variants at 20p11 associated detection: Improving the standard
Estimating the quantitative relation with body fat mass in the European serum neutralization assay. Journal of
between food energy intake and changes population. Obesity (Silver Spring, Md.) Virological Methods 239:69–74.
in body weight. The American Journal of 25(4):757–764. 144. Flegal, K. M., Troiano, R. P., Pamuk, E.
Clinical Nutrition 91(3):816; author reply 129. Locke, A. E., Kahali, B., Berndt, S. I., et R., et al. 1995. The influence of smoking
817. al. 2015. Genetic studies of body mass cessation on the prevalence of overweight
114. Leibel, R. L., Rosenbaum, M., Hirsch, index yield new insights for obesity biol- in the united states. The New England
J. 1995. Changes in energy expenditure ogy. Nature 518(7538):197–206. Journal of Medicine 333(18):1165–1170.
resulting from altered body weight. 130. Robinson, M. R., English, G., Moser, 145. Filozof, C., Fernandez Pinilla, M. C.,
The New England Journal of Medicine G., et al. 2017. Genotype-covariate Fernandez-Cruz, A. 2004. Smoking ces-
332(10):621–628. interaction effects and the heritability of sation and weight gain. Obesity Reviews:
115. Hall, K. D. 2010. Predicting metabolic adult body mass index. Nature Genetics An Official Journal of the International
adaptation, body weight change, and 49(8):1174–1181. Association for the Study of Obesity
energy intake in humans. American 131. Huypens, P., Sass, S., Wu, M., et al. 2016. 5(2):95–103.
Journal of Physiology. Endocrinology Epigenetic germline inheritance of diet- 146. Tian, J., Venn, A., Otahal, P., et al. 2015.
and Metabolism 298(3):E449–66. induced obesity and insulin resistance. The association between quitting smok-
116. Nielsen, S. J., Popkin, B. M. 2003. Nature Genetics 48(5):497–499. ing and weight gain: A systemic review
Patterns and trends in food portion sizes, 132. Demerath, E. W., Guan, W., Grove, M. and meta-analysis of prospective cohort
1977–1998. The Journal of the American L., et al. 2015. Epigenome-wide associa- studies. Obesity Reviews: An Official
Medical Association 289(4):450–453. tion study (EWAS) of BMI, BMI change Journal of the International Association
117. Duffey, K. J., Popkin, B. M. 2011. Energy and waist circumference in African for the Study of Obesity 16(10):883–901.
density, portion size, and eating occa- American adults identifies multiple rep- 147. Bush, T., Levine, M. D., Deprey, M., et
sions: Contributions to increased energy licated loci. Human Molecular Genetics al. 2008. Prevalence of weight concerns
intake in the united states, 1977–2006. 24(15):4464–4479. and obesity among smokers calling a
PLoS Medicine 8(6):e1001050. 133. Wahl, S., Drong, A., Lehne, B., et al. quitline. Journal of Smoking Cessation
118. Gortmaker, S. L., Swinburn, B. A., Levy, 2017. Epigenome-wide association 4(5):74–78.
D., et al. 2011. Changing the future study of body mass index, and the 148. Chiolero, A., Faeh, D., Paccaud, F., et al.
of obesity: Science, policy, and action. adverse outcomes of adiposity. Nature 2008. Consequences of smoking for body
Lancet 378(9793):838–847. 541(7635):81–86. weight, body fat distribution, and insulin
470 Chapter 36 Epidemiology of Adult Obesity
resistance. The American Journal of and generational trends. Pediatrics Obesity Reviews: An Official Journal
Clinical Nutrition 87(4):801–809. 111(2):302–307. of the International Association for the
149. Veldheer, S., Yingst, J., Zhu, J., et al. 164. Bonnet, M. H., Arand, D. L. 1995. We Study of Obesity 14(11):883–894.
2015. Ten-year weight gain in smok- are chronically sleep deprived. Sleep 179. Dor, A., C. Ferguson, C. Langwith, et al.
ers who quit, smokers who continued 18(10):908–911. 2010. A Heavy Burden: The Individual
smoking and never smokers in the 165. Patel, S. R., Malhotra, A., White, D. Costs of Being Overweight and Obese.
united states, NHANES 2003–2012. P., et al. 2006. Association between The George Washington University
International Journal of Obesity reduced sleep and weight gain in women. School of Public Health and Health
39(12):1727–1732. American Journal of Epidemiology Services Department of Health Policy.
150. Flegal, K. M. 2007. The effects of 164(10):947–954. 180. Popkin, B. M., Kim, S., Rusev, E. R., et
changes in smoking prevalence on 166. Patel, S. R., Hu, F. B. 2008. Short sleep al. 2006. Measuring the full economic
obesity prevalence in the united states. duration and weight gain: A systematic costs of diet, physical activity and
American Journal of Public Health review. Obesity (Silver Spring, Md.) obesity-related chronic diseases. Obesity
97(8):1510–1514. 16(3):643–653. Reviews: An Official Journal of the
151. Lycett, D., Munafo, M., Johnstone, E., 167. Clemente, J. C., Ursell, L. K., Parfrey, International Association for the Study
et al. 2011. Associations between weight L. W., et al. 2012. The impact of the gut of Obesity 7(3):271–293.
change over 8 years and baseline body microbiota on human health: An integra- 181. W ithrow, D., Alter, D. A. 2011. The
mass index in a cohort of continuing and tive view. Cell 148(6):1258–1270. economic burden of obesity world-
quitting smokers. Addiction (Abingdon, 168. Garmey, E. G., Liu, Q., Sklar, C. A., et wide: A systematic review of the direct
England) 106(1):188–196. al. 2008. Longitudinal changes in obesity costs of obesity. Obesity Reviews: An
152. Taheri, S., Lin, L., Austin, D., et al. and body mass index among adult sur- Official Journal of the International
2004. Short sleep duration is associated vivors of childhood acute lymphoblastic Association for the Study of Obesity
with reduced leptin, elevated ghrelin, leukemia: A report from the childhood 12(2):131–141.
and increased body mass index. PLoS cancer survivor study. Journal of Clinical 182. Bierl, M., Marsh, T., Webber, L., et al.
Medicine 1(3):e62. Oncology: Official Journal of the 2013. Apples and oranges: A comparison
153. Van Cauter, E. 2011. Sleep distur- American Society of Clinical Oncology of costing methods for obesity. Obesity
bances and insulin resistance. Diabetic 26(28):4639–4645. Reviews: An Official Journal of the
Medicine: A Journal of the British 169. Reis, J. P., Macera, C. A., Araneta, M. International Association for the Study
Diabetic Association 28(12):1455–1462. R., et al. 2009. Comparison of overall of Obesity 14(9):693–706.
154. Trenell, M. I., Marshall, N. S., Rogers, obesity and body fat distribution in pre- 183. Finkelstein, E. A., Trogdon, J. G., Cohen,
N. L. 2007. Sleep and metabolic con- dicting risk of mortality. Obesity (Silver J. W., et al. 2009. Annual medical spend-
trol: Waking to a problem? Clinical Spring, Md.) 17(6):1232–1239. ing attributable to obesity: Payer-and
and Experimental Pharmacology and 170. D’Agostino, R. B., Jr, Hamman, R. F., service-specific estimates. Health Affairs
Physiology 34(1–2):1–9. Karter, A. J., et al. 2004. Cardiovascular (Project Hope) 28(5):w822–w831.
155. Taheri, S., Thomas, G. N. 2008. Is sleep disease risk factors predict the develop- 184. Trogdon, J. G., Finkelstein, E. A.,
duration associated with obesity-where ment of type 2 diabetes: The insulin Hylands, T., et al. 2008. Indirect
do U stand? Sleep Medicine Reviews resistance atherosclerosis study. Diabetes costs of obesity: A review of the cur-
12(4):299–302. Care 27(9):2234–2240. rent literature. Obesity Reviews: An
156. Taheri, S. 2006. The link between short 171. Katzmarzyk, P. T., Janssen, I., Ardern, C. Official Journal of the International
sleep duration and obesity: We should I. 2003. Physical inactivity, excess adipos- Association for the Study of Obesity
recommend more sleep to prevent obe- ity and premature mortality. Obesity 9(5):489–500.
sity. Archives of Disease in Childhood Reviews: An Official Journal of the 185. Tucker, L. A., Friedman, G. M. 1998.
91(11):881–884. International Association for the Study Obesity and absenteeism: An epidemio-
157. Taheri, S. 2007. Sleep and metabolism: of Obesity 4(4):257–290. logic study of 10,825 employed adults.
Bringing pieces of the jigsaw together. 172. Kenchaiah, S., Gaziano, J. M., Vasan, R. American Journal of Health Promotion
Sleep Medicine Reviews 11(3):159–162. S. 2004. Impact of obesity on the risk of 12(3):202–207.
158. Spiegel, K., Knutson, K., Leproult, R., et heart failure and survival after the onset 186. Pronk, N. P., Martinson, B., Kessler,
al. 2005. Sleep loss: A novel risk factor of heart failure. The Medical Clinics of R. C., et al. 2004. The association
for insulin resistance and type 2 diabetes. North America 88(5):1273–1294. between work performance and physi-
Journal of Applied Physiology (Bethesda, 173. Guh, D. P., Zhang, W., Bansback, N., et cal activity, cardiorespiratory fitness,
Md.: 1985) 99(5):2008–2019. al. 2009. The incidence of co-morbidities and obesity. Journal of Occupational
159. Knutson, K. L., Galli, G., Zhao, X., et related to obesity and overweight: A sys- and Environmental Medicine/
al. 2011. No association between leptin tematic review and meta-analysis. BMC American College of Occupational and
levels and sleep duration or quality in Public Health 9:88. Environmental Medicine 46(1):19–25.
obese adults. Obesity (Silver Spring, Md.) 174. Wang, Y. C., McPherson, K., Marsh, 187. Robbins, A. S., Chao, S. Y., Russ, C.
19(12):2433–2435. T., et al. 2011. Health and economic R., et al. 2002. Costs of excess body
160. Knutson, K. L., Van Cauter, E. 2008. burden of the projected obesity trends weight among active duty personnel,
Associations between sleep loss and in the USA and the UK. Lancet U.S. air force, 1997. Military Medicine
increased risk of obesity and diabetes. 378(9793):815–825. 167(5):393–397.
Annals of the New York Academy of 175. Renehan, A. G., Tyson, M., Egger, M., et 188. Ricci, J. A., Chee, E. 2005. Lost
Sciences 1129:287–304. al. 2008. Body-mass index and incidence productive time associated with excess
161. Knutson, K. L., Van Cauter, E., Zee, P., of cancer: A systematic review and meta- weight in the U.S. workforce. Journal
et al. 2011. Cross-sectional associations analysis of prospective observational of Occupational and Environmental
between measures of sleep and markers studies. Lancet 371(9612):569–578. Medicine/American College of
of glucose metabolism among subjects 176. Tremmel, M., Gerdtham, U. G., Nilsson, Occupational and Environmental
with and without diabetes: The coronary P. M., et al. 2017. Economic burden of Medicine 47(12):1227–1234.
artery risk development in young adults obesity: A systematic literature review. 189. Cawley, J., Rizzo, J. A., Haas, K.
(CARDIA) sleep study. Diabetes Care International Journal of Environmental 2007. Occupation-specific absentee-
34(5):1171–1176. Research and Public Health 14(4):435. ism costs associated with obesity and
162. Centers for Disease Control and doi: 10.3390/ijerph14040435. morbid obesity. Journal of Occupational
Prevention (CDC). 2011. Insufficient 177. Dee, A., Kearns, K., O’Neill, C., et al. and Environmental Medicine/
Sleep is a Public Health Epidemic [cited 2014. The direct and indirect costs of American College of Occupational
October 12, 2011]. Available from http:// both overweight and obesity: A system- and Environmental Medicine
www.cdc.gov/features/dssleep/ (accessed atic review. BMC Research Notes 7:242. 49(12):1317–1324.
October 12, 2011). 178. Grieve, E., Fenwick, E., Yang, H. C., et 190. Gates, D. M., Succop, P., Brehm, B. J., et
163. Iglowstein, I., Jenni, O. G., Molinari, al. 2013. The disproportionate eco- al. 2008. Obesity and presenteeism: The
L., et al. 2003. Sleep duration from nomic burden associated with severe and impact of body mass index on workplace
infancy to adolescence: Reference values complicated obesity: A systematic review. productivity. Journal of Occupational
References 471
and Environmental Medicine/ of obesity in the workplace. Journal 194. O stbye, T., Dement, J. M., Krause, K.
American College of Occupational and of Occupational and Environmental M. 2007. Obesity and workers’ com-
Environmental Medicine 50(1):39–45.
191. Poston, W. S. C., Jitnarin, N., Haddock,
C. K., et al. 2011. Obesity and injury-
Medicine/American College of
Occupational and Environmental
Medicine 52(10):971–976.
pensation: Results from the duke health
and safety surveillance system. Archives
of Internal Medicine 167(8):766–773.
36
related absenteeism in a population- 193. Soteriades, E. S., Hauser, R., Kawachi, I., 195. Fontaine, K. R., Redden, D. T.,
based firefighter cohort. Obesity et al. 2008. Obesity and risk of job dis- Wang, C., et al. 2003. Years of life
19(10):2076–2081. ability in male firefighters. Occupational lost due to obesity. The Journal of
192. Finkelstein, E. A., DiBonaventura, M., Medicine (Oxford, England) the American Medical Association
Burgess, S. M., et al. 2010. The costs 58(4):245–250. 289(2):187–193.
37
CHAPTER
Key Points.................................................................................. 473 37.4 Weight Loss Variability in Response to Physical Activity.........477
37.1 Introduction...................................................................... 473 37.4.1 Biological Factors................................................. 477
37.2 Effect of Physical Activity on Prevention of Weight Gain........473 37.4.2 Influence of Physical Activity on Other
37.3 Effect of Physical Activity on Weight Loss...........................474 Components of Energy Expenditure��������������������� 477
37.3.1 Cardiovascular (Aerobic) Activity............................474 37.4.3 Influence of Physical Activity on Energy Intake...... 477
37.3.2 Resistance Exercise...............................................474 37.4.4 Factors Influencing Adherence to Physical Activity..... 477
37.3.3 Yoga......................................................................474 37.5 Physical Activity, Fitness, and Health Outcomes................ 478
37.3.4 Lifestyle Activity................................................... 475 37.5.1 Effects on Mortality.............................................. 478
37.3.5 Sedentary Behavior.............................................. 475 37.5.2 Effects on Risk Factors for Cardiovascular Disease�����478
37.3.6 Duration of Physical Activity Bouts........................ 475 37.5.2.1 Blood Pressure...................................... 478
37.3.7 Physical Activity Combined with Reductions in 37.5.2.2 Lipids.................................................... 479
Energy Intake������������������������������������������������������ 476 37.5.2.3 Inflammatory Markers........................... 479
37.3.8 The Role of Physical Activity in Surgically 37.6 Summary and Clinical Applications................................... 479
Induced Weight Loss�������������������������������������������� 476 References................................................................................ 480
there is cross-sectional evidence to support that an inverse of resistance exercise on weight loss. It has been proposed
relationship exists between physical activity and both that resistance exercise may influence body weight by
BMI6–12 and body fatness.6,8,10–13 There are also prospec- increasing lean mass. This preservation of lean mass may
tive data from the NHANES-I Epidemiology Follow-Up increase resting metabolic rate, increased strength that
Study.14 Aerobics Center Longitudinal Study,15 Women’s will result in an increase in free-living physical activity,
Health Study,16 and Harvard Alumni Study17 to support and increased total daily energy expenditure from per-
the importance of physical activity for the prevention of forming the resistance exercise. 20 However, numerous
weight gain. Others have also demonstrated that physi- systematic reviews have concluded that resistance exercise
cal activity is important for maintaining a healthy body has a modest influence on weight loss when performed in
weight, defined as a BMI of ≥18.5 to <25 kg m 2 18 and for the absence of reductions in energy intake. 20,27 While it
reducing the odds of developing obesity.19 Moreover, there is possible that the resulting increase in lean mass that is
may be a threshold of physical activity that is needed to proposed to occur with resistance exercise may offset the
prevent significant weight gain, defined as a weight gain reductions in fat mass causing absolute weight to remain
of at least 3% of current body weight, with this threshold relatively unchanged, 28–31 it should not be expected that
ranging from 150 to 250 minutes per week. 20 energy expenditure from resistance exercise will be suffi-
Additional clinical implications for engaging in physi- cient to result in significant reductions in body weight over
cal activity, and as addressed elsewhere in this chapter, is a period of three to six months. There are limited data
that physical activity may influence the retention of lean available from longer-term studies to determine if this pat-
body mass, 21 and physical activity can contribute to pre- tern would change with a longer intervention period. 20,27
vention or lessening of weight gain following significant Despite the lack of evidence that resistance exercise will
weight loss. 22 These may result in important health ben- result in significant reductions in total body fatness, resis-
efits to patients. tance exercise may reduce subcutaneous abdominal adi-
posity.32 Thus, the benefits of resistance exercise in the
treatment of obesity may not be in reductions in total
37.3 EFFECT OF PHYSICAL body fatness, but rather improvements in lean mass and
strength, and the reductions in abdominal adiposity.
ACTIVITY ON WEIGHT LOSS
37.3.1 Cardiovascular (Aerobic) Activity 37.3.3 Yoga
Physical activity has been recommended as a key behav-
ior within interventions that target overweight and obe- Yoga participation has been increasing in recent years,
sity.4 However, the effects of physical activity on weight and this form of physical activity may be beneficial for
loss, when not coupled with a concurrent reduction in the management of body weight. However, yoga has many
energy intake, appear to be modest. For example, aver- different styles and components that need to be considered
age weight loss of 2% at six months and 1% at 18 months when determining the efficacy of yoga within the context
was reported in a study of overweight adults who were of body weight and obesity prevention and treatment.
prescribed home-based physical activity without a pre- Representing a major component of yoga practice are
scribed reduction in energy intake. 23 Others have reported the asanas (poses), and how these asanas are performed
a similar magnitude of weight loss for interventions last- may have implications for body weight control. For exam-
ing three to six months that also focused on physical activ- ple, asanas that are performed in a manner designed for
ity without prescribing a reduction in energy intake. 24,25 relaxation or the holding of various body postures in a
This is also consistent with the 0.5–3.0 kg weight loss in static manner have been shown to elicit an energy expen-
response to 180–270 minutes per week of physical activity diture that is classified as light-intensity (from 1.5 up to
that was reported in the 2008 Physical Activity Guidelines 3.0 metabolic equivalents [METs]).33 However, when the
Advisory Committee Report. 26 However, there may be a asanas are performed in a continuous pattern that flows
dose-response effect, with the magnitude of weight loss through a dynamic series of movements, similar to a
increasing as dose of physical activity increases. For exam- Vinyasa style of yoga, the energy expenditure is at a mod-
ple, a systematic review of the literature conducted for the erate-to-vigorous intensity (e.g. >3.0 METs), 34 which has
2009 Position Stand of the American College of Sports implications for increasing energy expenditure. Moreover,
Medicine (ACSM)20 concluded that there was no signifi- it has been shown that adults who are overweight or obese
cant change in body weight in response to <150 minutes are also able to engage in yoga with the energy expendi-
per week of physical activity, whereas 2.0–3.0 kg and 5.0– ture being similar to what is achieved in adults who are
7.5 kg are observed with >150 and 225–420 minutes per not overweight or obese. These findings may suggest that
week of physical activity, respectively. yoga can be an acceptable alternative to other forms of
physical activity for eliciting energy expenditure that may
impact body weight regulation.
In addition to the energy expenditure that can result
37.3.2 Resistance Exercise from engagement in yoga, there may be additional aspects
While the majority of research related to the effect of that can be of benefit within the context of body weight
physical activity, in the absence of restrictions in energy regulation and the treatment of obesity. For example, many
intake, has focused on cardiovascular (aerobic) forms of forms of yoga also include components of mindfulness
physical activity, there is a body of literature on the effects meditation, which may assist in making conscious decisions
37.3 Effect of Physical Activity on Weight Loss 475
related to behaviors that can influence body weight (e.g. 10,000 steps per day with approximately 3,500 steps per
37
eating behaviors, activity behaviors, etc.). Mindfulness day performed at a moderate-to-vigorous intensity in
meditation may influence psychological functioning and bouts of at least 10 minutes in duration.40
flexibility, awareness, self-regulation, and stress. However,
there are mixed data on whether mindfulness meditation
can be effective for weight loss. The results of a randomized
trial that added mindfulness to a diet and exercise program
37.3.5 Sedentary Behavior
showed no added benefit to weight loss compared to the Sedentary behavior is considered an important lifestyle
diet and exercise program that did not include mindful- target to reduce health risk. With regard to the influence of
ness.35 In contrast, Spadaro et al.36 reported that there was sedentary behavior on weight status and weight loss, the
additional weight loss achieved when mindfulness medita- scientific evidence is less compelling. The 2018 Physical
tion was added to a behavioral weight loss intervention that Activity Guidelines Advisory Committee Scientific
included diet and exercise. However, it is unclear whether Report41 identified two systematic reviews that examined
the addition of mindfulness meditation that is incorporated the relationship between sedentary behavior and indices
into a yoga practice will influence weight loss. of obesity.42,43 These systematic reviews concluded that
there was limited or insufficient evidence that sedentary
behavior was associated with weight gain or other indi-
ces of overweight or obesity. Based on these systematic
37.3.4 Lifestyle Activity reviews, and the review of original research studies, the
It has been recommended that non-structured forms of Physical Activity Guidelines Advisory Committee con-
physical activity can also contribute to increases in energy cluded that there was limited evidence of a relationship
expenditure and should be a component of interventions between greater time spent in sedentary behavior and
for obesity. The term “nonexercise activity thermogen- higher levels of adiposity.41
esis” (NEAT) is used to described energy expenditure Evidence from studies of adults who are overweight or
that does not result from sleeping, eating, or structured obese, which included diet modification to reduce energy
exercise.37 A common methodology to increase NEAT intake, also suggests that targeting sedentary behavior
is through the use of pedometers, with patients recom- may have limited influence on weight loss. For example,
mended to increase the number of steps walked. When Jakicic et al.44 reported that decreases in sedentary behav-
this methodology has been used to promote an increase in ior were not associated with weight loss achieved during a
physical activity, it has been shown to result in an increase six-month behavioral weight loss intervention. However,
of 2100 steps per day, and this results in a modest decrease this study also demonstrated that both increases in total
in BMI of 0.38 units, 20 which is the equivalent of approxi- volume of light-intensity physical activity and volume of
mately 2.0–3.0 kg of weight loss. However, others have moderate-to-vigorous physical activity performed in bouts
reported that a 12-week pedometer intervention increased that were at least 10 minutes in duration were predictive
steps by 3000 per day; however, there was no association of weight loss.
between steps walked and change in BMI, but there was Collectively, these findings suggest that simply tar-
an association between steps walked and change in waist geting reductions in sedentary behavior may not be suf-
circumference.38 Thus, it may be necessary to combine the ficient to significantly influence body weight. This may be
increase in energy expenditure resulting from NEAT with a result of simple strategies to reduce sedentary behavior
the increased energy expenditure resulting from struc- (e.g. changing posture from sitting to standing) not result-
tured forms of activity (exercise) to maximize increases in ing in a sufficient increase in energy expenditure. For
total energy expenditure, which can contribute to weight example, Creasy et al.45 demonstrated that transitioning
loss in overweight and obese adults. from sitting to stationary standing results in an increase
Within the context of a behavioral weight loss inter- of approximately 9 kcal/hour, whereas transitioning from
vention, Creasy et al.39 examined the effect of prescribing either sitting or stationary standing to self-paced walking
physical activity as steps per day, and compared this pre- results in a 2.4 and 2.7 fold increase in energy expendi-
scription to supervised and home-based forms of struc- ture, respectively. Thus, collectively, these data may sug-
tured physical activity. When prescribed physical activity gest that targeting reductions in sedentary behavior that
that progressed to 10,000 steps per day, with a target of at result in a sufficient increase in physical activity, rather
least 25% of those steps accumulated in bouts that were than simply body posture changes, may be needed to influ-
at least 10 minutes in duration at a moderate-to-vigorous ence indices of weight status and to influence weight loss.
intensity, there was no difference in weight loss achieved
compared to the weight loss achieved with supervised or
unsupervised structured periods of moderate-to-vigorous
intensity exercise. Because this intervention was 12 weeks
37.3.6 Duration of Physical Activity Bouts
in duration, this study was not able to determine the long- The 1995 report of the United States Centers for Disease
term impact of physical activity accumulated as steps per Control and Prevention and the American College of
day on weight loss in adults who are overweight or obese. Sports Medicine suggested there could be favorable ben-
However, secondary data analysis from a randomized efits of physical activity accumulated in 8–10 minutes
clinical trial suggests that to successfully lose and main- bouts.46 Since then, studies that have examined physi-
tain weight loss of at least 10% of initial body weight for cal activity performed in this bout duration have found
a period of at least 18 months, one needs to accumulate favorable effects on weight loss that can be comparable
476 Chapter 37 Exercise Management for the Obese Patient
or may exceed the weight loss achieved with more tradi- restricted diet results in 20% greater weight loss than the
tional continuous bouts of exercise.47–49 This has resulted weight loss achieved with an energy restricted diet alone.
in most intervention studies focusing on physical activ- Physical activity may also be important for enhancing
ity bouts that need to be at least 10 minutes in duration. weight loss beyond the initial six months of treatment,
However, evidence from the systematic review conducted improving long-term weight loss maintenance, and mini-
and reported in the 2018 Physical Activity Guidelines mizing weight regain. An important observation is that
Advisory Committee Report appears to suggest that relatively high levels of physical activity may be necessary
physical activity accumulated in bouts of even less than 10 to improve long-term weight loss.53–55 We have contributed
minutes in duration may have beneficial effects on body to the scientific literature supporting the need for physi-
weight and obesity.41 This review showed evidence from cal activity to improve long-term weight loss. Results of
cross-sectional studies of an association between physical a 24-month intervention in overweight and obese women
activity accumulated in bouts of <10 minutes with lower showed that an increase in physical activity of 1500 kcal/
BMI6–8,10 and body fatness.6,8,10–12 wk above baseline levels was associated with weight loss
Not all of the evidence, however, supports a favor- of 14.2 kg (16.8% of initial body weight), whereas sig-
able effect of physical activity performed in bouts of <10 nificantly less weight loss was observed at 24 months with
minutes on outcomes related to obesity and weight loss. lower amounts of physical activity. 56 We estimated that
For example, results from a prospective cohort study the 1500 kcal/wk of physical activity above baseline levels
reported that a lower incidence of obesity was associated was reflective of approximately 275 minutes per week of
with physical activity accumulated in bouts of at least 10 brisk walking above what was being performed prior to
minutes; whereas physical activity accumulated in bouts the start of the 24-month intervention. Additional analy-
of a shorter duration was not associated with a lower inci- sis of the data showed that physical activity was an impor-
dence of obesity. 50 Moreover, secondary analyses of data tant behavior in the ability to achieve an initial weight loss
from intervention studies supports that physical activity of ≥10% at six months and to sustain this magnitude of
may need to be performed in bouts that are ≥10 minutes weight loss at the conclusion of the 24-month intervention
in duration to impact weight loss. Within the context of a period.57 This magnitude of physical activity is similar
six-month comprehensive behavioral weight loss interven- to what we have reported in other studies. For example,
tion, moderate-to-vigorous physical activity performed in 18-month weight loss of 13.1 kg was found in women who
bouts of at least 10 minutes in duration was associated reported participating in an average of 280–300 minutes
with weight loss, whereas moderate-to-vigorous physical per week of physical activity throughout the entire inter-
activity performed in bouts less than 10 minutes in dura- vention period, and this weight loss was significantly
tion was not associated with weight loss.44 An 18-month greater than the weight loss achieved when participating
study showed similar findings, with moderate-to-vigorous in lower amount of physical activity.48
physical activity performed in bouts of at least 10 minutes Despite the abovementioned associations between
in duration being associated with enhanced weight loss physical activity and weight loss, most of the studies in this
and physical activity performed in bouts less than 10 min- area have relied on self-reported physical activity. However,
utes in duration not being associated with weight loss. 22 studies that have used objective physical activity monitoring
Thus, there may be advantages to encouraging patients have also found associations between moderate-to-vigorous
to engage in activity regardless of the length of the activ- physical activity and weight loss. Jakicic et al.44 reported
ity bout, as this may have an influence on body weight. that moderate-to-vigorous physical activity performed in
However, for successful weight loss, bouts of physical bouts of at least 10 minutes in duration was associated
activity that are at least 10 minutes in duration may need with weight loss within the context of a six-month com-
to be recommended. prehensive behavioral weight loss intervention. Moreover,
in a separate study, Jakicic et al.22 reported that moderate-
to-vigorous physical activity performed in bouts of at least
37.3.7 Physical Activity Combined with 10 minutes in duration that accumulated to 200–300 min-
utes per week was associated with improved weight loss at
Reductions in Energy Intake 18 months within the context of a comprehensive behav-
It is commonly recommended that physical activity be ioral weight loss intervention. These findings support that
combined with a reduction in energy intake for the treat- physical activity is an important lifestyle target to enhance
ment of obesity.4 Examination of the evidence suggests weight loss in adults who are overweight or obese.
that the addition of physical activity to an energy restricted
diet will result in an additional 2.0–3.0 kg beyond what is
achieved with an energy restricted diet alone. For exam- 37.3.8 The Role of Physical Activity in
ple, Goodpaster et al. 51 and Wing et al. 25 reported that
the addition of physical activity to an energy restricted
Surgically Induced Weight Loss
diet increased weight loss at six months by 2.7 kg and 1.2 Bariatric surgery has become a popular, and effective,
kg, respectively, above what was achieved with an energy method in the treatment of obesity. However, unpublished
restricted diet that did not include physical activity. These data from our laboratory have suggested that many patients
results are similar to results reported by Hagan et al. 24 who have undergone bariatric surgery are not provided
While this magnitude of additional weight loss appears information to participate in physical activity, and when
to be modest, Curioni and Lourenco52 have suggested they are provided information related to physical activity,
that the combination of physical activity and an energy it is not consistent with public health recommendations
37.4 Weight Loss Variability in Response to Physical Activity 477
for physical activity. This is of concern because there is a between pairs of twins. Thus, the variability in weight
37
growing body of literature to support the need for physi- loss observed between individuals may have biological
cal activity in patients who have undergone bariatric sur- underpinnings.
gery. For example, greater weight loss has been observed in
bariatric surgery patients who participate in ≥150 minutes
per week of physical activity compared to patients partici- 37.4.2 Influence of Physical Activity
pating in <150 minutes per week.58 This is consistent with
other research showing improvements in weight loss at six
on Other Components of
to 24 months following bariatric surgery with the inclusion Energy Expenditure
of physical activity.58–60 Despite the long-term effects, the A state of negative energy balance in which energy expen-
added benefits of physical activity for weight loss may not diture exceeds energy intake is necessary to induce weight
be achieved in the six months following bariatric surgery.61 loss. It has been suggested that physical activity is the most
Given the need for long-term engagement in physical variable component of total energy expenditure, and there-
activity to have a beneficial effect on weight loss follow- fore this component of energy expenditure may have the
ing bariatric surgery, it is concerning that few patients greatest influence on the ability to create this state of nega-
meet thresholds of physical activity to experience this tive energy balance.68 However, it has been suggested that
benefit.62,63 Thus, it is important to identify strategies to physical activity may also influence other components of
enhance adoption and maintenance of physical activity energy expenditure, namely resting metabolic rate (RMR),
in these patients. A recent study that examined a variety which can further affect total energy expenditure. There
of psychosocial factors found that social support was a appears to be an acute increase in RMR in response to
consistent predictor of physical activity in patients who physical activity, and chronic physical activity participation
undergo bariatric surgery.64 Thus, this may be an impor- may be associated with a higher RMR.69 This may be of
tant consideration when developing and implementing importance for overweight and obese individuals because
interventions to enhance engagement in physical activity RMR tends to decrease in the presence of weight loss,
in these patients. which can decrease total energy expenditure and possibly
affect weight loss and weight loss maintenance. However,
even when physical activity is included as a component
37.4 WEIGHT LOSS VARIABILITY of the intervention, RMR has been shown to decline in
response to significant weight loss.70 Thus, healthcare and
IN RESPONSE TO health-fitness professionals should refrain from promoting
PHYSICAL ACTIVITY that physical activity will increase or at least prevent the
decline observed in RMR with weight loss.
As described above, on average, modest weight loss on
the magnitude of 0.5–3.0 kg is observed with physical
activity. However, as reported by Donnelly and Smith,65 37.4.3 Influence of Physical Activity
there is significant inter-individual variability observed in on Energy Intake
weight loss in response to physical activity. Thus, there is
a possibility that physical activity may result in greater There is evidence of inter-individual variability in energy
weight loss for some individuals than what is commonly intake in response to physical activity, and this may pro-
reported in the literature. Moreover, it is possible that vide some evidence of why physical activity results in
there will be differences in weight loss between individu- greater weight loss in some individuals compared to oth-
als in response to participation in similar doses of physi- ers. For example, in response to 50 minutes of physical
cal activity. Bouchard et al.66 reported that weight loss activity, Finlayson et al.71 reported a positive increase in
in response to four months of highly controlled exercise energy balance in 50% of study participants. This is very
resulted in a range of weight loss equivalent to approxi- similar to the findings of a study conducted in our labora-
mately 3.0–12.0 kg. Thus, it is important to consider fac- tory in which 58% of participants consumed more calories
tors that may contribute to this variability in weight in following a 35- to 45-minute period of activity compared
response to physical activity. to following a seated rest period.72 This may suggest that
for some overweight and obese adults, physical activity
increases hunger and appetite, whereas in others physical
activity may enhance satiety, which can influence energy
37.4.1 Biological Factors intake.
Bouchard et al.67 have suggested that there may be biologi-
cal factors that contribute to the weight loss observed in
response to physical activity. These investigators studied 37.4.4 Factors Influencing Adherence
seven pairs of identical male twins examined over a period
of 93 days in which energy intake was held constant and
to Physical Activity
physical activity performed twice daily. Subjects were also The variability in weight loss observed in response to
monitored 24 hours per day to minimize any variability free-living physical activity may also be a reflection of
in energy intake or physical activity. The results from this one’s ability to adopt and adhere to an adequate dose of
study showed that weight loss was similar within each physical activity to promote weight loss. There may also
pair of twins; however, weight loss was highly variable be genetic factors that contribute to physical activity
478 Chapter 37 Exercise Management for the Obese Patient
participation.73–75 However, there is also evidence of more level of adiposity. The findings reported by Blair et al.81
traditional behavioral factors contributing to physical showed an association between fitness and mortality, and
activity participation in overweight and obese adults. For this association remained even after controlling for level
example, we have previously reported that higher levels of of body mass index. Additional findings from the Aerobics
physical activity self-efficacy are associated with higher Center Longitudinal Study have consistently supported
levels of physical activity in response to a six-month the finding that a higher level of fitness remains an impor-
behavioral weight loss intervention,76 and recent unpub- tant factor in reducing the risk of mortality, and this effect
lished data supports the continued association between appears to be independent of the influence of BMI82–85 or
long-term physical activity participation and physical body fatness.86,87
activity self-efficacy. Moreover, identifying and overcom- Despite these findings, not all data support the con-
ing barriers to physical activity contribute to physical tention that fitness will completely ameliorate the risk
activity participation in overweight and obese adults.76,77 of a higher level of BMI or body fatness on these out-
This appears to suggest that overweight and obese adults comes. A prospective examination of data from older
need to engage in interventions to increase self-efficacy men in the Veterans Exercise Testing Study found that
and to reduce barriers for physical activity. Thus, sim- both cardiorespiratory fitness and BMI were associated
ply instructing overweight and obese adults to engage in with all-cause mortality.88 Data from the Lipid Research
physical activity without addressing the behavioral fac- Clinics Study also suggest that both fitness and fatness
tors that are associated with physical activity may not be contribute to risk of mortality.89 Moreover, secondary
effective. (See also: the chapter “Cognitive and Behavioral analysis from the multi-center Look AHEAD Study,
Approaches to Enhancing Physical Activity Participation which was an intervention study to examine the effects
and Decreasing Sedentary Behavior”). This may require of an intensive lifestyle intervention on cardiovascular
healthcare and health-fitness professionals to receive disease in patients with type 2 diabetes, showed that
training in these areas of behavior change when treating achieving weight loss of at least 10% after one year of
overweight and obese adults and recommending physical treatment resulted in a 20% reduction in the primary
activity as a component of the intervention plan. outcome of cardiovascular disease (composite of death
from cardiovascular disease, non-fatal acute myocar-
dial infarction, non-fatal stroke, hospital admission for
37.5 PHYSICAL ACTIVITY, angina).90 Fitness, however, was not shown to be associ-
ated with the primary outcome, but an increase in fit-
FITNESS, AND HEALTH ness of ≥2 METs was associated with a 23% reduction in
OUTCOMES secondary outcomes (composite of the primary outcome
plus coronary artery bypass grafting, carotid endarter-
In addition to the potential benefits of physical activity on ectomy, percutaneous coronary intervention, admission
weight loss, overweight and obese adults also experience to the hospital for congestive heart failure, peripheral
significant improvements in cardiorespiratory fitness in vascular disease, total mortality). These findings appear
response to engaging in sufficient amounts of physical activ- to suggest that interventions for overweight and obese
ity. Numerous studies have shown that cardiorespiratory fit- adults should focus on both weight loss and improving
ness improves only when physical activity is included as a fitness to elicit reduced risk of all-cause and cardiovascu-
component of the intervention program, and these improve- lar disease mortality.
ments are present regardless of whether or not the inter-
vention results in weight loss.78 However, fitness does not
improve significantly when weight loss is induced by energy 37.5.2 Effects on Risk Factors for
restriction alone.78,79 Thus, physical activity is an important Cardiovascular Disease
component of interventions for overweight and obese adults
that results in improved cardiorespiratory fitness. However, Cardiovascular disease is a leading cause of death, and
the magnitude of improvement in fitness depends on the dose results in significant healthcare costs in the United States.
of physical activity performed. For example, a dose-response As described above, cardiorespiratory fitness appears to
relationship has been reported between the improvement in partially contribute to reductions in cardiovascular dis-
cardiorespiratory fitness and prescribed dose of physical ease mortality in overweight and obese adults. This may
activity in overweight adults across an 18-month interven- be a result of the influence of cardiorespiratory fitness on
tion.23 Church et al. reported similar findings in response risk factors known to be associated with cardiovascular
to six months of supervised physical activity in overweight disease such as blood pressure, lipids, inflammatory bio-
and obese post-menopausal women.80 Thus, these data sup- markers, and diabetes. However, as described in detail
port the need for clinicians to recommend physical activity below, fitness may not completely eliminate the associa-
to overweight and obese adults. tion between adiposity and these risk factors for cardio-
vascular disease.
appears to have mixed findings. For example, Rankinen of the impact of physical activity and cardiorespira-
37
et al.91 have reported a significant association between tory fitness on other cardiovascular disease risk fac-
BMI and risk of developing hypertension; however, this tors, one could hypothesize that physical activity and
association was attenuated with cardiorespiratory fit- cardiorespiratory fitness would also have an influence
ness. Conversely, Chen et al.92 reported that both BMI on inflammatory markers that may contribute to car-
and cardiorespiratory fitness are associated with sys- diovascular disease. However, both Church et al.95 and
tolic blood pressure, yet when both variables were con- Nicklas et al.98 have reported that physical activity does
sidered concurrently, BMI but not fitness continued to not improve the markers of inflammation. Moreover,
be associated with systolic blood pressure. Wing et al.93 Hamer and Steptoe99 reported no association between
reported that both BMI and cardiorespiratory fitness cardiorespiratory fitness and measures of inflamma-
were significantly associated with systolic blood pressure tion. Thus, physical activity may not be the optimal
in women regardless of whether medication was being therapy for improving measures of inflammation that
taken for blood pressure control. However, in men not can reduce cardiovascular disease risk in overweight
taking medication for blood pressure control, BMI but and obese adults.
not fitness was associated with systolic blood pressure.
Thus, these findings appear to suggest that both BMI
and fitness may be important for blood pressure control
in overweight and obese adults, and both should be tar-
37.6 SUMMARY AND CLINICAL
gets of clinical interventions. APPLICATIONS
Physical activity is an important lifestyle behavior that
37.5.2.2 Lipids can contribute to numerous health-related benefits.41 One
An abnormal blood lipid profile is considered a primary of the important health-related outcomes is the manage-
risk for cardiovascular disease. Because of the associa- ment of body weight that leads to prevention of weight
tion between obesity and blood lipids,4 interventions that gain or weight loss in the presence of overweight or obe-
target obesity may also have a favorable influence on sity. The summary of the evidence presented supports the
blood lipids. However, physical activity appears to have following:
a modest influence on blood lipids in overweight and
obese adults. For example, the results of a meta-analysis • Physical activity contributes to the prevention of
of studies that included overweight and obese adults con- weight gain and incidence of obesity.
cluded that total cholesterol was reduced by 3.4 mg/dl, • Physical activity results in short-term weight loss
LDL was reduced by 3.0 mg/dl, and HDL was increased (typically <6 months) of approximately 0.5–3.0 kg.
by 1.6 mg/dl in response to physical activity interventions • When combined with a reduction in energy
that did not include dietary restriction or result in sig- intake, physical activity can enhance weight loss
nificant weight loss.94 This same meta-analysis reported by approximately 20% beyond the magnitude of
that physical activity interventions significantly reduced weight loss achieved through a reduction in energy
triglycerides by 16.1 mg/dl in overweight and obese intake alone.
adults.94 Church et al.95 reported no influence of four • Physical activity is important for enhancing long-
months of exercise that did not also include concurrent term weight loss and prevention of weight regain
caloric restriction on blood lipid parameters compared to following initial weight loss.
a control condition. • There is limited evidence that focusing solely on
When combined with caloric restriction, there are reducing sedentary behavior, without a concurrent
mixed results for the effect of physical activity on blood increase in moderate-to-vigorous intensity physical
lipids. For example, Goodpaster et al.51 reported that activity, will prevent weight gain or contribute sig-
the addition of physical activity to an energy restricted nificantly to weight loss.
diet did not improve blood lipids when compared to the • Moderate-to-vigorous physical activity that is
improvements observed with an energy restricted diet accumulated in bouts of less than 10 minutes per
without exercise in severely obese adults.51 However, bout can contribute effective body weight control.
results from the CALERIE Study showed when physi- However, there may be added benefits to progress-
cal activity was added to calorie restriction, there were ing these bouts to at least 10 minutes per bout.
significant reductions in both total cholesterol and LDL, • Physical activity is an important treatment compo-
and these improvements were not observed with calorie nent that can contribute to the long-term weight loss
restriction that did not include physical activity as part of success following bariatric surgery.
the intervention.96 • Physical activity contributes additional health ben-
efits beyond weight control, which further supports
the need for adults who are overweight or obese to
37.5.2.3 Inflammatory Markers engage in adequate amounts of physical activity.
It has been suggested that biomarkers of inflamma-
tion such as C-reactive protein (CRP), interleukin-6 Given these findings, healthcare and health-fitness
(IL-6), tissue necrosis factor-α (TNFα), and the anti- professionals should emphasize the need for patients to
inflammatory molecule, adiponectin, contribute to the engage in sufficient amounts of physical activity within
prothrombotic processes of atherosclerosis.97 Because efforts to prevent weight gain or for weight loss in adults.
480 Chapter 37 Exercise Management for the Obese Patient
REFERENCES
1. Flegal KM, Kruszon-Moran D, Carroll 14. Williamson DF, Madans J, Anda 29. Hunter GR, Wetzstein CJ, Fields
MD, Fryar CD, Ogden CL. Trends in RF, Kleinman JC, Kahn HS, Byers DA, Bamman MM. Resistance
obesity among adults in the United T. Recreational physical activity and t raining increases total energy expendi-
States, 2005 to 2014. JAMA 2016;315: ten-year weight change in a US national ture and free-living physical activity in
2284–2291. cohort. Int J Obes 1993;17: 279–286. older adults. J Appl Physiol 2000;89:
2. National Center for Health Statistics. 15. DiPietro L, Dziura J, Blair SN. Estimated 977–984.
Health, United States, 2016: With change in physical activity level (PAL) 30. Olson TP, Dengel DR, Leon AS, Schmitz
Chartbook on Long-Term Trends in and prediction of 5-year weight change in KH. Changes in inflammatory biomark-
Healthy. Hyattsville, MD, 2017. men: The Aerobics Center Longitudinal ers following one-year of moderate
3. Jensen MD, Ryan DH, Apovian CM, Study. Int J Obes 2004;28: 1541–1547. resistance exercise in overweight women.
Ard JD, Comuzzie AG, Donato KA, et al. 16. Lee IM, Djousse L, Sesso HD, Wang L, Int J Obes 2007;31: 996–1003.
2013 AHA/ACC/TOS guideline for the Buring JE. Physical activity and weight 31. Schmitz KH, Jensen MD, Kugler KC,
management of overweight and obesity gain prevention. JAMA 2010;303: Jeffery RW, Leon AS. Strength training
in adults: A report of the American 1173–1179. for obesity prevention in midlife women.
College of Cardiology/American Heart 17. Shiroma EJ, Sesso HD, Lee IM. Physical Int J Obes Relat Meta Disord 2003;27:
Association Task Force on Practice activity and weight gain prevention in 326–333.
Guidelines and The Obesity Society. J Am older men. Int J Obes (Lond) 2012;36: 32. Janssen I, Ross R. Effects of sex on the
Coll Cardiol 2014;63: 2985–3023. 1165–1169. change in visceral, subcutaneous adipose
4. National Institutes of Health National 18. Brown WJ, Kabir E, Clark BK, Gomersall tissue and skeletal muscle in response
Heart Lung and Blood Institute. Clinical SR. Maintaining a healthy BMI. Data to weight loss. Int J Obes Relat Meta
Guidelines on the Identification, from a 16-year study of young Australian Disord 1999;23: 1035–1046.
Evaluation, and Treatment of Overweight women. Am J Prev Med 2016;51: 33. Hagins M, Moore W, Rundle A.
and Obesity in Adults—The Evidence e165–e178. Does practicing hatha yoga satisfy
Report. Obes Res 1998;6(suppl.2): 19. Rosenberg L, Kipping-Ruane KL, Boggs recommendations for intensity of
51S–210S. DA, Palmer JR. Physical activity and the physical activity which improves
5. Jakicic JM, Rogers RJ, Davis KK, Collins incidence of obesity in young African- and maintains health and cardio-
KA. Role of physical activity and exercise American women. Am J Prev Med vascular fitness? BMC Complement
in treating patients with overweight and 2013;45: 262–268. Altern Med 2007;7: 40. doi:
obesity. Clin Chem 2018;64(1): 99–107. 20. Donnelly JE, Blair SN, Jakicic JM, 10.1186/1472–6882-1187–1140.
doi: 10.1373/clinchem.2017.272443. Manore MM, Rankin JW, Smith BK. 34. Sherman SA, Rogers RJ, Davis KK,
6. Cameron N, Nichols JF, Hill L, Patrick ACSM position stand on appropriate Minster RL, Creasy SA, Mullarkey
K. Associations betweeen physical intervention strategies for weight loss and NC, et al. Energy expenditure in vin-
activity and BMI, body fatness, and prevention of weight regain for adults. yasa yoga versus walking. J Phys Act
visceral adiposity in overweight or obese Med Sci Sports Exerc 2009;42: 459–471. Health 2017;14:597–605. Epub ahead
Latino and non-Latino adults. Int J Obes 21. Donnelly JE, Smith BK. Is exercise of print: April 1, 2017. doi: 10.1123/
2017;41: 873–877. effective for weight loss with ad libitum jpah.2016-0548.
7. Fan JX, Brown BB, Hanson H, diet? Energy balance, compensation, and 35. Daubenmier J, Moran PJ, Kristeller J,
Kowaleski-Jones L, Smith KR, Zick CD. gender differences. Exerc Sport Sci Rev Acree M, Bacchetti P, Kemeny ME, et al.
Moderate to vigorous physical activity 2005;33: 169–174. Effects of a mindfulness-based weight
and weight outcomes: Does every minute 22. Jakicic JM, Tate DF, Lang W, Davis KK, loss intervention in adults with obesity:
count? Am J Prev Med 2013;28: 41–49. Polzien K, Neiberg R, et al. Objective A randomized clinical trial. Obesity
8. Glazer NL, Lyass A, Esliger DW, Blease physical activity and weight loss in adults: 2016;24: 794–804.
SJ, Freedson PS, Massaro JM, et al. The Step-Up randomized clinical trial. 36. Spadaro KC, Davis KK, Sereika SM,
Sustained and shorter bouts of physical Obesity 2014;22: 2284–2292. Gibbs BB, Jakicic JM, Cohen S. Effects
activity are related to cardiovascular 23. Jakicic JM, Otto AD, Semler L, Polzien of mindfulness meditation on short-term
health. Med Sci Sports Exerc 2013;45: K, Lang W, Mohr K. Effect of physical weight loss and eating behaviors in over-
109–115. activity on 18-month weight change in weight and obese adults: A randomized
9. Jakicic JM, Gregg E, Knowler W, Kelley overweight adults. Obesity 2011;19: controlled trial. J Complement Integr
DE, Lang W, Miller GD, et al. Physical 100–109. Med 2017; Epub Dec 5, 2017.
activity patterns of overweight and obese 24. Hagan RD, Upton SJ, Wong L, Whittam 37. Levine JA, Vander Weg MW, Hill
individuals with type 2 diabetes in the J. The effects of aerobic conditioning JO, Klesges RC. Non-exercise activ-
Look AHEAD Study. Med Sci Sports and/or calorie restriction in overweight ity thermogenesis: The crouching tiger
Exerc 2010;42: 1995–2005. men and women. Med Sci Sports Exerc hidden dragon of societal weight gain.
10. Jefferis BJ, Parsons TJ, Sartini C, Ash 1986;18: 87–94. Arterioscler Thromb Vasc Biol 2006;26:
S, Lennon LT, Wannamethee SG, et al. 25. Wing RR, Venditti EM, Jakicic JM, 729–736.
Does duration of physical activity bouts Polley BA, Lang W. Lifestyle interven- 38. Chan CB, Ryan DA, Tudor-Locke
matter for adiposity and metabolic tion in overweight individuals with a C. Health benefits of a pedometer-
syndrome? A cross-sectional study of family history of diabetes. Diabetes Care based physical activity intervention in
older British men. Int J Behav Nutr 1998;21: 350–359. sedentary workers. Prev Med 2004;39:
Phys Act 2016;13: 36. doi: 10.1186/ 26. US Department of Health and Human 1215–1222.
s12966-12016-10361-12962. Services. Physical Activity Guidelines 39. Creasy SA, Rogers RJ, Gibbs BB, Davis
11. Loprinzi PD, Cardinal BJ. Association Advisory Committee Report 2008. KK, Kershaw EE, Jakicic JM. Effects of
between biologic outcomes and objec- Washington, DC: US Department of supervised and unsupervised physical
tively measured physical activity accumu- Health and Human Services; 2008 activity programmes for weight loss.
lated in >10-minute bout and <10-minute [January 19, 2009]. Available from: http: Obes Sci Pract 2017;3: 143–152.
bouts. Am J Health Promot 2013;27: //www.healt h.gov/pagu ideli nes/commi 40. Creasy SA, Lang W, Tate DF, Davis
143–151. tteereport.aspx. KK, Jakicic JM. Pattern of daily steps is
12. Wolff-Hughes DL, Fitzhugh EC, Bassett 27. Donnelly JE, Jakicic JM, Pronk NP, associated with weight loss: Secondary
DR, Churilla JR. Total activity counts Smith BK, Kirk EP, Jacobsen DJ, et al. analysis from the Step-Up randomized
and bouted minutes of moderate-to- Is resistance exercise effective for weight trial. Obesity 2018;26: 977–984. doi:
vigorous physical activity: Relationships management? Evid Based Prev Med 10.1002/oby.22171.
with cardiometabolic biomarkers using 2004;1: 21–29. 41. Physical Activity Guidelines Advisory
2003–2006 NHANES. J Phys Act Health 28. Hunter GR, Bryan DR, Wetzstein CJ, Committee. Physical Activity
2015;12: 694–700. Zuckerman PA, Bamman MM. Reistance Guidelines Advisory Committee
13. Strasser B. Physical activity in obesity and training and intra-abdominal adipose Scientific Report. Washington, DC:
metabolic syndrome. Ann N Y Acad Sci tissue in older men and women. Med Sci U.S. Department of Health and Human
2013;1281: 141–159. Sports Exerc 2002;34: 1023–1028. Services, 2018.
References 481
42. Proper KI, Singh AS, van Mechelen 56. Jakicic JM, Marcus BH, Lang W, Janney 71. Finlayson G, Bryant E, Blundell JE, King
W, Chinapaw MJ. Sedentary behaviors C. Effect of exercise on 24-month weight NA. Acute compensatory eating follow-
and health outcomes among adults: A
systematic review of prospective studies.
Am J Prev Med 2011;40: 174–182.
loss in overweight women. Arch Int Med
2008;168: 1550–1559.
57. Unick JL, Jakicic JM, Marcus BH.
ing exercise is associated with implicit
hedonic wanting for food. Physiol Behav
2009;97: 62–67.
37
43. Thorpe AA, Own N, Neuhaus Contribution of behavior interven- 72. Unick JL, Otto AD, Helsel D, Dutton
M, Dunstan DW. Sedentary behaviors tion components to 24 month weight C, Goodpaster BH, Jakicic JM. The
and subsequent health outcomes in loss. Med Sci Sports Exerc 2010;42: acute effect of exercise on energy intake
adults: A systematic review of longitu- 745–753. in overweight/obese women. Appetite
dinal studies. Am J Prev Med 2011;41: 58. Evans RK, Bond DS, Wolfe LG, Meador 2010;55: 413–419.
207–215. JG, Herrick JE, Kellum JM, et al. 73. Cai G, Cole SA, Butte N, Bacino C,
44. Jakicic JM, King WC, Marcus MD, Davis Participation in 150 minuts/week of mod- Diego V, Tan K, et al. A quantitative trait
KK, Helsel D, Rickman AD, et al. Short- erate or higher intensity physical activity locus on chromosome 18q for physical
term weight loss with diet and physical yields greater weight loss following activity and dietary intake in Hispanic
activity in young adults: The IDEA Study. gastric bypass surgery. Surg Obes Relat children. Obesity 2006;14: 1596–1604.
Obesity 2015;23: 2385–2397. Dis 2007;3: 526–530. 74. Rankinen T. Genetics and physical activ-
45. Creasy SA, Rogers RJ, Byard TD, 59. Bond DS, Evans RK, Wolfe LG, Meador ity level. In: Bouchard C, Katzmarzyk PT
Kowalsky RJ, Jakicic JM. Energy expen- JG, Sugerman HJ, Kellum JM, et al. (eds). Physical Activity and Obesity, 2nd
diture during acute periods of sitting, Impact of self-reported physical activity edition. Champaign, IL: Human Kinetics,
standing, and walking. J Phys Act Health participation on proportion of excess 2010, pp. 73–76.
2016;13: 573–578. weight loss and BMI among gastric 75. Stubbe JH, Boomsma DI, Vink JM,
46. Pate RR, Pratt M, Blair SN, Haskell WL, bypass surgery patients. Am Surg Cornes BK, Martin NG, Skytthe A, et al.
Macera CA, Bouchard C, et al. Physical 2004;70: 811–814. Genetic influences on exercise participa-
activity and public health: A recommen- 60. Bond DS, Phelan S, Wolfe LG, Meador tion in 37,051 twin pairs from seven
dation from the Centers for Disease and JG, Kellum JM, Maher JW, et al. countries. PLoS ONE 2006;20: e22.
Prevention and the American College Becoming physically activity after bariat- 76. Gallagher KI, Jakicic JM, Napolitano
of Sports Medicine. JAMA 1995;273: ric surgery is associated with improved MA, Marcus BH. Psychosocial factors
402–407. weight loss and quality of life. Obesity related to physical activity and weight
47. Jakicic JM, Wing RR, Butler BA, 2009;17: 78–83. loss in overweight women. Med Sci
Robertson RJ. Prescribing exercise in 61. Coen PM, Tanner CJ, Helbling NL, Sports Exerc 2006;38: 971–980.
multiple short bouts versus one continu- Dubis GS, Hames KC, Hui X, et al. 77. Jakicic JM, Otto AD. Physical activity
ous bout: Effects on adherence, cardio- Clinical trial demonstrates exercise recommendations in the treatment of
respiratory fitness, and weight loss in following bariatric surgery improves obesity. Psychiatr Clin N Am 2005;28:
overweight women. Int J Obes 1995;19: insulin sensitivity. J Clin Invest 2015;125: 141–150.
893–901. 248–257. 78. Ross R, Dagnone D, Jones PJH, Smith H,
48. Jakicic JM, Winters C, Lang W, Wing 62. Bergh I, Kvalem IL, Mala T, Hansen Paddags A, Hudson R, et al. Reduction in
RR. Effects of intermittent exercise BH, Sniehotta FF. Predictors of physical obesity and related comorbid conditions
and use of home exercise equipment on activity after gastric bypass - a pro- after diet-induced weight loss or exercise-
adherence, weight loss, and fitness in spective study. Obes Surg 2017;27: induced weight loss in men. Annu Inter
overweight women: A randomized trial. 2050–2057. Med 2000;133: 92–103.
JAMA 1999;282: 1554–1560. 63. Josbeno DA, Kalarchian MA, Sparto PJ, 79. Donnelly JE, Pronk NP, Jacobsen DJ,
49. Snyder KA, Donnelly JE, Jacobsen DJ, Otto AD, Jakicic JM. Physical activity Pronk SJ, Jakicic JM. Effects of a very-
Hertner G, J.M. J. The effects of long- and physical function in individuals post- low-calorie diet and physical-training
term, moderate intensity, intermittent bariatric surgery. Obes Surg 2011;21: regimenson body composition and resting
exercise on aerobic capacity, body compo- 1243–1249. metabolic rate in obese females. Am J
sition, blood lipids, insulin and glucose in 64. Kovacs SI. Factors associated with Clin Nutr 1991;54: 56–61.
overweight females. Int J Obes 1997;21: physical activity in patients undergoing 80. Church TS, Earnest CP, Skinner JS,
1180–1189. bariatric surgery. 2017. Blair SN. Effects of different doses of
50. White DK, Pettee Gabriel K, Kim Y, 65. Donnelly JE, Smith BK. Is exercise physical activity on cardiorespiratory
Lewis CE, Sterfeld B. Do short spurts effective for weight loss with ad-libitum fitness among sedentary, overweight
of physical activity benefit health? The diet? Energy balance, compensation, and or obese postmenopausal women with
CARDIA Study. Med Sci Sports Exerc gender differences. Exerc Sport Sci Rev elevated blood pressure. JAMA 2007;297:
2015;47: 2353–2358. 2005;33: 169–174. 2081–2091.
51. Goodpaster BH, DeLany JP, Otto 66. Bouchard C, Tremblay A, Nadeau A, 81. Blair SN, Kohl III H, Paffenbarger RS,
AD, Kuller LH, Vockley J, South-Paul Dussault J, Despres JP, Theriault G, et al. Clark DG, Cooper KH, Gibbons LW.
JE, et al. Effects of diet and physical Long-term exercise training and constant Physical fitness and all-cause mortality.
actvity interventions on weight loss and energy eintake. 1: Effect on body compo- A prospective study of healthy men and
cardiometabolic risk factors in severely sition and selected metabolic variables. women. JAMA 1989;262: 2395–2401.
obese adults: A randomized trial. JAMA Int J Obes 1990;14: 57–73. 82. Barlow CE, Kohl HW, Gibbons LW,
2010;304: 1795–1802. 67. Bouchard C, Tremblay A, Despres JP, Blair SN. Physical activity, mortality, and
52. Curioni CC, Lourenco PM. Long-term Theriault G, Nadeau A, Lupien PJ, et al. obesity. Int J Obes 1995;19: S41–S44.
weight loss after diet and exercise: The response to exercise with constant 83. Church TS, LaMonte MJ, Barlow CE,
Systematic review. Int J Obes 2005;29: energy intake in identical twins. Obes Blair SN. Cardiorespiratory fitness
1168–1174. Res 1994;2: 400–410. and body mass index as predictors of
53. Jeffery RW, Wing RR, Sherwood NE, 68. Ravussin E, Bogardus C. Relationship of cardiovascular disease mortality among
Tate DF. Physical activity and weight loss: genetics, age, and physical fitness to daily men with diabetes. Arch Intern Med
Does prescribing higher physical activity energy expenditure and fuel utilization. 2005;165: 2114–2120.
goals improve outcome? Am J Clin Nutr Am J Clin Nutr 1989;49: 968–975. 84. Farrell SW, Braun L, Barlow CE, Cheng
2003;78: 684–689. 69. Tremblay A, Fontaine E, Poehlman ET, YJ, Blair SN. The relation of body mass
54. Klem ML, Wing RR, McGuire MT, Mitchell D, Perron L, Bouchard C. The index, cardiorespiratory fitness, and
Seagle HM, Hill JO. A descriptive study effect of exercise-training on resting all-cause mortality in women. Obes Res
of individuals successful at long-term metabolic rate in lean and moderately 2002;10: 417–423.
maintenance of substantial weight loss. obese individuals. Int J Obes 1986;10: 85. Wei M, Kampert J, Barlow CE,
Am J Clin Nutr 1997;66: 239–246. 511–517. Nichaman MZ, Gibbons LW,
55. Schoeller DA, Shay K, Kushner RF. 70. Tremblay A. Physical activity level and Paffenbarger RS, et al. Relationship
How much physical activity is needed resting metabolic rate. In: Bouchard C, between low cardiorespiratory fitness
to minimize weight gain in previously Katzmarzyk PT (eds). Physical Activity and mortality in normal-weight, over-
obese women. Am J Clin Nutr 1997;66: and Obesity, 2nd edition. Chamaign, IL: weight, and obese men. JAMA 1999;282:
551–556. Human Kinetics, 2010. 1547–1553.
482 Chapter 37 Exercise Management for the Obese Patient
86. Lee CD, Blair SN, Jackson AS. with long-term cardiovascular disease 95. Church TS, Earnest CP, Thompson
Cardiorespiratory fitness, body composi- outcomes in overweight or obese people AM, Priest EL, Rodarte RQ, Saunders
tion, and all-cause and cardiovascular with type 2 diabetes: A post-hoc analysis T, et al. Exercise without weight loss
disease mortality in men. Am J Clin Nutr of the Look AHEAD randomised clini- does not reduce C-reactive protein: The
1999;69: 373–380. cal trial. Lancet Diabetes Endocrinol INFLAME study. Med Sci Sports Exerc
87. Sui X, LaMonte MJ, Laditka JN, 2016;4: 913–921. 2010;42: 708–716.
Hardin JW, Chase N, Hooker SP, et al. 91. Rankinen T, Church TS, Rice T, 96. Larson-Meyer DE, Redman L, Heilbronn
Cardiorespiratory fitness and adiposity Bouchard C, Blair SN. Cardiorespiratory LK, Martin CK, Ravussin E. Caloric
as mortality predictors in older adults. fitness, BMI, and risk of hypertension: restriction with or without exercise: The
JAMA 2007;298: 2507–2516. The HYPGENE study. Med Sci Sports fitness versus fatness debate. Med Sci
88. McAuley P, Pittsley J, Myers J, Abella Exerc 2007;39: 1687–1692. Sports Exerc 2010;42: 152–159.
J, Froelicher VF. Fitness and fatness as 92. Chen J, Das S, Barlow CE, Grundy S, 97. Van Gaal LF, Mertens IL, DeBlock
mortality predictors in healthy older Lakoski SG. Fitness, fatness, and systolic CE. Mechanisms linking obesity with
men: The veterans exercise testing study. blood pressure: Data from the Cooper cardiovascular disease. Nature 2006;444:
J Gerontol A Biol Sci Med Sci 2009;64: Center Longitudinal Study. Am Heart J 875–880.
695–699. 2010;160: 166–170. 98. Nicklas BJ, Ambrosius W, Messier SP,
89. Stevens J, Cai J, Evenson KR, 93. Wing RR, Jakicic J, Neiberg R, Lang W, Miller GD, Penninx BW, Loeser RF, et al.
Thomas R. Fitness and fatness as Blair SN, Cooper L, et al. Fitness, fatness, Diet-induced weight loss, exercise, and
predictors of mortality from all causes and cardiovascular risk factors in type 2 chronic inflammation in older, obese
and from cardiovascular disease in men diabetes: Look AHEAD Study. Med Sci adults: A randomized controlled clinical
and women in the lipid research clin- Sports Exerc 2007;39: 2107–2116. trial. Am J Clin Nutr 2004;79: 544–551.
ics study. Am J Epidemiol 2002;156: 94. Kelley GA, Kelley KS, Tran ZV. Aerobic 99. Hamer M, Steptoe A. Prospective study
832–841. exercise, lipids and lipoproteins in over- of physical fitness, adiposity, and inflam-
90. The Look AHEAD Research Group. weight and obese adults: A meta-analysis matory markers in healthy middle-
Association of the magniture of weight of randomized controlled trials. Int J aged men and women. Am J Clin Nutr
loss and changes in physical fitness Obes 2005;29: 881–893. 2009;89: 85–89.
38
CHAPTER
Dietary Management of
Overweight and Obesity
Nina Crowley, PhD, RDN, LD, Katherine R. Arlinghaus, MS, RD, LD, and
Eileen Stellefson Myers, MPH, RDN, LDN, CEDRD, FADA, FAND
these markers provide additional baseline measures from one’s body weight, total energy expenditure (TEE) must be
which patients’ progress can be monitored and evaluated. equivalent to total energy intake (TEI). Weight loss ulti-
During the medical examination and history, genetic mately involves the creation of an energy deficit. Typically,
syndromes as well as endocrine disorders such as hypo- an energy deficit of 500–750 kcal/day is recommended.3
thyroidism, Cushing’s disease, polycystic ovary syndrome, TEE consists of three components: basal energy expendi-
and other metabolic conditions should be ruled out as con- ture (BEE), thermic effect of food (TEF), and an adjust-
tributing reasons for a patient’s weight status. For female ment factor for the physical activity level (PAL). In practice,
patients, it is also important to inquire about the possibility resting energy expenditure (REE) is used in lieu of the BEE
of pregnancy before making weight loss recommendations. because it is impractical to measure energy expended in
The Institute of Medicine has set guidelines for total and the basal state. The REE is considered to be ~10% above
rate of weight gain during pregnancy by pre-pregnancy the basal state and is substituted for the more difficult-to-
BMI.5 Recommendations for weight gain during pregnancy measure TEF, which is also approximately 10% of TEE.
should be individualized based on pre-pregnancy BMI to
improve pregnancy outcome, avoid excessive maternal TEE = TEI
postpartum weight retention, and reduce the risk of the
child acquiring chronic disease later in life.6 Acquiring BEE + TEF + PAL = TEI
medication history is also essential in identifying if any
drugs are associated with weight gain and can be modified. REE + PAL = TEI
physical activity is a critical factor in the maintenance of size, and method of preparation. Mobile applications that
38
weight loss.12 The assessment of activity patterns is crucial enable self-monitoring of dietary intake may make the
to being able to tailor recommendations. process of keeping a seven-day food record more conve-
nient for patients. When done correctly, seven-day food
records reflect a good pattern on which to base any dietary
interventions or recommendations for change.
38.4.2 Determining Energy Intake
There are multiple ways to assess TEI and dietary compo-
sition including 24-hour recall, food frequency question- 38.5 DETERMINING EATING
naires, food records, and digital photography. Strengths
and limitations of these methods are listed in Table 38.1.
ENVIRONMENT AND READINESS
Regardless of the method of dietary assessment, the goal is FOR INTERVENTION
to determine a representative pattern from which dietary
interventions and recommendations can be made. The The practicalities of a patient’s eating environment are
establishment of such a pattern requires inquiry into not important to assess. Recommendations are more relevant
just what patients eat, but the time, place, and occasion of and feasible when the clinician understands the patient’s
eating, as well as the method of preparation and portion access to food, food budget, delineation of responsibility for
size of foods eaten. shopping and preparation, location of meals, cultural food
Many individuals with obesity unintentionally under- practices, and with whom meals are eaten. Assessing the
estimate their intake and are unable to adequately recall environment may help the clinician and the patient identify
their intake. In an office setting, dietary assessment should potential barriers to carrying out recommendations.
be timely. Patients are often instructed to bring in a food Although recommendations may focus on timing
diary (1–7 days or a typical day). Prior to assigning a food and meal frequency, there is limited evidence to support
diary, patients should be provided with detailed instruc- such recommendations.3 Consistent with the principles of
tions on how to keep a food record and counseled with energy balance, solely changing the frequency of meals,
regard to why it is important to establish a true baseline without decreasing TEI, does not appear to induce a
before dietary intervention. Seven-day, prospective food change in weight. Increased eating frequency has been
records should be kept by patients in as much detail as associated with increased energy intake through snacks,
possible, and should reflect the patient’s “usual” diet prior and individuals rarely compensate at meal times for previ-
to intervention. Food records should also be sensitive to ously eaten snacks.13 It is important for snacks to be low
the pattern of eating (time, place, and occasion), portion in calories (<200 calories) for patients to meet restricted
energy intake required for weight loss. Breakfast con- from normal eating patterns and can serve as a venue for
sumption has not been found to lead to greater weight loss reeducation about and/or reformulation of what foods can
in randomized control trials. 3 However, research looking be substituted or reintroduced.
at the relationship between circadian rhythm and weight Other dietary approaches achieve a caloric deficit
loss has indicated that eating a higher proportion of TEI through the restriction of particular foods or macro-
earlier in the day may be helpful in weight loss.14 Assessing nutrients. Results of randomized control trials indicate
patients’ schedules and lifestyle patterns can aid in the no difference in the rate or magnitude of weight loss
determination of how patients may be most successful in between diets of differing macronutrient composition
incorporating recommendations into their day. when caloric intake is held constant. 3 On the indi-
Current guidelines also recommend assessment of vidual level, however, it is likely that some approaches
motivation, readiness, and self-efficacy for weight man- will be superior to others at helping a patient achieve
agement based on behavior change theories and models the necessary caloric deficit and adhere to the diet long-
(cognitive-behavioral therapy, transtheoretical model, term. Additionally, cardio-metabolic outcomes may dif-
and social cognitive theory/social learning theory). Patient fer based on the dietary approach taken. For example,
motivation is a key component of success in a weight loss greater reductions in low-density lipoprotein cholesterol
program and is essential for any weight loss treatment. have been achieved through a low-fat diet compared to a
Motivational Interviewing (MI) is a collaborative, goal- low-carbohydrate diet; however, low-carbohydrate diets
oriented method of communication between a practitio- have produced a greater reduction in triglycerides and
ner and a client with a focus on drawing out a client’s larger increase in high-density lipoprotein cholesterol
personal motives by allowing a person to find answers on than a low-fat diet of equivalent energy restriction.4
his or her own. MI is believed to enhance motivation and In addition to weight loss, the Dietary Approaches to
self-efficacy, which are both considered to be key for mak- Stop Hypertension (DASH) diet with energy restric-
ing and sustaining behavior changes.8,11 Asking a patient tion produces reductions in blood pressure, and the
to rate on a scale from 0 to 10 the importance of behav- Mediterranean diet with energy restriction may also
ior change and their confidence in being able to make the result in cardiovascular risk factor improvements greater
change is a quick and effective tool that all clinicians can than those seen with low-fat diets. 3
use to gauge a patient’s readiness to change. Eating foods with low energy density, the ratio of
energy in a food to the weight of the food (kcal/g), may
be a strategy for appetite control and subsequent achieve-
ment of energy restriction as it allows for a greater
38.6 DIETARY INTERVENTION amount of food to be eaten relative to energy consumed.
Before beginning intervention, it is critical for the reg- It is important to note that for an energy deficit to occur
istered dietitian to discuss expectations and set realistic using this strategy, high energy-density foods must be
weight loss goals. As little as a 3–5% weight loss has been replaced by lower energy-density foods.15 Randomized
shown to improve clinical cardiovascular markers, and control trials have shown that solely increasing fruits
5–10% weight loss improves even more cardiovascular and vegetables (foods with low energy density) does not
risk factors.4 While clinically meaningful, this amount produce weight loss.16 Although this approach warrants
of weight loss may differ from a patient’s expectation. further research, a lack of standardized methods and
Addressing this potential mismatch prior to treatment can consensus on how to include beverages prohibits con-
be critical to a patient’s success. clusions to be drawn on the efficacy of this strategy for
A caloric deficit is necessary to accomplish desired weight loss at this time.17
weight loss. Therefore, any effective dietary intervention Similarly, because people typically do not compensate
must reduce energy consumption. Although many dietary for energy consumed from beverages by reducing their
approaches exist that reduce energy consumption, the energy from foods, it is recommended that caloric bever-
ideal composition of the diet for weight loss and weight ages be reduced or eliminated from the diet. For exam-
maintenance has not been established.3 Low and very low ple, reducing sugar sweetened beverage consumption has
calorie diets focus specifically on the creation of an energy been shown in randomized control trials to aid in weight
deficit. Very low calorie diets (≤800 kcal/day) are only loss.18 Nonnutritive sweeteners and fat substitutes have a
appropriate for use among patients with a BMI≥30. While role in the dietary management of overweight and obese
very low-calorie diets have been shown to produce signifi- individuals primarily because they can potentially lower
cantly greater weight loss than low calorie (>800kcal/day, caloric intake overall. For this reason nonnutritive sweet-
usually 1200–1600kcal/day) diets short-term, long-term eners have been endorsed by Academy of Nutrition and
weight loss is equivalent between the two diets.3 Meal Dietetics as a strategy to reduce energy intake by replacing
replacements (liquids, bars, frozen entrees) are an effec- sugar.19 It is important that sugar and fat substitutes are
tive strategy to increase adherence to the energy restric- used in the context of a regular diet, taken in modera-
tion imposed by either diet and are helpful with long-term tion and balanced with other foods, appreciated for total
weight management.3 Meal replacements, which are energy and nutrient value, and do not replace other nutri-
generally formulated products such as shakes or portion tious foods.19,20
controlled entrees, have value because they provide a regu- Finally, while total energy intake is of central impor-
lated amount of calories per serving, are usually fortified tance, reductions in intake are too often accompanied by a
with essential nutrients and fiber, and are economical, decline in essential nutrients and overall quality of the diet.
safe, and convenient to use. They also provide a departure Dietary supplements should be considered when eating
38.7 Intensity of Intervention 487
patterns are compromised, erratic, limited in choices, or average, a weight loss approaching 5–10% of initial
38
<1200 kcal/day.3 Vitamin and mineral supplements should weight.4 Energy needs change as weight is lost. Continual
never be used in lieu of a healthy diet, and their use should monitoring and evaluation of energy requirements enables
be evaluated on a case-by-case basis. adjustments to energy intake recommendations to be
Regardless of the dietary approach taken, close col- made as needed. This will help to prevent the weight loss
laboration with the patient will help to create a realis- plateau that occurs around six months for many patients.
tic diet plan that takes into consideration weight loss For weight maintenance after weight loss, there is also
and adequate nutrition. The dietary intervention should strong evidence for monthly visits of MNT over at least
begin with the patient’s usual pattern in mind. The diet one year.4 Alternative modes of delivery, including elec-
plan should build on the strengths of the patient’s cur- tronically providing visits through phone, internet, or tele-
rent diet and incorporate modifications necessary to man- health technology may be indicated.
age comorbid conditions. The usual food pattern derived If patients are unable to meet health and weight loss
from the seven-day food record can be used to determine goals, more intensive behavioral treatment, pharmacology,
recommendations for change. The plate method (choos- or evaluation for bariatric surgery should be considered as
emyplate.gov) provides a helpful tool for joint evaluation appropriate. Dietary intervention plays an important role
with the patient of foods eaten out of proportion to plate in all of these treatment approaches. Working with the
recommendations. Realistic strategies (e.g. increasing or patient’s medical team, the RDN can tailor the dietary
decreasing food groups, assessing portion sizes, changing approach to be appropriate for the patient’s specific treat-
or substituting foods especially of high caloric and/or high ment plan.
fat value, altering eating patterns when feasible, etc.) to For those with a BMI ≥ 27 kg/m 2 and an obesity-
impose a practical energy deficit should be decided upon related comorbid condition, or a BMI ≥ 30kg/m 2 ,
through collaboration with the patient. Using the approxi- pharmacotherapy can be considered as adjunctive to com-
mation of reduction in calories of about 500 kcal per day prehensive lifestyle intervention to achieve targeted weight
for a goal weight loss of approximately 1 lb per week, gen- loss and health goals.4 Clinicians should be aware of the
erally a reduction of 250–1000 kcal per day will result in current FDA-approved medications indicated for weight
0.5–2 lb of weight loss per week. loss through appetite suppression or absorption of fat.
Although the concept of energy balance seems The potential risk of the medication should be weighed
straightforward, great individual variation exists in against the potential benefit of weight loss for the indi-
weight loss treatment response and maintenance of vidual. Patients taking weight loss medications may be
weight loss. Dietary intake is complicated by the complex more likely to consistently adhere to a lower-calorie diet,
interplay between behavioral, psychological, and envi- increase physical activity, and experience weight loss and
ronmental factors. Individual variations in microbiome maintenance.4
have been suggested to explain some of the individual Patients who have a BMI ≥ 35 kg/m 2 with obesity-
variation in how much energy is absorbed from foods. 21 related comorbid conditions or BMI ≥ 40 kg/m 2 who are
Established genetic and epigenetic variability underscore motivated to lose weight but for whom behavioral treat-
the importance of individualizing dietary intervention, ment has not resulted in sufficient weight loss should be
however it is unknown how to effectively do this. 22 offered a referral to an experienced bariatric surgeon with
Long-term adherence to dietary interventions is affected an interdisciplinary team of medical, nutritional, and psy-
by how well the diet composition meets the most impor- chological professionals for evaluation.4 Several factors
tant of these established needs. The magnitude of weight are involved in the decision to undergo surgery: patient
loss achieved in the first few months of treatment is the motivation, treatment adherence, operative risk, optimi-
best predictor of overall outcomes. 23,24 For these reasons, zation of comorbid conditions, and insurance coverage.4
realistic goals and expectations for weight loss need to Although bariatric surgery is the most clinically and
be addressed prior to beginning intervention and dietary cost-effective treatment for severe obesity, less than 1%
approaches taken need to be decided on iteratively with of patients with severe obesity undergo it. The decision
the patient. to discuss surgical options is subjective and inconsistent,
likely due to bias towards people with obesity and the
stigma associated with having surgery.
38.7 INTENSITY OF INTERVENTION Patients rely on recommendations from primary care
providers and other healthcare practitioners for treat-
After dietary intervention and appropriate weight loss ment recommendations for chronic diseases, including
goals are determined with the patient, discussion about obesity. 25 Providers often incorrectly assume that people
the intensity of the intervention is important. The AHA/ with obesity are well-aware of their excess weight, and
ACC/TOS Guideline recommends referral for comprehen- report feeling ineffective at helping patients with obesity
sive lifestyle intervention for all patients encouraged to lose weight. 25 Using compassion of the complexities of the
lose weight, including those for whom medical or surgi- disease of obesity and following a shared decision-mak-
cal intervention is recommended.4 Frequency of contact is ing approach, it is imperative that healthcare providers
an important characteristic in achievement of weight loss. tell patients when their weight is a health concern, that
There is strong evidence for at least 14 medical nutrition there are treatment options for overweight and obesity,
therapy (MNT) encounters (group or individual) with an that the provider recommends treatment, and that the pro-
RDN over a period of at least six months.4 High-intensity, vider will support the patient throughout treatment and
comprehensive weight loss interventions produce, on maintenance.4
488 Chapter 38 Dietary Management of Overweight and Obesity
REFERENCES
1. Bray GA. Obesity: The disease. recommendations 2014” Academy of American Journal of Clinical Nutrition
Journal of Medicinal Chemistry Nutrition and Dietetics. https: //www.and 2010;91(4):913–22.
2006;49(14):4001–7. eal.org/topic.cf m?menu=5276&cat=469 16. Kaiser KA, Brown AW, Bohan Brown
2. Wing RR, Lang W, Wadden TA, 0. Accessed December 13, 2017. MM, Shikany JM, Mattes RD, Allison
Safford M, Knowler WC, Bertoni AG, 9. Esper DH. Utilization of nutrition- DB. Increased fruit and vegetable intake
et al. Benefits of modest weight loss in focused physical assessment in identifying has no discernible effect on weight loss: A
improving cardiovascular risk factors micronutrient deficiencies. Nutrition in systematic review and meta-analysis. The
in overweight and obese individuals Clinical Practice 2015;30(2):194–202. American Journal of Clinical Nutrition
with type 2 diabetes. Diabetes Care 10. Frankenfield D, Roth-Yousey L, Compher 2014;100(2):567–76.
2011;34(7):1481–6. C. Comparison of predictive equations 17. Perez-Escamilla R, Obbagy JE, Altman
3. Raynor HA, Champagne CM. Position of for resting metabolic rate in healthy JM, Essery EV, McGrane MM, Wong
the Academy of Nutrition and Dietetics: nonobese and obese adults: A systematic YP, et al. Dietary energy density and
Interventions for the treatment of over- review. Journal of the American Dietetic body weight in adults and children:
weight and obesity in adults. Journal of Association 2005;105(5):775–89. A systematic review. Journal of the
the Academy of Nutrition and Dietetics 11. Mifflin MD, St Jeor ST, Hill LA, Scott Academy of Nutrition and Dietetics
2016;116(1):129–47. BJ, Daugherty SA, Koh YO. A new 2012;112(5):671–84.
4. Jensen MD, Ryan DH, Apovian CM, predictive equation for resting energy 18. Tate DF, Turner-McGrievy G, Lyons
Ard JD, Comuzzie AG, Donato KA, et al. expenditure in healthy individuals. The E, Stevens J, Erickson K, Polzien K, et
2013 AHA/ACC/TOS guideline for the American Journal of Clinical Nutrition al. Replacing caloric beverages with
management of overweight and obesity 1990;51(2):241–7. water or diet beverages for weight loss
in adults: a report of the American 12. Donnelly JE, Blair SN, Jakicic JM, in adults: Main results of the Choose
College of Cardiology/American Heart Manore MM, Rankin JW, Smith BK. Healthy Options Consciously Everyday
Association Task Force on Practice American College of Sports Medicine (CHOICE) randomized clinical trial. The
Guidelines and The Obesity Society. Position Stand. Appropriate physical American Journal of Clinical Nutrition
Journal of the American College of activity intervention strategies for weight 2012;95(3):555–63.
Cardiology 2014;63(25 Pt B):2985–3023. loss and prevention of weight regain for 19. Fitch C, Keim KS. Position of the acad-
5. American College of Obstetricians adults. Medicine and Science in Sports emy of nutrition and dietetics: Use of
and Gynecologists. ACOG Committee and Exercise 2009;41(2):459–71. nutritive and nonnutritive sweeteners.
opinion no. 548: Weight gain during 13. Bes-Rastrollo M, Sanchez-Villegas A, Journal of the Academy of Nutrition and
pregnancy. Obstetrics and Gynecology Basterra-Gortari FJ, Nunez-Cordoba Dietetics 2012;112(5):739–58.
2013;121(1):210–212. JM, Toledo E, Serrano-Martinez M. 20. Position of the American Dietetic
6. Rasmussen KM, Catalano PM, Yaktine Prospective study of self-reported Association: Fat replacers. Journal of
AL. New guidelines for weight gain usual snacking and weight gain in a the American Dietetic Association
during pregnancy: What obstetrician/ Mediterranean cohort: The SUN project. 2005;105(2):266–75.
gynecologists should know. Current Clinical Nutrition 2010;29(3):323–30. 21. Krajmalnik-Brown R, Ilhan ZE,
Opinion in Obstetrics and Gynecology 14. St-Onge MP, Ard J, Baskin ML, Chiuve Kang DW, DiBaise JK. Effects of
2009;21(6):521–526. SE, Johnson HM, Kris-Etherton P, et al. gut microbes on nutrient absorp-
7. Academy of Nutrition and Dietetics. Meal timing and frequency: Implications tion and energy regulation.
Nutrition Terminology Reference for cardiovascular disease preven- Nutrition in Clinical Practice
Manual (eNCPT): Dietetics Language for tion: A scientific statement from the 2012;27(2):201–14.
Nutrition Care. http://ncpt.webauthor. American Heart Association. Circulation 22. MacLean PS, Wing RR, Davidson T,
com. Accessed December 13, 2017. 2017;135(9):e96–121. Epstein L, Goodpaster B, Hall KD, et al.
8. Academy of Nutrition and Dietetics 15. Rolls BJ, Roe LS, Meengs JS. Portion NIH working group report: Innovative
Evidence Analysis Library. “Adult weight size can be used strategically to increase research to improve maintenance of
management: Executive summary of vegetable consumption in adults. The weight loss. Obesity 2015;23(1):7–15.
References 489
23. Unick JL, Hogan PE, Neiberg RH, 24. Wing RR, Hamman RF, Bray GA, 25. Funk LM, Jolles S, Fischer LE, Voils
Cheskin LJ, Dutton GR, Evans-Hudnall Delahanty L, Edelstein SL, Hill JO, et CI. Patient and referring practitioner
G, et al. Evaluation of early weight
loss thresholds for identifying nonre-
sponders to an intensive lifestyle interven-
al. Achieving weight and activity goals
among diabetes prevention program
lifestyle participants. Obesity Research
characteristics associated with the likeli-
hood of undergoing bariatric surgery:
A systematic review. JAMA Surgery
38
tion. Obesity 2014;22(7):1608–16. 2004;12(9):1426–34. 2015;150(10):999–1005.
39
CHAPTER
Pharmacological Management
of the Patient with Obesity
Magdalena Pasarica, MD, PhD and Nikhil V. Dhurandhar, PhD
(HTN), dyslipidemia, sleep apnea, several cancers, experts and medical providers have a renewed and intensi-
and gall bladder disease, 3 all of which contribute to the fied interest in the drug industry, together with the support
increase in morbidity and mortality.4 In addition, obesity of the Food and Drug Administration (FDA), to develop
increases the risk for other diseases including rheumatoid new and more effective obesity medications for the acute
arthritis, nonallergic rhinitis, major depressive disorder, and long-term management of obesity and weight mainte-
and other types of cancer. 3 The number of deaths related nance. Many adults affected with obesity will have tried
to high BMI are increasing, as shown by a 28.3% increase several self-help approaches available through advertise-
from 1990 to 2015, when it reached 4 million globally. ments, social media, and on the advice of friends and fam-
This represents 7.1% of the deaths from any cause and ily before consulting with their HCPs for advice about
120 million disability adjusted life years. 5 Most impor- their unhealthy weight. Public awareness is increasing
tantly, modest weight loss improves multiple comorbidi- about the medical and lifestyle consequences of being an
ties.6 Therefore, more effective measures to prevent and individual with obesity. Medical professionals are at the
treat obesity are needed, as well as an increase in the use forefront of treating patients with obesity. Their actions
of currently available weight loss methods. are supported by newly released obesity management
guidelines.9,10 This chapter will discuss the FDA approved
pharmacological treatment of obesity. Specifically, we will
39.2 OBESITY TREATMENT focus on the mechanisms, indications, efficacy, and side
effects of the nine obesity drugs approved for short-term
Historically, clinical treatment of obesity has focused on and long-term weight loss. We will also provide detailed
lifestyle modification but has recently evolved to include clinical considerations for providers who are considering
various drug therapies and bariatric surgery. Although pharmacological therapy in the management of patients
each component claims efficacy, a successful treatment with obesity.
of obesity often needs more than just a single approach. In the past, when only one or two drugs for weight loss
Combinations of some of these components are recom- were available with limited efficacy or concerns for safety,
mended for maximum weight loss and successful main- healthcare providers were more likely to use either drugs
tenance. Healthcare providers have often been reluctant approved for other indications with side effects of weight
to prescribe anti-obesity drugs. In the past, this was due loss or natural compounds with limited data on weight
to the addictive potential of amphetamines (which are no loss that do not need FDA approval. Drugs used off-label
longer used as obesity drugs), and the belief that obesity for weight loss include antidepressants (fluoxetine, bupro-
drugs do not work in the long term. Currently available pion), anti-seizure drugs (topiramate, zonisamide, atom-
obesity drugs approved for short-term and long-term use oxetine) and anti-diabetic drugs (metformin, acarbose,
can be effective, with maximal potential when used as rec- exenatide, amylin, pramlintide); non-prescription medica-
ommended, in addition to lifestyle changes. Some people, tion used for weight loss include ephedra, laxatives, dietary
including some physicians and healthcare professionals supplements, and phenylpropanolamine.11,12 However,
seem to believe that people with obesity have little or no due to the newly FDA-approved weight loss drugs for long
personal control over their eating and behavior patterns term and short term, strong safety data, and guideline
and attitudes about their weight control. This leads to a recommendations from multiple societies to use only the
misconception that a simple change in patient’s attitude FDA approved drugs, we predict that most providers will
and behavior is all that is necessary to achieve medically increase the use of FDA-approved obesity drugs, which
needed weight loss. More than this, some healthcare pro- are presented below. In addition, the Endocrine Society
viders (HCPs) and administrators believe that lifestyle recommends against the use of off-label medications for
changes are easy to achieve, and therefore they do not weight loss for clinical management of patients with obe-
provide adequate support for the patients struggling with sity, with the exception of research trials or providers with
lifestyle changes. Furthermore, since obesity is perceived extensive expertise dealing with very informed patients.13
to be a self-imposed issue, drug side effects of any degree
are considered unacceptable for treating this “behavioral”
condition. The reality is that it is hard to achieve success- 39.3 THE FDA-APPROVED OBESITY
ful weight management for the majority of the population
with obesity if the option of drug therapy is underutilized DRUGS
due to multiple contributing factors, including miscon-
ceptions. This environment has created reluctance on the 39.3.1 Drugs Approved for Short-term Use
part of some HCPs to use obesity drugs.7 Research from
past several decades has revealed that lifestyle modifica- 39.3.1.1 Phentermine (Adipex, Ionamin, Lomaira)
tion alone as a treatment for obesity, even if difficult to Phentermine is the most commonly prescribed obesity
achieve, may help some individuals, but is inadequate to drug in the United States, as shown by the 2012–2015
bring about the changes at the community level or to stop National Prescription Audit database. U.S. providers pre-
the global obesity epidemic. Concerted efforts are required scribe phentermine nearly two times more compared with
from various angles to prevent or treat obesity, and this other weight loss drugs.14 The FDA approved phentermine
includes the use of pharmacological agents to supplement for short-term treatment of obesity in 1959, and it is a
the weight loss efforts of individuals. New discoveries on schedule IV drug. It is approved for short-term weight loss
the genetic and chemical basis for obesity8 have led to a as an adjunct to lifestyle changes in patients with a BMI
rapid expansion of research on obesity drugs. Obesity of 30 kg/m 2 or greater or patients with a BMI of 27 kg/m 2
39.3 The FDA-Approved Obesity Drugs 493
or greater in the presence of at least one weight-related sleep, and increased time in stage 1 sleep.17 In this study, the
39
comorbidity. However, reports show that in practice it is dropout rate was high, 82%. Diethylpropion is not recom-
also commonly used for longer periods.15 It is a centrally mended for patients with heart disease, high blood pressure,
active adrenergic drug, a sympathomimetic amine that hyperthyroidism, or glaucoma. The recommended dose is
stimulates norepinephrine release in synaptic terminals. 75 mg/day. A recent pre-clinical study showed that admin-
With phentermine use, patients can experience increased istering the drug in the active phase of the day increases the
satiety and less hunger, craving, binging, and night time amount of weight loss produced.26 The most recent clini-
eating. Clinical trials show effectiveness and safety16,17 cal trial with diethylpropion showed that long-term (six
including studies in combination with fenfluramine.18–21 months) administration of the drug with a hypocaloric diet
Due to a possible association with valvular heart disease, causes a difference in weight loss of 6.6% from baseline
fenfluramine was removed from the market by the FDA in compared to a placebo.27
1997. Phentermine was not shown to contribute to valvu- Diethylpropion was approved in 1959 for short-term
lar heart disease and was not withdrawn. (few weeks) treatment of weight loss in addition to caloric
The popularity of phentermine over the other sched- restriction in patients with a BMI at or above 30 kg/m 2
ule IV drugs is most likely due to the long-term medical and who have not responded to a lifestyle management
research and the subsequent clinical experience gathered of obesity. It is dispensed as either 25 mg tablets to be
with the drug combination of phentermine and fenflura- taken three times a day, one hour before meals, or as a
mine.18–20 Also, phentermine is associated with a rapid 75 mg extended release to be taken mid-morning. Serious
onset of appetite control and the improvement in patient side effects include tachycardia, HTN, pulmonary HTN,
attitude and weight management program adherence.18–20 valvular heart disease, psychosis, and hallucinations.
The most common side effects of phentermine include Common side effects include constipation, xerostomia,
decreased appetite, dry mouth, headache, insomnia, irri- nausea, vomiting, anxiety, dizziness, and insomnia (http
tability, nervousness, euphoria, palpitations, tachycardia, s://w w w.ac c essd a ta.f d a.go v /dru g satf d a_do c s/la b el/2
and an elevated blood pressure. Phentermine should be 004/11722s029,12546s032lbl.pdf).
avoided in patients with active cardiovascular disease,
moderate to severe HTN, hyperthyroidism, agitated
states, glaucoma, and a history of drug abuse. Drug abuse 39.3.1.3 Benzphetamine (Didrex)
potential and addiction is reported as minimal. 22 There Benzphetamine is a sympathomimetic amine approved
have been a few case reports of primary pulmonary hyper- in 1960 for short-term (few weeks) treatment of weight
tension in patients taking phentermine alone. 23 loss in addition to caloric restriction in patients with a
Phentermine is available as a 37.5 mg scored tablet BMI at or above 30 kg/m 2 who have not responded to a
and in 15 and 30 mg capsule form. These are also the lifestyle management of obesity. A systematic review of
maximum approved doses (Adipex: https: //www.accessda clinical trials shows reports that benzphetamine produces
ta.fda .gov/drugs atfda _docs /label/201 2/085128s 0 65lb on average 3.3 kg of weight loss over 16 to 17 weeks of
l.pdf; Ionamin: https: //ww w.accessdata.fda.gov/drugsatfd treatment compared to a placebo. 28 It shouldn’t be used
a_docs/label/2012/011613s027lbl.pdf). In 2016, the FDA with other anorectic drugs. Even though no cases of val-
approved a new formulation of phentermine containing vulopathy have been reported with benzphetamine use
only 8 mg of active substance as a tablet (Lomaira: https: // alone, it is recommended to carefully assess the benefits
lomaira.com/Prescribing _Information.pdf), for the same of weight loss vs. the potential risks for serious side effects
indications as the higher dosage. The advantage of this such as valvular heart disease and pulmonary hyperten-
lower dosage formulation is that it can be used for patients sion (https://w w w.accessdata.fda.gov/drugsatfda_docs/
who are sensitive to higher dosages, and it can be taken up label/2010/012427s026lbl.pdf). It is rarely used to treat
to three times a day. This therefore increases the options obesity with only 4% of total weight loss prescriptions
for a personalized treatment plan. However, there is no reported between 2008 and 2011 when only six drugs
available data comparing the efficacy of these dosages. 24 were approved for weight loss.15 This may be due to the
drug being Schedule III, with abuse potential higher than
the more favored and low-risk Schedule IV drugs. Due to
39.3.1.2 Diethylpropion (Tenuate) the similarity between the structures of benzphetamine
Diethylpropion is a centrally active adrenergic sympa- and amphetamines, it is recommended not to discontinue
thomimetic agent with an action similar to phentermine. abruptly in order to avoid extreme fatigue and mental
Diethylpropion is structurally similar to the FDA approved depression. Serious side effects include psychosis, HTN,
antidepressant drug bupropion. Short-term studies25 have dependency/abuse, cardiomyopathy, and cardiac isch-
compared diethylpropion to a placebo in a six-month trial emia. Common side effects include palpitations, tachy-
where the diethylpropion treated group lost 12.3% of initial cardia, insomnia, tremor, and elevated blood pressure
body weight compared to 2.8% loss in the placebo group. In (https://w w w.accessdata.fda.gov/drugsatfda_docs/label/2
a 24-week study comparing continuous diethylpropion use 010/012427s026lbl.pdf).
daily vs. every other month, the continuous therapy group
was the most successful. Blood pressure reduction occurred
in proportion to the weight lost.17 Adverse effects included 39.3.1.4 Phendimetrazine (Bontril, Prelu-2)
dry mouth, euphoria, asthenia, nervousness, decreased Phendimetrazine is a sympathomimetic amine similar to
appetite, insomnia, and sleeplessness with frequent awak- amphetamine. Phendimetrazine was FDA approved in
ening. There was a delay of rapid eye movement (REM) 1982 for short-term (few weeks) treatment of weight loss
494 Chapter 39 Pharmacological Management of the Patient with Obesity
in addition to caloric restriction in patients with a BMI type 2 diabetes. The study aim was to investigate the
at or above 30 kg/m 2 or BMI at or above 27 kg/m 2 in the effect of orlistat on weight regain and cardiovascular risk
presence of other risk factors for patients who have not factors following a very-low-energy diet (VLED). Subjects
responded to a lifestyle management of obesity. It shouldn’t who lost at least 5% of their body weight (309 of 383 sub-
be used with other anorectic drugs. Even though no cases jects) were then randomized to receive lifestyle counseling
of valvulopathy have been reported with phendimetra- together with a placebo or orlistat of 120 mg, three times
zine use alone, it is recommended to carefully assess the a day for three years. Study results identified that com-
benefits of weight loss vs. the potential risks for serious pared to the placebo group, orlistat plus lifestyle inter-
side effects such as valvular heart disease and pulmonary vention resulted in an additional 2.4 kg weight loss after
HTN. Other serious side effects include psychosis and VLED and a reduced occurrence of type 2 diabetes for up
withdrawal syndrome if discontinued abruptly. Common to three years. The authors concluded that orlistat may be
side effects include tachycardia, palpitations, HTN, and a useful adjunct to conventional dietary and lifestyle treat-
insomnia (https://w w w.accessdata.fda.gov/drugsatfda_do ment of high-risk subjects with obesity.39
cs/label/2012/018074s034lbl.pdf). Due to its potential for Another study examined the effect of orlistat on eat-
addiction, it is a Schedule III drug and is rarely prescribed ing behavior in a three-year weight maintenance trial.
by providers, similar to benzphetamine.15 Three hundred and six women and men with obesity
(19–45 years old), who were a part of the Scandinavian
Multicenter study of subjects with obesity and the meta-
39.3.2 Drugs Approved for Long-Term Use bolic syndrome, were selected. Subjects were treated with
orlistat after VLED-induced weight loss and followed for
39.3.2.1 Orlistat (Xenical TM, Alli TM) the next three years in a maintenance program. Results
Orlistat acts through inactivating gastrointestinal lipase showed that dietary restraint increased, and disinhibition,
thereby partially inhibiting the digestion of fat. This action hunger, and binge eating decreased in orlistat and placebo
results in a decrease in fat absorption and energy intake, and groups in a similar fashion. The authors pointed out that
the promotion of malabsorption.29–32 Fat absorption can these changes in eating behaviors are needed for success-
be reduced by approximately one-third in subjects eating a ful weight maintenance.38
meal containing 30% fat. Less than 1% of this peripherally Several attempts to decrease the gastrointestinal side
acting drug is absorbed. Gastro-intestinal (GI) side effects effects caused by orlistat have been made. A 12-week study
can occur in up to 40% of patients. Malabsorption can with adult subjects with obesity taking flaxseed fiber and
result in diarrhea, fecal incontinence, or urgent, oily stool dietary calcium in addition to orlistat showed no improve-
anal leakage, bloating, abdominal pain, and gas. There may ment in the gastrointestinal side effects. However, fecal
be the need for fat-soluble vitamin replacement. Higher fat excretion was increased while the side effects were not
dietary fat content increases the likeliness of GI-adverse worsened.40
events.33 In a two-year orlistat study, drug-treated subjects In 1999, the FDA approved orlistat for weight loss
lost nearly 10% body weight in the first year compared to and weight maintenance as Xenical, containing 120 mg
5–6% weight loss in the placebo group.33 The study dose active substance to be taken three times a day. In 2007,
of orlistat was 120 mg, three times a day (TID). There was FDA approved orlistat (Alli) as an over-the-counter (OTC)
about a 4-lb weight regain during the second year in the obesity drug for adults. Alli contains 60 mg of active
treatment group vs. 8 lbs in the placebo group. This signified drug to be taken three times a day, in conjunction with
a sustained weight reduction in study year two. During the a reduced calorie and low-fat diet. Exercise and a multi-
study, fasting, low-density lipoprotein cholesterol and insu- vitamin are also recommended. Side effects of the OTC
lin levels improved. Some lipid values improved more than orlistat are similar to prescription orlistat. The FDA has
can be explained with weight reduction alone. Lipid-soluble received reports of rare cases of severe liver injury in the
vitamins A, D, E and β-carotene concentrations may be use of orlistat by prescription or OTC use. In response,
slightly reduced after treatment with orlistat. Some nutrients the FDA has added a drug label (NIH Publication No.
and some medications might have decreased absorption. 07–4191November 2004, Updated December 2010).
Antihypertensive agents, warfarin, and oral contraceptive Serious adverse reactions of orlistat include hypersensitiv-
concentrations are not affected by orlistat.33–35 ity, anaphylaxis, angioedema, leukocytoclastic vasculitis,
In studies of subjects with obesity and with or with- fat-soluble vitamin deficiency, hepatotoxicity, nephrotox-
out type 2 diabetes, orlistat demonstrated an improve- icity, and oxalate nephropathy. Common side reactions
ment in glucose metabolism and a reduction in high blood include oil-spotting, flatus with discharge, fecal urgency,
pressure. 36,37 In a three-year orlistat weight maintenance and fecal incontinence (https://ww w.accessdata.fda.gov/
study, there was no change in eating behavior, except in drugsatfda_docs/label/20 09/020766s026lbl.pdf).
a subgroup that selectively decreased their intake of fatty
foods. The subgroup had an enhanced weight mainte-
nance, which the study’s authors ascribed to a change 39.3.2.2 Lorcaserin (Belviq TM, Belviq XR TM)
in fat consumption behavior. 38 Education on lowering Lorcaserin is a selective serotonin receptor agonist influ-
dietary fat consumption is needed for maximizing weight encing hunger.41 A 12-week weight loss study used dif-
loss with the help of orlistat. ferent doses of lorcaserin vs. a placebo in 469 adults.
A three-year orlistat study involved 383 adults who had Compared to the placebo group, there was more weight
abdominal obesity and metabolic risk factors, including loss in the lorcaserin groups proportionate to the dose.
dyslipidemia, impaired fasting glucose, and diet-treated Side effects included headache, dizziness, and nausea.42
39.3 The FDA-Approved Obesity Drugs 495
In a one-year lorcaserin study, 4,008 adults with obesity A two-phase trial was designed to determine if lor-
39
and overweight received either lorcaserin 10 mg once or caserin with lifestyle modifications could be effective for
twice daily. All subjects received a lifestyle intervention weight maintenance. After losing at least 5% of the base-
program. Weight loss (in the 5%–10% range) was statisti- line weight with lifestyle modifications and meal replace-
cally significant in the lorcaserin group compared to the ment therapy, participants will be randomized to either
placebo group and was dose-dependent. No increase in lorcaserin and lifestyle education or lifestyle education,
valvulopathy was seen in serial echocardiograms.43 alone. If this trial confirms that lorcaserin is efficient for
A two-year clinical trial involved 3,182 adults who weight maintenance, it will constitute a needed alternative
were overweight or had obesity. They received 10mg of for weight maintenance.46
a placebo or lorcaserin twice a day, as well as counseling. A recent tolerability study showed that no dose adjust-
The treatment group showed significant weight loss at one ments are necessary for elderly patients (older than 65)
year and maintenance of weight loss at two years. First- with normal renal function or patients with mild/moder-
year weight loss in the lorcaserin treated group averaged ate renal or hepatic impairment.47
5.8 kg compared to 2.2 kg in the placebo group. Weight
loss was maintained in year two in almost 70% of the lor-
caserin group compared to 50% for those on placebo. The 39.3.2.3 Phentermine-Topiramate ER (Qsymia)
most common side effects were headache, nausea, and Phentermine-topiramate ER is a combination of the appe-
dizziness. There were no increased cardiac valvulopathy tite suppressant phentermine together with the anticon-
findings.41 vulsant topiramate, which acts on Gamma-aminobutyric
To address the concerns of valvulopathy, data from acid (GABA) receptors. Phentermine was discussed in the
three prospective high-quality placebo-controlled trials previous section. Topiramate, by itself, was FDA approved
for 52 weeks of 5,249 subjects showed that 5% weight for treatment of epilepsy in 1996 and for migraine prophy-
loss was associated with an odds ratio of 1.15 for valvu- laxis in 2004; however, it was long studied as a treatment
lopathy. Even if the lorcaserin group lost more weight, the for weight loss. A meta-analysis of randomized controlled
rate of echocardiographic valvulopathy was not different trials showed that topiramate induced 5.34 kg (95% con-
in the placebo (2.04%) vs. lorcaserin group (2.37%).44 fidence interval [95%CI]: −6.12 to −4.56) of additional
Currently, a multicenter, randomized, double-blind, weight loss as compared with a placebo. However, the
placebo-controlled, parallel group study (CAMELLIA- adverse events (paresthesia, taste impairment, psycho-
TIMI) is examining the incidence of major adverse car- motor disturbance) lead to significant dropout rates (odd
diovascular events in 12,000 subjects with cardiovascular ratio of withdrawal from adverse events was 1.94, 95%
disease or multiple cardiovascular factors (https://clinic CI: 1.64 to 2.29).48 This led to the consideration of topira-
altrials.gov/ct2 /show/NCT02019264). mate as an adjunct medication, where a lower dose of the
Lorcaserin was approved in 2012 by the FDA as an topiramate could be enhanced with another drug—in this
adjunct to lifestyle changes for chronic weight manage- case, phentermine.
ment in patients with a BMI of 30 kg/m 2 or greater or A 56-week, phase III study of phentermine plus topi-
patients with a BMI of 27 kg/m 2 or greater in the presence ramate assessed the efficacy and safety of the drug combi-
of at least one weight-related comorbidity. Lorcaserin is nation on body weight and comorbidities in 2,487 adults
available as 10 mg tablets to be taken twice daily or 20 who had overweight or obesity and two or more of the fol-
mg XR to be taken once daily. It should be discontinued lowing comorbidities: hypertension, dyslipidemia, type 2
if the patient does not lose more than 5% of initial body diabetes, prediabetes, or abdominal obesity.49 The drug
weight after 12 weeks of treatment. The most common doses were a once-daily phentermine 7.5 mg plus topira-
adverse events caused by lorcaserin include headache, diz- mate 46.0 mg, or phentermine 15.0 mg plus topiramate
ziness, fatigue, nausea, dry mouth, and constipation (in 92.0 mg. All subjects received counseling for lifestyle
patients without diabetes) and hypoglycemia, headache, management. The change in body weight was minimal
back pain, cough, and fatigue (in patients with diabetes). in the placebo group (−1.4 kg) but significant and dose-
Lorcaserin may cause serious side effects such as sero- dependent in the drug groups (−8.1 kg and −10.2 kg,
tonin syndrome or neuroleptic malignant syndrome-like respectively). The most common side effects in the treat-
reactions, as well as valvular heart disease. Due to these ment groups were also dose related. At the higher dose,
possibilities, it is recommended that lorcaserin should not they included dry mouth and paresthesia (21%), constipa-
be used in conjunction with selective serotonin reuptake tion (17%), insomnia, dizziness and dysgeusia (10%), anx-
inhibitors, serotonin-norepinephrine reuptake inhibitors, iety-related adverse events (8%), and depression-related
monoamine oxidase inhibitors, triptans, bupropion, dex- adverse events (7%).
tromethorphan, and St. John’s wort. (https://ww w.accessd A 52-week, placebo-controlled, double-blind exten-
ata.fda.gov/drugsatfda_docs/label/2012/022529lbl.pdf) sion study tested the long-term efficacy and safety of phen-
Recently, lorcaserin has been studied in combina- termine/topiramate ER (7.5/46 mg, 15/93 mg). Selected
tion with phentermine in a 12-week double-blind pilot subjects (676) completed an additional 52 weeks of either
safety study in patients without diabetes. Results showed active drug or placebo, in addition to lifestyle therapy.
that the addition of phentermine to lorcaserin treatment This length of treatment was not only well-tolerated but
increased weight loss while not increasing the incidence caused clinically significant improvement in systolic and
of potentially serotonergic side effects.45 These results diastolic blood pressure, triglycerides, HDL cholesterol,
are promising and may constitute the beginning of a new LDL cholesterol, and insulin sensitivity compared to pla-
combination drug for obesity. cebo. Continuing the treatment for another 52 weeks did
496 Chapter 39 Pharmacological Management of the Patient with Obesity
not continue to cause a significant average weight loss but weight loss. 50 The two study doses included sustained-
increased the percentage of subjects who lost more than release bupropion 360 mg per day, plus either 16 mg or
5%, 10%, 15%, and 20% weight from baseline. The 32 mg of sustained-release naltrexone. The third group
incidence rate of diabetes significantly decreased in the received a placebo. Weight losses were 6.1% and 5.0% at
phentermine-topiramate ER 15/93 mg group. The sub- the higher and lower doses of drugs, respectively. The pla-
group of participants with diagnosed type 2 diabetes had cebo group lost 1.3% of body weight. Side effects included
a decrease in HbA1C (0.4% and 0.2%, respectively) with- a transient rise in systolic and diastolic blood pressure of
out a change in the anti-diabetic medication9. 1.5 mmHg, followed by a 1 mm Hg reduction below base-
Certain safety concerns about phentermine-topira- line. There was no increase in depression or suicidal events
mate ER have been raised. The small increase in heart compared with the placebo, whereas headache, constipa-
rate has prompted the FDA to recommend a long-term tion, dizziness, vomiting, and dry mouth were experienced
study to evaluate the effect of the combination drug on more frequently in the drug groups.
heart attacks and strokes, which has not been completed In 2013, a 56-week, double-blind, placebo-controlled
yet (https://w w w.fda.gov/ ForConsumers/ConsumerUpd study of 1,496 subjects with obesity or overweight with
ates/ucm312380.htm). Meanwhile, the company recom- at least one weight-related comorbidity was reported. The
mends monitoring the heart rate of all patients taking combination of naltrexone 32 mg/day and bupropion 360
this treatment (https://ww w.qsymia.com/pdf/prescribing- mg/day caused a significant weight loss of 6.4% vs 1.2%
information.pdf). Because phentermine-topiramate ER in the placebo-controlled group. Moreover, the com-
increases the risk for cleft palate in pregnant women in bination drug caused more than a 5% weight loss in a
the first trimester, there is a required negative pregnancy significantly higher percentage of subjects (50.5%) com-
test before the beginning of the treatment and every four pared to placebo (17.1%) after the 56 weeks of treatment.
weeks after that. In addition, all prescribing healthcare Similar effects were observed after 28 weeks of treatment.
providers and dispensing pharmacies need a special certi- Additionally, the combination drug caused an improve-
fication (https://w w w.fda.gov/downloads/drugs/drugsafe ment in several cardiometabolic risk factors, and partici-
ty/po s tmar ketdr u gsaf e tyin forma t ionf o rpat i ents a ndpr pants reported increased control of eating impulses. This
oviders/ucm312598.pdf). study also showed no association with depression or sui-
Phentermine-topiramate ER was approved in 2012 as cidality. However, transient nausea was observed. 51
an adjunct to lifestyle changes in adults with a BMI at or The combination drug was also studied in 505 subjects
above 30 kg/m 2 or at or above 27 kg/m 2 in the presence of with overweight or obese and with type 2 diabetes in a
at least one weight-related comorbidity. The trade name double-blind, placebo-controlled trial. Naltrexone 32 mg/
is Qsymia and is dispensed in 3.75 mg/23 mg, 7.5 mg/46 upropion 360 mg per day for 56 weeks caused 5% weight
mg, 11.25 mg/69 mg, and 15 mg/92 mg of phentermine loss compared to 1.8% in the placebo group, and 44.5%
and topiramate ER combination, respectively, and to be of subjects achieved more than 5% weight loss compared
taken once a day in the morning. Providers are instructed with 18.9% on the placebo. Interestingly, the combination
to start with the lowest dose and increase to the next dose drug achieved a significantly greater reduction in HbA1C
in 14 days. It should be discontinued if, after 12 weeks, (−0.6%) compared to that of the placebo (−0.1%). The
the weight loss is less than 3% (with 7.5 mg/46 mg dosage) percentage of subjects taking the recommended American
or 5% (with 15 mg/92 mg). The two largest dosages are Diabetes Association target of 7% HbA1C was doubled
contraindicated in patients with moderate or severe renal in the treatment group compared to that of the placebo
impairment or patients with moderate hepatic impair- (44.1 vs. 26.3%). Moreover, the treatment group observed
ment. Patients should avoid concomitant use of alcohol an improvement in cardiovascular risk factors, triglycer-
and monitor irregular bleeding in women using oral con- ides, and HDL cholesterol. Also, there was no difference
traceptives and potassium levels in patients using non- observed in the incidence of depression or suicidality. 52
potassium sparring diuretics. Serious adverse reactions A very large trial including 8,910 subjects with over-
include cardiac ischemia, tachycardia, pulmonary HTN, weight and obesity and with cardiovascular risk was
and psychosis. Common side effects include paresthesia, undertaken to study the effects of naltrexone ER (32
xerostomia, constipation, and insomnia (https://ww w.qs mg/day)-bupropion SR (360 mg/day) on cardiovascular
ymia.com/pdf/prescribing-information.pdf). events. This was a randomized, multicenter, placebo-con-
trolled, double-blind non-inferiority trial. Major adverse
cardiovascular events occurred in 1.3% of subjects in the
39.3.2.4 Naltrexone ER-Bupropion SR (Contrave) placebo group vs. 0.8% of the subjects in the treatment
Naltrexone ER-bupropion SR was FDA approved for long- group (HR, 0.59; 95% CI: 0.39–0.90). However, the FDA
term management of weight loss in 2014. Both component determined that there was an inappropriate breach of con-
drugs have been approved by the FDA for almost 25 years. fidentiality by the sponsor, and, therefore, this trial would
Bupropion is a dopamine and norepinephrine reuptake not be taken into consideration for the post-approval
inhibitor approved for depression and smoking cessation. regulatory requirement. Therefore, the study was stopped
Naltrexone is an opioid receptor antagonist approved for early and unable to demonstrate the cardiovascular safety
alcohol and opioid dependence, which in this combina- of naltrexone ER-bupropion SR. 53
tion antagonizes the feedback loop that limits the anorec- Naltrexone ER-bupropion SR is indicated as an adjunct
tic effects of bupropion. Therefore, the combination drugs to lifestyle changes in adults with a BMI at or above 30 kg/m2
work synergistically to suppress appetite. A 56-week study or at or above 27 kg/m2 in the presence of at least one
involving 1,742 subjects studied the drug combination for weight-related comorbidity. The trade name is Contrave
39.3 The FDA-Approved Obesity Drugs 497
and is dispensed in 8 mg naltrexone HCl/90 mg bupro- of treatment, liraglutide caused 5.6 kg body weight more
39
pion HCl tablets to be taken as two tablets twice a day by than the placebo control. Significantly, more subjects (63%
mouth. Providers are instructed to start with one tablet in vs. 27%) lost more than 5% of their initial body weight
the morning for one week; then one tablet twice a day for in the treatment vs. placebo group. An even bigger differ-
one week; then two tablets in the morning and one tablet ence (33% vs. 11%) was observed for the subjects who lost
in the evening for 1 week; followed by two tablets twice a more than 10% of their initial body weight. In addition,
day as the maximum dose. Naltrexone ER-bupropion SR is the liraglutide treatment was accompanied by an improve-
contraindicated in patients with uncontrolled hypertension, ment in the cardiometabolic profile.56
seizure disorders, anorexia nervosa, bulimia, and chronic Liraglutide was also studied as a potential drug for the
opioid use, or patients taking bupropion-containing prod- prevention of type 2 diabetes in patients with prediabetes.
ucts, monoamine oxidase inhibitors (during or within 14 A large, double-blind, placebo-controlled trial of 2,254
days of discontinuation), and patients undergoing abrupt subjects with prediabetes and a BMI at or above 30 kg/m 2
discontinuation of alcohol, benzodiazepine, barbiturates, or those at or above 27 kg/m 2 in the presence comorbidi-
or antiepileptic drugs. Serious adverse reactions include ties was undertaken for three years. A lower proportion of
neuropsychiatric disorders, homicidal ideation, suicidality, conversion to type 2 diabetes was observed in the liraglu-
depression exacerbation, HTN, hepatotoxicity, and closed tide group (2%) compared to the control group (6%), with
angle glaucoma. Common side effects include nausea, a HR being calculated at 0.21 (95% CI: 0.13–0.34). In
vomiting, constipation, headache, dizziness, and insomnia. addition, the subjects with prediabetes treated with lira-
Contrave has a black box warning for the use in patients glutide lost significantly more weight compared to the pla-
with major depression disorders or other psychiatric dis- cebo treatment (4.3% difference). Both groups reported
orders as it may cause suicidality (https://www.accessdata. serious adverse events (15% in the treatment group vs.
fda.gov/drugsatfda_docs/label/2014/200063s000lbl.pdf). 13% in the placebo group). 57
In 1,361 subjects with type 2 diabetes who also had
overweight or obesity, liraglutide for 56 weeks caused 6%
39.3.2.5 Liraglutide (Saxenda) weight loss (for the 3 mg/day dosage) and 4.7% weight loss
Liraglutide is a human glucagon-like peptide-1 (GLP-1) (for the 1.8 mg/day dosage) compared to 2% weight loss in
analog approved by the FDA in 2014 for long-term weight the placebo group. More than 5% weight loss occurred in
loss. It is important to note that a different dosage (lower) 54% of the subjects treated with liraglutide 3 mg/day vs.
of liraglutide has been used as Victoza from 2010 for the 40% in the liraglutide 1.8 mg/day group and 19% in the
treatment of type 2 diabetes. placebo group. Similar effects were observed for subjects
A two-year clinical trial with liraglutide involved 564 who lost more than 10% of their body weight (25% vs.
individuals aged 18–65 years. 54 The trial evaluated the 16% vs. 7%, respectively). In this study, liraglutide caused
safety, tolerability, and sustained weight loss using lira- more gastrointestinal side effects, but no pancreatitis was
glutide treatment for obesity for over two years. A report reported.58
of the initial 20 weeks of the trial compared subcutaneous Liraglutide was also shown to improve obstructive
liraglutide treatment with orlistat and a placebo arm. 55 sleep apnea, as shown by the apnea-hypopnea index. In
Liraglutide was initially given once daily subcutaneously this 32-week study, liraglutide or a placebo was admin-
at doses from 1.2 mg to 3.0 mg. The other treatment istered in addition to counseling for lifestyle changes.
groups received 120 mg of orlistat three times a day or a The majority of subjects had prediabetes, but none of
placebo. The liraglutide subjects treated at the 3.0 mg dur- them had type 2 diabetes. Liraglutide caused a signifi-
ing the initial 20 weeks lost more weight than the other cant improvement in the apnea-hypopnea index (−12.2 vs.
study groups, and body fat decreased by 15.4% and lean −6.1 events h[-1]), and this improvement was related to the
tissue by 2.0%. All liraglutide groups lost more weight degree of weight loss. As previously reported, this study
than the other two groups. There was an 84%–96% also demonstrated that liraglutide produced a significantly
reduction in the prevalence of prediabetes in the 1.8 mg larger percentage of weight loss compared to the placebo
to 3.0 mg dose range and a reduction of blood pressure (4.3% difference) and an improvement in HbA1C and sys-
at all liraglutide doses. Side effects included nausea and tolic blood pressure. 59
vomiting that rarely lead to study discontinuation. In the A large, double-blind trial studied the cardiovascular
report on the 84-week extension of the study, the liraglu- side effects of liraglutide in 9,340 subjects with type 2 dia-
tide group maintained a 7.8 kg weight loss, which was also betes and with high cardiovascular risk. Subjects were fol-
much greater than the other groups. 54 The study authors lowed for 3.8 years. The primary composite outcome was
also reported that the two-year prevalence of prediabe- death from cardiovascular cause, nonfatal myocardial
tes and metabolic syndrome decreased by 52% and 59%. infarction, or nonfatal stroke and occurred in significantly
There were improvements in blood pressure and lipid val- fewer subjects treated with liraglutide (13.0%) compared
ues. The most frequent drug-related side effects were mild to the placebo (14.9%), with a hazard ratio of 0.87 (95%
to moderate transient nausea and vomiting. CI: 0.78 to 0.97). The rate of death from cardiovascular
The weight loss effect of liraglutide 3 mg/day was stud- events was lower in the liraglutide group (4.7%) compared
ied in a large, double-blind, placebo-controlled trial of to placebo group (6%). There was no significant differ-
3,731 subjects with a BMI at or above 30 kg/m2 or at or ence in the rate of nonfatal stroke, myocardial infarction,
above 27 kg/m2 with hyperlipidemia or hypertension. Both and pancreatitis in the liraglutide group compared to the
groups received lifestyle change counseling. After 56 weeks placebo.60
498 Chapter 39 Pharmacological Management of the Patient with Obesity
Liraglutide is indicated as an adjunct to lifestyle with type 2 diabetes, it may be worth considering either
changes in adults with a BMI at or above 30 kg/m 2 or at an angiotensin-converting enzyme inhibitor, an angioten-
or above 27 kg/m 2 in the presence of at least one weight- sin receptor blocker, or a calcium channel blocker, and to
related comorbidity. The trade name is Saxenda and is avoid, if possible, beta-blockers. For treatment of depres-
to be administered subcutaneously daily at any time of sion, psychosis, and epilepsy, the society recommends
day, regardless of meal timing. Providers are instructed weight-neutral agents, if possible, and a discussion about
to start with 0.6 mg/day for 1 week, then increase the the amount of potential weight gain for different agents
dose weekly to 1.2 mg, then 1.8 mg, then 2.4 mg until the and the estimated length of treatment. For women inter-
maximum dose of 3 mg/day is reached. Liraglutide is con- ested in contraception, providers should consider oral
traindicated in patients with personal or family history drugs over weight-gaining injectables, if possible. For
of medullary thyroid carcinoma or multiple endocrine patients on antiretroviral therapy, it is recommended to
neoplasia syndrome type 2, hypersensitivity to liraglutide, monitor their weight and fat distribution periodically for
or pregnancy and should not be used concomitantly with early detection of metabolic risk. For patients with rheu-
insulin or other GLP-1 receptor agonists. Serious adverse matoid arthritis or other chronic inflammatory disease,
reactions include thyroid C-cell tumor, medullary thyroid it is recommended to avoid, if possible, use of cortico-
carcinoma, papillary thyroid carcinoma, colorectal malig- steroids and replace them with nonsteroidal anti-inflam-
nancy, first-degree AV block, and pancreatitis. Common matory drugs or disease-modifying antirheumatic drugs.
side effects include nausea, diarrhea, constipation, vom- When choosing an antihistamine, it is recommended to
iting, headache, dyspepsia, fatigue, dizziness, abdomi- choose one that causes less sedation.
nal pain, flatulence, and insomnia. Saxenda has a black
box warning for use in patients with medullary thyroid
carcinoma history or family history, or in patients with 39.4.2 Who Should Receive
multiple endocrine neoplasia syndrome type 2 (http s://
w w w.acc essdata.fd a.gov/drugsatfd a_doc s/lab el/2014/2 Pharmacotherapy for Obesity
06321Orig1s000lbl.pdf). BMI guidelines for identifying overweight and obesity,
evaluation, and treatment were recently published by the
American Heart Association, the American College of
39.4 CLINICAL CONSIDERATIONS Cardiology, and the Obesity Society.10 by the American
FOR PHARMACOTHERAPY Association of Clinical Endocrinology and American
College of Endocrinology,9 and by the United States
MANAGEMENT OF OBESITY Preventive Tasks Force Service (http s://w
w w.uspreve
ntiveservicestaskforce.org /Page /Docu ment / Recom mend
39.4.1 Special Considerations for ationStatementFinal/obesit y-in-adults-screening-and-man
ageme nt). These guidelines emphasize the importance
Concurrent Pharmacotherapy of early identification of overweight and obesity with
Providers should follow the most updated guidelines for the measurement of BMI and waist circumference as an
comprehensive obesity management.9,10 In addition, the important first step for both prevention and treatment.
Endocrine Society published a very detailed stepwise Primary care physicians see 11.3% of the U.S. popula-
approach for the clinical encounter with a patient with tion monthly, and patients with obesity represent a high
overweight or obesity.13 Patients should be screened for proportion of those visits.61,62 However, primary care
diseases associated with obesity either annually or when practices do not carry the entire burden of early detec-
they have relevant symptoms. A special reminder is to tion of overweight and obesity. There is a wider spectrum
closely follow national guidelines for cancer screening, as of medical subspecialists, nurse practitioners, physician
there is strong data showing association of obesity with assistants, and surgeons who see these patients for their
multiple malignancies. Providers should get a comprehen- comorbidities associated with obesity. These referral doc-
sive history of the patients with obesity or overweight, tors could be educated to discuss and guide patients about
which should include comprehensive lifestyle history, their obesity risks. The prescribing of anti-obesity drugs,
sleep disorder, eating disorders, genetics, family history, however, should be the responsibility of HCPs who have
and social history. If the history and/or physical sug- specific knowledge of the pharmacology of obesity medi-
gest a secondary cause for obesity, then patients should cation, their side effects and safety profile, and access to
be screened for those conditions. Providers should care- HCPs who can provide the important behavior modifica-
fully examine the medical list and try as much as pos- tion and dietary components of overweight and obesity
sible to replace any drugs promoting weight gain with management to their patients.
drugs that are weight-neutral or that promote weight A decision not to discuss obesity or not to treat obe-
loss. Specifically, in patients with type 2 diabetes, provid- sity may be based on a patient’s readiness to commit to a
ers should consider using weight-losing or weight-neutral weight management program. For a patient to get maxi-
drugs. When not possible, discuss the potential effect of mum benefit from pharmacotherapy, a HCP needs to
the medicine on weight. For the patients with insulin- gauge a patient’s compliance, ability, and willingness to
dependent type 2 diabetes, providers should consider follow medical directions. This information significantly
adding a weight-losing, anti-diabetes drug (metformin, improves a HCP’s ability to pick the right time to initiate
pramlintide, GLP-1 agonist) to counteract the weight gain successful pharmacotherapy. There are screening ques-
effect of insulin. For the treatment of HTN in patients tionnaires that could provide such information.63
39.4 Clinical Considerations for Pharmacotherapy Management of Obesity 499
If weight loss is medically necessary, patients may a variety of non-medically supervised diet and exercise
39
be self-motivated to follow a weight management plan, programs.
but health is usually not a compelling motivator from a As with any pharmacological agent, the risk and bene-
patient’s standpoint; if used as the only argument by a fit possibilities must be weighed before prescribing an obe-
provider, it may be unsuccessful. Patients who claim cos- sity drug. Treating obesity in patients older than 65 years
metic reasons for wanting to lose weight and who qualify should be done with caution.18 Some drugs have several
for obesity pharmacotherapy should not be turned away. contraindications, or conditions for which we are advised
Vanity can be a motivating force for success and is not a to use them with caution. The FDA did not approve the use
reason to deny drug treatment if the patient fulfills the of drugs in all patients, with none of them being approved
medical criteria. A patient’s request for pharmacotherapy for use in pregnancy (Table 39.1). It is important to rec-
during initial obesity consultations is not unusual and is ognize that, at present, obesity can be controlled but can-
not necessarily a sign of a patient looking for a “short not be cured. Therefore, a relapse is possible if an obesity
cut.” A patient who insists on a pill to lose weight could drug is discontinued. If a patient loses and/or maintains
likely be one of your least successful patients now seeking weight loss on an obesity drug and no serious side effects
a different approach. Failed previous weight loss attempts have been identified, then the drug may be continued and
or even Yo-Yo dieting is not a contraindication to drug the drug efficacy and safety should be monitored for the
treatment. duration of its use.65
It is not uncommon that an obesity management pro-
gram includes pharmacotherapy sooner rather than later.
This may mean including drug therapy at the onset of a 39.4.3 Special Consideration for FDA
comprehensive program.64
Guidelines indicate that pharmacotherapy for adults
Indications and the State Law
with obesity may be appropriate for those with a BMI of All the drugs approved by the FDA for short-term or long-
27–29.9 kg/m 2 if comorbidities are present or for those term weight loss should be used as indicated, in addition
with a BMI ≥ 30 kg/m 2 with or without comorbidities. to counseling and education for lifestyle changes. And, as
It is also suggested that pharmacotherapy be considered per recent obesity management guidelines,9,10 the lifestyle
in conjunction with and after a patient has tried behav- changes should match the characteristics of comprehen-
ior therapy, including diet, exercise, and lifestyle change, sive intensive lifestyle intervention. This is an important
and has had limited or no response. In reality, most aspect that needs to be considered by clinicians and prac-
patients have had some exposure to non-pharmacological tice managers. Just offering the weight loss drugs, with-
approaches before seeking medical help for weight loss out the indicated lifestyle management changes, may not
since various establishments and online programs offer results in the desired/studied weight loss effects. Currently
TABLE 39.1 Weight loss drugs, DEA schedule, weight loss effects and approved patient population
Weight loss caused by
Drug commercial drug compared to Approved patient
Drug generic name name DEA schedule placebo population
Drugs approved for short term weight loss (weight loss effect after a variable period as described in table)
Phentermine Adipex, Ionamin, IV 3.6 kg (2–24 weeks) (28) 18 and older.
Lomaira Pregnancy category X
Diethylproprion Tenuate IV 3.0 kg (6–52 weeks) (28) 16 and older.
Pregnancy category B
Benzphetamine Didrex III 3.3 kg (1.6–17 weeks) (28) 12 and older.
Pregnancy category X
Phendimetrazine Bontril, Prelu-2 III There were no trials to meet 17 and older.
the selection criteria (28) Pregnancy category X
Drugs approved for long term weight loss (weight loss effect after 1 year of treatment)
Orlistat Xenical, Alli None, over the 3.1% (71) 12 and older.
counter drug Pregnancy category X
Lorcaserin Belviq, Belviq SR IV 3.6% (41) 18 and older.
Pregnancy category X
Phenermine-Topiramate Qsymia IV 6.6% (49) 18 and older.
Pregnancy category X
Naltrexone-Buproprion Contrave None 4.8% (50) 18 and older.
Pregnancy category X
Liraglutide Saxenda None 5.4% (56) 18 and older.
Pregnancy category X
500 Chapter 39 Pharmacological Management of the Patient with Obesity
available obesity drugs are supplements and not substi- is discontinued, the resulting weight could be easily main-
tutes to lifestyle management. tained only with the lifestyle changes undertaken at the
Another fact that clinicians need to consider is that in beginning of the treatment. Strong data to debunk this
some states there are special set of laws associated with myth come from a double-blind, placebo-controlled clini-
the prescription of obesity drugs. For example, in Florida, cal trial of 3,182 subjects with obesity treated with either
providers who prescribe obesity drugs needs to get a writ- lorcaserin 10 mg twice daily or a placebo, in addition to
ten informed consent from patients, which includes the lifestyle changes. Subjects treated for one year with lorcase-
statement that “there is lack of scientific data regarding the rin lost 5.8 kg vs. 2.2 kg in the placebo group. Subsequently,
potential danger of long term use of combination weight subjects in the treatment group were assigned to either stay
loss treatments.” Providers should also give to patients and in the treatment group or receive the placebo for another
post in the treatment room the weight-loss consumer bill of year. From the subjects losing more than 5% of their ini-
rights as per Florida rules (http://www.leg.state.fl.us/statute tial weight after the first year of treatment with lorcaserin,
s/ind e x.cf m ?App _ mode = Disp l ay_S t atut e &URL = 0500 a significantly greater proportion of subjects continuing
-0599/0501/Sections/0501.0575.html) and Department with lorcaserin treatment (67.9%) maintained their weight
of Health regulations. (https://www.flrules.org/gateway/ compared to those re-assigned to the placebo (50.3%).
ruleno.asp?id=64B8-9.012). This is part of the “Standard However, the subjects who were on lorcaserin for one year
for Medical Doctors”, released in 1998. There has been and then placebo for one year had a similar final weight
no update to this rule, even after the new data regarding with subjects who received placebo for two years. Subjects
the safety of pharmacological treatment of obesity and the who maintained in the lorcaserin treatment group had
variety of weight loss drugs was approved. significantly lower body weight compared to placebo or
lorcaserin-placebo group.41 These trends are confirmed by
other trials to date.66–68
39.4.4 Deciding What Weight Loss
Drug to Use and for How Long 39.4.5 Optimizing Weight
In addition to the merits, limitations, adverse effects, and Management During Long-
the mechanism of action of various drugs, the selection of
an obesity drug should be personalized to accommodate
term Continuity of Care
considerations for a patient’s past medical and social his- Many obesity researchers and clinicians believe that long
tory, current medical and mental health issues, and cur- term and possibly lifelong use of obesity drugs may be nec-
rent medications including OTC drugs. essary for individuals with significant obesity.69 Current
We will comment below on the drugs most prescribed guidelines recommend that if a weight loss drug, used as
in the U.S.: phentermine, orlistat, lorcaserin, phentermine- indicated in conjunction with lifestyle management, does
topiramate ER, naltrexone ER-bupropion SR and liraglu- not cause at least 5% weight loss in three months or if it
tide. The most inexpensive obesity drugs are phentermine causes non-tolerable side effects, then the drug should be
and orlistat, so if this is a limiting factor for the patient, discontinued and an alternative approach discussed with
they may be a good choice to start weight loss treatment the patient.13,70 This approach may include the prescrip-
in addition to lifestyle changes. Naltrexone ER-bupropion tion of a different drug, more intensive lifestyle manage-
SR’s price is mid-level, while the other drugs are reported ment, or the addition of bariatric surgery. Changing the
as expensive. Phentermine is the only drug without long- time of drug administration may be needed to promote
term safety data from trials. Except liraglutide, which is an better compliance. The possibility should be considered
injectable medicine, all the other drugs are administered that other prescription or non-prescription drugs may
orally. Orlistat is the only drug that is not absorbed system- interfere with drug effectiveness or may cause side effects
ically. A bothersome side effect profile is a consideration for that the patient may wrongly attribute to an obesity drug.
phentermine, orlistat, and naltrexone ER-bupropion SR. Another consideration is the patient’s compliance with
Drugs that seem to be tolerated with minimal side effects dietary changes and physical activity. As the daily need of
are lorcaserin and liraglutide. As for safety in pregnancy, energy decreases with decreasing weight, consider if the
only phentermine-topiramate ER is labeled as a teratogen, calorie goals need to be redefined for continued weight
but they are all pregnancy category X.13 loss. Is the rate and amount of weight loss appropriate
Another important consideration for a provider is how for the patient’s medical needs? Should the drug now be
long to use the indicated drugs. This is an important dis- used to maintain the weight lost? As far as possible, the
cussion to have with the patient at the beginning of the class of drug chosen should consider the eating behaviors
treatment period, when all options are discussed. Providers of each patient, their lifestyle preferences, cultural beliefs,
need to make sure that patients do not have the misconcep- socioeconomic status, and previous weight loss attempts.
tions that weight loss drugs cause significant weight loss Information about hunger, cravings, eating between meals,
as advertised if used without lifestyle changes, and that binging, and night time eating issues should be obtained
using the weight loss drugs for a certain period of time by using validated questionnaires or through questioning
will change their body weight regulation in a permanent of all patients by HCPs or staff. A written questionnaire
way. In other words, the myth that taking weight loss drugs detailing eating habits may help patients better focus on
for a few months will make you skinny forever needs to their eating issues, if any. Food preferences and types of
be debunked at the first visit. Another myth held by some foods frequently overeaten may influence the type and
patients and providers is that once the weight loss drug timing of obesity drug administration.
References 501
39
increasing weight loss and maintenance, and possibly also
Obesity is a chronic disease that requires lifelong treat- alleviating comorbidities of obesity. Obesity is a serious
ment. There is currently no cure for obesity. However, in medical condition and not a moral failure or a character
the United States, there are six drugs with a relatively good flaw. Behavioral treatment of obesity has marginal suc-
safety profile that are approved for short- and long-term cess, and pharmacotherapy should be given a serious con-
obesity management. Just like with any other drug, care- sideration as an adjunct to lifestyle management.
ful selection of a drug, its dose and duration, follow-up
and continuous assessment of efficacy, and due diligence
on recognizing side effects are mandatory. In addition to CLINICAL APPLICATIONS
the unusual requirements for pharmacotherapy, providers
need to be aware of extra state laws regarding weight loss • Follow the most updated guidelines for comprehen-
management with pharmacotherapy. sive obesity management.
As most patients want to either lose weight or main- • Screen for diseases associated with obesity either
tain their weight,7 and obesity is associated with multiple annually or when they have relevant symptoms.
comorbidities from various specialties, it seems that all • Weigh the risks and benefits before prescribing an
providers should be prepared to treat patients with obe- obesity drug.
sity. In some cases for which pharmacotherapy is indi- • Use obesity drugs with cautions for patients older
cated, they will need to prescribe, monitor and optimize than 65 years.
the treatment with weight loss drugs. A lot of progress has • Only some obesity drugs are approved for patients
been made in this direction. First, obesity was declared a younger than 18.
disease (http://www.npr.org/documents/2013/jun/ama-re • When weight loss is achieved, monitor for the con-
solution-obesity.pdf), which should increase the number trol of the obesity-related diseases and adjust the
of insurance companies covering obesity management dosage as needed.
with reimbursement of providers time and reasonable
co-pays for patients. Second, an obesity medicine certifi-
cation has been developed and is available for any pro- ACKNOWLEDGEMENTS
vider to complete in order to become an expert in clinical
management of obesity (http://abom.org/). Third, obesity This chapter is built on and expanded from the previous
medicine competencies have been developed in order version authored by Drs. Nikhil Dhurandhar and Donald
to target objectives for educational activities as well as Schemacher.
assessment activities (https://bipartisanpolicy.org/library/
provider-competencies-for-the-prevention-and-managem
ent-of-obesity/). Last, but not least, the obesity manage- POTENTIAL CONFLICT OF INTEREST
ment guidelines have been revised and updated with the
new available drugs and other management therapies Nikhil V. Dhurandhar has ongoing research support from
available.9,10 the Egg Nutrition Center and Vital Health Interventions.
Few patients treated for their obesity may reach their He has received U.S. and international patents to protect
goal weight and almost no one reaches the “ideal” weight, intellectual property about virus-induced obesity and the
with or without drug therapy. This, however, is not a rea- development of drugs to treat diabetes and non-alcoholic
son to withhold pharmacotherapy. Obesity drugs are not fatty liver disease from a protein. He has been a consul-
substitutes, but rather supplements to other lifestyle inter- tant to and a speaker for many organizations including
ventions for weight loss. Obesity drugs are expected to Novo Nordisk, Vivus, Novartis, and Dhurandhar Weight
empower a person to adhere to a reduced calorie intake, in Management.
some cases providing better control over aberrant eating Magdalena Pasarica has no conflict of interest.
REFERENCES
1. Flegal KM, Kruszon-Moran D, Loos RJF, et al. Obesity. Nat Rev Dis 8. Heymsfield SB, Wadden TA.
Carroll MD, Fryar CD, Ogden CL. Primers. 2017;3:17034. Mechanisms, pathophysiology, and
Trends in obesity among adults in the 5. Collaborators GBDO, Afshin A, management of obesity. N Engl J Med.
United States, 2005 to 2014. JAMA. Forouzanfar MH, Reitsma MB, Sur P, 2017;376(3):254–66.
2016;315(21):2284–91. Estep K, et al. Health effects of overweight 9. Garvey WT, Mechanick JI, Brett EM,
2. Collaboration NCDRF. Trends in adult and obesity in 195 countries over 25 years. Garber AJ, Hurley DL, Jastreboff AM,
body-mass index in 200 countries from N Engl J Med. 2017;377(1):13–27. et al. American Association of Clinical
1975 to 2014: A pooled analysis of 1698 6. Ryan DH, Yockey SR. Weight loss and Endocrinologists and American College
population-based measurement studies improvement in comorbidity: Differences of Endocrinology comprehensive clini-
with 19.2 million participants. Lancet. at 5%, 10%, 15%, and over. Curr Obes cal practice guidelines for medical care
2016;387(10026):1377–96. Rep. 2017;6(2):187–94. of patients with obesity. Endocr Pract.
3. Apovian CM. Obesity: Definition, . Petrin C, Kahan S, Turner M, Gallagher
7 2016;22 Suppl 3:1–203.
comorbidities, causes, and burden. Am J C, Dietz WH. Current attitudes and 10. Jensen MD, Ryan DH, Apovian CM,
Managed Care. 2016;22(7 Suppl):s176–85. practices of obesity counselling by health Ard JD, Comuzzie AG, Donato KA,
4. Gonzalez-Muniesa P, Martinez-Gonzalez care providers. Obes Res Clin Pract. et al. 2013 AHA/ACC/TOS guideline
MA, Hu FB, Despres JP, Matsuzawa Y, 2017;11(3):352–9. for the management of overweight
502 Chapter 39 Pharmacological Management of the Patient with Obesity
and obesity in adults: A report of when it is given (day vs. night) and under ratings of gastrointestinal comfort. Nutr
the American College of Cardiology/ conditions of high fat dietary restriction. Metab. 2017;14:13.
American Heart Association Task Force Appetite. 2016;100:152–61. 41. Smith SR, Weissman NJ, Anderson CM,
on Practice Guidelines and The Obesity 27. Cercato C, Roizenblatt VA, Leanca CC, Sanchez M, Chuang E, Stubbe S, et al.
Society. Circulation. 2014;129(25 Suppl Segal A, Lopes Filho AP, Mancini MC, et Multicenter, placebo-controlled trial of
2):S102–38. al. A randomized double-blind placebo- lorcaserin for weight management. N
11. Diet, drugs, and surgery for weight loss. controlled study of the long-term efficacy Engl J Med. 2010;363(3):245–56.
The Medical letter on drugs and thera- and safety of diethylpropion in the 42. Smith SR, Prosser WA, Donahue DJ,
peutics. 2015;57(1462):21–8. treatment of obese subjects. Int J Obes Morgan ME, Anderson CM, Shanahan
12. Hendricks EJ. Off-label drugs for weight (Lond). 2009;33(8):857–65. WR. Lorcaserin (APD356), a selective
management. Diabetes Metab Syndr 28. Haddock CK, Poston WS, Dill PL, Foreyt 5-HT(2C) agonist, reduces body weight
Obes. 2017;10:223–34. JP, Ericsson M. Pharmacotherapy for in obese men and women. Obesity (Silver
13. Apovian CM, Aronne LJ, Bessesen DH, obesity: A quantitative analysis of four Spring). 2009;17(3):494–503.
McDonnell ME, Murad MH, Pagotto decades of published randomized clinical 43. Fidler MC, Sanchez M, Raether B,
U, et al. Pharmacological management trials. Int J Obes Relat Metab Disord. Weissman NJ, Smith SR, Shanahan
of obesity: An endocrine Society clinical 2002;26(2):262–73. WR, et al. A one-year randomized trial
practice guideline. J Clin Endocrinol 29. Drent ML, van der Veen EA. Lipase of lorcaserin for weight loss in obese
Metab. 2015;100(2):342–62. inhibition: A novel concept in the treat- and overweight adults: The BLOSSOM
14. Thomas CE, Mauer EA, Shukla AP, ment of obesity. Int J Obes Relat Metab trial. J Clin Endocrinol Metab.
Rathi S, Aronne LJ. Low adoption of Disord. 1993;17(4):241–4. 2011;96(10):3067–77.
weight loss medications: A comparison 30. Drent ML, van der Veen EA. First clini- 44. Weissman NJ, Sanchez M, Koch GG,
of prescribing patterns of antiobesity cal studies with orlistat: A short review. Smith SR, Shanahan WR, Anderson
pharmacotherapies and SGLT2s. Obesity Obes Res. 1995;3 Suppl 4:623S–5S. CM. Echocardiographic assessment
(Silver Spring). 2016;24(9):1955–61. 31. Heck AM, Yanovski JA, Calis of cardiac valvular regurgitation with
15. Hampp C, Kang EM, Borders-Hemphill KA. Orlistat, a new lipase inhibi- lorcaserin from analysis of 3 phase 3
V. Use of prescription antiobesity drugs tor for the management of obesity. clinical trials. Circ Cardiovasc Imaging.
in the United States. Pharmacotherapy. Pharmacotherapy. 2000;20(3):270–9. 2013;6(4):560–7.
2013;33(12):1299–307. 32. Hollywood A, Ogden J. Taking orlistat: 45. Smith SR, Garvey WT, Greenway
16. Munro JF, MacCuish AC, Wilson EM, Predicting weight loss over 6 months. J FL, Zhou S, Fain R, Pilson R, et al.
Duncan LJ. Comparison of continuous Obes. 2011;2011:806896. Coadministration of lorcaserin and
and intermittent anorectic therapy in 33. Davidson MH, Hauptman J, DiGirolamo phentermine for weight manage-
obesity. Br Med J. 1968;1(5588):352–4. M, Foreyt JP, Halsted CH, Heber D, et ment: A 12-week, randomized, pilot
17. Le Riche WH, Csima A. A long-acting al. Weight control and risk factor reduc- safety study. Obesity (Silver Spring).
appetite suppressant drug studied for 24 tion in obese subjects treated for 2 years 2017;25(5):857–65.
weeks in both continuous and sequen- with orlistat: A randomized controlled 46. Tronieri JS, Alfaris N, Chao AM, Pearl
tial administration. Can Med Assoc J. trial. JAMA. 1999;281(3):235–42. RL, Alamuddin N, Bakizada ZM, et al.
1967;97(17):1016–20. 34. de Castro JJ, Dias T, Chambel P, Lorcaserin plus lifestyle modification for
18. Atkinson RL, Blank RC, Schumacher Carvalheiro M, Correia LG, Guerreiro weight loss maintenance: Rationale and
D, Dhurandhar NV, Ritch DL. Long- L, et al. A randomized double-blind design for a randomized controlled trial.
term drug treatment of obesity in a study comparing the efficacy and Contemp Clin Trials. 2017;59:105–12.
private practice setting. Obes Res. safety of orlistat versus placebo in 47. Christopher RJ, Morgan ME, Tang Y,
1997;5(6):578–86. obese patients with mild to moderate Anderson C, Sanchez M, Shanahan W.
19. Weintraub M. Long-term weight control: hypercholesterolemia. Rev Port Cardiol. Pharmacokinetics and tolerability of lorca-
The National Heart, Lung, and Blood 2009;28(12):1361–74. serin in special populations: Elderly patients
Institute funded multimodal inter- 35. Derosa G, Cicero AF, D’Angelo A, Fogari and patients with renal or hepatic impair-
vention study. Clin Pharmacol Ther. E, Maffioli P. Effects of 1-year orlistat ment. Clin Ther. 2017;39(4):837–48 e7.
1992;51(5):581–5. treatment compared to placebo on insulin 48. Kramer CK, Leitao CB, Pinto LC, Canani
20. Weintraub M, Hasday JD, Mushlin resistance parameters in patients with LH, Azevedo MJ, Gross JL. Efficacy and
AI, Lockwood DH. A double-blind type 2 diabetes. J Clin Pharm Ther. 2011. safety of topiramate on weight loss: A
clinical trial in weight control. Use of 36. Hollander PA, Elbein SC, Hirsch IB, meta-analysis of randomized controlled
fenfluramine and phentermine alone Kelley D, McGill J, Taylor T, et al. Role trials. Obes Rev. 2011;12(5):e33847.
and in combination. Arch Intern Med. of orlistat in the treatment of obese 49. Gadde KM, Allison DB, Ryan DH,
1984;144(6):1143–8. patients with type 2 diabetes. A 1-year Peterson CA, Troupin B, Schwiers ML,
21. Spitz AF, Schumacher D, Blank RC, randomized double-blind study. Diabetes et al. Effects of low-dose, controlled-
Dhurandhar NV, Atkinson RL. Long- Care. 1998;21(8):1288–94. release, phentermine plus topiramate
term pharmacologic treatment of morbid 37. Jacob S, Rabbia M, Meier MK, combination on weight and associated
obesity in a community practice. Endocr Hauptman J. Orlistat 120 mg improves comorbidities in overweight and obese
Pract. 1997;3(5):269–75. glycaemic control in type 2 diabetic adults (CONQUER): A randomised,
22. Griffiths RR, Brady JV, Bradford LD. patients with or without concurrent placebo-controlled, phase 3 trial. Lancet.
Predicting the abuse liability of drugs weight loss. Diabetes Obes Metab. 2011;377(9774):1341–52.
with animal drug self-administration 2009;11(4):361–71. 50. Greenway FL, Fujioka K, Plodkowski
procedures:psychomotor stimulants and 38. Svendsen M, Rissanen A, Richelsen B, RA, Mudaliar S, Guttadauria M,
hallucinogens. Adv Behav Pharmacol. Rossner S, Hansson F, Tonstad S. Effect Erickson J, et al. Effect of naltrex-
1979(2):163–208. of orlistat on eating behavior among one plus bupropion on weight loss in
23. Rich S, Rubin L, Walker AM, participants in a 3-year weight main- overweight and obese adults (COR-I): A
Schneeweiss S, Abenhaim L. Anorexigens tenance trial. Obesity (Silver Spring). multicentre, randomised, double-blind,
and pulmonary hypertension in the 2008;16(2):327–33. placebo-controlled, phase 3 trial. Lancet.
United States: Results from the surveil- 39. Richelsen B, Tonstad S, Rossner S, 2010;376(9741):595–605.
lance of North American pulmonary Toubro S, Niskanen L, Madsbad S, et al. 51. Apovian CM, Aronne L, Rubino D, Still
hypertension. Chest. 2000;117(3):870–4. Effect of orlistat on weight regain and C, Wyatt H, Burns C, et al. A random-
24. In brief: Phentermine (Lomaira) for cardiovascular risk factors following ized, phase 3 trial of naltrexone SR/
weight loss. The Medical letter on drugs a very-low-energy diet in abdominally bupropion SR on weight and obesity-
and therapeutics. 2016;58(1509):158. obese patients: A 3-year randomized, related risk factors (COR-II). Obesity
25. McKay RH. Long-term use of diethyl- placebo-controlled study. Diabetes Care. (Silver Spring). 2013;21(5):935–43.
propion in obesity. Curr Med Res Opin. 2007;30(1):27–32. 52. Hollander P, Gupta AK, Plodkowski
1973;1(8):489–93. 40. Kristensen M, Juul SR, Sorensen KV, R, Greenway F, Bays H, Burns C, et al.
26. Kalyanasundar B, Solorio J, Perez CI, Lorenzen JK, Astrup A. Supplementation Effects of naltrexone sustained-release/
Hoyo-Vadillo C, Simon SA, Gutierrez R. with dairy calcium and/or flaxseed fibers bupropion sustained-release combination
The efficacy of the appetite suppressant, in conjunction with orlistat augments therapy on body weight and glycemic
diethylpropion, is dependent on both fecal fat excretion without altering parameters in overweight and obese
References 503
patients with type 2 diabetes. Diabetes 58. Davies MJ, Bergenstal R, Bode B, 65. Pi-Sunyer FX. Guidelines for the approval
Care. 2013;36(12):4022–9. Kushner RF, Lewin A, Skjoth TV, et al. and use of drugs to treat obesity. A
53. Nissen SE, Wolski KE, Prcela L, Wadden
T, Buse JB, Bakris G, et al. Effect of
naltrexone-bupropion on major adverse
Efficacy of liraglutide for weight loss
among patients with type 2 diabetes:
The SCALE diabetes randomized clinical
position paper of the North American
Association for the Study of Obesity.
Obes Res. 1995;3(5):473–8.
39
cardiovascular events in overweight trial. JAMA. 2015;314(7):687–99. 66. Verrotti A, Parisi P, Agostinelli S,
and obese patients with cardiovascular 59. Blackman A, Foster GD, Zammit G, Loiacono G, Marra F, Coppola G, et al.
risk factors: A randomized clinical trial. Rosenberg R, Aronne L, Wadden T, et al. Weight regain after discontinuation of
JAMA. 2016;315(10):990–1004. Effect of liraglutide 3.0 mg in individu- topiramate treatment in patients with
54. Astrup A, Carraro R, Finer N, Harper als with obesity and moderate or severe migraine: A prospective observational
A, Kunesova M, Lean ME, et al. Safety, obstructive sleep apnea: The SCALE study. CNS Drugs. 2015;29(2):163–9.
tolerability and sustained weight loss over Sleep Apnea randomized clinical trial. Int 67. Liraglutide (SAXENDA(0)) and obesit.
2 years with the once-daily human GLP-1 J Obes (Lond). 2016;40(8):1310–9. Still no satisfactory weight loss drugs.
analog, liraglutide. Int J Obes (Lond). 60. Marso SP, Daniels GH, Brown-Frandsen Prescrire Int. 2016;25(167):5–8.
2012;36(6):843. K, Kristensen P, Mann JF, Nauck MA, 68. Sjostrom L, Rissanen A, Andersen T,
55. Astrup A, Rossner S, Van Gaal L, et al. Liraglutide and cardiovascular out- Boldrin M, Golay A, Koppeschaar HP, et
Rissanen A, Niskanen L, Al Hakim M, et comes in type 2 diabetes. N Engl J Med. al.; European Multicentre Orlistat Study
al. Effects of liraglutide in the treatment 2016;375(4):311–22. Group. Randomised placebo-controlled
of obesity: A randomised, double-blind, 61. Ma J, Xiao L, Stafford RS. Adult obesity trial of orlistat for weight loss and pre-
placebo-controlled study. Lancet. and office-based quality of care in the vention of weight regain in obese patients.
2009;374(9701):1606–16. United States. Obesity (Silver Spring). Lancet. 1998;352(9123):167–72.
56. Pi-Sunyer X, Astrup A, Fujioka K, 2009;17(5):1077–85. 69. Dhurandhar NV, Blank RC, Schumacher
Greenway F, Halpern A, Krempf M, et al. 62. Noel M, Hickner J, Ettenhofer T, D, Atkinson RL. Initial weight loss
A randomized, controlled trial of 3.0 mg Gauthier B. The high prevalence of obe- as a predictor of response to obesity
of liraglutide in weight management. N sity in Michigan primary care practices. drugs. Int J Obes Relat Metab Disord.
Engl J Med. 2015;373(1):11–22. An UPRNet study. Upper Peninsula 1999;23(12):1333–6.
57. le Roux CW, Astrup A, Fujioka K, Research Network. J Fam Pract. 70. Astrup A, Rossner S. Lessons from obe-
Greenway F, Lau DCW, Van Gaal L, 1998;47(1):39–43. sity management programmes: Greater
et al. 3 years of liraglutide ver- 63. Wadden TA, Phelan S. Assessment of initial weight loss improves long-term
sus placebo for type 2 diabetes risk quality of life in obese individuals. Obes maintenance. Obes Rev. 2000;1(1):17–9.
reduction and weight management in Res. 2002;10 Suppl 1:50S–7S. 71. Yanovski SZ, Yanovski JA. Long-
individuals with prediabetes: A ran- 64. Kushner RF, Foster GD. Obesity term drug treatment for obesity: A
domised, double-blind trial. Lancet. and quality of life. Nutrition. systematic and clinical review. JAMA.
2017;389(10077):1399–409. 2000;16(10):947–52. 2014;311(1):74–86.
40
CHAPTER
505
506 Chapter 40 Surgery for Severe Obesity
40.2 BARIATRIC SURGICAL
PROCEDURES
Weight loss surgeries have traditionally been classified
into three categories on the basis of anatomic changes:
restrictive, restrictive-malabsorptive, and malabsorp-
tive. More recently, however, the clinical benefits of bar-
iatric surgery in achieving weight loss and alleviating
metabolic comorbidities have been attributed largely to
changes in the physiologic responses of gut hormones,
bile acid metabolism, the microbiota, and adipose tissue
metabolism.8 Metabolic effects resulting from bypassing
the foregut include altered responses of ghrelin, gluca-
gon-like peptide 1, peptide YY3-36, and oxyntomodu-
lin. Additional effects on food intake and body weight
control may be attributed to changes in vagal signaling. (A) (B)
The loss of fat mass, particularly visceral fat, is associ-
ated with multiple metabolic, adipokine, and inflamma-
tory changes that include improved insulin sensitivity and
glucose disposal; reduced free fatty acid flux; increased
adiponectin levels; and decreased interleukin 6, tumor
necrosis factor α, and high-sensitivity C-reactive protein
levels. The surgical procedures commonly performed are
shown in Figure 40.1.
Restrictive surgeries limit the amount of food that the
stomach can hold and slow the rate of gastric emptying.
The Laparoscopic Adjustable Gastric Banding (LAGB) is
the prototype of this category. The first banding device, the
LAP-BAND™, was approved for use in the U.S. in 2001.
A second device, the REALIZE™ band, was approved in
the U.S. in 2007. In contrast to previous devices, the diam-
eter of these bands is adjustable by way of its connection
to a reservoir that is implanted under the skin. Injection (C) (D)
or removal of saline into the reservoir tightens or loosens
the band’s internal diameter, respectively, thus changing the
size of the gastric opening. Since there is no rerouting of
the intestine with LAGB, the risk for developing nutritional
deficiencies is entirely dependent on the patient’s diet and
eating habits. However, due to poor long-term weight loss
response, the LAGB has fallen into disfavor and accounts
for only 5.7% of all bariatric surgeries performed in 2015.9
The most commonly performed procedure (accounting
for 53.8% of all procedures) is the laparoscopic sleeve
gastrectomy (LSG). In this procedure, the stomach is
restricted by stapling and dividing it vertically and remov-
ing approximately 80% of the greater curvature, leaving
a slim “banana-shaped” remnant stomach along the lesser
curvature.
The restrictive, malabsorptive bypass procedure (E)
combines the elements of gastric restriction with lim-
ited macronutrient malabsorption, primarily of fat. In
the RYGB procedure (accounting for 23.1% of all pro- Figure 40.1 A. Laparoscopic Adjustable Gastric Banding
cedures) a 10 to 30 ml proximal gastric pouch is formed (LAGB). B. Laparoscopic Sleeve Gastrectomy (LSG). C.
by surgically separating the stomach across the fundus. The Roux-en-Y Gastric Bypass (RYGB). D. Biliopancreatic
Outflow from the pouch is created by performing a Diversion (BPD). E. Biliopancreatic Diversion with Duodenal
narrow (10 mm) gastrojejunostomy. The distal end of Switch (BPDDS).
jejunum is then anastomosed 50 to 150 cm below the
gastrojejunostomy. “Roux-en-Y” refers to the Y-shaped connected. “Bypass” refers to the exclusion or bypass-
section of small intestine created by the surgery; the Y ing of the distal stomach, duodenum, and proximal jeju-
is created at the point where the pancreo-biliary con- num. RYGB may be performed with an open incision or
duit (afferent limb) and the Roux (efferent) limb are laparoscopically.
40.5 Weight Loss Outcomes and Improvement in Obesity-Related Medical Conditions 507
There are two malabsorptive procedures that account groups. Many centers offer panel discussions between
40
for less than 1% of all procedures performed in the U.S. candidate patients and patients who have already under-
In the BPD, a subtotal gastrectomy is performed, leaving a gone a procedure to provide a peer-to-peer discussion
much larger gastric pouch compared with the RYGB. The of risks, benefits, and challenges of life after bariatric
small bowel is divided 250 cm proximal to the ileocecal surgery.
valve and connected directly to the gastric pouch, produc- Although it is reasonable to encourage weight loss
ing a gastroileostomy. The remaining proximal limb (bil- prior to surgery, the literature is conflicting regarding
iopancreatic conduit) is then anastomosed to the side of the benefit of mandating preoperative weight loss as a
the distal ileum 50 cm proximal to the ileocecal valve. In criterion to undergo surgery. The primary rationale for
this procedure, the distal stomach, duodenum, and entire requiring routine preoperative weight loss is to decrease
jejunum are bypassed, leaving only a 50 cm distal ileum the short-term operative morbidity and mortality.
common channel for nutrients to mix with pancreatic and Furthermore, the patient’s motivation for and ability to
biliary secretions. The BPDDS is a variation of the BPD adhere to the dietary restrictions considered essential
that preserves the first portion of the duodenum. In this for a successful surgical outcome can be assessed. While
procedure, a vertical subtotal gastrectomy is performed 5–10% of preoperative weight loss has been shown in
and the duodenum is divided just beyond the pylorus. The some studies to reduce postoperative complications,11
distal small bowel is connected to the short stump of the hospital length of stay,12 and operating room time,13
duodenum, producing a 75–100 cm ileal-duodenal “com- as well as improve one-year weight loss,14 other studies
mon channel” for absorption of nutrients. The other end of have not shown a benefit in longer-term weight loss out-
the duodenum is closed, and the remaining small bowel is comes.15–17 An additional compelling reason to endorse
connected onto the enteral limb at about 75–100 cm from preoperative weight loss is to optimize the operative
the ileocecal valve. field by reducing liver volume and visceral adipose tissue
(VAT). Two prospective studies have confirmed the ben-
efit of prescribing a very low-calorie liquid diet (VLCD)
for nine to 12 weeks on preoperative loss of body
40.3 IMPORTANCE OF LIFESTYLE weight, VAT and subcutaneous adipose tissue (SAT),
INTERVENTION liver volume, and comorbid risk factors.18,19 Based on
the existing literature, it is reasonable to include modest
Since obesity is fundamentally a disorder of energy bal- preoperative weight loss as an expectation during the
ance, all treatments must include attention to caloric preoperative period. 20
intake (energy in) and physical activity (energy out). By
altering gastrointestinal anatomy and physiology, weight
loss surgery is a powerful tool to reduce caloric intake. 40.5 WEIGHT LOSS OUTCOMES AND
Nonetheless, patients need counseling on diet and nutri-
tion that is consistent with the specific surgical procedure IMPROVEMENT IN OBESITY-
(restrictive vs. malabsorptive) and with optimal health. RELATED MEDICAL CONDITIONS
They also need guidance on implementing dietary changes
within the structure of their daily life. Similarly, patients Several meta-analyses and systematic reviews of bariatric
benefit from education and advice about increasing daily surgery outcomes have been conducted. 21–24 In general,
physical activity and implementing an exercise routine. weight loss is greatest with the malabsorptive procedures
(BPD, BPDDS), followed by the restrictive-malabsorptive
procedure (RYGB), and least with the restrictive pro-
40.4 PREPARING THE PATIENT cedures (LAGB, LSG). As compared to standard care,
differences in BMI levels from baseline at year one are
FOR SURGERY –11.3 kg/m 2 for BPD, −9.0 kg.m 2 for RYGB, −10.1 kg/m 2
for LGS, and −2.4 kg.m 2 for LAGB. 25 Mean weight loss at
All patients who are considering weight loss surgery two to three years following a surgical procedure ranges
should undergo a comprehensive assessment by a mul- from 20 to 34% of initial body weight, depending on
tidisciplinary team of healthcare providers that includes the procedure. The trajectory of weight loss also differs
a physician or advanced practice provider, registered between procedure types. Whereas the rate of weight loss
dietitian, and mental health professional.10 Preparation is slower with LAGB, with maximal weight loss achieved
for surgery commonly spans six months depending on after two or three years, maximal weight loss with RYGB
the patient's medical condition and criteria for insurance and LSG is achieved at 12–18 months. 26,27
approval. During the preoperative process, patients are Significant improvement in multiple obesity-related
typically instructed on healthy eating and physical activ- comorbid conditions have been reported, including type 2
ity patterns, behavioral strategies to implement the life- diabetes, hypertension, dyslipidemia, and obstructive sleep
style changes, and the importance of stress reduction and apnea. 28–37 One of the most significant clinical outcomes
social support for long-term success. Specific dietary and is the role of bariatric surgery in the treatment of patients
nutritional recommendations pertinent to the surgical with type 2 diabetes (T2D). A substantial body of evi-
procedures include use of protein supplements, consump- dence from 12 randomized controlled trials demonstrate
tion of multiple meals and snacks, and slowing the rate that bariatric/metabolic surgery achieves superior glyce-
of eating. Patients are seen either individually or in small mic control in patients with T2D compared with various
508 Chapter 40 Surgery for Severe Obesity
medical and lifestyle interventions. The improvement in Regardless of the types of foods consumed, regurgita-
diabetes control appears to be due to both weight loss tion or vomiting can occur when patients eat too quickly,
and weight loss independent effects.38 Based on this data, fail to chew food thoroughly, or eat in excess of what the
the Second Diabetes Surgery Summit (DSS-II) Consensus gastric pouch will hold. However, it should be noted that
Conference published guidelines in 2015 that were vomiting is not an intended consequence of bariatric sur-
endorsed by more than 50 other organizations interested gery and it should not be viewed as normal, particularly
in the treatment of diabetes. 5 According to the guidelines, in the late postoperative period. Patients who have per-
metabolic surgery should be recommended to treat T2D in sistent vomiting or regurgitation after surgery should be
patients with class II obesity (BMI of 35.0 to 39.9 kg/m 2) evaluated for the presence of maladaptive eating behaviors
when hyperglycemia is inadequately controlled with life- as well as anatomical or functional issues such as stomal
style and optimal medical therapy, and it should be simi- stenosis or ulceration, reflux, and gastric dysmotility.10,47
larly considered for those with class I obesity (BMI of 30.0 Patients with symptoms of dumping syndrome can
to 34.9 kg/m 2). The 2018 Standards of Care for Diabetes usually be managed by dietary modification, including
from the American Diabetes Association includes bariat- avoidance of concentrated sweets and simple sugars,
ric surgery in the treatment algorithm for T2D.39 consumption of small frequent meals, and inclusion of
protein at every meal. Patients with symptoms suggestive
of postprandial hypoglycemia that are not ameliorated
40.6 LIFESTYLE INTERVENTIONS IN by dietary modification should undergo evaluation for
the presence of endogenous (or “post-bypass”) hyperin-
THE POSTOPERATIVE CARE OF sulinemic hypoglycemia.10,48 Patients with more severe
BARIATRIC SURGICAL PATIENTS neuroglycopenic symptoms (such as confusion or loss of
consciousness) should also undergo evaluation for this
National guidelines suggest that continued attention to condition, which can occur after gastric bypass. For most
diet, physical activity, and emotional health after bar- patients with post-bypass hypoglycemia, dietary modifi-
iatric surgery is essential to ensure optimal outcomes.10 cation, including carbohydrate restriction to less than 30
Accordingly, patients are encouraged to participate in post- grams per meal, can significantly reduce the frequency and
operative programs that support lifestyle modification. severity of symptoms.49 However, when symptoms per-
sist, pharmacologic therapies, such as acarbose, diazox-
ide, somatostatin analogs, and calcium channel blockers,
40.7 NUTRITIONAL CARE may be required.
Sleeve gastrectomy has been reported to produce similar along with appropriate clinical follow up and routine
40
deficiencies as gastric bypass but at a somewhat lower fre- biochemical surveillance. Expert guidelines are available
quency.52 As compared to RYGB, the BPDDS is much more regarding recommended vitamin and mineral supple-
likely to produce deficiencies of the fat-soluble vitamins, mentation after surgery and the frequency of laboratory
including vitamin A.53 Purely restrictive procedures such as screening for deficiency states.10,55 Tables 40.1 and 40.2
LAGB are infrequently associated with specific nutritional summarize these recommendations. Patients who are
deficiencies.54 found to have evidence of specific micronutrient deficien-
In many cases, micronutrient deficiencies can be pre- cies will need additional vitamin or mineral supplementa-
vented by regular vitamin and mineral supplementation tion, as indicated.
Patient subgroups at higher risk requiring additional supplementation are indicated. Adapted from the American Society for Metabolic and Bariatric Surgery Integrated Health
Nutritional Guidelines for the Surgical Weight Loss Patient. See Ref.55
LAGB, laparoscopic adjustable gastric banding; RYGB, Roux-en-Y gastric bypass; SG, sleeve gastrectomy; BPD/DS, BPDDS.
a Obtained from a multiple vitamin-mineral supplements.
b Calcium should be given in divided doses, calcium carbonate should be taken with meals, calcium citrate may be taken with or without meals.
TABLE 40.2 Recommended laboratory tests and frequency of routine biochemical surveillance
Recommended frequency
Procedure of biochemical surveillance Recommended laboratory tests
LAGB, RYGB, 1st year: every 3-6 months. CBC, electrolytes, glucose, iron studies, ferritin, vitamin B12, liver function, lipids,
and SG Thereafter: annually 25-hydroxyvitamin D
As needed: intact PTH, thiamine, RBC folate, MMA, HCy
BPD/DS 1st year: every 3 months. Every 3-6 months: CBC, electrolytes, glucose, iron studies, ferritin, vitamin B12, RBC
Thereafter: every 3-6 months folate, liver function, albumin, prealbumin, lipids
Every 6–12 months: 25-hydroxyvitamin D, vitamin A, vitamin E, vitamin K, INR, intact
PTH
Every 12 months: urine N-telopeptide, metabolic stone evaluation (24-hour urine
calcium, citrate, uric acid and oxalate), zinc and selenium
As needed: osteocalcin, carnitine, essential fatty acid chromatography
Adapted from the American Association of Clinical Endocrinologists/The Obesity Society/American Society for Metabolic and Bariatric Surgery Medical Guidelines for Clinical
Practice for the Perioperative Nutritional, Metabolic, and Nonsurgical Support of the Bariatric Surgery Patient. See Ref.10
LAGB, laparoscopic adjustable gastric banding; RYGB, Roux-en-Y gastric bypass; SG, sleeve gastrectomy; BPD/DS, BPDDS; CBC, complete blood count; PTH, parathyroid
hormone; RBC, red blood cell; MMA, methylmalonic acid; HCy, homocysteine; INR, international normalized ratio.
510 Chapter 40 Surgery for Severe Obesity
40.7.4 Physical Activity patients who did not exercise, and it was also associ-
ated with an increase in functional and aerobic capacity.
Among individuals who have lost weight with nonsurgi- In another small, randomized, controlled trial, investi-
cal treatment approaches, physical activity clearly plays gators randomly assigned 33 obese (BMI ≥ 35.5 kg/m2)
a vital role in long-term maintenance of weight loss. 56,57 postoperative patients to either high-volume exercise
Much less is known about the role of physical activity in (with a goal of expending ≥2000 kcal/week in moderate
weight control after bariatric surgery, but it is likely an intensity aerobic exercise) or a usual activity control for
important factor. 12 weeks.67 Subjects assigned to the exercise intervention
reported a greater than three-fold increase in time spent in
moderate physical activity and a nearly two-fold increase
40.7.5 Physical Activity Levels in recorded step counts. In this small study, intervention
after Bariatric Surgery group subjects did not have greater weight loss or greater
improvements in body composition, fasting glucose or
Numerous studies suggest that self-reported levels of phys- insulin levels, lipids, or blood pressure, as compared to
ical activity increase significantly after bariatric surgery.58 controls. However, they did have significantly greater
However, there is little objective data regarding changes in improvements in physical fitness and glucose levels after
physical activity levels in the postoperative period, and self- an oral glucose challenge. Additional data are needed to
reported increases are likely to be overestimated. In one further characterize the benefits of exercise in postopera-
study, patients reported a large increase in moderate-to- tive bariatric surgery patients and to determine the opti-
vigorous intensity activity after surgery, but accelerometer mal physical activity levels in this group.
data suggested that such an increase did not actually occur
in most individuals.60 The data suggest that only 6–24%
of post-bariatric surgery patients meet national guide-
lines regarding minimal physical activity levels for general 40.7.7 Barriers to Physical Activity
health promotion (i.e. ≥150 min/week or moderate-to-vig- after Bariatric Surgery
orous physical activity in bouts of 10 minutes or more).61,62 Significant weight loss, such as that achieved after bar-
Data from the National Weight Control Registry indicate iatric surgery, may enable patients with severe obesity to
that patients who have lost weight through bariatric sur- become more active. However, cognitive barriers to physi-
gery tend to be less physically active than individuals who cal activity may persist after bariatric surgery and may
have lost similar amounts of weight through nonsurgical influence patients’ activity levels.59 These barriers include
approaches.63 reduced awareness of the health benefits of exercise, fear
of injury, a lack of confidence in the ability to participate
in physical activity, and self-consciousness or embarrass-
40.7.6 Benefits of Physical Activity ment. Treatment strategies which address these barriers
in Postoperative Bariatric may help patients become more physically active.
Surgery Patients
In epidemiologic studies of postoperative patients, 40.7.8 Recommendations for Physical
increased self-reported physical activity has been repeatedly
associated with improved weight loss, mood and psycho-
Activity after Bariatric Surgery
social functioning.63,64 Similarly, in a cross-sectional study National guidelines suggest that for optimal weight con-
that used armband accelerometers to measure activity in trol most overweight individuals will need to accumulate
patients who had undergone RYGB two to five years ear- at least 150–300 minutes of moderate physical activity per
lier, higher levels of moderate-to-vigorous physical activity week, or 30–60 minutes most days of the week.68 In one
were associated with greater postoperative weight loss.61 study of subjects who have successfully maintained large
However, there are limited data from intervention weight losses over time after surgical or nonsurgical treat-
studies regarding the impact of physical activity training ments, nearly 70% engage in 150 minutes or more of mod-
on perioperative outcomes. In a small, randomized con- erate-to-vigorous physical activity per week, and over 30%
trolled trial, bariatric patients who participated in a six are physically active for at least 300 minutes per week.57
month preoperative exercise program (including 80 min- Other data from the National Weight Control Registry
utes of supervised aerobic exercise and resistance training indicate that walking is the preferred form of physical
three times a week) had greater step counts, more time activity in this group of individuals.69 In randomized con-
spent in light and moderate physical activity, improved fit- trolled trials, as well as epidemiologic studies, individuals
ness parameters, and greater BMI reductions at one year who use pedometers to reach a specific step-count goal
postoperatively than patients assigned to usual care.65 In (such as >10,000 steps/day) increase their activity levels
contrast, in a non-randomized, prospective study, partici- more and lose slightly more weight than those who do not
pation in a postoperative exercise program (including 75 use pedometers.70 Regular pedometer use may therefore
minutes of supervised aerobic exercise and resistance train- be a practical and helpful strategy for patients who have
ing three times a week) for three months did not signifi- had bariatric surgery. However, a recent, randomized con-
cantly increase weight loss after RYGB surgery.66 However, trolled trial suggested that the provision of pedometers to
the intervention did prevent the observed decrease in bariatric surgery patients may be an ineffective strategy
dynamic muscle strength that was seen in postoperative unless it is coupled with ongoing exercise counseling.71
40.7 Nutritional Care 511
40.7.9 Behavioral/Psychological Care and after surgery, and that their depression persists even
40
if they have excellent weight loss results81 These reports
Bariatric surgical patients experience a variety of psycho- highlight the importance of continued attention to psy-
social challenges in the postoperative period. Initially, chosocial health in the postoperative period, regardless of
patients must adjust to the postoperative diet and to their weight loss outcomes.
altered relationship with food. As weight loss progresses,
patients must adapt to changes in their appearance and
their interactions with others. Dramatic weight loss,
however desirable to the patient, can lead to unexpected
40.7.11 Disordered Eating
consequences, such as body image issues related to excess Data from the LABS study have provided information
skin, unwanted sexual attention from others, and jealousy regarding the effect of weight loss surgery on eating pathol-
from friends and loved ones. As a result of these many ogy.82 Following a cohort of 183 patients for up to three
challenges, mood disorders, disordered eating patterns, years postoperatively, investigators found that pathologi-
and substance abuse are common among postoperative cal eating behaviors and eating-related experiences are
patients. common prior to bariatric surgery and improve following
surgery. For example, pre- and one-year prevalence rates
for bulimic episodes declined from 11.6% to 1.3%, loss
40.7.10 Mood Disorders of control eating declined from 18.3% to 6.2%, picking/
nibbling diminished from 36.0% to 20.2%, and evening
Mood disorders are prevalent among candidates for bar-
hyperphagia reduced from 16.5% to 5.0%. In contrast,
iatric surgery. For example, in one prospective study utiliz-
hunger increased from one to three years of follow up.
ing structured clinical interviews to assess mood pre- and
Post-surgery eating-related variables associated with poor
postoperatively, clinical depression was present in approxi-
weight outcomes included loss of control eating, hunger,
mately one-third and anxiety was present in almost 20%
and the eating disorder examination global score (which
of preoperative patients.72 In this population, the preva-
combines several factors such as restraint and shape/
lence of clinical depression decreased by over 50% in the
weight concerns). It is important to probe for eating
three years following surgery, but the prevalence of anxiety
pathology since patients may not report these behaviors
remained relatively stable. Other studies have reported sig-
unless they are prompted by a clinician.
nificant improvements in depressive symptoms that persist
for up to five years postoperatively.73–74 Data from the large
Swedish Obese Subjects (SOS) study suggest that after dra-
matic improvements in both depression and anxiety in the
40.7.12 Alcohol Misuse
first postoperative year, there may be some deterioration The concern about the potential for development of alcohol
of mood over time.75 However, even 10 years postopera- dependence or abuse in postoperative patients was previ-
tively, the prevalence of mood disorders did not return to ously raised as a possible “addiction transfer” phenome-
baseline levels in this cohort. Data from the Longitudinal non.83 Although there is little support for this hypothesis,
Assessment of Bariatric Surgery (LABS) study, a prospec- it does raise the question of whether patients who drink
tive, observational study of patients undergoing bariatric alcohol preoperatively are at increased risk for continued
surgery, have provided further information regarding the use, and what effect (if any) bariatric surgery may have
effect of weight loss surgery on psychiatric disorders.76 At on development of alcohol use disorder (AUD). In a sub-
pre-surgery, 30% of patients met the diagnostic criteria for study of LABS, patients completed baseline and follow
an Axis 1 disorder. The prevalence dropped to 17% and up assessments of alcohol consumption using the Alcohol
18% at two and three years after surgery, respectively. The Use Disorders Identification Test (AUDIT), a 10-item test.
corresponding prevalence rates at baseline and at years A score of ≥8 (range 0–40) suggests harmful and hazard-
two and three for any anxiety disorder was 17.2%, 12.3%, ous alcohol use and possible dependence. After RYGB,
and 7.8%, respectively. Of note, however, was that use of there was an increase in the prevalence of AUD at baseline
any psychiatric medication or anti-anxiety medication (pre-surgery) (6.6%) to year two (9.6%) and year seven
remained relatively stable over time despite the reduced (16.4%).84–86 Five-year cumulative incidence of AUD treat-
number of patients meeting the diagnostic criteria for any ment was 20.8%. Male sex, younger age, smoking, and any
psychiatric disorder. There was no explanation of this dis- or regular alcohol consumption pre-surgery were associ-
crepancy provided in the report. ated with increased risk for developing AUD. In another
It is important to note that some studies have yielded comprehensive review of the literature,84 a preoperative
discrepant findings. In one small cohort, levels of depres- history of substance use (including alcohol) was a reliable
sion and anxiety did not change significantly after sur- predictor of postoperative use.
gery.41 Furthermore, patients who have undergone The absorption and metabolism of alcohol may be
bariatric surgery may be at an increased risk of suicide, altered after bariatric surgery, and, as a result, postopera-
particularly in the first three years after surgery.77–79 In tive patients may be more susceptible to the intoxicating
a large, retrospective cohort study, individuals who had effects of alcohol.87–90 Patients should therefore be coun-
undergone gastric bypass surgery were twice as likely seled to exercise caution when consuming alcohol after
to commit suicide as obese control subjects matched for surgery. In addition, clinicians who care for bariatric
sex, age, and baseline BMI.80 Case studies suggest that surgery patients should ask patients about alcohol intake
patients who commit suicide after bariatric surgery often after surgery and remain alert to the possible presence of
have a history of recurrent major depression, both before AUD in this population.91
512 Chapter 40 Surgery for Severe Obesity
40.7.13 Psychological Counseling factors that have been associated with variability in post-
surgical weight loss, including binge eating, depression,
and Peer Support in the motivation, and coping skills. Eight of the studies assessed
Postoperative Period outcome at a one-year follow up, and seven used a non-
Data suggest that patients with postoperative depression randomized controlled trial design. They concluded that
experience poorer weight loss than those who are not both psychotherapeutic interventions and support groups
depressed.73 Similarly, postoperative patients who exhibit provided a modest beneficial effect on post-surgical weight
disordered eating patterns, such as grazing and loss of loss with an overall effect size of 0.18. In a subsequent
control over eating, have poorer weight loss and greater review by Kushner and Sorenson100 in 2014, seven RCTs
weight regain.92,93 Clearly, patients who are found to have were identified investigating the efficacy of behavioral,
mood disorders, disordered eating behavior, or substance dietary, or exercise counseling for postoperative weight
abuse after bariatric surgery should be offered expert loss. The authors concluded that the lifestyle interven-
psychological counseling and support. It is not known, tions had either no effect or were only modestly effective
however, whether such treatment improves weight loss or in enhancing further weight loss and influencing lifestyle-
other outcomes. related behaviors among post-bariatric surgery patients.
In epidemiologic studies, attendance at postoperative More recently, additional pilot studies using cognitive
support groups is associated with improved weight loss behavioral therapy (CBT),101 CBT and dialectical behav-
outcomes.94–96 There is a lack of data regarding the effects ioral therapy,102 and acceptance-based therapy103 have
of other types of postoperative psychological support, been published. However, enhancement of weight loss
such as group or individual therapy, on weight loss and
other outcomes. TABLE 40.3 Etiological factors for weight regain following
Interestingly, patients who exhibit disordered eating bariatric surgery
patterns may be more receptive to a behavioral interven-
tion after surgery than before surgery. In one small, non- Anatomical
randomized, prospective study, pre- and postoperative LAGB malfunction or mismanagement
bariatric surgical patients with binge eating or other dis-
ordered eating patterns were referred to a 10-week cogni- Band or port breakage, band too loose
tive behavioral therapy program designed to address and RYGB
improve the maladaptive eating patterns.97 Patients who
Pouch enlargement
were referred to the program postoperatively were much
more likely to attend the initial session and to complete Gastrojejunal anastomosis dilation
the program than patients referred preoperatively. Gastro-gastro fistula
Physiological
40.7.14 Comprehensive Lifestyle Pregnancy
Interventions after Bariatric Surgery Menopause
There are limited data regarding the benefits of comprehen- Medications which cause weight gain
sive lifestyle interventions in the postoperative period. Two
Smoking cessation
systematic reviews and meta-analyses on behavioral98 and
psychotherapeutic99 interventions in the bariatric surgical Endocrine disorders: hypothyroidism, Cushing's Syndrome,
population have been published. In the review by Rudolf insulinoma
and Hilbert,98 they identified 15 behavioral management Intestinal or hormonal adaptation
studies published prior to 2012. Eight provided cogni-
tive behavioral therapy and seven included group support Behavioral
attendance. Five of the behavioral studies were conducted Dietary
as randomized controlled trials (RCT) while all of the group
unhealthy eating patterns e.g. grazing, nibbling, mindless
support studies were of retrospective cohort design. Surgical
eating
procedures were primarily RYGB or LAGB and weight loss
outcomes ranged from three to 36 months postoperatively. consumption of energy-dense foods and beverages
Across all of the behavioral studies, patients in the treat- loss of dumping syndrome symptoms
ment groups showed greater weight loss than patients in
the control groups; however, differences did not reach sig- loss of control over urges, binges
nificance in any samples. For the group support studies, reduced vigilance
the majority found greater weight loss among those who
Physical activity
attended support group meetings than in those that did not,
though the difference was once again marginal. reduced leisure time activity
In the review by Beck et al.,99 they identified nine
increased sedentary behaviors
studies investigating the effect of psychotherapeutic
interventions and support groups on weight loss follow- insufficient moderately- and vigorously-intensity exercise
ing bariatric surgery that were published prior to 2012. development of physical limitations to exercise
Psychotherapeutic treatment targets the psychological
References 513
REFERENCES
1. NIH conference. Gastrointestinal obesity in the United States, 2011–2012. 12. Still DO, Benotti P, Wood GC, et
surgery for severe obesity. Consensus JAMA 311(8):806–814. al. Outcomes of preoperative weight
Development Conference Panel. Ann 7. American Society for Metabolic and loss in high-risk patients undergo-
Intern Med 1991;115(12):956–961. Bariatric Surgery. https: //asmbs.org/re ing gastric bypass surgery. Arch Surg
2. Jones DB, Provost DA, De Maria EJ, sources/estimate -of-bariat ric-surger y-nu 2007;142:994–998.
Smith CD, Morgenstern L, Schirmer B. mbers. Accessed December 10, 2017. 13. Alami RS, Morton JM, Schuster R, et al.
Optimal management of the morbidly 8. Madsbad S, Dirksen C, Holst JJ. Is there a benefit to preoperative weight
obese patient. SAGES appropriateness Mechanisms of changes in glucose loss in gastric bypass patients? A prospec-
conference statement. Surg Endosc metabolism and bodyweight after bar- tive randomized trial. Surg Obes Relat
2004;18:1029–1037. iatric surgery. Lancet Diabetes Metab Dis 2007;3:141–146.
3. Buchwald H. Bariatric surgery for morbid 2014;2:152–164. 14. Solomon H, Liu GY, Alami R, et al.
obesity: Health implications for patients, 9. Kizy S, Jahansouz C, Downey MC, et al. Benefits to patients choosing preopera-
health professionals, and third-party pay- National trends in bariatric surgery 2012– tive weight loss in gastric bypass surgery:
ers. J Am Coll Surg 2005;200:593–604. 2015: Demographics, procedure selec- New results of a randomized trial. J Am
4. Jensen MD, Ryan DH, Apovian CM, et tion, readmissions, and cost. Obes Surg Coll Surg 2009;208:241–245.
al. 2013 AHA/ACC/TOS guidelines for 2017;27:2933–2999 (published online). 15. Jantz EJ, Larson CJ, Mathiason MA,
the management of overweight and obe- 10. Mechanick JI, Youdim A, Jones DB, et al. et al. Number of weight loss attempts
sity is adults: A report of the American Clinical practice guidelines for the periop- and maximum weight loss before
College of Cardiology/American Heart erative nutritional, metabolic, and nonsurgi- Rouz-en-Y laparoscopic gastric bypass
Association task force on practice guide- cal support of the bariatric surgery patient surgery are not predictive of postopera-
lines and the Obesity Society. Circulation – 2013 update: Cosponsored by American tive weight loss. Surg Obes Relat Dis
2014;129:S102. Association of Clinical Endocrinologists, 2009;5:208–211.
5. Rubino F, Nathan DM, Eckel RH, et al. The Obesity Society, and American Society 16. Ali MR, Baucom-Pro S, Broderick-
Metabolic surgery in the treatment algo- for Metabolic & Bariatric Surgery. Endocr Villa GA, et al. Weight loss before
rithm for type 2 diabetes. Diabetes Care Pract 2013;19(2):e1–e36. gastric bypass: Feasibility and effect on
2016;39(6):861–872. 11. Benotti PN, Still CD, Wood GC, et al. postoperative weight loss and weight
6. Ogden CL, Carroll MD, Kit BK, Flegal Preoperative weight loss before bariatric loss maintenance. Surg Obes Relat Dis
KM. Prevalence of childhood and adult surgery. Arch Surg 2009;144:1150–1155. 2007;3:515–520.
514 Chapter 40 Surgery for Severe Obesity
17. Eisenberg D, Duffy AJ, Bell RL. Does Surg 2017;27:2733–2739. doi: 10.1007/ 49. van Meijeren J, Timmer I, Brandts H,
preoperative weight change predict post- s11695-017-2869-1. Janssen I, Hans deBoer H. Evaluation of
operative weight loss after laparoscopic 34. Müller-Stich BP, Senfit JD, Warschkow carbohydrate restriction as primary treat-
Roux-en-Y gastric bypass in the short R, et al. Surgical versus medical treat- ment for post-gastric bypass hypoglyce-
term? J Obes 2010: ment of type 2 diabetes mellitus in mia. SOARD 2017;13(3):404–410.
18. Colles SL, Dixon JB, Marks P, et al. nonseverely obese patients. Ann Surg 50. Thomas JG, Bond DS, Ryder BA, et al.
Preoperative weight loss with a very-low- 2015;261:421–429. Ecological momentary assessment of
energy diet: Quantitation of changes in 35. Gloy VL, Briel M, Bhatt DL, et al. recommended postoperative eating and
liver and abdominal fat by serial imaging. Bariatric surgery versus non-surgical activity behaviors. Surg Obes Relat Dis
Am J Clin Nutr 2006;84:304–311. treatment for obesity: A systematic 2011;7(2):206–212.
19. Collins J, McCloskey C, Tichner R, et al. review and meta-analysis of randomized 51. Shah M, Simha V, Garg A. Long-term
Preoperative weight loss in high-risk controlled trials. BMJ 2013;347:f5934. impact of bariatric surgery on body
superobese bariatric patients: A computed doi: 10.1136/bmj.f5934. weight, comorbidities, and nutritional
tomography-based analysis. Surg Obes 36. Kwok CS, Pradhan A, Khan MA, et status. J Clin Endocrinol Metab
Relat Dis 2011;7:480–485. al. Bariatric surgery and its impact on 2006;91(11):4223–4231.
20. Livhits M, Mercado C, Yermilov R, et al. cardiovascular disease and mortality: A 52. Gehrer S, Kern B, Peters T, et. al. Fewer
Does weight loss immediately before systematic review and meta-analysis. Int J nutrient deficiencies after laparoscopic
bariatric surgery improve outcomes: A Cardiol 2014;173:20–28. sleeve gastrectomy (LSG) than after
systematic review. Surg Obes Relat Dis 37. Ricci C, Gaeta M, Rausa E, et al. laparoscopic Roux-Y-gastric bypass
2009;5:713–721. Long‑term effects of bariatric surgery (LRYGB)—A prospective study. Obes
21. Buchwald H, Avidor Y, Braunwald on type II diabetes, hypertension and Surg 2010;20(4):447–453.
E, et al. Bariatric surgery: A system- hyperlipidemia: A meta-analysis and 53. Aasheim ET, Björkman S, Søvik TT, et al.
atic review and meta-analysis. JAMA meta-regression study with 5-year Vitamin status after bariatric surgery:
2004;292:1724–1737. follow‑up. Obes Surg 2015;25:397–405. A randomized study of gastric bypass
22. Maggard MA, Shugarman LR, Suttorp 38. Madsbad S, Dirksen C, Holst JJ. and duodenal switch. Amer J Clin Nutr
M, et al. Meta-analysis: Surgical Mechanisms of changes in glucose 2009;90(1):15–22.
treatment of obesity. Ann Intern Med metabolism and bodyweight after 54. Schouten R, Wiryasaputra D, van Dielen
2005;142:547–559. bariatric surgery. Lancet Diabetes F, et al. Long-term results of bariatric
23. O’Brien PE, McPhail T, Chaston TB, Endocrinol 2014;2:152–164. restrictive procedures: A prospective
et al. Systematic review of medium-term 39. American Diabetes Association. study. Obes Surg 2010;20(12):1617–1626.
weight loss after bariatric operations. Obesity Management for the Treatment of 55. Parrott J, Frank L, Rabena R. American
Obes Surg 2006;16:1032–1040. Type 2 Diabetes: Standards of Medical Society for Metabolic and Bariatric
24. Wolfe BM, Kvach E, Eckel RH. Care in Diabetes—2018. Diabetes Care Surgery integrated health nutritional
Treatment of obesity. Weight loss 2018;41(Supplement 1): S65–S72. guidelines for the surgical weight loss
and bariatric surgery. Circ Res 40. Das SK, Roberts SB, McCrory MA, et al. patient 2016 update: Micronutrients.
2016:118:1844–1855. Long-term changes in energy expendi- SOARD 2017;13:727–741.
25. Padwal R, Klarenbach S, Wiebe N, et al. ture and body composition after massive 56. Bartfield JK, Stevens VJ, Jerome GJ, et al.
Bariatric surgery: A systematic review weight loss induced by gastric bypass sur- Behavioral transitions and weight change
and network meta-analysis of random- gery. Am J Clin Nutr 2003;78(1):22–30. patterns within the PREMIER trial.
ized trials. Obes Rev 2011;12:602–621. 41. Kruseman M, Leimgruber A, Zumbach Obesity 2011;19(8):1609–1615.
26. Dixon JB, Straznicky NE, Lambert EA, F, et al. Dietary, weight, and psychologi- 57. Catenacci VA, Grunwald GK,
Schlaich MP, Lambert GW. Laparoscopic cal changes among patients with obesity, Ingebrigtsen JP, et al. Physical activ-
adjustable gastric banding and other 8 years after gastric bypass. J Am Diet ity patterns using accelerometry in the
devices for the management of obesity. Assoc. 2010;110(4):527–534. National Weight Control Registry.
Circulation 2012;126:774–785. 42. Kanerva N, Larsson I, Peltonen M, Obesity 2011;19(6):1163–1170.
27. Smith BR, Schauer P, Nguyen NT. Lindroos AK, Carlsson LM. Changes in 58. Herring LY, Stevinson C, Davies MJ, et
Surgical approaches to the treatment total energy intake and macronutrient al. Changes in physical activity behav-
of obesity: Bariatric surgery. Med Clin composition after bariatric surgery pre- iour and physical function after bariatric
North Am 2011;95:1009–1030. dict long-term weight outcome: Findings surgery: A systematic review and meta-
28. Poirier P, Cornier MA, Mazzone T, et al. from the Swedish Obese Subjects (SOS) analysis. Obes Rev 2016;17(3):250–261.
Bariatric surgery and cardiovascular risk study. Am J Clin Nutr 2017;106:136–145. 59. Bond DS, Jakicic JM, Unick JL, et al.
factors: A scientific statement from the 43. Silver H, Torquati A, Jensen G, et al. Pre- to postoperative physical activity
American Heart Association. Circulation Weight, dietary and physical activity changes in bariatric surgery patients: Self
2011;123(15):1683–1701. behaviors two years after gastric bypass. report vs. objective measures. Obesity
29. Sjöström L, Peltonen M, Jacobson P, Obes Surg 2006;16(7):859–864. 2010;18(12):2395–2397.
et al. Association of bariatric surgery 44. Mallory G, Macgregor A, Rand C. The 60. Josbeno D, Kalarchian M, Sparto P,
with long-term remission of type 2 influence of dumping on weight loss after Otto AD, Jakicic JM. Physical activ-
diabetes and with microvascular and gastric restrictive surgery for morbid ity and physical function in individu-
macrovascular complications. JAMA obesity. Obes Surg 1996;6(6):474–478. als post-bariatric surgery. Obes Surg
2014;311:2297–2304. 45. Olbers T, Bjorkman S, Lindroos A, et al. 2011;21(8):1243–1249.
30. Arterburn DE, Olsen MK, Smith VA, Body composition, dietary intake, and 61. King WC, Chen JY, Bond DS, et al.
et al. Association between bariatric energy expenditure after laparoscopic Objective assessment of changes in physi-
surgery and long-term survival. JAMA Roux-en-Y gastric bypass and laparo- cal activity and sedentary behavior: Pre-
2015;313:62–70. scopic vertical banded gastroplasty. Ann through 3 years post-bariatric surgery.
31. Mingrone G, Panunzi S, DeGaetano A, Surg 2006;244(5):715–722. Obesity 2015;23(6):1143–1150.
et al. Bariatric-metabolic surgery versus 46. Mitchell J, Lancaster K, Burgard M, 62. Bond DS, Phelan S, Leahey TM, et al.
conventional medical treatment in obese et al. Long-term follow-up of patients’ Weight-loss maintenance in successful
patients with type 2 diabetes: 5 year status after gastric bypass. Obes Surg weight losers: Surgical vs non-surgical
follow-up of an open-label, single-centre, 2001;11(4):464–468. methods. Int J Obes 2008;33(1):173–180.
randomized controlled trial. Lancet 47. Heber D, Greenway F, Kaplan L, et al. 63. Rosenberger P, Henderson K, White M,
2015;386:964–973. Endocrine and nutritional management et al. Physical activity in gastric bypass
32. Schauer PR, Bhatt DL, Kirwan JP, et al. of the post-bariatric surgery patient: patients: Associations with weight loss
Bariatric surgery versus intensive medical An Endocrine Society Clinical Practice and psychosocial functioning at 12-month
therapy for diabetes – 5 year outcomes. N Guideline. J Clin Endocrinol Metab follow-up. Obes Surg. 2010:1–6.
Engl J Med 2017;376:641–651. 2010;95(11):4823–4843. 64. Baillot A, Vallée CA, Mampuya WM,
33. Cohen R, LeRoux CW, Junqueira S, et 48. Goldfine A, Mun E, Patti M. Dionne IJ, Comeau E, Méziat-Burdin A,
al. Roux-en-Y gastric bypass in type 2 Hyperinsulinemic hypoglycemia following Langlois MF. Effects of a pre-surgery
diabetes patients with mild obesity: A sys- gastric bypass surgery for obesity. Curr Opin supervised exercise training 1 year
tematic review and meta-analysis. Obes Endocrinol Diabetes 2006;13:419–424. after bariatric surgery: A randomized
References 515
controlled study. Obes Surg 2017. doi: 78. Kalarchian MA, King WC, Devlin MJ, Two high-risk factors following bariatric
10.1007/s11695–017-2943–8. [Epub et al. Psychiatric disorders and weight surgery. Obesity 2008;16(3):615–622.
65.
ahead of print].
Bond DS, Phelan S, Wolfe LG, et al.
Becoming physically active after
change in a prospective study of bariatric
surgery patients: A 3-year follow-up.
Psychosom Med 2016;78:373–381.
94. Livhits M, Mercado C, Yermilov I, et al.
Behavioral factors associated with suc-
cessful weight loss after gastric bypass.
40
bariatric surgery is associated with 79. Tindle HA, Omalu B, Courcoulas A, Am Surg 2010;76(10):1139–1142.
improved weight loss and health- et al. Risk of suicide after long-term 95. Orth W, Madan A, Taddeucci R, et al.
related quality of life. Obesity follow-up from bariatric surgery. Am Support group meeting attendance is
2008;17(1):78–83. J Med 2010;123(11):1036–1042. associated with better weight loss. Obes
66. Stegen S, Derave W, Calders P, et al. 80. Adams TD, Gress RE, Smith SC, Surg 2008;18(4):391–394.
Physical fitness in morbidly obese et al. Long-term mortality after 96. Song Z, Reinhardt K, Buzdon M, Liao
patients: Effect of gastric bypass sur- gastric bypass surgery. N Engl J Med P. Association between support group
gery and exercise training. Obes Surg 2007;357(8):753–761. attendance and weight loss after Roux-
2011;21(1):61–70. 81. Omalu BI, Cho P, Shakir AM, et al. en-Y gastric bypass. Surg Obes Relat Dis
67. Wouters E, Larsen J, Zijlstra H, et Suicides following bariatric surgery for 2008;4(2):100–103.
al. Physical activity after surgery for the treatment of obesity. Surg Obes Relat 97. Leahey TM, Bond DS, Irwin SR, et al.
severe obesity: The role of exercise Dis 2005;1(4):447–449. When is the best time to deliver behav-
cognitions. Obes Surg 2010:1–6. Epub 82. Devlin MJ, King WC, Kalarchian MA, ioral intervention to bariatric surgery
Sep 14, 2010. et al. Eating pathology and experience and patients: Before or after surgery? Surg
68. Shah M, Snell PG, Rao S, et al. High- weight loss in a prospective study of bar- Obes Relat Dis 2009;5(1):99–102.
volume exercise program in obese iatric surgery patients: 3-year follow-up. 98. Rudolph A, Hilbert A. Post-operative
bariatric surgery patients: A randomized, Int J Eating Disord 2016;49:1058–1067. behavioral management in bariatric
controlled trial. Obesity 2011;19:1826– 83. Sogg S. Alcohol misuse after bariatric surgery: A systematic review and meta-
1834 (Epub June 16). surgery: Epiphenomenon or “Oprah” analysis of randomized controlled trials.
69. US Department of Health and Human phenomenon? Surg Obes Relat Dis Obes Rev 2013;14:292–302.
Services. 2008 Physical Activity 2008;3(3):366–368. 99. Beck NN, Johannsen M, Stoving
Guidelines for Americans. Washington, 84. King WC, Chen JY, Mitchell JE, et al. RK, et al. Do postoperative psycho-
DC: US Department of Health and Prevalence of alcohol use disorders therapeutic interventions and support
Human Services, 2008. before and after bariatric surgery. JAMA groups influence weight loss following
70. Catenacci VA, Ogden LG, Stuht J, et al. 2012;307:2516–2525. bariatric surgery? A systematic review
Physical activity patterns in the National 85. King WC, Chen JY, Courcoulas AP, et and meta-analysis of randomized and
Weight Control Registry. Obesity al. Alcohol and other substance use after nonrandomized trials. Obes Surg
2007;16(1):153–161. bariatric surgery: Prospective evidence 2012;22(11):1790–1797.
71. Creel DB, Schuh LM, Reed CA, from a U.S. multicenter cohort study. 100. Kushner RF, Sorensen KW. Prevention of
Gomez AR, Hurst LA, Stote J, Cacucci SOARD 2017;13:1392–1404. weight regain following bariatric surgery.
BM. A randomized trial comparing 86. Li L, Wu LT. Substance use after bariatric Curr Obes Rep 2015;4(2):198–206.
two i nterventions to increase physi- surgery: A review. J Psychiatric Res 101. Gade H, Friborg O, Rosenvinge JH,
cal activity among patients under- 2016;76:16–29. et al. The impact of a preoperative
going bariatric surgery. Obesity 87. Klockhoff H, Näslund I, Jones AW. cognitive behavioural therapy (CBT)
2016;24(8):1660–1668. Faster absorption of ethanol and higher on dysfunctional eating behaviors,
72. Bravata DM, Smith-Spangler C, peak concentration in women after affective symptoms and body weight 1
Sundaram V, et al. Using pedometers to gastric bypass surgery. Brit J Clin Pharm year after bariatric surgery: A ran-
increase physical activity and improve 2002;54(6):587–591. domized controlled trial. Obes Surg
health. JAMA 2007;298(19):2296–2304. 88. Hagedorn JC, Encarnacion B, Brat GA, 2015;25:2112–2119.
73. de Zwaan M, Enderle J, Wagner S, et et al. Does gastric bypass alter alco- 102. Himes SM, Grothe KB, Clark MM,
al. Anxiety and depression in bariatric hol metabolism? Surg Obes Relat Dis et al. Stop Regain: A pilot psycho-
surgery patients: A prospective, follow-up 2007;3(5):543–548. logical intervention for bariatric patients
study using structured clinical interviews. 89. Woodard GA, Downey J, Hernandez- experiencing weight regain. Obes Surg
J Affect Dis 2011;133(1–2):61–8. Boussard T, et al. Impaired alcohol 2015;25:922–927.
74. Hayden M, Dixon J, Dixon M, et metabolism after gastric bypass surgery: 103. Bradley LE, Forman EM, Kerrigan SC,
al. Characterization of the improve- A case-crossover trial. J Am Coll Surg et al. A pilot study of an acceptance-
ment in depressive symptoms fol- 2011;212(2):209–214. based behavioral intervention for weight
lowing bariatric surgery. Obes Surg 90. Maluenda F, Csendes A, De Aretxabala regain after bariatric surgery. Obes Surg
2011;21(3):328–335. X, et al. Alcohol absorption modifica- 2016;26:2433–2441.
75. Dixon J, Dixon M, O’Brien P. Depression tion after a laparoscopic sleeve gas- 104. Courcoulas AP, Chirstian NJ, Belle SH,
in association with severe obesity: trectomy due to obesity. Obes Surg et al. Weight change and health outcomes
Changes with weight loss. Arch Intern 2010;20(6):744–748. at 3 years after bariatric surgery among
Med 2003;163(17):2058–2065. 91. Parikh M, Johnson JM, Ballem N, et al. individuals with severe obesity. JAMA
76. Velcu LM, Adolphine R, Mourelo R, ASMBS position statement on alcohol 2013;310:2416–2425.
et al. Weight loss, quality of life and use before and after bariatric surgery. 105. Mitchell JE, Christian NJ, Flum
employment status after Roux-en-Y SOARD 2016;12:225–230. DR, et al. Postoperative behavioral
gastric bypass: 5-year analysis. Surg Obes 92. Kofman MD, Lent MR, Swencionis variables and weight change 3 years
Relat Dis 2005;1(4):413–416. C. Maladaptive eating patterns, after bariatric surgery. JAMA Surg
77. Karlsson J, Taft C, Ryden A, et al. quality of life, and weight outcomes 2016;151:752–757.
Ten-year trends in health-related qual- following gastric bypass: Results 106. Maleckas A, Gudaityte R, Petereit R,
ity of life after surgical and conven- of an Internet survey. Obesity Venclauskas L, Veliekiene D. Weight
tional treatment for severe obesity: 2010;18(10):1938–1943. regain after gastric bypass: Etiology
The SOS intervention study. Int J Obes 93. Colles SL, Dixon JB, O’Brien PE. Grazing and treatment options. Gland Surg
2007;31(8):1248–1261. and loss of control related to eating: 2016;5:617–624.
41
CHAPTER
517
518 Chapter 41 Adiposity-based Chronic Disease a New Diagnostic Term
Condition
Relative
risk ABCD component Reference
41
Abnormal
Adiposity Characteristic Adipocyte
Amount Adipose Distribution Function
Metabolic
Type 2 diabetes 7.7 ++++ ++++ ++++ 130
Cardiovascular
Hypertension 2.0 ++ ++ + 130,137
Orthopedic
Osteoarthritis 1.39 + + − 130,141
Gonadal function
Infertility (women) 1.2 + ++ ++ 146,147
Gastrointestinal
Cholelithiasis 1.8 ++ + ++ 130,149
Psychiatric
Depression 2.0 ++ +++ +++ 150
Cancer
Obesity-related (esophageal, 1.5 ++ + + 130,151
It may be difficult to define specific populations at risk for processed foods and sugar-containing beverages provides
ABCD, though the vast differences in modern lifestyles the greatest benefit to patients with ABCD.6,27 Some of the
and built environments, compared to those of prior gen- most widely studied dietary patterns with these attributes
erations and even distant ancestors, are suggestive that the include the Mediterranean diet, the New Nordic diet, the
current population would benefit from healthy lifestyle Ornish diet, the Dietary Approaches to Stop Hypertension
interventions. (DASH) diet, among others. 28–31 In the largest published
Among the most obvious aspects is the choice of randomized trial, the group of patients assigned to the
dietary pattern. Any demonstrably healthy dietary pattern Mediterranean diet had the greatest amount of weight
is recommended, provided a durable effect can be real- loss, as well as reduction in T2D, reduction in cardiovas-
ized. 25 Enhanced adherence and sustainability will require cular events, and reduction in mortality compared with
motivational interviewing and behavioral assessments of low-fat or low-carbohydrate diets. 28 The New Nordic
food preferences, daily activities and logistics, cultural diet, the Ornish diet, and the DASH diet, which overlap
mores, tastes, religion-based rules, and other idiosyncra- substantially with the Mediterranean diet in categorized
sies. 26 HCPs should exercise flexibility and poise to offer food content, may have similar benefits. A very useful
up quick alternatives for a successful trajectory when clin- tactic to enhance adherence is to have at the ready web-
ical progress has stalled. A dietary pattern that is high in site addresses, electronic and printed materials, and other
fruits, vegetables, nuts, complex carbohydrates, with con- information modalities for these dietary patterns for every
trolled amounts of meats, fish, and negligible amounts of patient. Various wearable technologies that synchronize
520 Chapter 41 Adiposity-based Chronic Disease a New Diagnostic Term
with smartphones and access cloud-based software can be demonstrate to melatonin secretion, which is itself dimin-
trialed and optimized for individual patients.32 ished in disrupted circadian rhythms.39
In addition to total body adipose content, the local- In the modern era, average sleep duration has been
ized distribution and function of adipose tissue can declining. Time spent sleeping by adults has decreased
be improved with adoption of healthy dietary pat- from an average of nine hours per night to seven hours
terns. In one randomized trial, subjects assigned to the per night over the past 40 years.40 In children, sleep time
Mediterranean diet demonstrated improvement in insu- has reduced an average of 0.75 min/night/year for the past
lin resistance by 37%, reduced inflammation by 37%, century.41 These trends continue to spread worldwide.40,41
and increased adiponectin by 43% after one year, sug- In addition to reduced sleep time, the presence of insom-
gesting improved adipose function. 33 A population study nia, defined as waking in the middle of the night at least
of 5,079 individuals demonstrated reduced visceral adi- three times weekly, is reported among 25–35% of adults.42
pose, reduced cardiac adipose tissue, and less hepatic In children, no upper limit of healthy sleep has been
steatosis, but no change in subcutaneous adipose among identified, and a longer duration of sleep is associated
those who followed dietary patterns that closely resem- with reduced amounts of adiposity, improved quality of
bled the Mediterranean diet. 34 life, and improved academic success.43 In a meta-analysis
Increased physical activity and exercise should also be of longitudinal trials in children, longer sleep duration
incorporated into daily routines. Although the amount was associated with reduced adiposity by an odds ratio
and type of exercise has not been fully settled, regular of 1.89.43 For every one hour of sleep duration, the annual
participation in physical activity is important. Many stud- rate of BMI increase was reduced by 0.05 kg/m 2 .
ies and organizations suggest that at least 150 minutes of In adults, between seven and nine hours of sleep are
physical activity divided over five to seven days per week recommended nightly, and eight to 10 hours of sleep are
constitutes a reasonable minimum.6 Strength training pro- recommended in adolescents.44 As with studies in chil-
vides benefit of increased muscle mass, reducing myocyte dren, adults exhibit increased adiposity, especially visceral
adipose content, while cardiovascular exercise promotes adiposity, in association with shorter sleep duration.45 In
reduction of visceral adipose accumulation.35 Both of one observational trial, an increase in sleep time from less-
these endpoints are desirable in ABCD. Adipose function, than-six to seven-to-eight hours resulted in a reduction of
assessed by adipokine production and inflammation, is visceral fat gain over six years of follow-up.46
also greatly enhanced through regular physical activity Several randomized trials demonstrate that even
and exercise.36 short-term sleep restriction for five days causes weight
In addition to optimizing the choice of dietary pattern gain in adults. This is attributed to increased calorie
and amount of physical activity, many other individual consumption by 130% in the sleep-deprived group com-
lifestyle factors can impact the risk of ABCD (Table 41.4).1 pared to the control group.47,48 In a crossover study, a
52% increase in consumption of sweets and desserts
was observed during times of sleep deprivation.49 These
41.4 SLEEP HYGIENE results may be explained by elevation in circulating ghre-
lin levels and reduction in leptin levels that are observed
Sleep affects metabolic regulation. As a defining feature in periods of sleep restriction. 50 Both of these hormonal
of circadian rhythm, the amount, quality, and timing of markers of adipose dysfunction within ABCD would
sleep cycles affect hypothalamic function, cortisol release, be expected to increase appetite and exacerbate insulin
thyroid function, hepatic glucose production, brown fat resistance. 38,50
activation, and insulin resistance. 37 Additionally, pancre- The importance of adequate sleep combined with
atic β-cell function is impaired in states of sleep depriva- other lifestyle interventions has also been demonstrated
tion.38 This may reflect the responsiveness that β-cells in a series of cross-sectional trials.45 One observational
study demonstrated an association of decreased sleep time fat accumulation are associated with increased stress.60
41
and increased calorie consumption among obese women, Interventions to reduce stress are central to any healthy
compared to normal weight controls. 51 In another study, lifestyle (Table 41.5).
an inverse linear relationship between self-reported Given the multiple stressors that are regularly pres-
sleep duration and BMI was observed. 52 Data from the ent in everyday life, simple avoidance of stressful situa-
National Health and Nutrition Examination Survey also tions is often not possible. Modalities to address stress
demonstrate a strong association between reduced sleep and activities to lessen pathophysiologic effects of stress
time and adiposity. 53 Additionally, patients with obesity may be beneficial in ABCD.1 In studies of stress reduc-
demonstrate increased sleep latency and reduced percent- tion techniques, mindfulness-based stress reduction
age of time in REM sleep.40 A concerted effort to attain may reduce cardiovascular events and has been shown
sufficient time for sleep is an important part of a healthy to improve markers of inflammation and adipokine
lifestyle, especially in the prevention and treatment of levels in patients with obesity.61,62 In one randomized
ABCD. 37,40 controlled trial, women with obesity or who were over-
Disordered sleep is disruptive to circadian rhythms weight were assigned to either a mindfulness group that
and associated with weight gain.40 Obstructive sleep met once weekly to discuss stress reduction techniques
apnea (OSA) is highly prevalent in adults with obesity and and given recommendations for daily home sessions for
disruptive to healthy sleep. In one longitudinal study, a 30–45 minutes each.63 The control group met weekly
10% increase in body weight was associated with a six- with a dietitian to review nutritional recommendations.
fold increase risk of OSA. 54 By eight weeks, depression and anxiety declined in the
The use of devices that provide continuous positive air- mindfulness group, and quality of life improved. These
way pressure can reduce the cardiovascular impact of OSA effects persisted at 16 weeks after the end of intervention.
and improve symptoms of daytime drowsiness. However, Additionally, fasting insulin and systolic blood pressure
this modality fails to affect proximate, causative meta- improved in the mindfulness group compared to controls
bolic derangements, such as abnormal adipose distribu- at both the end of the trial and 16 weeks after its con-
tion and function, in patients with OSA. 55 On the other clusion. Mindfulness techniques of stress reduction are
hand, weight loss through intensive lifestyle modification promising lifestyle interventions in ABCD. This approach
can improve measures of OSA, simultaneously improving has also been shown to reduce binge-eating episodes in
overall sleep hygiene. 56 at-risk patients.64
Another method for stress reduction is through reg-
ular participation of low-impact exercises such as yoga.
41.5 STRESS REDUCTION In a randomized trial of women with overweight or obe-
sity, those assigned to the treatment group sustained a
The human response to chronic stress is associated with 2.4 kg weight loss and a 3.8 cm decrease in waist circum-
ABCD and involves hypothalamic dysfunction, increased ference after 12 weeks of twice weekly 90-minute yoga
consumption of palatable and calorie-dense foods, and classes.65 Additionally, self-assessment measures of stress
reduced physical activity. 57,58 The hormonal profile with declined, while measures of quality of life and of self-
chronic stress includes elevations of cortisol, catechol- esteem improved with yoga treatment. Another published,
amines, and insulin as part of an insulin-resistant state. 58 randomized trial in men with overweight or obesity dem-
In one cross-sectional study, chronic stress was associated onstrates reduction in weight by 2.2 kg and reduction in
with increased food cravings despite increased leptin lev- perceived stress score.66 These results are similar to earlier
els, suggesting the presence of leptin resistance and adi- observational studies indicating the practice of yoga can
pose dysfunction in response to stress.59 Another study improve stress and adipose tissue accumulation over the
demonstrated that elevated cortisol and increased visceral short term.67
41.6 ANTIBIOTIC USE AND study, oral vancomycin significantly altered the species
composition of GI microflora of subjects with obesity but
THE MICROBIOME did not demonstrate metabolic changes both during this
trial or afterward.77 Amoxicillin also had no discernable
41.6.1 Antibiotic Use by Humans effect on metabolism. In another trial, 11 patients with
obesity, insulin resistance, and with detectable methane
Since their discovery, antibiotics have been critical for the
on breath testing were treated with neomycin and rifa-
treatment of infectious disease of bacterial or fungal ori-
maxin until methane could no longer be detected, which
gin. Clear success has led to widespread use and overuse
took an average of 10 days of treatment.78 The bacterium
of antibiotics, including dubious medical practices that
Methanobrevibacter smithii is presumed responsible for
employ antibiotic use for conditions that may not be bac-
methane production, and stool levels of M. smithii were
terial in origin. A 2011 survey found 263 million separate
eradicated in eight of 11 subjects after the treatment
outpatient antibiotic prescriptions had been filled by phar-
course. In all subjects, low-density lipoprotein levels
macies in the U.S. during that year, an annual rate of 0.8
declined and insulin sensitivity by oral glucose tolerance
per citizen.68 This trend leads to concerns regarding the
testing improved after treatment. This trial suggests a
development of antibiotic resistance and pathologic meta-
potential cardiometabolic risk benefit with GI microflora
bolic effects.
manipulation.
Antibiotic use can affect microflora residing within
Though other confounding factors within many of
the gastrointestinal (GI) tract serving as an exemplar of
these reported studies may influence the results, the pru-
how other lifestyle changes that affect gut microbiota can
dent and minimal use of antibiotics in medical practice
indirectly lead to ABCD. Hundreds of species of bacteria
may help to prevent weight gain, and may influence other
and fungi are present within the colon of each individ-
aspects of ABCD, especially among infants and chil-
ual and take part in a complex relationship between the
dren. Certain classes of antibiotics, such as sulfonamides,
host and other species of microflora.69 These microbes
appear to have neutral effects on weight and may be pre-
directly affect host energy homeostasis through metabo-
ferred in appropriate clinical settings. Protocols for the
lism of sugars and fiber present in the intestinal chyme
active manipulation of GI microflora to generate benefi-
to produce short-chain fatty acids that are available for
cial metabolic effects require more study before firm rec-
utilization by the host. Approximately 5–10% of the
ommendations can be made.
total daily calorie consumption is obtained in this fash-
ion.70 Additionally, through multiple routes of signaling
with the host, the GI microflora can influence the degree
of insulin resistance, systemic inflammation, metabolic 41.6.2 Antibiotic Use in Farming
rate, and may affect other health aspects of the host such The use of antibiotics outside of the medical field may also
as mood and cardiovascular function. 69,71,72 play an indirect role in the development of ABCD and lead
While the specific molecular mechanisms for GI to sound conjecture about optimal food sourcing as part of
microflora-host metabolic interactions continue to be healthy lifestyles. Widespread use of antibiotics by livestock
investigated, a number of population studies have been farmers yields animals that gain weight faster and require less
published that associate the use of antibiotics with weight feed.79 Nutrient changes within food products yielded by this
gain and obesity. This is especially evident among infants practice have not been formally evaluated. However, changes
and children treated with antibiotics. In a study of chil- within the livestock microbiome have been reported.80 These
dren born to normal-weight mothers within the Danish observations of accelerated growth and altered microbiome
National Birth Cohort, the use of any class of antibiot- are suggestive that the nutrient makeup of meat derived from
ics in early-life was associated with an increased risk of antibiotic treated livestock may be altered, though further
overweight by age seven (odds ratio of 1.54).73 A large, study is warranted in this field.
international study demonstrated increased BMI at ages
five to eight among boys who were treated with antibiot-
ics within the first year of life.74 In another international
cohort involving eight medical centers located in low-
41.6.3 Endocrine Disruptors
resource settings, 1,954 infants followed until age two Multiple classes of industrially produced chemical com-
demonstrated significant weight gain without change pounds demonstrate biological properties that affect hor-
in body length among those treated with one or more mone signaling. A subset of these endocrine disrupting
courses of various classes of antibiotics.75 In this trial, compounds (EDC) has been shown to affect adipose tis-
penicillins, cephalosporins, macrolides, and metronida- sue accumulation, distribution, and function.81 In several
zole had the largest effects on weight gain. There was no studies, childhood exposure to bisphenol A, among the
associated weight gain observed in those infants given more well studied EDC, is associated with weight gain and
trimethoprim-sulfamethoxazole. Similarly, a post-hoc obesity.82 Exposure to bisphenol A is also associated with
analysis of a randomized trial designed to investigate use reduced adiponectin and increased resistin gene expres-
of prophylactic trimethoprim-sulfamethoxazole for vesi- sion in children.83 Exposure to octylphenol, another EDC,
coureteral reflux showed no effect on weight with this is also associated with increased resistin gene expres-
class of antibiotic.76 sion.84 Visceral adipose accumulation has been associated
Few studies have been conducted regarding the met- with exposure to organic pollutants that likely function as
abolic effect of antibiotics in adults. In one seven-day EDC.85 As patients with ABCD successfully lose weight,
41.9 Community Engagement 523
lipid soluble EDC may be released into the circulation, Atypical antipsychotics, which may be applied in major
41
especially from visceral adipose depots that may concen- depressive disorder, induce intense weight gain, insulin
trate toxins in close proximity to vital organs.86 Many resistance, increased circulating leptin and reduced adi-
other EDC can affect energy metabolism and mechanisms ponectin.103 Still, the successful treatment of depression is
leading to ABCD, requiring ongoing clinical study. often accompanied by significant weight loss and improve-
ment in ABCD.104 Moreover, weight loss in patients with
ABCD has been shown to reduce depressive symptoms
41.7 ALCOHOL MODERATION and improve quality of life.105
Aside from pharmacologic therapies, cognitive behav-
High amounts of alcohol intake are associated with ioral therapy (CBT) can improve mood disorders and
adverse health outcomes, including death. In contrast, weight loss efforts. In one trial, patients with depression
moderate alcohol consumption, especially consumption and obesity randomized to receive modified CBT that
of wine, has been demonstrated to improve markers of included aspects of healthy living had more sustainable
insulin resistance, cholesterol levels, and systemic inflam- weight loss and improved mood compared to standard
mation, suggesting improvement in adipose function.87 CBT practices over 48 weeks of observation.106 In another
Recently published trials continue to support the findings trial, CBT was associated with weight loss among ado-
that of moderate alcohol intake, defined as 14 drinks per lescents with obesity and depression.107 Multiple studies
week for men and nine drinks per week for women, is in adult patients with obesity and depression demonstrate
associated with a lower incidence of T2D, and, in many effectiveness of CBT in addressing both conditions.108
cases, prevention of weight gain.88 In a study of 224 Improvements in adipose function and distribution would
subjects with T2D who were provided either 150 mL of be expected in association with weight loss; however, these
red wine, white wine, or water daily, both of the groups effects of CBT have not been assessed.107,108 Practically
given wine showed reduced insulin resistance measured speaking, with proper training, HCPs outside of the spe-
by fasting insulin levels, with increases in high-density cialty of psychiatry can successfully implement CBT for
lipoprotein levels in the red wine group.89 Adipose tissue the treatment of ABCD.109
distribution is not affected by moderate alcohol intake.90
The drawbacks of alcohol consumption include the
risk of dependence and the potential for cognitive impair-
ment, especially while operating motor vehicles, or simply 41.9 COMMUNITY ENGAGEMENT
walking along a busy street. Another concern is the theo-
Close personal contacts and community involvement
retical risk of accelerated hepatosteatosis when patients
exhibit considerable influence on individual behavior pat-
at high risk for non-alcoholic fatty liver disease consume
terns and on patterns of weight gain.110 Moreover, efforts
alcohol regularly.91 The DIONYSOS study appeared
within communities to emphasize healthy lifestyle choices
to support this claim; however, in this trial, an increase
can reduce the impact of ABCD.
in steatosis was observed only in subjects with obesity
Community programs that engage whole families in
that consumed more than 60 g alcohol, or four standard
healthy dietary patterns, physical activity, and wellbeing
drinks, daily.92 Within the trial, this group was known as
have been shown to diminish childhood obesity.111 These
the “heavy drinkers.” Moderate alcohol consumption was
programs regularly meet as a group, create and nur-
not associated with increased hepatosteatosis in patients
ture self-encouragement behaviors, and result in better
with obesity.
health.112 Improvements in quality of life and reductions
in adiposity have been observed with these type of inter-
ventions.112 In one randomized trial, a community-based
41.8 MOOD intervention induced weight loss of 7.8%, adiponectin
increase by 27%, and leptin decrease by 22% after one
Disorders of mood, such as depression and anxiety, have a year, suggesting improvement in adipose function and an
complex relationship with weight gain and risk of ABCD. overall decrease in ABCD related risks.113
Obesity and depression often occur together in the same Several barriers to program efficacy have been observed
patient, in part due to common molecular mechanisms including the main driver of program avoidance: parental
including altered hypothalamic-pituitary-adrenal axis sig- concerns of psychosocial well-being with little regard for
naling, increased oxidative stress, and increased systemic other long-term sequelae of ABCD.112 Denial or lack of
inflammation.93 In a published cohort, an increased prev- recognition by parents also presents a significant barrier
alence of depression is associated with increased leptin to program initiation. With any lifestyle intervention, care
levels, suggesting adipose function is affected in patients should be taken to avoid incurring body dissatisfaction,
with depression.94 The presence of depression is also asso- reduced self-esteem, or other detrimental effects to men-
ciated with increased risk for the development of obesity tal health to the target audience.114 Programs that frame
later in life.95–98 their central message as promotion of a healthy lifestyle
Patients with obesity demonstrate a poorer response are more successful than programs that specifically target
to antidepressant therapy.99–101 Additionally, many anti- weight loss.115
depressant medications induce weight gain and adipos- The direct involvement of families may be funda-
ity, including tricyclic antidepressants, selective serotonin mental to this process; implementation of a five-year
reuptake inhibitors, and monoamine oxidase inhibitors.102 health and well-being intervention program through
524 Chapter 41 Adiposity-based Chronic Disease a New Diagnostic Term
elementary schools with minimal parent involvement ABCD phenotypes. Traditional measures of obesity, such
had no effect on adiposity.116 In contrast, faith-based as waist-to-hip ratio or BMI do not capture the full risk
programs may represent important modes of community conferred by adiposity in Eastern Asian and Indian popu-
outreach for ABCD prevention.117 In one randomized lations.11 As a model of cardiometabolic risk, the distri-
study involving congregations of 20 churches, hourly, bution, function, and amount of adiposity among these
weekly meetings emphasized dietary patterns and populations are more predictive than BMI alone.126,127
physical activity achieved in the Diabetes Prevention As an example, when matched for age and BMI, Asian
Project (DPP) was compared to a control intervention patients demonstrate higher circulating leptin and lower
that involved just general information.118 The DPP arm adiponectin, emphasizing the importance of adipose func-
showed a 2.4 kg weight loss after six months, compared tion rather than BMI.128
to a 0.4 kg weight gain by the control group. Several
other observational trials of faith-based community
intervention programs also show promise of improved 41.11 CONCLUSION
weight reduction.119,120
The recognition of community engagement as a means The growing and worldwide epidemic of obesity is among
to drive healthy behaviors has prompted the development the highest intervention priorities in health care. A num-
of online virtual communities with the goal of improved ber of important lifestyle factors have been identified in
health.121 Though these have received much fanfare, addition to the individualization of dietary patterns and
results are inconsistent and depend on perceived emotional physical activity. Unfortunately, a slow rate of success
support (though levels of support can vary greatly).121 coupled with therapeutic inertia on local and national
In-person, family-oriented, community engagement is a scales require new ways to regard the problem. ABCD is
successful approach to adapting a healthy lifestyle. a new diagnostic term that incorporates not only body
weight and BMI, which is all that current obesity defi-
nitions and interventions rely on, but also healthy and
41.10 TRANSCULTURIZATION unhealthy distributions and secretory functions of body
fat. This broader conceptualization of this metabolic
The cultural background of each individual has signifi- problem permits a better understanding of pathophysi-
cant impact on lifestyle choices and response to medi- ology, analysis of current evidence, and formulation of
cal advice. To be sustainable, suggested dietary patterns effective interventions. Future directions in this field may
should be congruent with a patient’s cultural tradition.122 yield the incorporation of body scanning for adipose dis-
This approach garners community support and pro- tribution assessment and broad molecular testing to iden-
motes durable and successful healthy lifestyle changes. tify multiple adipokine abnormalities in the pathologic
In contrast, recommended dietary patterns at odds with state of ABCD.1
a patient’s own culture will often incur transgressions if Healthy lifestyle interventions to mitigate ABCD
they are not adequately addressed.122 include individualization and adoption of healthy dietary
Some cultures traditionally place value on weight gain patterns and physical activity programs. Improvements in
as a marker of wealth, high social standing, and overall sleep hygiene, reduction in stress, and treatment of both
well-being. However, the worldwide increased prevalence clinical and subclinical disorders of mood can also impact
of adiposity has triggered responses by governments, cul- weight gain, improve adipose tissue function and distri-
tural leaders, international charitable organizations, the bution, and improve overall well-being among patients
World Health Organization, and the United Nations to with ABCD. Judicious and minimal use of antibiotics,
address non-communicable chronic diseases, including especially among infants and children, can also mitigate
ABCD.123–125 Recommendations to address ABCD among weight gain and possibly prevent the development of
various nations include the identification and education ABCD. Avoidance of EDC wherever possible, population-
of physicians and cultural leaders within different regions based improvements in food sourcing, and moderation of
who would serve as agents of change.122 A respectful alcohol intake among adults may also be incorporated in
understanding of local culture can allow adaptation of a healthy lifestyle. Beyond the individual, the involvement
lifestyle interventions to curtail ABCD and associated of community and culturally-sensitive medical practices
complications, with potential for broad impact when can help to redirect normative trends in clinical practice.
implemented globally. When optimized, these important lifestyle factors can
In addition to cultural adaptations for lifestyle medi- significantly reduce ABCD and its associated detrimental
cine approaches, ethnic variation can lead to a range of effects.
REFERENCES
1. Mechanick JI, Hurley DL, Garvey WT. 2. Dulloo AG, Montani JP. 2012. Body Huang AC, Lin WL, Hsieh KC. 2017.
2017. Adiposity-based chronic disease composition, inflammation and thermo- Discrepancies between leg-to-leg bioelec-
as a new diagnostic term: The American genesis in pathways to obesity and the trical Impedance analysis and computer-
Association of Clinical Endocrinologists metabolic syndrome: An overview. Obes ized tomography in abdominal visceral
and American College of Endocrinology Rev 13 Suppl 2:1–5. fat measurement. Sci Rep 7:9102.
position statement. Endocr Pract 3. Lu HK, Chen YY, Yeh C, Chuang CL, 4. Kouli GM, Panagiotakos DB, Kyrou I,
23:372–378. Chiang LM, Lai CL, Casebolt KM, Georgousopoulou EN, Chrysohoou C,
References 525
Tsigos C, Tousoulis D, Pitsavos C. 2017. subsequent to serious orthopedic injury: 29. Shai I, Schwarzfuchs D, Henkin Y,
Visceral adiposity index and 10-year A systematic review. Arch Phys Med Shahar DR, Witkow S, Greenberg I,
cardiovascular disease incidence: The
ATTICA study. Nutr Metab Cardiovasc
Dis 27:881–889.
18.
Rehabil.
Lin JS, O’Connor E, Evans CV, Senger
CA, Rowland MG, Groom HC. 2014.
Golan R, Fraser D, Bolotin A, Vardi H,
Tangi-Rozental O, Zuk-Ramot R, Sarusi
B, Brickner D, Schwartz Z, Sheiner E,
41
5. Mechanick JI, Zhao S, Garvey WT. 2016. Behavioral counseling to promote a Marko R, Katorza E, Thiery J, Fiedler
The adipokine-cardiovascular-lifestyle healthy lifestyle in persons with cardio- GM, Bluher M, Stumvoll M, Stampfer
network: translation to clinical practice. vascular risk factors: A systematic review MJ. 2008. Weight loss with a low-carbo-
J Am Coll Cardiol 68:1785–1803. for the U.S. Preventive Services Task hydrate, Mediterranean, or low-fat diet.
6. Garvey WT, Mechanick JI, Brett EM, Force. Ann Intern Med 161:568–578. N Engl J Med 359:229–241.
Garber AJ, Hurley DL, Jastreboff 19. Schuch F, Vancampfort D, Firth J, 30. Ornish D, Scherwitz LW, Billings JH,
AM, Nadolsky K, Pessah-Pollack Rosenbaum S, Ward P, Reichert T, Brown SE, Gould KL, Merritt TA,
R, Plodkowski R. 2016. American Bagatini NC, Bgeginski R, Stubbs B. Sparler S, Armstrong WT, Ports TA,
Association of Clinical Endocrinologists 2017. Physical activity and sedentary Kirkeeide RL, Hogeboom C, Brand RJ.
and American College of Endocrinology behavior in people with major depressive 1998. Intensive lifestyle changes for
Comprehensive Clinical Practice disorder: A systematic review and meta- reversal of coronary heart disease. JAMA
Guidelines for medical care of patients analysis. J Affect Disord 210:139–150. 280:2001–2007.
with obesity. Endocr Pract 22 Suppl 20. Shokoueinejad M, Fernandez C, Carroll 31. Fritzen AM, Lundsgaard AM, Jordy
3:1–203. E, Wang F, Levin J, Rusk S, Glattard AB, Poulsen SK, Stender S, Pilegaard H,
7. Via MA, Mechanick JI. 2014. Obesity as N, Mulchrone A, Zhang X, Xie A, Astrup A, Larsen TM, Wojtaszewski JF,
a Disease. Curr Obes Rep 3:291–297. Teodorescu M, Dempsey J, Webster J. Richter EA, Kiens B. 2015. New nordic
8. Brodesser-Akner T. 2017. Losing it in the 2017. Sleep apnea: A review of diagnos- diet-induced weight loss is accompanied
anti-dieting age. The New York Times, tic sensors, algorithms, and therapies. by changes in metabolism and AMPK
Aug 6, Page MM35. Physiol Meas 38:R204–R252. signaling in adipose tissue. J Clin
9. Johnson Z. 2017. Lena Dunham: I’m not 21. Avenell A, Brown TJ, McGee MA, Endocrinol Metab 100:3509–3519.
a “hypocrite” because i lost weight. E! Campbell MK, Grant AM, Broom J, Jung 32. Hutchesson MJ, Rollo ME, Krukowski
News, Mar 27. RT, Smith WC. 2004. What are the long- R, Ells L, Harvey J, Morgan PJ, Callister
10. Sifferlin A. 2016. Why the biggest loser term benefits of weight reducing diets in R, Plotnikoff R, Collins CE. 2015.
contestants gain back the weight. TIME, adults? A systematic review of random- eHealth interventions for the prevention
May 2. ized controlled trials. J Hum Nutr Diet and treatment of overweight and obesity
11. Zheng W, McLerran DF, Rolland B, 17:317–335. in adults: A systematic review with meta-
Zhang X, Inoue M, Matsuo K, He J, 22. Wing RR, Marcus MD, Epstein LH, analysis. Obes Rev 16:376–392.
Gupta PC, Ramadas K, Tsugane S, Irie Salata R. 1987. Type II diabetic subjects 33. Maiorino MI, Bellastella G, Petrizzo M,
F, Tamakoshi A, Gao YT, Wang R, Shu lose less weight than their overweight Scappaticcio L, Giugliano D, Esposito K.
XO, Tsuji I, Kuriyama S, Tanaka H, nondiabetic spouses. Diabetes Care 2016. Mediterranean diet cools down the
Satoh H, Chen CJ, Yuan JM, Yoo KY, 10:563–566. inflammatory milieu in type 2 diabetes:
Ahsan H, Pan WH, Gu D, Pednekar 23. Khan MA, St Peter JV, Breen GA, The MEDITA randomized controlled
MS, Sauvaget C, Sasazuki S, Sairenchi Hartley GG, Vessey JT. 2000. Diabetes trial. Endocrine 54:634–641.
T, Yang G, Xiang YB, Nagai M, Suzuki disease stage predicts weight loss out- 34. Shah RV, Murthy VL, Allison MA,
T, Nishino Y, You SL, Koh WP, Park comes with long-term appetite suppres- Ding J, Budoff M, Frazier-Wood AC,
SK, Chen Y, Shen CY, Thornquist M, sants. Obes Res 8:43–48. Lima JA, Steffen L, Siscovick D, Tucker
Feng Z, Kang D, Boffetta P, Potter 24. Pasquali R, Gambineri A, Biscotti D, KL, Ouyang P, Abbasi SA, Danielson
JD. 2011. Association between body- Vicennati V, Gagliardi L, Colitta D, K, Jerosch-Herold M, Mozaffarian D.
mass index and risk of death in more Fiorini S, Cognigni GE, Filicori M, 2016. Diet and adipose tissue distribu-
than 1 million Asians. N Engl J Med Morselli-Labate AM. 2000. Effect of tions: The multi-ethnic study of athero-
364:719–729. long-term treatment with metformin sclerosis. Nutr Metab Cardiovasc Dis
12. Zarrett N, Sorensen C, Skiles B. 2013. added to hypocaloric diet on body com- 26:185–193.
Environmental and social-motivational position, fat distribution, and androgen 35. Di Meo S, Iossa S, Venditti P. 2017.
contextual factors related to youth physi- and insulin levels in abdominally obese Improvement of obesity-linked skeletal
cal activity: Systematic observations of women with and without the polycys- muscle insulin resistance by strength
summer day camps. Int J Behav Nutr tic ovary syndrome. J Clin Endocrinol and endurance training. J Endocrinol
Phys Act 10:63. Metab 85:2767–2774. 234:R159–R181.
13. Phillips CM. 2017. Metabolically 25. Dansinger ML, Gleason JA, Griffith 36. Laursen TL, Zak RB, Shute RJ, Heesch
healthy obesity across the life course: JL, Selker HP, Schaefer EJ. 2005. MWS, Dinan NE, Bubak MP, La Salle
Epidemiology, determinants, and implica- Comparison of the Atkins, Ornish, DT, Slivka DR. 2017. Leptin, adiponec-
tions. Ann N Y Acad Sci 1391:85–100. Weight Watchers, and Zone diets for tin, and ghrelin responses to endurance
14. Kim NH, Seo JA, Cho H, Seo JH, Yu JH, weight loss and heart disease risk exercise in different ambient conditions.
Yoo HJ, Kim SG, Choi KM, Baik SH, reduction: A randomized trial. JAMA Temperature (Austin) 4:166–175.
Choi DS, Shin C, Cho NH. 2016. Risk of 293:43–53. 37. Gruber R, Carrey N, Weiss SK, Frappier
the development of diabetes and cardio- 26. Leung AWY, Chan RSM, Sea MMM, JY, Rourke L, Brouillette RT, Wise MS.
vascular disease in metabolically healthy Woo J. 2017. An overview of factors asso- 2014. Position statement on pediatric
obese people: The Korean Genome ciated with adherence to lifestyle modifi- sleep for psychiatrists. J Can Acad Child
and Epidemiology Study. Medicine cation programs for weight management Adolesc Psychiatry 23:174–195.
(Baltimore) 95:e3384. in adults. Int J Environ Res Public Health 38. Schmid SM, Hallschmid M, Schultes B.
15. Roberson LL, Aneni EC, Maziak W, 14:922. 2015. The metabolic burden of sleep loss.
Agatston A, Feldman T, Rouseff M, 27. Sotos-Prieto M, Bhupathiraju SN, Mattei Lancet Diabetes Endocrinol 3:52–62.
Tran T, Blaha MJ, Santos RD, Sposito J, Fung TT, Li Y, Pan A, Willett WC, 39. Persaud SJ, Jones PM. 2016. A wake-up
A, Al-Mallah MH, Blankstein R, Budoff Rimm EB, Hu FB. 2017. Association of call for type 2 diabetes? N Engl J Med
MJ, Nasir K. 2014. Beyond BMI: The changes in diet quality with total and 375:1090–1092.
“Metabolically healthy obese” phenotype cause-specific mortality. N Engl J Med 40. Keith SW, Redden DT, Katzmarzyk
& its association with clinical/subclini- 377:143–153. PT, Boggiano MM, Hanlon EC, Benca
cal cardiovascular disease and all-cause 28. Estruch R, Ros E, Salas-Salvado J, Covas RM, Ruden D, Pietrobelli A, Barger
mortality—A systematic review. BMC MI, Corella D, Aros F, Gomez-Gracia JL, Fontaine KR, Wang C, Aronne LJ,
Public Health 14:14. E, Ruiz-Gutierrez V, Fiol M, Lapetra J, Wright SM, Baskin M, Dhurandhar
16. Bluher M. 2014. Are metabolically Lamuela-Raventos RM, Serra-Majem L, NV, Lijoi MC, Grilo CM, DeLuca
healthy obese individuals really healthy? Pinto X, Basora J, Munoz MA, Sorli JV, M, Westfall AO, Allison DB. 2006.
Eur J Endocrinol 171:R209–219. Martinez JA, Martinez-Gonzalez MA. Putative contributors to the secular
17. Ekegren CL, Beck B, Climie RE, Owen 2013. Primary prevention of cardiovascu- increase in obesity: Exploring the
N, Dunstan DW, Gabbe BJ. 2017. lar disease with a Mediterranean diet. N roads less traveled. Int J Obes (Lond)
Physical activity and sedentary behavior Engl J Med 368:1279–1290. 30:1585–1594.
526 Chapter 41 Adiposity-based Chronic Disease a New Diagnostic Term
41. Matricciani L, Olds T, Petkov J. 2012. In 56. Cayanan EA, Marshall NS, Hoyos CM, 71. Most J, Goossens GH, Reijnders D,
search of lost sleep: Secular trends in the Phillips CL, Serinel Y, Wong KKH, Yee Canfora EE, Penders J, Blaak EE. 2016.
sleep time of school-aged children and BJ, Grunstein RR. 2018. Maintenance Gut microbiota composition strongly
adolescents. Sleep Med Rev 16:203–211. diets following rapid weight loss in correlates to peripheral insulin sensitivity
42. Ohayon MM. 2002. Epidemiology of obstructive sleep apnea: A pilot 1-year in obese men but not in women. Benef
insomnia: What we know and what we still clinical trial. J Sleep Res 27:244–253. Microbes 8:557–562.
need to learn. Sleep Med Rev 6:97–111. 57. Adam TC, Epel ES. 2007. Stress, eating 72. Alam R, Abdolmaleky HM, Zhou JR.
43. Chaput JP, Gray CE, Poitras VJ, and the reward system. Physiol Behav 2017. Microbiome, inflammation, epigen-
Carson V, Gruber R, Olds T, Weiss SK, 91:449–458. etic alterations, and mental diseases. Am
Connor Gorber S, Kho ME, Sampson 58. Wardle J, Chida Y, Gibson EL, Whitaker J Med Genet B Neuropsychiatr Genet
M, Belanger K, Eryuzlu S, Callender L, KL, Steptoe A. 2011. Stress and adipos- 174:651–660.
Tremblay MS. 2016. Systematic review of ity: A meta-analysis of longitudinal stud- 73. Ajslev TA, Andersen CS, Gamborg M,
the relationships between sleep duration ies. Obesity (Silver Spring) 19:771–778. Sorensen TI, Jess T. 2011. Childhood
and health indicators in school-aged 59. Chao AM, Jastreboff AM, White MA, overweight after establishment of the gut
children and youth. Appl Physiol Nutr Grilo CM, Sinha R. 2017. Stress, cortisol, microbiota: The role of delivery mode,
Metab 41:S266–S282. and other appetite-related hormones: pre-pregnancy weight and early adminis-
44. Buman MP, Kline CE, Youngstedt Prospective prediction of 6-month tration of antibiotics. Int J Obes (Lond)
SD, Phillips B, Tulio de Mello M, changes in food cravings and weight. 35:522–529.
Hirshkowitz M. 2015. Sitting and Obesity (Silver Spring) 25:713–720. 74. Murphy R, Stewart AW, Braithwaite
television viewing: Novel risk factors 60. Donoho CJ, Weigensberg MJ, Emken BA, I, Beasley R, Hancox RJ, Mitchell EA.
for sleep disturbance and apnea risk? Hsu JW, Spruijt-Metz D. 2011. Stress 2014. Antibiotic treatment during infancy
results from the. 2013. National Sleep and abdominal fat: Preliminary evidence and increased body mass index in boys:
Foundation Sleep in America Poll. Chest of moderation by the cortisol awakening An international cross-sectional study.
147:728–734. response in Hispanic peripubertal girls. Int J Obes (Lond) 38:1115–1119.
45. Chaput JP, Tremblay A. 2012. Adequate Obesity (Silver Spring) 19:946–952. 75. Rogawski ET, Platts-Mills JA, Seidman
sleep to improve the treatment of obesity. 61. Godsey J. 2013. The role of mindfulness JC, John S, Mahfuz M, Ulak M, Shrestha
CMAJ 184:1975–1976. based interventions in the treatment of S, Soofi SB, Yori PP, Mduma E, Svensen
46. Chaput JP, Bouchard C, Tremblay A. obesity and eating disorders: An integra- E, Ahmed T, Lima AAM, Bhutta Z,
2014. Change in sleep duration and tive review. Complement Ther Med Kosek M, Lang D, Gottlieb M, Zaidi A,
visceral fat accumulation over 6 years in 21:430–439. Kang G, Bessong P, Houpt ER, Guerrant
adults. Obesity (Silver Spring) 22:E9–12. 62. O’Reilly GA, Cook L, Spruijt-Metz D, RL. 2017. Early antibiotic exposure in
47. Spaeth AM, Dinges DF, Goel N. 2013. Black DS. 2014. Mindfulness-based low-resource settings is associated with
Effects of experimental sleep restric- interventions for obesity-related eating increased weight in the first two years
tion on weight gain, caloric intake, and behaviours: A literature review. Obes Rev of life. J Pediatr Gastroenterol Nutr
meal timing in healthy adults. Sleep 15:453–461. 65:350–356.
36:981–990. 63. Raja-Khan N, Agito K, Shah J, Stetter 76. Edmonson MB, Eickhoff JC. 2016.
48. Markwald RR, Melanson EL, Smith MR, CM, Gustafson TS, Socolow H, Weight gain and obesity in infants and
Higgins J, Perreault L, Eckel RH, Wright Kunselman AR, Reibel DK, Legro RS. young children exposed to prolonged
KP, Jr. 2013. Impact of insufficient sleep 2017. Mindfulness-based stress reduction antibiotic prophylaxis. JAMA Pediatr
on total daily energy expenditure, food in women with overweight or obesity: A 171:150–156.
intake, and weight gain. Proc Natl Acad randomized clinical trial. Obesity (Silver 77. Reijnders D, Goossens GH, Hermes GD,
Sci U S A 110:5695–5700. Spring) 25:1349–1359. Neis EP, van der Beek CM, Most J, Holst
49. Simon SL, Field J, Miller LE, DiFrancesco 64. Kristeller JL, Wolever RQ. 2011. JJ, Lenaerts K, Kootte RS, Nieuwdorp
M, Beebe DW. 2015. Sweet/dessert foods Mindfulness-based eating awareness M, Groen AK, Olde Damink SW,
are more appealing to adolescents after training for treating binge eating dis- Boekschoten MV, Smidt H, Zoetendal EG,
sleep restriction. PLoS One 10:e0115434. order: The conceptual foundation. Eat Dejong CH, Blaak EE. 2016. Effects of gut
50. Spiegel K, Tasali E, Penev P, Van Cauter Disord 19:49–61. microbiota manipulation by antibiotics on
E. 2004. Brief communication: Sleep cur- 65. Cramer H, Thoms MS, Anheyer D, host metabolism in obese humans: A ran-
tailment in healthy young men is associ- Lauche R, Dobos G. 2016. Yoga in domized double-blind placebo-controlled
ated with decreased leptin levels, elevated women with abdominal obesitya random- trial. Cell Metab 24:341.
ghrelin levels, and increased hunger and ized controlled trial. Dtsch Arztebl Int 78. Mathur R, Chua KS, Mamelak M,
appetite. Ann Intern Med 141:846–850. 113:645–652. Morales W, Barlow GM, Thomas R,
51. Corbalan-Tutau MD, Madrid JA, 66. Rshikesan PB, Subramanya P, Nidhi R. Stefanovski D, Weitsman S, Marsh
Garaulet M. 2012. Timing and duration 2016. Yoga practice for reducing the male Z, Bergman RN, Pimentel M. 2016.
of sleep and meals in obese and normal obesity and weight related psychological Metabolic effects of eradicating breath
weight women. Association with increase difficulties—A randomized controlled methane using antibiotics in prediabetic
blood pressure. Appetite 59:9–16. trial. J Clin Diagn Res 10:OC22–OC28. subjects with obesity. Obesity (Silver
52. Vorona RD, Winn MP, Babineau TW, 67. Kristal AR, Littman AJ, Benitez D, White Spring) 24:576–582.
Eng BP, Feldman HR, Ware JC. 2005. E. 2005. Yoga practice is associated 79. Jukes TH. 1970. Antibiotics in animal
Overweight and obese patients in a with attenuated weight gain in healthy, feeds. N Engl J Med 282:49–50.
primary care population report less sleep middle-aged men and women. Altern 80. Looft T, Allen HK, Casey TA, Alt DP,
than patients with a normal body mass Ther Health Med 11:28–33. Stanton TB. 2014. Carbadox has both
index. Arch Intern Med 165:25–30. 68. Hicks LA, Bartoces MG, Roberts RM, temporary and lasting effects on the
53. Gangwisch JE, Malaspina D, Boden- Suda KJ, Hunkler RJ, Taylor TH, Jr., swine gut microbiota. Front Microbiol
Albala B, Heymsfield SB. 2005. Schrag SJ. 2015. US outpatient anti- 5:276.
Inadequate sleep as a risk factor for obe- biotic prescribing variation according 81. Nadal A, Quesada I, Tuduri E,
sity: Analyses of the NHANES I. Sleep to geography, patient population, and Nogueiras R, Alonso-Magdalena P. 2017.
28:1289–1296. provider specialty in 2011. Clin Infect Endocrine-disrupting chemicals and the
54. Peppard PE, Young T, Palta M, Dempsey Dis 60:1308–1316. regulation of energy balance. Nat Rev
J, Skatrud J. 2000. Longitudinal study of 69. Cox LM, Blaser MJ. 2015. Antibiotics Endocrinol 13:536–546.
moderate weight change and sleep-disor- in early life and obesity. Nat Rev 82. Vafeiadi M, Roumeliotaki T, Myridakis
dered breathing. JAMA 284:3015–3021. Endocrinol 11:182–190. A, Chalkiadaki G, Fthenou E,
55. Feng Y, Zhang Z, Dong ZZ. 2015. 70. Wang LL, Guo HH, Huang S, Feng CL, Dermitzaki E, Karachaliou M, Sarri K,
Effects of continuous positive airway Han YX, Jiang JD. 2017. Comprehensive Vassilaki M, Stephanou EG, Kogevinas
pressure therapy on glycaemic control, evaluation of SCFA production in the M, Chatzi L. 2016. Association of early
insulin sensitivity and body mass index intestinal bacteria regulated by berberine life exposure to bisphenol A with obesity
in patients with obstructive sleep apnoea using gas-chromatography combined and cardiometabolic traits in childhood.
and type 2 diabetes: A systematic review with polymerase chain reaction. J Environ Res 146:379–387.
and meta-analysis. NPJ Prim Care Respir Chromatogr B Anal Technol Biomed Life 83. Menale C, Grandone A, Nicolucci C,
Med 25:15005. Sci 1057:70–80. Cirillo G, Crispi S, Di Sessa A, Marzuillo
References 527
P, Rossi S, Mita DG, Perrone L, Diano N, serum leptin and severe major depressive 109. Liao KL. 2000. Cognitive-behavioural
Miraglia Del Giudice E. 2017. Bisphenol episode. Psychiatry Res 228:866–870. approaches and weight management:
A is associated with insulin resistance
and modulates adiponectin and resistin
gene expression in obese children. Pediatr
95. Luppino FS, de Wit LM, Bouvy PF,
Stijnen T, Cuijpers P, Penninx BW,
Zitman FG. 2010. Overweight, obesity,
An overview. J R Soc Promot Health
120:27–30.
110. Christakis NA, Fowler JH. 2007. The
41
Obes 12:380–387. and depression: A systematic review and spread of obesity in a large social network
84. Lee MJ, Lin H, Liu CW, Wu MH, Liao meta-analysis of longitudinal studies. over 32 years. N Engl J Med 357:370–379.
WJ, Chang HH, Ku HC, Chien YS, Ding Arch Gen Psychiatry 67:220–229. 111. Oude Luttikhuis H, Baur L, Jansen H,
WH, Kao YH. 2008. Octylphenol stimu- 96. Kim WK, Shin D, Song WO. 2016. Shrewsbury VA, O’Malley C, Stolk RP,
lates resistin gene expression in 3T3-L1 Are dietary patterns associated with Summerbell CD. 2009. Interventions for
adipocytes via the estrogen receptor and depression in U.S. adults? J Med Food treating obesity in children. Cochrane
extracellular signal-regulated kinase 19:1074–1084. Database Syst Rev:CD001872.
pathways. Am J Physiol Cell Physiol 97. Breland JY, Fox AM, Horowitz CR. 112. Kelleher E, Davoren MP, Harrington JM,
294:C1542–C1551. 2013. Screen time, physical activity and Shiely F, Perry IJ, McHugh SM. 2016.
85. Dirinck EL, Dirtu AC, Govindan M, depression risk in minority women. Ment Barriers and facilitators to initial and
Covaci A, Van Gaal LF, Jorens PG. 2014. Health Phys Act 6:10–15. continued attendance at community-
Exposure to persistent organic pollut- 98. Vallance JK, Winkler EA, Gardiner PA, based lifestyle programmes among fami-
ants: Relationship with abnormal glucose Healy GN, Lynch BM, Owen N. 2011. lies of overweight and obese children: A
metabolism and visceral adiposity. Associations of objectively-assessed systematic review. Obes Rev 18:183–194.
Diabetes Care 37:1951–1958. physical activity and sedentary time with 113. Miller GD, Isom S, Morgan TM, Vitolins
86. Dirinck E, Dirtu AC, Jorens PG, depression: NHANES (2005–2006). Prev MZ, Blackwell C, Brosnihan KB, Diz
Malarvannan G, Covaci A, Van Gaal Med 53:284–288. DI, Katula J, Goff D. 2014. Effects of a
LF. 2015. Pivotal role for the visceral fat 99. Khan A, Schwartz KA, Kolts RL, Brown community-based weight loss interven-
compartment in the release of persistent WA. 2007. BMI, sex, and antidepressant tion on adipose tissue circulating factors.
organic pollutants during weight loss. J response. J Affect Disord 99:101–106. Diabetes Metab Syndr 8:205–211.
Clin Endocrinol Metab 100:4463–4471. 100. Kloiber S, Ising M, Reppermund S, 114. Gibbs L, O’Connor T, Waters E,
87. Brien SE, Ronksley PE, Turner BJ, Horstmann S, Dose T, Majer M, Zihl Booth M, Walsh O, Green J, Bartlett J,
Mukamal KJ, Ghali WA. 2011. Effect of J, Pfister H, Unschuld PG, Holsboer F, Swinburn B. 2008. Addressing the poten-
alcohol consumption on biological mark- Lucae S. 2007. Overweight and obesity tial adverse effects of school-based BMI
ers associated with risk of coronary heart affect treatment response in major assessments on children’s wellbeing. Int J
disease: Systematic review and meta- depression. Biol Psychiatry 62:321–326. Pediatr Obes 3:52–57.
analysis of interventional studies. BMJ 101. U her R, Mors O, Hauser J, Rietschel 115. Smith KL, Straker LM, McManus A,
342:d636. M, Maier W, Kozel D, Henigsberg N, Fenner AA. 2014. Barriers and enablers
88. Traversy G, Chaput JP. 2015. Alcohol Souery D, Placentino A, Perroud N, for participation in healthy lifestyle pro-
consumption and obesity: An update. Dernovsek MZ, Strohmaier J, Larsen grams by adolescents who are overweight:
Curr Obes Rep 4:122–130. ER, Zobel A, Leszczynska-Rodziewicz A qualitative study of the opinions of
89. Gepner Y, Golan R, Harman-Boehm A, Kalember P, Pedrini L, Linotte S, adolescents, their parents and community
I, Henkin Y, Schwarzfuchs D, Shelef I, Gunasinghe C, Aitchison KJ, McGuffin stakeholders. BMC Pediatr 14:53.
Durst R, Kovsan J, Bolotin A, Leitersdorf P, Farmer A. 2009. Body weight as a 116. Waters E, Gibbs L, Tadic M, Ukoumunne
E, Shpitzen S, Balag S, Shemesh E, predictor of antidepressant efficacy in OC, Magarey A, Okely AD, de Silva A,
Witkow S, Tangi-Rosental O, Chassidim the GENDEP project. J Affect Disord Armit C, Green J, O’Connor T, Johnson
Y, Liberty IF, Sarusi B, Ben-Avraham S, 118:147–154. B, Swinburn B, Carpenter L, Moore
Helander A, Ceglarek U, Stumvoll M, 102. Serretti A, Mandelli L. 2010. G, Littlecott H, Gold L. 2018. Cluster
Bluher M, Thiery J, Rudich A, Stampfer Antidepressants and body weight: A randomised trial of a school-community
MJ, Shai I. 2015. Effects of initiating comprehensive review and meta-analysis. child health promotion and obesity pre-
moderate alcohol intake on cardiometa- J Clin Psychiatry 71:1259–1272. vention intervention: Findings from the
bolic risk in adults with type 2 diabetes: 103. Freyberg Z, Aslanoglou D, Shah R, evaluation of fun 'n healthy in Moreland!
A 2-year randomized, controlled trial. Ballon JS. 2017. Intrinsic and antipsy- BMC Public Health 18:92.
Ann Intern Med 163:569–579. chotic drug-induced metabolic dysfunc- 117. Maynard MJ. 2017. Faith-based institu-
90. Golan R, Shelef I, Shemesh E, Henkin tion in schizophrenia. Front Neurosci tions as venues for obesity prevention.
Y, Schwarzfuchs D, Gepner Y, Harman- 11:432. Curr Obes Rep 6:148–154.
Boehm I, Witkow S, Friger M, Chassidim 104. Jantaratnotai N, Mosikanon K, Lee Y, 118. Sattin RW, Williams LB, Dias J, Garvin
Y, Liberty IF, Sarusi B, Serfaty D, Bril McIntyre RS. 2017. The interface of JT, Marion L, Joshua TV, Kriska A,
N, Rein M, Cohen N, Ben-Avraham depression and obesity. Obes Res Clin Kramer MK, Narayan KM. 2016.
S, Ceglarek U, Stumvoll M, Bluher M, Pract 11:1–10. Community trial of a faith-based lifestyle
Thiery J, Stampfer MJ, Rudich A, Shai I. 105. Faulconbridge LF, Wadden TA, Thomas intervention to prevent diabetes among
2017. Effects of initiating moderate wine JG, Jones-Corneille LR, Sarwer DB, African-Americans. J Community Health
intake on abdominal adipose tissue in Fabricatore AN. 2013. Changes in 41:87–96.
adults with type 2 diabetes: A 2-year ran- depression and quality of life in obese 119. Vincent D, McEwen MM, Hepworth
domized controlled trial. Public Health individuals with binge eating disorder: JT, Stump CS. 2014. The effects of a
Nutr 20:549–555. Bariatric surgery versus lifestyle modifi- community-based, culturally tailored
91. Falck-Ytter Y, Younossi ZM, Marchesini cation. Surg Obes Relat Dis 9:790–796. diabetes prevention intervention for high-
G, McCullough AJ. 2001. Clinical fea- 106. Jelalian E, Jandasek B, Wolff JC, risk adults of Mexican descent. Diabetes
tures and natural history of nonalcoholic Seaboyer LM, Jones RN, Spirito A. Educ 40:202–213.
steatosis syndromes. Semin Liver Dis 2016. Cognitive-Behavioral therapy 120. Islam NS, Zanowiak JM, Wyatt LC,
21:17–26. plus healthy lifestyle enhancement for Kavathe R, Singh H, Kwon SC, Trinh-
92. Bellentani S, Saccoccio G, Masutti F, depressed, overweight/obese adolescents: Shevrin C. 2014. Diabetes prevention in
Croce LS, Brandi G, Sasso F, Cristanini Results of a pilot trial. J Clin Child the New York City Sikh Asian Indian
G, Tiribelli C. 2000. Prevalence of Adolesc Psychol:1–10. community: A pilot study. Int J Environ
and risk factors for hepatic steatosis 107. Jelalian E, Mehlenbeck R, Lloyd- Res Public Health 11:5462–5486.
in Northern Italy. Ann Intern Med Richardson EE, Birmaher V, Wing RR. 121. Reifegerste D, Wasgien K, Hagen LM.
132:112–117. 2006. ‘Adventure therapy’ combined with 2017. Online social support for obese
93. Bornstein SR, Schuppenies A, Wong cognitive-behavioral treatment for over- adults: Exploring the role of forum activ-
ML, Licinio J. 2006. Approaching the weight adolescents. Int J Obes (Lond) ity. Int J Med Inform 101:1–8.
shared biology of obesity and depression: 30:31–39. 122. Mechanick JI, Marchetti AE, Apovian
The stress axis as the locus of gene- 108. Lang A, Froelicher ES. 2006. C, Benchimol AK, Bisschop PH,
environment interactions. Mol Psychiatry Management of overweight and obesity Bolio-Galvis A, Hegazi RA, Jenkins
11:892–902. in adults: Behavioral intervention for D, Mendoza E, Sanz ML, Sheu WH,
94. Ubani CC, Zhang J. 2015. The role of long-term weight loss and maintenance. Tatti P, Tsang MW, Hamdy O. 2012.
adiposity in the relationship between Eur J Cardiovasc Nurs 5:102–114. Diabetes-specific nutrition algorithm:
528 Chapter 41 Adiposity-based Chronic Disease a New Diagnostic Term
A transcultural program to optimize 132. Polak K, Czyzyk A, Simoncini T, 142. Gaida JE, Cook JL, Bass SL. 2008.
diabetes and prediabetes care. Curr Diab Meczekalski B. 2017. New markers of Adiposity and tendinopathy. Disabil
Rep 12:180–194. insulin resistance in polycystic ovary Rehabil 30:1555–1562.
123. Coates JC, Colaiezzi BA, Bell W, syndrome. J Endocrinol Invest 40:1–8. 143. Rechardt M, Viikari-Juntura E, Shiri
Charrondiere UR, Leclercq C. 2017. 133. Browning JD, Szczepaniak LS, Dobbins R. 2014. Adipokines as predictors of
Overcoming dietary assessment R, Nuremberg P, Horton JD, Cohen recovery from upper extremity soft tis-
challenges in low-income countries: JC, Grundy SM, Hobbs HH. 2004. sue disorders. Rheumatology (Oxford)
Technological solutions proposed by the Prevalence of hepatic steatosis in an urban 53:2238–2242.
international dietary data expansion population in the United States: Impact of 144. He CL, Cheng N, Rong YM, Li HY, Li
(INDDEX) project. Nutrients 9:289. ethnicity. Hepatology 40:1387–1395. JS, Ding J, Hu XB, Pu HQ, Ren XW,
124. Gostin LO, Abou-Taleb H, Roache SA, 134. D’Incao RB, Tovo CV, Mattevi VS, Bai YN. 2017. Risk factors of gout in
Alwan A. 2017. Legal priorities for Borges DO, Ulbrich JM, Coral GP, Jinchang cohort: A Cox regression analy-
prevention of non-communicable dis- Ramos MJ, Meinhardt NG. 2017. sis. Zhonghua Liu Xing Bing Xue Za Zhi
eases: Innovations from WHO’s Eastern Adipokine levels versus hepatic histo- 38:897–901.
Mediterranean region. Public Health pathology in bariatric surgery patients. 145. Inokuchi T, Tsutsumi Z, Takahashi
144:4–12. Obes Surg 27:2151–2158. S, Ka T, Moriwaki Y, Yamamoto T.
125. Gulland A. 2016. WHO calls for tax on 135. Hamilton GS, Joosten SA. 2017. 2010. Increased frequency of metabolic
sugary drinks to tackle child obesity. BMJ Obstructive sleep apnoea and obesity. syndrome and its individual metabolic
352:i475. Aust Fam Physician 46:460–463. abnormalities in Japanese patients
126. Joshi SR, Mohan V, Joshi SS, Mechanick 136. Salord N, Gasa M, Mayos M, Fortuna- with primary gout. J Clin Rheumatol
JI, Marchetti A. 2012. Transcultural Gutierrez AM, Montserrat JM, Sanchez- 16:109–112.
diabetes nutrition therapy algorithm: The de-la-Torre M, Barcelo A, Barbe F, 146. Maheshwari A, Stofberg L, Bhattacharya
Asian Indian application. Curr Diab Rep Vilarrasa N, Monasterio C. 2014. Impact S. 2007. Effect of overweight and obesity
12:204–212. of OSA on biological markers in morbid on assisted reproductive technology—A
127. Su HY, Tsang MW, Huang SY, obesity and metabolic syndrome. J Clin systematic review. Hum Reprod Update
Mechanick JI, Sheu WH, Marchetti A. Sleep Med 10:263–270. 13:433–444.
2012. Transculturalization of a diabetes- 137. Seven E. 2015. Overweight, hypertension 147. Dos Santos E, Duval F, Vialard F,
specific nutrition algorithm: Asian appli- and cardiovascular disease: Focus on adi- Dieudonne MN. 2015. The roles of leptin
cation. Curr Diab Rep 12:213–219. pocytokines, insulin, weight changes and and adiponectin at the fetal-maternal
128. Gandhi R, Sharma A, Kapoor M, natriuretic peptides. Dan Med J 62:B5163. interface in humans. Horm Mol Biol Clin
Sundararajan K, Perruccio AV. 2016. 138. Liberale L, Bonaventura A, Vecchie A, Investig 24:47–63.
Racial differences in serum adipokine Matteo C, Dallegri F, Montecucco F, 148. Phillips GB, Jing T, Heymsfield SB. 2003.
and insulin levels in a matched osteo- Carbone F. 2017. The role of adipocyto- Relationships in men of sex hormones,
arthritis sample: A pilot study. J Obes kines in coronary atherosclerosis. Curr insulin, adiposity, and risk factors for
2016:8746268. Atheroscler Rep 19:10. myocardial infarction. Metabolism
129. Lee JJ, Pedley A, Hoffmann U, Massaro 139. Wanahita N, Messerli FH, Bangalore 52:784–790.
JM, Fox CS. 2016. Association of S, Gami AS, Somers VK, Steinberg JS. 149. Sarac S, Atamer A, Atamer Y, Can AS,
changes in abdominal fat quantity and 2008. Atrial fibrillation and obesity- Bilici A, Tacyildiz I, Kocyigit Y, Yenice
quality with incident cardiovascular -results of a meta-analysis. Am Heart J N. 2015. Leptin levels and lipoprotein
disease risk factors. J Am Coll Cardiol 155:310–315. profiles in patients with cholelithiasis.
68:1509–1521. 140. Hatem SN, Redheuil A, Gandjbakhch J Int Med Res 43:385–392.
130. Zheng Y, Manson JE, Yuan C, Liang E. 2016. Cardiac adipose tissue and 150. I shii S, Chang C, Tanaka T, Kuroda
MH, Grodstein F, Stampfer MJ, Willett atrial fibrillation: The perils of adiposity. A, Tsuji T, Akishita M, Iijima K. 2016.
WC, Hu FB. 2017. Associations of weight Cardiovasc Res 109:502–509. The association between sarcopenic
gain from early to middle adulthood 141. Toussirot E, Michel F, Bereau M, Dehecq obesity and depressive symptoms
with major health outcomes later in life. B, Gaugler B, Wendling D, Grandclement in older Japanese adults. PLoS One
JAMA 318:255–269. E, Saas P, Dumoulin G. 2017. Serum 11:e0162898.
131. Norman RJ, Davies MJ, Lord J, Moran adipokines, adipose tissue measurements 151. Ackerman SE, Blackburn OA,
LJ. 2002. The role of lifestyle modifica- and metabolic parameters in patients Marchildon F, Cohen P. 2017. Insights
tion in polycystic ovary syndrome. Trends with advanced radiographic knee osteoar- into the link between obesity and cancer.
Endocrinol Metab 13:251–257. thritis. Clin Rheumatol 36:2531–2539. Curr Obes Rep 6:195–203.
42
CHAPTER
Key Points.................................................................................. 529 42.3.2 Accounting for Complex Systems Driving Obesity......531
42.1 Introduction...................................................................... 529 42.4 Research Priorities............................................................ 532
42.2 Removing Barriers to Better Outcomes............................. 530 42.4.1 Advances in Pharmacotherapy.............................. 532
42.2.1 Entrenched Bias and Stigma................................. 530 42.4.2 Precision Medicine................................................ 532
42.2.2 Inadequate Resources for Obesity Care................. 530 42.4.3 Attention to Long-Term Outcomes......................... 533
42.2.3 Payment Systems that Favor Treating Obesity 42.4.4 Translation Science............................................... 533
Complications������������������������������������������������������ 530 42.5 Conclusion........................................................................ 533
42.3 More Effective Public Health Strategies............................. 531 Clinical Applications................................................................... 533
42.3.1 A Narrow Focus on Food Policy............................. 531 References................................................................................ 533
529
530 Chapter 42 Future Directions in Obesity and Weight Management
obesity, while fully covering treatment for most of its Subsequent experience proved that they were right
42
complications. about the need for prevention, and considerable resources
Significant financial resources go toward treating those have been applied to this effort. In the U.S., two presi-
complications, which include diabetes, cardiovascular dis- dents for more than a decade made obesity prevention
ease, many forms of cancer, arthritis, liver disease, and a national priority. 29,30 And yet, the prevalence of both
more. A 2014 analysis estimated that direct medical costs childhood and adult obesity has grown relentlessly.
amount to $149 billion in the U.S. 21 Waters and DeVol Meanwhile, obesity has progressed from an epidemic into
estimate that the total U.S. economic burden of obesity is a global pandemic.31
$1.4 trillion. 22
Even after the passage of the Affordable Care Act, blan-
ket exclusions for coverages of obesity treatment, regard- 42.3.1 A Narrow Focus on Food Policy
less of medical necessity, remained common, especially in
the market for individual and small employer health plans. Public health strategies to address obesity focus primarily
Most U.S. adults report that they do not believe that their upon food policy, even in recent publications that purport
health plan will cover evidence-based obesity care, such as to present “new thinking”.32 Beyond nutrition, other strat-
dietary counseling, pharmacotherapy, and bariatric sur- egies target the promotion of physical activity, reflecting
gery. 23 As a preventive service, the Affordable Care Act the theme behind the Obama administration’s Let’s Move!
mandated coverage of intensive lifestyle therapy to prevent program. Promoting better nutrition and more physical
diabetes, but implementation and uptake of such coverage activity might be a reasonable means for promoting gen-
has been exceedingly slow. One study found that utiliza- erally better health. However, as a strategy for reducing
tion of this option under Medicare amounts to less than obesity, little evidence can support a claim that either of
1% of the patients with a medical need for it. 24 those strategies will have a discernable effect.
Coverage of pharmacotherapy for obesity is perhaps The Cochrane review of childhood obesity prevention
the most limited. Gomez and Stanford found that only found mixed evidence for its effectiveness:
11% of policies in only nine states covered these drugs.
They reported that only seven state Medicaid programs Although many studies were able to improve chil-
provided coverage. 25 dren’s nutrition or physical activity to some extent,
Possibly because of dramatic health benefits, bar- only some studies were able to see an effect of the
iatric surgery coverage is relatively more common than program on children’s levels of fatness. When we
either lifestyle therapy or pharmacotherapy. 26 Since combined the studies, we were able to see that these
2006, Medicare has covered this form of obesity care. programs made a positive difference, but there was
Nonetheless, restrictions, exclusions, and large co-pay much variation between the study findings which we
requirements remain common. could not explain. Also, it appeared that the findings
Relatively few patients seek clinical care for obesity, may be biased by missing small studies with negative
perhaps because internalized stigma leads most to pre- findings.33
sume that this is a self-inflicted condition that they must
bear the full responsibility for resolving.14 Presumably, Consistent with this conclusion, Christina Roberto
those patients who are sufficiently motivated to seek care and colleagues noted in 2015 that progress on obesity
might be persistent with therapy and avoid the complica- prevention has been patchy, scarce, and fitful. 32 Jannah
tions of untreated obesity. A recent economic analysis esti- Jones and colleagues suggest that real world implemen-
mated the potential benefits expanded Medicare coverage tation of prevention programs in a childcare setting may
offers for obesity care. Covering care by qualified profes- be inadequate for delivering meaningful outcomes in the
sionals, such as registered dietitians, and for obesity phar- community.34
macotherapy could result in substantial cost savings for
the program over a ten-year horizon. Those savings would
result from cost reductions for treating complications of 42.3.2 Accounting for Complex
untreated obesity. 27 Thus, improved access to well-estab-
lished and effective obesity care represents an untapped Systems Driving Obesity
opportunity for improved outcomes in the health of the However, it may also be that programs to promote healthy
population affected by obesity. eating and active living are sound in theory, but too nar-
row in scope to have a meaningful effect on obesity preva-
lence. The global pandemic of obesity is best understood
42.3 MORE EFFECTIVE PUBLIC as the product of complex, adaptive systems interacting in
unpredictable ways.35 This framework includes domains
HEALTH STRATEGIES of social psychology, individual psychology, individual
physical activity, physical activity environment, human
More than 40 years ago, editors of the Lancet warned that: physiology, individual physiology, food consumption, and
food production.
We need to be more vigilant in preventing obesity The focus of many obesity prevention programs is to
throughout childhood. Probably the obese adult can promote physical activity and improved nutrition by indi-
never be “cured,” but most obesity could, with care, viduals. Some governments have implemented policies
be prevented. 28 that would affect the entire population, but the scope of
532 Chapter 42 Future Directions in Obesity and Weight Management
these policies has been relatively narrow. Taxes on sugar- three drugs it reviewed for obesity—phentermine/topira-
sweetened beverages, for example, may have an impact mate, bupropion/naltrexone, and lorcaserin.43
on consumption of the taxed beverages, but no impact Most pharmaceutical companies responded by shut-
on obesity prevalence has yet been found.36,37 Likewise, ting down drug development programs for obesity.
investments in the built environment might promote phys- Sanofi’s CEO described his company’s decision to aban-
ical activity, but it is unclear that those investments will don the field in 2010:
yield a reduction in obesity. 38
Finegood, Merth, and Rutter suggest that a systems As long as we’re so worried about obesity being a
approach will be necessary to finding more effective strate- lifestyle choice – that anyone can choose to be fat
gies than we have seen to date from public health advo- or thin – then I don’t think we’re going to have an
cates.39 It will require teams from multiple disciplines and ability to develop drugs. I don’t think right now we
multiple sectors. This requirement alone will challenge the have a regulatory environment, a risk/benefit envi-
status quo of isolated sectors and like-minded profession- ronment that would allow me as a CEO to take the
als that resist challenges from outside their relatively fixed risk of developing a drug for obesity.
networks for collaboration. More collaboration between
industry, academia, government, and non-profits will be That harsh environment eased within three years. The
essential. FDA began approving obesity drugs again in 2013. By
A systems approach to public health strategies will also 2014, the agency had approved four new drugs for obe-
require functional goals and more attention to measur- sity, evidently shifting its focus from a conservative view
ing progress toward those goals.40 These strategies must of short-term weight loss toward managing obesity as a
provide for continuous feedback between activities, out- chronic disease.44 At about the same time, the American
comes, and new research findings. Medical Association joined obesity experts in regarding
In short, after four decades of efforts to prevent obe- obesity as a complex, chronic disease that requires careful
sity, progress has been scant. Better results will only come medical management.45
with a new approach that is more grounded in evidence This shift brought renewed investment in develop-
and rigorous, continuous evaluation. More of the same ing new obesity drugs, most notably by Novo Nordisk.46
strategies will deliver only more disappointing results. In addition to that company’s long-term investment in
developing a broad portfolio of new obesity drugs, many
smaller biotech firms are developing highly targeted drugs
42.4 RESEARCH PRIORITIES for obesity.
As a result, the future now holds good possibili-
Biomedical research has great potential to provide bet- ties for innovative new drugs for managing obesity. The
ter therapeutic options for people living with obesity. next agent to reach the market may be semaglutide. In a
Advances are likely to come in three areas of focus: phar- 52-week phase II obesity study, Novo Nordisk reported
macotherapy, precision medicine, and attention to long- outcomes of 13.8% weight loss, which is more than the
term health outcomes. 5–10% weight loss typical of current medications.47
Likewise, other new agents under development show
promise for incremental gains in efficacy. In a phase I
42.4.1 Advances in Pharmacotherapy study of two patients with a rare genetic POMC defect,
setmelanotide produced impressive short-term reductions
Prior to 2013, very little innovation in pharmacother- in weight and hunger.48 In patients with other POMC
apy could be found. The FDA approved phentermine defects, the results were more modest.49
for weight loss in 1959. The first significant new drug New drug development is unpredictable. But these and
approval after that came in 1996 with dexfenfluramine. other agents under study suggest that future drugs may
In 1997, it was withdrawn from the market after reports offer substantial gains in efficacy for carefully selected
of an unacceptable risk of valvular heart disease.41 The patients with obesity. 50
FDA approved two other prescription drugs, sibutra-
mine and orlistat, shortly after dexfenfluramine. Both
of those drugs were marketed more for weight loss than
for chronic disease management of obesity, and both had
42.4.2 Precision Medicine
disappointing results in market. Sibutramine was with- The heritable nature of obesity has long been apparent.51
drawn in 2010.42 But more recent advances have brought deeper insight into
Following those failures, two developments marked the biological basis for that heritability. Research is iden-
a significant shift in the environment for obesity drug tifying a growing number of single-gene defects that can
development. First, the FDA responded to the safety cause severe obesity in childhood. In addition, multiple
issues raised by dexfenfluramine’s withdrawal by raising genetic traits can interact to explain an individual’s sus-
the safety threshold for approving new drugs targeted for ceptibility to obesity. 52 Other contributing factors interact
use in weight loss. Sanofi had completed its full clinical to cause obesity, including epigenetics, the microbiome,
drug development program for rimonabant and obtained social environment, economic environment, food environ-
approval to market in Europe. But the FDA balked at ment, and adverse life experiences. These many factors can
approving it for the U.S. because of concerns about depres- produce many different subtypes of obesity, potentially
sion and suicide. Then the agency turned down the next with different responses to different forms of therapy. 53
References 533
Advances in multiple omics technologies are creating has hardly translated into improved public health out-
42
possibilities for more precise diagnosis of a wide array of comes or improved health and quality of life for the grow-
obesity phenotypes.54 Those advances are opening new ing population of people living with obesity.
possibilities for highly personalized therapies with much Nonetheless, prospects for progress are bright.
more efficacy than current therapies reliably provide. 55 Immediate progress can come from removing barriers to
better outcomes. These barriers include pervasive weight
bias, stigma, and discrimination. Broadly, this subject is
42.4.3 Attention to Long-Term Outcomes receiving considerable attention, both in the research lit-
erature and in popular culture.
Much clinical research for obesity care focuses on weight Progress toward overcoming inadequate resources for
loss endpoints. Acute weight loss outcomes are impor- obesity care is evident already. For example, obesity medi-
tant to patients, but even more important are longer-term cine has become one of the fastest growing fields of medi-
outcomes such as sustained loss over the longer term, cal care. The formation of the American Board of Obesity
resolution of obesity complications, and prevention of Medicine is a key milestone in this success.
serious adverse outcomes such as heart attacks, strokes, The third and perhaps most challenging barrier is
and death. More robust data on long-term outcomes have payment systems that favor treating obesity complica-
already come from research on bariatric surgery and tions over providing obesity care that could prevent those
intensive behavioral therapy for diabetes prevention. complications. Improvements in those systems are coming
Longer-term studies of outcomes from obesity phar- slowly, but they will favor better utilization of evidence-
macotherapy are more recent and have not yet provided based care that prevents or slows the progression of obe-
a substantial evidence base. However, data on cardiovas- sity and its complications.
cular survival benefits of weight-sparing type 2 diabetes Beyond simply removing barriers to applying current
drugs illustrate the possibilities for gains with these types knowledge for reducing the impact of obesity, progress
of studies. will come from new evidence in two realms: public health
strategies and biomedical research for better therapeutic
options.
42.4.4 Translation Science After forty years of disappointing efforts to prevent
Tremendous progress in understanding the biological obesity with a near-exclusive focus on dietary behavior
basis for obesity has only slowly been translated into clini- and physical activity, the need for more effective pub-
cal practices for the benefit of people who are living with lic health policies is obvious. The time is ripe for a new
obesity. Some of this slow progress is due to inadequate approach, one that is more grounded in objective evidence
resources, as discussed previously. Health systems are bet- and rigorous, continuous evaluation.
ter equipped to care for the complications of obesity than Finally, new insights into the biological basis for obe-
to deliver evidence-based care to prevent those complica- sity are already bringing promising new therapies into
tions. But integrated models of disease prevention and view. Pharmacotherapy innovation, precision medicine,
clinical care are beginning to evolve to surround patients and clinical care focused on long-term health outcomes
with a more complete approach to obesity manage- have great potential to support a much higher standard of
ment. Active disease management can be integrated with care for people living with obesity.
community initiatives to reduce the burden of disease.
Achieving this goal will require more healthcare providers
trained in obesity care. Perhaps even more importantly, it CLINICAL APPLICATIONS
will require better incentives for health systems to prevent
chronic diseases. 56 • Better clinical outcomes will result from increased
utilization of the full range of emerging clinical ther-
apies–lifestyle, pharmacotherapy, and surgery.
42.5 CONCLUSION • The options for pharmacotherapy are growing and
will soon set a higher bar for efficacy.
Progress in understanding the biological and environmen- • Future therapies will be more highly targeted to
tal basis for obesity has been substantial, even though it individual patient profiles through precision medi-
is far from complete. Unfortunately, that progress to date cine and rapidly maturing omics technologies.
REFERENCES
1. Kyle TK. CDC: Learning from a and Human Services, Centers for Disease health. American Journal of Public
Shortfall on Obesity Goals [Internet]. Control and Prevention, National Center Health. 2010;100(6):1019–28.
ConscienHealth. 2016 [cited Feb. 12, for Health Statistics; 2017 Oct. 5. de la Haye K, Dijkstra JK, Lubbers MJ,
2018]. Available from: http://conscien 3. GBD 2015 Obesity Collaborators. van Rijsewijk L, Stolk R. The dual role of
health.org / 2016/12/cdc-lea rning-fro Health effects of overweight and friendship and antipathy relations in the
m-shor tfall-obesity-goals / obesity in 195 countries over 25 years. marginalization of overweight children in
2. Hales CM, Carroll MD, Fryar CD, New England Journal of Medicine. their peer networks: The TRAILS Study.
Ogden CL. Prevalence of obesity 2017;377(1):13–27. PloS One. 2017;12(6):e0178130.
among adults and youth: United States, . Puhl RM, Heuer CA. Obesity stigma:
4 . Skinner AC, Payne K, Perrin AJ, Panter
6
2015–2016. US Department of Health Important considerations for public AT, Howard JB, Bardone-Cone A, Bulik
534 Chapter 42 Future Directions in Obesity and Weight Management
CM, Steiner MJ, Perrin EM. Implicit Available from: https: //www.businesswire. 35. Vandenbroeck IP, Goossens J, Clemens M.
weight bias in children age 9 to 11 years. com/news/home/20170216005152/en / Building the obesity system map. Foresight
Pediatrics. 2017;140(1):e20163936. 21. Kim DD, Basu A. Estimating the medi- Tackling Obesities: Future Choices (http://
7. Puhl RM, King KM. Weight discrimi- cal care costs of obesity in the United www.foresight.gov.uk). 2007.
nation and bullying. Best Practice & States: Systematic review, meta-analysis, 36. Colchero MA, Rivera-Dommarco J,
Research Clinical Endocrinology & and empirical analysis. Value in Health. Popkin BM, Ng SW. In Mexico, evidence
Metabolism. 2013;27(2):117–27. 2016;19(5):602–13. of sustained consumer response two
8. Thompson HR, Madsen KA. The report 22. Waters H, DeVol R. Weighing down years after implementing a sugar-
card on BMI report cards. Current America: The health and economic sweetened beverage tax. Health Affairs.
Obesity Reports. 2017;6(2):163–7. impact of obesity. 2017;36(3):564–71.
9. Puhl RM, Phelan SM, Nadglowski 23. Wilson ER, Kyle TK, Nadglowski JF, 37. Brand-Miller JC, Barclay AW. Declining
J, Kyle TK. Overcoming weight bias Cody Stanford F. Obesity coverage gap: consumption of added sugars and sugar-
in the management of patients with Consumers perceive low coverage for sweetened beverages in Australia: A
diabetes and obesity. Clinical Diabetes. obesity treatments even when workplace challenge for obesity prevention, 2. The
2016;34(1):44–50. wellness programs target BMI. Obesity. American Journal of Clinical Nutrition.
10. AMA Destigmatize Obesity Resolution 2017;25(2):370–7. 2017;105(4):854–63.
[Internet]. Obesity Medicine Association. 24. Batsis JA, Bynum JP. Uptake of the 38. Monsivais P, Burgoine T. The built
2017 [cited Feb. 12, 2018]. Available centers for medicare and medicaid environment and obesity in UK Biobank:
from: https: //obesitymedici ne.org/am obesity benefit: 2012–2013. Obesity. Right project, wrong data? The Lancet
a-destigmatize-obesit y-resolution/ 2016;24(9):1983–8. Public Health. 2018;3(1):e4–5.
11. Pont SJ, Puhl R, Cook SR, Slusser W. 25. Gomez G, Stanford FC. US health policy 39. Finegood DT, Merth TD, Rutter H.
Stigma experienced by children and and prescription drug coverage of FDA- Implications of the foresight obesity
adolescents with obesity. Pediatrics. approved medications for the treatment of system map for solutions to childhood
2017:e20173034. obesity. International Journal of Obesity. obesity. Obesity. 2010;18(S1):S13–6.
12. Bergland C. Sizeism Is Harming Too 2017;42:495. 40. Committee on Evaluating Progress of
Many of Us: Fat Shaming Must Stop 26. Tsai AG, Asch DA, Wadden TA. Obesity Prevention Effort. Evaluating
[Internet]. Psychology Today. Sussex Insurance coverage for obesity treat- Obesity Prevention Efforts: A Plan for
Publishers; 2017 [cited Feb. 12, 2018]. ment. Journal of the American Dietetic Measuring Progress. National Academies
Available from: https: //www.psycholo Association. 2006;106(10):1651–5. Press; 2014.
gytoday.com /blog /the-athletes-way/2 27. Su W. The Impact of Medicare Coverage 41. Elliot WT, Chan J. Fenfluramine and
01708/sizeism-is-harm ing-too-many-u for Anti-Obesity Interventions [Internet]. Dexfenfluramine Withdrawn from
s-fat- sham i ng-must-stop Obesity Care Advocacy Network. IHS Market. AHC Media; 1997.
13. Salam M. Why ‘Radical Body Love’ Markit; 2017 [cited Feb. 12, 2018]. 42. In Brief: Sibutramine (Meridia)
Is Thriving on Instagram [Internet]. Available from: http://www.obesityca Withdrawn [Internet]. The Medical
The New York Times. 2017 [cited Feb. readvocacy network.com /the-impac t-of Letter on Drugs and Therapeutics.
12, 2018]. Available from: https://nyti. -medicare-coverage-for-anti-obesity-inte Medical Letter, Inc.; 2010 [cited Feb.
ms/2s4oZI7 rventions/ 12, 2018]. Available from: https://secure.
14. Kaplan LM, Golden A, Jinnett K, 28. Editorial: Infant and adult obesity. medicalletter.org/w1350d
Kolotkin RL, Kyle TK, Look M, Lancet. 1974;303(7845):17–8. 43. Pollack A. F.D.A. Fails to Approve
Nadglowski J, O’Neil PM, Parry T, 29. White House Takes Aim at Obesity Contrave, a New Diet Pill [Internet].
Tomaszewski KJ, Stevenin B. Perceptions [Internet]. CNN. Cable News Network; The New York Times. 2011 [cited Feb.
of barriers to effective obesity care: 2004 [cited Feb. 12, 2018]. Available 12, 2018]. Available from: https://nyti.
Results from the National ACTION from: http://www.cnn.com/20 04/H ms/2rX1C3b
Study. Obesity. 2018;26(1):61–9. EALTH /diet.fitness/03/12/obesit y.ca 44. Kyle TK. Favoring Innovation in Obesity
15. Tsai AG, Histon T, Kyle TK, Rubenstein mpaig n / [Internet]. ConscienHealth. 2014 [cited
N, Troy Donahoo W. Evidence of a 30. Givhan R. First lady Michelle Obama: Feb. 12, 2018]. Available from: http://con
gap in understanding obesity among ‘Let’s Move’ and Work on Childhood scienhealth.org / 2014/ 09/favoring-innovat
physicians. Obesity Science & Practice. Obesity Problem [Internet]. The ion-in-obesity/
2018;4:46–51. Washington Post. WP Company; 2010 45. Pollack A. A.M.A. Recognizes Obesity
16. Kyle TK. Childhood Obesity Treatment [cited Feb. 12, 2018]. Available from: as a Disease [Internet]. The New York
Programs: A Few to Serve Many http://www.washi ngtonpost.com/w p-dy Times. 2013 [cited Feb. 12, 2018].
[Internet]. ConscienHealth. 2017 [cited n/content/a rticle/2010/02/09/A R 2010 Available from: https://nyti.ms/2kt3fCZ
Feb. 12, 2018]. Available from: http://con 02090 0791.html 46. Hirschler B. Novo Nordisk Bets on New
scienhealth.org / 2017/02/ch ildhood-obesit 31. Swinburn BA, Sacks G, Hall KD, Obesity Drug Recipes [Internet]. Reuters.
y-treatment-prog rams- serve -many/ McPherson K, Finegood DT, Moodie Thomson Reuters; 2017 [cited Feb. 12,
17. Wilfley DE, Staiano AE, Altman M, ML, Gortmaker SL. The global obesity 2018]. Available from: https: //www.reu
Lindros J, Lima A, Hassink SG, Dietz pandemic: Shaped by global drivers ters.com/ar ticle /us-novo-nordisk-ceo/nov
WH, Cook S. Improving access and and local environments. The Lancet. o-nord isk-bets-on-new-obesity-d rug-recip
systems of care for evidence-based child- 2011;378(9793):804–14. es-idU SKBN1871Q J
hood obesity treatment: Conference 32. Roberto CA, Swinburn B, Hawkes 47. Holst JJ, Madsbad S. Semaglutide seems
key findings and next steps. Obesity. C, Huang TT, Costa SA, Ashe M, to be more effective the other GLP-
2017;25(1):16–29. Zwicker L, Cawley JH, Brownell KD. 1Ras. Annals of Translational Medicine.
18. Bleich SN, Bandara S, Bennett WL, Patchy progress on obesity prevention: 2017;5(24).
Cooper LA, Gudzune KA. US health Emerging examples, entrenched bar- 48. Kühnen P, Clément K, Wiegand S,
professionals’ views on obesity care, riers, and new thinking. The Lancet. Blankenstein O, Gottesdiener K, Martini
training, and self-efficacy. American 2015;385(9985):2400–9. LL, Mai K, Blume-Peytavi U, Grüters A,
Journal of Preventive Medicine. 33. Waters E, de Silva-Sanigorski A, Burford Krude H. Proopiomelanocortin deficiency
2015;48(4):411–8. BJ, Brown T, Campbell KJ, Gao Y, treated with a melanocortin-4 recep-
19. Kushner RF, Butsch WS, Kahan S, Armstrong R, Prosser L, Summerbell tor agonist. New England Journal of
Machineni S, Cook S, Aronne LJ. Obesity CD. Interventions for preventing obesity Medicine. 2016;375(3):240–6.
coverage on medical licensing exami- in children. The Cochrane Library. 2011. 49. Collet TH, Dubern B, Mokrosinski J,
nations in the United States. What is 34. Jones J, Yoong SL, Wyse R, Ward DS, Connors H, Keogh JM, de Oliveira EM,
being tested? Teaching and Learning in Wolfenden L. Improving the impact Henning E, Poitou-Bernert C, Oppert
Medicine. 2017;29(2):123–8. of obesity prevention interventions in JM, Tounian P, Marchelli F. Evaluation
20. American Board of Obesity Medicine the childcare setting: The need for a of a melanocortin-4 receptor (MC4R)
Surpasses 2,000 Diplomates [Internet]. systematic application of implementation agonist (Setmelanotide) in MC4R
Business Wire. American Board of Obesity science. Journal of Paediatrics and Child deficiency. Molecular Metabolism.
Medicine; 2017 [cited Feb. 12, 2018]. Health. 2017;53(3):211–3. 2017;6(10):1321–9.
References 535
50. Valsamakis G, Konstantakou P, DC. Genetic studies of body mass index 55. Yanovski SZ, Yanovski JA. Toward
Mastorakos G. New targets for drug yield new insights for obesity biology. precision approaches for the preven-
treatment of obesity. Annual Review
of Pharmacology and Toxicology.
2017;57:585–605.
Nature. 2015;518(7538):197.
53. Field AE, Camargo CA, Ogino S. The
merits of subtyping obesity: One size does
tion and treatment of obesity. JAMA.
2018;319(3):223–4.
56. Dietz WH, Solomon LS, Pronk N,
42
51. Musani SK, Erickson S, Allison DB. not fit all. JAMA. 2013;310(20):2147–8. Ziegenhorn SK, Standish M, Longjohn
Obesity--still highly heritable after all 4. Piening BD, Zhou W, Contrepois K,
5 MM, Fukuzawa DD, Eneli IU, Loy L,
these years. The American Journal of Röst H, Urban GJ, Mishra T, Hanson Muth ND, Sanchez EJ. An integrated
Clinical Nutrition. 2008;87(2):275. BM, Bautista EJ, Leopold S, Yeh CY, framework for the prevention and
52. Locke AE, Kahali B, Berndt SI, Justice AE, Spakowicz D. Integrative personal omics treatment of obesity and its related
Pers TH, Day FR, Powell C, Vedantam S, profiles during periods of weight gain and chronic diseases. Health Affairs.
Buchkovich ML, Yang J, Croteau-Chonka loss. Cell Systems. 2018;6:157–70. 2015;34(9):1456–63.
IX
PA RT
537
43
CHAPTER
Key Points.................................................................................. 539 43.6 Moderate Physical Activity and URTI Risk.......................... 541
43.1 Introduction...................................................................... 539 43.7 Moderate Physical Activity and Enhanced
43.2 Chronic Anti-Inflammatory Influence of Exercise Training.......539 Immunosurveillance......................................................... 543
43.3 Physical Activity, Fitness, and Chronic Inflammation.......... 540 43.8 Conclusions...................................................................... 543
43.4 Potential Mechanisms....................................................... 540 Clinical Applications................................................................... 543
43.5 URTI Risk Reduction from Regular, Moderate Exercise References................................................................................ 543
Training............................................................................ 541
539
540 Chapter 43 Exercise, Inflammation, and Respiratory Infection
43.3 PHYSICAL ACTIVITY, FITNESS, vegetables. 23,24 For example, if an obese, older individual
adds three weekly 30-minute walking sessions to their life-
AND CHRONIC INFLAMMATION style, reductions in chronic inflammation are unlikely to
be experienced unless the exercise workload is increased
Large population observational studies consistently show in combination with significant weight loss and improved
reduced WBC, CRP, IL-6, TNF-α, and other inflamma- diet quality.
tory biomarkers in adults with higher levels of physical
activity and fitness, even after adjustment for potential
confounders.10–15 The inverse association between physi- 43.4 POTENTIAL MECHANISMS
cal activity/fitness and inflammation is related in part to
the effect of activity on fat mass.12 In most studies, how- When successful, exercise training may exert anti-
ever, adjustment for body mass index (BMI) and adiposity inflammatory influences through a reduction in visceral
attenuates but does not negate the strength of the rela- fat mass25 and the induction of an acute anti-inflam-
tionship between inflammatory biomarkers and physi- matory environment with each bout of exercise that
cal activity/fitness.12,16 For example, in a study of 1,002 over time becomes chronic. 26,27 Exercise-induced anti-
community-dwelling adults (age range: 18–85 years), a inflammatory adaptations are, in turn, associated with
general linear model (GLM) analysis adjusted CRP means the improved management of chronic diseases associated
for frequency of physical activity, BMI, and several other with low-grade inflammation, including obesity, insulin
lifestyle and demographic factors.16 resistance, cardiovascular disease, and atherosclerosis. 28
BMI had the strongest effect on CRP, followed by gen- These effects may be mediated in part through muscle-
der (higher in females), exercise frequency, age, and smok- derived peptides or myokines, such as IL-6, but this pro-
ing status (Figure 43.1). posed mechanism needs further testing. 29 Contracting
Randomized, controlled, exercise-intervention stud- skeletal muscles release myokines (e.g., IL-6, IL-8, IL-15)
ies provide equivocal support for the inverse relationship that may exert both direct and chronic anti-inflamma-
between increased physical activity and reduced systemic tory effects.
inflammation.12,17–23 Nonetheless, data from both large The first identified and most studied myokine is IL-6.
population and randomized, controlled, exercise-inter- During prolonged and intense exercise, IL-6 is produced
vention study formats support that, in order for reduc- by muscle fibers and stimulates the appearance in the cir-
tions in chronic inflammation to be experienced, a large culation of other anti-inflammatory cytokines such as
change in a combination of lifestyle factors is needed, IL-1ra and IL-10.30 IL-6 also inhibits the production of the
including weight loss, near-daily moderate-to-vigorous proinflammatory cytokine TNF-α and stimulates lipolysis
physical activity of 30–60 minute duration, avoidance and fat oxidation. 30 With weight loss from energy restric-
of cigarette smoking, and increased intake of fruits and tion and exercise, plasma levels of IL-6 fall, skeletal muscle
Figure 43.1 The relative influence of aerobic exercise frequency and other lifestyle and demographic factors on C-reactive
protein. Means are adjusted statistically after weighting for each factor through a general linear model.
(From Shanely, R.A. et al., Scand. J Med. Sci Sports. 2013; 23:215–23.)
43.6 Moderate Physical Activity and URTI Risk 541
43
Thus, IL-6 release from the exercising muscle may help
mediate some of the health benefits of exercise including
metabolic control of type 2 diabetes.31,32
There is evidence, however, that the magnitude or
presence of muscle IL-6 release is a product of the inten-
sity and/or duration of exercise. Muscle IL-6 release is
very low during moderate, prolonged physical activity.
For example, during a 30-minute brisk walk on a tread-
mill, plasma IL-6 concentrations increased from 1.3 to
2.0 pg/mL in female subjects. 33 The increase in IL-6
during brisk walking is probably insufficient to mediate
anti-inflammatory and other beneficial health effects,
and additional research is needed to determine the rela-
tive contribution of myokines compared to other exer-
cise-induced factors.
Conversely, there is a more pronounced, acute, exer-
cise-induced increase in IL-6 after prolonged, heavy exer-
tion (e.g. typically above 5, 10, and 50 pg/mL following 1, Figure 43.2 J-Curve model on the relationship between
2 h, and marathon-race running bouts, respectively) may exercise workload and URTI risk. Animal and human data
support a reduction in URTI risk with moderate activity in con-
indeed orchestrate anti-inflammatory influences, lipoly-
trast to an elevated risk following heavy exertion.
sis, and improved insulin sensitivity, but this amount of
physical activity is beyond levels achievable by most over-
weight/obese individuals. Low- to high-exercise workloads have a unique effect
Recent studies investigating the effects of short bursts on URTI risk, and they can be modeled using a J-curve
of activity on cytokine release via interval training have relationship.39 (Figure 43.2). Regular physical activity
elicited similar results as those found with prolonged improves immune function and lowers URTI risk while
training. High intensity interval exercise (10 × 60 seconds sustained and intense exertion has the opposite effect.
at 85–90%max) elicited increased systemic levels of IL-6 Marathon race competitions and heavy exercise training
and IL-10 in both lean and obese males. However, moder- regimens increase URTI risk, but relatively few individuals
ate intensity interval exercise (70–75%max) of the same exercise at this level, limiting public health concerns. The
duration had no effect. Therefore, the release of IL-6 and second half of this chapter will review the benefits of regu-
other cytokines may be dependent on a combination of lar, moderate activity in improving immunosurveillance
intensity and duration.34 against pathogens and lowering URTI risk. This informa-
A moderate exercise program of near-daily 30-minute tion has broad public health significance and appeal, and
walking bouts, without diet control, has small influences provides the clinician with an additional inducement to
on visceral fat, even in long-term studies.35 This is fur- encourage increased physical activity among patients.
ther evidence that the myokine hypothesis does not apply
at the activity level attainable by most middle-aged and
elderly individuals. Thus, moderate physical activity train-
ing must be increased to the highest levels acceptable to an 43.6 MODERATE PHYSICAL
individual (e.g. 60 min/day) and combined with weight loss ACTIVITY AND URTI RISK
through tight control of energy intake and improved diet
quality to achieve reductions in systemic inflammation. Several lines of evidence support the link between moder-
ate physical activity and improved immunity and lowered
infection rates. Prospective epidemiologic studies have
measured URTI incidence in large groups of moderately
43.5 URTI RISK REDUCTION active and sedentary individuals. Collectively, the epide-
FROM REGULAR, MODERATE miologic studies consistently show reduced URTI rates in
physically active or fit individuals. A one-year epidemiolog-
EXERCISE TRAINING ical study of 547 adults showed a 23% reduction in URTI
risk in those engaging in regular vs. irregular moderate-
URTI is the most frequently occurring infectious disease in to-vigorous physical activity (Figure 43.3).40 In a group of
humans worldwide. 36–38 More than 200 different viruses 145 elderly subjects, URTI symptomatology during a one-
cause the common cold, and rhinoviruses and coronavi- year period was reduced among those engaging in higher
ruses are the culprits 25–60% of the time. The National compared to lower amounts of moderate physical activ-
Institute of Allergy and Infectious Diseases reports that ity.41 During a one-year study of 142 males aged 33–90,
people in the United States suffer 1 billion colds each year the odds of having at least 15 days with URTI was 64%
with an incidence of two to four for the average adult and lower among those with higher physical activity patterns.42
six to ten for children.36 URTI imposes an estimated $40 Randomized experimental trials provide important
billion burden in direct and indirect costs on the U.S. data in support of moderate physical activity in reducing
economy.37 URTI symptomatology. In a randomized, controlled study
542 Chapter 43 Exercise, Inflammation, and Respiratory Infection
frequency of walking experienced an 18% lower risk of finding for the practicing clinician that has emerged from
43
pneumonia compared with women who walked the least.47 exercise immunology studies during the past two decades.
In the same cohort, women who reported running or jog- Animal and human data indicate that during each exercise
ging more than 2 hours/week had a reduced pneumonia bout, transient immune changes take place that over time
risk compared with women who spent no time running may improve immunosurveillance against pathogens,
or jogging.47 thereby reducing URTI risk. The magnitude of reduction
in URTI risk with near-daily moderate physical activity
exceeds levels reported for most medications and supple-
43.7 MODERATE PHYSICAL ments, and bolsters public health guidelines urging indi-
viduals to be physically active on a regular basis.
ACTIVITY AND ENHANCED Regular physical activity should be combined with
IMMUNOSURVEILLANCE other lifestyle strategies to more effectively reduce
URTI risk. These strategies include stress management,
During moderate exercise, several transient changes occur regular sleep, avoidance of malnutrition, and proper
in the immune system.33,48–50 Moderate exercise increases hygiene.38,57–60 URTI is caused by multiple and diverse
the recirculation of immunoglobulins and neutrophils, pathogens, making it unlikely that a unifying vaccine
and natural killer cells, two cells that play a critical role in will be developed.38 Thus, lifestyle strategies are receiv-
innate immune defenses. Animal data indicate that lung ing increased attention by investigators and public health
macrophages play an important role in mediating the ben- officials, and a comprehensive lifestyle approach is more
eficial effects of moderate exercise on lowered suscepti- likely to lower the burden of URTI than a focus on physi-
bility to infection. 51 Stress hormones, which can suppress cal activity alone.
immunity, and pro- and anti-inflammatory cytokines, The anti-inflammatory effect of near-daily physi-
indicative of intense metabolic activity, are not elevated cal activity may play a key role in many health benefits,
during moderate exercise.33 including reduced CVD, type 2 diabetes, various types
Although the immune system returns to pre-exer- of cancer, sarcopenia, and dementia.10–19 This is an excit-
cise levels within a few hours after the exercise session ing area of scientific endeavor, and additional research is
is over, each session may represent an improvement in needed to determine how immune perturbations during
immune surveillance that reduces the risk of infection each exercise bout accumulate over time to produce an
over the long term. Other exercise-immune-related anti-inflammatory influence. As with URTI, multiple life-
benefits include enhanced antibody-specific responses style approaches to reducing chronic inflammation should
to vaccinations. For example, several studies indicate be employed with a focus on weight loss, high volume of
that both acute and chronic moderate exercise training physical activity, avoidance of smoking, and improved
improves the body’s antibody response to the influenza diet quality.
vaccine. 52–55 In one study, a 45-minute moderate exercise
bout just before influenza vaccination improved the anti-
body response. 52 CLINICAL APPLICATIONS
These data provide additional evidence that moderate
exercise favorably influences overall immune surveillance • Chronic systemic inflammation has been linked to
against pathogens. Taken together, the data on the rela- many disease states.
tionship between moderate exercise, enhanced immunity, • Lifestyle modifications, in this case, chronic physical
and lowered URTI risk are consistent with guidelines activity, have been shown to reduce systemic inflam-
urging the general public to engage in near-daily brisk mation, and thus should be prescribed for all adults.
walking. • URTIs are the most common infection in the world,
and in the U.S. alone cost $40 billion annually.
• Regular physical activity has been shown to reduce
43.8 CONCLUSIONS the incidence of URTIs and reduce the duration of
symptoms.
Although methodology varies widely and evidence is still
emerging, 56 epidemiologic and randomized exercise train- For these reasons, clinicians are encouraged to prescribe
ing studies consistently report a reduction in URTI inci- 60 minutes of moderate physical activity per day to all
dence or risk of 18%–67%. This is the most important adults.
REFERENCES
1. Shephard RJ. Development of the dis- Muscle damage is linked to cytokine 5. Arsenault BJ, Earnest CP, Després JP, Blair
cipline of exercise immunology. Exerc changes following a 160-km race. Brain SN, Church TS. Obesity, coffee consump-
Immunol Rev. 2010; 16:194–222. Behav Immun. 2005; 19:398–403. tion and CRP levels in postmenopausal
2. Nieman DC, Henson DA, Smith LL et al. 4. Bernecker C, Scherr J, Schinner S, Braun overweight/obese women: Importance of
Cytokine changes after a marathon race. S, Scherbaum WA, Halle M. Evidence for hormone replacement therapy use. Eur J
J Appl Physiol. 2001; 91:109–114. an exercise induced increase of TNF-α Clin Nutr. 2009; 63:1419–1424.
3. Nieman DC, Dumke CL, Henson DA, and IL-6 in marathon runners. Scand J 6. Khansari N, Shakiba Y, Mahmoudi M.
McAnulty SR, Gross SJ, Lind RH. Med Sci Sports. 2013; 23:207–214. Chronic inflammation and oxidative
544 Chapter 43 Exercise, Inflammation, and Respiratory Infection
stress as a major cause of age-related 20. Stewart LK, Earnest CP, Blair SN, 35. Nicklas BJ, Wang X, You T et al. Effect
diseases and cancer. Recent Pat Church TS. Effects of different doses of of exercise intensity on abdominal fat loss
Inflamm Allergy Drug Discov. 2009; physical activity on C-reactive protein during calorie restriction in overweight
3:73–80. among women. Med Sci Sports Exerc. and obese postmenopausal women: A
7. Devaraj S, Valleggi S, Siegel D, Jialal I. 2010; 42:701–707. randomized, controlled trial. Am J Clin
Role of C-reactive protein in contribut- 21. Thompson D, Markovitch D, Betts JA, Nutr. 2009; 89:1043–1052.
ing to increased cardiovascular risk in Mazzatti D, Turner J, Tyrrell RM. Time 36. National Institute of Allergy and
metabolic syndrome. Curr Atheroscler course of changes in inflammatory mark- Infectious Diseases. The Common Cold.
Rep. 2010; 12:110–118. ers during a 6-mo exercise intervention in http://www.niaid.nih.gov/topics /com
8. Pearson TA, Mensah GA, Alexander sedentary middle-aged men: A random- moncold (Accessed 3 July 2010).
RW et al. Markers of inflammation and ized-controlled trial. J Appl Physiol. 37. Fendrick AM, Monto AS, Nightengale
cardiovascular disease: Application to 2010; 108:769–779. B, Sarnes M. The economic burden of
clinical and public health practice: A 22. Stewart LK, Flynn MG, Campbell WW non-in uenza-related viral respiratory
statement for healthcare professionals et al. The influence of exercise training tract infection in the United States. Arch
from the Centers for Disease Control on in ammatory cytokines and C-reactive Intern Med. 2003; 163:487–494.
and Prevention and the American protein. Med Sci Sports Exerc. 2007; 38. Monto AS. Epidemiology of viral
Heart Association. Circulation. 2003; 39:1714–1719. respiratory infections. Am J Med. 2002;
107:499–511. 23. Christiansen T, Paulsen SK, Bruun 112(6A):4S–12S.
9. Dekker MJ, Lee S, Hudson R et al. An JM, Pedersen SB, Richelsen B. Exercise 39. Nieman DC. Is infection risk linked to
exercise intervention without weight loss training versus diet-induced weight-loss exercise workload? Med Sci Sports Exerc.
decreases circulating interleukin-6 in lean on metabolic risk factors and inflam- 2000; 32(suppl 7):S406–S411.
and obese men with and without type 2 matory markers in obese subjects: A 40. Matthews CE, Ockene IS, Freedson PS,
diabetes mellitus. Metabolism 2007; 12-week randomized intervention study. Rosal MC, Merriam PA, Hebert JR.
56:332–338. Am J Physiol Endocrinol Metab. 2010; Moderate to vigorous physical activ-
10. Hsu FC, Kritchevsky SB, Liu Y et al. 298:E824–E831. ity and risk of upper-respiratory tract
Association between inflammatory 24. Herder C, Peltonen M, Koenig W et al. infection. Med Sci Sports Exerc. 2002;
components and physical function in Anti-inflammatory effect of life- 34:1242–1248.
the health, aging, and body composition style changes in the Finnish Diabetes 41. Kostka T, Praczko K. Interrelationship
study: A principal component analysis Prevention Study. Diabetologia 2009; between physical activity, symptomatol-
approach. J Gerontol A Biol Sci Med Sci. 52:433–442. ogy of upper respiratory tract infec-
2009; 64:581–589. 25. van Hall G, Steensberg A, Sacchetti M, tions, and depression in elderly people.
11. Lavoie ME, Rabasa-Lhoret R, Doucet E Fischer C, Keller C, Schjerling P et al. Gerontology 2007; 53:187–193.
et al. Association between physical activ- Interleukin-6 stimulates lipolysis and fat 42. Kostka T, Drygas W, Jegier A, Praczko
ity energy expenditure and inflammatory oxidation in humans. J Clin Endocrinol K. Physical activity and upper respiratory
markers in sedentary overweight and Metab. 2003; 88:3005–10. tract infections. Int J Sports Med. 2008;
obese women. Int J Obes (Lond). 2010; 26. Brandt C, Pedersen BK. The role of 29:158–162.
34:1387–1395. exercise-induced myokines in muscle 43. Nieman DC, Nehlsen-Cannarella SL,
12. Beavers KM, Brinkley TE, Nicklas BJ. homeostasis and the defense against Markoff PA et al. The effects of moder-
Effect of exercise training on chronic chronic diseases. J Biomed Biotechnol. ate exercise training on natural killer
inflammation. Clin Chim Acta 2010; 2010; doi:10.1155/2010/520258. cells and acute upper respiratory tract
411:785–793. 27. Pedersen BK. The diseasome of physical infections. Int J Sports Med. 1990;
13. Ford ES. Does exercise reduce inflamma- inactivity—And the role of myokines in 11:467–473.
tion? Physical activity and C-reactive pro- muscle—Fat cross talk. J Physiol. 2009; 44. Nieman DC, Henson DA, Gusewitch G
tein among U.S. adults. Epidemiology. 587(Pt 23):5559–5568. et al. Physical activity and immune func-
2002; 13:561–568. 28. Gleeson M, Bishop N, Oliveira M, Tauler tion in elderly women. Med Sci Sports
14. Borodulin K, Laatikainen T, Salomaa V, P. Influence of training load on upper Exerc. 1993; 25:823–831.
Jousilahti P. Associations of leisure time respiratory tract infection incidence and 45. Nieman DC. Immune function. In
physical activity, self-rated physical antigen-stimulated cytokine produc- Gisol CV, Lamb DR, Nadel E (eds).
fitness, and estimated aerobic fitness tion. Scand J Med Sci Sports. 2013; Perspectives in Exercise Science and
with serum C-reactive protein among 23:451–457. Sports Medicine, Vol. 8: Exercise in Older
3,803 adults. Atherosclerosis 2006; 29. Pedersen BK. Anti-inflammatory Adults. Carmel, IN: Cooper Publishing
185:381–387. effects of exercise: Role in diabetes Group, 1995, pp. 435–461.
15. Brooks GC, Blaha MJ, Blumenthal RS. and cardiovascular disease. European 46. Chubak J, McTiernan A, Sorensen B et al.
Relation of C-reactive protein to Journal of Clinical Investigation. 2017; Moderate-intensity exercise reduces the
abdominal adiposity. Am J Cardiol. 2010; 47(8):600–611 incidence of colds among postmenopausal
106:56–61. 30. Petersen AM, Pedersen BK. The anti- women. Am J Med. 2006; 119:937–942.
16. Shanely RA, Nieman DC, Henson DA, inflammatory effect of exercise. J Appl 47. Neuman MI, Willett WC, Curhan GC.
Jin F, Knab AM, Sha W. Inflammation Physiol. 2005; 98:1154–1162. Physical activity and the risk of commu-
and oxidative stress are lower in physi- 31. Ryan AS, Nicklas BJ. Reductions in nity-acquired pneumonia in US women.
cally fit and active adults. Scand J Med plasma cytokine levels with weight Am J Med. 2010; 123:281.e7–281.e11.
Sci Sports. 2013; 23:215–23. loss improve insulin sensitivity in 48. Nehlsen-Cannarella SL, Nieman DC,
17. Church TS, Earnest CP, Thompson overweight and obese postmeno- Jessen J et al. The effects of acute moder-
AM et al. Exercise without weight loss pausal women. Diabetes Care 2004; ate exercise on lymphocyte function and
does not reduce C-reactive protein: The 27:1699–1705. serum immunoglobulins. Int J Sports
INFLAME study. Med Sci Sports Exerc. 32. Ferrier KE, Nestel P, Taylor A, Drew Med. 1991; 12:391–398.
2010; 42:708–716. BC, Kingwell BA. Diet but not aerobic 49. Nieman DC. Exercise effects on systemic
18. Arsenault BJ, Cote M, Cartier A exercise training reduces skeletal muscle immunity. Immunol Cell Biol. 2000;
et al. Effect of exercise training on TNF-alpha in overweight humans. 78:496–501.
cardiometabolic risk markers Diabetologia 2004; 47:630–637. 50. Nieman DC, Nehlsen-Cannarella SL.
among sedentary, but metabolically 33. Nieman DC, Henson DA, Austin MD, The immune response to exercise. Semin
healthy overweight or obese post- Brown VA. The immune response to a Hematol. 1994; 31:166–179.
menopausal women with elevated 30-minute walk. Med Sci Sports Exerc. 51. Murphy DA, Davis JM, Brown AS et al.
blood pressure. Atherosclerosis 2009; 2005; 37:57–62. Role of lung macrophages on suscepti-
207:530–533. 34. Dorneles GP, Haddad DO, Fagundes bility to respiratory infection following
19. Kelley GA, Kelley KS. Effects of aerobic VO, Vargas BK, Kloecker A, Romao PR, short-term moderate exercise training.
exercise on C-reactive protein, body Peres A. High intensity interval exercise Am J Physiol Regul Integr Comp Physiol.
composition, and maximum oxygen decreases IL-8 and enhances the immu- 2004; 287:R1354–R1358.
consumption in adults: A meta-analysis of nomodulatory cytokine interleukin-10 in 52. Edwards DM, Burns VE, Reynolds T,
randomized controlled trials. Metabolism lean and overweight-obese individuals. Carroll D, Drayson M, Ring C. Acute
2006; 55:1500–1507. Cytokine. 2016; 77:1–9. stress exposure prior to influenza
References 545
vaccination enhances antibody response 55. Lowder T, Padgett DA, Woods JA. predictors of susceptibility to respiratory
in women. Brain Behav Immun. 2006; Moderate exercise early after influenza infectious illness. Int J Behav Med. 2005;
20:159–168.
53. Kohut ML, Arntson BA, Lee W et al.
Moderate exercise improves antibody
virus infection reduces the Th1 inflam-
matory response in lungs of mice. Exerc
Immunol Rev. 2006; 12:97–111.
12:123–131.
58. Spiegel K, Sheridan JF, Van Cauter E.
Effect of sleep deprivation on response
43
response to in uenza immuniza- 56. Fondell E, Christensen SE, Bälter O, Bälter to immunization. JAMA 2002;
tion in older adults. Vaccine 2004; K. Adherence to the Nordic Nutrition 288:1471–1472.
22:2298–2306. Recommendations as a measure of a healthy 9. Cohen S, Doyle WJ, Alper CM, Janicki-
5
4. Kohut ML, Lee W, Martin A et al. The
5 diet and upper respiratory tract infection. Deverts D, Turner RB. Sleep habits and
exercise-induced enhancement of influ- Public Health Nutr. 2011; 14:860–869. susceptibility to the common cold. Arch
enza immunity is mediated in part by 57. Cohen S. Keynote Presentation at Intern Med. 2009; 169:62–67.
improvements in psychosocial factors in the Eight International Congress of 60. Keusch GT. The history of nutrition:
older adults. Brain Behav Immun. 2005; Behavioral Medicine: The Pittsburgh Malnutrition, infection and immunity.
19:357–366. common cold studies: Psychosocial J Nutr. 2003; 133:336S–340S.
44
CHAPTER
547
548 Chapter 44 Chronic Exercise and Immunity
44
Clinical symptoms of overtraining syndrome are many
ON ADAPTIVE IMMUNITY and include: lethargy, fatigue, mood disturbances, under-
performance, immune suppression, and poor healing of
44.3.1 T and B Lymphocytes cuts and scratches. The etiology of OTS is not fully under-
stood, and in addition to training load, other variables
T and B cells are the primary circulating cells of the adap-
such as micro- and macronutrient intakes, recovery, and
tive immune system. T cells are involved in cell-mediated
sleep quality may also contribute to risk and development
immunity and B cells are primarily responsible for pro-
of OTS.
ducing antigen specific antibodies (humoral immunity).
As noted above, resting immunity is not substantially
There are aging-related changes in adaptive immu-
different between athletes and healthy, sedentary indi-
nity—immunosenescence refers to the natural decline in
viduals, but it appears that intensive training could neg-
immune function that occurs with aging and is believed
atively affect several immune measures. Changes in NK
to contribute to age-associated morbidity.44 Regular exer-
cell activity and T-cell function have been observed after
cise may impact the number, function, and ex vivo prolif-
intensified training programs, but it is unclear whether the
erative response of T cell populations in older adults, and,
changes in the immune system induced by hard training
as such, may be an important modality for maintaining
are to blame for a higher incidence of infection in ath-
immune health as one grows older. The ex vivo lympho-
letes.38 Nevertheless, the collective toll of excessive train-
cyte proliferative response to mitogen (PHA) was sig-
ing on the immune system would appear to render athletes
nificantly higher in older runners than non-runners.45,46
more susceptible to infection.
Koizumi et al. reported that exercise training increased
The immune variable that responds most consistently
the absolute numbers of T cells and T-helper cells in older
to repeated, hard exercise is the mucosal secretion or
adults (2003), and a six-month aerobic exercise training
secretion rate of immunoglobulin A (IgA), considered a
intervention increased T-cell proliferation in response to
first line of defense against infection. IgA has also been
mitogen. 38 However, others have reported that ex vivo
more strongly and consistently linked to infection risk in
lymphocyte responses are not affected by shorter exer-
athletes than other measurable aspects of immunity.52 The
cise interventions or resistance training. Ex vivo T-cell
influence of intensive training on salivary IgA is discussed
proliferation did not change after 12 weeks of exercise
in detail below.
training. 28 Resistance training for 10 to 12 weeks did
not alter proliferative response to mitogens, 36,47 and
a 12-month moderate resistance exercise program for
elderly women did not alter circulating numbers of lym- 44.4.1 Th1/Th2 Balance
phocytes. 37 Currently, there is a lack of consensus on the
CD4+ T-helper cells can be divided into several dis-
effects of regular exercise on ex vivo lymphocyte prolif-
tinct subpopulations, including Th1, Th2, Th17, and
erative response.
T-regulatory (Tregs) cells. Specifically, Th1 cells are part
An emerging area of research in the adaptive immune
of cell-mediated immunity and produce TNF and INFγ;
system is the potential elements of an acute exercise
Th2 cells release IL-4, -5, and -10, and respond to para-
response that can be attributed to infection history or
sites; Th17 produce IL-17 and seem to have a large role
latent virus infection. Specifically, subjects who are
in autoimmune disorders; and Tregs suppress the activ-
seropositive for cytomegalovirus (CMV) will have a
ity of other immune cells and maintaining discrimination
higher acute aerobic exercise response to total lympho-
between self and non-self antigens during an immune
cytes, KLRG1+CD28-CD4+ and CD8+ T cells, and
response, thereby preventing autoimmune diseases. In
CD45RA+CCR7-CD8+ T cells than CMV negative sub-
some respects, the ratio of T cell subsets cells may be a
jects.48,49 Interestingly, when young and older subjects
better indicator of health than the absolute numbers. For
completed the same relative intensity, acute, aerobic
example, the ratio of Thelper1/Thelper2 (Th1/Th2) cyto-
exercise bout, the CMV+ young and older subjects had
kines is often used as an index of inflammatory signaling.
the same redeployment of total CD8+ T cells as well as
The Th1/Th2 distribution has been consistently shown to
CD45RA+CCR7+ and KLRG1-CD28+ CD8+ subsets,
be influenced by intensive training, with a shift toward
but the CMV- older adults had an impaired response. 50
Th2 dominance. 53 A pronounced shift in cytokine produc-
Infection history of some viruses may protect an athlete
tion, typical of the Th2 anti-inflammatory milieu, could
from subsequent illnesses, 51 and not controlling for infec-
render the vigorous exerciser more susceptible to infec-
tion history could account for some of the conflicting
tion. 52,54 However, moderate training appears to induce
results often reported in the literature.
a positive, subtle shift toward a Th2 cytokine profile,
balancing the Th1/Th2 response and inducing the anti-
44.4 EXCESSIVE TRAINING inflammatory influences of regular exercise. 54
Treg and Th17 cells are not well studied in an exer-
AND IMMUNITY cise or physical activity context. In the limited research
available, Yeh et al. reported an increased Treg function
Excessive training can result in a wide range of negative in both healthy, middle-aged adults55 and subjects with
clinical signs and symptoms. This symptom complex is Type2 diabetes56 after 12 weeks of Tai Chi training. In
quite often referred to as overtraining syndrome (OTS), response to a strenuous acute aerobic exercise event, ath-
but the reader will also frequently see “overtraining” or letes had a decrease in absolute numbers of Tregs and an
550 Chapter 44 Chronic Exercise and Immunity
increase in Th17 cells. Furthermore, there was a decrease due to a lack of the presence of an infectious pathogen in
in percent circulating Treg cells that remained depressed the sputum of athletes reporting symptoms of URTI.60
below pre-race levels 10 days after the event. 57 Treg and However, most researchers also acknowledge that the
Th17 cells both have a role in regulating inflammation and ability to detect these pathogens in sputum is far from an
need further examination in a physical activity context. exact science. It is interesting to note that the daily use of
an anti-inflammatory throat spray, one week before and
two weeks after a half-marathon, did not influence the
44.4.2 Toll-like Receptors number of reported URTI episodes in a relatively small
group of runners (n = 25 treatment; n = 20 controls), but
High-intensity bouts of exercise have also been linked
may have influenced the severity scores (trend).61 Thus,
to down-regulation of TLR4-cell surface expression.58
while evidence is mounting that regular, modest exer-
Oliveira and Gleeson found that cycling for 90 minutes
cise reduces the risk of URTI 28 and prolonged, intense or
(75% VO2peak) resulted in a transient reduction in TLR4
excessive exercise training increases the risk of URTI, 59
that was sustained for one to four hours after exercise. 58
there is considerable controversy in this area that prevents
Toll-like receptors help orchestrate the innate immune
us from making concrete conclusions about the links
response to a wide range of pathogens, which led the
between hard exercise and illness.
Oliveira and Gleeson to conclude that post-exercise TLR4
No increase in the rate of infectious episodes was
depression could contribute to post-exercise immune
found in marathon runners when runners with a pre-
depression. This premise, however, was based on a single
race infection were removed from the cohort,62 casting
bout of exercise and there is a lack of research examin-
further doubt on the relationship between hard exercise
ing the response of sustained, intensified training on TLR
and URTI. Thus, while there is conflicting data on the
down-regulation. Therefore, while it is possible that regu-
relationship between infection risk and hard training, the
lar bouts of hard exercise might transiently reduce TLR
conflict is difficult to rectify when considering feasibility
expression and increase susceptibility to infection, moder-
and research design issues. Logistically, the excessive time
ate intensity, long-term exercise reduces TLR4 expression
and cost make it difficult to include quantitative cellular
in hyper-inflammatory groups (sedentary, overweight/
immune measures in large cohort studies of infection inci-
obese, and elderly). Reduced TLR4 expression is gener-
dence and prevalence. There are some larger-scale studies
ally viewed as a positive adaptation due to its potential
in which salivary IgA has been measured and negatively
to influence systemic inflammation. Thus, there is likely a
correlated with URTI incidence.35 Gleeson et al.52 moni-
differential response to repeated bouts of intense exercise
tored 80 athletes for several months, with training and ill-
where the goal is improved performance, which could lead
ness logs recorded and blood and saliva samples obtained.
to immune depression and long-term, moderate exercise
These authors identified a sub-group of “illness-prone”
programs where the goal is to improve fitness, which can
subjects who had higher training loads, higher levels of
lead to overall health improvement.
multi-antigen-stimulated anti-inflammatory cytokines—
illustrating a Th2 dominant response—and lower salivary
S-IgA secretion and flow rates. In addition, the highest
44.4.3 Excessive Training: URS or URTI? quartile of IL-10 producers had higher training loads,
Athletes who train hard are frequently reported to higher production of inflammatory and anti-inflamma-
have an increased incidence of upper-respiratory symp- tory cytokines, lower IgA, and higher URTI incidence
toms (URS) related to upper-respiratory tract infection than the lowest quartile. The authors suggested that IL-10
(URTI). 59 Elite athletes are believed to have a higher might be a useful predictor of infection risk in physically
incidence of URTI than fitness exercisers or sedentary active individuals. 52 There is clearly an increase in upper-
individuals. These findings, along with the fact that sev- respiratory symptoms associated with hard training.
eral indices of immune function are suppressed by heavy Further research is required to document what proportion
exercise, led to the assertion that heavy exercise lowers of these illnesses are pathogen-based or linked to airway
immune defenses and increases URTI risk. Two impor- inflammation/irritation.
tant factors remain unclear in this regard. First, whether A relatively new area of research is related to the rela-
or not excessive training suppresses immune function tionship between the microbiome and overall health.
to the extent possible to result in an increased suscep- Much of this research specifically relates to gut microbi-
tibility to infection has not been determined. 38 There is ota, as the results from numerous studies link gut micro-
a general consensus that several immune parameters are biota to health concerns such as obesity and diabetes.63,64
depressed following prolonged or severe exercise, most Studies of gut microbiota and health include the poten-
notably and consistently mucosal immunoglobulin A, tial for dietary supplements to reduce the risk of vari-
but it is not known whether the immune depression is ous infections in athletes. The wide range of the types of
causative of an increased incidence of URTI. Second, it is supplements, doses, and subject populations in this new
not clear whether the URTIs reported by athletes in the research area make it difficult to define an optimal regime
majority of studies are pathogen-based or a result of local for intestinal microbiota health in an athlete. However,
airway irritation or inflammation.60 Problematically, there is some evidence that altering gut microbiota may
most of the studies in which the incidence of URTI has reduce infection risk or length of symptoms in athletes.
been assessed in conjunction with heavy training largely Highly-trained male and female athletes who received a
relied on self-report. Researchers from a small number multi-species probiotic had a lower incidence of URTI,
of studies have called that practice into question, largely but no improvement in athletic performance.65 Other
44.5 Moderate Training and Immunity 551
researchers have also found a decrease in URTI infec- in which self-reported physical activity level was linked to
44
tion incidence and length of symptoms in athletes tak- biomarkers of inflammation, and an additional nine stud-
ing probiotics, but the benefit may be dependent on the ies during which the fitness level was measured. These
type of probiotic.66–68 Additionally, more work is needed authors concluded that accounting for obesity “…attenu-
to determine if a sex difference exists in the responses to ated, but did not negate, the strength of the relationship
probiotics.69 between inflammatory biomarkers and physical activity.”
However, in an analysis of 1,703 adults (55–74 years),
BMI was associated with more serum markers of inflam-
44.5 MODERATE TRAINING mation than self-reported vigorous activity.81 The conflict-
AND IMMUNITY ing results of these studies underscore the differences that
may be attributed to type and intensity of exercise. There
are few studies in which an exercise intervention with and
44.5.1 Exercise and Inflammation without body weight losses has been compared. The few
Evidence of the role that inflammation plays in the devel- in which comparisons were made do not allow for consen-
opment and exacerbation of chronic disease has grown sus, and it is difficult to control for the changes attributed
substantially. Inflammation or inflammatory biomark- to exercise training, changes in dietary patterns, and small
ers have been clearly linked to cardiovascular disease,70 changes in visceral fat.6,77,82
type 2 diabetes,71 osteoporosis72 and several other chronic In summary, moderate exercise has anti-inflammatory
diseases not previously believed to have an inflammatory effects. It is possible that there is an intensity threshold
etiology. For example, cardiovascular disease was long but evidence in support of low-intensity exercise exerting
believed to be a disease of lipid storage; however, it is now anti-inflammatory effects suggests the need for further
clear that inflammation plays a major role in the patho- study. It appears that exercise can exert anti-inflammatory
physiology of atherosclerosis and CVD.73 effects in the absence of significant changes in body fat,
Exercise is known to provide substantial benefits but the lack of controlled studies in which exercise and
for the prevention and management of chronic dis- diet have been studied alone and in combination preclude
eases. There is growing evidence that exercise has anti- definitive conclusions. Exercise is known to exert anti-
inflammatory effects, but it is not clearly known how inflammatory effects in persons with type 2 diabetes and
much of the benefit of exercise is due to contribution of a concomitant improvement in diabetic state and amelio-
an anti-inflammatory effect or to other actions of exer- ration of symptoms without significant body fat changes.
cise. Regardless of the relative contribution, inflamma- Thus, while some mechanisms remain to be determined,
tory biomarkers are significantly lower in segments of the anti-inflammatory effect of exercise has important
the population with moderate-to-high levels of physical health implications.
activity.74 Not surprisingly, intervention studies provide
less consistent support of an anti-inflammatory effect of
exercise. Small subject numbers, different exercise modes
and intensities, supervised vs. unsupervised exercise, and
44.5.2 Wound Healing
different choice of biomarkers all likely contribute to Aging and chronic conditions are known to slow the rate at
these inconsistencies. Nevertheless, there is fairly strong which wounds heal. Bed sores are fairly common in older,
intervention literature to support the observation that institutionalized patients and are difficult and expensive
exercise training has anti-inflammatory effects in serum to treat. Thus, it is important to examine potential low-
or circulating cells,6,15,21 muscle,75,76 and, to a lesser cost interventions such as exercise on wound healing. The
extent, adipose tissue. 25,77 influence of exercise training or physical activity levels on
Inflammatory biomarkers and inflammation have been wound healing has been studied in a relatively small num-
linked to the risk of several chronic diseases, including ber of investigations, but the limited available information
type 2 diabetes. High levels of inflammation are linked is promising. As such, the inability of aging macrophages
to peripheral tissue insulin resistance, impaired insulin to produce angiogenic proteins could be modified by exer-
receptor function, and severity of diabetic complications. cise training, and the anti-inflammatory effect of exercise
TLR4 activation has also been shown to mimic several training could also play a role in enhanced wound healing.
features of the diabetic state, but regular exercise reduces Emery et al.83 divided 28 older adults into an exercise and
nuclear factor kappaB (NFκB) and TLR4 expression in non-exercise group and found a significantly improved
diabetic subjects.78,79 Thus, it appears that the ability of healing rate of an experimental wound in the exercised
exercise to ameliorate the symptoms of chronic disease group, compared with the non-exercise group. Although
may be linked, in part, to its anti-inflammatory effects. this research was limited by a fairly small number of sub-
It seems reasonably clear that increasing physical jects, the exercise effect in Emery’s study was substantial,
activity level or engaging in an exercise training regi- with 55% of the subjects in the exercised group showing
men can exert anti-inflammatory effects. An issue that complete healing at day four compared with 0% on the
remains unresolved is whether exercise training can exert non-exercised group. In an intent-to-treat intervention
an anti-inflammatory effect in the absence of changes in study of patients with venous leg ulcers, 77% of those
body fat.77,80 The literature in this area is mixed, but there randomized into an exercise intervention healed after
are several examples of exercise providing an indepen- 12 weeks, compared to 53% in the usual care group.84
dent anti-inflammatory effect. In one review by Beavers, Furthermore, subjects who completed at least 75% of
Brinkley, and Nicklas,74 the authors identified 19 studies their exercise sessions were more likely to heal and had
552 Chapter 44 Chronic Exercise and Immunity
a faster rate for wound healing. More work is needed to The mechanisms responsible for mediating the effects
determine if simple, cost-effective interventions, such as of exercise on vaccine efficacy are not fully understood.
exercise training, can alter the rate at which wounds heal. However, immunosenescence in aging is associated with
However, the paucity of literature on the topic prevents us an elevation in the ratio of memory T cells to naive T cells,
from making solid conclusions regarding practical strate- potentially reducing the ability of the adaptive immune
gies for clinicians or patients. system to respond to novel antigens. Exercise training has
been previously shown to reduce the memory to naive
T-cell ratio. 38 Exercise may prolong antibody response,
44.5.3 Exercise and Efficacy of Vaccines potentially by restoring the naive T cell level and subse-
quent ability to respond to novel antigen exposure.
Aging is associated with a decline in immune function,85
an increase in susceptibility to infections,86 and it can also
result in low-grade chronic inflammation.87 Aging-related
immunosenescence contributes to the increased incidence
44.6 CONCLUSION
and severity of infectious disease among older adults, who It is clear that regular, moderate, or extreme exercise has
experience a greater mortality rate from influenza infec- the potential to alter indices of immune function. While
tion and generally exhibit reduced vaccine efficacy com- it appears that regular exercise may offer some protection
pared to young adults.88,89 against upper-respiratory tract infection, provide anti-
Exercise training may improve immune competence inflammatory actions, and enhance the response to vac-
among older adults who have been administered an influ- cines, many unanswered questions remain. For example,
enza vaccine. Several cross-sectional studies in which excessive training (overtraining) has been linked to an
physically active older adults were compared to seden- increased risk of URTI, but researchers have questioned
tary controls have shown a greater influenza vaccine the reliability of both self-report of URTI and the direct
response.45,90,91 A cross-sectional comparison of older, method to detect pathogens in sputum.
physically active, moderately active, and sedentary groups The ability of exercise to improve the course of
showed that physical activity was associated with greater chronic disease via anti-inflammatory and other immune
response to influenza immunization. The older physically changes is an exciting avenue for researchers. These stud-
active group developed greater flu specific IgG and IgM ies will help to close the gap between the myriad ben-
titers two weeks post immunization, compared to mod- efits of exercise training and the available mechanisms
erate activity and sedentary groups.91 Peripheral blood to explain the benefits. Despite the gaps in our knowl-
mononuclear cell proliferation in vitro was also lower edge, it is clear that athletes can train effectively without
in the sedentary group. Keylock et al. demonstrated that excessive illness and that fitness exercisers adapt in pri-
physically active, highly fit, elderly individuals have higher marily positive immunological fashion to regular, mod-
antibody responses to the fluzone vaccine and a Th2 skew- erate exercise.
ing of the antibody response to tetanus toxoid when com-
pared to sedentary, low-fit, older adults.90 Taken together
these studies suggest that lifestyle factors, including regu-
lar exercise, may influence immune response to influenza
CLINICAL APPLICATIONS
immunization. • Regular exercise shifts circulating T cells toward a
A number of longitudinal studies have also been more anti-inflammatory profile, and reduces pro-
conducted to examine the role of exercise training on inflammatory cell surface receptors on monocytes.
influenza vaccine response. Kohut et al. reported that a • Excessive training may increase the risk of develop-
10-month exercise intervention in older adults resulted ing an URTI, possibly in part by alterations in sali-
in a greater increase in the influenza-specific antibody vary IgA secretion and flow rate.
titer and IFN-γ production following flu vaccine.92 These • Participation in regular exercise may improve wound
researchers also identified psychosocial factors such as healing and response to vaccine.
depression and sense of coherence as potential media- • High inflammation is implicated in many diseases,
tors of response to influenza vaccine. In a larger trial, and people who regularly exercise have lower pro-
144 sedentary, older adults were randomized to either a inflammatory immune cells. An anti-inflammatory
10-month aerobic training (n = 74) or a flexibility and effect of exercise training at least partially explains
balance program (n = 70).38 The intervention resulted in the lower chronic disease rate observed in people
a significant increase in seroprotection, determined as a who regularly exercise.
Hemagglutination Inhibition (HI) titer of >40, 24 weeks
after vaccination (30–100%). This is significant as it sug-
gests that an enhanced vaccine response following exer- ACKNOWLEDGMENTS
cise training can be maintained over a period greater than
the length of a typical flu season. However, and possibly This research was supported (in whole or in part) by HCA
more significantly, there was no difference in the incidence and/or an HCA affiliated entity. The views expressed in
of URTI between the two groups, although the aerobic this publication represent those of the author(s) and do not
exercise group exhibited reduced overall illness severity necessarily represent the official views of HCA or any of
and less sleep disturbance. its affiliated entities.
References 553
REFERENCES
1. Johannsen, N.M., et al., Effect of
different doses of aerobic exercise on
18. Ancuta, P., et al., Fractalkine preferen-
tially mediates arrest and migration of
33. Peters, C., et al., Influence of a moderate
exercise training on natural killer cyto-
44
total white blood cell (WBC) and WBC CD16+ monocytes. J Exp Med. 2003; toxicity and personality traits in cancer
subfraction number in postmenopausal 197(12): 1701–7. patients. Anticancer Res. 1994; 14(3A):
women: Results from DREW. PLoS One. 19. Hakkinen, T., K. Karkola, and S. Yla- 1033–6.
2012; 7(2): e31319. Herttuala, Macrophages, smooth muscle 34. Fairey, A.S., et al., Randomized con-
2. Lamina, S. and C.G. Okoye, Effect of cells, endothelial cells, and T-cells express trolled trial of exercise and blood immune
interval training program on white blood CD40 and CD40L in fatty streaks and function in postmenopausal breast cancer
cell count in the management of hyper- more advanced human atherosclerotic survivors. J Appl Physiol. 2005; 98(4):
tension: A randomized controlled study. lesions. Colocalization with epitopes of 1534–40.
Niger Med J. 2011; 52(4): 271–7. oxidized low-density lipoprotein, scaven- 35. Fahlman, M.M. and H.J. Engels,
3. Loprinzi, P.D. and S.M. Richart, White ger receptor, and CD16 (Fc gammaRIII). Mucosal IgA and URTI in American col-
blood cell counts mediate the effects of Virchows Arch. 2000; 437(4): 396–405. lege football players: A year longitudinal
physical activity on prostate-specific 20. Randolph, G.J., et al., The CD16(+) study. Med Sci Sports Exerc. 2005; 37(3):
antigen levels. Res Q Exerc Sport. 2014; (FcgammaRIII(+)) subset of human 374–80.
85(3): 409–13. monocytes preferentially becomes migra- 36. Flynn, M.G., et al., Effects of resistance
4. Horn, P.L., et al., Lower white blood cell tory dendritic cells in a model tissue set- training on selected indexes of immune
counts in elite athletes training for highly ting. J Exp Med. 2002; 196(4): 517–27. function in elderly women. J Appl
aerobic sports. Eur J Appl Physiol. 2010; 21. Coen, P.M., et al., Adding exercise to Physiol. 1999; 86(6): 1905–13.
110(5): 925–32. rosuvastatin treatment: Influence on 37. Raso, V., et al., Effect of resistance
5. Timmerman, K.L., et al., Exercise train- C-reactive protein, monocyte toll-like training on immunological parameters of
ing-induced lowering of inflammatory receptor 4 expression, and inflammatory healthy elderly women. Med Sci Sports
(CD14+CD16+) monocytes: A role in the monocyte (CD14+CD16+) population. Exerc. 2007; 39(12): 2152–9.
anti-inflammatory influence of exercise? J Metabolism. 2010; 59(12): 1775–83. 38. Walsh, N.P., et al., Position statement.
Leukocyte Biol. 2008; 84(5): 1271–1278. 22. Timmerman, K.L., et al., Exercise train- Part one: Immune function and exercise.
6. Markofski, M.M., et al., Resistance ing-induced lowering of inflammatory Exerc Immunol Rev. 2011; 17: 6–63.
exercise training-induced decrease in (CD14+CD16+) monocytes: A role in the 39. Mackinnon, L.T. and S.L. Hooper,
circulating inflammatory CD14+CD16+ anti-inflammatory influence of exercise? J Plasma glutamine and upper respiratory
monocyte percentage without weight loss Leukoc Biol. 2008; 84(5): 1271–8. tract infection during intensified training
in older adults. Eur J Appl Physiol. 2014; 23. Dam, V., T. Sikder, and S. Santosa, From in swimmers. Med Sci Sports Exerc.
114(8): 1737–48. neutrophils to macrophages: Differences 1996; 28(3): 285–90.
7. Randolph, G.J., C. Jakubzick, and C. in regional adipose tissue depots. Obes 40. Gleeson, M. and N.C. Bishop, The T cell
Qu, Antigen presentation by monocytes Rev. 2016; 17(1): 1–17. and NK cell immune response to exercise.
and monocyte-derived cells. Curr Opin 24. Odegaard, J.I. and A. Chawla, Ann Transplant. 2005; 10(4): 43–8.
Immunol. 2008; 20(1): 52–60. Mechanisms of macrophage activation 41. Michishita, R., et al., Effect of exercise
8. Cheong, C., et al., Microbial stimula- in obesity-induced insulin resistance. therapy on monocyte and neutrophil
tion fully differentiates monocytes to Nat Clin Pract Endocrinol Metab. 2008; counts in overweight women. Am J Med
DC-SIGN/CD209(+) dendritic cells for 4(11): 619–26. Sci. 2010; 339(2): 152–6.
immune T cell areas. Cell. 2010; 143(3): 25. Bruun, J.M., et al., Diet and exercise 42. Hack, V., et al., PMN cell counts and
416–29. reduce low-grade inflammation and mac- phagocytic activity of highly trained ath-
9. Odegaard, J.I. and A. Chawla, rophage infiltration in adipose tissue but letes depend on training period. J Appl
Alternative macrophage activation and not in skeletal muscle in severely obese Physiol. 1994; 77(4): 1731–5.
metabolism. Annu Rev Pathol. 2011; 6: subjects. Am J Physiol Endocrinol Metab. 43. Smith, J.A., et al., Exercise, training and
275–97. 2006; 290(5): E961–7. neutrophil microbicidal activity. Int J
10. Rocha, V.Z. and P. Libby, Obesity, 26. Yan, H., et al., Effect of moderate exer- Sports Med. 1990; 11(3): 179–87.
inflammation, and atherosclerosis. Nat cise on immune senescence in men. Eur J 44. Pawelec, G., Immunity and ageing in
Rev Cardiol. 2009; 6(6): 399–409. Appl Physiol. 2001; 86(2): 105–11. man. Exp Gerontol. 2006; 41(12):
11. McFarlin, B.K., et al., Physical activity 27. Moro-García, M.A., et al., Frequent 1239–42.
status, but not age, influences inflamma- participation in high volume exercise 45. Shinkai, S., et al., Physical activity and
tory biomarkers and toll-like receptor 4. J throughout life is associated with a more immune senescence in men. Med Sci
Gerontol A Biol Sci Med Sci. 2006; 61(4): differentiated adaptive immune response. Sports Exerc. 1995; 27(11): 1516–26.
388–93. Brain Behav Immun. 2014; 39: 61–74. 46. Arai, M.H., A.J. Duarte, and V.M.
12. Sloan, R.P., et al., Aerobic exercise 28. Walsh, N.P., et al., Position statement. Natale, The effects of long-term endur-
attenuates inducible TNF production in Part two: Maintaining immune health. ance training on the immune and
humans. J Appl Physiol. 2007; 103(3): Exerc Immunol Rev. 2011; 17: 64–103. endocrine systems of elderly men: The
1007–11. 29. Bigley, A.B., et al., Acute exercise role of cytokines and anabolic hormones.
13. McFarlin, B.K., et al., TLR4 is lower preferentially redeploys NK-cells with Immun Ageing. 2006; 3: 9.
in resistance-trained older women and a highly-differentiated phenotype and 47. Rall, L.C., et al., Effects of progressive
related to inflammatory cytokines. Med augments cytotoxicity against lymphoma resistance training on immune response
Sci Sports Exerc. 2004; 36(11): 1876–83. and multiple myeloma target cells. Part II: in aging and chronic inflammation.
14. Stewart, L.K., et al., Influence of exercise Impact of latent cytomegalovirus infec- Med Sci Sports Exerc. 1996; 28(11):
training and age on CD14+ cell-surface tion and catecholamine sensitivity. Brain 1356–65.
expression of toll-like receptor 2 and Behav Immun. 2015; 49: 59–65. 48. Lavoy, E.C., et al., CMV amplifies T-cell
4. Brain Behav Immun. 2005; 19(5): 30. Rincon, H.G., et al., Exercise in frail redeployment to acute exercise inde-
389–97. elderly men decreases natural killer cell pendently of HSV-1 serostatus. Med Sci
15. Flynn, M.G., et al., Toll-like receptor 4 activity. Aging (Milano). 1996; 8(2): Sports Exerc. 2014; 46(2): 257–67.
and CD14 mRNA expression are lower in 109–12. 49. Turner, J.E., et al., Latent cytomegalovi-
resistive exercise-trained elderly women. J 31. Kong, Y.Z., et al., Evidence for vascular rus infection amplifies CD8 T-lymphocyte
Appl Physiol. 2003; 95(5): 1833–42. macrophage migration inhibitory factor mobilisation and egress in response to
16. Ziegler-Heitbrock, L., The CD14+ in destabilization of human atheroscle- exercise. Brain Behav Immun. 2010;
CD16+ blood monocytes: Their role in rotic plaques. Cardiovasc Res. 2005; 24(8): 1362–70.
infection and inflammation. J Leukoc 65(1): 272–82. 50. Spielmann, G., et al., The effects of age
Biol. 2007; 81(3): 584–92. 32. McFarlin, B.K., et al., Chronic resistance and latent cytomegalovirus infection on
17. Rogacev, K.S., et al., Monocyte heteroge- exercise training improves natural killer the redeployment of CD8+ T cell subsets
neity in obesity and subclinical atheroscle- cell activity in older women. J Gerontol A in response to acute exercise in humans.
rosis. Eur Heart J. 2010; 31(3): 369–76. Biol Sci Med Sci. 2005; 60(10): 1315–8. Brain Behav Immun. 2014; 39: 142–51.
554 Chapter 44 Chronic Exercise and Immunity
51. He, C.S., et al., Influence of CMV/EBV in trained athletes: A randomized, muscle from insulin-resistant subjects.
serostatus on respiratory infection inci- double-blinded, placebo-controlled trial. Diabetes. 2008; 57(10): 2595–602.
dence during 4 months of winter training Nutrients. 2016; 8(11): 752. 79. Sriwijitkamol, A., et al., Reduced skeletal
in a student cohort of endurance athletes. 66. West, N.P., et al., Probiotic supplementa- muscle inhibitor of kappaB beta content
Eur J Appl Physiol. 2013; 113(10): tion for respiratory and gastrointestinal is associated with insulin resistance in
2613–9. illness symptoms in healthy physically subjects with type 2 diabetes: Reversal by
52. Gleeson, M., et al., Respiratory infection active individuals. Clin Nutr. 2014; 33(4): exercise training. Diabetes. 2006; 55(3):
risk in athletes: Association with antigen- 581–7. 760–7.
stimulated IL-10 production and salivary 67. Gleeson, M., et al., Effects of a 80. Bays, H., L. Blonde, and R. Rosenson,
IgA secretion. Scand J Med Sci Sports. Lactobacillus salivarius probiotic inter- Adiposopathy: How do diet, exercise
2012; 22: 410–7. vention on infection, cold symptom dura- and weight loss drug therapies improve
53. Smith, L.L., Tissue trauma: The underly- tion and severity, and mucosal immunity metabolic disease in overweight patients?
ing cause of overtraining syndrome? J in endurance athletes. Int J Sport Nutr Expert Rev Cardiovasc Ther. 2006; 4(6):
Strength Cond Res. 2004; 18(1): 185–93. Exerc Metab. 2012; 22(4): 235–42. 871–95.
54. Martin, S.A., B.D. Pence, and J.A. 68. Gleeson, M., N.C. Bishop, and L. 81. Kitahara, C.M., et al., Body mass index,
Woods, Exercise and respiratory tract Struszczak, Effects of Lactobacillus physical activity, and serum markers of
viral infections. Exerc Sport Sci Rev. casei Shirota ingestion on common cold inflammation, immunity, and insulin
2009; 37(4): 157–64. infection and herpes virus antibodies in resistance. Cancer Epidemiol Biomarkers
55. Yeh, S.H., et al., Regular tai chi chuan endurance athletes: A placebo-controlled, Prev. 2014; 23(12): 2840–9.
exercise enhances functional mobility and randomized trial. Eur J Appl Physiol. 82. Kay, S.J. and M.A. Fiatarone Singh, The
CD4CD25 regulatory T cells. Br J Sports 2016; 116(8): 1555–63. influence of physical activity on abdomi-
Med. 2006; 40(3): 239–43. 69. West, N.P., et al., Lactobacillus fermen- nal fat: A systematic review of the litera-
56. Yeh, S.H., et al., Regular Tai Chi Chuan tum (PCC ®) supplementation and gas- ture. Obes Rev. 2006; 7(2): 183–200.
exercise improves T cell helper function trointestinal and respiratory-tract illness 83. Emery, C.F., et al., Exercise accelerates
of patients with type 2 diabetes mellitus symptoms: A randomised control trial in wound healing among healthy older
with an increase in T-bet transcription athletes. Nutr J. 2011; 10: 30. adults: A preliminary investigation.
factor and IL-12 production. Br J Sports 70. Golia, E., et al., Inflammation and car- J Gerontol A Biol Sci Med Sci. 2005;
Med. 2009; 43(11): 845–50. diovascular disease: From pathogenesis to 60(11): 1432–6.
57. Perry, C., et al., Endurance exercise therapeutic target. Curr Atheroscler Rep. 84. O’Brien, J., et al., Evaluating the effec-
diverts the balance between Th17 cells 2014; 16(9): 435. tiveness of a self-management exercise
and regulatory T cells. PLoS One. 2013; 71. Hotamisligil, G.S., Endoplasmic reticu- intervention on wound healing, func-
8(10): e74722. lum stress and inflammation in obesity tional ability and health-related quality
58. Oliveira, M. and M. Gleeson, The influ- and type 2 diabetes. Novartis Found of life outcomes in adults with venous leg
ence of prolonged cycling on monocyte Symp. 2007; 286: 86–94; discussion ulcers: A randomised controlled trial. Int
Toll-like receptor 2 and 4 expression in 94–8, 162–3, 196–203. Wound J. 2017; 14(1): 130–137.
healthy men. Eur J Appl Physiol. 2010; 72. Lacativa, P.G. and M.L. Farias, 85. Krabbe, K.S., M. Pedersen, and H.
109(2): 251–7. Osteoporosis and inflammation. Arq Bruunsgaard, Inflammatory mediators in
59. Heath, G.W., et al., Exercise and the Bras Endocrinol Metabol. 2010; 54(2): the elderly. Exp Gerontol. 2004; 39(5):
incidence of upper respiratory tract infec- 123–32. 687–99.
tions. Med Sci Sports Exerc. 1991; 23(2): 73. Puntmann, V.O., P.C. Taylor, and M. 86. Myles, P.R., et al., The incidence of
152–7. Mayr, Coupling vascular and myocar- pneumonia using data from a computer-
60. Spence, L., et al., Incidence, etiology, and dial inflammatory injury into a common ized general practice database. Epidemiol
symptomatology of upper respiratory phenotype of cardiovascular dysfunction: Infect. 2009; 137(5): 709–16.
illness in elite athletes. Med Sci Sports systemic inflammation and aging—A 87. Plackett, T.P., et al., Aging and innate
Exerc. 2007; 39(4): 577–86. mini-review. Gerontology. 2011; 57: immune cells. J Leukoc Biol. 2004; 76(2):
61. Cox, A.J., et al., Respiratory symptoms 295–303. 291–9.
and inflammatory responses to Difflam 74. Beavers, K.M., T.E. Brinkley, and B.J. 88. Goodwin, K., C. Viboud, and L.
throat-spray intervention in half-mara- Nicklas, Effect of exercise training on Simonsen, Antibody response to influenza
thon runners: A randomised controlled chronic inflammation. Clin Chim Acta. vaccination in the elderly: A quantitative
trial. Br J Sports Med. 2010; 44(2): 2010; 411(11–12): 785–93. review. Vaccine. 2006; 24(8): 1159–69.
127–33. 75. Lambert, C.P., et al., Exercise but not 89. Castilla, J., et al., Decline in influenza
62. Ekblom, B., O. Ekblom, and C. Malm, diet-induced weight loss decreases skel- vaccine effectiveness with time after vac-
Infectious episodes before and after a etal muscle inflammatory gene expres- cination, Navarre, Spain, season 2011/12.
marathon race. Scand J Med Sci Sports. sion in frail obese elderly persons. J Appl Euro Surveill. 2013; 18(5): 20388.
2006; 16(4): 287–93. Physiol. 2008; 105(2): 473–8. 90. Keylock, K.T., et al., Exercise accelerates
63. Nicolucci, A.C., et al., Prebiotics reduce 76. Olesen, J., et al., Exercise training, but cutaneous wound healing and decreases
body fat and alter intestinal microbiota not resveratrol, improves metabolic and wound inflammation in aged mice. Am
in children who are overweight or with inflammatory status in skeletal muscle J Physiol Regul Integr Comp Physiol.
obesity. Gastroenterology. 2017; 153(3): of aged men. J Physiol. 2014; 592(8): 2008; 294(1): R179–84.
711–722. 1873–86. 91. Kohut, M.L., et al., Exercise and psy-
64. Wu, H., et al., Metformin alters the gut 77. Christiansen, T., et al., Exercise train- chosocial factors modulate immunity to
microbiome of individuals with treat- ing versus diet-induced weight-loss on influenza vaccine in elderly individuals. J
ment-naive type 2 diabetes, contributing metabolic risk factors and inflammatory Gerontol A Biol Sci Med Sci. 2002; 57(9):
to the therapeutic effects of the drug. Nat markers in obese subjects: A 12-week M557–62.
Med. 2017; 23(7): 850–858. randomized intervention study. Am J 92. Kohut, M.L., et al., The exercise-induced
65. Strasser, B., et al., Probiotic supplements Physiol Endocrinol Metab. 2010; 298(4): enhancement of influenza immunity is
beneficially affect tryptophan-kynurenine E824–31. mediated in part by improvements in
metabolism and reduce the incidence 78. Reyna, S.M., et al., Elevated toll-like psychosocial factors in older adults. Brain
of upper respiratory tract infections receptor 4 expression and signaling in Behav Immun. 2005; 19(4): 357–66.
45
CHAPTER
555
556 Chapter 45 HIV and Exercise
with these burdens ultimately depends on their psycho- multiple concurrent symptoms. 24–26 Common physical
45
logical state, social support network, and their stage of symptoms reported include diarrhea, loss of appetite, nau-
HIV disease. sea, muscle weakness, peripheral neuropathy, fever, dry
Many of the psychological complications experienced skin, and persistent cough. These are often experienced
by PLWHA are known to be treatable, and therefore it in conjunction with antiretroviral side effects for those
is imperative for caregivers and health care providers to placed on an ART regimen. As a result, the management
learn to recognize the signs of these conditions so they may of multiple symptoms has become a daily task for PLWHA
refer them to a specialist for further evaluation. Effective in an effort to maintain an optimal quality of life. 25,27,28
treatment for depression, a common psychiatric condition and ultimately leads to a chronic state of deconditioning
among PLWHA, has been shown to result in fewer physi- leading to functional aerobic impairment.
cal symptoms, better sleep quality, and improvements in As was the case before the discovery of antiretrovirals,
health-related quality of life.12,13 the association between the number of self-reported symp-
Many studies of various chronic diseases have inves- toms and disease status still allows for the use of reported
tigated consequences of distress among patients and symptom frequency as an indicator of disease progres-
reported positive associations with mood disturbance, sion and health-related quality of life. This has been able
poor treatment adherence, and negative health out- to assist health professionals with monitoring how well
comes.14–16 Similar findings have been reported among a patient is responding to current ART regimens. 25,29
HIV-related investigations.12,13,17 Although distress has Symptoms lasting anywhere between a few days to a few
been identified as an important measure to manage men- weeks increase the burden of disease among individuals,
tal health, and self-reported symptoms have become a often resulting in negative lifestyle habits. The side effects
common method used to indicate health status, the lit- and symptoms of HIV infection often have many patients
erature on self-reported symptom distress within the HIV turning to self-medication either by altering their daily
population is scarce. ART regimen or seeking additional alternative treatments
Generally, a level of distress is experienced when that may include illegal narcotics. Although the discov-
symptoms are present, and emerging data have shown a ery of ART has led to an increased lifespan and decreased
negative impact of psychological distress on HIV disease reports of AIDS and AIDS-related deaths, many scientists
progression.18 Increases in symptom distress have poten- have reported a complex variety of symptoms and side
tially negative consequences to both physical and psycho- effects associated with ART regimens, creating a meta-
logical health, which have been recently discovered with bolic syndrome affect.
a growing body of evidence supporting the psychoneuro-
immunology (PNI) framework as discussed by McCain
et al.19 Recent investigations have begun to show consis- 45.4.3 Antiretroviral Therapy
tent reports of psychological distress and disturbances
The timing for initiating treatment varies depending on viral
impairing immune function 20 as well as cytokine-induced
infection as well as the patient’s primary healthcare pro-
changes in neurotransmitter and neuroendocrine function,
vider, but generally it is recommended that patients begin
which have been shown to correlate with onset of depres-
an antiretroviral regimen if symptomatic, or asymptom-
sion and/or fatigue. 21 The burden of frequent symptoms is
atic but with a CD4 cell count <500 cells/µL.23 However,
known to negatively affect disease management and men-
for optimal results, many clinicians suggest ART regimens
tal health. 22 Identifying factors that are associated with
for asymptomatic patients with CD4 cell counts >500
increased symptom distress may provide possible strat-
cells/µL.3,23 Options for treatment can range from early,
egies to lessen the burden of HIV infection and related
aggressive intervention to postponing ART until a mea-
symptoms while also improving treatment adherence.
surable increase in disease progression has been observed.
A few emerging themes in managing psychological
Recommendations were released by the International AIDS
stressors is mindful meditation and motivational inter-
Society-USA Panel in early 2012 (Table 45.2), stating the
viewing. These techniques could prove beneficial with
decision as to when patients should start treatment needs
populations such as HIV patients and should be further
to be established after weighing “the benefits of treatment
explored to assist with the psychological burden. Recent
on morbidity and mortality against its risks, including tox-
updates to primary care guidelines by the Infectious
icity, resistance, drug interactions, and the costs and incon-
Diseases Society of America (IDSA) suggest including
venience of lifelong treatment.”3
depression and posttraumatic stress disorder screening
More recently, certain ART medications, such as
as part of a patient’s initial evaluation and at periodical
Truvada, have also been recommended as a form as pre-
intervals thereafter. 23 Women have also been shown to
vention for high-risk individuals, such as the partner of a
have increased rates of sexual and/or domestic abuse and
person with HIV. It is still too early to draw any formative
twice the risk of depression, indicating increased needs for
conclusions about long-term use for someone not carrying
services able to accommodate these needs as well. 23
the HIV virus.
45.4.2 Physical Consequences
All clinical populations face a large variety of disease-
45.4.4 Toxic Side Effects
related physical and psychological symptoms, but preva- The majority of side effects associated with ART are
lence rates of self-reported symptoms are generally over physiological in nature and directly alter metabolic pro-
50% among PLWHA, ranging from a single symptom to cesses, resulting in increased circulating blood lipids,
558 Chapter 45 HIV and Exercise
exercise can be both safe and beneficial for this clinical there are no reported exercise-related interventions lasting
45
population. However, it is recommended that if aerobic longer than six months, making it impossible to determine
exercise is to be performed by this population, that they the long-term effects on overall health and life longev-
do so at a low- or moderate-intensity level, as data are ity. However, benefits observed in a short time frame as
lacking to draw the conclusion that a high-intensity aer- reported by multiple investigations would suggest long-
obic regimen will not have a negative impact on overall term gains in the physical and psychological well-being of
health or quality of life in this population. PLWHA who participate in routine physical activity.
Responses and adaptations to exercise training will
vary depending on current fitness level, disease status,
and whether or not that patient is currently on an ART CLINICAL APPLICATIONS
regimen. Asymptomatic individuals generally respond in
a manner similar to someone without HIV of the same • Increases in daily physical activity and/or weekly
body size, age, and gender. However, some may be more exercise have proven to have beneficial effects for
deconditioned due to psychological disturbances com- PLWHA with no indications of reductions in immu-
monly associated with daily sedentary behavior such as nity or negative health outcomes.
depression or anxiety, among others. Further, individu- • Chronic stress is a daily struggle for anyone manag-
als with symptomatic status will generally be on a current ing a clinical condition with added stigmatization.
ART regimen, which also puts them at an increased risk Weekly exercise regimens have proven to reduce
of CVD. Therefore, extra caution should be taken prior to physiological and psychological stress, but more
beginning an exercise prescription. attention should also be given to additional methods
Although exercise itself is not going to eliminate the of effective, stress-relieving practices in addition to
burdens of health care costs, social stigmatization, or exercise.
other daily stressors, it could potentially reduce the health • Regardless of disease status, all individuals with
consequences of chronic stress, improve quality of life, HIV are at an increased risk for cardiovascular dis-
and possibly increase the reduced lifespan of PLWHA. ease and therefore should seek consent from their
Most of the negative side effects from both the virus primary care doctor prior to initiating a new exer-
itself and treatment-related toxicities, including impaired cise regimen. Individuals can safely begin with daily
glucose tolerance, fatigue, increased blood lipid profile, walks at a light intensity prior to receiving consent if
chronic inflammation, anxiety, depression, circulating no other health concerns are evident.
cortisol, and others, are known to improve with rou- • For individuals in a deconditioned state of aerobic
tine exercise in various populations. Additional evidence impairment, it is important to set practical goals
from longitudinal studies have clearly shown that modest since all activity can take moderate or vigorous
increases in CRF can decrease the risk of all-cause mortal- efforts. Gradual increases in daily step counts by a
ity as well as the risk of most chronic diseases. Whether or few hundred steps each day may be more suitable
not PLWHA would have a similar response to long-term as opposed to 30 minutes of moderate intensity
exercise is unknown due to insufficient research. Further, activity.
REFERENCES
1. Samaras, K., Prevalence and pathogenesis infection determined by competitive PCR. among a population of HIV-infected
of diabetes mellitus in HIV-1 infection Science. 1993; 259(5102): 1749–54. adults in Nigeria. Int J STD AIDS. 2016;
treated with combined antiretroviral 7. Piatak, M., Jr., et al., Viral dynamics in 27(11): 938–49.
therapy. J Acquir Immune Defic Syndr. primary HIV-1 infection. Lancet. 1993; 13. Sheth, S.S., et al., Association between
2009; 50(5): 499–505. 341(8852): 1099. depression and nonadherence to antiret-
2. Samaras, K., et al., Prevalence of meta- 8. Gordon, S.N., et al., Severe depletion roviral therapy in pregnant women with
bolic syndrome in HIV-infected patients of mucosal CD4+ T cells in AIDS-free perinatally acquired HIV. AIDS Care.
receiving highly active antiretroviral simian immunodeficiency virus-infected 2015; 27(3): 350–4.
therapy using international diabetes sooty mangabeys. J Immunol. 2007; 14. Cohen, S., D. Janicki-Deverts, and G.E.
foundation and adult treatment panel III 179(5): 3026–34. Miller, Psychological stress and disease.
criteria associations with insulin resis- 9. Grossman, Z., et al., Pathogenesis of HIV JAMA. 2007; 298(14): 1685–7.
tance, disturbed body fat compartmental- infection: What the virus spares is as 15. Duijts, S.F., M.P. Zeegers, and B.V.
ization, elevated C-reactive protein, and important as what it destroys. Nat Med. Borne, The association between stress-
hypoadiponectinemia. Diabetes Care. 2006; 12(3): 289–95. ful life events and breast cancer risk: A
2007; 30(1): 113–119. 10. Mehandru, S., et al., Primary HIV-1 meta-analysis. Int J Cancer. 2003; 107(6):
3. Thompson, M.A., et al., Antiretroviral infection is associated with preferential 1023–9.
treatment of adult HIV infection: 2012 depletion of CD4+ T lymphocytes from 16. Shih, M. and P.A. Simon, Health-related
recommendations of the International effector sites in the gastrointestinal tract. quality of life among adults with seri-
Antiviral Society-USA panel. JAMA. J Exp Med. 2004; 200(6): 761–70. ous psychological distress and chronic
2012; 308(4): 387–402. 11. Anuurad, E., A. Semrad, and L. medical conditions. Qual Life Res. 2008;
4. Control, C.f.D. and Prevention, HIV/ Berglund, Human immunodeficiency 17(4): 521–8.
AIDS basic statistics. Online at http:// virus and highly active antiretroviral 17. Jaggers, J.R., et al., Psychological cor-
www.cdc.gov/hiv/basics/statistics. html. therapy-associated metabolic disorders relates of HIV-related symptom distress.
Accessed. 2014; 1. and risk factors for cardiovascular dis- J Assoc Nurses AIDS Care. 2014; 25(4):
5. Weber, J., The pathogenesis of HIV-1 ease. Metab Syndr Relat Disord. 2009; 309–17.
infection. Br Med Bull. 2001; 58: 61–72. 7(5): 401–10. 18. Robinson, F.P., H.L. Mathews, and L.
6. Piatak, M., Jr., et al., High levels of 12. Adejumo, O., et al., Psychiatric disorders Witek-Janusek, Stress and HIV disease
HIV-1 in plasma during all stages of and adherence to antiretroviral therapy progression: Psychoneuroimmunological
562 Chapter 45 HIV and Exercise
framework. J Assoc Nurses AIDS Care. 37. Jain, R.G., et al., Metabolic complica- randomized, controlled trial. Ann Intern
1999; 10(1): 21–31. tions associated with antiretroviral Med. 2000; 133(5): 348–355.
19. McCain, N.L., et al., Effects of stress therapy. Antiviral Res. 2001; 51(3): 54. Thoni, G., et al., Reduction of fat accu-
management on PNI-based outcomes 151–77. mulation and lipid disorders by individu-
in persons with HIV disease. Res Nurs 38. Collaboration, A.T.C., Causes of death alized light aerobic training in human
Health. 2003; 26(2): 102–17. in HIV-1—infected patients treated immunodeficiency virus infected patients
20. Miller, A.H., Depression and immunity: with antiretroviral therapy, 1996–2006: with lipodystrophy and/or dyslipidemia.
A role for T cells? Brain Behav Immun. Collaborative analysis of 13 HIV cohort Diabetes Metab. 2002; 28(5): 397–404.
2010; 24(1): 1–8. studies. Clin Infect Dis. 2010; 50(10): 55. Tiozzo, E., et al., Short-term combined
21. Moussavi, S., et al., Depression, chronic 1387–1396. exercise training improves the health of
diseases, and decrements in health: 39. Erlandson, K.M., et al., Self-reported HIV-infected patients. J AIDS HIV Res.
Results from the World Health Surveys. body fat change in HIV-infected men is 2013; 5(3): 80–89.
Lancet. 2007; 370(9590): 851–8. a marker of decline in physical health- 56. Perna, F.M., et al., Cardiopulmonary and
22. Holzemer, W.L., HIV and AIDS: The related quality of life with aging, inde- CD4 cell changes in response to exercise
symptom experience. What cell counts pendent of co-morbidity. PloS One. 2014; training in early symptomatic HIV infec-
and viral loads won’t tell you. Am J Nurs. 9(12): e114166. tion. Med Sci Sports Exerc. 1999; 31(7):
2002; 102(4): 48–52. 40. Tiozzo, E., et al., A cross-sectional assess- 973–9.
23. Aberg, J.A., et al., Primary care guide- ment of metabolic syndrome in HIV- 57. LaPerriere, A., et al., Exercise and
lines for the management of persons infected people of low socio-economic psychoneuroimmunology. Med Sci Sports
infected with HIV: 2013 update by status receiving antiretroviral therapy. Exerc. 1994; 26(2): 182–90.
the HIV Medicine Association of the Diabetol Metab Syndr. 2015; 7: 15. 58. LaPerriere, A.R., et al., Exercise interven-
Infectious Diseases Society of America. 41. Hand, G.A., et al., Impact of aerobic and tion attenuates emotional distress and
Clin Infect Dis. 2014; 58(1): 1–10. resistance exercise on the health of HIV- natural killer cell decrements following
24. Norval, D.A., Symptoms and sites of pain infected persons. Am J Lifestyle Med. notification of positive serologic status
experienced by AIDS patients. S Afr Med 2009; 3(6): 489–499. for HIV-1. Biofeedback Self-Regul. 1990;
J. 2004; 94(6): 450–4. 42. Jaggers, J.R. and G.A. Hand, Health 15(3): 229–242.
25. Portillo, C.J., W.L. Holzemer, and F.Y. benefits of exercise for people living with 59. Moore, G., et al., ACSM’s Exercise
Chou, HIV symptoms. Annu Rev Nurs HIV A review of the literature. Am J Management for Persons With Chronic
Res. 2007; 25: 259–91. Lifestyle Med. 2014: 1559827614538750. Diseases and Disabilities, 4E. Human
26. Lee, K.A., et al., Symptom experience in 43. O’Brien, K.K., et al., Effectiveness of Kinetics; 2016.
HIV-infected adults: A function of demo- aerobic exercise for adults living with 60. Jaggers, J.R. and K.M. King, Strategies
graphic and clinical characteristics. J Pain HIV: Systematic review and meta-analysis for increasing physical activity and
Symptom Manage. 2009; 38(6): 882–93. using the Cochrane Collaboration proto- healthy lifestyles for the individual with
27. Phillips, K.D., et al., Physiological and col. BMC Infect Dis. 2016; 16: 182. human immunodeficiency virus. ACSM’s
psychological correlates of fatigue in 44. Engelson, E.S., et al., Body composi- Health Fitness J. 2017; 21(4): 42–45.
HIV disease. Biol Res Nurs. 2004; 6(1): tion and metabolic effects of a diet and 61. LaPerriere, A., et al., Effects of aerobic
59–74. exercise weight loss regimen on obese, exercise training on lymphocyte subpopu-
28. Jaggers, J.R., et al., Associations between HIV-infected women. Metabolism. 2006; lations. Int J Sports Med. 1994; 15 Suppl
physical activity and sedentary time 55(10): 1327–1336. 3: S127–30.
on components of metabolic syndrome 45. Hand, G.A., et al., Moderate intensity 62. MacArthur, R.D., S.D. Levine, and
among adults with HIV. AIDS Care. exercise training reverses functional aero- T.J. Birk, Supervised exercise training
2014; 26(11): 1387–92. bic impairment in HIV-infected individu- improves cardiopulmonary fitness in
29. Bedell, G., Daily life for eight urban gay als. AIDS Care. 2008; 20(9): 1066–1074. HIV-infected persons. Med Sci Sports
men with HIV/AIDS. Am J Occup Ther. 46. Jaggers, J.R., et al., A home-based Exerc. 1993; 25(6): 684–8.
2000; 54(2): 197–206. exercise intervention to increase physical 63. Jaggers, J.R., et al., Aerobic and resis-
30. Church, T.S., et al., Associations between activity among people living with HIV: tance training improves mood state
cardiorespiratory fitness and C-reactive Study design of a randomized clinical among adults living with HIV. Int J
protein in men. Arterioscler Thromb trial. BMC Public Health. 2013; 13: 502. Sports Med. 2015; 36(2): 175–81.
Vasc Biol. 2002; 22(11): 1869–76. 47. Jaggers, J.R., et al., Results of a nine 64. Patil, R., et al., Effects of fitness training
31. Church, T.S., et al., Usefulness of month home-based physical activity inter- on physical fitness parameters and quality
cardiorespiratory fitness as a predictor vention for people living with HIV. Int J of life in human immunodeficiency virus-
of all-cause and cardiovascular disease Clin Trials. 2016; 3(3): 106–119. positive Indian females. 2016.
mortality in men with systemic hyperten- 48. MacArthur, R.D., S.D. Levine, and 65. Dolan, S.E., et al., Effects of a supervised
sion. Am J Cardiol. 2001; 88(6): 651–6. T.J. Birk, Supervised exercise training home-based aerobic and progressive
32. Eisenmann, J.C., et al., Combined influ- improves cardiopulmonary fitness in resistance training regimen in women
ence of cardiorespiratory fitness and body HIV-infected persons. Med Sci Sports infected with human immunodeficiency
mass index on cardiovascular disease risk Exerc. 1993. virus: A randomized trial. Arch Intern
factors among 8–18 year old youth: The 49. Dudgeon, W.D., et al., Moderate- Med. 2006; 166(11): 1225–31.
Aerobics Center Longitudinal Study. Int J intensity exercise improves body composi- 66. Mutimura, E., et al., Exercise training
Pediatr Obes. 2007; 2(2): 66–72. tion and improves physiological markers reduces central adiposity and improves
33. Katzmarzyk, P.T., et al., Metabolic syn- of stress in HIV-infected men. Isrn Aids. metabolic indices in HAART-treated
drome, obesity, and mortality: Impact of 2012; 2012: 145127. HIV-positive subjects in Rwanda: A ran-
cardiorespiratory fitness. Diabetes Care. 50. Neidig, J.L., B.A. Smith, and D.E. domized controlled trial. AIDS Res Hum
2005; 28(2): 391–7. Brashers, Aerobic exercise training for Retroviruses. 2008; 24(1): 15–23.
34. Sui, X., et al., A prospective study of car- depressive symptom management in 67. Fitch, K., et al., Effects of lifestyle modi-
diorespiratory fitness and risk of type 2 adults living with HIV infection. J Assoc fication and metformin on atherosclerotic
diabetes in women. Diabetes Care. 2008; Nurses AIDS Care. 2003; 14(2): 30–40. indices among HIV-infected patients with
31(3): 550–5. 51. Smith, B.A., et al., Aerobic exercise: the metabolic syndrome. AIDS. 2012;
35. Sui, X., M.J. LaMonte, and S.N. Blair, Effects on parameters related to fatigue, 26(5): 587–97.
Cardiorespiratory fitness and risk of dyspnea, weight and body composition in 68. Stringer, W.W., et al., The effect of exer-
nonfatal cardiovascular disease in HIV-infected adults. AIDS. 2001; 15(6): cise training on aerobic fitness, immune
women and men with hypertension. Am J 693–701. indices, and quality of life in HIV+
Hypertens. 2007; 20(6): 608–15. 52. Terry, L., et al., Exercise training in HIV- patients. Med Sci Sports Exerc. 1998;
36. Wang, C.Y., et al., Cardiorespiratory 1-infected individuals with dyslipidemia 30(1): 11–6.
fitness levels among US adults 20–49 and lipodystrophy. Med Sci Sports Exerc. 69. Terry, L., E. Sprinz, and J. Ribeiro,
years of age: Findings from the 1999– 2006; 38(3): 411–7. Moderate and high intensity exercise
2004 National Health and Nutrition 53. Grinspoon, S., et al., Effects of testoster- training in HIV-1 seropositive individu-
Examination Survey. Am J Epidemiol. one and progressive resistance training als: A randomized trial. Int J Sports Med.
2010; 171(4): 426–35. in eugonadal men with AIDS wastinga 1999; 20(02): 142–146.
46
CHAPTER
563
564 Chapter 46 Exercise, Aging, and Immunity
function of the vagus nerve is to control heart rate, which individuals. The immune risk profile (IRP)27–29 charac-
46
is typically measured by heart rate recovery following terizes multiple immune function biomarkers that are
exercise (HRR) and heart rate variability (HRV). A major used to predict morbidity and mortality in older adults,
adaptation to long-term exercise training is a decrease in including inverted CD4+/CD8+ T cell ratio, 30 reductions in
HRR and HRV, signifying the parasympathetic nervous naïve T cells, corresponding increases in memory T cells,
system is becoming more efficient in stimulating the recip- decreased T-cell proliferation and activation, reduced co-
rocating sympathetic nervous system. Thus, exercise train- stimulatory molecules expression, diminished cytokine
ing may increase efferent vagus nerve activity, and this signaling, and latent cytomegalovirus (CMV) and Epstein
increased activity may contribute to the anti-inflammatory Barr virus (EBV) infection. 29 Whereas age-related altera-
effect of exercise. This hypothesis is supported by our tions in antigen-presenting cells and antibody-producing
cross-sectional study that demonstrated HRR was the best B lymphocytes and their migration are apparent, 31–33 the
predictor of CRP in aged adults.20 However, this hypoth- dramatic decline in humoral and CMI responses to many
esis has not yet been fully investigated in a prospective immune challenges is predominantly the consequence of
or definitive manner. In a recently published study, it has senescent T cells.34 Indeed, virus-activated CD4+ T helper
been shown that lower HRR measured 60 seconds after (Th) cells provide critical cytokine signals that stimu-
cardiopulmonary exercise was associated with higher neu- late B cells to differentiate and produce antibodies. Th1
trophil-lymphocyte ratio (NLR), which is a marker of sys- cells stimulate antibody responses, interferon (IFN)-γ
temic inflammation and similar results for high-sensitivity production, and CTL memory, whereas Th2 cells stimu-
CRP in 1,624 human subjects.21 This finding supports late antibody responses and IL-10, which attenuates Th1
the hypothesized on parasympathetic effect on systemic responses.35,36 Aging results in reduced Th1 cytokine pro-
inflammation. duction in response to stimulation creating a cytokine
imbalance represented by low IFN-γ and high IL-10 pro-
duction, which is directly related to poor responses and
46.3.3 Gut Microbiota higher risk for infection.37–41
Recently, the relationship between the gut microbiome
and inflammaging has drawn the attention of many
researchers. Thevaranjan et al. demonstrated that, in
46.5 EFFECT OF EXERCISE
mice, aging is associated with dysbiosis of gut microbiota, ON T-CELL MEDIATED
increased intestinal permeability, and systemic inflam-
mation. 22 However, aged mice raised under germ-free IMMUNITY IN THE AGED
conditions did not express elevated pro-inflammatory
Cross-sectional studies report that elderly runners
cytokines, and their macrophages maintained anti-micro-
exhibited a higher in vitro stimulated T cell prolifera-
bial activity compared to their conventional counterparts.
tive response and improved effector cytokine production
Furthermore, a relationship between gut microbiota and
compared to elderly, sedentary individuals.42 Also, highly
skeletal muscle has been posited. 23 It is suggested that gut
conditioned elderly women43 and older male recreational
microbiota may affect skeletal muscle metabolic activity,
runners42 displayed higher T cell proliferative responses
muscle size, composition, and function, 24 which could
at rest to mitogens than those of age-matched sedentary
have implications for sarcopenia and muscle function in
peers without any differences in absolute T-cell number.
older adults. Taken together, modulation of an age-dys-
Masters athletes have increased Treg mRNA expression
related gut microbiome may be a potential therapeutic
for FoxP3 and TGF-β and higher plasma IL-10 after an
strategy to reduce inflammaging. Indeed, our recent work
incremental exercise to exhaustion, compared to age-
suggests that endurance exercise training can alter the gut
matched controls.44 Lymphocyte proliferation to the influ-
microbiome and its metabolites, albeit in young adults. 25
enza antigen is greater in participants reporting either
Of interest are short-chain fatty acids, specifically butyr-
regular activity or less intense activity compared to sed-
ate, which can act in an anti-inflammatory fashion by
entary individuals.45 Therefore, regular exercise training
promoting differentiation of T-regulatory cells. 26 In our
may be an effective method of preventing or retarding
study, we reported an endurance exercise training-induced
impaired immune function in aging individuals. Results
increase in gut bacteria capable of producing butyrate as
from these studies indicate that older regular exercisers
well as increased butyrate concentrations. 25 However, as
may have an improved Th1 response, which may enhance
this study was performed in younger adults, the role that
CMI, improve defense against intracellular pathogens,
this form of exercise plays in age-related dysbiosis, butyr-
and reduce the risk of morbidity due to infections. It is
ate production, and inflammaging is unknown.
not known, however, if exercise only acts in a preventative
manner to delay immunosenescence or whether exercise
46.4 AGING AND T CELL- has immune restorative properties in previously sedentary
individuals.
MEDIATED IMMUNITY Results from exercise training studies in this popula-
tion have not reported consistent findings. Our group has
Cell mediated immunity (CMI), which largely involves the reported no significant difference between high-fit, low-fit,
antigen-specific activation of T cells that mediate the acti- and sedentary older adults in IFN-γ or IL-10 production.46
vation of other effector immune cells (e.g. macrophages, Although Kapsai et al. found no effect after eight months
NK cells, B cells, and other T cells), is diminished in older of endurance and resistance training on CD4+/CD8+ T
566 Chapter 46 Exercise, Aging, and Immunity
cell co-receptor expression in frail, elderly individuals,47 support the hypothesis that moderate exercise enhances
Shimizu et al. reported that six months of combined T-cell immune function in older adults. Unfortunately,
moderate exercise was shown to be effective in increas- at this time, the mechanism for these improvements are
ing co-stimulatory receptor CD28 expression on circulat- unknown.
ing T cells in elderly subjects.48 Later, their group found
a 12-week, combined endurance and resistance training
significantly elevated CD28+CD8+ cells and CD80+CD14+ 46.6 EXERCISE AND
cells.49 Since co-stimulation through CD28 enhances pro-
duction of IL-2 and IFN-γ in T cells activated by anti- HUMORAL IMMUNITY
gens and/or mitogens, these results indicate that longer
Among the many effects of aging is a general decrease
term, multi-modal exercise interventions can be effec-
in the ability of the body to respond to antigenic agents
tive in restoring T-cell responsiveness in this population
including not only pathogens, but also vaccines.60 An
while promoting strength and cardiovascular fitness. It
immune response to infection or vaccination results in the
was reported that 10 months of aerobic exercise training
production of antibodies that are capable of binding to
enhanced the antibody responses and granzyme B activ-
and neutralizing foreign invaders such as pathogenic bac-
ity to the influenza vaccine in older adults. 50 However, a
teria and viruses. This response is commonly known as
12-month aerobic exercise intervention did not change
humoral immunity and is one of the major components of
natural killer cell cytotoxicity and T-lymphocyte prolif-
the adaptive immune system. Antibodies are secreted into
eration in postmenopausal women. 51
body fluids by plasma cells—mature B cells that respond
In order to gain a better understanding of the potential
to pathogens in an antigen-specific manner. The aging
mechanisms by which exercise might improve CMI with
process is associated with a loss of both B-cell number as
aging, we have shown that four months of treadmill run-
well as a reduction in B-cell function.61
ning in mice improved naïve to memory T-cell subset ratios
in both CD4+ and CD8+ cells in the spleen of old mice, 52
and that six months of moderate aerobic exercise training
in elderly individuals may be sufficient to lead to minimal 46.6.1 Cross-Sectional Studies
increases in some measure of immune function, while not A cross-sectional examination of antibody response to
affecting others in previously sedentary elderly. 53 Further, influenza vaccine in older highly-fit men and women com-
Kohut et al. reported greater Th1 cytokine production, pared to less-fit older adults demonstrated that the highly-
IL-2, and IFN-γ in response to HSV-1 infection after eight fit, physically-active individuals had a greater antibody
weeks of moderate aerobic training in mice. 54 Conversely, response to both the H1N1- and B-strains of the influ-
not all studies report conclusive evidence that exercise enza vaccine than did their less-active counterparts.62
definitively improves CMI. 55,56 Reasons for this may be Additionally, the highly-fit subjects had a greater produc-
a product of small sample size, relatively short interven- tion of more potent IgG2 vs. less potent IgG1 antibod-
tions, and differences in exercise modality and intensity ies after recall vaccination with a tetanus toxoid booster,
in which exercise is performed during these interventions. suggesting an exercise effect on antibody isotype switch-
Few studies have examined the impact of exercise on ing, which may be important for defense against infec-
in vivo measures of CMI. Delayed-type hypersensitiv- tion in older individuals. In a similar study, it was found
ity (DTH) reactions in the skin have been used to assess that older individuals who exercised vigorously had higher
CMI in vivo. Sedentary elderly men have been shown to antibody responses, including both IgM and IgG isotype,
have decreased DTH response when compared to their to the influenza vaccine when compared to individuals of
physically-active counterparts. 57 High-intensity resistance the same age who exercised either moderately or not at
training has not been shown to change DTH responsive- all.45 Elderly men with a moderate or intense training life-
ness in aged individuals, 58 but aerobic exercise combined style had significantly stronger and longstanding antibody
with an enriched diet in an elderly population found a responses to influenza vaccine compared to the individu-
small exercise effect on the DTH response that was sus- als without a training lifestyle.63
tained over a 17-week period when compared to the con- This evidence is further supported by a study which
trol group that exhibited a decline.59 An important aspect found that physical activity level is positively correlated
of these studies is the clinical relevance of DTH response, with antibody response to influenza vaccination in older
which has long been used as an overall indicator of the adults.64 Recently, a study of patients with coronary heart
strength of cell-mediated immunity. However, a major disease demonstrated that regular physical activity in this
limitation to using DTH as a functional measure of CMI population is independently associated with increased
is the large variability typically observed, making it dif- anti-influenza antibody titer after vaccination,65 a result
ficult to interpret studies with small sample numbers. that extends this finding to a population that has risk
Clearly, further study is warranted with larger samples factors for poor immunological responses beyond that
sizes to determine the effects of exercise training on CMI of the normal aging process. In addition to these results
in aged individuals. from influenza and tetanus toxoid vaccination, some evi-
In summary, there is evidence that regular physical dence exists that exercise can improve antibody response
activity can have a beneficial effect on specific aspects of to novel immune activators. Administration of keyhole
T-cell mediated immune status in elderly individuals, with limpet hemocyanin (KLH) was found to elicit increased
endurance exercise being the most beneficial. Both ani- antibody responses in physically-active compared to sed-
mal and human cross-sectional and interventional studies entary, older adults, 57 importantly demonstrating that
Clinical Applications 567
exercise can generate greater protective immune responses Several studies have examined some of the aforemen-
46
even to antigens to which an individual has no prior expo- tioned measures in rodent models of aging, which allow
sure history. for a more in-depth look at potential mechanisms by which
exercise might cause these changes. However, results from
these studies have not always been consistent with those
46.6.2 Prospective Training Studies undertaken in humans for reasons that are not yet clear. A
These cross-sectional studies are further supported by training program involving eight weeks of treadmill run-
prospective exercise training studies which examine the ning failed to elicit a higher antibody response to herpes
antibody responses in previously sedentary, older individu- simplex virus in mice, although other markers of immune
als who undergo a standardized training program under function including lymphocyte production of cytokines
the supervision of the researchers. A 10-month aerobic were increased by exercise training. 54 A similar study,
exercise training program increased antibody responses which subjected rats to 10 weeks of treadmill training,
to the influenza vaccine out to three months post-vacci- demonstrated no increase in antibody or other responses
nation in older adults when compared to sedentary con- to administration of KLH when these rats were compared
trol subjects.50 A similar clinical study using a relatively to sedentary control animals.73
large number of subjects (n = 144) found that although 10 Despite these challenges, mechanistic studies in older
months of aerobic exercise training did not induce higher rodents have shed some light as to possible causes for the
peak anti-influenza antibody responses in older adults changes in antibody responses to vaccination and infec-
when compared to older individuals who underwent a non- tion seen in older adults. Blockage of β-adrenergic recep-
aerobic, flexibility-only training program, it did increase tors via nadolol ablated the exercise-induced increase
the duration of the protective antibody response, which in antibody- and cell-mediated immune function seen
was sufficient to cover the entire influenza season.66 This is in response to herpes simplex virus infection in mice.74
important because aging results in a quicker reduction in Similarly, blockage of endogenous opioid activity, which
protective antibody levels when compared to younger indi- is increased with exercise, decreased antibody response
viduals’ response to vaccination.67 This increase in dura- to albumin injection compared to exercised mice that
tion of protection was concomitant with reduced symptom received a placebo implantation.75 Although these stud-
severity of upper respiratory tract infections in this group. ies provide some insight into possible causes for exercise-
In a smaller cohort of the same group of participants, the induced increases in immune responses in older adults,
exercise training program increased the antibody response much more work remains to be done on this front before a
to KLH administration,68 providing more evidence that satisfactory mechanism for these changes can be provided.
endurance exercise can increase immune responses to anti-
genic agents even in the absence of prior exposure.
Besides the commonly used aerobic exercise interven- 46.7 CONCLUSION
tion, we examined the effects of Tai Chi and Qigong (a
fusion of martial arts with meditation and traditional Overall, in healthy older adults, regular aerobic exercise
Chinese medicine) training on the antibody response to appears to reduce chronic low-level inflammation and aug-
influenza vaccine in older adults. Participants who prac- ment both cell- and antibody-mediated immune responses.
ticed moderate 3 × 60 min Tai Chi and Qigong for 20 The benefits of regular exercise on the immune system and
weeks had significantly higher antibody responses at three other systems should persuade practitioners to suggest regu-
and 20 weeks post-vaccine, whereas the control group did lar exercise to otherwise healthy older adults. Unfortunately,
not (Yang 2007). at this time, the mechanism(s) responsible for the beneficial
Supporting the above data on plasma antibody effects on the aged immune system are unknown.
responses, several investigators have found positive effects
of exercise on general salivary antibody levels, an impor-
tant first line of defense against pathogens introduced by CLINICAL APPLICATIONS
oral routes. Moderate-intensity cycling for six months
caused a 40% increase in salivary IgA levels in older • Aging is associated with chronic, low-grade inflam-
men and women with no change in the sedentary control mation, a condition referred to as “inflammaging.”
group.69 A separate study demonstrated that an acute bout • “Inflammaging” is associated with increased mor-
of exercise can increase both concentration and secretion bidity and mortality among the aged
rate of salivary IgA even in individuals > 75 years of age.70 • Aging-induced changes in the immune system,
However, 16 weeks of aerobic exercise in older adults including reduced innate and adaptive immune
did not change salivary IgA levels, although exercise did response, is referred to immunosenescence.
increase plasma IgA as well as plasma IgG and IgM anti- • Immunosenescence results in poor vaccine efficacy
bodies as seen in other studies,71 suggesting that duration, and defense against microbial infection.
intensity, or mode of exercise may play a major role in • Regular, moderate-intensity exercise training may
determining immunological outcomes. This is partially improve both these age-associated conditions of
supported by a study that included both endurance and inflammaging and immunosenescence.
resistance exercise components in a training program for • While the mechanisms are largely unknown,
older adults and which resulted in significant increases in exercise-induced changes in body fat, parasympa-
both salivary IgA concentrations and secretion rates com- thetic activity, and/or the gut microbiome may be
pared to the pre-exercise intervention time point.72 responsible.
568 Chapter 46 Exercise, Aging, and Immunity
REFERENCES
1. Franceschi, C. and M. Bonafe, 18. Kawanishi, N., et al., Exercise training Reduced activation ex vivo, decreased
Centenarians as a model for healthy inhibits inflammation in adipose tissue expansion in CTL culture in vitro, and
aging. Biochem Soc Trans. 2003; 31(2): via both suppression of macrophage infil- blunted response to influenza vaccination
457–61. tration and acceleration of phenotypic in vivo in the elderly. J Immunol. 2004;
2. Woods, J.A., T.W. Lowder, and K.T. switching from M1 to M2 macrophages 172(6): 3437–46.
Keylock, Can exercise training improve in high-fat-diet-induced obese mice. 36. McElhaney, J.E. and J.P. Dutz, Better influ-
immune function in the aged? Ann N Y Exerc Immunol Rev. 2010; 16: 105–18. enza vaccines for older people: What will it
Acad Sci. 2002; 959: 117–27. 19. Tracey, K.J., Reflex control of immunity. take? J Infect Dis. 2008; 198(5): 632–4.
3. Nicklas, B.J. and T.E. Brinkley, Exercise Nat Rev Immunol. 2009; 9(6): 418–28. 37. McElhaney, J.E., et al., T cell responses
training as a treatment for chronic 20. Vieira, V.J., et al., Independent relation- are better correlates of vaccine protection
inflammation in the elderly. Exerc Sport ship between heart rate recovery and in the elderly. J Immunol. 2006; 176(10):
Sci Rev. 2009; 37(4): 165–70. C-reactive protein in older adults. J Am 6333–9.
4. Vieira, V.J., et al., Reduction in trunk fat Geriatr Soc. 2007; 55(5): 747–51. 38. Bernstein, E., et al., Immune response to
predicts cardiovascular exercise training- 21. Ackland, G.L., et al., Autonomic regula- influenza vaccination in a large healthy
related reductions in C-reactive protein. tion of systemic inflammation in humans: elderly population. Vaccine. 1999; 17(1):
Brain Behav Immun. 2009; 23(4): A multi-center, blinded observational 82–94.
485–91. cohort study. Brain Behav Immun. 2018; 39. McElhaney, J.E., et al., Granzyme B:
5. Kohut, M.L., et al., Aerobic exercise, but 67: 47–53. Correlates with protection and enhanced
not flexibility/resistance exercise, reduces 22. Thevaranjan, N., et al., Age-associated CTL response to influenza vaccination
serum IL-18, CRP, and IL-6 independent microbial dysbiosis promotes intestinal in older adults. Vaccine. 2009; 27(18):
of beta-blockers, BMI, and psychoso- permeability, systemic inflammation, 2418–25.
cial factors in older adults. Brain Behav and macrophage dysfunction. Cell Host 40. Murasko, D.M., et al., Role of humoral
Immun. 2006; 20(3): 201–9. Microbe. 2017; 21(4): 455–466.e4. and cell-mediated immunity in protection
6. Nicklas, B.J., et al., Exercise training and 23. Backhed, F., et al., Mechanisms underly- from influenza disease after immuniza-
plasma C-reactive protein and interleu- ing the resistance to diet-induced obesity tion of healthy elderly. Exp Gerontol.
kin-6 in elderly people. J Am Geriatr Soc. in germ-free mice. Proc Natl Acad Sci U S 2002; 37(2–3): 427–39.
2008; 56(11): 2045–52. A. 2007; 104(3): 979–84. 41. Corsini, E., et al., High interleukin-10
7. Martins, R.A., et al., The effect of 24. Grosicki, G.J., R.A. Fielding, and M.S. production is associated with low anti-
aerobic versus strength-based training Lustgarten, Gut microbiota contrib- body response to influenza vaccination in
on high-sensitivity C-reactive protein in ute to age-related changes in skeletal the elderly. J Leukoc Biol. 2006; 80(2):
older adults. Eur J Appl Physiol. 2010; muscle size, composition, and function: 376–82.
110(1): 161–9. Biological basis for a gut-muscle axis. 42. Shinkai, S., et al., Physical activity and
8. Martins, R.A., et al., Effects of aerobic Calcif Tissue Int. 2017. immune senescence in men. Med Sci
and strength-based training on metabolic 25. Allen, J.M., et al., Exercise alters gut Sports Exerc. 1995; 27(11): 1516–26.
health indicators in older adults. Lipids microbiota composition and function in 43. Nieman, D.C., et al., Physical activity and
Health Dis. 2010; 9: 76. lean and obese humans. Med Sci Sports immune function in elderly women. Med
9. Starkweather, A.R., The effects of exer- Exerc, 2017. Sci Sports Exerc. 1993; 25(7): 823–31.
cise on perceived stress and IL-6 levels 26. Furusawa, Y., et al., Commensal 44. Minuzzi, L.G., et al., Lifelong training
among older adults. Biol Res Nurs. 2007; microbe-derived butyrate induces the dif- improves anti-inflammatory environment
8(3): 186–94. ferentiation of colonic regulatory T cells. and maintains the number of regulatory
10. Rodriguez-Miguelez, P., et al., Whole- Nature. 2013; 504(7480): 446–50. T cells in masters athletes. Eur J Appl
body vibration improves the anti-inflam- 27. Koch, S., et al., Cytomegalovirus infec- Physiol. 2017; 117(6): 1131–1140.
matory status in elderly subjects through tion: A driving force in human T cell 45. Kohut, M.L., et al., Exercise and psy-
toll-like receptor 2 and 4 signaling immunosenescence. Ann N Y Acad Sci. chosocial factors modulate immunity to
pathways. Mech Ageing Dev. 2015; 150: 2007; 1114: 23–35. influenza vaccine in elderly individuals.
12–9. 28. Pawelec, G., et al., Human immunose- J Gerontol A Biol Sci Med Sci. 2002;
11. MacNee, W., R.A. Rabinovich, and nescence: Does it have an infectious 57(9): M557–62.
G. Choudhury, Ageing and the border component? Ann N Y Acad Sci. 2006; 46. Keylock, K.T., et al., Higher antibody,
between health and disease. Eur Respir J. 1067: 56–65. but not cell-mediated, responses to vacci-
2014; 44(5): 1332–52. 29. Simpson, R.J. and K. Guy, Coupling nation in high physically fit elderly. J Appl
12. Beavers, K.M., et al., Long-term physical aging immunity with a sedentary lifestyle: Physiol (1985). 2007; 102(3): 1090–8.
activity and inflammatory biomarkers in Has the damage already been done?—A 47. Kapasi, Z.F., et al., Effects of an exercise
older adults. Med Sci Sports Exerc. 2010; mini-review. Gerontology. 2010; 56(5): intervention on immunologic parameters
42(12): 2189–96. 449–58. in frail elderly nursing home residents. J
13. Valentine, R.J., et al., Stronger relation- 30. Wikby, A., et al., The immune risk Gerontol A Biol Sci Med Sci. 2003; 58(7):
ship between central adiposity and profile is associated with age and gender: 636–43.
C-reactive protein in older women than Findings from three Swedish popula- 48. Shimizu, K., et al., Effect of moder-
men. Menopause. 2009; 16(1): 84–9. tion studies of individuals 20–100 years ate exercise training on T-helper cell
14. Wu, D., et al., Aging up-regulates expres- of age. Biogerontology. 2008; 9(5): subpopulations in elderly people. Exerc
sion of inflammatory mediators in mouse 299–308. Immunol Rev. 2008; 14: 24–37.
adipose tissue. J Immunol. 2007; 179(7): 31. Shurin, M.R., G.V. Shurin, and G.S. 49. Shimizu, K., et al., Monocyte and T-cell
4829–39. Chatta, Aging and the dendritic cell responses to exercise training in elderly
15. Starr, M.E., et al., Age-associated system: Implications for cancer. Crit Rev subjects. J Strength Cond Res. 2011;
increase in cytokine production during Oncol Hematol. 2007; 64(2): 90–105. 25(9): 2565–72.
systemic inflammation-II: The role of 32. Siegrist, C.A. and R. Aspinall, B-cell 50. Kohut, M.L., et al., Moderate exercise
IL-1beta in age-dependent IL-6 upregula- responses to vaccination at the extremes improves antibody response to influenza
tion in adipose tissue. J Gerontol A Biol of age. Nat Rev Immunol. 2009; 9(3): immunization in older adults. Vaccine.
Sci Med Sci. 2015; 70(12): 1508–15. 185–94. 2004; 22(17–18): 2298–306.
16. Vieira, V.J., et al., Effects of exercise and 33. Wols, H.A., et al., Migration of immature 51. Campbell, P.T., et al., Effect of exercise
low-fat diet on adipose tissue inflamma- and mature B cells in the aged microen- on in vitro immune function: A 12-month
tion and metabolic complications in obese vironment. Immunology. 2010; 129(2): randomized, controlled trial among
mice. Am J Physiol Endocrinol Metab. 278–90. postmenopausal women. J Appl Physiol
2009; 296(5): E1164–71. 34. Linton, P. and M.L. Thoman, T cell (1985). 2008; 104(6): 1648–55.
17. Vieira, V.J., et al., Effects of diet and senescence. Front Biosci. 2001; 6: 52. Woods, J.A., et al., Exercise training
exercise on metabolic disturbances in D248–61. increases the naive to memory T cell ratio
high-fat diet-fed mice. Cytokine. 2009; 35. Deng, Y., et al., Age-related impaired in old mice. Brain Behav Immun. 2003;
46(3): 339–45. type 1 T cell responses to influenza: 17(5): 384–92.
References 569
53. Woods, J.A., et al., Effects of 6 months 61. Frasca, D., R.L. Riley, and B.B. hemocyanin (KLH) in previously seden-
of moderate aerobic exercise training on Blomberg, Humoral immune response tary older adults. Brain Behav Immun.
immune function in the elderly. Mech
Ageing Dev. 1999; 109(1): 1–19.
54. Kohut, M.L., G.W. Boehm, and J.A.
and B-cell functions including immu-
noglobulin class switch are downregu-
lated in aged mice and humans. Semin
69.
2008; 22(6): 923–32.
Shimizu, K., et al., Effects of exercise, age
and gender on salivary secretory immu-
46
Moynihan, Moderate exercise is associ- Immunol. 2005; 17(5): 378–84. noglobulin A in elderly individuals. Exerc
ated with enhanced antigen-specific cyto- 62. Keylock, K.T., et al., Higher antibody, Immunol Rev. 2007; 13: 55–66.
kine, but not IgM antibody production but not cell-mediated, responses to vacci- 70. Sakamoto, Y., et al., Effect of exer-
in aged mice. Mech Ageing Dev. 2001; nation in high physically fit elderly. J Appl cise, aging and functional capacity
122(11): 1135–50. Physiol. 2007; 102(3): 1090–8. on acute secretory immunoglobulin
55. Ogawa, K., et al., Habitual exercise 63. de Araujo, A.L., et al., Elderly men with A response in elderly people over 75
did not affect the balance of type 1 and moderate and intense training lifestyle years of age. Geriatr Gerontol Int.
type 2 cytokines in elderly people. Mech present sustained higher antibody 2009; 9(1): 81–8.
Ageing Dev. 2003; 124(8–9): 951–6. responses to influenza vaccine. Age 71. Martins, R.A., et al., Effects of aerobic
56. Flynn, M.G., et al., Effects of resistance (Dordr). 2015; 37(6): 105. conditioning on salivary IgA and plasma
training on selected indexes of immune 64. Schuler, P.B., P.A. Leblanc, and T.S. IgA, IgG and IgM in older men and
function in elderly women. J Appl Marzilli, Effect of physical activity on women. Int J Sports Med. 2009; 30(12):
Physiol. 1999; 86(6): 1905–13. the production of specific antibody in 906–12.
57. Smith, T.P., S.L. Kennedy, and M. response to the 1998–99 influenza virus 72. Akimoto, T., et al., Effects of 12 months
Fleshner, Influence of age and physical vaccine in older adults. J Sports Med Phys of exercise training on salivary secretory
activity on the primary in vivo antibody Fitness. 2003; 43(3): 404. IgA levels in elderly subjects. Br J Sports
and T cell-mediated responses in men. J 65. Keshtkar-Jahromi, M., et al., Antibody Med. 2003; 37(1): 76–9.
Appl Physiol. 2004; 97(2): 491–8. response to influenza immunization in 73. Barnes, C.A., et al., Exercise does not
58. Rall, L.C., et al., Effects of progressive coronary artery disease patients: A con- modify spatial memory, brain autoim-
resistance training on immune response trolled trial. Vaccine. 2009; 28(1): 110–3. munity, or antibody response in aged
in aging and chronic inflammation. 66. Woods, J.A., et al., Cardiovascular exer- F-344 rats. Neurobiol Aging. 1991; 12(1):
Med Sci Sports Exerc. 1996; 28(11): cise training extends influenza vaccine 47–53.
1356–65. seroprotection in sedentary older adults: 74. Kohut, M.L., et al., Exercise training-
59. Chin, A.P.M.J., et al., Immunity in frail The immune function intervention trial. J induced adaptations of immune response
elderly: A randomized controlled trial Am Geriatr Soc. 2009; 57(12): 2183–91. are mediated by beta-adrenergic recep-
of exercise and enriched foods. Med Sci 67. Goodwin, K., C. Viboud, and L. tors in aged but not young mice. J Appl
Sports Exerc. 2000; 32(12): 2005–11. Simonsen, Antibody response to influenza Physiol. 2004; 96(4): 1312–22.
60. Vu, T., et al., A meta-analysis of effec- vaccination in the elderly: A quantitative 75. Kapasi, Z.F., et al., The role of endog-
tiveness of influenza vaccine in persons review. Vaccine. 2006; 24(8): 1159–69. enous opioids in moderate exercise
aged 65 years and over living in the 68. Grant, R.W., et al., Cardiovascular exer- training-induced enhancement of the
community. Vaccine. 2002; 20(13–14): cise intervention improves the primary secondary antibody response in mice.
1831–6. antibody response to keyhole limpet Phys Ther. 2001; 81(11): 1801–9.
X
PA RT
Pulmonary Medicine
Nicholas A. Smyrnios, MD, FACP, FCCP
571
47
CHAPTER
Respiratory Symptoms
Jeremy B. Richards, MD and Richard M. Schwartzstein, MD
573
574 Chapter 47 Respiratory Symptoms
of ventilation, tachypnea, or an inability to speak in full to dyspnea (e.g. CCQ, OCD). As dyspnea manifests as a
sentences. Nevertheless, symptoms characterize what constellation of symptoms not solely defined by perceived
patients are experiencing and can only come from them. functional limitation, multidimensional assessment using
The timing of respiratory symptoms and conditions that the MDP instrument has been increasingly used in clinical
precipitate or alleviate the discomfort can clarify the and research settings.4,5 MDP measurements, as compared
impact of the symptom on the patient. Understanding to other objective dyspnea scales, have demonstrated ade-
the “language of dyspnea,” developed from descriptive quate sensitivity to detect changes in symptoms of dys-
research of patients with a variety of respiratory diseases, pnea over time. 2 In addition, the MDP gives us insight
can help clinicians understand the significance of their into the relationship between the sensations of breathing
patients’ symptoms. discomfort and the affective or emotional responses asso-
This chapter focuses on the physiologic and clinical ciated with this frequently debilitating symptom. Anxiety,
significance of several common respiratory symptoms. fear, and frustration are commonly associated with cer-
The clinical utility of quantitative dyspnea scales, the tain types of dyspnea. 5
multidimensional nature of breathing discomfort, and Quantitative dyspnea scales can be used for any
the consequences of dyspnea are briefly discussed. The patients with respiratory disease but may be of most use
role for and utility of pulmonary function tests (PFTs) for patients with COPD as a component of determin-
are briefly reviewed below, but a more complete descrip- ing the Global Initiative for Obstructive Lung Disease
tion is beyond the scope of this discussion. Clinical and (GOLD) stage of disease severity, which has prognostic
pathophysiologic details of specific disease states such and therapeutic value for this patient population.6
as asthma and chronic obstructive pulmonary disease
(COPD) will be addressed in other chapters. This chapter
does cover how specific elements of the physical examina- 47.2.2 Pulmonary Function Tests
tion, in concert with reported symptoms, can narrow the
differential diagnosis. Pulmonary function testing refers to maneuvers in which
spirometry, lung volumes, inspiratory and expiratory
pressures, and/or diffusion limitation of carbon monoxide
47.2 OBJECTIVE ASSESSMENT OF (DLCO) are measured. Confusion regarding PFTs arises
from imprecise use of the term “pulmonary function tests”
RESPIRATORY SYMPTOMS in clinical practice to refer to measurements of spirometry
alone. It is more precise to consider PFTs to include spi-
Respiratory symptoms can be due to a variety of patho- rometry, lung volume, and DLCO measurements.
physiological processes involving disparate organ systems. PFTs can provide objective data regarding a patient’s
A general understanding of the use of PFTs is helpful in specific respiratory impairment and can provide impor-
developing a preliminary, physiologically based approach tant insight into the cause of respiratory symptoms. Not
to respiratory symptoms. We will also comment briefly on all respiratory symptoms are best assessed by PFTs, but
some of the common pitfalls associated with the use of several common symptoms are due to diseases that may be
pulse oximetry. diagnosed by PFTs. For example, the diagnosis of COPD,
which may affect between 4 and 10% of adults in the
United States,7 is dependent on spirometric measurements.
47.2.1 Objective Dyspnea Scales COPD is typically suspected based on clinical symptoms,
There are several quantitative scoring systems designed but further evaluation by measuring spirometry confirms
to assess the severity and impact of dyspnea in patients or excludes the actual diagnosis.
with respiratory disease. Examples of such scales include When obtaining PFTs, a trained respiratory therapist
the Medical Research Council (MRC) dyspnea question- or technologist can influence the quality of data obtained;
naire, the modified MRC (mMRC), the COPD assessment the instructions, prompts, and encouragement provided to
test (CAT), the oxygen cost diagram (OCD), the COPD the patient prior to and during the test significantly affect
Clinical Questionnaire (CCQ), the multidimensional dys- the patient’s respiratory maneuvers. Normal values for
pnea profile (MDP), and other scoring systems. These PFTs are determined from predictive equations developed
scales assess different components of the sensation of from large, descriptive studies and incorporate an indi-
breathless.1,2 The scoring systems demonstrate relatively vidual patient’s age, gender, race and height.8
similar performance with regard to assessing symptom
severity in clinical practice, such that one scale is not
clearly superior to another.3 Assessing dyspnea severity 47.2.2.1 Spirometry
using a quantitative scale can be useful to characterize Spirometry refers to measurements of the flow and volume
baseline symptom burden, but following dyspnea scales generated when a patient performs a forced vital capacity
in response to therapeutic interventions is of less certain (FVC) exhalation; these tests are critical for assessment
clinical utility. 2 of airway resistance. To perform a FVC exhalation, the
The majority of available dyspnea scales assess patient- patient takes in as big a breath as possible to completely
reported perceptions of functional disability attributable fill the lungs with air (to total lung capacity or TLC), and
to dyspnea (e.g. MRC, mMRC, CAT) or more general per- then forcibly exhales as rapidly as possible until no more
ceptions of healthcare-associated quality of life attributed air can be emptied from the lungs (to the residual volume
47.2 Objective Assessment of Respiratory Symptoms 575
or RV). In addition to measuring the FVC, determining 47.2.2.3 Diffusion Limitation of Carbon Monoxide
47
the volume of air the patient is able to exhale in one sec- The DLCO measures the transfer of carbon monoxide
ond (FEV1) is important in diagnosing obstructive air- (CO) across the alveolar-capillary basement membrane.
ways diseases. If a patient has increased airways resistance DLCO is considered a surrogate for oxygen transfer
and is unable to generate high flows from total lung capac- across the basement membrane and into the circulation.
ity, the FEV1 relative to the FVC will be reduced. A patient performs the DLCO maneuver by inhaling air
Patients may develop increased airways resistance due with a small, known concentration of CO to TLC and
to airway narrowing from airway inflammation, mucus holding his breath for 10 seconds to allow sufficient time
accumulation, and smooth muscle hypertrophy (e.g. as for diffusion of CO into alveoli and for transfer of CO
a consequence of chronic asthma) or from loss of teth- across the alveolar-capillary basement membrane. The
ering of the airways leading to airway collapse during amount of CO transferred into the blood stream is deter-
active exhalation (e.g. COPD). Increased airways resis- mined by the difference in the quantity of CO in inhaled
tance causes obstruction of airflow during exhalation, air (which is known) minus the quantity of CO in exhaled
which results in a decreased FEV1 out of proportion to air (which is measured).
the FVC. Therefore, the ratio of the FEV1 to the FVC The severity of the reduction is expressed as the percent
(FEV1/FVC) will be reduced in such patients. In patients predicted. A DLCO between 60 and 79% of predicted is
with severe airways resistance, expiratory time is insuf- consistent with a mild reduction in DLCO, between 40
ficient to permit exhalation of a full vital capacity and and 59% is a moderate reduction, and <40% a severe
RV may be elevated. An elevated RV is referred to as “air reduction. The DLCO is reduced when there is destruc-
trapping.” tion of the alveolar-capillary interface (reduced surface
Obstructive airways diseases are conditions that area for diffusion) or there is an increase in the distance
decrease the FEV1/FVC ratio. COPD and asthma are by between the alveolus and the capillary across which the
far the most common causes of obstructive airways dis- gas must diffuse. Table 47.1 lists diseases associated with
ease. Bronchiectasis, tracheobronchomalacia, and sar- a decreased DLCO.
coidosis are much less common causes. While a reduced
FEV1, FVC, and a preserved (or increased) FEV1/FVC
ratio suggest a restrictive pulmonary disease, lung vol- 47.2.2.4 Pulse Oximetry
umes (particularly TLC) must be measured separately to Assessment of oxygen saturation with a pulse oximeter is
confirm restrictive disease. common in both inpatient and ambulatory environments.
Normal oxygen saturation does not mean that a patient’s
47.2.2.2 Lung Volume Testing lungs are functioning appropriately. Patients with many
cardiopulmonary conditions leading to dyspnea (e.g.
Lung volumes may be measured by one of two methods. asthma, pulmonary embolism, pneumonia, CHF) may
Plethysmography refers to measuring lung volumes based hyperventilate, leading to normal oxygen saturation with
on the change of pressure and volume of a known quantity a low PaCO2 . Such hyperventilation can mask the pres-
of air in a closed container (a so-called “body box”) to ence of severe pulmonary disease. An accurate interpre-
calculate lung volumes via Boyle’s Law. Helium dilution tation of the oxygen saturation must include an overall
refers to the measurement of lung volumes based on the assessment of the patient’s clinical status and an accompa-
differential exhaled helium concentration and the helium nying arterial blood gas.
concentration in a closed, external container. Since helium
is an inert gas that does not cross the alveolar-capillary
basement membrane, the concentration of helium after TABLE 47.1 Causes of decreased DLCO categorized by
the gas has equilibrated between the patient’s lungs and lung volume
the external container of helium provides a measure-
ment of a patient’s lung volumes. This technique is used Causes of decreased DLCO
to measure functional residual capacity (FRC), or relax- High lung • Advanced COPD
ation volume at the end of a passive exhalation. Once this volumes • Bronchiectasis
volume is known, other volumes (TLC and RV) can be • Cystic fibrosis
determined with spirometric determinants of the change
Normal lung • Pulmonary vascular disease (e.g. pulmonary
in volume as the patient goes through various maneu- volumes vasculitis or primary pulmonary hypertension)
vers. Helium dilution may underestimate lung volumes in • Early pulmonary fibrosis
patients with poor ventilation (e.g. patients with large bul- • Anemia*
lae) or patients with global hypoventilation (e.g. patients
Low lung • Pulmonary fibrosis
with severe COPD and air trapping). volumes • Sarcoidosis
A TLC measurement below 80% of predicted is con- • Congestive heart failure
sistent with restrictive disease. When FRC is greater than • Pneumonectomy**
the predicted value, one should consider reduced elastic
recoil of the lung as a potential cause, most commonly due *Anemia causes reduced DLCO by reducing hemoglobin binding sites for carbon
monoxide; this will occur even in the presence of normal lungs and pulmonary
to emphysema. Specifically, a TLC of >120% of predicted vasculature
is consistent with hyperinflation. Gas-trapping and an ele- **DLCO corrected for alveolar volume (DLCO/VA) should be normal assuming the
vated RV will commonly also be present in such patients. remaining lung tissue functions normally
576 Chapter 47 Respiratory Symptoms
47
Figure 47.1 Physiologic mechanisms producing dyspnea. Respiratory symptoms included in the term dyspnea result from stim-
ulation of a range of receptors throughout the respiratory system, as well as from corollary discharge thought to originate in the
motor cortex when efferent neural discharges are sent to the ventilatory muscles. Qualitative phrases used to describe the sen-
sations are noted based on research on and interviews with patients experiencing dyspnea. N Engl J Med 1995;333:1547–1553.
Copyright 1995 Massachusetts Medical Society. All rights reserved.
TABLE 47.4 The language of dyspnea: association of qualitative descriptors and physiologic mechanisms of shortness of
breath
Qualitative descriptors Pathophysiology
Chest tightness or constriction Bronchoconstriction, interstitial edema (asthma, myocardial ischemia)
Increased work or effort of breathing Airway obstruction, neuromuscular disease, chest wall disease (COPD, moderate to severe
asthma, myopathy, kyphoscoliosis)
Inability to get a deep breath Hyperinflation (COPD, asthma)
Air hunger, need to breathe, urge to Increased drive to breathe (CHF, pulmonary embolism, moderate to severe airway
breathe obstruction)
Heavy breathing, rapid breathing, Deconditioning
breathing more
hunger,” or an increased urge to breathe. 27 Air hunger of “inability to get a deep breath” or “air hunger” despite
occurs in diseases associated with an increased urge to the absence of pulmonary or cardiovascular pathology.
breathe (e.g. severe asthma, pulmonary embolism, acute
hypoxia, exercise in patients with underlying lung dis-
ease). Air hunger may include the sense of an inability to 47.3.4 Essentials of the History
get a deep breath, as seen with hyperinflation. Patients
may express several of these sensations simultaneously, as 47.3.4.1 Timing: Acute vs. Chronic Dyspnea
many diseases are characterized by multiple pathophysi- There are relatively few conditions that result in an abrupt
ological derangements (e.g. asthma may result in chest onset of breathing discomfort (Table 47.5). These tend
tightness due to bronchoconstriction and increased effort to be due to sudden changes in airway resistance, sud-
of breathing due to hyperinflation and airway resistance). den hypoxemia, or sudden increases in pulmonary vas-
Deconditioning, the inability to achieve maximal cular pressures. With treatment, these conditions often
workloads with exertion because of reduced aerobic capac- improve as rapidly as they begin. On occasion, dyspnea
ity of the heart and limb muscles, afflicts both healthy may develop acutely in a patient with a chronic pulmo-
people and patients with cardiopulmonary diseases. It nary disease and limited pulmonary reserve from a sud-
deserves special attention because deconditioning is a den metabolic stress (e.g. a patient with severe COPD who
state that can be corrected with an exercise program.28–30 develops an infection with a high fever and metabolic aci-
Patients with underlying cardiopulmonary diseases are dosis). The need to increase ventilation in the setting of
often assumed to be limited by their disease when they are
actually deconditioned. For example, when patients with
asthma were asked why they had reduced exercise capac- TABLE 47.5 Acute causes of dyspnea
ity, they stated that it was because of their asthma. When
Laryngospasm
that same group was subjected to formal exercise testing,
their primary limit was cardiovascular deconditioning, Paroxysmal vocal cord dysfunction
not airway reactivity. 28 Patients with COPD, even those Exercise-induced laryngeal obstruction
with severe airway obstruction (FEV1 < 40% predicted),
are often limited by leg fatigue rather than by poor venti- Bronchospasm
latory reserve. 31 Dyspnea associated with deconditioning Acute asthma
has been characterized as “heavy breathing,” “breathing
more”,19 or “huffing and puffing.” Acute interstitial edema
When questioning a patient with shortness of breath, Hypoxemia
it is best to inquire about the nature of the “breathing dis-
Acute mucous plugging of airways
comfort.” This phrase is generic and allows one to elicit
specific qualities of a patient’s distress without introduc- Acute foreign body aspiration
ing bias toward a particular sensation. At times it may Pulmonary embolism
be helpful to show patients a dyspnea questionnaire and
ask them to select up to three phrases that best describe Pneumothorax
their breathing discomfort. Patients may have different Increases in Pulmonary Vascular Pressures
sensations (and different kinds of dyspnea due to differ-
ent problems) under varying conditions (e.g. a patient with Myocardial ischemia
interstitial lung disease and superimposed airway reactiv- Acute mitral valve regurgitation
ity, or a patient with asthma who also is deconditioned).
Pulmonary embolism
It is also important to distinguish between dyspnea due to
chest wall pain and breathing discomfort that is a primary Sudden Increased Demand for Ventilation
sensation. For example, a patient with fractured ribs may Acute metabolic acidosis
have severe pain with inspiration and express a sensation
47.3 Dyspnea 579
a sudden metabolic stress to meet increased demands for edema fluid to the central circulation during the night
47
oxygen consumption and/or carbon dioxide elimination with consequent increases in pulmonary vascular pres-
may result in both increased work of breathing and an sures in a patient with compromised left ventricular func-
increased urge to breathe. tion is believed to be the pathophysiologic basis for this
Chronic dyspnea tends to develop slowly over the condition. Acute myocardial ischemia at night may mimic
course of weeks or months. Often patients have difficulty PND, but it is unlikely to have a recurring pattern, may be
pinpointing the exact onset of symptoms or attribute associated with chest pain, and is less likely to be relieved
symptoms to a respiratory infection despite resolution by sitting upright.
of all systemic infectious symptoms except for chronic One cause of dyspnea that never occurs while sleep-
breathing discomfort. Not infrequently, the date that a ing is hyperventilation syndrome. The primary clinical
patient gives up cigarette smoking is, in retrospect, con- manifestations of hyperventilation syndrome are inter-
sciously or unconsciously related to the onset of dyspnea. mittent episodes of tachypnea and subjective discom-
Causes of chronic dyspnea include COPD, fibrotic lung fort characterized by air hunger or an urge to breathe.
disease, pleural effusion, progressive chest wall deformi- Despite taking large tidal volumes, patients perceive that
ties, chronic CHF, and recurrent pulmonary emboli. The they cannot get a deep breath. Patients with hyperventi-
chronicity of these conditions may be masked by lifestyle lation syndrome experience dyspnea during the day, but
changes. As walking up stairs becomes progressively dif- objective assessment reveals normal spirometry, normal
ficult, a patient with COPD may move to a building with DLCO, and normal chest imaging. While sleeping, these
elevators or to the ground floor. Children are called upon patients have normal breathing patterns and appear
to do shopping. Deconditioning becomes superimposed quite comfortable.
on the underlying cardiopulmonary disorder, making even
routine tasks uncomfortable. Patients may present with
seemingly new symptoms over the course of a few weeks; 47.3.4.3 Position
however, the reality is that the patient has a chronic condi- Dyspnea that occurs with or is relieved by changes in posi-
tion and is only able to avoid recurring dyspnea because of tion should prompt a consideration of abnormalities in the
avoidance of physical activity. ventilatory pump (i.e., the muscles of ventilation and the
configuration of the chest wall), focal lung abnormalities
that lead to hypoxemia when blood flow is increased to
47.3.4.2 Timing: Night vs. Day that area, or redistribution of fluid into the central circula-
Nocturnal dyspnea, waking in the middle of the night with tion in patients with a history of CHF.
acute respiratory distress, can be an extremely frightening Orthopnea is dyspnea that occurs in the recumbent
experience for a patient. The majority of cases are due to position. The most common explanation is the redistri-
one or more of three problems: bronchospasm, aspiration, bution of blood pooled from dependent veins into the
and CHF. central circulation, leading to increased pulmonary vas-
Patients with asthma may have worsening symptoms cular pressures in the setting of compromised cardiac
at night because of a trough in the level of bronchodilator function. However, given the very rapid onset and resolu-
medications, triggering a bronchospasm by gastroesopha- tion of orthopnea with a change in position, it is probably
geal reflux through a reflex mediated by the vagus nerve secondary to stimulation of intracardiac (possibly right
when acid enters the esophagus, or as a result of exposure atrial) or pulmonary vascular receptors rather than the
to allergens localized to the bedroom. Nocturnal sensa- development of interstitial edema. In very obese patients
tions are usually similar to daytime asthma attacks (e.g. or patients with a distended abdomen due to ascites, the
chest tightness and increased effort to breathe), though large abdomen increases the work of breathing with posi-
the precipitating factors are generally different. At times, tional changes as it now requires more force to initiate an
patients may cough without discernible wheezing. The inspiration due to the weight of the abdomen on the chest
association of symptoms with changes in the home envi- wall.32 Severe dyspnea when bending over to tie shoes is
ronment (e.g. new carpeting or a new pet) may give clues common in these patients; there is little room for the dia-
to the precipitant. phragm to move downward during in inspiration. Lying
Recurrent aspiration causing nocturnal dyspnea can supine, which removes gravity as a factor in pulling the
be an elusive diagnosis. Reports of witnessed aspiration or abdomen away from the diaphragm, worsens dyspnea in
gagging are rare. The presence of partially digested food these individuals. Patients with cervical spinal cord injury
on a patient’s pillow is infrequently reported, but if pres- or bilateral phrenic nerve paralysis, who lack active inter-
ent it is suggestive of regurgitation and aspiration. The costal inspiratory muscles or diaphragm, may also suffer
diagnosis is usually suspected in a patient with a history from orthopnea.
of gastroesophageal reflux or hiatal hernia, infiltrates on Arteriovenous malformations (AVMs) in the pulmo-
chest imaging in dependent portions of the lung, and no nary circulation lead to shunting of blood from the right
history of asthma. to the left side of the heart (i.e. the blood never passes
Nocturnal dyspnea characterized as a sense of air hun- through the pulmonary capillaries and is sent to the sys-
ger or a suffocating feeling is most typical of CHF and is temic circulation with a low oxygen saturation). Any posi-
termed paroxysmal nocturnal dyspnea (PND). Clues to tion that increases the gravity-dependent flow of blood
the diagnosis of PND include the presence of peripheral through an AVM can lead to worsening hypoxemia and
edema and relief of the respiratory discomfort shortly dyspnea. Focal areas of atelectasis or pneumonia will lead
after assuming an upright position. Redistribution of to similar gas exchange derangements when the body
580 Chapter 47 Respiratory Symptoms
position is such that blood flow to that region of lung is as blowing cool air on a patient’s face can significantly
enhanced. Consequently, the guiding principle in these reduce the severity of dyspnea in normal subjects with
circumstances is “good lung down” when positioning a induced breathlessness, indicating that this intervention is
patient to maximize gas exchange and minimize dyspnea. likely of benefit in dyspneic patients.36
Platypnea describes the development of tachypnea Benzodiazepines induce drowsiness in patients with
and hyperventilation when the patient is in the upright dyspnea refractory to medical treatment, but they do not
position. It is a physical finding rather than a symptom; clearly improve symptoms of breathlessness. Multiple ran-
although, the patient may also complain of associated domized trials assessing the effects of benzodiazepines
breathing discomfort. The exact mechanism of platypnea do not provide compelling evidence for or against ben-
is unclear, but it probably relates to pathology at the lung zodiazepines for the management of dyspnea.37 As such,
bases with stimulation of pulmonary receptors or worsen- benzodiazepines should be reserved for patients with
ing gas exchange when blood flow increases to these areas persistent dyspnea despite treatment with other palliative
with the patient upright. interventions.
Finally, while supplemental oxygen is frequently pre-
scribed to patients with severe dyspnea, the available evi-
dence does not support this intervention for patients who
47.3.5 Palliative Management are not hypoxemic.38 Administration of humidified air
Management of dyspnea primarily involves treating the and providing high-flow air may provide some palliative
underlying pathophysiologic process causing the patient’s benefit, but supplemental oxygen does not improve dys-
breathlessness, and a detailed review of different treat- pnea for patients who are not hypoxemic.
ments for the variety of medical conditions that can cause
dyspnea is beyond the scope of this chapter. However,
despite appropriate medical management, severe and
debilitating dyspnea may persist for some patients. In
47.4 COUGH
these cases, symptomatic management may be indicated
to achieve some degree of palliation of dyspnea.
47.4.1 Definition and Physiology
Palliative management of persistent and severe dys- A cough is a sudden expiratory maneuver, associated with
pnea has been assessed in different patient populations high intrathoracic pressures, intended to clear secretions
and diseases, and systemic opioids have consistently dem- and foreign material from the airways. An effective cough
onstrated efficacy in ameliorating dyspnea in patients starts with a deep breath, which expands the lungs and
with cancer, COPD, and interstitial lung disease. 33 chest wall to a point of elevated elastic recoil. This elas-
Opioids act by agonizing central µ-receptors, decreasing tic recoil works in synchrony with optimally contracting
cerebral responses to afferent neuronal signals, as well as expiratory muscles to produce high intrathoracic pres-
inducing cerebral depression and neurosystemic analge- sures against a closed glottis. The sound of the cough is
sia. Inhaled opioids may provide targeted symptom relief associated with the sudden opening of the glottis and the
for patients with dyspnea while decreasing the effects of subsequent explosive release of pressurized intrathoracic
somnolence; however, the available data do not demon- gas with vibration of the vocal cords. Vibration may help
strate superiority of inhaled opioids as compared to sys- to loosen secretions from the larynx.
temic opioids. 34 Impaired inspiratory or expiratory muscle func-
Non-pharmacologic interventions, such as developing tion leads to weakened cough. Patients with vocal cord
coping strategies for managing the physical and psycho- paralysis or tracheostomy are unable to seal the glottis
logical aspects of breathless, have demonstrated effective- and cannot generate the high intrathoracic pressures
ness in helping patients manage dyspnea. A significant needed to effectively clear secretions. Such patients are
proportion of patients with COPD, up to 40–50%, have at increased risk for lower respiratory infection and may
clinical evidence of depression, and counseling and cogni- complain of increased chest congestion. The triggers for
tive behavioral therapy can both address depression and cough are complex; selected examples are reviewed in
dyspnea. 35 In addition, environmental interventions such Table 47.6.
TABLE 47.7 Common clinical causes of cough 47.4.4 Subacute and Chronic Cough
Acute Cough
Respiratory infection, airway inflammation
with Clear Chest X-Ray
Chronic cough is defined as a cough lasting for more than
47
Bronchospasm eight weeks, while subacute cough lasts three to eight
Inhalational injury weeks.39 There is considerable overlap in causes of sub-
Aspiration
acute and chronic cough, and they are generally consid-
Subacute Cough
Infectious or post-infectious cough (Bordetella pertussis) ered together in this section. However, post-infectious
Sinus infection/inflammation resulting in post-nasal drip etiologies are an important cause of subacute, but not
Chronic Cough with Clear Chest X-ray chronic, cough. A history of recent airways or sinus infec-
Upper airway cough syndrome (post-nasal drip) tion should be sought in patients with subacute cough.
Bronchospasm Subacute cough with a normal pulmonary exam may
Gastroesophageal reflux be due to sinus infection and inflammation resulting in
Chronic bronchitis
Bronchiectasis
post-nasal drip. In the appropriate clinical scenario, sinus
Endobronchial neoplasms imaging and/or treatment with nasal decongestants and
Nonasthmatic eosinophilic bronchitis antibiotics for bacterial sinusitis may be warranted.40
Chronic Cough with Abnormal Chest X-ray Paroxysms of cough resulting in post-tussive emesis or,
Interstitial lung disease less frequently, cough that produces a “whooping” sound,
Recurrent aspiration are clues to a potential diagnosis of Bordetella pertussis
Endobronchial neoplasm
Indolent infections (e.g. Pneumocystis jerovici, pneumonia,
infection. For patients with cough and these symptoms,
tuberculosis) B pertussis infection should be considered the diagnosis
barring clinical evidence of another cause being more
likely. 39 Although infants are typically vaccinated against
pertussis, immunity wanes over five to ten years. As such,
47.4.2 Clinical Causes of Cough adolescents and adults are at risk for developing infections
The most common etiologies of cough are outlined in from B pertussis.41 While early antibiotic treatment (mac-
Table 47.7. The differential diagnosis for cough varies rolides are particularly effective) can reduce the severity
whether a patient has an acute, subacute, or chronic cough. and duration of cough due to B pertussis, the efficacy
The differential diagnosis for chronic cough is further sub- of antibiotics after two weeks of symptoms is unclear.
divided based on a normal vs. abnormal chest X-ray. General consensus based on the available studies is that,
after four weeks of symptoms, it is not appropriate to pro-
vide antibiotics; rather, care should focus on symptom
management.39,42
47.4.3 Acute Cough Chronic cough without significant dyspnea and with
Acute cough is a cough that has been present for less than a normal chest X-ray is commonly seen both by primary
three weeks.39 The most common cause of acute cough is care physicians and pulmonary specialists. This entity has
a respiratory infection, and it is characterized by sputum been well-studied,40,43 and the vast majority of patients
production and may be accompanied by a “raw,” sub- will have one or a combination of three findings: upper
sternal sensation. Chest congestion may also be present. airway cough syndrome (UACS), asthma, and gastro-
Fever, malaise, and other systemic symptoms of a viral or, esophageal reflux disease (GERD).
less likely, bacterial infection are likely to coexist. UACS includes the spectrum of rhinosinus causes of
Subclinical bronchospasm is another cause of acute post-nasal drip. From perennial rhinitis to the sequela
(as well as chronic) cough. In patients with mild asthma, of upper respiratory infections, UACS encompasses the
wheezing may not be present. Sudden exposures to aller- breadth of diseases that result in posterior nasopharyngeal
gens, cold air, or exercise may result in transient cough. secretions descending to the larynx, causing an irritating
A high index of suspicion, along with appropriate PFTs feeling or “tickle” in the throat. Cough due to UACS may
including spirometry and possibly bronchoprovocation be nonproductive or result in small amounts of white spu-
maneuvers, is needed to make this diagnosis. tum; however, UACS due to chronic sinus infections may
Inhalation of toxic fumes (e.g. cleaning agents, smoke) result in purulent sputum. Typically, the cough worsens
can damage the airway epithelium and precipitate cough. when patients assume a supine position to go to sleep,
Airway hyperreactivity may also result. As with acute both because of positional worsening of nasal drainage
infections, a raw substernal sensation is often present. and a greater awareness of the “irritation” in the absence
Dyspnea commonly accompanies inhalational exposures. of typical distractions one encounters during the day. Not
Foreign body aspiration (e.g. food particle or, in children, uncommonly, patients will not be aware of a “drip,” per
a small toy) may not be recalled by the patient. Cough may se, but when questioned about the source of the cough (i.e.
occur immediately after aspiration, but in some cases can where the cough seems to be originating), they will local-
be delayed for hours or days at which point airway inflam- ize it to the throat rather than the chest. Frequent “throat
mation is probably contributing to the cough. A focal clearing” may be a clue suggestive of UACS. Friends or
wheeze is appreciated on examination of the chest in some family members may be more aware of frequent throat
cases, and post-obstructive pneumonia can develop if clearing than the patient, and frequent throat clearing may
the foreign material occludes a sufficient diameter of the be observed during the interview. A history of allergies
airway lumen. may be suggestive of UACS due to rhinitis, particularly if
582 Chapter 47 Respiratory Symptoms
there is seasonal variation of cough frequency or severity. disease, which tends to drain well throughout the day,
However, in most cases, patients are unaware of specific may be associated with a dry cough or scant secretions.
allergens, and skin testing may be necessary if symptoms Sputum may be occasionally streaked with blood. A his-
persist despite treatment. tory of prior pneumonia(s) is suggestive but not diagnostic.
Hyperactive airways without wheezing can pres- Bronchiectasis increases the risk of recurring respiratory
ent as chronic cough and has been termed cough variant infections associated with low-grade fever, worsening
asthma.44 In a patient without a prior history of asthma, cough, and sputum production. Growth of Pseudomonas
symptoms often follow a respiratory infection. Systemic, aeruginosa on repeated sputum cultures is very suggestive
infectious symptoms will clear over several weeks but of bronchiectasis. Although a chest X-ray is often normal,
cough persists. In many cases, the cough will resolve spon- focal areas of fibrosis or fibrocystic disease may be pres-
taneously in eight to 12 weeks, but it can continue indefi- ent, and a chest CT scan is quite sensitive in defining the
nitely. Typically, the cough will be nonproductive or result extent of disease.
in small amounts of clear-to-white sputum. In contrast to Chronic bronchitis is defined as a productive cough
cough due to UACS, patients with cough variant asthma present for ≥3 months of the year for ≥2 years. Chronic
localize the origin of the cough to the chest. Exposure to bronchitis is due to chronic airway inflammation induced
cold air, exercise, smoke, and toxic fumes characteristically by cigarette smoking or other environmental irritants. The
worsens cough arising from airway reactivity. Spirometry cough is typically most pronounced early in the morning
is often normal during routine evaluation, and the diagno- and tends to diminish as the day progresses. Patients local-
sis may be made based on response to a therapeutic trial of ize the cough to the chest. Sputum is occasionally mixed
bronchodilators or by bronchoprovocation tests. Patients with blood. Due to associated obstructive lung disease,
with cough variant asthma are typically quite responsive these patients can have dyspnea on exertion.
to treatment and generally achieve symptom control more Endobronchial neoplasms in central airways can
easily than patients with classic asthma symptoms.44,45 produce cough and, in the absence of significant airway
GERD completes the triad of common causes of chronic obstruction leading to focal atelectasis, will usually have
cough. GERD may produce cough on its own or exac- a normal chest X-ray. Although bronchogenic carcinoma
erbate cough in a patient with airway reactivity. Cough can present in this manner, bronchial adenomas or carci-
due to GERD is typically nonproductive and localizes to noid tumors are more likely. These tumors, which usually
the chest. A history of heartburn or reflux symptoms is behave as low-grade malignancies with a small potential
helpful if present, but is frequently absent. “Waterbrash,” for distant metastases, may have a polypoid appearance
the sudden sensation of a sour taste in the mouth, is typi- that in some cases leads to a postural cough due to inter-
cally associated with reflux of gastric contents. A detailed mittent positional airway obstruction from the adenoma.
dietary history is very valuable in identifying patients at
risk for cough due to GERD. Treatment of cough due to
GERD should focus on lifestyle modifications (e.g. raising 47.4.5 Chronic Cough with an
the head of the bed at night, avoiding foods that dilate the
lower esophageal sphincter, and avoiding eating shortly
Abnormal Chest X-Ray
before lying down.) Proton pump inhibitors are no better Interstitial lung disease typically presents with the gradual
than placebo in treating cough due to GERD.46 onset of dyspnea on exertion, but nonproductive cough
Other less common causes of chronic cough with a nor- may be the prominent (or only) symptom early in the dis-
mal chest X-ray include nonasthmatic eosinophilic bron- ease. Patients localize the cough to the chest. In severe
chitis (NAEB), bronchiectasis, chronic bronchitis, and cases, cough can be quite debilitating and refractory to
bronchial carcinoid. NAEB causes cough by allergic air- cough suppressants. Chest X-ray findings may be subtle
way inflammation in response to an environmental stimu- in early disease; later, in the clinical course, the chest
lus. NAEB is associated with normal chest imaging and X-ray frequently demonstrates low lung volumes and
normal spirometry. NAEB, in contrast to chronic cough reticular interstitial changes.48 For patients with normal
due to asthma, is not associated with airway hyperrespon- chest X-rays but suspected interstitial disease, CT scans
siveness in response to bronchoprovocation maneuvers are a very sensitive tool for confirming the diagnosis.49
such as a methacholine challenge. The definitive diagnosis The interview should include questions about the occu-
of NAEB requires identification of eosinophils in sputum pational history (e.g. exposure to inorganic or organic
or bronchial washings, or bronchial mucosal biopsy dem- dusts), tobacco use, joint symptoms, or peripheral skin
onstrating increased eosinophil concentrations.47 Given nodules suggesting collagen-vascular disease (e.g. rheu-
that these diagnostic modalities are not clinically practical matoid arthritis, systemic lupus erythematosus), and eye
for most patients with cough, empiric treatment may be symptoms or lower extremity joint pain suggesting sar-
appropriate when NAEB is suspected. The best treatment coidosis. Patients with symptomatic interstitial fibrosis
for NAEB is identification and avoidance of a causative typically have a restrictive defect on spirometry and lung
environmental stimulus. When that is not possible or not volume testing.
effective, empiric treatment with glucocorticoids can be Bronchogenic carcinomas in the central airways
attempted. Typically, patients with NAEB return to their may cause partial or complete obstruction of a segmen-
premorbid baseline after treatment with glucocorticoids tal or lobar bronchus, leading to focal atelectasis on the
or avoidance of causative environmental stimuli. chest X-ray and chronic cough. The cough is typically
Patients with bronchiectasis typically have a cough nonproductive but may be associated with intermittent
productive of purulent sputum, although, upper lobe hemoptysis.
47.5 Hemoptysis 583
Foreign body aspiration can lead to hemoptysis either associated with exposure to inhaled allergens or irritants,
by causing direct airway trauma or local inflammation. cold air, and exercise. Decreased wheezing in response to
Pulmonary contusions result most commonly from blunt inhaled bronchodilators also suggests asthma. Physical
chest trauma and are associated with other injuries such examination reveals diffuse expiratory wheezing when a
as rib fractures, pneumothorax, and cardiac contusion. patient is suffering acute asthmatic symptoms, and is usu-
Hemoptysis in these settings is usually small in quantity. ally normal in the absence of symptoms. With acute symp-
toms, spirometry demonstrates an obstructive ventilatory
defect with decreased FEV1 and reduced FEV1/FVC. In
47.6 WHEEZING the absence of symptoms between asthma exacerbations,
PFTs are typically normal. Airway hyperresponsiveness
can be elicited by performing bronchoprovocation maneu-
47.6.1 Definition and Physiology vers such as a methacholine challenge, which is sensitive
Wheezing is a sound that emanates from lower airways but not specific for diagnosing asthma.
(i.e. below the larynx), resulting from turbulent flow. It Mucus hypersecretion due to infections and/or airway
is a “continuous” sound, as compared to the intermittent inflammation may also cause wheezing. Since lower respi-
or staccato sounds that accompany chest congestion with ratory tract infections can also produce transient airway
mucus in the airways. Wheezing may occur during expi- hyperreactivity, it may be difficult to distinguish wheezing
ration, inspiration, or throughout the respiratory cycle. It from infection and/or inflammation from asthma. Rapid
is both a symptom, a sound that patients report hearing improvement of wheezing after cough or with broncho-
with breathing, as well as a physical finding appreciated pulmonary clearance, however, is more suggestive of
when one examines a patient. mucus hypersecretion than asthma.
The sound is produced by turbulent flow through nar- “Cardiac asthma,” wheezing in association with
rowed airways, and in some cases may reflect rapid oscil- increased pulmonary capillary pressures and interstitial
lation of the airway walls. 53 There are multiple causes edema, is another common cause of wheezing. Generally,
of airway narrowing (Table 47.9). Wheezing, which is a there are other symptoms or signs of CHF in the history
sound originating in the lower airways, should be dis- (orthopnea, PND) and physical examination (distended
tinguished from stridor, an inspiratory sound arising jugular veins, S3 gallop, peripheral edema). However,
primarily from the larynx and upper airways. During acute CHF secondary to myocardial ischemia may be dif-
inspiration, transmural pressure across the intratho- ficult to distinguish from asthma in a patient with a his-
racic airways favors expansion (due to negative pleural tory of airway reactivity.
pressures). As such, inspiratory wheezing is relatively Partial endobronchial obstruction can lead to focal
uncommon. In contrast, atmospheric pressure surround- or localized wheezing. The patient may not recognize the
ing extrathoracic airways is greater than the negative focal origin of the sound nor be able to localize any inter-
pressure inside of them; consequently, the extrathoracic nal sensations associated with the wheeze. Bronchogenic
airways tend to collapse during inspiration. The collapse neoplasms, either carcinomas or adenomas, and aspirated
of extrathoracic airways during inspiration accentuates foreign bodies can cause focal wheezing.
any pre-existing airway narrowing. Thus, a continuous Expiratory wheezing may originate from the upper
sound that worsens during inspiration is likely due to an airways when laryngospasm is present. Termed paradoxi-
obstruction in the extrathoracic airways, whereas wheez- cal vocal cord dysfunction (PVD), this condition is due to
ing that is more pronounced on expiration likely origi- adduction of the vocal cords during expiration; expira-
nates in the intrathoracic airways. When the intensity of tory wheezing originating from the upper airways can be
wheezing is constant throughout both inspiration and extremely difficult to distinguish from asthma by history
expiration, a fixed obstruction is likely. alone. Frequently, PVD occurs in young women, often
with a history of emotional and/or psychiatric difficulties.
When paradoxical vocal cord movement occurs only in
47.6.2 Etiology the setting of exertion, particularly strenuous exertion,
it is referred to as exercise-induced laryngeal obstruction
The most common cause of wheezing is asthma; however, (EILO). 54 PVD and EILO are commonly treated as asthma
asthma may occur in the absence of wheeze. Elements for months or years before the diagnosis is recognized. 54,55
of the history that suggest asthma include: wheezing Clues to the diagnosis of PVD are a very rapid symptom
onset, an association of psychological stress with wheez-
ing, and an inconsistent bronchodilator response. EILO
TABLE 47.9 Common causes of wheezing is characterized by exertional expiratory wheezing and
Primary airway reactivity (e.g. asthma) excessive breathlessness, symptom resolution with exer-
cise cessation, and normal resting spirometry results.
Interstitial edema Fiberoptic laryngoscopy during an attack of either PVD
Airway inflammation and mucous hypersecretion or EILO can confirm the diagnosis by directly visualizing
adduction of the vocal cords during expiration. Treatment
Endobronchial obstruction (e.g. neoplasm or foreign body)
is primarily speech therapy and psychological counseling
Vocal cord dysfunction to assist patients in understanding the cause and nature of
their symptoms and to teach techniques to develop better
Exercise-induced laryngeal obstruction
vocal cord control.
47.7 Nocturnal Respiratory Symptoms: Snoring and Apnea 585
Vocal cord swelling from infection, allergic reaction, per hour of sleep (the “apnea-hypopnea index” [AHI]).
47
or chemical or smoke inhalation narrows the upper air- Polysomnography (i.e. a “sleep study”) must be performed
way, increases turbulent flow, and may lead to stridor. As to accurately measure the AHI.
inhalational injuries can damage both upper and lower The clinical syndrome of OSA is the combination of
airways, laryngeal edema and inspiratory wheezing may an AHI of ≥5 with daytime symptoms due to chronic noc-
be associated with intrathoracic airway hyperresponsive- turnal hypoventilation. Daytime symptoms associated
ness and expiratory wheezing. Allergic reactions causing with the OSA syndrome include fatigue, somnolence, and
laryngeal edema can be differentiated from inhalational morning headache. These symptoms are common even in
injuries both from the history and from an association patients without nocturnal hypoventilation, but clinical
with urticaria and angioedema. suspicion of OSA syndrome is increased in patients with
concomitant obesity, snoring, and/or comorbid condi-
tions such as hypertension, coronary artery disease, and
47.7 NOCTURNAL RESPIRATORY cerebrovascular disease. Cognitive issues (specifically
difficulty concentrating), erectile dysfunction, enuresis,
SYMPTOMS: SNORING and depression may also be associated with the OSA syn-
AND APNEA drome, due to end-organ damage from the systemic conse-
quences of chronic nocturnal hypoventilation and cyclical
hypoxemia.
47.7.1 Definition and Physiology The severity of daytime somnolence can be assessed and
The prevalence, clinical importance, and societal impact quantified by the Epworth Sleepiness Scale (ESS).60 The
of nocturnal respiratory symptoms have increased mark- ESS asks patients to rank their sleepiness in eight scenarios,
edly in the 21st century. The primary cause of the increased such as “sitting quietly after a lunch without alcohol” or
frequency and severity of nocturnal respiratory symptoms “in a car, while stopped for a few minutes in traffic” (see
is likely the marked increase in obesity in the general Table 47.10).60 Patients with a high score (≥9) have increased
population. In 2016, 1.9 billion adults were overweight of daytime sleepiness, but the ESS has not been validated as an
whom 600 million were obese.56 In the United States, the independent predictor of the OSA syndrome.
National Health and Nutrition Examination Surveys have There are multiple pathophysiologic mechanisms in
demonstrated progressive increases in obesity (defined as a the OSA syndrome that account for the epidemiologic
body mass index of ≥30 kg/m 2) since the 1960s. association between OSA and cardio- and cerebrovascu-
Snoring is defined as noisy breathing during sleep and lar disease (see Table 47.11). Essential hypertension occurs
is very common in the general population. The prevalence in at least 50% of patients with the OSA syndrome.61
of snoring varies between studies, ranging from 10% to Congestive heart failure, arrhythmias, coronary artery
60%. 57 Loud snoring is more commonly reported by men disease, and myocardial infarction and cerebrovascu-
than women. 58 The prevalence of snoring increases with lar disease, including stroke, are all associated with and
age up to 50–60 years, after which time the prevalence likely due to systemic physiologic derangements caused by
decreases.59 OSA.62
Snoring occurs due to vibration of the soft palate and The “obesity-hypoventilation syndrome” (OHS) is
faucial pillars. The likelihood that snoring will occur is the combination of chronic hypoventilation with chronic
dependent upon the size of the airway, the tone of the soft hypercapnia and obesity. Right ventricular dysfunction,
tissue structures in the airway, and body position. due to elevated pulmonary arterial pressures and left heart
The clinical significance of snoring is uncertain. dysfunction, is commonly present in patients with OHS.
Generally, in the absence of observed or measured apneic Of note, certain cerebral pathologies, particularly
episodes, snoring is considered to be benign. However, abnormalities involving areas of non-voluntary respira-
the decrease in the prevalence of snoring that occurs with tory control, may result in a rare condition called central
advancing age (>50–60 years of age) may indicate a sur- sleep apnea syndrome. Central sleep apnea is not asso-
vivorship phenomenon.57 It is unknown whether snoring ciated with obesity, while OSA and obesity are clearly
indicates pathologically narrowed airways causing comor- directly correlated.
bid conditions and death, or whether snoring is simply a
marker of comorbid conditions that ultimately cause mor-
bidity and death. Regardless, when a patient (or a patient’s
bed-partner) complains of snoring, a history to assess for
47.7.2 Etiology
signs or symptoms of obstructive sleep apnea (OSA) syn- While snoring can be a normal finding, it may be associ-
drome should be performed. ated with the OSA syndrome. As noted previously, extra-
Nocturnal apneas are defined as a cessation of air- thoracic airways, including the hypopharynx, are prone
flow during sleep. The term apnea specifically describes a to collapse during inspiration due to the combination of
cessation of airflow for ≥10 seconds; hypopnea is a tran- positive atmospheric pressure outside the airway and neg-
sient reduction in airflow (a reduction in the respiratory ative intraluminal pressure during inspiration. Snoring is
rate and/or tidal volume) that lasts for ≥10 seconds and more likely to occur in obese patients, as the hypophar-
is associated with a ≥4% decrease in oxygen saturation. ynx is already narrowed from increased soft tissue fat.
Frequent nocturnal apneas and hypopneas may result in Conditions that reduce the muscle tone of the surrounding
hypoventilation. The diagnostic criteria for clinically sig- tissue (e.g. alcohol, sedative agents) further increase the
nificant OSA is an average of >5 apneas and/or hypopneas risk of hypopharyngeal obstruction and snoring. Rapid
586 Chapter 47 Respiratory Symptoms
eye movement (REM) sleep is associated with decreased valuable to distinguish between nasal and mouth snoring,
muscle tone, and snoring occurs most commonly during as nasal snoring is generally not considered indicative of a
this phase of sleep. pathologic process. If possible, the physician should ascer-
The tongue is a major component of the anterior wall tain whether the patient has been observed to experience
of the hypopharynx, and movement of the tongue can apneas, either central (when there is no evidence of airflow
contribute to upper airway obstruction. When the tongue or chest wall movement) or obstructive (no airflow but
falls posteriorly, obstruction is worsened. Given the lack preserved chest wall motion). Loud snoring or loud snorts
of bony support to maintain hypopharyngeal patency, (which may occur at the end of the obstructive episode)
intact glossal and pharyngeal muscle tone is necessary to indicates intermittent airway obstructions. Additional
keep the airway from collapsing. Patients who sleep in the questions are focused on daytime symptoms of the OSA
supine position are more likely to snore or develop more syndrome as outlined above.
severe obstruction because of the propensity of the tongue The chronicity of snoring, changes in weight, and/
to be pulled posteriorly by gravity. or drug and alcohol use are also important components
Children with large tonsils or adenoids may present of the history. For example, a middle-aged, non-obese
with snoring, although significant airway obstruction is woman whose snoring dates back to adolescence and
unusual. who has otherwise been clinically well is likely to have a
benign condition. Alternatively, a middle-aged man with
a 20-pound weight gain over the last year and six months
of snoring should be questioned about symptoms of the
47.7.3 Essentials of the History OSA syndrome.
Snoring, unlike many symptoms, is less likely to be The definitive diagnosis of OSA requires the pres-
reported by patients than by bed-partners. It may be ence of associated daytime symptoms and an AHI of ≥5.
References 587
AHI can only be measured by formal polysomnography, symptoms augments one’s intellectual enjoyment when
47
which requires a patient to spend a night in a sleep labora- caring for patients with these symptoms.
tory. There is no role for PFTs or chest imaging in diagnos-
ing OSA, but these studies may be helpful in searching for
associated conditions. CLINICAL APPLICATIONS
• Treatment of dyspnea is primarily dependent on
treating the underlying disease process, but pal-
47.8 CONCLUSION liative interventions with both pharmacologic or
non-pharmacologic interventions can provide symp-
Respiratory symptoms are extremely common in clinical tomatic relief.
practice. As the lungs and upper airways have fairly lim- • Cough, like dyspnea, is most effectively treated
ited ways to respond to pathologic changes, the challenge when the cause is found and treated specifically.
for clinicians is to understand the nuances of descriptions • Hemoptysis is classified as massive (≥600cc of blood
of the sensations and the sounds that patients report, and over 24 hours) or non-massive.
to ask probing questions that elicit these subtle distinc- • Snoring is of uncertain clinical significance, but a
tions. Understanding the physiology underlying respira- patient or bed-partner complaining of snoring should
tory symptoms can help a physician perform a focused yet prompt questions regarding signs or symptoms of
thorough history and physical exam, determine what fur- obstructive sleep apnea.
ther testing is needed, and recommend targeted and effec- • Obstructive sleep apnea syndrome is the combina-
tive interventions. Additionally, and importantly, having tion of an AHI of >5 and symptoms of daytime som-
a better understanding of the physiology of respiratory nolence and fatigue.
REFERENCES
1. Mahler DA, Wells CK. 1988. Evaluation symptoms, self-reported asthma attacks, cardiorespiratory diseases. Am J Respir
of clinical methods for rating dyspnea. and use of asthma medication in the Crit Care Med 154:1357–1363.
Chest 93(3):580–586. European Community Respiratory 20. Moosavi SH, Binks AP, Lansing RW, et
2. Meek PM, Banzett R, Parshall MB, Health Survey (ECRHS). Eur Resp J al. 2007. Effect of inhaled furosemide on
Gracely RH, Schwartzstein RM, Lansing 9(4):687–695. air hunger induced in healthy humans.
R. 2012. Reliability and validity of the 11. Axelsson M, Lindberg A, Kainu Respir Physiol Neurobiol 156:1–8.
multidimensional dyspnea profile. Chest A, Ronmark E, Jansson SA. 2016. 21. O’Donnell CR, Lansing RW,
141(6):1546–1553. Respiratory symptoms increase health Schwartzstein RM, Banzett R. 2017. The
3. Maher DA, Ward J, Waterman LA, care consumption and affect everyday Effect of aerosol saline on laboratory-
Baird JC. 2012. Longitudinal changes in life—A cross-sectional population-based induced dyspnea. Lung 195(1):37–42.
patient-reported dyspnea in patients with study from Finland, Estonia, and Sweden. 22. MacParland C, Krishnan B, Wang Y,
COPD. COPD 9(5):622–627. Eur Clin Respir J 3:31024. Gallagher C. 1992. Inspiratory muscle
4. Banzett RB, O’Donnell CR, Guilfoyle 12. Schwartzstein RM, Adams L. 2010. weakness and dyspnea in chronic heart
TE, et al. 2015. Multidimensional Dyspnea. In Murray and Nadel’s failure. Am Rev Respir Dis 146:467–472.
dyspnea profile: An instrument for clini- Textbook of Respiratory Medicine, sect 23. Rubin SA, Brown HV. 1984. Ventilation
cal and laboratory research. Eur Resp J H. Symptoms of Respiratory Disease and gas exchange during exercise in
45(6):1681–1691. and Their Management, eds. Mason RJ, severe chronic heart failure. Am Rev
5. Banzett RB, Pedersen SH, Schwartzstein Broaddus VC, Martin T, et al., 613–627. Respir Dis 129:S63.
RM, Lansing RW. 2008. The affective Philadelphia, PA: Saunders. 24. Clark A, Poole-Wilson P. 1996.
dimension of laboratory dyspnea: Air 13. Schwartzstein RM, Manning HL, Weiss Breathlessness in heart disease. In
hunger is more unpleasant than work/ JW, Weinberger SE. 1990. Dyspnea: A Respiratory Sensation, eds. Adams L
effort. Am J Respir Crit Care Med sensory experience. Lung 168:185–199. and Guz A, 263–283. New York: Marcel
177(12):1384–1390. 14. O’Donnell DE, Webb KA. Exertional Dekker.
6. GOLD: Global Initiative for Obstructive breathless in patients with chronic air- 25. Simon PM, Schwartzstein RM, Weiss
Lung Disease Global Strategy for the flow limitation. Am Rev Respir Dis 1993 JW, et al. 1989. Distinguishable sensa-
Diagnosis, Management and Prevention of 148:1351–1357. tions of breathlessness induced in
Chronic Obstructive Pulmonary Disease. 15. Parshall MB, Schwartzstein RM, Adams normal volunteers. Am Rev Respir Dis
2011. Available from: http://www.gold- L, et al. 2012. An official American 140:1021–1027.
copd.com. Accessed on August 2, 2017. Thoracic Society statement: Update on 26. O’Donnell DE, Bertley JC, Chau LK,
7. Halbert RJ, Isonaka S, George D, et al. the mechanisms, assessment, and man- Webb KA. 1997. Qualitative aspects
2003. Interpreting COPD prevalence agement of dyspnea. Am J Respir Crit of exertional breathlessness in chronic
estimates: What is the true burden of Care Med 185(14):435–452. airflow limitation: Pathophysiologic
disease? Chest 123:1684–1692. 16. Moosavi SH, Golestanian E, Binks AP, et mechanisms. Am J Respir Crit Care Med
8. Hankinson JL, Odencrantz JR, Fedan al. 2003. Hypoxic and hypercapnic drives 155:109–115.
KB. 1999. Spirometric reference values to breathe generate equivalent levels of 27. Banzett RB, Lansing RW, Brown R,
from a sample of the general U.S. air hunger in humans. J Appl Physiol et al. 1990. “Air hunger” arising from
population. Am J Resp Crit Care Med 94:141–154. increased P CO2 persists after complete
159(1):179–187. 17. Simon PM, Schwartzstein RM, Weiss JW, neuromuscular block in humans. Respir
9. Voll-Aanerud M, Eagan TML, Omenaas et al. 1990. Distinguishable types of dys- Physiol 81:1–17.
ER, et al. 2010. Respiratory symptoms pnea in patients with shortness of breath. 28. Garfinkel SK, Kesten S, Chapman
in adults are related to impaired quality Am Rev Respir Dis 142:1009–1014. KR, Rebuck AS. 1992. Physiology and
of life, regardless of asthma and COPD: 18. Elliott MW, Adam L, Cockroft A, et al. nonphysiologic determinants of aerobic
Results from the European community 1991. The language of breathlessness: Use fitness in mild to moderate asthma. Am
respiratory health survey. Health Qual of verbal descriptors. Am Rev Respir Dis Rev Respir Dis 145:741–745.
Life Outcomes 8:107. 144:826–832. 29. Sue DY, Wasserman K, Moricca RB,
10. Burney P, Chinn S, Jarvis D, et al. 1995. 19. Mahler DA, Harver A, Lentine T, et al. Casaburi R. 1988. Metabolic acidosis
Variations in the prevalence of respiratory 1996. Descriptors of breathlessness in during exercise in patients with chronic
588 Chapter 47 Respiratory Symptoms
obstructive pulmonary disease. Chest 40. Irwin RS, Madison JM. 2000. The diag- 51. Jackson CV, Savage PJ, Quinn DL.
94:931–938. nosis and treatment of cough. N Engl J 1985. Role of fiberoptic bronchoscopy
30. Leite MR, Ramos EM, Kalva-Filho CA, Med 343:1715–1721. in patients with hemoptysis and a
et al. 2015. Effects of 12 weeks of aerobic 41. Guris D, Strebel PM, Bardenheier B, normal chest roentgenogram. Chest
training on autonomic modulation, muco- et al. 1999. Changing epidemiology of 87:142–144.
ciliary clearance, and aerobic parameters pertussis in the United States: Increasing 52. Pierucci P, Murphy J, Henderson KJ, et
in patients with COPD. Int J Chron reported incidence among adolescents al. 2008. New definition and natural
Obstruct Pulmon Dis 10:2549–2557. and adults, 1990–1996. Clin Infect Dis history of patients with diffuse pul-
31. Killian KJ, Summer, E, Jones NL, 28:1230–1237. monary arteriovenous malformations:
Campbell EJM. 1992. Dyspnea and leg 42. Tiwari T, Murphy TV, Moran J, et al. Twenty-seven year experience. Chest
effort during incremental cycle ergome- 2005. Recommended antimicrobial 133:653–661.
try. Am Rev Respir Dis 145:1339–1345. agents for the treatment and postex- 53. Hollingsworth HM. 1987. Wheezing and
32. Behazin N, Jones SB, Cohen RI, Loring posure prophylaxis of pertussis: 2005 stridor. Clin Chest Med 8:231–240.
SH. 2010. Respiratory restriction and CDC guidelines. MMWR Recomm Rep 54. Roksund OD, Heimdal JH, Clemm
elevated pleural and esophageal pressures 54(RR-14):1–16. H, Vollsaeter M, Halvorsen T. 2017.
in morbid obesity. J Appl Physiol (1985) 43. Pratter MR. 2006. Overview of the Exercise inducible laryngeal obstruction:
108(1):212–218. common causes of chronic cough. Chest Diagnostics and management. Paediatr
33. Ben-Aharon I, Gafter-Gvili A, Paul 129:59S–62S. Respir Rev 21:86–94.
M, Leibovici L, Stemmer SM. 2008. 44. Dicplinigaitis PV. 2006. Chronic cough 55. Bahrainwala AH, Simon MR. 2001.
Interventions for alleviating cancer- due to asthma: ACCP evidence-based Wheezing and vocal cord dysfunction
related dyspnea: A systemic review. J Clin clinical practice guidelines. Chest mimicking asthma. Curr Opin Pulm Med
Oncol 26(14):2396–2404. 129:75S–79S. 7:8–13.
34. Bausewein CL, Simon ST. 2014. Inhaled 45. Brightling CE. 2010. Cough due to 56. World Health Organization. Obesity and
nebulized and intranasal opioids for asthma and nonasthmatic eosinophilic overweight factsheet. Available from:
the relief of breathlessness. Curr Opin bronchitis. Lung 188(Suppl 1):S13–S17. http: //www.who.i nt/mediacentre /fact
Support Palliat Care 8(3):208–212. 46. Chang AB, Lasserson TJ, Gaffney J, et al. sheets /fs311/en/. Accessed on August 3,
35. Yohannes AM, Alexopoulos GS. 2014. 2011. Gastro-oesophageal reflux treat- 2017.
Depression and anxiety in patients with ment for prolonged non-specific cough in 57. Wolkove N, Osama E, Baltzan M, et al.
COPD. Eur Respir Rev 23:345–349. children and adults. Cochrane Database 2007. Sleep and aging: 1. Sleep disorders
36. Schwartzstein RM, Lahive K, Pope A, Syst Rev 1:CD004823. commonly found in older people. CMAJ
Weinberger SE, Weiss JW. 1988. Cold 47. Brightling CE, Ward R, Goh KL, et 176:1299–1304.
facial stimulation reduces breathlessness al. 1999. Eosinophilic bronchitis is an 58. Enright PL, Newman AB, Wahl PW, et
induced in normal subjects. Am Rev important cause of chronic cough. Am J al. 1996. Prevalence and correlates of
Respir Dis 139:58–61. Respir Crit Care Med 160:406–410. snoring and observed apneas in 5201
37. Simon ST, Higginson IJ, Booth S, 48. Mueller-Mang C, Grosse C, Schmid older adults. Sleep 19:531–538.
Harding R, Weingartner V, Bausewein K, et al. 2007. What every radiologist 59. Lindberg E, Taube A, Janson C, et al.
C. 2016. Benzodiazepines for the relief should know about idiopathic inter- 1998. A 10-year follow-up of snoring in
of breathlessness in advanced malig- stitial pneumonias. Radiographics men. Chest 114:1048–1055.
nant and non-malignant diseases in 27:595–615. 60. Johns MW. 1991. A new method
adults. Cochrane Database Syst Rev 49. Raghu G, Collard HR, Egan JJ, et al.; for measuring daytime sleepiness:
10:CD007354. ATS/ERS/JRS/ALAT Committee on The Epworth sleepiness scale. Sleep
38. Ergan B, Nava S. 2017. Long-term oxy- Idiopathic Pulmonary Fibrosis. 2011. An 14:540–545.
gen therapy in COPD patients who do not official ATS/ERS/JRS/ALAT statement: 61. Silverberg DS, Oksenberg A, Iaina A.
meet the actual recommendations. COPD Idiopathic pulmonary fibrosis: Evidence- 1998. Sleep-related breathing disorders
14(3):351–366. based guidelines for diagnosis and as a major cause of essential hyperten-
39. Irwin RS, Baumann MH, Bolser DC, management. Am J Respir Crit Care Med sion: Fact or fiction? Curr Opin Nephrol
et al. 2006. Diagnosis and management 183:788–824. Hypertens 7:353–357.
of cough executive summary: ACCP 50. Jean-Baptiste E. 2000. Clinical assess- 62. Somers VK, White DP, Amin R, et al.
evidence-based practice guidelines. Chest ment and management of massive hemop- 2008. Sleep apnea and cardiovascular
129(1 suppl):1S–23S. tysis. Crit Care Med 28:1642–1647. disease. J Am Coll Cardiol 52:686–717.
48
CHAPTER
Asthma
David E. Ciccolella, MD and Gilbert E. D’Alonzo, DO
589
590 Chapter 48 Asthma
48
(Adapted from National Heart, Lung, and Blood Institute. National Asthma Education and Prevention Program: Expert Panel
Report 3 [EPR 3]. Guidelines for the Diagnosis and Management of Asthma. NIH Publication no. 08-4051, Full Report 2007.)
partially explains the enhanced cholinergic-mediated air- Hyperresponsiveness is assessed by measuring air-
way hyperreactivity found in asthma. flow before and after the inhalation of increasing doses
Inflammation can be acute or chronic. The acute of inhaled methacholine or histamine 4 (Figure 48.3).
inflammatory response involves early recruitment of cells Hyperresponsive airways will develop obstruction at
to the airway. This is followed by an evolving inflamma- lower cumulative doses of these chemicals than normal
tory reaction, as recruited and resident cells are activated airways. This increased “twitchiness” of the airways
and produce a complex pattern of inflammation. Chronic is thought to protect the lungs from the detrimental
inflammation can lead to permanent airway damage. effects of irritating inhalants. Airway hyperrespon-
siveness is not unique to asthma. Hyperresponsive air-
ways are found in other airway inflammatory diseases,
48.3.3 Airway Hyperresponsiveness like chronic bronchitis and sarcoidosis. The treatment
of asthma, by improving airway inflammation, does
Airway hyperresponsiveness is a hallmark of asthma. As diminish airway responsiveness but may not eradicate
depicted in Figure 48.2, airway inflammation induces air- airway responsiveness, suggesting that additional fac-
way hyperresponsiveness. This hyperresponsiveness, along tors are involved.
with the inflammatory changes of the airways, contributes
further to airflow obstruction. Certain triggers may not
only activate but also propagate inflammation and drive
airway responsiveness to a more severe state. The mag-
48.3.4 Management
nitude of airway hyperresponsiveness seems to correlate The National Asthma Education and Prevention Program
with the activity of airway inflammation. Furthermore, (NAEPP) 2007 Guidelines recommend a written asthma
airway hyperresponsiveness seems to correlate with the action plan for all asthmatics based on signs and symp-
clinical symptoms and signs of asthma. toms, changes in PEFR, or both. 2 Written asthma action
592 Chapter 48 Asthma
60 (A) Individuals with fixed values for the normal range. The FEV1 is the most
50 hyperactive airway important airflow measurement, and usually, the asth-
(B) disease
40 matic has a reduction in the FEV1. These measurements
30 are generally taken before and after a bronchodilator.
20
The asthmatic typically shows significant improvement
in these airflows following a beta-2 agonist treatment,
10
indicating reversible airways disease. This is determined
0 by an increase in either FVC or FEV1 by 12% or more
0.025 0.25 2.5 10.0 25.0 and having a minimum absolute change of 200 mL pre-/
Melthacholine dose (mg/mL)
post-bronchodilator in the same parameter. The asth-
matic can also measure airflow from large airways as
Figure 48.3 Asthmatics have hyperresponsive airways that peak expiratory flow rate (PEFR) in L/min at home on a
are overly sensitive to immunologic or non-immunologic daily basis, using one of the multiple available handheld
stimuli. Bronchial provocation testing can serve as a useful plastic Peak Flow meters. The patient should determine
tool to measure the severity of bronchial hyperresponsiveness a personal best PEFR using the highest of three mea-
and helpful to confirm the diagnosis of asthma. surements on the same peak flow meter when they are
optimal. Peak flow monitoring can be considered in asth-
plans may be particularly helpful for those with poorly matics who have a history of frequent or severe exacer-
controlled asthma, moderate-to-severe persistent asthma, bations, who are poor perceivers of airflow obstruction
or a history of severe exacerbations. Action plans are use- or worsening asthma, or who have moderate or severe
ful in clarifying the roles of the medications and the med- persistent asthma. 2
ication plan, especially in less knowledgeable patients, The airflow obstruction of asthma waxes and wanes
and for adjusting treatment according to symptoms and with variations in the degree of inflammation and smooth
peak flow as needed. The more chronic and severe the muscle constriction. With these changes, there are altera-
asthma, the greater is the importance of a written asthma tions in FEV1 and PEFR (Figure 48.4). There are vari-
action plan. able needs for the use of medication to relieve symptoms.
48.4 Treatment 593
9
5 Post Bronchodilator 8
7
Post Bronchodilator
Pre FEV1 2.71 L
48
4 Post FEV1 3.07 L (13% increase)
6
Flow (L/s)
Volume (L)
3 5
4 Pre Bronchodilator
Pre Bronchodilator
2 Pre FEV1 2.71 L 3
Post FEV1 3.07 L (13% increase)
1 2
1
0 0
0 1 2 3 4 5 6 7 8 9 10 0 1 2 3 4 5
Time (s) Volume (L)
Figure 48.4 Spirometry pre-/post-bronchodilator in the asthmatic. Administration of an inhaled bronchodilator improves air-
flow significantly. The left panel depicts the volume-time curve and shows improvement in FEV1. The right panel shows the flow-
volume curve and improvement in peak expiratory flow over exhaled lung volume. The dependent portion of the curve is also
curvilinear (not straight) consistent with airflow obstruction.
As the asthmatic becomes better controlled with thera- compared to guideline-based treatment.13,14 Accordingly,
peutic interventions, overall airflow improves, variabil- the International ERS/ATS guidelines 2014 for severe
ity in airflow decreases, and the need for short-acting asthma do not recommend using FENO for guiding ther-
beta-2 agonist medication to relieve symptoms substan- apy in adults, more so because of increased cost with an
tially decreases, leading to an overall improvement in uncertain benefit.12
quality of life. This translates into better sleep at night In summary, currently minimally invasive biomark-
and improved resistance to asthma exacerbation during ers sputum eosinophil count-guided and FENO-guided
exposure to environmental challenges such as exercise or therapies are not recommended for the routine manage-
cigarette smoke. It is important to teach patients to recog- ment of the typical asthmatic, and further studies are
nize symptom patterns that indicate inadequate asthma needed to better define who will benefit from these types
control. of monitoring.9,12
Spirometry and peak flow both measure asthma control
based on the degree of airflow obstruction, but it would
be helpful to have (more directly measured) biomarkers
of airway inflammation, such as quantifying eosinophils
48.4 TREATMENT
in expectorated sputum and measured fraction of exhaled
nitric oxide (FENO).8 Sputum quantification for eosino-
48.4.1 Environmental Control
philia obtained by either spontaneous or hypertonic saline Environmental control measures, such as allergen avoid-
has limited utility for the diagnosis of asthma because ance, should always be included in asthma management
other illnesses may have sputum eosinophilia, and some strategies. 2 Generally, a comprehensive approach to
asthmatics may have a non-eosinophilic pattern. However, control of allergen or irritant exposure is needed since
it may be helpful for monitoring or guiding treatment in single measures for avoidance of allergens is not effec-
adults.9 The presence of sputum eosinophilia during taper- tive. Exposure of asthma patients to certain irritants or
ing of inhaled steroids or oral steroids is associated with allergens increases asthma symptoms and often precipi-
an increased risk for asthma exacerbation.10 Accordingly, tates exacerbations. As a team, the physician and patient
treatment of asthma guided by percent of sputum eosino- should do try to identify those allergens and irritants
phils has been shown to reduce exacerbations.11 However, causing asthma symptoms. The common inhalant aller-
the use of sputum eosinophil counts and clinical param- gens that are known to cause asthma exacerbations are
eters to guide therapy in severe asthmatics is recom- animal allergens; house dust mites; cockroaches; indoor
mended only in specialized centers experienced in this and outdoor fungi; and outdoor plant allergens such as
technique.12,13 tree, grass, and weed pollens. The NAEPP guidelines
Nitric oxide is produced by inflammatory cells and 2007 recommend environmental control at each step and
other cells in the airway. The fraction of exhaled nitric have a questionnaire to help determine environmental fac-
oxide, which is easily measured even with handheld tors and other factors that worsen asthma symptoms. 2,15
devices, correlates with eosinophilia and is elevated in A history of likely sensitivity to seasonal allergens from
non-smokers with eosinophilic asthma but also in other the questionnaire and positive skin testing or allergen
illnesses such as allergic rhinitis, eosinophilic bronchi- immunoassay IgE blood testing to assess the sensitivity
tis, and hypersensitivity pneumonitis.9 In adult asthmat- to perennial allergens can be helpful in identifying these
ics, unlike in children and young adults, FENO-guided allergens.15 Generally, seasonal allergens in early spring
treatment did not show a reduction in exacerbations as are trees; late spring, grasses; late summer to autumn,
594 Chapter 48 Asthma
weeds; summer and fall, Alternaria, Cladosporium, mites; Molds are fungi which proliferate in humid environ-
and in cold months in temperate climates, animal dander. 2 ments, especially homes that have dampness problems.
Allergy skin or allergen immunoassay for allergen-specific Creating a drier environment by fixing old water leaks
IgE blood testing is the only way to reliably determine sen- and eliminating water sources reduces mold growth.
sitivity to year-round indoor allergens. Reducing indoor humidity to less than 50% substantially
Certain environmental exposure rules should be fol- limits mold growth.
lowed. If an asthmatic knows what irritants, foods, or If cockroach infestation is present in the home, it is
allergens destabilize his or her disease, they should avoid very important to institute chemical control measures
these exposures. Exposure to tobacco smoke should be to reduce this antigen load. 2 Asthma severity seems to
avoided.16,17 Asthmatic patients should avoid beta-blocker increase with increasing levels of cockroach antigen. Food
therapies, if possible, but these do have an established ben- should be kept out of bedrooms, and food and garbage
efit in cardiovascular disease and should be utilized on an should be kept in closed containers. When chemical agents
individual basis.18,19 Asthmatics should avoid foods and are used to control infestation, the home should be well
drinks that contain sulfite preservatives such as shrimp, ventilated and the patient should not return to the home
dried fruit, processed potatoes, sauerkraut, beer, and wine, until the odor has substantially dissipated.
which can cause exacerbations in a small percentage of A variety of measures can be taken to reduce allergens
asthmatics.10 Aspirin and other non-steroidal anti-inflam- in the home by modifying indoor air. Vacuuming car-
matory agents should be avoided, especially by patients pets twice a week, preferably with a vacuum loaded with
who have nasal polyps.21,22 Finally, rhinosinusitis and a high-efficiency particulate air filter; can reduce house
gastroesophageal reflux, which have been implicated as dust accumulation, but the patient should not be in the
asthma destabilizers, should be controlled.23,24 room when the vacuuming is occurring. Air-conditioning
and the use of a dehumidifier are helpful. Humidifiers
and evaporative coolers are not recommended for use
48.4.2 Indoor Allergens around dust mite-sensitive patients with asthma. Indoor
air cleaning devices should not substitute for the measures
Perhaps the most important step in controlling allergen- previously described. High- particulate air filters and elec-
induced asthma is to reduce exposure to relevant indoor trostatic precipitating filters have been shown to reduce
and outdoor allergens. Major indoor allergens that are of certain animal dander, mold spores, and the particulates
particular importance are animal pet dander, dust mites, from tobacco smoke. However; these devices do not have
mold, mice, and cockroaches. All warm-blooded pets an impact on house dust mite and cockroach allergens,
can cause allergic reactions. Although of unproven effec- which are heavy particulates and do not remain airborne,
tiveness, if there are pets in the patient’s home and the and thus are not affected by air filtering.
patient is sensitive to that animal, then the patient should
be encouraged to remove the animal from the house but
to keep in mind that it can be months for allergen levels
to decrease. 2 Otherwise, we would encourage keeping the
48.4.3 Outdoor Allergens
animal out of the bedroom by keeping the bedroom door A variety of tree, grass, and weed pollens and seasonal
closed, and if possible depending on expense, remove any spores contribute to the outdoor allergen loads that affect
carpets and cloth-covered furniture from the home. The many asthmatic patients. By staying indoors with win-
bedroom should be kept clean and all air ducts that lead dows closed, generally in an air-conditioned environment,
into it should be covered with a filter. 25 patients with outdoor allergen problems can be relatively
House dust mite allergen is a major environmental fac- protected. Pollen and spore counts are highest during the
tor in asthma. 2 House dust mites are universal in areas of midday and afternoon, at periods of brightest sunlight.
high humidity, which include most of the United States. In For the asthmatic who has a significant outdoor allergen
addition to high humidity, mites depend upon human dan- problem, conducting outdoor activity shortly after sunrise
der for survival. Dust mites thrive in mattresses, pillows, or before sunset can result in a reduced pollen exposure.
carpets, upholstered furniture, and soft toys. In patients Allergen immunotherapy can be helpful in certain
who are house dust mite sensitive and demonstrate a clini- allergic asthmatic patients. 2,27,28 According to the NAEPP
cal picture consistent with allergy to the mite allergens, Expert Panel Report 3, subcutaneous immunotherapy can
there are a variety of desirable control measures that be considered for patients who have prominent allergies,
should be considered. 2 as with allergic rhinoconjunctivitis, and who have mild
Mattresses and pillows should be encased in aller- to moderate persistent asthma (steps 2 to 4). 2,13 However,
gen-impermeable covers. The sheets and blankets on the it is preferable to have clear evidence of a relationship
patient’s bed should be washed weekly in hot water, which between asthma symptoms and exposure to the allergen
must be >130˚F to kill mites. Indoor humidity should be in question. Finally, symptoms should be nearly peren-
maintained at less than 50%, and carpets, upholstered nial and difficult to control with pharmacotherapy alone.
furniture, and stuffed animals should be removed from The whole concept of allergen immunotherapy is under
the area. Although there are a variety of chemical agents constant debate, in terms of long-term benefit. If aller-
available for killing mites and denaturing the antigens, gen immunotherapy is started, it should be given under
they are not as effective as the environmental control mea- the careful guidance of a well-trained immunotherapist
sures described earlier. who is capable of treating any life-threatening reaction
48.5 Pharmacologic Therapy 595
mild to moderate asthma and the improvements seen are with inhaled corticosteroids and LABA despite adequate
modest in nature when compared to inhaled corticoste- inhaler technique, medication compliance, and other
roid therapy (but some studies show no difference).41,42 controller options.13 It moderately improves lung func-
These agents have been shown to reduce bronchocon- tion and moderately increases time to severe exacerba-
striction caused by exercise, aspirin, and inhaled allergen tion requiring corticosteroids. 54,55 However, if the patient
exposure. 38,43–46 is using a short-acting beta-2 agonist several times a day,
Theophylline, a methylxanthine compound, acts as then stopping the LABA should be considered. In a meta-
a modest bronchodilator and may also improve asthma analysis in 2018, the addition of a LAMA to inhaled ste-
through certain anti-inflammatory effects and reductions roids resulted in lower asthma exacerbations but was no
in bronchial reactivity.47,48 When theophylline is adminis- different than a LABA. 56 However, triple therapy (inhaled
tered in a sustained-release oral therapy form, it has a long steroids+LABA+LAMA) did not further reduce exacerba-
duration of action and can further control asthma when tions, but spirometry was improved compared to inhaled
used in combination with inhaled corticosteroid ther- steroids and LABA. 56
apy.49,50 However, theophylline is rarely used in asthma
treatment because it has a narrow therapeutic margin of
safety, multiple medication interactions, and weak bron- 48.5.4 Biologic Therapies
chodilating effect which has placed it as a third-line con-
Patients who continue to have asthma symptoms that are
troller therapy for chronic asthma.
not controlled despite high-dose inhaled corticosteroids
Some patients may adhere better to an oral regimen
in addition to one or more non-corticosteroid control-
than an inhaler administered regimen. For each patient
ler medications may be candidates for injectable biologic
using theophylline, the dose would be titrated to a thera-
monoclonal antibody therapies such as anti-Immunoglob-
peutic level, but more importantly, to minimize the poten-
ulin E(anti-IgE) (e.g., omalizumab), or anti-interleukin-
tial for drug toxicity. The target level for theophylline
5(anti-IL-5) agents such as mepolizumab, reslizumab, and
has been recommended to be approximately 5–15 mg per
benralizumab.
liter. 2,51,52 Theophylline levels may be affected by several
factors, including smoking, which decrease the level, and
medical conditions that increase the level, such as heart
failure, cor pulmonale, cirrhosis, hypoxia, hypothyroid- 48.5.5 Omalizumab
ism, febrile illness, pregnancy. Levels can also be affected Omalizumab is a subcutaneously injected recombinant
by the addition of drugs inhibiting metabolism (clarithro- humanized monoclonal IgG antibody that binds to cir-
mycin, ciprofloxacin) or the removal of drugs increasing culating IgE antibody that is used for the treatment
metabolism (rifampin, phenobarbital, phenytoin, carba- of patients with moderate-to-severe persistent allergic
mazepine). After the patient is on a stable dose of the- asthma and sensitivity to perennial allergens such as dust
ophylline, drug levels should be checked at least once a mites, animal dander, cockroaches, or molds. 57–60
year provided that the patient remains stable and has no Other controller medications such as corticosteroids
changes in health or other medications. do not inhibit IgE production. Recommendations from
the NAEPP 2007 guidelines, however, consider omali-
zumab for perennial allergen-associated severe persistent
48.5.2 Long-Acting Beta-2 Agonist asthmatics, in steps 5 (inadequately controlled on high-
In addition to anti-inflammatory therapy, long-acting dose inhaled corticosteroids and LABAs) or 6 (requiring
inhaled beta agonist (LABA) is used as add-on controller oral corticosteroids on a daily or alternate day basis). 2
therapy to inhaled corticosteroids. Patients with moder- The injectable medication is a recombinant humanized
ate-to-severe asthma generally require at least two or three monoclonal IgG antibody that binds to IgE antibody.
controller medications to optimize their pharmacologic Omalizumab prevents IgE binding to high-affinity recep-
therapy. 2 Inhaled beta-agonists, which are more selective tors on mast cells, basophils, and other cells, and leads to
for the beta-2 receptor, are preferred. Long-acting beta decreased mediator release from these cells. 2
agonist inhalers can have a duration of action of at least Patients on omalizumab have been able to reduce the
12 hours, far longer than that of the short-acting beta ago- dose of their inhaled steroids and frequency of exacerba-
nists that are needed by inhalation for the acute control of tions, including those requiring hospitalization. 57,61–68
symptoms. 53 However, in patients already on therapy for asthma, omal-
izumab does not improve spirometry, that is FEV1.60,68
There is also little to no effect on bronchial hyperrespon-
48.5.3 Long-Acting Muscarinic siveness, but it does decrease some airway inflammatory
markers.62,63,69,70
Antagonists In a recent multicenter “real life” retrospective study
Tiotropium is an example of the long-acting muscarinic in severe allergic asthmatics, response to omalizumab
antagonist class of medication. The standard dose of as measured by improvement in symptoms and a >40%
2.5 mcg is delivered by mist inhaler and approved in the reduction in exacerbation rate suggested that omalizumab
United States for the maintenance treatment of asthma. may be similarly effective in patients with high (>300) or
In the GINA 2018 guidelines, Tiotropium is currently low eosinophil (<300) levels.71
included as an optional addition for patients who have Omalizumab is an expensive medication even in
persistent symptoms or exacerbations not well controlled the lowest doses, determined by both body weight and
48.5 Pharmacologic Therapy 597
IgE levels, and may require injections every two to four 48.5.7 Reslizumab
48
weeks. Treatment will also affect the accuracy of most
allergen-specific assays. The drug is not recommended Reslizumab is a monoclonal anti-IL-5 antibody for treat-
for use in pregnant women. In rare circumstances, it ment of patients 18 years and older with severe persistent
has been used in occupational asthma with beneficial asthma and eosinophilia, defined in the clinical stud-
effects.72,73 It can have adverse effects, including anaphy- ies as an absolute eosinophilia of 400/ul or higher.81–83
laxis and local reactions such as injection site reactions, Reslizumab reduces asthma exacerbations by approxi-
among others.74 Anaphylaxis associated with omali- mately 50% and improves airway function.81,82 It is
zumab has been reported as any combination of bron- given as an intravenous infusion at a dose of 3 mg/kg
chospasm, angioedema of throat or tongue, hypotension, over 20–50 minutes. The most important side effect is
syncope, and/or urticaria. Anaphylaxis may occur at a anaphylaxis.
rate of less than one in 500 patients but in our experi-
ence, anaphylaxis has been less common than reported
in the original studies. 48.5.8 Benralizumab
Of the patients who develop anaphylaxis, approxi- Benralizumab is a more recently approved treatment of
mately 40% do so after the first dose and 20% after the severe eosinophilic asthma using a monoclonal antibody
second dose.61 Most patients (68%) who develop anaphy- that does not bind to IL-5 but to the IL-5 receptor alpha
laxis will develop it within the first three injections and present on eosinophils and basophils. It not only blocks
within two hours after a dose, but a smaller number of the IL-5 receptor but leads to a reduction of eosinophils
patients do not develop symptoms for more than 12 hours and basophils in blood and sputum through an antibody-
after a dose.61,74 Overall, 75% of the reactions would be dependent cell-mediated cytotoxicity.79 It is administered
seen if monitored for a period of two hours for the first subcutaneously 30 mg every four weeks for three doses
three doses and 30 minutes for subsequent omalizumab and then every eight weeks. It has been shown to reduce
injections. A Joint Task Force Report on omalizumab- exacerbations, improve airflow obstruction as by FEV1,
associated anaphylaxis in 2007 has made safety and man- and improve asthma symptom scores.84 As with the
agement recommendations for patients being prescribed other biological agents, the most important side effect is
omalizumab.75 anaphylaxis.
48.5.10 Quick-Relief Medications inflammation that is present, and the stronger is the need
for optimization of inhaled anti-inflammatory therapy.
In order to achieve immediate relief of bronchoconstriction Using a short-acting beta-2 agonist inhaler at the rate
and the discomforting symptoms associated with asthma, of one or more canisters per month has been associ-
quick-relief medications, such as fast-acting/short-acting ated with an increase in asthma morbidity and mor-
beta-2 agonists and anticholinergics are employed. Short- tality.87 Seventy to 80% of chronic asthma patients in
acting beta-2 agonists relax airway smooth muscle within this country should be able to be controlled to a level
minutes and improve airflow. These agents are the drugs of of mild episodic asthma. Mild episodic asthmatics have
choice for treating acute asthma symptoms and exacerba- two or fewer mild asthmatic attacks a week. Therefore,
tions. 2 They are also used for preventing exercise-induced if more than four puffs of a short-acting beta agonist are
bronchospasm. 2 Inhaled anticholinergic therapy, such as used weekly, then enhanced asthma control is necessary.
ipratropium bromide, can also be used as a bronchodila- A well-controlled asthmatic should only need one or two
tor in this setting, but a beta agonist should be used first. canisters of a short-acting beta-2 agonist per year, not
Ipratropium bromide may provide some additional benefit counting the therapy that would be used to prevent exer-
during a moderate-to-severe asthma exacerbation and it cise-induced bronchospasm.
may also be considered as an alternative for those who
absolutely cannot tolerate beta agonists. 2
Systemic corticosteroid therapy can speed the resolu-
tion of airflow obstruction and reduce the rate of relapse 48.6 MANAGEMENT OF ASTHMA
of treated severe asthma. 2 Therefore, systemic corticoste-
roid therapy is used in more serious asthma exacerbations
ACCORDING TO SEVERITY AND
as part of the quick-relief medical plan. CONTROL CLASSIFICATION
Because short-acting beta-2 agonist therapy like alb-
uterol should only be used for the symptomatic relief As shown in Figure 48.5 a stepwise approach has been
of asthma, the use of this medication can also serve as proposed for the pharmacologic therapy of asthma. 2
a marker of asthma stability. The more albuterol nec- The amount and frequency of medication are dictated
essary to control symptoms, the greater the airway by asthma severity in those patients not currently on
Figure 48.5 Stepwise approach for managing asthma. Abbreviations: EIB, exercise-induced bronchospasm; ICS, inhaled cor-
ticosteroid; LABA, inhaled long-acting beta2-agonist; LTRA, leukotriene receptor antagonist; SABA, inhaled short-acting beta2-
agonist. § Theophylline is less desirable due to need to monitor serum concentration levels. ‡‡ Zileuton is less desirable because
of limited studies and need for liver function monitoring. §§ Before oral corticosteroids are introduced, a trial of high-dose ICS +
LABA + either LTRA, theophylline, or zileuton.
(Adapted from: Asthma Care Quick Reference, National Heart, Lung and Blood Institute. National Asthma Education and
Prevention Program: Expert Panel Report 3 (EPR 3). Guidelines for the Diagnosis and Management of Asthma. NIH Publication no.
no. 12-5075, Revised September 2012.)
48.6 Management of Asthma according to Severity and Control Classification 599
medication (Figures 48.1 and 48.5). The level of severity Patients should be evaluated within at least two to six
48
is determined by assessment of both impairment and risk weeks after starting therapy. Once the patient returns for
components. 2 According to the Expert Panel 3, the level a follow-up appointment or for a patient already on long-
of severity is based on the most severe impairment or risk term controller therapy, the asthma control is assessed to
category. The components of impairment based on the adjust the current therapy (Figure 48.6). Determination or
last two to four weeks include symptom frequency, medi- measurement of asthma control is based on impairment
cation use (short-acting beta agonist), and lung function and risk components. 2 According to the NAEPP guide-
measurement by spirometry. lines Expert Panel Report 3, the level of control is based
The risk assessment includes frequency of exacerbations on the most severe impairment or risk category. The com-
of asthma requiring systemic corticosteroids over the last ponents of impairment include symptom frequency, medi-
year. However, there is not enough information to corre- cation use (short-acting beta agonist), and lung function
late the frequency (specific number of exacerbations) and measurement by either FEV1 or peak flow. The impair-
severity of exacerbations with the various step classifica- ment component is based on the last two to four weeks,
tion levels of asthma severity. The guidelines suggest that and if a longer period, it is recommended to use an overall
patients with a risk component of two or more exacerba- assessment by the patient as to whether their asthma is
tions per year would be considered as having persistent better or worse. There are also validated questionnaires
asthma despite impairment levels that would not indicate that can be used to assess impairment, but these do not
this degree of severity. Once the severity level is assessed, the assess the lung function component or even risk category.
suggested step level of therapy can be determined (Figure The three validated questionnaires include the Asthma
48.5). Therapy is directed toward treating airway inflam- Therapy Assessment Questionnaire (ATAQ), Asthma
mation. Therefore, controller therapies are emphasized, Control Questionnaire (ACQ), and the Asthma Control
with anti-inflammatory therapy considered the mainstay. Test (ACT). The ACT can be administered quickly, and
Adapted from National Heart, Lung and Blood Institute. National Asthma Education and Prevention Program: Expert Panel Report
3 (EPR 3). Guidelines for the Diagnosis and Management of Asthma. NIH Publication no. 08-4051, Full Report 2007.
600 Chapter 48 Asthma
the score is based on the answers to five questions assessing This group of patients should see an asthma specialist on
symptoms, interference with activities, and beta agonist a regular basis.
use over the past four weeks.88 Based on these parameters, With regular follow-up visits, the clinician may be able
asthma control is determined to be well controlled, not to reduce inhaled corticosteroid therapy by 25% every
well controlled, or very poorly controlled. three months until an optimal daily dose is achieved and
After control has been achieved, then therapy is reduced disease control is maintained. A chronic asthmatic who
or stepped down. Step-down therapy (Figure 48.5) is is completely withdrawn from inhaled corticosteroid
essential if one is to identify the minimum medication nec- therapy often relapses.90 Therefore, there should be an
essary to maintain disease control. During this process, excellent reason why inhaled corticosteroid therapy or
it is helpful that airflow is monitored and correlated with other anti-inflammatory controller therapy is completely
asthma symptoms and signs and the intermittent use of an discontinued. If the asthma is not well controlled, then
inhaled short-acting beta-2 agonist. Patients may relapse the following factors must be considered before increasing
if inhaled corticosteroids are completely discontinued. therapy:
Patients with intermittent symptoms are treated with a
beta-2 agonist, which has a quick onset and short duration 1. Patient medication adherence and inhaler technique
of action. Albuterol by metered-dose inhaler or nebulizer, should be checked on the initial visit and then peri-
used on an as-needed basis, is the quick-relief therapy of odically based on the clinician’s evaluation of patient
choice, but other medications can be used. 2 However, skill and understanding.
when any one of these medications is being used on more 2. Environmental control issues must be carefully
than two occasions per week for the relief of asthma, then reviewed for adherence and technique (See discus-
the patient no longer has episodic asthma and must be sion above).
classified as having a more persistent form of asthma. 3. Review of the following comorbid conditions:
Persistent asthma is most effectively controlled with the Allergic bronchopulmonary aspergillosis, GE
daily long-term use of a controller medication. reflux, smoking, obesity, obstructive sleep apnea,
The clinician must treat each individual patient, pay- rhinosinusitis, paradoxical vocal cord dysfunction,
ing attention to the needs and circumstances of the patient and chronic stress or depression.
in his or her stepwise treatment process. In order to ini-
tially gain disease control, it is often necessary to initiate
anti-inflammatory therapy at a more aggressive level than 48.6.1 Other Issues in Long-Term
that required in the long run by the patient’s actual clini-
cal disease severity. 2 This often helps establish quicker Asthma Management
control, and then therapy can be reduced. Many times To enhance compliance with anti-inflammatory medi-
a short course of systemic corticosteroid therapy is used cation regimen, it is often helpful to patients to try to
to gain control, along with a reasonable, perhaps more integrate the medication frequency into their lifestyle
intermediate, daily dose of inhaled corticosteroids. Once or their ability to adhere to the regimen. For patients
asthma is controlled, oral therapy is quickly reduced and who are uncontrolled or even controlled on their cur-
stopped. Within a brief period of time, inhaled cortico- rent regimen, it is important to determine if they are
steroid may even be reduced to a lower daily dose. With taking their medication as prescribed, especially inhaled
reduced inflammation, asthma symptoms and signs corticosteroids, because it is not uncommon to find that
should improve, PEFR should increase, the variability in patients dosed on a twice-daily regimen will remember
airflow over each 24-hour time period should decrease, their morning dose but tend to forget their evening dose.
and finally, the dependency on the rescue use of inhaled This may also depend on their work schedule, whether
albuterol should decrease. Enhanced control should elimi- they work days, evenings, or nights. To improve patient
nate nocturnal awakenings and activity limitation. adherence to their inhaled corticosteroid dose regimen,
Most patients with moderate-to-severe chronic it may be better to determine if it is easier for the patient
asthma require not only a higher daily dose of inhaled to take the medication (e.g., inhaled corticosteroids) all
corticosteroid therapy but a second- or third-line control- in the morning or evening instead of two divided doses
ler medication. These medications include the preferred (Table 48.2).
long-acting inhaled beta agonist like salmeterol or for-
moterol, or alternatively a leukotriene modifier or per-
haps a sustained-release theophylline. However, before 48.6.2 Asthma Complications
going to daily doses of an oral corticosteroid at step 6,
you may consider a trial of high-dose inhaled corticoste- Complications from asthma can occur acutely or chroni-
roids, a long-acting beta-2 agonist, and either a leukotri- cally. An acute asthmatic attack is associated with a
ene modifier or sustained-release theophylline to enhance variety of complications, including pneumothorax, pneu-
disease control, thereby improving the asthmatic’s overall momediastinum, a variety of cardiac arrhythmias, lung
quality of life. A long-acting beta-2 agonist or theoph- atelectasis, and respiratory failure. Rarely, death can
ylline may be especially helpful in controlling nocturnal occur. The young and the elderly are at particular risk
breakthrough symptoms.89 Based on established guide- for death because the severity of their disease is either not
lines, patients at step 5 or 6 may also be candidates for appreciated or is ignored. Asthma death can be sudden in
biological agents. The most severe persistent asthmatics onset, possibly associated with laryngospasm. However,
may also require continuous systemic steroid therapy. most asthmatic deaths are slow in evolution to the point
48.6 Management of Asthma according to Severity and Control Classification 601
Adapted from National Heart, Lung and Blood Institute. National Asthma Education and Prevention Program: Expert Panel Report 3 (EPR 3). Guidelines for the Diagnosis and
Management of Asthma. NIH Publication no. 08-4051, Full Report 2007.
TABLE 48.3 Factors associated with increased risk of asthma exacerbations or mortality
1. Severe airflow obstruction, as detected by spirometry
2. Two or more ED visits or hospitalizations for asthma in the past year; past intubation or ICU admission, especially in past five years
3. Patients feeling in danger or frightened by their asthma
4. Patient characteristics: female, nonwhite, nonuse of ICS therapy, and current smoking
5. Psychosocial factors: depression increased stress, socioeconomic factors
6. Attitudes and beliefs about taking medications
Adapted from National Heart, Lung and Blood Institute. National Asthma Education and Prevention Program: Expert Panel Report 3 (EPR 3). Guidelines for the Diagnosis and
Management of Asthma. NIH Publication no. 08-4051, Full Report 2007.
at which respiratory failure occurs, as a multitude of met- sensitive than allergy immunoassay tests, often providing
abolic problems develop.91 Table 48.3 shows the factors results within one hour. There are two types of skin tests.
that have been implicated in asthma exacerbation and The epicutaneous test is the main skin test for evaluating
mortality. allergy and is often referred to as the scratch or prick tech-
With poorly controlled asthma over a long period nique. Also, there is an intracutaneous or intradermal test.
of time, irreversible airflow obstruction develops.92,93 These skin tests are generally easy to perform and cause
Recurrent airway infection is associated with fixed air- little patient discomfort. The results are dependent in part
flow obstruction.94 In a few patients, allergic bronchopul- on the use of standardized extracts and the expertise of
monary aspergillosis occurs, often with mucoid airway the tester.
impaction and secondary bacterial infection. Allergic When the skin test is positive, the patient can see the
bronchopulmonary aspergillosis associated with asthma positive skin test, which encourages patient compliance
is characterized by episodes of severe recurrent asthmatic with environmental control measures. Measurement by
exacerbations.95 Fever can be associated with this condi- allergy immunoassay does not require expertise in tech-
tion, as can chest pain, and mucus impaction causes tran- nique for the ordering physician; no allergen extracts are
sient infiltrates to develop on the chest x-ray, usually in necessary; there is no risk of an allergic systemic reaction;
the upper lung fields. Associated blood eosinophilia and and an allergy immunoassay can be performed on patients
an increased serum IgE level are associated with allergic who are taking medications that often suppress the skin
bronchopulmonary aspergillosis, but a positive skin prick test reaction (e.g., antihistamines, montelukast, predni-
test and serum precipitating antibodies to the fungus sone, and tricyclic antidepressants).
Aspergillus fumigatus are confirmatory for this particular A positive allergy test, however, does not indicate that
form of chronic asthma. This condition generally requires the allergy is causing the patient’s symptoms. However,
high doses of inhaled corticosteroids each day, often with when a positive result is found with skin testing or allergy
oral corticosteroid therapy. immunoassay, the clinician is obliged to look for clinical
significance of the positive allergy test in the context of
the patient’s medical history. If this relationship is clear, the
allergen cannot be avoided, and symptoms are difficult to
48.6.3 Allergy Testing and Immunotherapy control with pharmacologic therapy (NAEPP 2007 steps
The discovery of IgE as the antibody responsible for aller- 2–4, mild to moderate persistent asthma), then immuno-
gic reactions has led to the development of certain allergy therapy can be considered.2 Evidence is strongest for house
immunoassay blood tests that can measure the amount of dust mites, animal dander, and pollens.2 However, immu-
allergen-specific IgE.15 Obtaining a total IgE is not use- notherapy should not be used until environmental control
ful for determining the absence or presence of allergy due has been maximized. Allergen immunotherapy should be
to the large variation and does not tell you the specific administered by a physician in the office or the hospital
allergen. Allergy skin testing is less expensive and more where facilities are available to treat the serious adverse
602 Chapter 48 Asthma
reactions that can occur as a result of this form of therapy.96 in which minute ventilation is increased. The main fac-
It is better to use immunotherapy for a single allergen—the tors affecting the severity of EIB during exercise are the
more allergens that are being treated for, the higher the amount of minute ventilation attained and sustained as
incidence of failure.2 Although multiple-allergen mixes are well as the inspired air-water content and temperature.
used for immunotherapy, only a few studies clearly support Because of the high minute ventilation, there is a cooling
this practice.97 Allergy immunotherapy is typically admin- and drying effect on the airway that somehow influences
istered for three to five years. airway inflammation in a way that expresses itself more
There are controlled studies and a meta-analysis intensely.4,101,102 During exercise, the airways cool down
that support the use of immunotherapy in the treatment as minute ventilation increases. This cooling and drying
of asthma and that do show some benefit for asthma effect of the airways sets the stage also for rapid rewarm-
symptoms, bronchial reactivity, and reduced medication ing of the airways that occurs with resting. The high-flow
use. 2,98–100 Immunotherapy is felt to reduce not only the ventilation may dry the surfaces of the airways and cause
frequency of symptoms but the extent of symptoms and an increase in osmolarity, which may trigger the release of
to minimize the need for bronchodilator medications in inflammatory mediators.
the control of asthma. Immunotherapy is most effective Effective control of chronic asthma includes the con-
for some types of seasonal pollens (tree, grass, weed) and trol of asthma during and following exercise. It is realis-
house dust mites, with some success in pet allergy, par- tic to believe that if chronic asthma is controlled, patients
ticularly cat in controlled studies.98–100 Immunotherapy can participate in exertional, even athletic, activities at a
is not a cure but may reduce asthma and allergic rhinitis reasonable level to maintain body conditioning and enjoy
symptoms and signs. The success of immunotherapy is themselves. This is important because the lifestyle changes
dependent upon identifying the correct allergens. of reduced exercise may increase the risk of asthma.103
There are certain risks associated with immunother- There are certain interventions that should be followed to
apy.96 The most common reaction to an allergy shot is control exercise-induced bronchospasm.
swelling, erythema, and pruritus at the site of the injec- Exercise-induced bronchospasm can be diagnosed sim-
tion. This type of a reaction is usually short-lived and ply for many patients. After an exercise challenge (e.g.,
can be minimized by using topical anti-inflammatory running one mile at a moderate pace) airflow is measured
therapy in the form of a cream or an oral antihistamine. sequentially at 5, 15, and 30 minutes. The patient with EIA
The most serious reaction from an allergy shot is ana- often has a fall in airflow within this time period. When
phylaxis. Anaphylaxis can occur quickly after the injec- airflow falls, especially when associated with symptoms
tion. Therefore, immunotherapy should be performed consistent with asthma, the diagnosis can be made. This
in the presence of a physician experienced in treating evaluation can be done by a physician or under the guid-
anaphylaxis. ance of a physician by instructed individuals such as train-
Sufficient time should be allowed for the reaction to ers or coaches. Patients who are known to have asthma
occur if it will develop, so most patients have to stay in should be screened for EIB breakthrough. Also, individu-
a physician’s office for a period of 15 to 30 minutes after als who may be at high risk for EIB should be screened.
each injection so anaphylaxis can be treated. Less serious We have found that as many as 14% of high-performance
reactions include nasal congestion and sneezing, asthma athletes will have bronchial hyperresponsiveness, includ-
itself, difficulty swallowing and talking because of a swol- ing bronchoconstriction associated with exertion. There is
len tongue or larynx, and lightheadedness. With these also a substantial rate of unrecognized EIB among urban
reactions, there is often an increase in heart rate and per- varsity athletes. In one study, it was reported that during
haps even a slight change in blood pressure. screening for asthma and EIB, approximately 10% of 238
students had a history of treated asthma and that another
9% had unrecognized EIB during screening. This suggests
that active screening for EIB, especially for students resid-
48.6.4 Exercise and Asthma ing in poverty areas, may be indicated.104
Exercise-induced asthma (EIA) or bronchoconstriction The prevention and control of EIB can be accom-
(EIB) is a transient airway narrowing and airflow obstruc- plished by both non-pharmacologic and pharmacologic
tion that occurs during or after exercise.4,101 Nearly 90% approaches. For some athletes, it is important to choose
of persistent asthmatics have ElB, and patients with aller- a sport that does not require sustained exercise, perhaps
gic rhinitis and even normal relatives of asthmatics can baseball, golf, or even weightlifting. When exercise is
demonstrate this phenomenon. As with asthma, the com- performed, it is good to avoid cold, dry environments.
mon symptoms are a cough, wheezing, chest tightness, However, in cases when exercise is performed in colder
shortness of breath, and what the patient describes as an environments, a mask or scarf covering the mouth may
inability to take in a full breath of air during or follow- help reduce exercise-induced bronchospasm.105 A warm
ing exercise. Symptoms start several minutes after exercise (but not too warm) and moist environment can often be
has stopped and usually improve within one hour, even helpful in minimizing EIB. Finally, it is not only the type
without medication. The airflow decline is seen between of sport that one plays but the position selected. For exam-
five and 20 minutes after exercise and resolves in about ple, a football lineman is at less risk than a running back.
60 minutes. EIB can seriously and adversely affect athletic The use of an extended warm-up session and special
performance if not recognized and controlled. breathing techniques that help minimize hyperventilation
EIB is thought to be associated with the exchange of and promote relaxation can be helpful. There are some
heat and water that occurs in the airways during exercise reports that a warm-up period before exercise results in a
48.6 Management of Asthma according to Severity and Control Classification 603
refractory period or reduction in EIB in more than 50% agonists crucial. Inhaled corticosteroids can decrease air-
48
of individuals for up to two hours.102,106,107 The athlete way responsiveness over the long term and decrease EIB.
should begin warming up slowly to loosen the muscles When chronic asthma is controlled, the frequency and
and elevate the heart rate. With the beginning of a light severity of EIB are reduced.111
sweat, the patient can perform the exercise at or close to
his or her maximum exertion for up to five minutes and
then take a rest. More accomplished athletes can continue 48.6.5 Occupational Asthma
this warm-up process recurrently for 30 to 40 minutes.
Another strategy is to do brief bouts of exercise for two It has been estimated that occupational factors account
to three minutes followed by three to five minutes of rest. for approximately 9–15% of cases of asthma in adults of
These repetitive exertional challenges should occur over a working age, including new onset or recurrent disease.112
30- or 40-minute period. It is important for the individual A variety of substances in the workplace have been impli-
athlete to find out which warm-up protocol works best for cated in the development of asthma, including a large vari-
him or her. ety of animal proteins, flour and grain dust, wood dust,
Just as important as warming up appropriately is con- cotton dust, chemical compounds such as isocyanates
centrating on breathing maneuvers during and following and hydrides, metal salts, and even pharmaceuticals.112
exercise. Symptoms can be reduced by breathing warm, The workers most commonly reported for occupational
humid air rather than cold, dry air. Therefore, swimmers asthma include paint sprayers, bakers and pastry makers,
are likely to tolerate their disease better than football play- animal handlers, nurses, chemical workers, welders, food
ers. Certain athletes have learned to breathe through their processing workers, and timber workers.112
nose instead of their mouth. This is a difficult technique The causes of occupational asthma can be grouped
to master. When athletes learn how to breathe through into immunologic and non-immunologic (e.g., smoke,
their nose, especially during periods where heavy breath- aerosols, fumes) causative agents. Up to 90% of cases
ing is unnecessary, the air that is brought into their lungs have been of the immunologic type. Some causative
is humidified and heated. By breathing deeper and more agents can produce occupational asthma through both
slowly, the cooling and drying effect of the hyperventila- immunologic and non-immunologic mechanisms, such as
tion phenomena can be minimized. toluene diisocyanate resulting from airway damage and
The post-exercise period is also very important. The sensitization. The immunologic agents can be divided into
cool-down phase after a workout or competition should high- and low- molecular weight substances (Table 48.4).
consist of taking deep, slow breaths. Cooling down in a The high-molecular-weight agents are complete sensitiz-
warmer environment, but not too warm, can be helpful. ing agents, while the low-molecular-weight agents need
Often, drug therapy is necessary to prevent EIB. There to combine with a protein to form a sensitizing agent.
are numerous inhaled beta agonist medications that can be The high-molecular-weight agents are usually mediated
used shortly before, during, or even after exercise to pre- through IgE.
vent or relieve asthma symptoms.2 Beta agonists adminis-
tered by inhalation will prevent EIB in more than 80% of
TABLE 48.4 Select causes of allergic and non-allergic
patients. Administering a short-acting inhaled beta agonist
occupational asthma
such as albuterol approximately 15 to 30 minutes before
exercise provides protection for two to three hours. When Allergic
asthma breaks through, these medications can be safely
High-Molecular-Weight
administered by a metered-dose inhaler. The inhaled long- Substance Occupations
acting beta-2 agonists (formoterol, salmeterol) can be
helpful for controlling the frequent need for short-acting Animal Protein Laboratory workers
beta-2 agonists. Salmeterol has been shown to prevent EIB Papain Brewers, lens workers
for 10 to 20 hours and is valuable for prolonged preven-
tion when the athlete will re-expose himself or herself to Wheat Flour Bakers, millers
the exercise challenge over this time period.108 Long-acting Trypsin Plastic/pharmaceutical workers
beta-2 agonists should not be used alone as daily prophy-
Soybean dust Farmers, food workers
laxis of EIB, as the duration of effect is reduced and may be
masking suboptimally controlled asthma.2 Other therapies Vegetable Gums Printers, food workers
can be used in addition to the beta agonist. If available, Low-Molecular-Weight Substance
inhaled cromolyn can be taken approximately 30 minutes
to 1 hour prior to exercise, often in addition to the pre- Platinum Jewelers, refiners
exercise use of the short-acting inhaled beta agonist for Trimellitic anhydride Plastic and epoxy resin workers
further control in those patients who fail single preventa-
tive therapy.109 Administered in a single dose at least two Phthalic anhydride Plastic and epoxy resin workers
hours before exercise, the leukotriene receptor antagonists Non-Allergic
can decrease EIB in more than half of patients for a period
Isocyanates Spray painters, foundry workers
of 12 hours or more.2,110
Most EIB occurs in the chronic asthmatic, making Polyvinylchloride Meat wrappers
control of chronic asthma with inhaled corticosteroids, Western Red Cedar Carpenters
leukotriene receptor antagonists and long-acting beta
604 Chapter 48 Asthma
It is extremely important to recognize occupational measurement of variable airflow obstruction. There are
asthma as soon as possible because the likelihood of various strategies for weight reduction. However, as part
complete resolution of symptoms decreases over time. 2 of a lifestyle change, the addition of exercise twice a week
Occupational asthma is suspected when either the patient or a weight loss program in obese asthmatics can improve
or the clinician realizes that there is a relationship between asthma control, pulmonary function, and inflammatory
asthma symptoms and work exposure. There is often a markers.115
time delay between exposure to the offending agent and
the development of symptoms of occupational asthma.
Many times, the patient will improve on the days that he 48.6.7 Stress
or she is away from the workplace, particularly during
vacations. Sometimes, coworkers have similar symptoms, Asthma is not a psychosomatic illness. However, there is
and sometimes asthma can occur during the night. Serial emerging evidence that stress plays an important role in
peak flow measurements at work and away from work can precipitating asthma exacerbation and may act as a risk
help diagnose occupational asthma.112 There are also some factor for the increased prevalence of this disease.116 Since
allergens available, which are not well standardized, for emotional upset does contribute to the asthma symptom
skin prick testing or blood tests for specific IgE for high- picture, a variety of psychological interventions may be
molecular weight agents but only a few for low-molecu- necessary to enhance overall asthma care. In some cases,
lar-weight agents. Occupational asthma can usually be a patient may need help to distinguish asthma flares and
diagnosed without using specific bronchial provocation panic attacks. Stress exacerbation of asthma may involve
testing. although occasionally a specific bronchial provo- enhanced generation of pro-inflammatory cytokines, but
cation challenge, done in a specialized laboratory with a more importantly, psychosocial factors associated with
suspected allergen or irritant from the workplace, can be stress influence the asthmatic’s personal sphere and often
helpful.112 lead to a poor outcome.117 Conflict that develops between
The management of occupational asthma can be dif- the patient, the family, and the medical staff often inter-
ficult, and the patient may have to be referred to an occu- feres with appropriate asthma care. It is true that the
pational asthma specialist. Diagnosing patients early and poorly controlled chronic asthmatic can despair, and his
avoiding further exposure to the causative agent will give or her disease can have a significant negative effect on per-
the worker the best opportunity for a complete recovery. sonal relationships, family life, and self-image. Enhanced
Often, the employee must avoid the triggering substance. asthma control, and careful discussion of these issues with
If impossible, the employee should be moved to an area of the patient and family, can help the overall asthma care
low or occasional exposure with increased health moni- process. The asthmatic who needs psychosocial assistance
toring. The use of respiratory protection by wearing a ven- should take advantage of appropriate professional coun-
tilator mask can be helpful. Many times, the patient must seling with a psychologist, psychiatrist, social worker,
completely avoid exposure to the irritating agent; there- or other licensed practitioner. 2 There are a variety of
fore, a new job position may be necessary. psychologically oriented approaches to asthma care that
The outcome of any intervention for patients with con- can be helpful, including family counseling, educational
firmed occupational asthma depends on factors such as seminars, and even psychotherapy. Ignoring one’s asthma
age and the type of agent.112 Unfortunately, some patients symptoms and neglecting to use medication can seriously
will have persistent asthma despite the removal of the adversely affect overall asthma control. Asthma education
inciting substance. A variety of chemicals, dust, and other is associated with enhanced confidence in the patient’s
particulates can sensitize the airways and induce chronic management of chronic asthma. 2
asthma.113 This is different than allergen- or irritant-
induced asthma, in which these substances aggravate
preexisting asthma but do not actually initiate the dis- 48.6.8 Food Hypersensitivity
ease process. A single high-intensity exposure to a non- Food allergens may rarely precipitate asthma symptoms
immunologic irritant can produce the syndrome known as alone but more commonly are associated with extra-
reactive airways dysfunction syndrome (RADS), in which pulmonary involvement such as skin and gastrointestinal
asthma-like symptoms occur in minutes and may last for signs and symptoms. 2,118
years.
48.6.9 Medication-Induced Asthma
48.6.6 Obesity The ingestion of aspirin in sensitive individuals may result
Asthma is more common and more difficult to control in in nasal congestion, eye irritation, facial flushing, and an
obese patients.13,114 Some obese patients with asthma have asthma exacerbation, which usually occurs rapidly after
prominent respiratory symptoms and little eosinophilic ingestion, often within 30 minutes.119 Approximately
inflammation. These symptoms need to be distinguished 4–20% of asthmatics are sensitive to aspirin and related
from those of obese patients who have respiratory symp- compounds, especially non-steroidal anti-inflammatory
toms due to deconditioning, chest restriction, and obstruc- agents.120,121 Severe and even fatal asthma exacerbations
tive sleep apnea.13,114 Because of the potential contributors have been associated with aspirin ingestion. Adult patients
to dyspnea and wheeze in obese patients, it is impor- with severe persistent asthma who have nasal polyps should
tant to confirm the diagnosis of asthma with objective be carefully instructed not to use any aspirin or aspirin-like
48.6 Management of Asthma according to Severity and Control Classification 605
medication. Some safe alternatives to aspirin to consider of their asthma.130,131 If GE reflux symptoms are pres-
48
include salsalate and acetaminophen celecoxib, but highly ent, medical management includes (1) avoidance of eat-
sensitive patients may even react to these.2,21,122,123 Nasal ing food and drinking liquids within three hours prior
polyposis and chronic rhinosinusitis occur in nearly 90% to bedtime; (2) sleeping with the head of the bed elevated
of patients with aspirin sensitivity (Samter’s syndrome).124 by using six- to eight-inch blocks; (3) eating smaller, and
The prevalence of aspirin sensitivity increases with age if necessary, more frequent meals; (4) using appropri-
and the severity of the asthma. There is no known famil- ate pharmacologic therapy such as H2 receptor block-
ial predilection to aspirin sensitivity. It is not known to be ers or proton pump inhibitors; (5) cessation of alcohol,
associated with atopy. The mechanism seems to be related cigarettes, and caffeinated foods. 2 Also, theophylline can
to altered arachidonic metabolism and to inhibition of the reduce the lower esophageal sphincter tone and predis-
enzyme cyclo-oxygenase (COX-1), in which arachidonic pose the asthmatic to GE reflux. Patients, especially with
acid metabolites are passed through the leukotriene path- nocturnal symptoms and/or regurgitation, are more likely
way resulting in increased production of the leukotrienes to show improvement in their asthma with treatment. 2,132
C4, D4, and E4 (the slow reacting substance of anaphy- However, studies have indicated that treatment of asth-
laxis).126 Therefore, medications that interfere with leu- matics without GE reflux symptoms did not improve their
kotriene synthesis or leukotriene receptor antagonists are asthma.133
helpful in the management of aspirin-induced asthma. If the medical management as described above fails or
Patients are treated according to asthma guidelines, but the patient has other disturbing symptoms, then further
usually, a leukotriene modifying agent is added, which evaluation by a gastroenterologist and other treatment
may also diminish nasal symptoms.43,44,126 The treatment options should be considered. Some patients may have
of aspirin-induced asthma also includes either avoiding all further diagnostic interventions like an esophago-gastro-
NSAIDs that inhibit COX-1 enzyme or performing aspirin duodenoscopy, and others may have to be referred to a
desensitization and maintaining daily aspirin therapy.2 surgeon for evaluation.
Tartrazine or yellow food dye No. 5 can induce asthma
symptoms in some individuals. This food coloring is found
in a number of foods and in some medications.
Beta blockers, including a variety of eye drop prepara-
48.6.11 Pregnancy and Asthma
tions, can induce asthma symptoms and should be avoided Asthma is the most common medical condition during
in asthmatic patients. 2,127,128 The more cardioselective pregnancy occurring in 4–8% of pregnant women.134 The
agents may be better tolerated by the asthmatic, but in risk of asthma exacerbation during pregnancy is higher
order to be safe, an asthmatic should avoid beta-blocker for women especially in the second trimester.13,135 As a
therapy, unless this form of medication is unavoidable for general rule, one-third of all pregnant asthma patients
the cardiac or ophthalmologic condition.129 The NAEPP improve, one-third remain the same, and one-third have
Asthma Guidelines 2007 suggest avoiding non-selective worsening disease during pregnancy. 2,13,136 Whatever
beta blockers. 2 However, many patients who have mild way the asthma changes during the first pregnancy, it is
to moderate airflow obstruction are able to tolerate selec- likely that similar symptoms will occur with subsequent
tive beta blockers, and the NAEPP guidelines recommend pregnancies. Patients with more severe and difficult-to-
using them only after careful consideration in patients control asthma generally have worse symptoms during
with cardiac disorders. 2 Fortunately, there are satisfactory pregnancy. It is important for every asthma patient who
alternatives to beta blockers for most of these patients. becomes pregnant to be carefully managed medically dur-
ing obstetrical care.
Asthma may also have an effect on pregnancy com-
plications.137 Uncontrolled asthma is a risk for the fetus.
48.6.10 Gastroesophageal Reflux One large study showed that asthmatic patients had an
Gastroesophageal (GE) reflux results from some of the increased risk of infant mortality, preterm birth, and low
acidic liquid contents of the stomach being regurgitated birth weight infants than non-asthmatics.137 Those with
into the esophagus. This fluid substance is irritating to the more severe asthma have a higher risk of complications.137
esophagus. The GE reflux material does not have to be However, this study did not find an increased risk of con-
aspirated into the lungs to induce asthma. Reflux of the genital defects.137 A mother whose asthma is well con-
acidic fluid into the esophagus likely destabilizes asthma trolled and free of complications imposes no additional
by enhancing the cholinergic autonomic nervous system risk to the fetus.
influence or microaspiration, or both. GE reflux should The goals of asthma treatment during pregnancy are
be suspected in patients with poorly controlled asthma, to prevent acute exacerbations and to optimize lung func-
particularly those who have nocturnal symptom break- tion, which should provide maximum benefit to the health
throughs. 2 Reflux symptoms do not have to be present, of the mother and the fetus. 2,138 If asthma medications are
which makes the diagnosis difficult. However, when necessary during pregnancy, one must keep in mind the
GE reflux is symptomatic, patients usually complain of benefit of keeping asthma under control against the small
“heartburn” or sometimes note food regurgitated into the potential risk for adverse effects from the asthma medi-
throat. 2 A patient who has a hiatal hernia is at particular cations during pregnancy. The majority of asthma medi-
risk for GE reflux. cations that are used in practice present little to no risk
Treatment of patients with symptomatic GE reflux during pregnancy, although prospective well-designed
has been associated with improvement in some aspects and well-controlled clinical trials do not exist for most
606 Chapter 48 Asthma
medications that are used during pregnancy.139 In one be altered. Furthermore, allergen immunotherapy should
study, inhaled corticosteroids, beta-2 agonists, theophyl- not be started during pregnancy.
line, or montelukast were not associated with an increased Inhaled therapy should be selected over systemic ther-
frequency of fetal abnormalities.13,139 For prescription apies during pregnancy. Over-the-counter medications
drug labeling, the U.S. FDA has had a five-category medi- should be avoided. The obstetrician and primary care phy-
cation classification system (A-D and X) related to their sician should work together to create the safest treatment
potential for adverse effects on pregnancy but recently has regimen for the pregnant asthmatic patient. When ques-
begun to phase it out and replace it with a requirement for tions arise, the local asthma expert, generally an allergist
information from human and animal studies on known or pulmonary specialist, should be consulted.
possible maternal or fetal risks, medication dose adjust-
ments, and risk/benefit considerations.
These medication classifications are based on animal CLINICAL APPLICATIONS
and human data and also risk-benefit. The best category
is A, but there are no asthma medications in this group. • Asthma is diagnosed by identifying reversible air-
Both systemic and inhaled corticosteroids can be used flow obstruction, either at baseline or in response to
during pregnancy. The inhaled steroid budesonide has a bronchoprovocation challenge test, that is consis-
long been listed as category B and preferred during preg- tent with the clinical syndrome.
nancy because of the large amount of safety data obtained • Mild asthmatics may be managed with an occa-
from the medical birth registry in Sweden. 2 However, sional dose of a short-acting bronchodilator,
patients who are doing well on other inhaled corticoste- although persistent asthma almost always requires
roids could be continued. Inhaled beta agonist therapy an anti-inflammatory controller medication.
with albuterol, which has the most safety data during • Exercise-induced bronchospasm is present in most
human pregnancy, should be used for symptom break- asthmatics and can be treated or prevented with a
through. 2 During pregnancy, the leukotriene inhibitors variety of agents.
montelukast, and zafirlukast are not preferred therapy for • Certain special features such as occupation, stress,
mild persistent asthma. The Merck Pregnancy Registry, obesity, gastroesophageal reflux, medications, and
although small and unpublished, has not shown an pregnancy can make asthma more difficult to control
increase in perinatal complications. Allergy immunother- and should be looked for and managed in parallel
apy can be continued through pregnancy but should not with asthma.
REFERENCES
1. Centers for Disease Control and nitric oxide levels (FENO) for clinical in adult patients exposed to envi-
Prevention (CDC). Summary Health applications. Am J Respir Crit Care Med. ronmental tobacco smoke. Chest.
Statistics Tables for U.S. Adults: National 2011;184:602–615. 1994;106:746–749.
Health Interview Survey(NHIS) data, 9. Global Initiative for Asthma. Global 17. Marquette CH, Saulnier F, Leroy O, et
2016. Available at: https: //www.cdc Strategy For Asthma Management and al. Long-term prognosis of near-fatal
.gov/nchs/fastats/ast hma.htm. www.cdc. Prevention-Online Appendix, 2018. asthma. A 6-year follow-up study of
gov/nchs/fastats/asthma.htm Web site. Available from: www.ginasthma.org. 145 asthmatic patients who underwent
www.cdc.gov/nchs/fastats/asthma.htm. Accessed February, 2018. mechanical ventilation for a near-fatal
Accessed April. Accessed April, 2018. 10. Leuppi JD, Salome CM, Jenkins CR, attack of asthma. Am Rev Respir Dis.
2. National Asthma Education and et al. Predictive markers of asthma exac- 1992;146:76–81.
Prevention Program. Expert Panel erbation during stepwise dose reduction 18. Schoene RB, Abuan T, Ward RL, et al.
Report III: Guidelines for the diagnosis of inhaled corticosteroids. Am J Respir Effects of topical betaxolol, timolol,
and management of asthma. 2007; NIH Crit Care Med. 2001;163:406–412. and placebo on pulmonary function in
Publication No. 07-4051. 11. Petsky HL, Cates CJ, Lasserson TJ, asthmatic bronchitis. Am J Ophthalmol.
3. National Health Interview Survey. et al. A systematic review and meta- 1984;97:86–92.
Summary Health Statistics Tables for US analysis: Tailoring asthma treatment 19. Odeh M, Oliven A, Bassan H. Timolol
Adults and Children: National Health on eosinophilic markers (exhaled nitric eyedrop-induced fatal bronchospasm
Interview Survey, 2015–2018. oxide or sputum eosinophils). Thorax. in an asthmatic patient. J Fam Pract.
4. Crapo RO, Casaburi R, Coates AL, et al. 2012;67:199–208. 1991;32:97–98.
Guidelines for methacholine and exercise 12. Chung KF, Wenzel SE, Brozek JL, et al. 20. Taylor SL, Bush RK, Selner JC,
challenge testing-1999. This official International ERS/ATS guidelines on defi- et al. Sensitivity to sulfited foods
statement of the American Thoracic nition, evaluation and treatment of severe among sulfite-sensitive subjects with
Society was adopted by the ATS Board asthma. Eur Respir J. 2014;43:343–373. asthma. J Allergy Clin Immunol.
of Directors, July 1999. Am J Respir Crit 13. Global Initiative for Asthma. Global 1988;81:1159–1167.
Care Med. 2000;161:309–329. Strategy For Asthma Management and 21. Szczeklik A, Gryglewski RJ,
5. Li JT, O’Connell EJ. Clinical evalua- Prevention, 2018. Available from: www. Czerniawska-Mysik G. Clinical pat-
tion of asthma. Ann Allergy Asthma ginasthma.org. Accessed February, 2018. terns of hypersensitivity to nonsteroidal
Immunol. 1996;76:1–13; quiz 13-5. 14. Petsky HL, Kew KM, Turner C, et al. anti-inflammatory drugs and their
6. Pellegrino R, Viegi G, Brusasco V, et al. Exhaled nitric oxide levels to guide treat- pathogenesis. J Allergy Clin Immunol.
Interpretative strategies for lung function ment for adults with asthma. Cochrane 1977;60:276–284.
tests. Eur Respir J. 2005;26:948–968. Database Syst Rev. 2016;9:CD011440. 22. Spector SL, Wangaard CH, Farr RS.
7. Miller MR, Crapo R, Hankinson J, et al. 15. Franzese C. Diagnosis of inhalant Aspirin and concomitant idiosyncrasies
General considerations for lung function allergies: Patient history and test- in adult asthmatic patients. J Allergy Clin
testing. Eur Respir J. 2005;26:153–161. ing. Otolaryngol Clin North Am. Immunol. 1979;64:500–506.
8. Dweik RA, Boggs PB, Erzurum SC, 2011;44:611–623. 23. Watson WT, Becker AB, Simons FE.
et al. An official ATS clinical practice 16. Jindal SK, Gupta D, Singh A. Indices Treatment of allergic rhinitis with
guideline: Interpretation of exhaled of morbidity and control of asthma intranasal corticosteroids in patients
References 607
with mild asthma: Effect on lower airway receptor antagonist, causes dose-related ICS) versus LABA/ICS for adults with
responsiveness. J Allergy Clin Immunol. improvements in chronic asthma. asthma. Cochrane Database Syst Rev.
24.
1993;91:97–101.
Nelson HS. Gastroesophageal reflux
and pulmonary disease. J Allergy Clin 40.
Montelukast Asthma Study Group. Eur
Respir J. 1998;11:1232–1239.
Reiss TF, Chervinsky P, Dockhorn RJ,
56.
2016;(1):CD011721. doi: CD011721.
Sobieraj DM, Baker WL, Nguyen E, et al.
Association of inhaled corticosteroids
48
Immunol. 1984;73:547–556. et al. Montelukast, a once-daily leukotri- and long-acting muscarinic antagonists
25. Klucka CV, Ownby DR, Green J, et al. ene receptor antagonist, in the treatment with asthma control in patients with
Cat shedding of Fel d I is not reduced of chronic asthma: A multicenter, ran- uncontrolled, persistent asthma: A sys-
by washings, Allerpet-C spray, or domized, double-blind trial. Montelukast tematic review and meta-analysis. JAMA.
acepromazine. J Allergy Clin Immunol. Clinical Research Study Group. Arch 2018;319:1473–1484.
1995;95:1164–1171. Intern Med. 1998;158:1213–1220. 57. Busse WW, Massanari M, Kianifard F,
26. Platts-Mills TA, Tovey ER, Mitchell EB, 41. Malmstrom K, Rodriguez-Gomez G, et al. Effect of omalizumab on the need
et al. Reduction of bronchial hyperreac- Guerra J, et al. Oral montelukast, inhaled for rescue systemic corticosteroid treat-
tivity during prolonged allergen avoid- beclomethasone, and placebo for chronic ment in patients with moderate-to-severe
ance. Lancet. 1982;2:675–678. asthma. A randomized, controlled trial. persistent IgE-mediated allergic asthma:
27. Abramson MJ, Puy RM, Weiner JM. Montelukast/Beclomethasone A pooled analysis. Curr Med Res Opin.
Is allergen immunotherapy effective in Study Group. Ann Intern Med. 2007;23:2379–2386.
asthma? A meta-analysis of randomized 1999;130:487–495. 58. Rodrigo GJ, Neffen H, Castro-Rodriguez
controlled trials. Am J Respir Crit Care 42. Allen-Ramey FC, Duong PT, Riedel AA, JA. Efficacy and safety of subcutaneous
Med. 1995;151:969–974. et al. Observational study of the effects omalizumab vs placebo as add-on therapy
28. Creticos PS, Reed CE, Norman of using montelukast vs fluticasone in to corticosteroids for children and adults
PS, et al. Ragweed immunotherapy patients matched at baseline. Ann Allergy with asthma: A systematic review. Chest.
in adult asthma. N Engl J Med. Asthma Immunol. 2004;93:373–380. 2011;139:28–35.
1996;334:501–506. 43. Dahlen SE, Malmstrom K, Nizankowska 59. Fahy JV. Reducing IgE levels as a strategy
29. AAAI Board of Directors. Guidelines to E, et al. Improvement of aspirin-intoler- for the treatment of asthma. Clin Exp
minimize the risk from systemic reac- ant asthma by montelukast, a leukotriene Allergy. 2000;30 Suppl 1:16–21.
tions caused by immunotherapy with antagonist: A randomized, double-blind, 60. Barnes PJ. Anti-IgE therapy in
allergenic extracts. American Academy of placebo-controlled trial. Am J Respir Crit asthma: Rationale and therapeutic
Allergy and Immunology. J Allergy Clin Care Med. 2002;165:9–14. potential. Int Arch Allergy Immunol.
Immunol. 1994;93:811–812. 44. Lee DK, Haggart K, Robb FM, et al. 2000;123:196–204.
30. Newhouse MT, Dolovich MB. Control Montelukast protects against nasal 61. Corren J, Casale TB, Lanier B, et al.
of asthma by aerosols. N Engl J Med. lysine-aspirin challenge in patients with Safety and tolerability of omalizumab.
1986;315:870–874. aspirin-induced asthma. Eur Respir J. Clin Exp Allergy. 2009;39:788–797.
31. National Asthma Education and 2004;24:226–230. 62. Soler M, Matz J, Townley R, et al. The
Prevention Program. Expert Panel Report 45. Richter K, Gronke L, Janicki S, et al. anti-IgE antibody omalizumab reduces
3 (EPR-3): Guidelines for the Diagnosis Effect of azelastine, montelukast, and exacerbations and steroid requirement
and Management of Asthma-Summary their combination on allergen-induced in allergic asthmatics. Eur Respir J.
Report 2007. J Allergy Clin Immunol. bronchoconstriction in asthma. Pulm 2001;18:254–261.
2007;120:S94–138. Pharmacol Ther. 2008;21:61–66. 63. Busse W, Corren J, Lanier BQ, et al.
32. Dutoit JI, Salome CM, Woolcock AJ. 46. Riffelmann FW, Droste G, Lauter H, Omalizumab, anti-IgE recombinant
Inhaled corticosteroids reduce the et al. Influence of montelukast on inha- humanized monoclonal antibody,
severity of bronchial hyperresponsive- lational bronchial allergen provocation. for the treatment of severe allergic
ness in asthma but oral theophyl- Pneumologie. 2002;56:493–497. asthma. J Allergy Clin Immunol.
line does not. Am Rev Respir Dis. 47. D’Alonzo GE, Smolensky M. The chrono- 2001;108:184–190.
1987;136:1174–1178. pharmacological application of theophyl- 64. Holgate ST, Chuchalin AG, Hebert J,
33. Juniper EF, Kline PA, Vanzieleghem MA, line therapy in asthma. Monaldi Arch et al. Efficacy and safety of a recombi-
et al. Long-term effects of budesonide Chest Dis. 1994;49:36–43. nant anti-immunoglobulin E antibody
on airway responsiveness and clinical 48. Vassallo R, Lipsky JJ. Theophylline: (omalizumab) in severe allergic asthma.
asthma severity in inhaled steroid- Recent advances in the understand- Clin Exp Allergy. 2004;34:632–638.
dependent asthmatics. Eur Respir J. ing of its mode of action and uses in 65. Lanier B, Bridges T, Kulus M, et al.
1990;3:1122–1127. clinical practice. Mayo Clin Proc. Omalizumab for the treatment of exac-
34. Juniper EF, Kline PA, Vanzieleghem MA, 1998;73:346–354. erbations in children with inadequately
et al. Effect of long-term treatment with 49. Weinberger M, Hendeles L. controlled allergic (IgE-mediated)
an inhaled corticosteroid (budesonide) Theophylline in asthma. N Engl J Med. asthma. J Allergy Clin Immunol.
on airway hyperresponsiveness and 1996;334:1380–1388. 2009;124:1210–1216.
clinical asthma in nonsteroid-depen- 50. Markham A, Faulds D. Theophylline. 66. Walker S, Monteil M, Phelan K, et al.
dent asthmatics. Am Rev Respir Dis. A review of its potential steroid Anti-IgE for chronic asthma in adults and
1990;142:832–836. sparing effects in asthma. Drugs. children. Cochrane Database Syst Rev.
35. Haahtela T, Jarvinen M, Kava T, et al. 1998;56:1081–1091. 2006;(2):CD003559.
Comparison of a beta 2-agonist, terbu- 51. Sullivan P, Bekir S, Jaffar Z, et al. Anti- 67. Humbert M, Beasley R, Ayres J, et al.
taline, with an inhaled corticosteroid, inflammatory effects of low-dose oral Benefits of omalizumab as add-on therapy
budesonide, in newly detected asthma. N theophylline in atopic asthma. Lancet. in patients with severe persistent asthma
Engl J Med. 1991;325:388–392. 1994;343:1006–1008. who are inadequately controlled despite
36. Peters-Golden M, Henderson WR, 52. Jenne JW. Reassessing the therapeutic best available therapy (GINA 2002 step
Jr. Leukotrienes. N Engl J Med. range for theophylline on laboratory 4 treatment): INNOVATE. Allergy.
2007;357:1841–1854. report forms: Another viewpoint. 2005;60:309–316.
37. Altman LC, Munk Z, Seltzer J, et al. A Pharmacotherapy. 1993;13:595–597. 68. Bousquet J, Cabrera P, Berkman N, et al.
placebo-controlled, dose-ranging study 53. D’Alonzo GE, Nathan RA, Henochowicz The effect of treatment with omalizumab,
of montelukast, a cysteinyl leukotriene- S, et al. Salmeterol xinafoate as an anti-IgE antibody, on asthma exacer-
receptor antagonist. Montelukast Asthma maintenance therapy compared with bations and emergency medical visits in
Study Group. J Allergy Clin Immunol. albuterol in patients with asthma. JAMA. patients with severe persistent asthma.
1998;102:50–56. 1994;271:1412–1416. Allergy. 2005;60:302–308.
38. Leff JA, Busse WW, Pearlman D, 54. Peters SP, Kunselman SJ, Icitovic N, et al. 69. Djukanovic R, Wilson SJ, Kraft M,
et al. Montelukast, a leukotriene- Tiotropium bromide step-up therapy for et al. Effects of treatment with anti-
receptor antagonist, for the treatment adults with uncontrolled asthma. N Engl immunoglobulin E antibody omalizumab
of mild asthma and exercise-induced J Med. 2010;363:1715–1726. on airway inflammation in allergic
bronchoconstriction. N Engl J Med. 55. Kew KM, Dahri K. Long-acting mus- asthma. Am J Respir Crit Care Med.
1998;339:147–152. carinic antagonists (LAMA) added to 2004;170:583–593.
39. Noonan MJ, Chervinsky P, Brandon M, combination long-acting beta2-agonists 70. Fahy JV, Fleming HE, Wong HH, et al.
et al. Montelukast, a potent leukotriene and inhaled corticosteroids (LABA/ The effect of an anti-IgE monoclonal
608 Chapter 48 Asthma
antibody on the early- and late-phase thermoplasty in the treatment of severe 106. Edmunds AT, Tooley M, Godfrey S. The
responses to allergen inhalation in asthma: A multicenter, randomized, refractory period after exercise-induced
asthmatic subjects. Am J Respir Crit Care double-blind, sham-controlled clini- asthma: Its duration and relation to the
Med. 1997;155:1828–1834. cal trial. Am J Respir Crit Care Med. severity of exercise. Am Rev Respir Dis.
71. Humbert M, Taille C, Mala L, et al. 2010;181:116–124. 1978;117:247–254.
Omalizumab effectiveness in patients 87. Spitzer WO, Suissa S, Ernst P, et al. The 107. de Bisschop C, Guenard H, Desnot P, et al.
with severe allergic asthma according to use of beta-agonists and the risk of death Reduction of exercise-induced asthma in
blood eosinophil count: The STELLAIR and near death from asthma. N Engl J children by short, repeated warm ups. Br
study. Eur Respir J. 2018. Med. 1992;326:501–506. J Sports Med. 1999;33:100–104.
72. Olivieri M, Biscardo CA, Turri S, et al. 88. Nathan RA, Sorkness CA, Kosinski M, 108. Kemp JP, Dockhorn RJ, Busse WW, et
Omalizumab in persistent severe bakers’ et al. Development of the asthma control al. Prolonged effect of inhaled salme-
asthma. Allergy. 2008;63:790–791. test: A survey for assessing asthma terol against exercise-induced bron-
73. Leynadier F, Doudou O, Gaouar H, control. J Allergy Clin Immunol. chospasm. Am J Respir Crit Care Med.
et al. Effect of omalizumab in health 2004;113:59–65. 1994;150:1612–1615.
care workers with occupational latex 89. D’Alonzo GE, Ciccolella DE. Nocturnal 109. Spooner CH, Spooner GR, Rowe BH.
allergy. J Allergy Clin Immunol. asthma: Physiologic determinants and Mast-cell stabilising agents to prevent
2004;113:360–361. current therapeutic approaches. Curr exercise-induced bronchoconstric-
74. Kim HL, Leigh R, Becker A. Opin Pulm Med. 1996;2:48–59. tion. Cochrane Database Syst Rev.
Omalizumab: Practical considerations 90. Waalkens HJ, Van Essen-Zandvliet EE, 2003;(4):CD002307.
regarding the risk of anaphylaxis. Allergy Hughes MD, et al. Cessation of long-term 110. Philip G, Villaran C, Pearlman DS, et al.
Asthma Clin Immunol. 2010;6:32. treatment with inhaled corticosteroid Protection against exercise-induced bron-
75. Cox L, Platts-Mills TA, Finegold I, et al. (budesonide) in children with asthma choconstriction two hours after a single
American Academy of Allergy, Asthma results in deterioration. The Dutch oral dose of montelukast. J Asthma.
& Immunology/American College of CNSLD Study Group. Am Rev Respir 2007;44:213–217.
Allergy, Asthma and Immunology Joint Dis. 1993;148:1252–1257. 111. Vathenen AS, Knox AJ, Wisniewski
Task Force Report on omalizumab- 91. Benatar SR. Fatal asthma. N Engl J Med. A, et al. Effect of inhaled budesonide
associated anaphylaxis. J Allergy Clin 1986;314:423–429. on bronchial reactivity to histamine,
Immunol. 2007;120:1373–1377. 92. Djukanovic R, Roche WR, Wilson JW, et exercise, and eucapnic dry air hyperven-
76. Farne HA, Wilson A, Powell C, et al. al. Mucosal inflammation in asthma. Am tilation in patients with asthma. Thorax.
Anti-IL5 therapies for asthma. Cochrane Rev Respir Dis. 1990;142:434–457. 1991;46:811–816.
Database Syst Rev. 2017;9:CD010834. 93. Laitinen A, Laitinen LA. Airway 112. Nicholson PJ, Cullinan P, Taylor AJ, et al.
77. Ortega HG, Yancey SW, Mayer B, et al. morphology: Epithelium/basement Evidence based guidelines for the preven-
Severe eosinophilic asthma treated with membrane. Am J Respir Crit Care Med. tion, identification, and management of
mepolizumab stratified by baseline eosino- 1994;150:S14–S17. occupational asthma. Occup Environ
phil thresholds: A secondary analysis of 94. Busse WW. Role and contribution of viral Med. 2005;62:290–299.
the DREAM and MENSA studies. Lancet respiratory infections to asthma. Allergy. 113. Pisati G, Baruffini A, Zedda S. Toluene
Respir Med. 2016;4:549–556. 1993;48:57–61; discussion 62-4. diisocyanate induced asthma: Outcome
78. Bel EH, Wenzel SE, Thompson PJ, et al. 95. Agarwal R. Allergic bronchopulmonary according to persistence or cessation of
Oral glucocorticoid-sparing effect of aspergillosis. Chest. 2009;135:805–826. exposure. Br J Ind Med. 1993;50:60–64.
mepolizumab in eosinophilic asthma. N 96. Koshkareva YA, Krouse JH. 114. Boulet LP. Asthma and obesity. Clin Exp
Engl J Med. 2014;371:1189–1197. Immunotherapy - traditional. Allergy. 2013;43:8–21.
79. McCracken JL, Tripple JW, Calhoun Otolaryngol Clin North Am. 115. Freitas PD, Ferreira PG, Silva AG, et al.
WJ. Biologic therapy in the manage- 2011;44:741–752. The role of exercise in a weight-loss
ment of asthma. Curr Opin Allergy Clin 97. Nelson HS. Multiallergen immu- program on clinical control in obese
Immunol. 2016;16:375–382. notherapy for allergic rhinitis and adults with asthma. A randomized con-
80. Ortega HG, Liu MC, Pavord ID, et al. asthma. J Allergy Clin Immunol. trolled trial. Am J Respir Crit Care Med.
Mepolizumab treatment in patients with 2009;123:763–769. 2017;195:32–42.
severe eosinophilic asthma. N Engl J 98. Walker SM, Pajno GB, Lima MT, et al. 116. Wright RJ. Epidemiology of stress and
Med. 2014;371:1198–1207. Grass pollen immunotherapy for seasonal asthma: From constricting communi-
81. Castro M, Zangrilli J, Wechsler ME, rhinitis and asthma: A randomized, ties and fragile families to epigenetics.
et al. Reslizumab for inadequately controlled trial. J Allergy Clin Immunol. Immunol Allergy Clin North Am.
controlled asthma with elevated blood 2001;107:87–93. 2011;31:19–39.
eosinophil counts: Results from two 99. Creticos PS, Reed CE, Norman 117. Busse WW, Kiecolt-Glaser JK, Coe C, et
multicentre, parallel, double-blind, ran- PS, et al. Ragweed immunotherapy al. NHLBI Workshop summary. Stress
domised, placebo-controlled, phase 3 tri- in adult asthma. N Engl J Med. and asthma. Am J Respir Crit Care Med.
als. Lancet Respir Med. 2015;3:355–366. 1996;334:501–506. 1995;151:249–252.
82. Castro M, Mathur S, Hargreave F, et al. 100. Abramson MJ, Puy RM, Weiner 118. Sampson HA. 9Food allergy. J Allergy
Reslizumab for poorly controlled, eosino- JM. Allergen immunotherapy for Clin Immunol. 2003;111:S540–7.
philic asthma: A randomized, placebo- asthma. Cochrane Database Syst Rev. 119. Pleskow WW, Stevenson DD, Mathison
controlled study. Am J Respir Crit Care 2003;(4):CD001186. DA, et al. Aspirin-sensitive rhinosinusitis/
Med. 2011;184:1125–1132. 101. Storms WW. Asthma associated with asthma: Spectrum of adverse reactions
83. Bjermer L, Lemiere C, Maspero J, et al. exercise. Immunol Allergy Clin North to aspirin. J Allergy Clin Immunol.
Reslizumab for inadequately controlled Am. 2005;25:31–43. 1983;71:574–579.
asthma with elevated blood eosinophil 102. Boulet LP, O’Byrne PM. Asthma 120. Jenkins C, Costello J, Hodge L.
levels: A randomized phase 3 study. and exercise-induced bronchocon- Systematic review of prevalence of aspirin
Chest. 2016;150:789–798. striction in athletes. N Engl J Med. induced asthma and its implications for
84. Bleecker ER, FitzGerald JM, Chanez P, 2015;372:641–648. clinical practice. BMJ. 2004;328:434.
et al. Efficacy and safety of benralizumab 103. Lucas SR, Platts-Mills TA. Physical activ- 121. Hedman J, Kaprio J, Poussa T, et al.
for patients with severe asthma uncon- ity and exercise in asthma: Relevance to Prevalence of asthma, aspirin intolerance,
trolled with high-dosage inhaled cortico- etiology and treatment. J Allergy Clin nasal polyposis and chronic obstructive
steroids and long-acting beta2-agonists Immunol. 2005;115:928–934. pulmonary disease in a population-based
(SIROCCO): A randomised, multicentre, 104. Kukafka DS, Lang DM, Porter S, et study. Int J Epidemiol. 1999;28:717–722.
placebo-controlled phase 3 trial. Lancet. al. Exercise-induced bronchospasm in 122. Gyllfors P, Bochenek G, Overholt J, et al.
2016;388:2115–2127. high school athletes via a free running Biochemical and clinical evidence that
85. Kheir F, Majid A. Bronchial thermo- test: Incidence and epidemiology. Chest. aspirin-intolerant asthmatic subjects
plasty: A nonpharmacologic therapy 1998;114:1613–1622. tolerate the cyclooxygenase 2-selective
for severe asthma. Clin Chest Med. 105. B euther DA, Martin RJ. Efficacy analgetic drug celecoxib. J Allergy Clin
2018;39:261–269. of a heat exchanger mask in cold Immunol. 2003;111:1116–1121.
86. Castro M, Rubin AS, Laviolette M, et al. exercise-induced asthma. Chest. 123. Settipane RA, Schrank PJ, Simon RA,
Effectiveness and safety of bronchial 2006;129:1188–1193. et al. Prevalence of cross-sensitivity with
References 609
acetaminophen in aspirin-sensitive asth- asthmatic subjects. Am Rev Respir Dis. health surveys. Ann Epidemiol.
matic subjects. J Allergy Clin Immunol. 1986;133:264–268. 2003;13:317–324.
1995;96:480–485.
124. Samter M, Beers RF, Jr. Intolerance to
aspirin. Clinical studies and consider-
130. Littner MR, Leung FW, Ballard ED,2nd,
et al. Effects of 24 weeks of lansoprazole
therapy on asthma symptoms, exacerba-
135. Murphy VE, Clifton VL, Gibson PG.
Asthma exacerbations during preg-
nancy: Incidence and association with
48
ation of its pathogenesis. Ann Intern tions, quality of life, and pulmonary adverse pregnancy outcomes. Thorax.
Med. 1968;68:975–983. function in adult asthmatic patients 2006;61:169–176.
125. Szczeklik A. The cyclooxygenase theory with acid reflux symptoms. Chest. 136. G luck JC, Gluck PA. The effect of
of aspirin-induced asthma. Eur Respir J. 2005;128:1128–1135. pregnancy on the course of asthma.
1990;3:588–593. 131. Kiljander TO, Junghard O, Beckman O, Immunol Allergy Clin North Am.
126. Dahlen B, Nizankowska E, Szczeklik et al. Effect of esomeprazole 40 mg once 2006;26:63–80.
A, et al. Benefits from adding the or twice daily on asthma: A randomized, 137. Kallen B, Rydhstroem H, Aberg A.
5-lipoxygenase inhibitor zileuton to placebo-controlled study. Am J Respir Asthma during pregnancy—A popula-
conventional therapy in aspirin-intolerant Crit Care Med. 2010;181:1042–1048. tion based study. Eur J Epidemiol.
asthmatics. Am J Respir Crit Care Med. 132. McCallister JW, Parsons JP, Mastronarde 2000;16:167–171.
1998;157:1187–1194. JG. The relationship between gastro- 138. National Heart, Lung, and Blood
127. Odeh M, Oliven A, Bassan H. Timolol esophageal reflux and asthma: An update. Institute, National Asthma Education
eyedrop-induced fatal bronchospasm Ther Adv Respir Dis. 2011;5:143–150. and Prevention Program Asthma and
in an asthmatic patient. J Fam Pract. 133. American Lung Association Asthma Pregnancy Working Group. NAEPP expert
1991;32:97–98. Clinical Research Centers, Mastronarde panel report. Managing asthma during
128. Schoene RB, Abuan T, Ward RL, et al. JG, Anthonisen NR, et al. Efficacy of pregnancy: Recommendations for pharma-
Effects of topical betaxolol, timolol, esomeprazole for treatment of poorly cologic treatment-2004 update. J Allergy
and placebo on pulmonary function in controlled asthma. N Engl J Med. Clin Immunol. 2005;115:34–46.
asthmatic bronchitis. Am J Ophthalmol. 2009;360:1487–1499. 139. Lim A, Stewart K, Konig K, et al.
1984;97:86–92. 134. Kwon HL, Belanger K, Bracken MB. Systematic review of the safety of
129. Dunn TL, Gerber MJ, Shen AS, et al. The Asthma prevalence among pregnant regular preventive asthma medications
effect of topical ophthalmic instillation of and childbearing-aged women in the during pregnancy. Ann Pharmacother.
timolol and betaxolol on lung function in United States: Estimates from national 2011;45:931–945.
49
CHAPTER
are over 200. Diisocyanates are the most common cause refractory moderate-severe cases. Oral steroids are used
of SIA in many industrialized areas.1 Other sensitizers for severe acute exacerbations, while immunotherapy has
include proteins, polysaccharides, animal dander, cas- been tried in a few small studies with variable efficacy.6 , 7
tor beans, latex, and vegetable gum. WRA is caused by
the activation of T-lymphocytes resulting in cytokine-
mediated airway inflammation. IIA, on the other hand, is 49.1.4 Chronic Obstructive Pulmonary
thought to be caused by a direct irritant effect of inhaled Disease
chemical compounds on the bronchial wall that results
Chronic obstructive pulmonary disease (COPD) is an
in the activation of inflammatory pathways that cause
inflammatory lung disease characterized by irreversible
reversible airway obstruction. It is less common than SIA.
airway obstruction.8 – 10 Smoking is the most important
risk factor, with more than two-thirds of COPD cases
linked to the long-term effects of cigarette smoking.11
49.1.2 Clinical Presentation and Diagnosis
Sensitizer-induced symptoms are variable and can occur at
any time during the workday or toward its end. Symptom 49.1.5 Epidemiology
remission or improvement typically occurs during week- COPD affects about 10% of the general population, with
ends and holidays when the patient is away from the work a prevalence that increases with age and smoking.9 , 10
environment. Making a confident diagnosis of WRA first Globally, 65 million people are affected, and COPD kills
requires establishing a diagnosis of asthma on the basis over 3 million people annually.12 , 13 In the United States,
of a consistent history, associated with reversible airway it is the third most common cause of death, affecting
obstruction on spirometry (defined as a reduced FEV1/ about 16 million people and causing over 120,000 annual
FVC ratio below the lower limit of normal that increases deaths.14 , 15 Healthcare costs from COPD are estimated to
by 12% and 200 ml with the administration of a broncho- be over $50 billion annually.15
dilator).3 In patients without airway obstruction, bron-
chial hyperresponsiveness demonstrated on bronchial
provocation testing with either methacholine or histamine 49.1.6 Clinical Presentation and Diagnosis
supports the diagnosis. Chest imaging in the form of a
A diagnosis of COPD should be considered in any patient
chest x-ray is recommended to exclude parenchymal lung
presenting with a chronic cough, shortness of breath, and
disease that may be causing symptoms.
sputum production in the context of a smoking history
Once a diagnosis of asthma is established, the next step
and suspected or established biomass fuel exposure. The
involves demonstrating an objective association between
latter should be considered in patients originating from
work-environment exposures and worsening lung function
low- and middle-income countries in sub-Saharan Africa,
as determined by an objective demonstration of airflow
parts of South America, and in Asia.16
obstruction measured by Peak Expiratory Flow Rate (PEFR)
COPD is a heterogeneous disease with different pheno-
or FEV1 on spirometry. The recommended minimum moni-
types that include chronic bronchitis and emphysema most
toring period should be two weeks at and away from work
prominently. Chronic bronchitis manifests as a cough and
during which asthma treatment should be kept constant.
sputum production on most days for three months in two
Worsening of symptoms during work that improves when
consecutive years. Patients with an emphysema phenotype
the patient is away from work is consistent with a diagno-
have an abnormal and permanent dilatation of airspaces
sis of work-related asthma. In patients who are unable to
distal to the terminal bronchioles. Emphysema is associ-
continue employment due to symptom limitation, referral
ated with the destruction of the alveolar walls. Symptoms
to specialized centers for bronchoprovocation testing using
common to these two major phenotypes include wheez-
occupational inhalational agents is recommended. 4 , 5
ing, fatigue, and loss of appetite.
Spirometry is required to make the diagnosis of COPD.
A post-bronchodilator FEV1/FVC less than 0.70 confi rms
49.1.3 Prevention and Treatment the presence of persistent airfl ow limitation and identifi es
Primary prevention of work-related asthma involves the presence of COPD in patients with appropriate symp-
employee education, avoidance of exposure to sensitiz- toms and predisposing risks.10 The use of an FEV1/FVC
ing agents; and where this is not possible, substitution of ratio of 0.7 as a diagnostic criterion is independent of ref-
known sensitizing agents with non-sensitizers. Periodic erence values and is a simple, easily reproducible measure
medical surveillance using respiratory questionnaires with that can be used in a physician’ s office. Physical examina-
or without spirometry and immunologic tests are recom- tion findings are nonspecific and rarely aid in the diagnosis
mended secondary preventative measures.4 except in advanced cases where chest wall deformities such
Pharmacotherapy is an adjunct to sensitizer and irri- a barrel-shaped chest may be present.17 The disease course
tant avoidance in the treatment of work-related asthma is variable, with extended periods of chronic daily symp-
and follows recommended guidelines, including the use toms punctuated by periods of acute exacerbations during
of short-acting beta agonists (SABA) on an “ as-needed which there is a sustained worsening of the patient’ s condi-
basis” for symptom relief, with the addition of an inhaled tion, from the stable state and beyond normal day-to-day
corticosteroid (ICS) inhaler in moderate cases. An inhaled variations that necessitate a change in regular medication.18
long-acting beta 2 − adrenergic (LABA) bronchodilator Once a diagnosis of COPD is made, a combined assess-
can be added to the regimen as a “ step-up” therapy in ment is performed to determine symptom burden, degree
49.1 Work-Related Asthma 613
of airflow limitation, and the risk of acute exacerbation. To Age-appropriate pneumococcal vaccination should be
49
assess symptoms, the modified Medical Research Council offered to all patients in accordance with established guide-
(MMRC) or COPD assessment test (CAT) score can be lines. The pneumococcal polysaccharide vaccine (PPSV23,
used. Next, the FEV1 is used to classify the degree of air- Pneumovax) is recommended for patients under age 65
flow obstruction based on the GOLD criteria. Finally, the years; while the pneumococcal conjugate vaccine (PCV13,
number of acute exacerbations and hospitalizations in the Prevnar) is recommended for patients aged 65 years and
preceding year is determined. Using these variables, pre- older.21
sented in Figure 49.1, patients are categorized into one of
four groups (A, B, C, and D). The GOLD criteria present
a framework on which treatment is instituted. 49.1.9 Pharmacologic Therapy
Bronchodilators are the first-line pharmacologic drug class
for symptom control and have been shown to improve lung
49.1.7 Prevention and Treatment aeration and exercise tolerance. In patients with low risk
The therapeutic objectives in COPD management include of acute exacerbation and fewer symptoms (Category A),
symptom control, prevention of acute exacerbations, the use of a short-acting beta agonist (SABA) alone or in
and improvement of exercise tolerance. This is usually combination with a short-acting muscarinic antagonist
achieved with a combination of non-pharmacologic and (SAMA) is appropriate for use as a reliever medication on
pharmacologic interventions. an as-needed basis. For low-risk patients with high symp-
tom scores (Category B) and high-risk patients (Categories
C and D), maintenance therapy is indicated for symptom
49.1.8 Non-pharmacologic Therapy control. This involves the use of long-acting bronchodilators
such as beta agonists (LABA) or a long-acting muscarinic
Smoking cessation is the most effective non-pharmaco- antagonists (LAMA) singly or in combination. Patients in
logic intervention in preventing COPD and slowing its categories C and D may also benefit from the addition of
progression. All patients should be offered tobacco cessa- an inhaled corticosteroid (ICS) as combination therapy in
tion counseling. refractory cases. ICS use as monotherapy is discouraged,
Assessing medication adherence and training in good and recent evidence suggests a better outcome in patients
inhaler technique are integral parts of patient educa- on LAMA/LABA compared to an ICS/LABA, with a lower
tion.19 , 20 Pulmonary rehabilitation is a multidisciplinary incidence of pneumonia in patients with moderate-to-severe
program that aims to improve exercise capacity, reduce COPD and higher dyspnea scores (Categories C and D).10 , 22
symptoms, and improve overall quality of life in patients
across the spectrum of disease severity and has been
shown to improve dyspnea, health status, and exercise
tolerance.19 It is therefore recommended that all patients
49.1.10 Asbestos-Related Lung Disease
with COPD be considered for pulmonary rehabilitation as Asbestos-related lung disease is a group of lung diseases
part of a multimodality treatment regime. caused by exposure to naturally occurring asbestos fibers
comprised of magnesium silicate minerals. These fibers which may be difficult to distinguish from other causes of
have desirable physical properties for industrial use, such pulmonary fibrosis. Chest CT may show honeycombing
as high tensile strength, flexibility, and resistance to chem- and upper lobe involvement in advanced stages of the dis-
ical and thermal degradation, hence their prior extensive ease. The presence of pleural plaques suggests prior asbes-
use in the construction, automotive, and textile indus- tos exposure and raises suspicion for asbestos-associated
tries. 23 Chrysotile (also known as white asbestos) is the pulmonary fibrosis but is not confirmatory. Such patients
most common and only type of asbestos currently used should be referred to specialists familiar with asbestos-
in manufacturing in the United States, while the more related lung disease for periodic monitoring of disease
toxic amphibole fibers, including crocidolite, amosite, and progression and the development of asbestos-associated
tremolite are still used in parts of sub-Saharan Africa, malignancies.31 , 32
South America, and Asia. 24 Asbestos fibers are highly car-
cinogenic and are known to cause lung cancer and malig-
nant mesothelioma. Asbestos is considered one of the 49.1.12 Silicosis
most important occupational carcinogens. 24
Silicosis is a fibrotic lung disease caused by inhalation
of free crystalline silicon dioxide or silica and is recog-
49.1.10.1 Epidemiology nized as one of the most important occupational diseases
worldwide. Silicon dioxide or silica is the most abundant
The use of asbestos has been banned in many countries,
mineral and occurs in crystalline and amorphous forms.33
including the United States. Therefore, exposure is lim-
The most common free crystalline forms of silica in work-
ited to certain occupations such as construction work-
places are quartz, tridymite, and cristobalite.33
ers, car mechanics, and plumbers working on old homes
and buildings where asbestos was used. 25 Global asbestos
exposure is unknown, although it is estimated that world-
wide over 40,000 people die of malignant mesothelioma 49.1.13 Epidemiology
each year. 24 Silica exposure is highest among individuals employed in
construction work involving masonry, heavy construction,
painting, and in iron and steel foundries. Metalworking
49.1.11 Clinical Presentation and Diagnosis occupations that involve sandblasting, grinding, or buff-
ing of metal parts are also considered high-risk jobs. 33
Individuals exposed to asbestos are mostly asymptom- Global disease burden is difficult to estimate due to lack
atic, and the latency period can be as long as 20– 30 years of disease surveillance in lower- and middle-income coun-
between initial exposure and the development of the clini- tries (LMICs); however countries like China and South
cally apparent disease. In patients who develop clinical Africa have reported significant silica exposure, suggest-
disease, benign asbestos pleural plaques are a common ing that the disease burden in these parts of the world
finding, the development of which suggests prior exposure may be high. In the United States, about 127,000 miners
and is reported to be prevalent in about 60– 70% of indi- are reportedly exposed, with a higher rate of disease in
viduals with an average cumulative exposure of about 32 African Americans compared to white workers with the
years. 26 , 27 The diagnosis is usually incidental and made same dust exposure.34 , 35
during chest imaging for other reasons. Chest x-ray may
show a diffuse pleural thickening in the lower portions
of the chest, sparing the apices and costophrenic angles,
which may be calcified in about 5– 15% of cases. 28 , 29
49.1.14 Clinical Presentation and Diagnosis
Chest CT has a higher sensitivity and specificity and can Acute silicosis is characterized by rapid onset of symptoms
detect noncalcified pleural plaques. including dyspnea, cough, weight loss, fatigue, and some-
Malignant pleural mesothelioma (MPM) is a dreaded times pleuritic pain and fever following acute exposure
consequence of asbestos exposure that typically occurs in to silica. 36 Lung examination may reveal crackles. Chest
older (median age 60) men. Patients with MPM present x-ray may be normal in the acute phase or may demon-
with nonspecific symptoms of dyspnea, cough, chest pain, strate bilateral consolidation and ground-glass infiltrates.
and constitutional symptoms including fever, chills, night Diagnosis of acute silicosis requires a high clinical index
sweats, malaise, and weight loss. Pleural effusions may be of suspicion and is contingent on establishing an occu-
present and are usually an exudate with an eosinophilic pational exposure to silica and the absence of other
cellular profile. Unfortunately, thoracentesis has a low differentials.
sensitivity for diagnosing MPM, hence a surgical pleu- Chronic silicosis is characterized by two clinical syn-
ral biopsy using a video-assisted thoracoscopic approach dromes on two ends of a disease spectrum, namely, simple
is the gold standard for diagnosis.30 Treatment of MPM silicosis (SS) and progressive massive fibrosis (PMF). In
involves multimodality treatment, including surgery in simple silicosis, a chest x-ray may show upper lobe predom-
patients who are good candidates for resection and chemo- inant ground-glass opacities; while in progressive massive
radiation therapy. In non-operable cases, chemotherapy, fibrosis, there are mass-like areas of dense consolidation.
palliative radiation, and tunneled pleural catheters have Pulmonary function tests may reveal a mixed obstructive
been employed for symptomatic relief. and restrictive ventilatory defect and a decreased DLCO.
Asbestos-associated pulmonary fibrosis (asbestosis) Bronchoscopy (when performed) is classically described as
is a less common form of asbestos-related lung disease demonstrating a milky lipoproteinaceous bronchoalveolar
49.2 Clinical Presentation and Diagnosis 615
Chronic beryllium disease is diagnosed when either small rounded opacities that may also be found in all lung
blood or bronchoalveolar lavage fluid BeLPT is posi- zones.43 Most cases are asymptomatic and are detected
tive in a patient with a documented history of beryllium incidentally as part of surveillance programs or in the con-
exposure. Other features supportive of the disease include text of a diagnostic workup for other conditions.
consistent radiographic abnormalities and lung pathology Progressive massive fibrosis (PMF) is a progressive form
demonstrating non-caseating granulomas with lympho- of CMDLD found in miners with greater dust exposure.
cytic infiltration. A recent study found PMF in about 63% of coal miners
with a mean coal mining tenure of 27 years in Kentucky
and Virginia.45 It may present with breathlessness, cough,
49.3 TREATMENT AND PREVENTION and the production of sputum that has been variably
described as mucoid, mucopurulent, and rarely discolored
Disease prevention involves the avoidance of inhalation as if mixed with black ink (melanoptysis). Clinical exam
and dermal exposures to beryllium by employing the use findings are nonspecific, and the average interval from
of personal protective equipment, administrative changes a normal chest radiograph to massive fibrosis can be as
such as the exclusion of workers from specific areas to long as 12 years.46 Spirometry findings include a restric-
prevent nonessential contact, and regular screening of tive, obstructive, or mixed pattern of impairment, and a
employees involved in activities with exposure to beryl- reduced DLCO depending on the severity of lung fibrosis.
lium. Patients with respiratory symptoms suspicious for An association between CWP and rheumatoid arthritis
berylliosis should be referred to a pulmonologist for diag- called Caplan syndrome, originally described by Anthony
nostic evaluation and treatment, which generally consists Caplan, describes the occurrence of multiple well-defined
of systemic corticosteroids. Methotrexate can be used as a opacities on chest radiographs of rheumatoid arthritis
second-line agent in corticosteroid-refractory cases. patients.47 CMDLD has also been associated with chronic
obstructive pulmonary disease and other pulmonary
infections which account for significant morbidity in
49.3.1 Coal Mine Dust Lung Disease patients with CWP.
Coal mine dust lung disease (CMDLD) refers to a broad
spectrum of lung diseases caused by exposure to coal
mine dust. It includes disease entities such as coal work- 49.5 PREVENTION AND TREATMENT
ers’ pneumoconiosis (CWP), progressive massive fibro-
In the United States, environmental controls are mandated
sis (PMF), Caplan Syndrome, and Chronic Obstructive
by federal law. Coal dust exposure can be minimized
Pulmonary Disease (COPD).42 , 43
using ventilation systems, water sprays, and other dust
capture devices as part of a continuous monitoring pro-
gram. There is no specific medical therapy that has proven
49.3.2 Epidemiology effective in reversing CMDLD. Management involves
Coal is the second largest energy source worldwide, periodic medical monitoring with periodic chest radio-
accounting for over 25% of global energy supply and graphs and spirometry.42 Patients with CMDLD should
more than one-third of the fuel used to generate electricity. be offered vaccinations against viral and bacterial patho-
Consequently, the number of individuals exposed to coal gens, and smoking cessation counseling should be offered
particles is considerable, with China, the United States, to patients who smoke.
and India being the top consumers accounting for over
70% of total global consumption. Coal production in the
United States is largely concentrated in a few states, includ- 49.5.1 High-Altitude Illnesses
ing Wyoming, West Virginia, Kentucky, Pennsylvania, and
Texas, accounting for over 70% of production.44 Most It is estimated that more than 30 million people each year
coal workers are men; therefore, CMDLD disproportion- travel to and from recreational areas with altitudes in
ately affects men, with about 38% of coal miners showing excess of 2,500 meters. This presents unique challenges
radiographic features of interstitial lung disease. Diagnosis for travelers to these areas, and therefore a good under-
of CMDLD is made clinically on the basis of a combination standing of common problems that arise from exposure to
of an appropriate exposure history, radiological or patho- high altitude is important in order to prevent the develop-
logical findings consistent with the diagnosis, and a lack ment of high-altitude illnesses.48
of alternative explanations for the patient’ s lung disease.43 High-altitude illnesses (HAI) are a group of pulmonary
and cerebral conditions that occur in the context of a rapid
initial ascent to altitudes at a rate that exceeds the body’ s
49.4 CLINICAL PRESENTATION ability to acclimatize to changes in oxygen tension. The
fraction of oxygen in inspired air is constant at 0.21 regard-
AND DIAGNOSIS less of altitude, but for each unit change in altitude, there is
a non-linear change in the barometric pressure of oxygen
Coal workers’ pneumoconiosis (CWP) is caused by the that affects the alveolar partial pressure and consequently,
accumulation of coal dust in the lungs and classically oxygen availability to tissues. The physiologic response to
presents as the occurrence of upper lobe predominant this change in oxygen tension is called acclimatization and
49.5 Prevention and Treatment 617
TABLE 49.1 Source : “ The Lake Louise Consensus on the Definition and Quantification of Altitude Illness” in Sutton JR,
Coates G, Houston CS (Eds), Hypoxia and Mountain Medicine . Queen City Printers, Burlington, Vermont, 1992 .
Acute Mountain Headache and at least one of the following symptoms:
Sickness • gastrointestinal (anorexia, nausea or vomiting)
• fatigue or weakness
• dizziness or lightheadedness
• difficulty sleeping
High-Altitude Cerebral The presence of a change in mental status and/or ataxia in a person with acute mountain sickness
Edema OR
the presence of both mental status changes and ataxia in a person without Acute Mountain Sickness
High-Altitude The presence of at least two of the following symptoms
Pulmonary Edema • dyspnea at rest
• cough
• weakness or decreased exercise performance
• chest tightness or congestion
AND
At least two of the following signs:
• crackles or wheezing in at least one lung field
• central cyanosis
• tachypnea
• tachycardia
618 Chapter 49 Occupational and Environmental Lung Diseases
AND DIAGNOSIS
CLINICAL APPLICATIONS
HP presents with intermittent dyspnea, wheezing, cough,
and constitutional symptoms, including fevers, chills, • A diagnosis of work-related asthma should be sus-
and malaise with a temporal relationship to an antigen pected in any patient with asthma that is difficult
exposure. 58 , 59 to control.
Chest CT is crucial in the diagnostic evaluation of • COPD should be considered as a diagnosis in any
patients in whom a diagnosis of HP is being entertained. patient with dyspnea from parts of the world where
Classical features include an upper lobe predominant cen- there is significant exposure to biomass fuel or coal
trilobular diffuse micronodular ground-glass opacifica- mining (even among non-smokers).
tion and mosaic attenuation (reflecting coexistent small • Employees involved in industries with exposure to
airways disease).60 , 61 silica, coal, asbestos, and beryllium should undergo
HP is classified into acute (inflammatory) HP, with periodic surveillance for pneumoconiosis using his-
a symptom duration less than six months and chronic tory, lung function testing, and chest imaging.
(fibrotic) HP, with symptom duration greater than six • Travelers to high altitudes should receive informa-
months. 56 Chronic HP is characterized by fibrotic changes tion on high-altitude illnesses and be counseled on
in high-resolution computed tomography images or lung how to prevent, recognize, and treat symptoms of
biopsy and is associated with a poorer outcome. 56 these syndromes.
REFERENCES
1. Tarlo, S. M. et al. Diagnosis and manage- 4. Tarlo, S. M. & Lemiere, C. Occupational 7. Leynadier, F., Herman, D., Vervloet, D.
ment of work-related asthma: American asthma. N. Engl. J. Med. 370, 640– 6 49 & Andre, C. Specific immunotherapy
College Of Chest Physicians Consensus (2014). with a standardized latex extract versus
Statement. Chest 134, 1S– 41S (2008). 5. American Thoracic Society. American placebo in allergic healthcare workers.
2. Henneberger, P. K. et al. An official Thoracic Society - Selected Specialized J Allergy Clin Immunol 106, 585– 590
American Thoracic Society state- Clinical Tests In EOH Evaluation (2016). (2000).
ment: Work-exacerbated asthma. Am Available at: http://www.thoracic.org/p 8. Tan, W. C. et al. Characteristics of
J Respir Crit Care Med 184, 368– 378 rofessionals/cli nical-resources /envi ronm COPD in never-smokers and ever-smok-
(2011). ental-and-occupational/cli nical-tests.php ers in the general population: Results
3. Horak, F. et al. Diagnosis and manage- (Accessed: 24 October 2017). from the CanCOLD study. Thorax 70,
ment of asthma— Statement on the 2015 6. Pereira, C. et al. Specific immunotherapy 822– 829 (2015).
GINA Guidelines. Wien Klin Wochenschr for severe latex allergy. Eur Ann Allergy 9. Oh, Y.-M. et al. Characteristics of stable
128, 541– 554 (2016). Clin Immunol 35, 217– 2 25 (2003). chronic obstructive pulmonary disease
References 619
patients in the pulmonology clinics of a prospective, nonrandomized feasibility Administration (EIA) (2015). Available at:
seven Asian cities. Int J Chron Obstruct trial— A n Alpe-adria Thoracic Oncology https: //ww w.eia.gov/tools /faqs /faq.php?i
10.
Pulmon Dis 8, 31– 39 (2013).
Vogelmeier, C. F. et al. Global strategy
for the diagnosis, management, and 28.
Multidisciplinary Group Study (ATOM
002). Oncologist 12, 1215– 1224 (2007).
Kim, K. I. et al. Imaging of occupa-
45.
d=69&t=2 (Accessed: 5 November 2017).
Blackley, D. J. et al. Progressive massive
fibrosis in coal miners from 3 clinics in
49
prevention of chronic obstructive lung tional lung disease. Radiographics 21, Virginia. JAMA 319, 500 (2018).
disease 2017 report. GOLD executive 1371– 1391 (2001). 46. Wade, W. A., Petsonk, E. L., Young, B. &
summary. Am J Respir Crit Care Med 29. Roach, H. D. et al. Asbestos: When Mogri, I. Severe occupational pneu-
195, 557– 582 (2017). the dust settles an imaging review of moconiosis among west Virginian coal
11. Landis, S. H. et al. Continuing to con- asbestos-related disease. Radiographics miners: One hundred thirty-eight cases of
front COPD International Patient Survey: 22 Spec No, S167– 184 (2002). progressive massive fibrosis compensated
Methods, COPD prevalence, and disease 30. Boutin, C. et al. Thoracoscopy in pleural between 2000 and 2009. Chest 139,
burden in 2012– 2013. Int J Chron malignant mesothelioma: A prospective 1458– 1462 (2011).
Obstruct Pulmon Dis 9, 597– 611 (2014). study of 188 consecutive patients. Part 47. Caplan, A. Certain unusual radiological
12. Halbert, R. J. et al. Global burden of 2: Prognosis and staging. Cancer 72, appearances in the chest of coal-miners
COPD: Systematic review and meta-anal- 394– 404 (1993). suffering from rheumatoid arthritis.
ysis. Eur Respir J 28, 523– 532 (2006). 31. ATSDR. Asbestos toxicity: How should Thorax 8, 29– 37 (1953).
13. Alam, D. S., Chowdhury, M. A., patients exposed to asbestos be treated 48. Basnyat, B. & Murdoch, D. R. High-
Siddiquee, A. T., Ahmed, S. & Clemens, and managed? | ATSDR - Environmental altitude illness. Lancet 361, 1967– 1974
J. D. Prevalence and determinants of Medicine & Environmental Health (2003).
chronic obstructive pulmonary disease Education - CSEM. Available at: https: // 49. Schoene, R. B. Illnesses at high altitude.
(COPD) in Bangladesh. COPD 12, ww w.atsd r.cdc.gov/csem /csem.asp?csem= Chest 134, 402– 416 (2008).
658– 667 (2015). 29&po=15 (Accessed: 7 February 2018). 50. Hackett, P., Rennie, D. & Levine, H.
14. Guarascio, A. J., Ray, S. M., Finch, C. K. 32. American Thoracic Society. Diagnosis The incidence, importance, and prophy-
& Self, T. H. The clinical and economic and initial management of nonmalignant laxis of acute mountain sickness. Lancet
burden of chronic obstructive pulmo- diseases related to asbestos. Am J Respir 308, 1149– 1155 (1976).
nary disease in the USA. Clinicoecon Crit Care Med 170, 691– 715 (2004). 51. Eide, C. R. P. I. & Asplund, C. A.
Outcomes Res 5, 235– 245 (2013). 33. Leung, C. C., Yu, I. T. S. & Chen, W. Altitude illness: Update on prevention
15. Martinez, F. D. Early-life origins of Silicosis. Lancet 379, 2008– 2018 (2012). and treatment. Curr Sports Med Rep 11,
chronic obstructive pulmonary disease. 34. Cohen, R. A. C., Patel, A. & Green, F. 124– 130 (2012).
N Engl J Med 375, 871– 878 (2016). H. Y. Lung disease caused by exposure to 52. van Patot, M. C. T. et al. Prophylactic
16. Adeloye, D. et al. Global and regional coal mine and silica dust. Semin Respir low-dose acetazolamide reduces the
estimates of COPD prevalence: Crit Care Med 29, 651– 661 (2008). incidence and severity of acute mountain
Systematic review and meta– analysis. 35. Linch, K. D., Miller, W. E., Althouse, sickness. High Alt Med Biol 9, 289– 293
J Glob Health 5 (2015). R. B., Groce, D. W. & Hale, J. M. (2008).
17. Palange, P. & Simonds, A. ERS Surveillance of respirable crystalline 53. Basnyat, B. et al. Efficacy of low-dose
Handbook of Respiratory Medicine silica dust using OSHA compliance data acetazolamide (125 mg BID) for the
(European Respiratory Society, 2013). (1979– 1995). Am J Ind Med 34, 547– 558 prophylaxis of acute mountain sickness:
18. Rodriguez-Roisin, R. Toward a consensus (1998). A prospective, double-blind, randomized,
definition for COPD exacerbations. Chest 36. Goodman, G. B. et al. Acute silicosis placebo-controlled trial. High Alt Med
117, 398S– 401S (2000). responding to corticosteroid therapy. Biol 4, 45– 52 (2003).
19. McCarthy, B. et al. Pulmonary Chest 101, 366– 370 (1992). 54. Solaymani-Dodaran, M., West, J., Smith,
rehabilitation for chronic obstruc- 37. NIOSH. CDC - NIOSH Pocket Guide C. & Hubbard, R. Extrinsic allergic alveo-
tive pulmonary disease. Cochrane to Chemical Hazards - Silica, crystalline litis: Incidence and mortality in the general
Database Syst Rev CD003793 (2015). (as respirable dust). Available at: https: // population. QJM 100, 233– 237 (2007).
doi:10.1002/14651858.CD003793.pub3 ww w.cdc.gov/n iosh /npg/npgd0684.ht ml 55. Rickman, O. B., Ryu, J. H., Fidler, M. E.
20. Rootmensen, G. N., van Keimpema, A. (Accessed: 31 October 2017). & Kalra, S. Hypersensitivity pneumonitis
R. J., Jansen, H. M. & de Haan, R. J. 38. Balmes, J. R. et al. An official American associated with Mycobacterium avium
Predictors of incorrect inhalation tech- Thoracic Society statement: Diagnosis complex and hot tub use. Mayo Clin Proc
nique in patients with asthma or COPD: and management of beryllium sensi- 77, 1233– 1237 (2002).
A study using a validated videotaped tivity and chronic beryllium disease. 56. Vasakova, M., Morell, F., Walsh, S.,
scoring method. J Aerosol Med Pulm Am J Respir Crit Care Med 190, e34– 59 Leslie, K. & Raghu, G. Hypersensitivity
Drug Deliv 23, 323– 328 (2010). (2014). pneumonitis: Perspectives in diagnosis
21. Centers for Disease Control and 39. Mü ller-Quernheim, J., Gaede, K. I., and management. Am J Respir Crit Care
Prevention. Pneumococcal Disease | Fireman, E. & Zissel, G. Diagnoses of Med 196, 680– 689 (2017).
Vaccines - PCV13 and PPSV23 | CDC chronic beryllium disease within cohorts 57. Mooney, J. J. et al. Radiographic fibrosis
(2017). Available at: https: //www.cdc of sarcoidosis patients. Eur Respir J 27, score predicts survival in hypersensitivity
.gov/pneumococcal/vaccination.html 1190– 1195 (2006). pneumonitis. Chest 144, 586– 592 (2013).
(Accessed: 24 November 2017). 40. Fireman, E., Haimsky, E., Noiderfer, M., 58. Sigsgaard, T. & Rask-Andersen, A.
22. Wedzicha, J. A. et al. Indacaterol- Priel, I. & Lerman, Y. Misdiagnosis of Hypersensitivity pneumonitis. In ERS
Glycopyrronium versus Salmeterol- sarcoidosis in patients with chronic beryl- Handbook of Respiratory Medicine
Fluticasone for COPD. N Engl J Med lium disease. Sarcoidosis Vasc Diffuse (European Respiratory Society, 2013).
374, 2222– 2 234 (2016). Lung Dis 20, 144– 148 (2003). 59. Salisbury, M. L. et al. Diagnosis and
23. Lazarus, A. A. Introduction. Disease-a- 41. Newman, L. S. & Kreiss, K. treatment of fibrotic hypersensitivity
Month 57, 6 (2011). Nonoccupational beryllium disease mas- pneumonia. Where we stand and where
24. Delgermaa, V. et al. Global mesothelioma querading as sarcoidosis: Identification by we need to go. Am J Respir Crit Care
deaths reported to the World Health blood lymphocyte proliferative response Med 196, 690– 699 (2016).
Organization between 1994 and 2008. to beryllium. Am Rev Respir Dis 145, 60. Johannson, K. A. et al. A diagnostic
Bull World Health Org 89, 716– 724C 1212– 1214 (1992). model for chronic hypersensitivity pneu-
(2011). 42. Petsonk, E. L., Rose, C. & Cohen, R. monitis. Thorax (2016). doi:10.1136/
25. Suvatne, J. & Browning, R. F. Asbestos Coal mine dust lung disease. New lessons thoraxjnl-2016-208286
and lung cancer. Disease-a-Month 57, from old exposure. Am J Respir Crit Care 61. Lynch, D. A., Rose, C. S., Way, D. &
55– 68 (2011). Med 187, 1178– 1185 (2013). King, T. E. Hypersensitivity pneumonitis:
26. Pairon, J.-C. et al. Pleural plaques and 43. Laney, A. S. & Weissman, D. N. Sensitivity of high-resolution CT in a
the risk of pleural mesothelioma. J Natl Respiratory diseases caused by coal mine population-based study. Am J Roentgenol
Cancer Inst 105, 293– 301 (2013). dust. J Occup Environ Med 56, S18– S22 159, 469– 472 (1992).
27. Fasola, G. et al. Low-dose computed (2014). 62. Bang, K. M. et al. Twenty-three years of
tomography screening for lung cancer 44. Energy Information Administration. hypersensitivity pneumonitis mortality
and pleural mesothelioma in an asbestos- Which states produce the most coal? surveillance in the United States. Am J
exposed population: Baseline results of - FAQ - U.S. Energy Information Ind Med 49, 997– 1004 (2006).
50
CHAPTER
621
622 Chapter 50 Venous Thromboembolic Disease
The morbidity and mortality of VTE are also difficult hypercoagulable state is likely insufficient for clot forma-
to quantify precisely and likely varies significantly with tion. While global stasis in the context of absent muscular
underlying patient comorbidities, characteristics of the contraction (such as during general anesthesia) has been
VTE itself, and access to treatment. 5 Pulmonary embo- linked to thrombosis, autopsy and physiological studies
lism is associated with the majority of directly attribut- have also demonstrated that the local effect of eddy cur-
able mortality. Population data collected over the last rents in venous sinuses adjacent to the valves of the large
several decades demonstrates an overall mortality rate veins creates a microenvironment of relative hypoxia and
of untreated PE as high as 30%, improving to 8% with increased viscosity which further enhances the propensity
prompt recognition and treatment. The highest mortality to clot.8,10 It has been theorized that this low-oxygen ten-
rates are observed in patients presenting in cardiogenic sion environment further contributes to clot formation as
shock due to massive PE (up to 65%) or mobile thrombus it promotes the downregulation of antithrombotic pro-
within the atria (up to 27%). It is estimated that up to teins that are otherwise expressed in greater concentra-
100,000 deaths annually in the United States are due to tions on the endothelial surface of such valves.11 A similar
complications of VTE.6 imbalance in pro and anticoagulants is also seen in loca-
Both PE and DVT contribute to the morbidity and tions of decreased endothelial cell surface to blood vol-
the societal costs associated with VTE. Much of the cost ume, such as is found in large vessels such as the femoral
comes from the impact of chronic thromboembolic pul- and iliac veins, and may explain the higher rates of clot
monary hypertension, VTE recurrence, and peripheral formation in those areas.12 The prothrombotic effect asso-
vascular dysfunction due to damage to the valves in the ciated with inherited or acquired defects in expression of
deep leg veins. Using data obtained from nearly 27,000 the constituents of the fibrinolytic and clotting pathways
U.S. cases of DVT and PE from 1997 to 2004, it has been is magnified at such sites.13
estimated that average annual individual healthcare costs
are estimated to increase from approximately $7,000 U.S.
(pre-event) to $17,500 and $25,000 in cases of DVT and
PE, respectively.7 In this data set, the presence of post- 50.4 EMBOLIZATION TO THE
thrombotic syndrome was also a strong driver of addi-
tional medical costs and was not limited to the time of
PULMONARY VASCULATURE
the inciting event. The relatively high pre-VTE annual A perfect understanding of the frequency of emboliza-
medical expenditure in this cohort was thought to be due tion of these lower extremity clots is impossible, given the
to preexisting comorbid diseases in this population (com- suspected frequency of asymptomatic DVT, though data
pared to less than $1,000 in annual healthcare costs in derived predominantly from the surgical literature have
age-matched “healthy” controls). The aggregate annual provided some insight into features impacting the likeli-
economic burden of VTE in the United States, including hood of progression.14 While it is true that the development
the longitudinal cost of therapy and management of side of de novo thrombosis of the large veins in the periphery is
effects, has been estimated to be between $7 billion to $10 dependent upon the factors noted above, the likelihood of
billion per year.6 embolization of these clots to the pulmonary vasculature
The costly, morbid, and frequently mortal nature of has been linked only to the proximity of the clot to the
VTE is reason enough to explore all reasonable avenues central circulation.15 Based on these data, it is suspected
of risk reduction and therapy optimization. As we will that nearly all venous thrombotic events are asymptomatic
see later in this chapter, application of the principles of until they reach the proximal veins (cephalad to the popli-
lifestyle medicine may be an inexpensive and efficacious teal circulation.16,17 In a consecutive series of 189 patients
adjunct to the growing technological arsenal of diagnosis with suspected lower extremity DVT, only 11% had distal
and therapy. calf DVT only, and more than 90% had continuous clot
extension from the calf to the proximal veins.14 It has been
estimated that nearly half of the patients with symptom-
50.3 PATHOPHYSIOLOGY atic proximal DVT will have imaging evidence of pulmo-
nary emboli at the time of diagnosis, and one-third will
The development of VTE is dependent on the local inter- be diagnosed with concurrent PE, even in the absence of
action of venous stasis, vascular endothelial injury, and chest or respiratory symptoms.18,19
intrinsic hypercoagulability in the paradigm attributed to The majority of these datasets were generated decades
Virchow in 1856.8 Though a detailed exploration of the ago. With the now-widespread use of the MDCT scan,
hematological mechanisms of clot formation is beyond the our ability to detect small PE is significantly improved.
scope of this text, there are several key ideas to under- It may be reasonable to expect that a higher sensitivity
stand as they pertain to the development of DVT and sub- test would only increase our estimate of the frequency
sequent PE. of asymptomatic embolization. The natural history of
The risk of thrombosis can be thought of as propor- untreated DVT, therefore, is suspected to be one of even-
tional to the cumulative impact of multiple risk factors, all tual progression and ultimately distal migration. The risk
in some way related to the presence of the three commonly of such an event is believed to be highest immediately
observed physiological derangements noted above.9 It has following the development of thrombosis, and this risk
also been observed that while venous stasis is likely the declines over a several-month period as the stabilization
most important contributor to DVT (and by extension PE), effects of partial resorption and endothelization of distal
stasis in the complete absence of endothelial disruption or clots progresses. 20
50.5 Risk Factors 623
50
described. As the modern office becomes more decentral-
It is likely that truly idiopathic VTE or PE is rare and that ized, and Americans spend more and more time with their
the majority of VTE occurs in the context of at least one, computers for both work and recreation, there has been an
and often multiple, risk factors. 21 The risk factors that increase in individual case reports and case series describ-
predispose the patient to clot can be divided generally into ing the development of significant DVT related to elective,
two groups: inherited (including anatomical variations non-flight-related immobility.35 In one of the largest series
and genetic clotting disorders) or acquired (e.g., undergo- of its kind, 61 consecutive patients with VTE were sur-
ing surgery or presence of comorbid disease such as can- veyed and tested for underlying thrombophilia. Multiple
cer). 22 Though these risk factors might appear varied and risk factors were present in the majority of patients.
unrelated, the final common pathway of clotting is the Prolonged seated immobility was the second most com-
perturbation of the local vascular microenvironment such mon risk factor after a family medical history of thrombo-
that some or all of Virchow’s triad is satisfied. 23 There are sis. This study defined “prolonged” as sitting a cumulative
several published datasets that enhance our understand- eight hours in a 24-hour period (with at least three hours
ing of both the relative individual strength of risk factors unbroken), 10 hours in a 24-hour period (with at least two
and the interplay of acquired and innate risks when pres- hours unbroken), or 12 hours in a 24-hour period (with at
ent concurrently. 24 least one hour of continuous sitting). Thirty-four percent
Describing the effect of a single risk factor is straight- of patients with a new diagnosis of DVT demonstrated
forward: surgery with general anesthesia and the presence this finding.36 A follow-up case-control study attempted to
of malignancy are implicated in as many as one-third of all describe the odds ratio specifically associated with work-
cases, and are likely the most important single risk factors related immobility. Ninety-seven consecutive patients
for the development of VTE.21,25–27 Delineating the syn- with radiographically confirmed VTE (both DVT and
ergistic effects of multiple concurrent risk factors is more PE) were administered a questionnaire almost identical to
complex, but more reflective of real patients and real risk. that used in the Aldington case series. These patients were
Using the example of surgery: in one of the largest case- then matched to controls from the same center admitted
control studies of VTE (the MEGA study, 4311 cases), it over the same time period. Following univariate analysis,
was observed that the combination of surgical immobility authors found that immobility due to work or recreation
of non-malignant medical illness (including renal or liver carried an odds ratio of 2.2 (CI 1.0–5.0) for the devel-
disease, heart failure, and CVA) increased the OR for the opment of VTE. While this was an important observa-
development of VTE by 10.9 (95% CI 4.2–28).28 The addi- tion, the effect was modest, especially when compared
tion of any of the inherited thrombophilias to that combi- to the effect of recent surgery or family history of VTE
nation increased the OR to as high as 88. For the purposes in this same dataset (OR 70.6 and 5.7, respectively). 37
of this text, we will focus primarily on the complex syner- Interestingly, the total duration of hours spent sitting,
gistic interaction between several pertinent lifestyle-related irrespective of frequency or duration of breaks, had a
health choices: risk of immobility or a sedentary lifestyle, direct relationship with an increasing risk of VTE. This
obesity, and smoking will also be further reviewed. final conclusion underscores the risks associated with a
sedentary lifestyle, as it highlights the challenge of simply
instituting preventative regimens.
50.5.1 Immobility
Interest in the development of VTE due to prolonged non-
surgical immobility has existed since it was first observed 50.5.2 Obesity
that there was a sixfold increase in the risk of fatal PE in The development of atherosclerotic arterial disease and the
patients who sat for prolonged periods of time in air raid development of venous thromboembolism have significant
shelters during the London Blitz of World War II. 29 More epidemiological overlap. The risk of VTE attributable to
recently, it was reported that rates of incidence of distal specific cardiovascular risk factors such as hypertension,
DVT in patients requiring cast immobilization without hyperlipidemia, and diabetes, however, has been inconsis-
surgery may be high as 19% (35/188).30 The risk associ- tently demonstrated or even refuted. 38 The same cannot be
ated with airline travel is likely the most intensely scru- said for obesity and smoking. Multiple population-based,
tinized, though it remains controversial. Estimates from retrospective and even prospective studies have observed
prospectively obtained data sets indicate the risk of DVT the link between these important lifestyle-related risk fac-
may be twice that of non-flyers.31 The overall incidence of tors, development of VTE, and cardiovascular disease.38– 40
PE may be as low as 4.8 per million patients traveling more In parallel with the rapid rise of the obesity epidemic
than 6,000 miles, but it is believed that we underestimate in Americans, there has been increasing interest in under-
the true incidence of minimally symptomatic and non- standing the role that obesity plays in the development
embolizing distal clots.32 Additionally, it has been sug- of DVT and PE. Although obesity has been theorized for
gested that it is not only the lack of movement while flying decades to exert a pro-coagulant effect in the model of
but concurrent mild hypoxemia (cabin PaO2 of 72 mmhg) Virchow’s triad, it is only in the last few decades that we
that promotes coagulation. 33,34 Given the frequency of have seen significant data in support of this association.41,42
multiple risk factors present in the same patients, it is also Several meta-analyses and large-population cohort studies
challenging to attribute the risk of immobility itself during have supported the link between increasing BMI and the
activities such as airline travel. risk of VTE. The largest of these meta-analyses includes
624 Chapter 50 Venous Thromboembolic Disease
data from 21 case-control and cohort studies and rep- respectively. The average BMI in those who suffered a
resents 63,552 patients diagnosed with PE or DVT over recurrence at all in the four years of the study was 28.5
the last five decades. Obesity, defined as BMI > 30kg/m 2 compared to 26.9 in those that were clot-free at the end of
carried an OR of 1.84 (95% CI, 1.55 to 2.18; I 2 = 69.2%; 46 months (P = 0.01).49 These data suggest that efforts to
P = 0.01) for the development of VTE. The average BMI in reduce BMI through healthier lifestyle choices may have
the cohort of patients who developed VTE was 1.7 kg/m 2 an impact on the management of VTE.
higher than their matched controls.43
Though focused on a homogenous population, data
published in 2010 from the Copenhagen City Heart Study
also found obesity to be an independent risk factor for
50.5.3 Smoking
the development of VTE.44 Based on their evaluation of Though smoking, and specifically cigarette smoking, has
more than 360,000 patient-years and nearly 1,000 indi- long been understood to be an independent risk factor for
vidual cases of VTE, they observed that a BMI of 30 the development of arterial atherosclerotic disease, its role
to 35 carried an HR of 1.65 (1.17–2.34, P = 0.005) for in the development of the venous thromboembolic disease
the development of DVT or PE. Their data set also sug- is less well understood. This controversy stems primar-
gested the possibility of graded risk with rising BMI, as ily from conflicting data collected through the 1990s
the subset of patients with BMI over 35 kg/m2 had an and early twenty-first century regarding smoke expo-
HR of 2.1 (1.39–3.16, P = <0.001). A similar trend was sure and the development of VTE disease. Central to this
observed by Tsai et al. in the Longitudinal Investigation controversy is a 2008 meta-analysis that did not support
of Thromboembolism Etiology (LITE) study, when they smoking as an independent risk factor for DVT or PE,
combined data from ARIC (a prospective epidemiologi- contrasted with multiple studies in recent years that have
cal study focused on four American communities) and the found smoking to exhibit not only a dose-dependent asso-
Cardiovascular Health Study (CHS).45,46 These authors ciation with an increased risk of clot but perhaps more
observed increasing HR for VTE proportional to rising importantly, that identified it as a cofactor in the presence
quintile of BMI from <25 to >40.38 Further understanding of other acquired or inherited risk factors. 50
of this proportional risk requires additional study. In 2008, Ageno et al. collated more than 20 years of
In addition to its independent impact on coagula- observational data regarding the overlap between VTE
tion, obesity has also been associated with a magnified and traditional cardiovascular disease risk factors.50
risk of DVT and PE not only in certain populations (most After evaluating 21 case-control and cohort studies (four
notably women) but also in the context of other acquired of which were prospective) containing data from more
and inherited risk factors. Data from both the all-female than 63,000 patients, they reported that smoking car-
Nurses Health Study and the Multiple Environmental and ried a (non-significant) increased risk of only 1.18 for the
Genetic Assessment (MEGA) study show increased risk of development of VTE (95% CI, 0.95 to 1.46). Around the
VTE in obese female patients on OCPs.47 Using subjects same time, the results of several small and more narrowly
with a BMI <25 and no OCP use as a baseline, it was focused population-based studies also argued against
observed that patients on OCPs and a BMI between 25 smoking as an independent risk for VTE.38,51,52
and 30 had an OR of 11.63 (95% CI, 7.46 to 18.14) for There were several important limitations of these data
the development of VTE. As BMI rose above 30, that OR that have prompted further investigation. The largely ret-
similarly rose to 23.78 (95% CI 13.35–42.34). rospective data set generated by Ageno could not be evalu-
The risk of VTE associated with obesity and the ated in a way that controlled for the coexistence of other
Factor V Leiden (FVL) gene mutation was also demon- VTE risk factors such as age, increasing BMI, recent sur-
strated to be significant. Though the presence of this gery, the presence of concurrent malignancy, or diagnosed
genetic abnormality was itself associated with an OR of thrombophilia. Six of the included studies were focused on
4.18 in normal weight patients (BMI <25), that OR rose the interplay of VTE and OCPs and thus had an exceed-
to 5.77 and 7.86 at BMI levels between 25–30 and >30, ingly narrow population focus. The presence of VTE was
respectively. The combined effect of obesity and pro- not necessarily confirmed by accepted diagnostic practices
thrombin gene mutation was of a similar scale. Although such as CT or ultrasound, and additionally, no distinction
it is unclear why obesity increases risk of VTS, investiga- was made between current and former smokers.
tors have recently shown that increasing levels of obesity Hypothesizing that the above limitations and the
correlate with increased levels of clotting factor VIII and exclusion of a large number of available published data
activated protein C resistance, possibly due to the estab- sets may have artificially reduced the apparent impact of
lishment of a chronic inflammatory state.48 smoking as a risk factor for VTE, Cheng et al. published a
In addition to its impact on the development of the first meta-analysis of 32 studies comprising 35,151 VTE events
episode of VTE, obesity has also been observed to increase in 2013. 53 Studies lacking additional risk factor data or
the risk of recurrence after treatment of an initial event. specific details regarding cigarette use were excluded
In a recent prospective study, investigators followed more from their analysis. They reported that after controlling
than 1,000 patients for an average of 46 months follow- for additional, known VTE risk factors in a generalizable
ing their first episode of unprovoked DVT and completion population, current smokers compared to never smokers
of anticoagulation therapy. They observed a recurrence had a statistically significant RR of 1.23 (95% CI 1.14 to
rate of 9.3% in patients with normal BMI (<25 kg/m2) 1.33) for the development of VTE. They also reported that
and 16.7% (95% CI, 11.0%–22.3%) and 17.5% (95% this risk increased by 10.2% (95% CI 8.6%–11.8%) for
CI, 13.0%–22.0%) among overweight and obese patients, every 10 additional cigarettes per day or by 6.1% (95% CI
50.5 Risk Factors 625
3.8–8.5%) for every additional 10 pack-years of smoking. four times that of matched controls.60 Variability in the
50
Similar modest increases in the observed RR of VTE in rates of VTE has in many large reviews and meta-analyses
smokers has been reported by several smaller studies.47,54 been attributed predominantly to differences in the pro-
Most recently, Mahmoodi et al. evaluated the role of gestin component of these medications.61 As with our pre-
CVD risk factors (such as smoking) in the development of vious examples, however, smoking (along with obesity) is
VTE using only prospectively identified and definitively an important synergistic actor in this patient population,
diagnosed cases of VTE. This meta-analysis included only potentially more than doubling the risk of VTE devel-
prospective trials with high-quality data that utilized CT opment in patients taking combined OCPs. Pomp, et al.
or ultrasound confirmation of the presence of VTE. It reported an OR of 8.79 (CI 95% 5.73–13.49) in the subset
demonstrated that while current smoking did carry mod- of patients on OCPs who identified themselves as current
estly increased HR of 1.19 (95% CI 1.08–1.32) for the smokers.47 Further, subgroup analysis of these data also
development of VTE, this overall effect was attributed demonstrated a direct, proportional increase in the risk
entirely to the effect observed in the subgroup of patients of VTE with daily smoking, similar in magnitude to that
ultimately diagnosed with a provoked clot over the 4.7 to effect observed by Cheng et al.
19.7 years of follow-up. 55 The conclusion, that most tra-
ditional CVD risk factors do not independently predis-
pose patients to the development of venous disease, lends
further support to a central theme of this chapter: it is
50.5.4 Diagnosis
likely the synergistic effects of multiple risk factors (both The diagnosis of PE is dependent on the maintenance
acquired and inherited) that leads to development of VTE. of a high degree of clinical suspicion, which is itself
The importance of smoking as a cofactor in the devel- enhanced by an awareness of the common risk factors
opment of VTE is further supported by a body of evidence described above. While the clinical presentation can be
that demonstrates the synergistic effect of smoking in the variable, and that variability can be independent of the
context of known, non-lifestyle-related risk factors such size or location of the clot, several large study popula-
as the presence of a thrombophilic gene mutation or recent tions have demonstrated a number of more commonly
surgery. observed features.19,40,62 These include dyspnea (present in
Of the many genetic risk factors for VTE that have nearly three-quarters of patients) and pleuritic chest pain
been identified, the most well established are FVL and (in two-thirds of patients). Tachypnea has been observed
prothrombin gene mutations. 56 It has been estimated that in half of the patients presenting with PE. A cough and
up to 8% of patients with DVT will carry one of these evidence of lower extremity DVT are present in nearly
mutations, and approximately 2% of the population in one-quarter of patients at the time of diagnosis of PE.
total will carry one. 57 Though estimates vary, heterozy- Rapidity of the onset of symptoms is seconds to minutes in
gosity for these mutations has been associated with statis- more than three-quarters of cases.19,40 High-risk presenta-
tically significant HR for VTE of approximately 2.6 for tions characterized by refractory hypoxemia, obstructive
each locus individually and as high as 5.66 when found shock, or cardiac arrest are comparatively rare but require
together.58It has also been observed that there is some specific approach to initial management: while it has been
degree of variability in the incidence of VTE in patients observed that the duration of symptoms prior to diagnosis
with known mutations, with many patients never develop- has a direct relationship with increasing size of clot bur-
ing VTE despite exposure to known potent cofactors.59 den, this relationship was not significantly associated with
Hypothesizing that lifestyle choices (specifically smoking these high morbidity presentations.63
and obesity) may, therefore, exert an influence over the A large meta-analysis, which included more than
variable development of VTE in these patients. Severinsen 25,000 cases of PE, suggested that the clinical impression
et al. examined the dose-response impact of smoking on of physicians, based predominantly on consideration of
the development of VTE in patients with known FVL and these symptoms, may carry a sensitivity of 85%, though
prothrombin gene mutations. Though the relatively small understandably a low specificity (51%) for the detection
number of VTEs in the study group may have overesti- of PE.62 Driven partly by these data, and in part by the
mated the effect of smoking, they reported a HR for VTE need of enhanced focus on healthcare expenditure and
of 4.46 (95% CI, 1.83–10.88) and 76.8 (95% CI 29.2– resource utilization in the last several years, there has
201.7) in patients with FVL and prothrombin gene muta- been increasing interest in simple, standardized schema to
tion, respectively, who smoked more than 25 g of tobacco identify very low-risk individuals.64 The PERC rule (pul-
(slightly more than one pack of cigarettes) per day. Also monary embolism rule-out criteria, a set of eight clinical
of note, matched wild-type controls in this study who and patient features used to predict risk of PE on initial
smoked less than 25 g/day of tobacco, were not observed presentation) was developed as a tool to accomplish just
to have an increased risk for development of VTE. Further that aim, and in early studies as well as a recently pub-
supporting the dose-effect reported by Cheng et al., they lished RCT, has demonstrated excellent performance.65
did observe a statistically significant and proportional More study is likely needed to move this approach into
increase in rates of VTE in those controls that smoked standard practice.
greater than the equivalent of one pack of cigarettes per Laboratory tests can play an important role in risk
day. stratification and in ruling out pulmonary embolism in
It is well established that use of estrogen and combined patients who have a low pre-test probability based on clini-
oral contraceptive pills is itself associated with an increased cal assessment or standardized scores (e.g., Wells), but they
risk of VTE that has historically ranged between two and are not strictly necessary for the diagnosis of PE. D-dimer
626 Chapter 50 Venous Thromboembolic Disease
specifically has been studied extensively, and a negative days, then 5 mg BID), do not require initial Rx with
test effectively rules out embolism and eliminates the need LMWH.
for further testing in these low-risk groups.66 The perfor- • These recommendations are based on these factors:
mance, and therefore utility, of this test is degraded signifi- • Risk reduction for recurrent VTE appears to be
cantly in populations with a high prevalence of PE or with a similar to warfarin.
medical history associated with elevated levels (hospitalized • Risk reduction among these drugs appears to be
patients, the elderly, or those with ESRD).67 This is espe- similar.
cially confounding given what has already been described • Risk of intracranial bleeding appears to be less
regarding the increased risk of thrombosis in individuals than warfarin.
with these features; many patients with these features but • Fatal bleeding is no higher than warfarin.
low-to-intermediate risk will undergo definitive testing, • These medications are more convenient for
and they will demonstrate higher rates of negative studies. patients and may lead to better compliance.
The standard of care in diagnosing those with a high • If a choice is made to use warfarin, initial LMWH is
pre-test probability of PE (or those otherwise appropriate used for a minimum of five days.
to undergo definitive testing) is well established. Studies • If a heparin product is used, low-molecular-weight
support the use of CT scan protocoled for opacification heparins are considered superior to unfractionated
of the pulmonary arteries. Performance characteristics heparins in most cases.75
of this test can vary with the pre-test probability of PE:
PIOPED II data demonstrated a sensitivity and specific- Duration of therapy is another extensively studied and
ity of 90% and 96%, respectively, in patients with high debated issue in the treatment of VTE. The nature of the
suspicion for PE.19 False negatives do occur across all underlying risk is of central importance to this decision.
groups, though as infrequently as 0.07% in high-suspicion The key consideration in addressing the duration of ther-
groups.68 Technical challenges such as obesity, movement apy is recurrence prevention, and data have shown that
artifact, or incorrect contrast bolus timing can dispropor- irrespective of the agent used in anticoagulation, there is
tionately reduce the accuracy of the test at the subsegmen- an elevated risk of recurrence following discontinuation
tal level; interobserver variability among radiologists has of treatment after three, six, or even 12 months.76 Risk of
been as high as 50% in such cases.69 recurrent VTE instead likely varies with the persistence
of provocative risk factors: the largest data set available
identifies the presence of malignancy, age, BMI, and per-
sistent neurological deficits as independent predictors of
50.5.5 Treatment recurrence.76 Conversely, the surgical literature demon-
The approach to the treatment of VTE is dependent upon strates that isolated DVT following surgery is adequately
a variety of disease and patient factors which influence treated with three months of anticoagulation, and treat-
the choice of therapeutic agents and duration of antico- ment duration beyond this point confers no benefit in
agulation therapy. These include the location of the clot recurrence prevention.77 It is possible that shorter courses
(distal lower extremity vs. proximal lower extremity/pul- of anticoagulation are feasible based on what we know
monary embolism), the presence of hemodynamic insta- about the kinetics of clot resorption, though several stud-
bility, features of the underlying provocative risk factors, ies have suggested that the thrombogenic effect of some
and vulnerability to serious adverse effects of treatment “transient” risk factors extends well beyond the acute
(i.e., bleeding risk). insult. Additionally, cohorts of patients with “unpro-
Many of the recent investigations center around the use voked” thrombosis likely have a higher rate of recurrence
of direct oral anticoagulants (rivaroxaban, dabigatran, than the general population, and as a reflection of that
etc.) in the treatment of DVT and PE. Historically, vita- observation, consideration should be given to indefinite
min K antagonists (such as warfarin), heparin infusions, anticoagulation.77
or subcutaneous low-molecular-weight heparin injections It has not been demonstrated whether clots arising
were the standard of care. Though in some cases they in the context only of the previously identified lifestyle-
remain as such, there is growing evidence to suggest that related risk factors are more or less likely to recur follow-
DOACs are safe and effective.70 –73 ing modification of the risk. While it is tempting to assume
The ACCP’s Antithrombotic Therapy for VTE that weight loss, avoidance of prolonged periods of sitting,
Disease, updated 2016, is the most widely accepted stan- and smoking cessation would return baseline thrombosis
dard for VTE management, and a highly condensed sum- risk to “normal” levels, this is unknown.
mary is included below. In patients with VTE but no The following special situations sometimes arise and
malignancy:74 require different consideration when being managed.
REFERENCES
1. Rosendaal FR. Thrombosis in the young: 2. Meignan M, Rosso J, Gauthier H, et al. venous thrombosis. Arch Intern Med.
Epidemiology and risk factors, a focus on Systematic lung scans reveal a high 2000;160(2):159–64.
venous thrombosis. Thromb Haemost. frequency of silent pulmonary embo- 3. Oger E, Groupe d’Etude de la Thrombose
1997;78(1):1–6. lism in patients with proximal deep de Bretagne Occidentale. Incidence of
628 Chapter 50 Venous Thromboembolic Disease
venous thromboembolism: A community- 22. Lijfering WM, Rosendaal FR, men born in 1913”. Arch Intern Med.
based study in Western France. Thromb Cannegieter SC. Risk factors for venous 1999;159(16):1886.
Haemost. 2000;83(5):657–60. thrombosis - current understanding from 40. Stein PD, Terrin ML, Hales CA, et al.
4. Bertina RM. Genetic approach to an epidemiological point of view. Br J Clinical, laboratory, roentgenographic,
thrombophilia. Thromb Haemost. Haematol. 2010;149(6):824. and electrocardiographic findings in
2001;86(1):92. 23. Lowe GD. Virchow’s triad revisited: patients with acute pulmonary embolism
5. Belohlavek J, Dytrych V, Linhart Abnormal flow. Pathophysiol Haemost and no pre-existing cardiac or pulmonary
A. Pulmonary embolism II: Thromb. 2003;33(5–6):455. disease. Chest. 1991;100(3):598.
Management. Exp Clin Cardiol. 2013 24. Ocak G, Vossen CY, Verduijn M, et al. 41. Folsom AR, Qamhieh HT, Flack
Spring;18(2):139–47. Risk of venous thrombosis in patients JM, et al. Plasma fibrinogen: Levels
6. Grosse SD, Nelson RE, Nyarko KA, with major illnesses: Results from the and correlates in young adults: The
et al. The economic burden of incident MEGA study. J Thromb Haemost. Coronary Artery Risk Development in
venous thromboembolism in the United 2013;11(1):116. Young Adults (CARDIA) study. Am J
States: A review of estimated attributable 25. Rogers MA, Levine DA, Blumberg N, Epidemiol. 1993;138:1023–36.
healthcare costs. Wien Klin Wochenschr. et al. Triggers of hospitalization for 42. Folsom AR, Wu KK, Rasmussen M, et al.
2002;114(17–18):766–72. venous thromboembolism. Circulation. Determinants of population changes in
7. MacDougall DA, Feliu AL, Boccuzzi 2012;125(17):2092. Epub 2012 Apr 3. fibrinogen and factor VII over 6 years:
SJ, Lin J. Economic burden of deep-vein 26. Sorensen HT, Horvath-Puho E, The Atherosclerosis Risk in Communities
thrombosis, pulmonary embolism, and Pedersen L, et al. Venous thromboem- (ARIC) study. Arterioscler Thromb Vasc
post-thrombotic syndrome. Am J Health bolism and subsequent hospitalisation Biol. 2000;20:601–6.
Syst Pharm. 2006;63(20 Suppl 6):S5–15. due to acute arterial cardiovascular 43. Ageno W, Becattini C, Brighton T, et al.
8. Stone J, Hangge P, Albadawi H, et al. events: A 20-year cohort study. Lancet Cardiovascular risk factors and venous
Deep vein thrombosis: Pathogenesis, 2007;370:1773–9. thromboembolism: A meta-analysis.
diagnosis, and medical management. 27. White RH, Zhou H, Romano PS. Circulation. 2008;117(1):93.
Cardiovasc Diagn Ther. 2017;7(Suppl 3): Incidence of symptomatic venous 44. Holst AG, Jensen G, Prescott E, et al.
S276–84. thromboembolism after different elective Risk factors for venous thromboem-
9. Wessler S, Reimer SM, Sheps MC. or urgent surgical procedures. Thromb bolism: Results from the Copenhagen
Biologic assay of a thrombosis-inducing Haemost. 2003;90(3):446. City Heart Study. Circulation.
activity in human serum. J Appl Physiol. 28. Ocak G, Vossen CY, Verduijn M, et al. 2010;121(17):1896.
1959;14:943–6. Risk of venous thrombosis in patients 45. ARIC Investigators. The atherosclero-
10. Sevitt S. The structure and growth of with major illnesses: Results from the sis risk in communities (ARIC) study:
valve-pocket thrombi in femoral veins. MEGA study. J Thromb Haemost. Design and objectives. Am J Epidemiol.
J Clin Pathol. 1974;27:517–28. 2013;11(1):116. 1989;129:687–702.
11. Brooks EG, Trotman W, Wadsworth 29. Simpson K. Shelter deaths from pulmo- 46. Fried LP, Borhani NO, Enright P, et al.
MP, et al. Valves of the deep venous nary embolism. Lancet. 1940;ii:744. The cardiovascular health study:
system: An overlooked risk factor. Blood. 30. Lassen MR, Borris LC, Nakov RL. Use Design and rationale. Ann Epidemiol.
2009;114:1276–9. of the low-molecular-weight heparin 1991;1:263–76.
12. Busch C, Cancilla PA, DeBault LE, et al. reviparin to prevent deep-vein thrombosis 47. Pomp ER, le Cessie S, Rosendaal FR, et al.
Use of endothelium cultured on microcar- after leg injury requiring immobilization. Risk of venous thrombosis: Obesity and
riers as a model for the microcirculation. N Engl J Med. 2002;347(10):726. its joint effect with oral contraceptive
Lab Invest. 1982;47:498–504. 31. Schwarz T, Siegert G, Oettler W, et al. use and prothrombotic mutations. Br J
13. Esmon CT. Basic mechanisms and patho- Venous thrombosis after long-haul flights. Haematol. 2007;139(2):289.
genesis of venous thrombosis. Blood Rev. Arch Intern Med. 2003;163:2759–64. 48. Christiansen SC, Lijfering WM, Naess
2009;23:225–9. 32. Lapostolle F, Surget V, Borron SW, et al. IA, et al. The relationship between body
14. Cogo A, Lensing AWA, Prandoni P, et al. Severe pulmonary embolism associ- mass index, activated protein C resistance
Distribution of thrombosis in patients ated with air travel. N Engl J Med. and risk of venous thrombosis. J Thromb
with symptomatic deep-vein thrombosis: 2001;345(11):779–83. Haemost. 2012;10(9):1761.
Implications for simplifying the diagnostic 33. Cannegieter SC, Doggen CJ, van 49. Eichinger S, Hron G, Bialonczyk C, et al.
process with compression ultrasound. Arch Houwelingen HC, et al. Travel-related Overweight, obesity, and the risk of
Intern Med. 1993;153:2777–80. venous thrombosis: Results from a recurrent venous thromboembolism. Arch
15. Kearon C. Natural history of venous large population-based case control Intern Med. 2008;168(15):1678.
thromboembolism. Circulation. study (MEGA study). PLoS Med. 50. Ageno W, Becattini C, Brighton T, et al.
2003;107:I22–30. 2006;3(8):e307. Cardiovascular risk factors and venous
16. Lagerstedt CI, Olsson CG, Fagher BO, 34. Gavish I, Brenner B. Air travel and the thromboembolism: A meta-analysis.
et al. Need for long-term anticoagulant risk of thromboembolism. Intern Emerg Circulation. 2008;117(1):93.
treatment in symptomatic calf-vein Med. 2011;6(2):113–6. 51. Helmerhorst FM, Bloemenkamp KW,
thrombosis. Lancet. 1985;2:515–8. 35. Lucerna A, Espinosa J, Ackley L, et al. Rosendaal FR, et al. Oral contraceptives
17. Kearon C, Julian JA, Newman TE, et al., A case report on VT from TV: DVT and and thrombotic disease: Risk of venous
for the McMaster Diagnostic Imaging PE from prolonged television watching. thromboembolism. Thromb Haemost.
Practice Guidelines Initiative. Non- Case Rep Pulmonol. 2017;2017:9347693. 1997;78(1):327.
invasive diagnosis of deep vein thrombo- 36. Aldington S, Pritchard A, Perrin K, et al. 52. Jee SH, Suh I, Kim IS, et al. Smoking
sis. Ann Intern Med. 1998;128:663–77. Prolonged seated immobility at work is a and atherosclerotic cardiovascular
18. Moser KM, Fedullo PF, LittleJohn JK, common risk factor for venous thrombo- disease in men with low levels of
et al. Frequent asymptomatic pulmonary embolism leading to hospital admission. serum cholesterol: The Korea Medical
embolism in patients with deep venous Intern Med J. 2008;38(2):133–5. Insurance Corporation Study. JAMA.
thrombosis. JAMA. 1994;27:223–5. 37. West J, Perrin K, Aldington S, et al. A case- 1999;282(22):2149.
19. Stein PD, Beemath A, Matta F, et al. control study of seated immobility at work 53. Cheng YJ, Liu ZH, Yao FJ, et al.
Clinical characteristics of patients with as a risk factor for venous thromboembo- Current and former smoking and risk for
acute pulmonary embolism: Data from lism. Soc Med. 2008;101(5):237–43. venous thromboembolism: A systematic
PIOPED II. Am J Med. 2007;120(10):871. 38. Tsai AW, Cushman M, Rosamond WD, review and meta-analysis. PLoS Med.
20. Coon WW, Willis PW. Recurrence of et al. Cardiovascular risk factors and 2013;10(9):e1001515.
venous thromboembolism. Surgery. venous thromboembolism incidence: The 54. Wattanakit K, Lutsey PL, Bell EJ, et al.
1973;73:823–7. longitudinal investigation of thrombo- Association between cardiovascular
21. Spencer FA, Emery C, Lessard embolism etiology. Arch Intern Med. disease risk factors and occurrence of
D, et al. The Worcester Venous 2002;162(10):1182. venous thromboembolism. A time-
Thromboembolism study: A population- 39. Hansson PO, Eriksson H, Welin L, et al. dependent analysis. Thromb Haemost.
based study of the clinical epidemiology Smoking and abdominal obesity: Risk 2012;108(3):508.
of venous thromboembolism. J Gen factors for venous thromboembolism 55. Mahmoodi BK, Cushman M, Anne
Intern Med. 2006;21(7):722. among middle-aged men: “the study of Næss I, et al. Association of traditional
References 629
cardiovascular risk factors with venous 66. Bass AR, Fields KG, Goto R, et al. 76. Heit JA, Mohr DN, Silverstein MD,
thromboembolism: An individual partici- Clinical decision rules for pulmonary Petterson TM, O’Fallon WM, Melton LJ
56.
pant data meta-analysis of prospective
studies. Circulation. 2017;135(1):7–16.
Dahlback, B. Advances in under-
embolism in hospitalized patients:
A systematic literature review and
meta-analysis. Thromb Haemost.
III. Predictors of recurrence after deep
vein thrombosis and pulmonary embo-
lism: A population-based cohort study.
50
standing pathogenic mechanisms 2017;117(11):2176. Arch Intern Med. 2000;160(6):761–8.
of thrombophilic disorders. Blood. 67. Rathbun SW, Whitsett TL, Vesely SK, et 77. Couturaud F, Sanchez O, Pernod G, et al.
2008;112(1):19–27. al. Clinical utility of D-dimer in patients Six months vs extended oral anticoagula-
57. Margaglione M, Brancaccio V, Giuliani with suspected pulmonary embolism and tion after a first episode of pulmonary
N, et al. Increased risk for venous nondiagnostic lung scans or negative CT embolism: The PADIS-PE randomized
thrombosis in carriers of the prothrombin findings. Chest. 2004;125(3):851. clinical trial. JAMA. 2015;314(1):31–40.
G-->A20210 gene variant. Ann Intern 68. Quiroz R, Kucher N, Zou KH, et al. 78. Meyer G, Vicaut E, Danays T, et al.
Med. 1998;129(2):89. Clinical validity of a negative computed Fibrinolysis for patients with intermedi-
58. Severinsen MT, Kristensen SR, Johnsen tomography scan in patients with sus- ate-risk pulmonary embolism. N Engl J
SP, et al. Anthropometry, body fat, pected pulmonary embolism: A systematic Med. 2014;370(15):1402–11.
and venous thromboembolism: A review. JAMA. 2005;293(16):2012. 79. Kucher N, Boekstegers P, Muller OJ,
Danish follow-up study. Circulation. 69. Miller WT Jr, Marinari LA, Barbosa Jr et al. Randomized, controlled trial of
2009;120(19):1850. E, et al. Small pulmonary artery defects ultrasound-assisted catheter-directed
59. Kristensen, S.R., Andersen-Ranberg, K., are not reliable indicators of pulmo- thrombolysis for acute intermediate-
Bathum, L, et al. Factor V Leiden and nary embolism. Ann Am Thorac Soc. risk pulmonary embolism. Circulation.
venous thrombosis in Danish centenarians. 2015;12(7):1022. 2014;129(4):479–86.
Thromb Haemost. 80:860–1. 70. Carrier M, Cameron C, Delluc A, 80. Kuo WT, Banerjee A, Kim PS, et al.
60. van Hylckama Vlieg A, Helmerhorst Castellucci L, Khorana AA, Lee AY. Pulmonary embolism response to frag-
FM, Vandenbroucke JP, et al. The venous Efficacy and safety of anticoagulant mentation, embolectomy, and catheter
thrombotic risk of oral contraceptives, therapy for the treatment of acute cancer- thrombolysis (PERFECT): Initial results
effects of oestrogen dose and progestogen associated thrombosis: A systematic from a prospective multicenter registry.
type: Results of the MEGA case-control review and meta-analysis. Thromb Res. Chest. 2015;148(3):667–73.
study. BMJ. 2009;339:b2921. 2014;134(6):1214–9. 81. Masuda EM, Kistner RL. The case for
61. de Bastos M, Stegeman BH, Rosendaal 71. Bauersachs R, Berkowitz SD, Brenner B, managing calf vein thrombi with duplex
FR, et al. Combined oral contraceptives: et al. Oral rivaroxaban for symptomatic surveillance and selective anticoagula-
Venous thrombosis. Cochrane Database venous thromboembolism. N Engl J Med. tion. Dis Mon. 2010;56(10):601–13.
Syst Rev. 2014. 2010;363(26):2499–510. 82. Chai-Adisaksopha C, Crowther M,
62. Lucassen W, Geersing GJ, Erkens PM, et al. 72. Schulman S, Kearon C, Kakkar Isayama T, Lim W. The impact of bleed-
Clinical decision rules for excluding pul- AK, et al. Dabigatran versus warfa- ing complications in patients receiving
monary embolism: A meta-analysis. Ann rin in the treatment of acute venous target-specific oral anticoagulants: A sys-
Intern Med. 2011;155(7):448. thromboembolism. N Engl J Med. tematic review and meta-analysis. Blood.
63. den Exter PL, van Es J, Erkens PM, et al. 2009;361(24):2342–52. 2014;124(15):2450–8.
Impact of delay in clinical presentation on 73. Fox BD, Kahn SR, Langleben D, 83. Carrier M, Righini M, Wells PS, et al.
the diagnostic management and prognosis Eisenberg MJ, Shimony A. Efficacy and Subsegmental pulmonary embolism
of patients with suspected pulmonary safety of novel oral anticoagulants for diagnosed by computed tomography:
embolism. Am J Respir Crit Care Med. treatment of acute venous thromboem- Incidence and clinical implications. A sys-
2013;187(12):1369–73. bolism: Direct and adjusted indirect tematic review and meta-analysis of the
64. Singh B, Mommer SK, Erwin PJ, metaanalysis of randomised controlled management outcome studies. J Thromb
et al. Pulmonary embolism rule-out trials. BMJ. 2012;345:e7498. Haemost. 2010;8(8):1716–22.
criteria (PERC) in pulmonary embo- 74. Kearon C, Akl EA, Ornelas J, et al. 84. Wiener RS, Schwartz LM, Woloshin S.
lism—revisited: A systematic review Antithrombotic therapy for VTE disease: When a test is too good: How CT pulmo-
and the meta-analysis. Emerg Med J. CHEST guideline and expert panel report. nary angiograms find pulmonary emboli
2013;30(9):701–6. Chest. 2016;149(2):315–52. that do not need to be found. BMJ.
65. Freund Y, Cachanado M, Aubry A, et al. 75. Robertson L, Jones LE. Fixed dose sub- 2013;347:f3368.
PROPER Investigator Group. Effect of the cutaneous low molecular weight heparins 85. Lee AY, Kamphuisen PW, Meyer G, et al.
pulmonary embolism rule-out criteria on versus adjusted dose unfractionated Tinzaparin vs warfarin for treat-
subsequent thromboembolic events among heparin for the initial treatment of venous ment of acute venous thromboembo-
low-risk emergency department patients: thromboembolism. Cochrane Database lism in patients with active cancer:
The PROPER randomized clinical trial. Syst Rev. 2017;2:DC001100. A randomized clinical trial. JAMA.
JAMA. 2018;319(6):559–66. 2015;314(7):677–86.
51
CHAPTER
Influenza
Gail Scully, MD, MPH
631
632 Chapter 51 Influenza
Only influenza A viruses are subtyped. Influenza A is sub- place between at least two strains of influenza A (usually
typed on the basis of two major surface proteins, neur- a human and an animal strain) to produce a new influenza
aminidase (NA) and hemagglutinin (HA). These surface subtype. This reassortment can take place when a cell is
proteins project like spikes, densely covering the surface infected with two (or more) different strains of influenza
of the virus, and are important for cell entry. One addi- virus. Antigenic shift can also occur by direct spread of
tional protein, membrane protein M2, is also present in an animal strain of influenza (usually an avian strain) to a
small amounts on the viral envelope. Influenza A viruses human. An example of this is the H5N1 “bird flu” which
are named for their HA and NA surface proteins, for continues to cause sporadic human infection in Egypt and
example, a virus called H3N2 will contain HA type 3 and Asia.3 Pandemic influenza can occur after antigenic shift,
NA type 2. In addition to subtype, influenza A viruses are when a new strain of the flu emerges to which little or no
further characterized on the basis of the place and time immunity is present in the population.
that the virus was first isolated (e.g., A/California/7/2009)
(H1N1).
At least 16 antigenically distinct HAs and nine distinct
NAs have been described in influenza A viruses. However,
51.5 EPIDEMIOLOGY OF
viruses that lead to human infection generally contain INFLUENZA
one of the three most common antigenic subtypes of HA
(either H1, H2, or H3) and one of the two most com- It is estimated that 5%–20% of persons in the United
mon subtypes of NA (N1 or N2). More recently, H5, H6, States are infected with an influenza virus each year.4
H7, H9, and H10 influenza viruses have been found to Influenza constitutes an epidemic when there is an out-
infect humans, primarily in Asia, after poultry exposure. break in a particular location. Outbreaks are detected by
Although a few small clusters have occurred, sustained monitoring patient visits for influenza-like illness and by
human-to-human transmission of these viruses has not surveillance of tests results that are ordered for the spe-
been seen. cific characterization of influenza-like illness. The Centers
All influenza viruses are capable of infecting humans. for Disease Control and Prevention (CDC) and the World
Influenza A viruses are capable of infecting many animal Health Organization (WHO) have collaborating laborato-
species as well, including swine, horses, marine mammals, ries for the purpose of influenza surveillance, viral detec-
and birds. Wild birds, particularly aquatic birds, are the tion, viral isolation, and characterization. Internet search
natural hosts of influenza A virus. Influenza viruses of low engine queries for influenza have also been shown to be
pathogenicity do not necessarily lead to clinical illness in reliable markers of epidemics in a community when they
the birds they infect, but viruses that cause severe disease show a rapid increase in frequency. 5 In temperate climates,
and death in birds do exist (e.g., H5N1). The isolation of epidemics of influenza occur most commonly in the win-
influenza virus from ferrets in the laboratory took place ter months. In the Northern Hemisphere, seasonal epi-
in 1933, and ferrets continue to be the ideal animal model demics of influenza typically occur between late fall and
for the study of influenza. Virus culture in embryonated early spring. Influenza epidemics often begin abruptly,
hen eggs was accomplished in 1936. These advancements reach a peak over several weeks, and last for two to three
allowed the study of virus properties and led to the devel- months. In general, 10%–20% of the population will
opment of vaccines in the 1940s. Animal cell culture become infected during an outbreak. A major factor in the
systems for propagating virus in tissue culture were devel- extent of the population that will become infected in an
oped in the 1950s. outbreak is the level of immunity in the population. The
major determinant of immunity is the presence of neutral-
izing antibody to the HA glycoprotein on the surface of
51.4 GENETIC VARIATION the virus. Children have the highest incidence of infection
overall. Adults over the age of 65, children younger than
Influenza viruses are constantly changing their antigenic- two years of age, and persons with certain underlying
ity. This evolution of influenza viruses is characterized on health problems are the most likely to suffer serious con-
the basis of the two primary mechanisms by which this sequences of influenza virus infection, including death.
genetic variation occurs, antigenic drift and antigenic Estimates by the CDC suggest that up to 56,000 people
shift. All influenza viruses (A, B, and C) undergo anti- in the United States die each year as a result of influenza
genic drift. Only influenza A virus undergoes antigenic virus infection and between 140,000 and 710,000 per-
shift. Antigenic drift occurs continuously due to point sons are hospitalized.6
mutations in the NA gene or (more commonly) the HA Pandemics often occur outside the usual influenza sea-
gene, both of which code for viral surface proteins. These son. On average, there have been five pandemics in each
mutations occur frequently, as the RNA polymerase of the century that have been documented in written history.
influenza virus has relatively low fidelity and lacks proof- The WHO defines an influenza pandemic as an animal
reading capacity. Minor changes in the surface proteins or human-animal reassortant virus causing sustained
occur due to these mutations and lead to what is known as person-to-person spread which leads to community out-
antigenic drift. These antigenic changes lead to virus vari- breaks in two or more countries in one WHO region and
ants that a previously immune host could now be suscep- an outbreak of the same virus in at least one other WHO
tible to, allowing for new outbreaks of disease. Antigenic region. Most pandemic viruses have been due to human-
shift in influenza A virus occurs in one of two ways. It animal reassortant viruses. Well-characterized pandemic
occurs when reassortment of genome segments takes influenza viruses from the past century include the 1918
51.8 Clinical Illness 633
H1N1 “Spanish Flu,” H2N2 “Avian Flu” in 1957, the influenza, though a typical case of influenza is associated
51
H3N2 “Hong Kong Flu” in 1968, and the latest pan- with three days lost from work or school.13 Total lost
demic, 2009 novel H1N1. The “Spanish Flu” pandemic in earnings due to illness with influenza virus are estimated
1918–1919 had the largest human impact of any recorded to be $16.4 billion yearly. The annual economic burden
influenza epidemic and is without a doubt one of the more of the influenza virus to the U.S. economy has been esti-
dramatic events of recorded medical history. Although mated at $87 billion.
given the name “Spanish Flu,” the first known outbreaks
of 1918–1919 pandemic influenza were seen in military
camps in the United States. This pandemic is estimated
to have caused more than 20 million deaths worldwide,
51.7 PATHOPHYSIOLOGY OF
more deaths than occurred due to combat in World War INFLUENZA
I. It is estimated that 25% of people living in the United
States and a fifth of the world’s population were infected The predominant means of spread of influenza virus is
during this pandemic. The brunt of this excess mortality from an infected person to a susceptible host at a dis-
was dealt to young people, with most deaths occurring tance of six feet or less.14 Large (≥5 μm diameter) respira-
in the 20- to 40-year-old age group. In a typical influ- tory droplets are disseminated when an infected person
enza epidemic, 0.1% of individuals who become infected coughs or sneezes. Transmission by aerosolized virus that
will suffer mortality. The death rate of those who became can travel long distances can occur but is not a common
infected with influenza virus in the 1918–1919 epidemic method of viral spread and is not of great clinical signifi-
was 2.5%.7 It is estimated that half of the deaths among cance. Although influenza virus can also be transmitted
American servicemen in World War I were due to influ- via hands contaminated with respiratory secretions or
enza, as compared to deaths due to battle injuries. by fomites, the virus degrades quickly on human hands
The most recent influenza pandemic began in February (within five min) and so this route probably plays a mini-
2009 with an outbreak in Mexico.8 In early April 2009, mal role in spread of infection.15 Once virus is deposited
the Mexican government began investigating increased on respiratory epithelium, it attaches to columnar epithe-
numbers of influenza-like illness. Almost simultaneously, lial cells through interaction of the viral HA glycoprotein
ongoing enhanced surveillance for Influenza A viruses with sialic acid residues on host-cell receptors and pen-
that could not be subtyped was able to identify a novel etrates via endocytosis. Virus replicates within the cells
influenza virus in two patients in Southern California.9 of the respiratory tract within four hours. Cell death in
This virus was characterized as a triple reassortant virus infected cells takes place due to both direct necrosis and
containing six genes from previously circulating North apoptosis. Dead and dying cells will then release virus that
American swine viruses and two genes of Eurasian avian- infect adjacent cells. The incubation period of influenza is
like swine virus origin. The geographic spread of virus one to four days (average two days), depending on inocu-
was unprecedented, covering in six weeks of time what lum, with more rapid onset of illness after a heavy viral
had taken a six-month period of time in previous pandem- exposure. Adults infected with influenza virus are able to
ics.10 The CDC estimates that approximately 61 million spread the infection via viral shedding beginning about
persons in the United States were infected during this lat- one day prior to the onset of symptoms and for 5–10 days
est pandemic; approximately 265,000 people required after onset, but the heaviest period of viral shedding is the
hospitalization and 12,000 deaths occurred between first three to four days of illness. Children may shed virus
April 2009 and February 2010. The virus preferentially for a longer period of time, including for several days prior
infected younger people (i.e., under 25 years of age), most to the onset of illness, probably due to a relative lack of
likely due to cross-protective antibodies in older persons immunity. Immunocompromised persons can shed virus
who may have been exposed to antigenically related influ- for months.
enza viruses earlier in life.
Approximately 25%–50% of patients who were hospi-
talized or died due to infection with 2009 H1N1 had no
reported coexisting medical conditions. Ninety percent of
51.8 CLINICAL ILLNESS
deaths due to 2009 H1N1 infection took place in persons
less than 65 years of age.11 Pregnant women were at par-
51.8.1 Seasonal Influenza
ticularly high risk, accounting for up to 10% of persons Influenza virus infection usually presents with the abrupt
who were hospitalized or who died from 2009 H1N1, onset of fever, headache, malaise, myalgias, sore throat,
even though they represent only 1%–2% of the general rhinitis, and cough. Illness in children also commonly
population. Spontaneous abortion, preterm labor and includes nausea and vomiting along with otitis media, but
birth, and fetal distress also occurred. these are not commonly present in adults. Some strains of
influenza may be associated with an increased incidence
(up to 25% of infected persons) of nausea, vomiting, and
51.6 ECONOMIC IMPACT diarrhea, and less rhinorrhea and pharyngitis.16,17 Mild ill-
ness without fever, similar to that seen with a common
The CDC has estimated that direct medical costs due to cold, can also occur after influenza virus infection. The
influenza in the United States amount to approximately incubation period is generally one to two days. The dura-
$10.4 billion annually (2003 values).12 Direct medical costs tion of illness ranges from three to seven days, though
only make up a fraction of the economic consequences of cough may persist for weeks.
634 Chapter 51 Influenza
Respiratory infection due to influenza virus is difficult influenza B virus infection than with influenza A. Most
to diagnose based on clinical symptoms alone, although patients with Reye’s syndrome present initially with nau-
systemic symptoms are generally more severe than those sea and vomiting. This is followed by altered mental status
due to other respiratory viruses. The likelihood that a manifesting variably as delirium, lethargy, and seizures,
respiratory illness is due to influenza virus will depend in progressing at times to coma and respiratory arrest. Most
part on whether influenza is currently circulating in the patients will have elevated ALT and AST; bilirubin is gen-
community. On physical examination, the patients may erally not elevated. Elevation in serum ammonia level is
look acutely ill. Although sore throat is common, the universal. If a lumbar puncture is performed to evaluate
pharynx is not usually infected and purulence over the altered mental status, cerebrospinal fluid will be unre-
tonsils is uncommon. Mild cervical lymphadenopathy is markable. Reye’s syndrome has become less common due
sometimes found. Lungs are generally clear on ausculta- to warnings to avoid the use of aspirin in children with
tion although rhonchi, wheezes, and rales can be found if acute respiratory illnesses. The exact etiology of Reye’s
pneumonia is present. syndrome is unclear.
Pneumonia can occur due to direct viral infection of
the lower airway or due to secondary bacterial infection.
Viral pneumonia due to seasonal influenza is uncommon 51.8.2 Avian Influenza
but may be quite severe. A common presentation of this
entity is the typical onset of clinical disease due to influ- Sporadic human infection with influenza A viruses that
enza, followed by rapid onset of shortness of breath and predominately infect birds has been noted, and involves
cyanosis. Primary viral pneumonia may occur more com- the H5, H6, H7, H9, and H10 subtypes. Most human
monly after infection with certain strains of influenza cases of avian influenza are due to either H5N1 or H7N9.
virus.18 When viral influenza is present, viral cultures of Despite concerns of a human pandemic due to avian
the sputum will reveal high titers of influenza virus, and influenza virus, these sporadic infections have not gener-
bacterial cultures will usually be notable for normal oral ally resulted in person-to-person transmission, with the
flora. The chest x-ray of primary viral pneumonia reveals exception of some limited spread between lengthy unpro-
bilateral infiltrates. Pathologic findings of influenza pneu- tected close contacts of those infected with H5N1 and
monia include necrotizing bronchitis, hyaline membranes, H7N9 avian influenza virus. In 1997, the first recognized
alveolar hemorrhage, and edema. case of severe human illness with H5N1 avian influenza
A significant proportion of the mortality associated virus was reported in Hong Kong. Millions of poultry
with influenza virus infection is due to pneumonia caused were slaughtered in order to try to contain the disease.
by secondary bacterial superinfection. The typical clinical Despite these efforts, H5N1 avian influenza has become
picture associated with pneumonia due to bacterial super- entrenched in Africa and Asia. Transmission to humans
infection is that of a typical influenza-like illness, then probably takes place via the respiratory route, but infec-
clinical improvement, followed by worsening with fever, tion via the gastrointestinal tract is possible and has been
cough productive of sputum, and dyspnea. The most com- demonstrated in zoo animals that were fed infected poul-
mon bacterial pathogens leading to secondary infection of try and in human infections presenting with diarrhea after
influenza are Streptococcus pneumoniae, Staphylococcus consuming raw duck blood.
aureus, Haemophilus influenzae, and Streptococcus
pyogenes. Severe necrotizing staphylococcal pneumonia
complicating influenza virus infection has been described
51.9 LABORATORY DIAGNOSIS
particularly in children and young adults.19,20 Both pri- OF INFLUENZA
mary viral pneumonia and pneumonia due to bacterial
superinfection occur most commonly in older persons Influenza virus can be readily isolated or detected from a
with underlying cardiopulmonary disease, although pri- variety of respiratory specimens. Nasopharyngeal swabs
mary viral pneumonia also has a predilection for pregnant are the most reliable specimen source for most assays.
women and young adults. Immunosuppressed individuals, Influenza can be diagnosed by rapid diagnostic methods
especially those with hematologic malignancies, persons including immunoassays, by polymerase chain reaction
who have had recent solid organ transplantation, and (PCR), or by more traditional and time-consuming meth-
those with HIV and low CD4 counts are at increased risk ods such as cell culture.22 Results are most likely to be pos-
for severe influenza infection, including pneumonia. itive in children, who shed higher titers of virus, and in any
Although influenza primarily affects the respira- patient during the first 48–72 h of clinical illness, when
tory tract, involvement of other organ systems has been viral shedding is the greatest. PCR assays can differentiate
described, including myositis with elevated creatinine between influenza subtypes and A and B. Immunoassay
phosphokinase, myoglobinuria, and occasionally rhabdo- and PCR results can be available quickly, often in 15 to 30
myolysis. Patients with myositis have muscle tenderness minutes. This can be useful for clinical decisions regarding
that most commonly affects the legs. 21 Myocarditis and provision of antiviral therapy. Limitations for rapid influ-
pericarditis have been reported but are rare. Guillain– enza immunoassays exist, however, primarily due to false
Barre syndrome has been reported after influenza but negative results. The sensitivity of the test is in the range
this may be coincidence rather than etiologic. Transverse of 40%–70%, with a specificity of 90%–95%. A negative
myelitis and encephalitis due to influenza are rare. rapid influenza test should not be used to withhold anti-
Reye’s syndrome is seen almost exclusively in children viral therapy in a patient with a clinical syndrome con-
who are taking aspirin. It appears more commonly after sistent with influenza virus infection when therapy would
51.10 Prevention 635
otherwise be indicated. Multiplex PCR assays can detect reinfection with the same viral strain and possibly some
51
not only influenza but a variety of respiratory viruses.23 In degree of protection within a subtype. Due to ongoing
patients with lower respiratory tract illness, endotracheal antigenic changes of influenza virus that lead to escape
or bronchoscopic aspirates may be more sensitive than from immunologic control, routine vaccination is the best
nasopharyngeal samples. Specimens for viral culture or for strategy for control of influenza epidemics. The Advisory
RT-PCR should be placed in containers of viral transport Committee on Immunization Practices (ACIP) issues
medium and brought promptly to the laboratory. Influenza yearly updated recommendations for influenza vaccina-
virus replicates in a variety of cell types; kidney cell cul- tion through the CDC. 26 In response to antigenic varia-
tures are most commonly employed, although embryo- tion of influenza viruses, the content of influenza vaccine
nated eggs can also be used for viral culture. More than may change on an annual basis. Seasonal influenza vac-
90% of influenza viral cultures are positive within three cines are formulated as both quadrivalent and trivalent
days, and the remainder of positive cultures will be positive preparations, with two influenza A components and one
by seven days after inoculation. Serologic testing can be or two influenza B component(s). The components of the
used to retrospectively diagnose influenza virus infection. seasonal vaccine may vary year to year and are chosen
As most people have been infected with influenza virus based on the viruses that are circulating at the end of the
in the past, diagnosis of a recent acute infection requires previous influenza season. Influenza vaccines are available
paired acute and convalescent serum specimens (the lat- as inactivated vaccine grown in tissue culture or recom-
ter should be obtained 10–20 days after acute illness) run binant vaccine. Live attenuated intranasal vaccine is not
simultaneously to assess for an increase in antibody titer. currently recommended due to concerns about effective-
Decisions regarding treatment of influenza should not ness. High-dose vaccine and influenza vaccine with an
be exclusively based on the results of tests for the pres- adjuvant have been approved for use in persons over age
ence of influenza virus, especially when the virus is known 65. Immunity develops about two weeks after vaccination
to be circulating in the community and a patient pres- but can take longer in children. Increases in HAI antibody
ents with signs and symptoms consistent with influenza. are seen in about 90% of healthy adults after vaccination
Several studies have demonstrated that the clinical diag- with influenza virus vaccine. Peak antibody titers occur
nosis of influenza can be made with 77%–90% accuracy about two to four months after vaccination and return to
when influenza is present in the community and patients baseline prior to the next influenza season. A recent meta-
present with typical symptoms. 24 It is reasonable to test nalysis suggested that vaccination is about 60% effective
only in those circumstances where the results will impact at preventing influenza in healthy adults, but lower vac-
clinical decision making. cine effectiveness has recently been seen for certain strains
of influenza.6
Currently, influenza vaccine is recommended yearly
51.10 PREVENTION for all persons over six months of age. Children aged six
months to eight years of age who have not had a previ-
Vaccination is the best way to prevent influenza virus ous influenza vaccination are recommended to receive two
infection. Some studies suggest that vaccinating children doses of vaccine. Side effects of vaccination are generally
against influenza may be more effective in preventing the mild. Local soreness at the site of injection is common
flu in the elderly than vaccinating older adults themselves, after inactivated influenza virus vaccine. Low-grade tem-
as children are very effective at spreading influenza, and perature elevations can be seen after vaccine administra-
older adults may have a suboptimal response to vaccina- tion, but these are only slightly more common than after
tion. 25 As influenza virus is spread primarily by inhalation placebo. Side effects of live attenuated intranasal influ-
of small droplet particles, maintaining a distance of six feet enza vaccine are nasal congestion and sore throat, which
from persons coughing or sneezing is prudent. Although occur at a slightly higher rate than that seen with placebo.
environmental contamination is a relatively unimportant Live attenuated vaccine viruses can be transmitted to close
mechanism for the spread of influenza, cleaning hands contacts, although this does not seem to occur frequently.
after contact with common high-touch public areas, such Hypersensitivity to hen eggs is a contraindication to
as doorknobs, makes sense especially during flu season. administration of inactivated influenza vaccine grown in
This is particularly important before making hand contact egg-based tissue culture systems. In 1976, an elevated rate
with one’s face or eyes. Alcohol-based hand rubs are very of Gillian–Barre syndrome (GBS) was observed in persons
effective and especially useful when water is not available who received the swine flu vaccine. It is recommended that
for washing. Persons ill with the flu or other respiratory persons who develop GBS within six weeks of an influ-
viruses should make an effort to “cover their cough” with enza vaccine refrain from further vaccination.
a tissue, or cough into their elbow or shoulder to avoid
exhaling viral particles into the air and infecting others.
After coughing into a tissue, it should be discarded in the 51.10.2 Chemoprophylaxis
trash and hands should be cleaned.
Antiviral medicines taken daily during a period of expo-
sure are 79%–90% effective at preventing influenza.
Chemoprophylaxis should be started within 48 h of expo-
51.10.1 Vaccination sure to be effective. Indiscriminate use of prophylaxis is not
Immunity to influenza virus is mediated by secretory IgA recommended as it can promote antiviral resistance, but
and serum IgG antibodies specific for the viral surface can be considered if there is an outbreak in a long-term
proteins HA and NA. Infection results in resistance to care facility or on a case-by-case basis after exposure in
636 Chapter 51 Influenza
a person at high risk of complications from influenza vac- well within achievable drug concentrations in humans. All
cine. The recommended dose of oseltamivir for chemopro- avian influenza strains, including H5N1, are sensitive to
phylaxis against influenza in adults is 75 mg orally once a NA inhibitors. Oseltamivir is rapidly absorbed from the
day. The recommended dose of zanamivir for prophylaxis gut and is converted in the liver to the active metabolite.
of influenza (types A and B) in adults in a household setting The metabolite is eliminated unchanged in the urine. Dose
is two inhalations (5 mg per inhalation) orally once daily. reduction is recommended for persons with creatinine
The recommended duration of post exposure prophylaxis is clearance of less than 60 mL/min. Persons on hemodialysis
generally 10 days after a household exposure or seven days (HD) should receive 30 mg initially and then 30 mg after
following exposure in other situations. The dose should be each HD. The most common side effect of oseltamivir is
given at approximately the same time each day.27 nausea and vomiting, which can be reduced if the drug is
taken with food. Oseltamivir is not licensed for children
under the age of one year but was used for younger chil-
51.10.2.1 Self-Care for Persons with Influenza dren during the H1N1 pandemic under an Emergency Use
Most persons with influenza virus infection do not need Authorization from the Food and Drug Administration.
antiviral drugs or require attention from a medical profes- Zanamivir is not orally bioavailable and is supplied as a
sional. Persons more likely to develop complications, such dry powder for oral inhalation, given as a dose of two
as the elderly, persons with chronic medical conditions, inhalations twice a day. It can precipitate bronchospasm
Native Americans and Alaska Natives, pregnant women, if given to patients with underlying pulmonary disease.
immunosuppressed patients, morbidly obese persons, and Zanamivir is not recommended for persons with underly-
those with asthma, who have an illness consistent with ing lung disease, that is, asthma or chronic obstructive
influenza, should consult their health care provider and pulmonary disease, or for children under the age of seven.
be evaluated for treatment with antivirals, as should any The tolerability and efficacy of inhaled zanamivir has not
person who is concerned about severe symptoms. The been studied in persons with severe influenza, but in some
CDC recommends that persons remain at home and avoid instances seriously ill persons given inhaled zanamivir
public places as much as possible until at least 24 h after have had respiratory distress. An intravenous NA inhibi-
fevers abate (without antipyretic use). Antipyretics can tor, peramivir, is available for adults who are unable to
reduce fever and aid in comfort, but aspirin should not be take oral medications. It is given as a single 600 mg dose,
used by children or teenagers who have influenza. Persons with a dose adjustment indicated for persons with a creati-
with fever should consume adequate fluids to compensate nine clearance of less than 50 mL/min. Longer courses of
for increased fluid losses associated with sweating and therapy have been used for severely ill persons.
increased respiration. Usual activities, including exercise Oseltamivir, peramivir, and zanamivir have similar
can be resumed when recovery is adequate and the person efficacy in clinical trials of persons infected with influ-
who had influenza feels ready to take part in those activi- enza A and influenza B. In healthy adults, early treatment
ties. Whether hand washing prevents influenza transmis- (within the first 36 h of illness) results in a 30%–40%
sion is unclear, as the virus is not known to survive for a shorter duration of symptoms and an earlier return to
long period of time on surfaces, and transmission through work. Antiviral medication can reduce the duration of
the air via respiratory droplets is felt to be the most impor- illness when started within two days of onset of clinical
tant means of transmission. However, hand washing has illness. In a study among healthy volunteers, NA inhibi-
been shown to be of benefit for preventing transmission of tors reduced the duration of illness by one to two days.
other respiratory viruses and gastrointestinal illnesses and The standard dose of oseltamivir for treatment of mild-
is prudent to practice. Covering the mouth when coughing moderate illness with susceptible influenza virus is 75 mg
should be practiced routinely no matter what the reason orally twice a day in adults with normal renal function.
for the cough; the same is true for using a tissue that is An increased duration of therapy has been used in severely
then discarded in a waste receptacle or by coughing into ill patients. 28,29
one’s shoulder if a tissue is not available. Antiviral therapy is indicated as early as possible for
persons hospitalized with influenza, those with severe
progressive illness, and those at higher risk of severe ill-
51.11 ANTIVIRAL THERAPY ness. 27,29 Some studies suggest that early therapy with osel-
tamivir may reduce the incidence of hospitalization and
Antiviral medicines active against influenza virus include the risk of progression to severe disease. Initiating therapy
the neuraminidase (NA) inhibitors oseltamivir, peramivir, after 48 h should be considered for persons at high risk for
and zanamivir, and the M2 inhibitors amantadine and complications of influenza and for hospitalized patients
rimantadine. The M2 inhibitors, classified as adaman- with severe illness. Persons at higher risk of severe illness
tanes, are only active against influenza A and are cur- recommended for antiviral therapy include children less
rently less useful due to high levels of resistance. The NA than two years of age, adults aged ≥65 years old, women
inhibitors are active versus both A and B viruses. who are pregnant or less than two weeks postpartum,
The NA inhibitors oseltamivir, peramivir, and zana- persons with chronic cardiac disease (except hypertension
mivir inhibit the function of the NA protein of influenza alone), chronic pulmonary disease, renal disease, hepatic
viruses. This protein cleaves sialic acid residues and is nec- disease, hematologic disease (including sickle cell), meta-
essary for budding of virus from infected cells. Although bolic disorders (including diabetes mellitus), neurologic
influenza A viruses are more sensitive to the NA inhibitors or neurodevelopmental conditions, immunocompromised
than influenza B viruses, influenza B viruses are inhibited states (including HIV), persons aged <19 on long-term
References 637
aspirin therapy (due to the risk of Reye’s syndrome), per- characteristics of the individual host. Complications of
51
sons who are morbidly obese, and residents of long-term influenza virus infection can occur directly from viral
care facilities. Selection of antiviral therapy should take infection and due to bacterial superinfection of the respi-
into consideration the susceptibility pattern of circulat- ratory tree. Efforts to prevent or minimize the impact of
ing influenza virus in the community. It is unclear at this seasonal influenza center on the use of vaccines. Antiviral
time what the therapeutic efficacy is of antiviral therapy medications are available and ameliorate disease in healthy
for H5N1 virus infection. Drug-resistant viruses have also adults and may also have an effect in seriously ill patients.
been detected in persons who had no history of treatment
with NA inhibitors.
CLINICAL APPLICATIONS
51.12 SUMMARY • Prevention of influenza through vaccination, atten-
tion to cleaning hands (especially during flu season),
Influenza is a common upper-respiratory infection caused and avoiding those who are likely sick with influ-
by a virus of the Orthomyxoviridae family. There are enza when possible, is highly recommended.
three viral subtypes, although most illness is caused by • Current medications to treat influenza are recom-
influenza A or B. Genetic variation allows the influenza mended for certain populations and for those hos-
virus to escape host defenses and infect an individual mul- pitalized with influenza, but efficacy is less than
tiple times during a lifetime. Clinical illness from influenza desired.
virus ranges from a mild upper-respiratory illness to a • When ill with influenza, patients should rest, main-
fatal viral pneumonia depending on the virulence charac- tain adequate fluid intake, and stay home as much as
teristics of the virus and the immune system and physical possible to avoid infecting others.
REFERENCES
1. Potter CM. 2001. A history of influenza. impact of seasonal influenza in the US: 22. Choi YJ, Nam HS, Park JS et al. 2010.
J Appl. Microbiol. 91(4): 572–579. Measuring disease burden and costs. Comparative analysis of the mul-
2. Taubenberger JK, Morens DM. 2010. Vaccine. 25(27): 5086–5096. tiple test methods for the detection of
Influenza: The once and future pandemic. 13. Keech M, Beardsworth P. 2008. Pandemic Influenza A/H1N1 2009
Public Health Rep. 125(Suppl 3): 16–26. The impact of influenza on working virus. J Microbiol Biotechnol. 20(10):
3. Gambotto A, Barratt-Boyes SM, de Jong days lost: A review of the literature. 1450–1456.
MD et al. 2008. Human infection with Pharmacoeconomics. 26(11): 911–924. 23. Faix DJ, Sherman SS, Waterman SH.
highly pathogenic H5N1 influenza virus. 14. Brankston G, Gitterman L, Hirji Z et 2009. Rapid-test sensitivity for novel
Lancet. 371(9622): 1464–1475. al. 2007. Transmission of influenza A in swine-origin influenza A (H1N1) virus
4. Lagace-Wiens PR, Rubinstein E, Gumel human beings. Lancet Infect. Dis. 7(4): in humans. N Engl J Med. 361(7):
A. 2010. Influenza epidemiology—past, 257–265. 728–729.
present, and future. Crit. Care Med. 15. Weber TP, Stilianakis NI. 2008. 24. Zambon M, Hays J, Webster A et al.
38(Suppl 4): e1–e9. Inactivation of influenza A viruses in the 2001. Diagnosis of influenza in the
5. Ginsberg J, Mohebbi MH, Patel RS. environment and modes of transmission: community: Relationship of clinical
2009. Detecting influenza epidemics A critical review. J Infect. 57(5): 361–373. diagnosis to confirmed virological,
using search engine query data. Nature. 16. Zhang J, Zhang Z, Fan X et al. 2010. serologic, or molecular detection of
457(7232): 1012–1014. 2009 pandemic H1N1 influenza virus influenza. Arch Intern Med. 161(17):
6. Influenza (Flu). Centers for Disease replicates in human lung tissues. J Infect 2116–2122.
Control and Prevention. https://www.cdc. Dis. 201(10): 1522–1526. 25. Cohen SA, Chui KK, Naumova EN.
gov/flu/index.htm 17. Belongia EA, Irving SA, Waring SC et al. 2011. Influenza vaccination in young
7. Neumann G, Noda T, Kawaoka Y. 2009. 2010. Clinical characteristics and 30-day out- children reduces influenza-associated
Emergence and pandemic potential of comes for influenza A 2009 (H1N1), 2008– hospitalizations in older adults,
swine-origin H1N1 influenza virus. 2009 (H1N1), and 2007–2008 (H3N2) 2002–2006. J Am Geriatr Soc. 59(2):
Nature. 459(7249): 931–939. infections. JAMA. 304(10): 1091–1098. 327–332.
8. Trifonov V, Khiabanian H, Rabadan R. 18. Nguyen-Van-Tam JS, Openshaw PJ, 26. Update: Recommendations of the
2009. Geographic dependence, surveil- Hashim A et al. 2010. Risk factors for Advisory Committee on Immunization
lance, and origins of the 2009 influenza hospitalisation and poor outcome with Practices (ACIP) regarding use of CSL
A (H1N1) virus. N. Engl. J. Med. 361(2): pandemic A/H1N1 influenza: United seasonal influenza vaccine (Afluria) in the
115–119. Kingdom first wave (May–September United States during 2010–2011. 2010.
9. Shinde V, Bridges CB, Uyeki TM et al. 2009). Thorax. 65(7): 645–651. MMWR Morb Mortal Wkly Rep. 59(31):
2009. Triple-reassortant swine influenza 19. Murray RJ, Robinson JO, White JN et 989–992.
A (H1) in humans in the United States, al. 2010. Community-acquired pneu- 27. Antiviral drugs for seasonal influenza.
2005–2009. N. Engl. J. Med. 360(25): monia due to pandemic A(H1N1)2009 Med Lett Drugs Ther. 60(1537): 1–4.
2616–2625. influenzavirus and methicillin resistant 28. Rodriguez A, Diaz E, Martin-Loeches I
10. Khan K, Arino J, Hu W et al. 2009. Staphylococcus aureus co-infection. et al. 2011. Impact of early oseltamivir
Spread of a novel influenza A (H1N1) PLoS One. 5(1): e8705. treatment on outcome in critically ill
virus via global airline transportation. N. 20. Lobo LJ, Reed KD, Wunderink RG. patients with 2009 pandemic influenza
Engl. J. Med. 361(2): 212–214. 2010. Expanded clinical presentation of A. J Antimicrob Chemother. 66(5):
11. Bautista E, Chotpitayasunondh T, Gao Z community-acquired methicillin-resistant 1140–1149.
et al. 2010. Clinical aspects of pandemic Staphylococcus aureus pneumonia. Chest. 29. Influenza Antiviral Medications:
2009 influenza A (H1N1) virus infection. 138(1): 130–136. Summary for Clinicians. Centers for
N. Engl. J. Med. 362(18): 1708–1719. 21. Rothberg MB, Haessler SD, Brown RB. Disease Control and Prevention. https: //
12. Molinari NA, Ortega-Sanchez IR, 2008. Complications of viral influenza. www.cdc.gov/flu/professionals/antivirals/
Messonnier ML et al. 2007. The annual Am J Med. 121(4): 258–264. index.htm.
52
CHAPTER
639
640 Chapter 52 Indoor Air Quality
composition (Table 52.1) of both sidestream and main- The term “thirdhand smoke” has been referred to as
stream smoke is similar in the number of compounds they cigarette by-products that cling to a smoker’s hair and
contain. However, the concentration and the physicochem- clothing as well as to household fabrics, carpets, and sur-
ical properties of these compounds can vary significantly. faces even after secondhand smoke has cleared.12 These
Secondhand smoke tends to linger in the local indoor invisible tobacco toxins pose danger to small children,
environment about 1.5–2 hours. With its composition of who are especially susceptible when they come in contact
oils and waxes, it may increase both the exposure period with contaminated surfaces.13
and entry into lung tissue and body cells more easily.10 Secondhand smoke exposure can be measured by test-
Sidestream smoke composition does not vary significantly ing indoor environments for nicotine and other chemicals
by tobacco product brand, but it remains as much as 10 in tobacco smoke. It can also be tested by measuring the
or more times toxic than mainstream smoke.11 Individuals level of cotinine (a by-product of the breakdown of nico-
may be exposed to secondhand smoke in homes, cars, the tine) in a nonsmoker’s blood, saliva, or urine.14 Nicotine,
workplace, public places, and recreational settings. In cotinine, carbon monoxide, and other smoke-related
the United States, the source of most secondhand smoke chemicals have been found in the body fluids of nonsmok-
is from cigarettes, followed by pipes, cigars, and other ers exposed to secondhand smoke by way of passive per-
tobacco products. sonal sampling exposure devices.15 The average exposure
is directly related to room size and ventilation rate within
that room.16,17 Older measuring devices would take days
TABLE 52.1 Carcinogens and suspected carcinogens in
to weeks to yield a result, but more modern devices can
secondhand cigarette smoke perform active sampling of the environment with more
efficacy. These devices can measure nicotine and several
Carcinogens Suspected carcinogens other markers, including carbon monoxide, nitrogen
Arsenic Acetaldehyde oxides, and polycyclic aromatic hydrocarbons.16
In June 2002, the International Agency for Research
Benzene Acetone on Cancer (IARC) concluded that “involuntary smok-
Beryllium Acrolein ing, exposure to secondhand smoke or ‘environmental’
tobacco smoke, is carcinogenic to humans.” The IARC
1,3-Butadiene Acrylonitrile
concluded further that there is a “statistically significant
Cadmium 2-aminonaphthalene and consistent association between lung cancer risk in
spouses of smokers and exposure to secondhand tobacco
Chromium Ammonia
smoke from their spouse who smokes. The excess risk is
Ethylene oxide Benzo[a]pyrene on the order of 20% for women and 30% for men”18.
Nickel Butyraldehyde In January 2005, the U.S. Public Health Service’s
National Toxicology Program issued its 11th report on
Polonium-210 Carbon monoxide carcinogens. This report unambiguously states “environ-
Vinyl chloride Catechol mental tobacco smoke is known to be a human carcinogen
based on sufficient evidence of carcinogenicity from stud-
Cresol
ies in humans that indicate a causal relationship between
Crotonaldehyde and passive exposure to tobacco smoke and human lung can-
Formaldehyde cer.”19 Some studies also support an association of envi-
Hydrogen cyanide ronmental tobacco with cancers of the nasal sinus cavity,
breast cancer, leukemia, lymphoma, and brain tumors in
Hydroquinone children. 20 Evidence of an increased cancer risk from envi-
Isoprene ronmental tobacco smoke stems from studies examining
nonsmoking spouses living with individuals who smoke
Lead cigarettes, 21–23 exposures of nonsmokers to environmental
Methyl ethyl ketone (MEK) tobacco smoke in occupational settings, and exposure to
parents’ smoking during childhood.6,12 Many epidemiolog-
Nicotine
ical studies, including large population-based case-control
Nitric oxide studies, demonstrate an increased risk of developing lung
NNN, NNK, and NAT cancer following prolonged exposure to environmental
tobacco smoke. Lifelong nonsmokers living with smokers
Phenol had, on average, a 24% higher chance of developing lung
Propionaldehyde cancer than those living with nonsmokers. Those exposed
to the heaviest smokers for the longest time had the high-
Pyridine
est risks. 23,24 Similarly, there is a growing body of evidence
Quinoline suggesting a higher risk of death from the association of
secondhand smoke exposure and ischemic heart disease.
Resorcinol
Most of the data surrounds spousal smoke exposure and
Styrene risk ratios that range between 20% to 30% and a twofold
Toluene excess risk of cardiac death in this population. 25–28 There
may be a confounding effect in these studies, as there may
52.5 Carbon Monoxide 641
be an innate risk in the U.S. population to develop cardio- progeny that include lead-210, which yields bismuth-210,
52
vascular disease. In addition, there are pathophysiologic which yields the stable isotopes polonium-210 and lead-
changes due to secondhand smoke that have not been 206. This whole decay process takes hundreds of years.
fully elucidated. It is known that the elevation in serum When inhaled into the lung, the alpha-particles can dam-
carboxyhemoglobin levels decreases exercise tolerance age cellular DNA and lead to mutagenesis in never-smok-
in both healthy persons and individuals with ischemic ing lung cancer cases.36
heart disease. 28 Also, “time until angina” decreases with Radon gas can seep into buildings through porous
increasing concentrations of serum carboxyhemoglobin, soil. The rate of diffusion is related to the pressure gra-
as does the frequency of arrhythmias during exercise, vas- dient created by the building structure across the soil,
cular endothelium damage, lower high-density lipoprotein which in turn, is influenced by atmospheric pressure,
cholesterol levels, and increase in fibrinogen with associ- wind flow over the structure, and the buoyancy of the air
ated fibrinogenesis. 28–31 taking advantage of cracks or gaps in building founda-
tions, floors, walls, along with gaps along pipes, pumps,
and drains. It can easily dissolve into and evaporate out
52.3 SECONDHAND SMOKE of water. Therefore, water drawn from private wells in
areas enriched with uranium can increase the exposure
EXPOSURE IN CHILDREN to radon. Inhaled radon poses a much higher risk for lung
cancer than the ingested form from drinking water.37,38
The Pro-Children Act of 1994 prohibits smoking in facili- Inhaled radon progeny have been linked to an increase
ties that routinely provide federally funded services to chil- in the risk of lung cancer in underground miners. 34 These
dren. Many state and local governments have passed laws progeny are the number one cause of lung cancer in never-
prohibiting smoking in public facilities such as schools, smokers and the second-leading cause of lung cancer over-
hospitals, airports, bus terminals, parks and beaches, and all. The EPA estimates that radon exposure may account
private workplaces, including restaurants and bars. There for over 21,000 lung cancer deaths each year, including
is no doubt that the impact caused by secondhand smoke 2,900 never-smokers, and the remaining deaths in smok-
exposure raises the frequency and severity of respiratory ers with radon exposure at concentrations as low as 2
illnesses and respiratory symptoms in children. In a 1993 pCi/L of air.39 It is difficult to ascertain the exact amount,
report, the EPA estimated between 150,000 and 300,000 length, and degree of exposure needed to cause lung can-
annual cases of bronchitis and pneumonia in children cer. Most studies causally link the exposure of uranium
could be attributed to secondhand smoke in the United in underground miners and lung cancer. A meta-analysis
States. Of these, between 7,000 and 15,000 will result in of 13 European case-control studies of uranium exposure
hospitalization. Secondhand smoke was also estimated to showed an increased risk of lung cancer, to smokers and
increase the rate of asthma exacerbations with between recent former smokers, and accounted for 2% of all can-
200,000 and 1,000,000 affected children.3 In addition, cer deaths in Europe, although it is difficult to accurately
secondhand smoke exposure increases the risk of sudden estimate the lifetime exposure to radon in these settings. 35
infant death syndrome (SIDS), and one survey found the The EPA recommends testing of radon in homes and
risk of SIDS to be up to threefold in children exposed to schools below the third floor, since toxic effects have not
active maternal smoking in utero and secondhand smoke been reported in high-rise dwellings. A “do-it-yourself”
exposure after birth.32 Aside from the obvious medical kit may be purchased at a local hardware store and can
implications, the economic burden associated with this be left in place for 48 to 72 hours in the bottommost floor
increase in morbidity is responsible for a rise in healthcare and first-floor rooms without fans, open windows, or
costs likely to be in the millions, if not billions, of dollars. open doors. Long-term or 90-day trackers give a better
A recent study in Israel educated parents of 29 families to estimate of year-round radon exposure. They may be used
the dangers of tobacco smoke exposure to their children when short-term devices yield a value higher than 4 pCi/L.
and showed a reduction in hair nicotine levels of the chil- If levels higher than 4 pCi/L are detected, interventions
dren, the number of cigarettes smoked by parents, and par- that range from sealing gaps or cracks in the foundation
ent reported child smoke exposure.33 More education and to installing a new ventilation or radon mitigation system
research is needed to identify opportunities for parents to that will ventilate air to the outside environment require a
reduce tobacco smoke exposure in their own children. professional contractor.39
are highest among adults over 65 years old, men, non- They should not be directly above or beside burning appli-
Hispanic whites, and non-Hispanic blacks. January has ances, as appliances may emit a small amount of CO upon
the highest number of averaged deaths, and in the United start-up. A detector should not be placed within 15 ft of
States, Nebraska has the highest mortality, whereas heating or cooking appliances or near very humid areas
California has the lowest mortality. Interestingly, weather such as bathrooms. 52
patterns of recent years have brought about large storms
that may increase the risk of CO exposure; Hurricane
Sandy in 2012 was associated with a marked spike in the 52.6 INDOOR MOLD
number of cases in the New York City area.45 CO binds
with a high affinity for hemoglobin, 200 times greater Mold is ubiquitous in the outside environment, and plays
than oxygen, forming carboxyhemoglobin (COHb) which an important role in breaking down organic matter such
disrupts oxygen transport. Additionally, CO binds to as trees and leaves. The abundance of mold in the out-
heme proteins in myoglobin and cytochrome oxidase.46–48 side environment allows for easy transportation into
Tissues with the highest oxygen demands including myo- the indoor environment, including homes, schools, and
cardium, brain, and exercising muscle are first affected. businesses, where they can raise concerns for long-term
The effects of CO are directly related to the level and adverse health effects and worsening of preexisting lung
duration of exposure. Initial symptoms include head- disease. Approximately 100 molds have been identified as
ache, fatigue, shortness of breath, nausea, dizziness, and potentially harmful to human health, although only a few
tachycardia. At higher concentrations, worsening cogni- are commonly found in indoor environments. The molds
tive impairment, loss of muscle coordination, coma, and most commonly found in the indoor environment include
death are possible. Symptom progression is illustrated in Cladosporium, Alternaria, Epicoccum, Fusarium,
Table 52.2. Reductions in maximal oxygen consumption Penicillium, Geotrichum, Rhodotorula, Chaetomium,
occur in normal young men with COHb levels near 5%.49 and Aspergillus. 53
Subjects with cardiovascular disease are considered to Molds are organisms with rigid cell walls that are a
be at high risk of morbidity with CO exposure. 50 A clear subset of the diverse group of organisms called fungi that
distinction should be made between angina and onset of lack chlorophyll and vascular tissue. Mold, like others in
cardiovascular disease as related to CO exposure. A link the kingdom Fungi, live on organic matter such as decaying
between morbidity and mortality has been shown with plants and living animal tissue. They have the capability
moderate to severe CO exposures resulting in myocardial to digest materials deemed unusable by other organisms,
injury. The correlation between low-level CO exposure which allows mold to grow on home materials such as car-
and heart disease has not been made, presumably because peting, drywall, ceiling tiles, and building materials made
of inaccurate measures of personal exposure in previous from organic matter. Molds do not produce leaves, and
studies. 51 they reproduce by germination of small particles called
The average level of CO in homes without gas stoves spores. Spores are not readily seen by the naked eye and
is generally low, at 0.5 to 5 parts per million (ppm). Levels range in size from 2 to 20 microns in diameter and up to
near properly adjusted gas stoves vary between 5–15 ppm, 100 mm in length, with characteristic microscopic shapes
but in poorly adjusted stoves, these levels can rise as high sizes and colors. Molds need a moisture rich environment
as 30 ppm or higher. At CO levels of 70 ppm, symptoms with an average humidity of greater than 65%, a tempera-
become more noticeable, and at levels greater than 150–200 ture of 50–90°F, and an organic substrate such as wood
ppm, disorientation, unconsciousness, and death may occur. on which to reproduce and germinate. Once germina-
CO levels can be monitored at home with a com- tion occurs, spores can grow, aerosolize, and be inhaled
mercially available detector. The Consumer Product or come in contact by humans in the environment. This
Safety Commission (CPSC) recommends that a detector was seen in the aftermath of hurricanes Katrina and Rita
be located near the home sleeping area to alert sleeping where many homes had to be demolished due to excessive
household members in the event of elevated CO levels. mold growth. 54
A small subset of molds in the indoor environment is
known to induce an immunoglobulin mediated antibody
TABLE 52.2 Carboxyhemoglobin levels and associated response in humans. 55 Molds produce antigens, which are
symptoms
substances known to cause allergic reactions, by either con-
CO-Hb Symptoms tact or direct inhalation. Illness brought on by molds can
be classified into two types, infectious or noninfectious.
10% Dyspnea on exertion, forehead tightness, dilatation
of cutaneous vessels
Noninfectious causes include allergic bronchopulmonary
aspergillosis (ABPA), hypersensitivity pneumonitis, and
20% Dyspnea on exertion, headache/throbbing temples worsening of preexisting asthma. Infectious causes are
30% Headache, irritability, altered judgment, fatigue, less common and very rarely cause disease in immuno-
dizziness, vision changes competent individuals. The most common infectious cause
is seen with the mold of the Aspergillus genus. Inhalation
40–50% Headache, confusion, syncope
may result in pulmonary infection and formation of
60–70% Coma, seizures, respiratory failure; death if a fungus ball called an aspergilloma. In severe cases of
prolonged exposure Aspergillus infection, invasion of the lung and blood ves-
80% Rapidly fatal sels may result in severe invasive Aspergillus and may be
seen in immunocompromised hosts who are HIV positive,
52.8 Dust Mites 643
post-organ transplantation, or receiving chemotherapy or approximately 2.5 µm in diameter and is easily inhaled
52
other immunosuppressive drugs.56 deep into the lower respiratory tract.64,65 Because of its
The most common symptoms of excessive indoor small size, up to one microgram of the Fel d1 protein may
mold exposure include non-asthmatic cough, wheez- be inhaled per day, which is similar to the amount used
ing, headache, and sneezing. This can be exacerbated by in sublingual immunotherapy.66 Even homes without cats
energy-efficient homes, so-called tight homes, with closed can have high concentrations of up to 80 micrograms of
ventilation systems with high indoor temperatures and Fel d1 per 1 gram of dust64,67 Current evidence suggests
humidity. 53 that early exposure to animal dander in childhood reduces
Fungal sensitization and exposure appear to play an the likelihood of sensitization and subsequent develop-
important role in the development of lower respiratory ment of asthma from both cats and dogs. It is important
tract disease. 57 A study done with severe asthmatics and to tell patients that completely non-allergenic animals do
fungal sensitization (SAFS) showed a 60% improvement not exist, but there are some breeds that are thought to
in asthma quality of life scores after treatment with the be less allergenic.68 Certain dog breeds are promoted as
antifungal medication itraconazole. This suggests that hypoallergenic breeds, such as the Labradoodle, Poodle,
controlling the mold burden may play a significant role Spanish Waterdog, and Airedale terrier.69,70 Recent studies
in reducing the severity of asthma. 58,59 However, the were performed comparing the amount of Can r1 and r2,
American Thoracic Society does not recommend antifun- antigens released by dogs, and found that these proteins
gal therapy for fungal sensitivity from causes not related to were significantly higher in breeds promoted as hypoal-
underlying ABPA.108). A 2008 study also estimated that up lergenic.69,71 The amount of protein was nearly double in
to 21% of asthma cases in the United States may be due to these “hypoallergenic” breeds as compared to ones clas-
excessive exposure to mold and damp living conditions.60 sified as allergenic. Reducing exposure to animal dander
The keys to preventing the potential harmful effects may be accomplished by using HEPA filters, frequent
of mold exposure include both identification of areas and bathing of the animal, or by removing the animal from
removal of both the mold and moisture rich environment. the environment altogether.
Mold growth is readily identified in areas of prior water
damage or constant high humidity. The mold can be
detected by both visual identification and by the pungent 52.8 DUST MITES
odors it produces from the breakdown of organic matter
into volatile organic compounds (VOCs) such as aldehydes Dust mites, Dermatophagoides pteronyssinus and
and ketones.61 Mold can be successfully removed from Dermatophagoides farinae, are arthropods from the class
hard non-porous surfaces with the use of a simple deter- Arachnida that colonize bedding sofas, carpets, and any
gent and water, and then allowing for complete drying of other woven material within the home. Dust mites are the
the area. Porous areas including ceiling tiles and carpets most common allergen worldwide. They are found infre-
should be disposed of, as the mold cannot be eliminated quently at high altitude, in arid conditions, and in areas
with cleaning alone.62 Areas with dead mold may cause exposed to long, cold winters due to low humidity. Aside
significant health effects and must also be removed. Mold from causing allergic disease, dust mites do not pose any
removal will not be complete until the moisture source other risk to human health. Mites, and the debris they
that is required for growth is eliminated. produce, are microscopic, absorb moisture from the envi-
ronment, and feed on dead animal and human skin cells.
It is not the mite itself, but its fecal particles, that result
52.7 ANIMAL DANDER in a strong allergic response in up to 26% of Americans.72
Dust mite particles are large and heavy and when dis-
Animal dander is most commonly associated with aller- persed from their source only remain aerosolized for up to
gens from the dead skin cells of animals such as cats, 15 minutes, settling very quickly.73 This makes air purifi-
dogs, and other furred pets. Cats and dogs seem to have ers such as HEPA filters ineffective with dust mite antigen
the greatest risk of causing sensitization and the poten- removal. Although dust mites are found frequently in car-
tial for causing health issues. Many epidemiologic stud- pets and upholstered furniture, the most common sources
ies have shown that sensitization to dog and cat allergens are bed mattresses. Dust mite allergens can worsen pre-
are strongly associated with asthma.63 Cats are well existing asthma but are not known to directly cause it.
known to induce sensitization by a protein Fel d1, which Table 52.3 contains control measures that can reduce dust
is found in the saliva and salivary glands. This protein is mite allergen burden.
secondhand smoke exposure are similar to that of ciga- at much lower concentrations than in combustible ciga-
52
rette smoking and does not support its use as a “safe” rettes.91,98–100 Studies have also identified the presence of
alternative.86 formaldehyde, a known carcinogen, when cigarette solu-
tions containing glycerol and propylene glycol are heated
during the “vaping” process.98 E-cigarettes can pro-
52.12 ELECTRONIC CIGARETTES duce high levels of metal and silicate particles, including
nanoparticles in the e-cigarette cartomizer fluid.99,100 that
In recent years there has been an exponential gain in the can trigger inflammation but at 15 times lower than tradi-
popularity of electronic cigarettes (e-cigarettes), espe- tional cigarettes.98
cially among youth, in part due to the perception that Even the flavoring products of e-cigarettes may not be
they are safer than combustible cigarettes.91 In addition safe for inhalation101 The California Department of Public
to e-cigarettes, other electronic products are available, Health issued an advisory for the potential of e-cigarettes
such as e-cigars, e-pipes, e-hookah, vapes, vape pens, to cause cancer and birth defects as well as other repro-
and electronic nicotine delivery systems (ENDS).92 The ductive harm.99 The potential for e-cigarettes to cause lung
most recent report published in the medical literature in cancer has been supported by a recent study in children.102
2014 identifies 466 distinct brands of e-cigarettes, not There is also a risk for secondhand toxin exposure with
all of which contain nicotine.93 As of January 2014, at e-cigarette emissions that may be inhaled by others, espe-
least 7,764 known flavors were available, including cot- cially indoors, for which the German Cancer Research
ton candy, berry intense, melon mania, chocolate treat, Center has issued an advisory.91 Thirdhand toxin expo-
vanilla dreams, menthol, and cherry crush.92–94 Users sure may also be possible through skin, inhalation, or
inhale vapor for a variety of reasons. Some like the flavor ingestion from residual nicotine and other chemicals that
or taste, some for curiosity, and some use them as a smok- may remain on indoor surfaces for weeks to months after
ing cessation tool. However, the long-term safety of these clearing of the aerosol.91,98
devices remains an open question, and public appetite has Although we have described the potential health risks
run ahead of health science. of e-cigarettes, the U.S. FDA recognizes that e-cigarettes
Based on CDC data in 2016, 3.2% of U.S. adults were may help some adults stop smoking combusted tobacco.
current e-cigarette users. Young adults have been more For that reason, on July 28, 2017, the FDA delayed rules
likely than older adults to use e-cigarettes. Part of the that regulate e-cigarettes until August 2022. Opponents
appeal is the availability of fruit and candy flavors with to this decreased regulatory policy seek more research
the notion of them being “safe.” However, teenager use to see if young nonsmokers will be enticed to start using
decreased from approximately three million in 2015 to 2.2 nicotine products or if it will reduce the number of current
million in 2016.95 This may be due to changes in federal smokers who try to quit.103
and statewide policies. In February 2015, U.S. Surgeon
General Vivek Murthy said health officials are “in desper-
ate need of clarity” on e-cigarettes to help guide policies.
In a policy updated in December 2017, the FDA banned 52.13 CONTAMINATION OF HOME
the sale of ENDS to anyone under 18 and required that
adults under the age of 27 show photo identification to
SHOWERHEADS, DISHWASHERS,
purchase them.96,97 AND CPAP DEVICES
E-cigarettes consist of a mouthpiece, a cartridge, an
atomizer, a battery, and an indicator light. Once activated Although showering is thought to cleanse us from bacteria
by the user, the battery-powered heating element aerosol- and other organisms we encounter throughout our day,
izes and delivers to the lung a mixture of solvents which bacterial contamination of household showerheads with
includes propylene glycol, vegetable glycerins, flavorants, potential pathogens has been reported. Organisms that
and nicotine.91 Each cartridge can contain six to 24 mg can cause pneumonia in humans such as Mycobacterium
of nicotine, which is highly addictive. The risk for e-cig- abscesses and Mycobacterium avium complex (MAC),
arettes to become a pathway to conventional smoking is both related genetically to tuberculosis, and Legionella
real.91,98 have been isolated from showerheads, raising concern for
On a cellular level, ENDS may promote vascular endo- potential infection of immunocompromised patients even
thelial dysfunction, increased inflammation, and oxida- in their own homes. Unhooking and allowing the shower-
tive stress in the lung. Impaired pulmonary immunity has head to dry did not reduce the risk of Legionella or MAC
been reported in animal studies.94 Propylene glycol and colonization.104,105
glycerol vapor are known upper airway irritants and the Home dishwashers may also be contaminated with
most common components of most e-cigarettes.91,98 The organisms such as Pseudomonas, Escherichia and
effect of such chemicals and inhalants is yet to be identi- Acinetobacter, which can also cause pneumonia in
fied due to lack of sufficient data to determine long-term humans.106 In addition to bacteria, in one study, 83% of
safety.91,98 dishwashers tested were positive for the presence of fungi.
Clinically, e-cigarette use may cause bronchitic symp- The most common sites of contamination were the side
toms, especially in adolescents.95 The FDA acknowledges nozzles, doors, and drains. Hot aerosols from dishwashers
the presence of potentially harmful tobacco-specific nitro- released into kitchens were also found to contain human
samines, aldehydes, metals, VOCs, toxic metals, and opportunistic yeast. The plumbing system supplying
diethylene glycol in ENDS, but most of these toxins are water to the home was the suspected site of dishwasher
646 Chapter 52 Indoor Air Quality
contamination.107 The organisms reported can cause Mayo Clinic, using this device, recommendations can be
infections in immunocompromised patients such as those made to improve the air quality of your home environ-
with cystic fibrosis. To date, there have been no scientifi- ment. Further research will be necessary to see if smart
cally tested regimens to rid dishwashers or showerheads of devices like this one can improve lung health.111
contamination.107
It is estimated that more than 18 million Americans
carry the diagnosis of obstructive sleep apnea (OSA) and 52.15 SUMMARY
that untreated sleep apnea may cost nearly $150 billion
annually because of the resultant workplace accidents, This chapter has identified key elements of indoor air
motor vehicle accidents, lost productivity, and comorbid quality which significantly impact the health of individu-
diseases. It is therefore essential that patients with OSA als in the United States. We have emphasized the relation-
be treated. Continuous positive airway pressure (CPAP) is ship between indoor air quality and health as it pertains
the therapy of first choice for patients with OSA. However, to exposure to the many different agents in the home.
contamination of CPAP devices may lead to pulmonary Many individuals remain unaware of the potential det-
disease due to growth of bacteria in the humidifier cham- rimental effects associated with these exposures. These
ber, contaminated tap water use and inconsistent cleaning range from secondhand smoke and radon to the family
of the device, hoses, and filters. To prevent this contami- pet. Lung health is important to all ages, and it is cru-
nation, distilled water, which is free from bacteria, is the cial to target environmental exposures that may increase
safest type of water to use in the CPAP humidifier. It is health risks, including asthma, allergic reactions, and lung
recommended that non-disposable CPAP filters be cleaned cancer. The U.S. government, through various agencies,
and reused weekly and changed every six months, and that continues to monitor and provide guidelines, reports, and
CPAP tubing should be cleaned with warm soapy water recommended testing for many of these agents. However,
every week and changed every three months. It is also rec- simple interventions that can promote lung health include
ommended that the cushions on a CPAP mask be replaced not allowing smoking indoors; checking home radon lev-
twice monthly and that a new mask should be obtained at els; reducing conditions which promote mold growth, dust
least every six months.108 Although commercially avail- mites, and animal dander; monitoring carbon monoxide
able CPAP equipment “sanitizers” are available, there has levels, and keeping home appliances clean. More research
been no scientific evidence to suggest that these devices is needed to identify potentially new home contaminants
are superior to routine cleaning at frequent recommended and pollutants and their potential respiratory health
intervals.109 effects. Lifelong awareness among family members and
housemates, elimination of potential indoor environmen-
tal hazards, and increased awareness by healthcare pro-
52.14 SMART DEVICES THAT ANALYZE viders are essential to promote long-term lung health and
wellness.
INDOOR AIR QUALITY
With the recent advent of smart phone technology, sev- CLINICAL APPLICATIONS
eral smart devices for our home are now available, such
as smart thermostats to personalize temperature control. 1. Keep pollution out of your home by not allowing
Sensors are also now available to monitor levels of com- smoking indoors, by checking for radon, and by
mon indoor air pollutants such as carbon dioxide, vola- protecting against carbon monoxide.
tile organic compounds (VOC), and particulate matter, 2. Control humidity in your home to decrease dust
which is solid particles and liquid droplets found in the mites and mold growth.
air.110 One smart device that measures indoor air quality 3. Avoid e-cigarette and water pipe hookah use and
is manufactured by a company that specializes in smart educate young adults about the potential dangers of
technology for home environmental analysis. The com- both.
pany also produces a smart phone application, or app, 4. Avoid adverse effects of furred pet exposure through
that can be downloaded, and based on the home indoor the use of HEPA filters and bathing of furred pets.
air quality shown by the device, the data can be analyzed 5. Keep CPAP apparatus clean by changing masks and
and sent to your personal phone. In conjunction with the cleaning hoses and filters at prescribed intervals.
REFERENCES
1. Sundell J. 2004. On the history of 3. U.S. Department of Health and Human 4. National Research Council. 1986.
indoor air quality and health. Indoor Air Services. 2014. The Health Consequences Environmental Tobacco Smoke:
14(Suppl 7)51–58. of Smoking: 50 Years of Progress. A report Measuring Exposures and Assessing
2. Kuschner WG, Blanc PD. 2010. Is this of the Surgeon General. U.S. DHHS, Health Effects. Washington, DC:
patient suffering as a result of an envi- Public Health Service, Centers for Disease National Academy Press.
ronmental exposure? In: Environmental Control and Prevention Office of Smoking 5. U.S. Environmental Protection Agency.
Medicine, eds Ayres JG, Harrison RM, and Health, National Center for Chronic 1992 Respiratory Health Effects of
Nichols GL et al. Boca Raton, FL: CRC Disease Prevention and Health promotion, Passive Smoking: Lung Cancer and
Press, Chap 59; pp. 640–643. Office of Smoking, Washington, DC. Other Disorders, Office of Health and
References 647
Environmental Assessment, Office of 23. Brennan P, Patricia B, Peggy R. 2004. Guide to Protecting Yourself and Your
Research and Development, Washington, Secondhand smoke exposure in adult- Family from Radon. Washington, DC:
6.
DC.
https: //www.cdc.gov/tobacco/data_statist
ics/fact_sheets /secondhand _smoke/he
hood and risk of lung cancer among never
smokers: A pooled analysis of two large
studies. Int J Cancer 109(1):125–131.
40.
US EPA; EPA 402-K-09-001.
https: //www.epa.gov/i ndoor-air- quality-i
aq/carbon-monoxides-i mpact-indoor-a
52
alth_effects/index.ht m (accessed: January 24. Alberg AJ, Yung R, Strickland PT, et al. ir-quality(accessed: January 20, 2018).
27, 2018). 2002. Respiratory cancer and exposure 41. www.osha.gov/Osh Doc/data_G ener
7. https: //ww w.surgeongeneral.gov/ libra ry/s to arsenic, chromium, nickel and polycy- al_Fac ts/ca rbonmonoxide-factsheet.pd f
econdhandsmoke/ (accessed: February 3, clic aromatic hydrocarbons. Clin Occup (accessed January 13, 2018).
2018). Environ Med 2(4):779–801. 42. https: //www.cdc.gov/features/copois
8. Hecht S. 1999. Tobacco smoke and 25. Hole DJ, Gillis CR, Chopra C et al. 1989. oning/index.html (accessed February 3,
lung carcinogens. J Natl Cancer Inst Passive smoking and cardiorespiratory 2018).
91(14):1194–1210. health in general population in the west 43. CDC. 2005. Unintentional non-fire
9. National Research Council. 1983. of Scotland. Br Med J 299:423–427. related carbon monoxide exposures in
Committee on the Institutional Means 26. Whinecup PH,Gliq JA, Emberson JR, the United States, 2001–2003. MMWR
for Assessment of Risks to Public Jarvis MJ. 2004. Passive smoking and the 54:36–39.
Health: Risk Assessment in the Federal risk of coronary heart disease and stroke: 44. http://www.cdc.gov/mmwr/preview/
Government: Managing the Process. prospective study with cotinine measure- mmwrhtml /mm6303a6.htm (accessed:
Washington, DC: National Academy ment. BMJ 329:200–205. February 3, 2018).
Press. 27. Glantz SA, Parmley WW. 1991. Passive 45. Chen BC, Shawn LK, Connors LJ,
10. Schikc S, Glantz G. 2005. Phillip Morris smoking and heart disease: Epidemiology, et al. 2013. Carbon monoxide expo-
toxicological experiments with fresh physiology, and biochemistry. Circulation sures in New York City following
sidestream smoke: more toxic than 83:1–12. Hurricane Sandy in 2012. Clin Toxicol
mainstream smoke. Tobacco Control 28. Law MR, Morris JK, Wald NJ. 1997. 51(9):879–885.
14:396–404. Environmental tobacco exposure and risk 46. Blumenthal I. 2001. Carbon monoxide
11. Schikc S, Glantz G. 2006. Sidestream of ischaemic heart disease: An evaluation poisoning. J R Soc Med 94:270–272.
cigarette smoke toxicity increases with of the evidence. BMJ 325:973–980. 47. Coburn RF. 1979. Mechanisms of carbon
aging and exposure duration. Tobacco 29. Alfred EN, Bleeker ER, Chaitman BR monoxide toxicity. Prev Med 8:310–322.
Control 15:424–429. et al. 1989. Short-term effects of carbon 48. Wittenberg BA, Whittenberg JB. Effects
12. Dreyfuss JH. 2010. Third hand smoke monoxide exposure on exercise perfor- of Carbon Monoxide on Isolated Heart
identified as potent, enduring carcinogen. mance of subjects with coronary artery Muscle Cells. Health Effects Institute,
CA: Cancer J Clin 60:203–204. disease. N Engl J Med 321:1426–1432. Research Report Number 62, December
13. Winickoff JP, Friebely J, Tanski SE, et al. 30. Sheps D, Herbst M, Hinderliter AL et 1993.
2009. Beliefs about the health effects of al. 1990. Production of arrhythmias by 49. Ekblom B, Huot R. 1972. Response to
“third hand” smoke and home smoking elevated carboxyhemoglobin in patients submaximal and maximal exercise at dif-
bans. Pediatrics 123: e74–e79. with coronary artery disease. Ann Intern ferent levels of carboxyhemoglobin. Acta
14. Benwitz NL. 1996. Cotinine as a bio- Med 113:343–351. Physiol Scand 86:474–482.
marker of environmental tobacco smoke 31. Svendsen KH, Kuller LM, Martin MJ, et 50. Satran D, Henry C, Adkinson C et al.
exposure. Epidemiol Rev 18(2):188–204. al. 1987. Effects of passive smoking in the 2005. Cardiovascular manifestations of
15. Apelberg BJ, Hepp LM, Avila-Tang E et multiple risk factor intervention trial. Am moderate to severe carbon monoxide poi-
al. 2013. Environmental monitoring of J Epidemiol 126:783–795. soning. J Am Coll Cardiol 45:1513–1516.
secondhand smoke exposure. Tobacco 32. Schoendorf KC, Kiley JL. 1992. 51. Wright J. 2002. Chronic and occult
Control 22:147–155. Relationship of sudden infant death syn- carbon monoxide poisoning: we don’t
16. Avila-Tang E, Al-Delaimy WK, Ashley drome to maternal smoking during and know what we’re missing. Emerg Med J
DL et al. 2013. Assessing secondhand after pregnancy. Pediatrics 90:905–908. 19:386–390.
smoke using biological markers. Tobacco 33. Rosen L, Guttman N, Myers V et al. 52. Seguel JM, Merrill R, Seguel D et al.
Control 22:156–163. 2018. Protecting young children from 2017. Indoor air quality. Am J Lifestyle
17. United States Department of Health tobacco smoke exposure: a pilot study Med 11:284–295.
and Human Services. 2006. The Health of Project Zero Exposure. Pediatrics 53. Bush RK, Portnoy JM, Saxon A et al.
Consequences of Involuntary Exposure 141:S107–S116. 2006. The medical effects of mold expo-
to Tobacco Smoke: A Report of the 34. National Research Council (US). 2006. sure. J Allergy Clin Immunol 117:326.
Surgeon General. Washington, DC: U.S Committee on the Health Risks of 54. Barbeau DN, Grimsley LF, White LE,
Government Printing Office. Exposure to Low Levels of Ionizing et al. 2010. Mold exposure and health
18. WHO. 2004. IARC Monographs on the Radiation (BEIR VII). Committee on the effects following hurricanes Katrina
Evaluation of Carcinogenic Risks to Biological Effects of Ionizing Radiations, and Rita. Annu Rev Public Health
Humans. Volume 83. Tobacco Smoke and Board of Radiation Effects Research, 31:165–178.
Involuntary Smoking. Lyon, France. Committee on Life Sciences, National 55. Wood RA, Eggleston PA, Lind P et
19. 2004. National Toxicology Program Research Council. Washington, DC: al. 1988. Antigenic analysis of house-
11th report on carcinogens. Resp National Academy Press. hold dust samples. Am Rev Respir Dis
Carcinog 11:1–A32. 35. Darby S, Hill D, Barros-Dios JM et al. 137:358–363.
20. Benninger M. 1999. The impact of ciga- 2005. Radon in homes and risk of lung 56. Kousha M, Tadi R, Soubani AO. 2011.
rette smoking and environmental tobacco cancer: collaborative analysis of individ- Pulmonary aspergillosis: a clinical review.
smoke on nasal and sinus passage: A ual data from 13 European case-control Eur Resp Rev 20:156–174.
review of the literature. Am J Rhinol studies. BMJ 330:223. 57. Knutsen AP, Bush RK, Demain JG,
13(6):435–438. 36. Ruano-Ravina A, Torres-Duran M, et al. 2012. Fungi and allergic lower
21. Hirayama T. 1981. Non-smoking wives Kelsey KT et al. 2016. Residential radon, respiratory tract diseases. J Allergy Clin
of heavy smokers have a higher risk of EGFR mutations and ALK alterations Immunol 129:280.
lung cancer: A study from Japan. Br Med in never smoking lung cancer cases. Eur 58. Denning DW, O’Driscoll BR, Hogaboam
J 282:183–185. Respir J 48:1462–1470. CM, et al. 2006. The link between fungi
22. U.S. Department of Health and 37. Samet JM. 2006. Residential radon and and severe asthma: a summary of the
Human Services. 2006. The Health lung cancer: End of the story? J Toxicol evidence. Eur Respir J 27:615.
Consequences of Involuntary Exposure Environ Health, Part A 69:527–531. 59. Denning DW, O’Driscoll BR, Powell G,
to Tobacco Smoke: A Report of the 38. Krewski D, Lubin JH, Zielinski JM, et et al. 2009. Randomized controlled trial
Surgeon General. U.S. Department of al. 2006. A combined analysis of North of oral antifungal treatment for severe
Health and Human Services, Centers American case-control studies of resi- asthma with fungal sensitization. Am J
for Disease Control and Prevention, dential radon and lung cancer. J Toxicol Respir Crit Care Med 179:11–18.
National Center for Chronic Disease Environ Health, Part A 69:5533–597. 60. Limper A, Knox K, Sarosi G et al. 2011.
Prevention and Health Promotion, Office 39. U.S. Environmental Protection Agency. An official American Thoracic Society
on Smoking and Health. 2009. A Citizen’s Guide to Radon: The statement: Treatment of fungal infections
648 Chapter 52 Indoor Air Quality
in adult pulmonary and critical care A work group report of the AAAAI 92. Barrington-Trimis JL, Samet JM,
patients. Am J Respir Crit Care Med indoor allergy/air pollution committee. J McConnell R. 2014. Flavorings in elec-
183:96–128. Allergy Clin Immunol 125:575–581. tronic cigarettes: An unrecognized respira-
61. Sahakian NM, Park JH, Cox-Gasner 77. Rosenstreich DL, Eggleston P, Kattan tory health hazard? JAMA 312:2493–2494.
JM. 2008. Dampness and mold in the M et al. 1997. The role of the cockroach 93. McConnell R, Barrington-Trimis JL,
indoor environment: Implications for allergy and exposure to cockroach Wang K et al. 2017. Electronic ciga-
asthma. Immunol Allergy Clin North Am allergen in causing morbidity among rettes use and respiratory symptoms in
28:485–505. inner-city children with asthma. N Engl J adolescents. Am J Respir Crit Care Med
62. USEPA. Reprinted 2012. Office of Air Med 336:1356–1363. 195:1043–1049.
and Radiation, Indoor Environments 78. Matsui EC, Hansel NN, McCormack 94. Lerner CA, Sundar IK, Yao H, et al.
Division, Washington, D.C. Available on MC et al. 2008. Asthma in the inner city 2015. Vapors produced by electronic cig-
www.epa.gov/iaq. Accessed January 31, and the indoor environment. Immunol arettes and e-juices with flavorings induce
2019. Allergy Clin North Am 28:665–686. toxicity, oxidative stress, and inflamma-
63. Ownby DR, Johnson CC, Peterson EL. 79. Phipatanakul W. 2002. Rodent allergens. tory response in lung epithelial cells and
2002. Exposure to dogs and cats in Curr Allergy Asthma Rep 2:412–416. in mouse lung. PLoS One 10:e0116732.
the first year of life and risk of allergic 80. Phipatanakul W, Eggelston PA, 95. Furlow B. Are e-cigarettes and tobacco
sensitization at 6 to 7 years of age. JAMA Wright EC, Wood RA. 2000. Mouse products losing their allure for US teenag-
288:963–972. allergen. The prevalence of mouse ers? Lancet Respir Med 5(8):612.
64. Bollinger ME, Eggleston PA, Flanagan allergen in inner-city homes. The 96. Moazed F, Calfee CS. 2017. The canary
E et al. 1996. Cat antigen in homes with National Cooperative Inner-City in the coal mine is coughing: Electronic
and without cats may induce allergic Asthma Study. J Allergy Clin Immunol cigarettes and respiratory symptoms in
symptoms. J Allergy Clin Immunol 106:1070–1074. adolescents. Am J Resp Crit Care Med
97:907. 81. Permaul P, Sheehan WJ, Baxi SN et al. 195(8):974–975.
65. Custis NJ, Woodfolk JA, Vaughan JW, 2013. Predictors of indoor exposure to 97. U.S. Department of Health and Human
Platts-Mills TA. 2003. Quantitative mea- mouse allergen in inner-city elementary Services. 2016. E-Cigarette Use Among
surement of airborne allergens from dust schools. Ann Allergy Asthma Immunol Youth and Young Adults. A Report of
mites, dogs, and cats using an ion-charg- 111:299–301. the Surgeon General. Atlanta, GA: U.S.
ing device. Clin Exp Allergy 33:986. 82. Sheehan WJ, Rangsithienchai PA, Department of Health and Human
66. Cox LS, Linnemann DL, Nolte H et al. Muilenberg ML et al. 2006. Mouse Services, Centers for Disease Control and
2006. Sublingual immunotherapy: A allergens in urban elementary schools Prevention, National Center for Chronic
comprehensive review. J Allergy Clin and homes of children with asthma. Ann Disease Prevention and Health Promotion,
Immunol 117:1021–1035. Allergy Asthma Immunol 97:514–520. Office on Smoking and Health.
67. Gelber LE, Seltzer LH, Bouzoukis JK 83. Pongriac JA, Visness CM, Gruchalla 98. Callahan-Lyon P. 2014. Electronic
et al. 1993. Sensitization and exposure RS et al. 2008. Effect of mouse allergen cigarettes: Human health effects. Tob
to indoor allergens as risk factors for and rodent intervention on asthma in Control 23: ii 36–ii 40.
asthma among patients presenting to inner-city children. Ann Allergy Asthma 99. Blanding M. The e-cig quandary. https
hospital. Am Rev Respir Dis 147:573. Immunol 101:35–41. ://www.hsph.harvard.edu/magazine/
68. National Heart, Lung and Blood Institute 84. Tourjusen EN, Diette GB, Breysse PN magazine _article/t he-e- cig-quanda ry//
(NHLBI). 2007. National Asthma et al. 2013. Dose response relationships (accessed: December 16, 2017).
Education and Prevention Program between mouse allergen exposure and 100. Zhang Y, Sumner W, Chen DR. 2013. In
(NAEPP), Expert panel report 3 (EPR 3) asthma morbidity among urban children vitro particle size distributions in elec-
Full report; pp. 1–440. and adolescents. Indoor Air 23:268–274. tronic and conventional cigarette aerosols
69. Lockey RF. 2012. The myth of hypoal- 85. American Lung Association. 2007. An suggest comparable deposition patterns.
lergenic dogs (and cats). J Allergy Clin Emerging Deadly Trend: Waterpipe Nicotine Tob Res 15:501–508.
Immunol 130:910–911. Tobacco Use. Washington, DC: American 101. Jancin B. 2017. E-cigarettes: A health
70. Vredegoor DW, Willemse T, Chapman Lung Association. threat or cessation tool? Chest Physician
MD et al. 2012. Can f 1 levels in hair 86. U.S. Department of Health and Human 12(9):8.
or homes of different dog breeds: Lack Services. 2012. Preventing Tobacco Use 102. Rubenstein ML, Delucchi K, Benowitz
of evidence to describe any dog breed as Among Youth and Young Adults: A NL et al. 2018. Adolescent exposure to
hypoallergenic. J Allergy Clin Immunol Report of the Surgeon General. Atlanta: toxic volatile organic chemicals from
130:904–909.e7. U.S. Department of Health and Human e-cigarettes. Pediatrics 141(4):e20173557.
71. Butt A, Rashid D, Lockey,R. 2012. Do Services, Centers for Disease Control 103. Fairchild AL, Lee JS, Bayer R et al. 2018.
Hypoallergenic cats and dogs exist? Ann and Prevention, Office on Smoking and E-cigarettes and the harm-reduction
Allergy Asthma Immunol 108:74–76. Health. continuum. N Engl J Med 378:216–221.
72. Arbes SJ, Gergen PJ, Elliott L et al. 87. Akl EA, Gaddam S, Gunukula SK et al. 104. Whiley H, Giglio S, Bentham R. 2015.
2005. Prevalence of positive skin test 2010. The effects of water pipe tobacco Opportunistic pathogens Mycobacterium
responses to 10 common allergens in the smoking on health outcomes: A system- avium complex (MAC) and Legionella
U.S. population: Results from the third atic review. Int J Epidemiol 39:834–857. spp. colonize model shower. Pathogens
national health and nutrition examina- 88. American Lung Association. 2011. 4:590–598.
tion survey. J Allergy Clin Immunol Hookah Smoking: A Growing Threat 105. Feazael LM, Baungartner LK, Peterson
116:377–383. to Public Health Issue Brief. Smoke free KL et al. 2009. Opportunistic pathogens
73. Price JA, Pollock I, Longbottom JL. Communities Project. enriched in showerhead biofilms. Proc
1990. Measurement of airborne mite 89. Asfar T, Ward KD, Eissenberg T et al. Natl Acad Sci USA 106:16393–16399.
antigens in homes of asthmatic children. 2005. Comparison of patterns of use, 106. Raghupathi PK, Zupancic J, Brejnroda
Lancet 336:895–897. beliefs, and attitudes related to water pipe AD et al. 2018. Microbial diversity and
74. Phipatanakul W. 2006. Environmental between beginning and established smok- putative opportunistic pathogens in
factors and childhood asthma. Pediatr ers. BMC Public Health 5:19. dishwasher biofilm communities. Appl
Ann 35:646–656. 90. Shafagoj YA, Mohammed FL, Hadidi Environ Microbiol 84(5):e02755–17.
75. Cohn RD, Arbes SJ Jr, Jaramillo R et al. KA. 2002. Hubble Bubble (water pipe) Doi 10.1128/AEM.02755-17.online 12
2006. National prevalence and expo- smoking: levels of nicotine and cotinine January 2018.
sure risk for cockroach allergens in U.S in plasma, saliva, and urine. Int J Clin 107. Zupancic J, Novak-Babic M, Zalar P
Households. Environ Health Perspect Pharmacol Ther 40:249–255. et al. 2016. The black yeast Exophiala
114:522–526. 91. Schraufnagel DE, Blasi F, Drummond dermatitidis and other selected oppor-
76. Sheehan WJ, Rangsithienchai PA, Wood MB et al. 2014. Electronic cigarettes. a tunistic human fungal pathogens spread
RA et al. 2010. Pest and allergen expo- position paper of the forum of interna- from dishwashers to kitchens. PLoS One
sure and abatement in inner city asthma: tional respiratory societies. Am J Resp 11(2):e0148166. Doi: 10.137/journal
Crit Care Med 190:611–618. pone.0148166. eCollection 2016.
References 649
651
53
CHAPTER
653
654 Chapter 53 Antenatal Care—Nutrition and Lifestyle to Improve Conception and Pregnancy Outcomes
of overweight and obese women have PCOS and that the both of which are best addressed with diet and lifestyle
condition is present in 5% of normal-weight women.6 changes.
Overall, PCOS affects one in eight women in the United As discussed previously, women with PCOS tend to
States. In cases of ovulatory infertility, 90% are a result have insulin resistance and elevated free insulin, which
of PCOS.7 As previously mentioned, the CDC reported suppress the synthesis of SHBG, resulting in elevated
that 71% of the population in the U.S. is overweight or androgen levels that prevent ovulation. A study done by
obese, which means that out of 100,000 reproductive- Barnard and colleagues showed that SHBG is increased
aged women, 71,000 are overweight or obese and 30% by 16% when women consume a low-fat plant-based
(21,300) of those women will have PCOS. That means diet, which could lead to improved ovulatory function.17
that 21.3% of adult women have an impaired capacity to Likewise, a study in the American Journal of Obstetrics
become pregnant secondary to oligo or anovulation. and Gynecology revealed that consuming 5% of total
Obesity impacts fertility beyond ovulation. Obese energy intake as animal protein, rather than in the form
women who receive donor eggs from normal-weight of carbohydrates, was associated with a 19% greater risk
women are 23% less likely to have successful implanta- of ovulatory infertility.18 In contrast, consuming 5% of
tion and 19% less likely to have a live birth.8 But even energy as vegetable protein, rather than as carbohydrates,
ovulatory obese women are less likely to conceive, their was associated with a 43% lower risk of ovulatory infer-
oocyte and embryo quality are reduced, and they have tility and consuming 5% of energy as vegetable protein, as
impaired endometrial receptivity,8 likely secondary to opposed to animal protein, was associated with a greater
oxidative stress.9 It appears that excessive reactive oxygen than 50% lower risk for ovulatory infertility.19
species production overpowers the body’s natural antioxi- Dietary behaviors resulting in obesity and malnutri-
dant defense system, creating an environment unsuitable tion are linked with oxidative disturbances and chronic,
for normal female physiologic reactions that are requisite low-grade inflammation. Studies have shown, repeatedly,
for successful reproduction.9 that animal foods, and their accompanying saturated
As chronic inflammation and oxidative stress have fats, trans fats, arachadonic acids, cholesterol, and pro-
been incriminated in the pathophysiology of PCOS, the teins, are associated with systemic inflammation. 20–28
role of advanced glycation end products (AGEs) is becom- And as stated before, AGEs have been implicated in the
ing more prominent. Elevated concentrations of AGEs, or pathophysiology of PCOS and are a source of oxidative
glycotoxins, which exert their effects through interaction stress. The primary sources of these glycotoxins are ciga-
with specific AGE receptors (RAGE), have been impli- rette smoke and food. Specifically, food-derived AGEs
cated in cellular and tissue damage. It’s been found that play an important role, as diet is a major source of these
women with polycystic ovarian syndrome have almost pro-inflammatory AGEs and there is ample evidence to
twice the circulating AGE levels in their bloodstream and show that reducing these dietary glycotoxins reduces
more than three times the expression of RAGE. This is the inflammatory response. 29,30 Foods with the highest
true for both obese women with PCOS and for lean, non- AGEs are of animal origin, and the method of cooking
insulin resistant women with PCOS. Additionally, immu- also impacts AGE levels. High temperature, dry cook-
nohistochemical studies have revealed that PCOS ovaries ing methods result in higher AGE levels than low heat,
have higher levels of AGEs within the ovary itself and have higher humidity cooking. Stewing, steaming, and boiling
stronger expression of RAGE, which could be contribut- result in lower AGE production than broiling, searing,
ing to the cause of polycystic ovary syndrome and its asso- and frying. 29,31,32
ciated infertility.10–14 AGE tissue levels are a strong predictor of overall mor-
Metformin has been utilized in the treatment of tality and are consistently lower in vegetarians. 33 There
PCOS-related infertility, as it improves insulin sensitivity is now evidence that reducing AGE intake improves insu-
of peripheral tissues, reducing circulating androgen lev- lin sensitivity, reduces oxidative stress biomarkers, and
els and leading to more menstrual regularity and resto- reduces testosterone in women with PCOS.34
ration of ovulation. Once thought of as a wonder drug, Additionally, women with PCOS have higher levels
the accumulating evidence on the efficacy of metformin of anti-mullerian hormone, and it has been shown that
has been disappointing. Based on the available evidence, one hour of exercise three times per week decreases BMI,
metformin does not replace the need for lifestyle modifi- total, and android fat mass and improves insulin sensi-
cation among obese and overweight PCOS women. The tivity as well as lowering AMH levels. This suggests that
evidence does not support its use to help with weight loss, mechanisms associated with ovarian dysfunction can be
and time to ovulation induction is longer than clomiphene improved by exercise in PCOS, possibly improving the
citrate, or Clomid, a drug used for ovulation induction, chances of conception. 35
in head-to-head studies. There is some benefit for the use
of metformin in IVF patients if only to help reduce the
incidence of ovarian hyperstimulation syndrome, which is 53.3 PREGNANCY OUTCOMES
important given its commonality among PCOS patients.
Metformin may also be useful for the prevention of gesta- Maternal and fetal outcomes are impacted significantly by
tional diabetes.15,16 lifestyle, and in a multitude of ways. Because the subject
However, the two primary causative agents in PCOS area of maternal and fetal medicine is so vast, we limit
that can lead to infertility are insulin resistance and our focus to the impacts of lifestyle on maternal morbidity
advanced glycation end-product-induced oxidative stress, and mortality, and some fetal outcomes.
53.5 Preeclampsia 655
53
festation of preeclampsia is variable, dependent upon
According to the CDC, the maternal mortality rate in number and degree of severity of risk factors, and can
1915 was 608 deaths per 100,000 live births. In 1986, it develop anytime after 20 weeks of gestation.
reached a nadir of 8.5. However, every year since it has Given the current demographics of the adults in this
risen. In 2003, it was 14.1 and is now 18.5 with the sug- country, it would be an obvious assumption that the inci-
gestion that this may be a low estimate.36 According to dence of preeclampsia is on the rise. And, of course, that
the WHO, the number is closer to 28, which is equivalent is exactly what we have seen. Within the United States,
to the U.S. maternal mortality rate in 1967. 37 This leaves the incidence of preeclampsia has risen steadily over the
the United States with the highest maternal mortality rate past three decades, from 2.4% of pregnancies in 1980 to
of any other industrialized nation and 60th among all 3.8% of pregnancies in 2010. And there has been a 322%
nations. Our previous ranking in 1996 was 50th.38 relative increase in the rate of severe preeclampsia.41 There
The causes of maternal mortality have changed in has been much research into prevention of preeclampsia,
developed nations. Historically in this country and still and some studies have shown that aspirin use in women at
in the developing world, hemorrhage has been respon- high risk of developing preeclampsia can reduce develop-
sible for one quarter of maternal deaths.36 Today in this ment of the disease by as much as 24%.42 A 2017, mul-
country, cardiovascular disease, stroke and hypertensive ticenter, double-blind, placebo-controlled trial of 1776
diseases of pregnancy combined cause 30% of maternal women with singleton pregnancies who were at high risk
deaths, while hemorrhage is now responsible for only for preterm preeclampsia showed that 150 mg of aspirin
11% of deaths. Pregnancy has become riskier, because taken daily from 14 weeks of gestation until 36 weeks of
there has been such a significant rise in reproductive-aged gestation, reduced the odds of developing preeclampsia.
women with obesity, diabetes, and pre-pregnancy hyper- Preterm preeclampsia occurred in (1.6%) in the aspirin
tension that can lead to preeclampsia, eclampsia, stroke, group, as compared with (4.3%) in the placebo group.43
and cardiomyopathy. This is presumably from the anti-inflammatory effects
of the aspirin.44
In regard to diet and prevention of preeclampsia, there
53.5 PREECLAMPSIA is one observational study that looked at a community of
vegan women. In this community of 775 women who gave
Preeclampsia is a constellation of signs and symptoms birth while living on the “the Farm” in Summertown,
that include hypertension, proteinuria, edema, and in Tennessee, only one met the criteria for preeclampsia.45
more severe cases, headache, elevated liver enzymes, pul- This is a rate of 0.001%, which is obviously much lower
monary edema, and thrombocytopenia, that can lead to than the 3.8% rate we see in this country. The authors
seizure, stroke, and death for both mother and infant. concluded that a vegan diet could alleviate most if not all
Preeclampsia is among the top six causes of maternal of the signs and symptoms of preeclampsia.
mortality, severe maternal morbidity, and adverse neona- Preeclampsia, like other cardiovascular diseases, is
tal outcomes in the United States and globally. a result of endothelial dysfunction and inflammation of
A 2012 study that assessed the epidemiological and the blood vessels. Chronic inflammation is also present in
healthcare cost burden of preeclampsia to both mothers diabetics, in the obese and in patients with autoimmune
and infants in the United States in that year found that disease. It has been well verified that dietary patterns that
preeclampsia increased the probability of an adverse event are high in fat, particularly saturated and trans fats, and
from 4.6% to 10.1% for mothers and from 7.8% to 15.4% highly refined carbohydrates cause systemic inflammation
for infants, while lowering gestational age by 1.7 weeks. resulting in disease.46–52 It has also been well verified that
Overall, the total cost burden of preeclampsia during the a diet based on whole or minimally processed plant foods
first 12 months after birth was $1.03 billion for mothers can reverse these inflammatory processes. 53–56
and $1.15 billion for infants. The cost burden per infant is The overconsumption of salt is likely also playing a
dependent on gestational age, ranging from $150,000 at role in the rise of preeclampsia in the use but also glob-
26 weeks gestational age to $1311 at 36 weeks gestational ally. A survey conducted in 2008 found that preeclampsia
age.39 and gestational hypertension were found to be higher in
Twelve percent of maternal deaths in this country are Bangladesh’s coastal regions compared to non-coastal
related to preeclampsia. The exact pathogenesis remains areas or during the dry season. Because of climate change
uncertain, but the presumption is that it has to do with and sea level rise, the salinity levels in surface and ground-
abnormal placentation, which can result in placental isch- water are higher on the coasts and during monsoon
emia and release of inflammatory and oxidative stress season. Salt from any source raises blood pressure, and
factors into the maternal bloodstream. In addition, even therefore, increases the risk of hypertensive disorders, like
with normal placentation, pre-existing hypertension, preeclampsia, in pregnancy. 57
diabetes and other inflammatory conditions (such as Preeclampsia and hypertensive disease during preg-
lupus) that lead to endothelial dysfunction can activate nancy do not just impact maternal health acutely but
systemic inflammatory and oxidative stress processes.40 also increase the risk of chronic disease in the long term.
This explains why obesity, diabetes, and hypertension are Emerging research shows that heart disease is an eight-
risk factors for development of the disease. Once a preg- fold, long-term threat for women who develop diabetes or
nant woman develops preeclampsia, the only treatment is high blood pressure during pregnancy, possibly advancing
656 Chapter 53 Antenatal Care—Nutrition and Lifestyle to Improve Conception and Pregnancy Outcomes
heart attacks and strokes by as many as 10 to 20 years.58 average cortisol concentrations were raised by 22% in the
A nationwide register-based cohort study in Denmark offspring of those mothers eating 14–16 portions per week
found that of women with a hypertensive disorder of preg- and 46% in those whose mothers ate at least 17 portions
nancy in a first pregnancy in their 20s, 14% developed per week. This was the first study in humans showing that
hypertension in the first decade postpartum, compared the diet a mother consumes in late pregnancy can alter
with 4% of women with normotensive first pregnancies in the stress response of her offspring, possibly setting the
their 20s. The corresponding percentages for women with states for greater susceptibility to cardiovascular prob-
a first pregnancy in their 40s were 32% and 11%, respec- lems and other forms of stress-related disease into adult-
tively. In the year after delivery, women with a hyperten- hood.63 Additionally, every daily portion of meat during
sive disorder of pregnancy had 12-fold to 25-fold higher the third trimester of pregnancy leads to a 1% greater fat
rates of hypertension than did women with a normoten- mass in their children by the time they reach adolescence.
sive pregnancy. And rates in women with a hypertensive This suggests that maternal high meat intake during preg-
disorder of pregnancy were threefold to 10-fold higher nancy may substantially increase fat mass in the offspring
1–10 years postpartum and remained twice as high even and increase the risk of those offspring becoming obese
20 or more years later. 58 in later life independent of gender, current energy intake,
Approximately 80% of U.S. women give birth to at and physical activity.64
least one baby, and one-fourth of these have complications Often fish is a subject of controversy because there is
during their pregnancies or labor, putting a significant evidence that the long-chain fatty acid, DHA, is impor-
number of women at risk. And because pregnancy mimics tant for fetal development and while increased fish con-
the stressors of age, it serves as a physiological stress test. sumption by women before and during pregnancy leads
As such, symptoms of cardiovascular disease in pregnant to increased exposure to DHA, it also leads to increased
and postpartum women should not be ignored. 59 exposure to mercury. It’s well known that mercury and
other heavy metals, like lead, are neurotoxic and can neg-
atively affect fetal brain development, whereas DHA can
53.6 FETAL IMPACTS OF stimulate it. However, research has shown that, taking the
mercury and DHA content of 33 fish species, the adverse
MATERNAL LIFESTYLE effect of mercury on the IQ score exceeds the beneficial
effect of DHA for most species of fish. In the case of long-
One fetal impact of maternal hypertension is obesity. lived predatory fish, a negative effect of up to 10 points
A prospective cohort study in southeast China found that of IQ was found. Research has shown that eating a single
among all women, maternal hypertension in the second serving a week, or less, of fish during pregnancy, results in
and third trimester was associated with a 49% and 14% infants having substantially more mercury in their bodies
higher risk of offspring overweight/obesity, respectively, than they would acquire from as many as six mercury-
and that this finding was independent of maternal body containing vaccines.65
size prior to pregnancy.60 Mercury has a 75-day half life, and so in order for
Maternal dietary patterns can also impact long- the body to rid itself of 99% of it, it requires one year.
term fetal outcomes. A study of men and women in Therefore, women should avoid polluted fish consumption
Motherwell, Scotland, whose mothers had been advised during a period of one year preceding pregnancy as well as
to eat a high animal-protein, low-carbohydrate diet in during pregnancy itself.66 Unfortunately, other industrial
pregnancy showed that a higher maternal intake of meat pollutants found in fish, such as PCBs, DDT, and diox-
and fish and a lower intake of green vegetables during ins can have half-lives as long as ten years.67 Because of
pregnancy was associated with higher adult blood pres- the concerns about fish, a significant amount of research
sure in their offspring. Elevated cortisol levels have been has been done to evaluate DHA supplementation. Four
shown to increase the risk of cardiovascular events and meta-analyses found that adding DHA to formula does
this study revealed that both the sons and daughters of not appear to help infant cognition, and giving women
women who had reported higher meat and fish consump- DHA supplements during pregnancy does not appear to
tion and lower green vegetable consumption in the sec- help with other outcomes like attention span or working
ond half of pregnancy had higher fasting plasma cortisol memory.68–70 Additionally, six trials have been done to
concentrations.61 evaluate DHA supplementation in pregnant women and
Interestingly, cortisol concentrations increased 5.4% the impact on fetal visual acuity. Four showed no effect,
per portion of maternal meat/fish consumption per day and the two that showed benefit were poorly designed.68
but decreased 3.3% per portion of maternal green vegeta- Despite no consistently demonstrable benefits, and the
ble consumption per week. It appears that these diets may absence of clear positive effects of DHA supplementation,
present a metabolic stress to the mother and program the it’s still known that breastfed infants have better cognitive
HPA axis of the offspring, leading to lifelong hypercorti- and visual development secondary to the DHA in breast-
solemia.62 Evidence for the lasting hypercortisolemia was milk, and so the current consensus guideline recommends
discovered when researchers put the offspring of women, that women should consume 200 mg per day of DHA dur-
who reported greater consumption of meat and fish in the ing pregnancy.71–74 The best DHA supplement source is an
second half of pregnancy, through stressful experiences. algae-based oil as they are nutritionally equivalent to fish
Compared with the offspring of mothers who had reported oil but are without the contamination.75 B12 is also an
eating no more than 13 meat/fish portions per week, the important consideration for proper neural development,
53.7 Autism 657
especially for vegans and vegetarians in pregnancy, and There are many factors that can contribute to the devel-
53
should also be supplemented. opment of autism. There is some component of heritabil-
Maternal obesity also poses increased risks for the ity.85 but epigenetics, and how those genes are expressed
fetus. Multiple studies have shown that obese mothers, based on exposures, is a bigger factor.86 Exposures, such
whether or not they have diabetes, are more likely to have as pesticides and other persistent environmental pollut-
a stillbirth. (76–79 These studies also show that the risk of ants, have been implicated as contributing factors in a
stillbirth increases in a dose-response fashion, with the genetically susceptible individual.87 The combination of
more obese the mother is, the higher the risk.79 Infants low folic acid consumption and regular exposure dur-
born to obese mothers are also at an increased risk of hav- ing pregnancy to pet pesticides or to outdoor sprays and
ing a congenital anomaly, including cleft lip and palate, foggers is responsible for a fourfold increased risk of an
neural tube defects, and cardiac defects.80 Additionally, ASD, while exposures to low folate and agricultural pes-
excessive gestational weight gain in early and late preg- ticide exposure three months before or after are respon-
nancy had a 2.4-fold increased risk for large-for-gesta- sible for a more than twofold increased risk. Pesticides
tional-age (LGA) infants, regardless of pre-pregnancy are neurotoxic by design, but in animal studies folic acid
BMI, putting these infants at risk of childhood obesity.81 has been shown to protect against effects resulting from
developmental exposure to a variety of environmen-
tal chemicals, including effects of insecticides and BPA.
53.7 AUTISM Additionally, several epidemiologic studies have reported
a reduced likelihood of ASD and autistic traits in children
The incidence and prevalence of autism spectrum disor- whose mothers took supplements containing folic acid
ders (ASD) have risen to epidemic levels. In 1981, it was near the time of conception. Previous work has suggested
one in 10,000. In 2000, it was one in 150 and our most that genetically susceptible individuals have less efficient
current estimate is one in 68. If the current rate of increase folate-dependent metabolism genes and thus experienced
continues, it will be one in two or 50% by the year 2050. a reduced risk for ASD associated with maternal folic
A debate has ensued regarding whether incidence of ASD acid intake.88
is falsely elevated secondary to changes in diagnostic cri- However, anything that results in elevated levels of
teria and improved surveillance, or whether there is some inflammatory mediators in the amniotic fluid can result
environmental factor that is causing an actual real rise in an autistic child. Maternal metabolic conditions associ-
in new cases. According to the CDC, there have been no ated with chronic inflammation, like obesity and diabetes,
changes in the criteria used to diagnose or treat cases of thus pose an increased risk.89 Obesity during pregnancy
autism spectrum disorders since 2012, yet there has been increases the risk of having a child with autism by 60%,
a 30% increase in the rate since then. The rate increased and diabetes during pregnancy doubles the risk.89 Higher
from 1:88 in 2012 to 1:68 in 2014.82 consumption of maternal dietary fat 90 and low consump-
New evidence reveals that the in utero environment is tion of preconception folate, found in fruits, vegetables,
having an effect on the development of ASDs. A recent and legumes,91 are also associated with an increased risk
study in the New England Journal of Medicine looked at of having a child with autism.
brains of children with autism who had died of unrelated This phenomenon is present with other inflammatory
causes and compared them to brains of unaffected chil- conditions as well. Infections like influenza and rubella or
dren.83 It is known that the brains of children with autism any other infection that results in a fever that lasts seven
tend to be larger with a relative increase in the overall days or more increase inflammatory mediators. The rela-
number of neurons in the prefrontal cortex. This is a nor- tive risk for autism with influenza and rubella infection in
mal finding in fetuses during the second trimester of preg- pregnancy are 4.1 and 3.3, respectively.87 Another study
nancy, but it resolves by birth or shortly thereafter when revealed that maternal influenza doubles the risk and a
there is maturation of the neuronal circuitry. In this study, fever during pregnancy lasting more than seven days tri-
they found that despite the increased numbers of neurons, ples the risk of an autistic child.92
there were focal patches with fewer cells expressing layer- The brain is particularly vulnerable to oxidative
specific markers that are normally present in fully differ- stress because of its high oxygen consumption, high
entiated cortical neurons. This means that the neuronal content of unsaturated fatty acids and transition met-
circuitry in these children is not maturing appropriately als, and low antioxidant defense capacities. There is a
through pruning and apoptosis and that proper neuro- long history of studies showing that ASD is associated
nal migration is not occurring. The primary implication with oxidative stress and diminished antioxidant capac-
of this study is that these abnormalities almost certainly ity.93 A 55% reduced gene expression of nuclear factor
occurred in utero during key developmental windows, erythroid 2 (Nrf2), a transcription factor involved in the
most likely between 19 and 30 weeks of gestation.83 The antioxidant response, has been found in children with
pregnancies of these women in this study were unremark- ASDs.94 Children with autism are also more likely to
able, but no discussion of routine exposures or obesity was have mitochondrial dysfunction.95 and neuroinflamma-
mentioned. There is debate and uncertainty as to what is tion secondary to overexpression of the NF-kappa-beta
causing this abnormal brain development and why it’s so protein, a master regulator of the inflammatory cascade.
much more prevalent as compared to even 15 to 20 years Researchers have demonstrated an active neuroinflamma-
ago, but it does appear that maternal inflammation plays tory process in the cerebral cortex and white matter of
a role.84 children with ASDs, and the cerebrospinal fluid of these
658 Chapter 53 Antenatal Care—Nutrition and Lifestyle to Improve Conception and Pregnancy Outcomes
REFERENCES
1. Martin JA, Hamilton BE, Ventura SJ, 6. Alvarez-Blasco F, Botella-Carretero JI, reproduction: A review. Reprod Biol
Osterman MJ, Wilson EC, Mathews TJ. San Millán JL, Escobar-Morreale HF. Endocrinol. 2010;10:49.
Births: Final data for 2010. Natl Vital Prevalence and characteristics of the 10. Diamanti-Kandarakis E, Katsikis I, Piperi
Stat Rep. 2012;61 (1):1–72. polycystic ovary syndrome in overweight C, Kandaraki E, Piouka A, Papavassiliou
2. Zinaman MJ, Clegg ED, Brown CC, and obese women. Arch Intern Med AG, Panidis D. Increased serum advanced
O’Connor J, Selevan SG. Estimates of 2006;166: 2081–2086. glycation end-products is a distinct
human fertility and pregnancy loss. Fertil 7. Balen A, Rutherford A. Managing anovu- finding in lean women with polycystic
Steril. 1996;65:503–509. latory infertility and polycystic ovary ovary syndrome (PCOS). Clin Endocrin.
3. Ford H, Schust D. Recurrent pregnancy syndrome. BMJ. 2007;335: 608–611. 2008;69:634–661.
loss: Etiology, diagnosis, and therapy. 8. Bellver J, Pellicer A, García-Velasco 1. Diamanti-Kandarakis E, Piperi C,
1
Rev Obstet Gynecol. 2009;2:76–83. JA, Ballesteros A, Remohí J, Meseguer Patsouris E, Korkolopoulou P, Panidis D,
4. http://www.cdc.gov/obesity/data/adult. M. Obesity reduces uterine receptiv- Pawelczyk L, Papavassiliou AG, Duleba
html ity: Clinical experiences from 9,587 AJ. Immunohistochemical localization of
5. Mehrabian F, Afghani M. Can sex- first cycles of ovum donation with advanced glycation end-products (AGEs)
hormone binding globulin considered as normal weight donors. Fertil Steril. and their receptor (RAGE) in polycystic
a predictor of response to pharmacologi- 2013;10:1050–1058. and normal ovaries. Histochem Cell Biol.
cal treatment in women with polycystic 9. Agarwal A, Aponte-Mellado A, 2007;127(6):581–589.
ovary syndrome? Int J Prev Med. 2013;4: Premkumar BJ, Shaman A, Gupta S. 12. Uribarri J, del Castillo MD, de la
1169–1174. The effects of oxidative stress on female Maza MP, Filip R, Gugliucci A,
References 659
Luevano-Contreras C, Macías-Cervantes 27. Bloomer RJ, Kabir MM, Trepanowski 40. Steegers EA, von Dadelszen P, Duvekot
MH, Markowicz Bastos DH, Medrano JF, Canale RE, Farney TM. A 21 day JJ, Pijnenborg R. Pre-eclampsia. Lancet.
A, Menini T, Portero-Otin M, Rojas
A, Sampaio GR, Wrobel K, Wrobel K,
Garay-Sevilla ME. Dietary advanced
Daniel Fast improves selected biomarkers
of antioxidant status and oxidative stress
in men and women. Nutr Metab (Lond).
2010;376:631–644.
41. Ananth CV, Keyes KM, Wapner RJ.
Pre-eclampsia rates in the United States,
53
glycation end products and their 2011;8:17. 1980–2010:Age-period-cohort analysis.
role in health and disease. Adv Nutr. 28. Johnston C. Functional foods as BMJ. 2013;347: f6564.
2015;6(4):461–473. modifiers of cardiovascular disease. Am J 42. Henderson JT, Whitlock EP, O’Conner E,
13. Diamanti-Kandarakis E, Piperi C, Lifestyle Med. 2009;3(1 suppl): 39S–43S. Senger CA, Thompson JH, Rowland MG.
Kalofoutis A, Creatsas G. Increased 29. Uribarri J, He JC. The low AGE diet: A Low-Dose Aspirin for the Prevention
levels of serum advanced glycation neglected aspect of clinical nephrology of Morbidity and Mortality from
end-products in women with polycystic practice? Nephron. 2015;130(1):48–53. Preeclampsia: A Systematic Evidence
ovary syndrome. Clin Endocrinol (Oxf). 30. Cerami C, Founds H, Nicholl I, Review for the U.S. Preventative Services
2005;62(1):37–43. Mitsuhashi T, Giordano D, Vanpatten S, Task Force (Report No. 14-05207-EF-1).
14. Merhi Z. Advanced glycation end Lee A, Al-Abed Y, Vlassara H, Bucala Rockville, MD: Agency for Healthcare
products and their relevance in R, Cerami A. Tobacco smoke is a source Research and Quality; April 2014.
female reproduction. Hum Reprod. of toxic reactive glycation products. 43. Rolnik DL, Wright D, Poon LC,
2014;29(1):135–145. Proc Natl Acad Sci U S A1997;94 O’gorman N, Syngelaki A, de Paco
15. Yang YM, Choi EJ. Efficacy and safety of (25):13915–13920. Matallana C, Akolekar R, Cicero
metformin or oral contraceptives, or both 31. Uribarri J, del Castillo MD, de la Maza S, Janga D, Singh M. Aspirin versus
in polycystic ovary syndrome. Ther Clin MP, Filip R, Gugliucci A, Luevano- placebo in pregnancies at high risk
Risk Manage. 2015;11:1345–1353. Contreras C, Macías-Cervantes MH, for preterm preeclampsia. NEJM.
16. Lahen H. Role of metformin in the Markowicz Bastos DH, Medrano A, 2017;377:613–622.
management of polycystic ovarian Menini T, Portero-Otin M, Rojas A, 44. Caritis S, Silxai B, Hauth J, Lindheimer
syndrome. Ther Adv Endocrinol Metab. Sampaio GR, Wrobel K, Wrobel K, MD, Klebanoff M, Thom E, VanDorsten
2010;1(3):117–128. Garay-Sevilla ME. Dietary advanced P, Landon M, Paul R, Miodovnik M,
17. Barnard ND, Scialli AR, Hurlock D, glycation end products and their Meis P. Low-dose aspirin to prevent pre-
Bertron P. Diet and sex-hormone binding role in health and disease. Adv Nutr. eclampsia in women at high risk. NEJM.
globulin, dysmenorrhea and premen- 2015;6(4):461–473. 1998;338:701–705.
strual symptoms. Obstet Gynecol 32. Uribarri J, Woodruff S, Goodman S, Cai 45. Carter JP, Furman T, Hutcheson HR.
2000;95:245–250. W, Chen X, Pyzik R, Yong A, Striker Preeclampsia and reproductive perfor-
18. Chavarro J, Rich-Edwards JW, Rosner GE, Vlassara H. Advanced glycation end mance in a community of vegans. South
BA, Willett WC. Protein intake and ovu- products in foods and a practical guide Med J. 1987;80:692–697.
latory infertility. Am J Obstet Gynecol to their reduction in the diet. J Am Diet 46. Vogel RA, Corretti MC, Plotnick GD.
2008;198:210.e1–210.e7. Assoc. 2010;110(6):911–916.e12. Effect of a single high fat meal on endo-
19. Alvarez-Blasco F, Botella-Carretero JI, 33. Nongnuch A, Davenport A. The effect of thelial function in healthy subjects. Am J
San Millán JL, Escobar-Morreale HF. vegetarian diet on skin autofluorescence Cardiol 1997;79:350–354.
Prevalence and characteristics of the measurements in haemodialysis patients. 47. Rosenkranz SK, Townsend DK,
polycystic ovary syndrome in overweight Br J Nutr. 2015;113(7):1040–1043. Steffens SE, Harms CA. Effect of a
and obese women. Arch Intern Med 34. Tantalaki E, Piperi C, Livadas S, high fat meal on pulmonary function
2006;166: 2081–2086. Kollias A, Adamopoulos C, Koulouri in healthy subjects. Eur J Appl Physiol.
20. Vogel RA, Corretti MC, Plotnick GD. A, Christakou C, Diamanti-Kandarakis 2010;109:499–506.
Effect of a single high fat meal on endo- E. Impact of dietary modification 48. Cani PD, Bibiloni R, Knauf C, Waget
thelial function in healthy subjects. Am J of advanced glycation end products A, Neyrinck AM, Delzenne NM,
Cardiol 1997;79:350–354. (AGEs) on the hormonal and metabolic Burcelin R. Changes in gut microbiota
21. Rosenkranz SK, Townsend DK, profile of women with polycystic ovary control metabolic endotoxemia-induced
Steffens SE, Harms CA. Effect of a syndrome (PCOS). Hormones (Athens). inflammation in high-fat diet-induced
high fat meal on pulmonary function 2014;13(1):65–73. obesity and diabetes in mice. Diabetes.
in healthy subjects. Eur J Appl Physiol. 35. Almenning I, Rieber-Mohn A, Lundgren 2008;57:1470–1481.
2010;109:499–506. KM, Løvvik TS, Garnæs KK, Moholdt T. 49. Galland L. Diet and inflammation. Nutr
22. Cani PD, Bibiloni R, Knauf C, Waget Effects of high intensity interval training Clin Pract. 2010;25:634–640.
A, Neyrinck AM, Delzenne NM, and strength training on metabolic, car- 50. Veloso Cde C, de Oliveira MC, Oliveira
Burcelin R. Changes in gut microbiota diovascular and hormonal outcomes in Cda C, Rodrigues VG, Giusti-Paiva A,
control metabolic endotoxemia-induced women with polycystic ovary syndrome: Teixeira MM, Duarte ID, Ferreira AV,
inflammation in high-fat diet-induced A pilot study. 2015;10:e0138793. Doi: de Castro Perez A.Hydroethanolic extract
obesity and diabetes in mice. Diabetes. 10.1371/journal.pone.0138793. of Pyrostegia venusta Miers flowers
2008;57:1470–1481. 36. Say L, Chou D, Gemmill A, Tunçalp improve inflammatory and metabolic
23. Galland L. Diet and inflammation. Ö, Moller AB, Daniels J, Gülmezoglu dysfunction induced by high-refined
Nutr Clin Pract. 2010;25:634–640. AM, Temmerman M, Alkema L Global carbohydrate diet. J Ethnopharmacol.
Highly refined carbohydrates have also causes of maternal death: A WHO 2014;151:722–728.
been implicated in the causation of systematic analysis. Lancet Glob Health. 51. Oliveira MC, Menezes-Garcia Z,
inflammation. 2014;2:e323–e333. Henriques MC, Soriani FM, Pinho
24. Oliveira MC, Menezes-Garcia Z, 37. Aune D, Saugstad OD, Henriksen V, Faria AM, Santiago AF, Cara DC,
Henriques MC, Soriani FM, Pinho T, Tonstad S. Maternal body mass Souza DG, Teixeira MM, Ferreira AV.
V, Faria AM, Santiago AF, Cara DC, index and the risk of fetal death, Acute and sustained inflammation
Souza DG, Teixeira MM, Ferreira AV. stillbirth and infant death. JAMA. and metabolic dysfunction induced by
Acute and sustained inflammation 2014;311:1536–1546. high refined carbohydrate- containing
and metabolic dysfunction induced by 38. Mocarelli P, Gerthoux PM, Needham LL, diet in mice. Obesity (Silver Spring).
high refined carbohydrate- containing Patterson Jr DG, Limonta G, Falbo R, 2013;21:E396–E406.
diet in mice. Obesity (Silver Spring). Signorini S, Bertona M, Crespi C, Sarto 52. Delibasi T, Cakir E. Is refined carbo-
2013;21:E396–E406. C, Scott PK. Perinatal exposure to low hydrate consumption related to allergic
25. Delibasi T, Cakir E. Is refined carbo- doses of dioxins can permanently impair diseases? Nutrition. 2014;30:401–402.
hydrate consumption related to allergic human semen quality. Environ Health 53. Watzl B. Anti-inflammatory effects of
diseases? Nutrition. 2014;30:401–402. Perspect. 2011;119:713–718. plant based foods and their constituents.
26. Alleman RJ Jr, Harvey IC, Farney 39. Stevens W, Shih T, Incerti D, Ton TG, Int J Vitam Nutr Res 2008;78:293–298.
TM, Bloomer RJ. Both a traditional Lee HC, Peneva D, Macones GA, Sibai 54. Alleman RJ Jr, Harvey IC, Farney TM,
and modified Daniel Fast improve the BM, Jena AB. Short-term costs of Bloomer RJ. Both a traditional and
cardio- metabolic profile in men and preeclampsia to the United States health modified Daniel Fast improve the cardio-
women. Int J Vitam Nutr Res. 2008;78: care system. AJOG. 2017;217(3):237– metabolic profile in men and women. Int
293–298. 248.e16. J Vitam Nutr Res 2008;78: 293–298.
660 Chapter 53 Antenatal Care—Nutrition and Lifestyle to Improve Conception and Pregnancy Outcomes
55. Bloomer RJ, Kabir MM, Trepanowski and infant cognition. Pediatrics. 83. Stoner R, Chow ML, Boyle MP, Sunkin
JF, Canale RE, Farney TM. A 21 day 2012;129(6):1141–1149. SM, Mouton PR, Roy S, Wynshaw-Boris
Daniel Fast improves selected biomarkers 69. Colombo J, Carlson SE. Is the mea- A, Colamarino SA, Lein ES, Courchesne
of antioxidant status and oxidative stress sure the message: The BSID and E. Patches of disorganization in the neo-
in men and women. Nutr Metab (Lond). nutritional interventions. Pediatrics. cortex of children with autism. N Engl J
2011;8:17. 2012;129(6):1166–1167. Med. 2014;370:1209–1219.
56. Johnston C. Functional foods as 70. Gould JF, Makrides M, Colombo J, 84. Atladóttir HÓ, Henriksen TB, Schendel
modifiers of cardiovascular disease. Am J Smithers LG. Randomized controlled DE, Parner ET. Autism after infection,
Lifestyle Med. 2009;3(1 suppl):39S–43S. trial of maternal omega-3 long-chain febrile episodes and antibiotic use dur-
57. Khan AE, Scheelbeek PF, Shilpi AB, PUFA supplementation during preg- ing pregnancy: An exploratory study.
Chan Q, Mojumder SK, Rahman A, nancy and early childhood develop- Pediatrics. 2012;130:e1447–e1454.
Haines A, Vineis P. Salinity in drink- ment of attention, working memory, 85. Sandin S, Lichtenstein P, Kuja-Halkola R,
ing water and the risk of (pre)eclampsia and inhibitory control. Am J Clin Nutr. Larsson H, Hultman CM, Reichenberg
and gestational hypertension in coastal 2014;99(4):851–859. A. The familial risk of autism. JAMA.
Bangladesh: A case-control study. PLOS 71. Agostoni C, Giobannini M. Cognitive 2014;311:1770–1777.
One. 2014;9: e0108715. Doi: 10.1371/ and visual development: Influence 86. Schendel DE, Grønborg TK, Parner ET.
journal.pone.0108715. of differences in breast and for- The genetic and environmental contribu-
58. Behrens I, Basit S, Melbye M, Lykke mula fed infants. Nutr Health tionsto autism: Looking beyond twins.
JA, Wohlfahrt J, Bundgaard H, 2001;15(3–4):183–188. JAMA. 2014;311:1738–1739.
Thilaganathan B, Boyd HA. Risk of 72. Birch EE, Garfield S, Castaneda Y, 87. Hertz-Picciotto I, Croen LA, Hansen R,
post-pregnancy hypertension in women Hughbanks-Wheaton D, Uauy R, Jones CR, van de Water J, Pessah IN. The
with a history of hypertensive disorders Hoffman D. Visual acuity and cognitive CHARGE study: An epidemiologic inves-
of pregnancy: Nationwide cohort study. outcomes at 4 years of age in a double- tigation of genetic and environmental
BMJ 2017;358: j3078. blind, randomized trial of long-chain factors contributing to autism. Environ
59. https: //khn.org/news/women-with-hig polyunsaturated fatty acid-supplemented Health Perspect. 2006;114:1119–1125.
h-risk-preg nancies-fa r-more-prone-to -hea infant formula. Early Hum Dev. 2007;83 88. Schmidt RJ, Kogan V, Shelton JF,
rt-disease/ (5):279–284. Delwiche L, Hansen RL, Ozonoff S,
60. Zheng JS, Liu H, Ong KK, Huang T, 73. Koo WW. Efficacy and safety of doco- Ma CC, McCanlies EC, Bennett DH,
Guan Y, Huang Y, Yang B, Wang F, Li D. sahexaenoic acid and arachidonic acid Hertz-Picciotto I, Tancredi DJ. Combined
Maternal blood pressure rise during preg- addition to infant formulas: Can one buy prenatal pesticide exposure and folic acid
nancy and at 4–7 years old: The Jiaxing better vision and intelligence? J Am Coll intake in relation to autism spectrum
Birth Cohort. J Clin Endocrin Metab Nutr. 2003;22(2):101–107. disorder. Environ Health Perspect. Doi:
2017;102:4315–4322. Doi: 10.1210/ 74. Koletzko B, Cetin I, Brenna JT. Dietary 10.1289/EHP604.
jc.2017-01500. fat intakes for pregnant and lactating 89. Krakowiak P, Walker CK, Bremer AA,
61. Shiell A, Campbell-Brown M, Haselden women. Br J Nutr. 2007;98:873–879. Baker AS, Ozonoff S, Hansen RL,
S, Robinson S, Godfrey KM, Barker 75. Arterburn LM, Oken HA, Hall EB, Hertz-Picciotto I. Maternal metabolic
DJ. High-meant, low-carbohydrate diet Hamersley J, Kuratko CN, Hoffman JP. conditionsand risk for autism and other
in pregnancy: Relation to adult blood Algal-oil capsules and cooked salmon: neurodevelopmental disorders. Pediatrics.
pressure in the offspring. Hypertension. Nutritionally equivalent sources of 2012;129:e1121–e1128.
2001;38:1282–1288. docosahexaenoic acid. J Am Diet Asccoc. 90. Lyall K, Munger KL, O’Reilly ÉJ,
62. Herrick K, Phillips DI, Haselden S, Shiell 2008;108:1204–1209. Santangelo SL, Ascherio A. Maternal
AW, Campbell-Brown M, Godfrey KM. 76. Aune D, Saugstad OD, Henriksen dietary fat intake in association with
Maternal consumption of a high-meat, T, Tonstad S. Maternal body mass autism spectrum disorders. Am J
low-carbohydrate diet in late pregnancy: index and the risk of fetal death, Epidemiol. 2013;178:209–220.
Relation to adult cortisol concentra- stillbirth and infant death. JAMA. 91. Schmidt RJ, Tancredi DJ, Ozonoff S,
tions in the offspring. J Clin Endocrinol 2014;311:1536–1546. Hansen RL, Hartiala J, Allayee H,
Metab. 2003;88(8):3554–3560. 77. Gardosi J, Williams M, Francis A. Schmidt LC, Tassone F, Hertz-Picciotto
63. Reynolds RM, Godfrey KM, Barker M, Clinical causes of stillbirth associated I. Maternal periconceptional folic acid
Osmond C, Phillips DI. Stress responsive- with maternal obesity. Am J Obstet intake and risk of autism spectrum
ness in adult life: Influence of mother’s Gynecol 2009;201:S223. disorders and developmental delay in the
diet in late pregnancy. J Clin Endocrinol 78. Yao R, Ananth CV, Park BY, Pereira CHARGE case- control study. Am J Clin
Metab. 2007;92(6):2208–2210. L, Plante LA; Perinatal Research Nutr. 2012;96:80–89.
64. Yin J, Quinn S, Dwyer T, Ponsonby AL, Consortium. Obesity and the risk of still- 92. Atladóttir HÓ, Henriksen TB, Schendel
Jones G. Maternal diet, breastfeeding and birth: A population-based cohort study. DE, Parner ET. Autism after infection,
adolescent body composition: A 16-year Am J Obstet Gynecol. 2014;210:457. febrile episodes and antibiotic use during
prospective study. Eur J Clin Nutr. e1–9. pregnancy: An exploratory studyPediat-
2012;66(12):1329–1334. 79. Francis et al. Maternal obesity and rics. 2012;130:e1447–e1454.
65. Dórea JG, Bezerra VLVA, Fajon V, perinatal mortality risk. Am J Obstet 93. Liu H, Talalay P, Fahey JW. Biomarker-
Horvat M. Speciation of methyl- and Gynecol 2009;201:S223–S224. guided strategy for treatment of
ethyl-mercury in hair of breastfed 80. Watkins ML, Rasmussen SA, Honein autism spectrum disorder (ASD).
infants acutely exposed to thimerosal- MA, Botto LD, Moore CA. Maternal CNS Neurol Disord Drug Targets.
containing vaccines. Clin Chim Acta obesity and risk for birth defects. 2016;15(5):602–613.
2011;412(17–18):1563–1566. Pediatrics. 2003;11(suppl 1):1152–1158. 94. Napoli E, Wong S, Hertz-Picciotto
66. Zeilmaker MJ, Hoekstra J, van Eijkeren 81. Broskey NT, Wang P, Li N, Leng J, Li W, I, Giulivi C. Deficits in bioenerget-
JCH, de Jong N, Hart A, Kennedy M, Wang L, Gilmore LA, Hu G, Redman ics and impaired immune response in
Owen H, Gunnlaugsdottir H. Fish LM. Early pregnancy weight gain exerts granulocytes from children with autism.
consumption during child bearing age: the strongest effect on birth weight, pos- Pediatrics. 2014;133(5):e1405–e1410.
A quantitative risk-benefit analysis on ing a critical time to prevent childhood 95. Giulivi C, Zhang YF, Omanska-Klusek
neurodevelopment. Food Chem Toxicol. obesity. Obesity. 2017;25(9):1569–1576. A, Ross-Inta C, Wong S, Hertz-Picciotto
2013 54(NA):30–34. 82. Developmental Disabilities Monitoring I, Tassone F, Pessah IN. Mitochondrial
67. Grandjean P, Budtz-Jørgensen E, Barr Network Surveillance Year 2010 dysfunction in autism. JAMA.
DB, Needham LL, Weihe P, Heinzow B. Principal Investigators; Centers for 2010;304(21):2389–2396.
Elimination half-lives of polychlorinated Disease Control and Prevention (CDC). 96. Vargas DL, Nascimbene C, Krishnan C,
biphenyl congeners in children. Environ Prevalence of autism spectrum disor- Zimmerman AW, Pardo CA. Neuroglial
Sci Technol. 2008;42:6991–6996. der among children aged 8 years— activation and neuroinflammation in
68. Qawasmi A, Landeros-Weisenberger Autism and Developmental Disabilities the brain of patients with autism. Ann
A, Leckman JF, Bloch MH. Meta- Monitoring Network, 11 sites, United Neurol. 2005;57(1):67–81.
analysis of long-chain polyunsaturated States, 2010. MMWR Surveill Summ. 97. Young AM, Campbell E, Lynch S,
fatty acid supplementation of formula 2014;63(2):1–21. Suckling J, Powis SJ. Aberrant NF-kappaB
References 661
expression in autism spectrum condition: 102. Parnell J, Reimer R. Prebiotic fiber modu- og.org /Resources-And- Publications/C
A mechanism for neuroinflammation. lation of the gut microbiota improves risk ommittee-Opinions/Com mittee-on- Obst
Front Psychiatry. 2011;2:27.
98. Heiss E, Herhaus C, Klimo K, Bartsch H,
Gerhäuser C. Nuclear factor kappa B is a
factors for obesity and the metabolic
syndrome. Gut Microbes. 2012;3:29–34.
103. Zimmer J, Lange B, Frick JS, Sauer H,
etric- Practice/ Physical-Ac tivit y-and-Exe
rcise- During-Pregnanc y-and-the- Post
partum-Period" https: //www.acog.org
53
molecular target for sulforaphane-medi- Zimmermann K, Schwiertz A, Rusch /Resou rces-And-P ublications/Com mitt
ated anti-inflammatory mechanisms. J Biol K, Klosterhalfen S, Enck P. A vegan or ee-Opi nions /Comm ittee -on- Obstet ric-
Chem. 2001;276(34):32008–32015. vegetarian diet substantially alters the Practice/Physical-Activity-and-Exercise-
99. Onore C, Yang H, Van de Water J, human colonic faecal microbiota. Eur J During-Preg nancy-and-the-Postpa rtum
Ashwood P. Dynamic Akt/mTOR signal- Clin Nutr. 2012;66:53–60. -Period.
ing in children with autism spectrum 104. Aagaard K, Ma J, Antony KM, 107. Veloso Cde C, de Oliveira MC, Oliveira
disorder. Front Pediatr. 2017;5:43. Ganu R, Petrosino J, Versalovic J. Cda C, et al. Hydroethanolic extract
100. Kim MS, Hwang SS, Park EJ, Bae JW. Microbiome: The placenta harbors a of Pyrostegia venusta Miers flowers
Strict vegetarian diet improves the risk unique microbiome. Sci Transl Med improve inflammatory and metabolic
factors associated with metabolic diseases 2014;6(237):237ra65. dysfunction induced by high-refined
by modulating gut microbiota and reduc- 105. Ma J, Prince AL, Bader D, Hu M, Ganu R, carbohydrate diet. J Ethnopharmacol.
ing intestinal inflammation. Environ Baquero K, Blundell P, Harris RA, Frias AE, 2014;151:722–728.
Microbiol Rep. 2013;5: 765–775. Grove KL, Aagaard KM. High-fat maternal 108. Watzl B. The data are also clear
101. David LA, Maurice CF, Carmody RN, diet during pregnancy persistently alters the that whole, minimally processed or
Gootenberg DB, Button JE, Wolfe BE, offspring microbiome in a primate model. unprocessed plant foods are anti-inflam-
Ling AV, Devlin AS, Varma Y, Fischbach Nat Commun. 2014;5:3889. matory in nature. (Anti-inflammatory
MA, Biddinger SB. Diet rapidly and 106. Committee Opinion No. 650. American effects of plant based foods and their
reproducibly alters the human gut micro- College of Obstetrics and Gynecology. constituents. Int J Vitam Nutr Res.
biome. Nature. 2014;505:559–563. 2015. HYPERLINK "https://ww w.ac 2008;78:293–298
54
CHAPTER
Exercise in Pregnancy
Kristin Bixel, MD and Christie Mitchell Cobb, MD
pregnancy and provided new recommendations for weight risk for macrosomia, maternal and neonatal birth injury,
gain based on pre-pregnancy body mass index.3 neonatal hypoglycemia and hyperbilirubinemia, and an
Exercising during pregnancy has been shown to increased risk of impaired glucose intolerance and type 2
reduce excess weight gain and decrease weight reten- diabetes mellitus in the years following pregnancy.14
tion postpartum. In one study of women who continued Insulin resistance in normal pregnancy is estimated to
their preconception exercise regimen compared to women increase by 40–70% and is related to the increase in corti-
who stopped or significantly reduced their level of physi- sol, growth hormone, human placental lactogen, estrogen,
cal activity during pregnancy, women who continued to progesterone, and prolactin associated with the growth of
exercise had a reduced rate of weight gain (though within the fetal-placental unit.14 An increase in insulin resistance
the normal range) and decreased subcutaneous fat depo- decreases maternal blood glucose uptake by the muscles,
sition later in the pregnancy.8 Stuebe et al. assessed the ensuring an adequate glucose supply for fetal growth
association of physical activity with excessive weight gain and development. This balance can tip, however, leading
among women enrolled in the Project Viva cohort study.4 to abnormally high maternal blood glucose and insulin
The cohort included women receiving prenatal care in one concentrations, yielding the diagnosis of GDM.15 Physical
of eight urban and suburban obstetrical offices in a mul- activity has long been known to improve glucose homeo-
tispecialty group practice in eastern Massachusetts. This stasis by increasing insulin sensitivity in maternal skeletal
study of 1,388 women included information about pre- muscle and increasing lean body mass.16 A sedentary life-
pregnancy weight, gestational weight gain, and dietary style is one of the modifiable risk factors associated with
and exercise habits. Within this cohort of women, 379 GDM.15 Physical activity decreases the risk of developing
(27%) were overweight entering the pregnancy and 703 GDM and can serve as an adjunctive therapy in the treat-
(51%) experienced excessive weight gain based on the ment of GDM. This is of particular importance since a
1998 Institute of Medicine guidelines for weight gain in significant number of women with GDM go on to develop
pregnancy. The study concluded that walking (30 min type 2 diabetes later in life.
daily), vigorous physical activity in the second trimester, Many studies have examined the impact of exercise
and increased total activity were inversely associated with before and during pregnancy on the development of ges-
excessive weight gain, while a sedentary lifestyle was asso- tational diabetes. Though there are no randomized con-
ciated with an insignificant increase in the risk of exces- trolled studies demonstrating exercise as a means for
sive weight gain.4 These are just two studies among many prevention of GDM, current evidence suggests a benefit.
that demonstrate the positive role of exercise in weight The influence of recreational activity on GDM risk was
management during pregnancy. evaluated in a case-control study of 155 women with
Postpartum weight retention is strongly related to GDM and 386 normotensive nondiabetic pregnant con-
weight gain during the pregnancy.9,10 Average estimates of trols. Both pre-pregnancy physical activity and physical
weight retention postpartum range from −0.27 kg (0.6 lb) activity during pregnancy were associated with a signifi-
to 3.0 kg (6.6 lb), though this varies significantly between cant reduction in GDM, by 51% and 48%, respectively,
different studies.9 Scholl et al. categorized the rate of ges- after adjustment for age, race, parity, pre-pregnancy BMI,
tational weight gain per trimester as more, less, or appro- and smoking.17 Similar results were confirmed in a pro-
priate compared to the recommended amount of weight spective cohort study of more than 900 normotensive non-
gain as per the Institute of Medicine guidelines at the time diabetic women.18 These data are supported by a recent
of the study. They found that at six-months postpartum, meta-analysis published by Tobias et al.19 Pre-pregnancy
women with an excessive rate of weight gain during the physical activity was assessed in 34,929 total participants,
pregnancy weighed 12% (7.9 kg or 17.4 lb) more than yielding a pooled odds ratio of 0.45 (95% CI 0.28–0.75)
they did pre-pregnancy and retained about 40% of the for developing GDM when comparing women in the high-
gestational weight gain. This was in contrast to women est category of pre-pregnancy physical activity with those
who gained weight at or below the recommended guide- in the lowest. Exercise during early pregnancy was also
lines, who were only 5–7% (3.2 kg or 7.1 lb) heavier at found to be protective, yielding an odds ratio of 0.76 (95%
six-months postpartum.11 Rooney and Schauberger found CI 0.7–0.83).
that women who gained excessive weight during preg- Exercise serves not only to prevent gestational diabe-
nancy and failed to lose the weight by six-months postpar- tes but also as an adjunctive treatment in women who
tum were as much as 15 lb heavier at 10-year follow-up.12 have been previously diagnosed. The American Diabetes
Women who exercise during pregnancy may be less likely Association suggests that women without medical or
to gain more than the recommended amount of weight obstetrical contraindications to exercise should be encour-
and be at less risk of postpartum weight retention and aged to start or continue a program of moderate exercise
lasting weight retention or obesity. as part of treatment for GDM.13 Jovanovic-Peterson et al.
randomized a small group of women diagnosed with
GDM (N = 19) to diet alone versus diet plus exercise
54.2 GLYCEMIC CONTROL with an arm ergometer. 20 They found lower glycosylated
hemoglobin, fasting, and one-hour postprandial plasma
Gestational diabetes mellitus (GDM) is one of the most glucose concentrations in the diet-plus-exercise group as
common pregnancy complications, affecting approxi- compared to diet alone. 20 Garcia-Patterson et al. found
mately 7% of pregnancies in the United States. It is highest that women with GDM who performed light postpran-
among obese and overweight women.13 GDM is associated dial walking also showed improvement in postprandial
with adverse perinatal outcomes, including an increased glucose concentrations. 21 Bung et al. randomized women
54.4 Psychological Benefits 665
diagnosed with GDM who failed to attain adequate glu- of proinflammatory cytokines, and decreasing insulin
54
cose control with diet alone to insulin plus diet versus resistance.15
exercise plus diet. There were no significant differences Sorensen et al. conducted a case-control study between
between the two groups in terms of glycemic control, 1998 and 2001 in order to characterize the relation
maternal outcomes, or fetal outcomes and thus Bung between recreational physical activity and the risk of pre-
et al. concluded exercise to be a valuable tool in the treat- eclampsia. 27 They identified 201 women with preeclamp-
ment of GDM. 22 sia and 383 normotensive controls. All patients were given
a structured questionnaire during their postpartum stay.
Women who participated in recreational physical activ-
54.3 REDUCTION OF ity (e.g., brisk walking, stair climbing) during the first
20 weeks of pregnancy experienced a 35% reduction in
RISK OF HYPERTENSIVE the risk of preeclampsia after controlling for maternal
DISORDERS IN PREGNANCY age, race, parity, tobacco use, and pre-pregnancy BMI.
Increased energy expenditure was inversely associated
Hypertensive disorders occur in approximately 12–22% with the risk of preeclampsia. These results were similar
of pregnancies and are among the leading causes of mater- to those published by Marcoux et al. in 1989. 28 In this
nal mortality in the United States, accounting for 15–20% case-control study, women participating in recreational
of maternal deaths. 23 There is a spectrum of hypertensive physical activity in the first 20 weeks of pregnancy were
disorders that affect pregnancy, including chronic hyper- significantly less likely to develop gestational hypertension
tension, gestational hypertension, preeclampsia, and or preeclampsia.
HELLP (hemolysis, elevated liver enzymes, and low plate- More prospective research is needed to further char-
lets) syndrome. Maternal complications resulting from acterize the relationship between exercise and maternal
hypertensive disorders in pregnancy can be catastrophic hypertensive disorders, but current data suggest that exer-
and include abruptio placentae, disseminated intravas- cise before pregnancy and during the first 20 weeks plays
cular coagulation, cerebral hemorrhage, seizure, hepatic a protective role.
failure, and acute renal failure. 24 There are also significant
risks to the fetus, including intrauterine growth restriction
(IUGR), oligohydramnios, preterm delivery, and intra- 54.4 PSYCHOLOGICAL BENEFITS
uterine fetal demise. 24
Metabolic disturbances associated with preeclamp- Maternal mental health has been reported to have a signif-
sia include but are not limited to hypertriglyceridemia, icant impact on physical health and pregnancy outcome.
excessive lipid peroxidation, antioxidant deficiency, Mood fluctuations are common during and after preg-
insulin resistance, plasma elevations of proinflamma- nancy, with the prevalence of prenatal depression nearly
tory cytokines and C-reactive protein, and a thrombox- 11%29 and postpartum depression up to 16%.30 Several
ane-prostacyclin imbalance favoring vasoconstriction.15 factors may increase the risk for mood disturbances
There is considerable overlap between the epidemiology during pregnancy, including reproductive hormones,
of preeclampsia with that of essential hypertension and psychosocial stressors, isolation, personal or family his-
atherosclerotic vascular disease.15 Nonpregnant women tory of depression, and chronic medical conditions.15
with hypertension or vascular disease are encouraged to Consequences of untreated perinatal mood disorders can
exercise in order to improve their blood pressures and/or be significant and are associated substance use, lack of
halt disease progression. 25 It is likely, then, that increased compliance with medical care, disruption of relationships,
physical activity would be associated with a decreased risk preterm delivery, low birth weight, impaired mother-child
of hypertensive disorders in pregnancy. bonding, and childhood behavioral issues.15,31,32
To date, there are few studies looking at the relation- Physical activity is linked with improvement of men-
ship between the hypertensive disorders of pregnancy tal health in nonpregnant women and likely confers
and maternal exercise. Yeo et al. suggest that exercise the same benefits during pregnancy. The advantageous
lowers blood pressure during pregnancy (as it does in effects of physical activity on mental health likely result
nonpregnant women) based on the results from a ran- from a combination of psychological and physiological
domized controlled trial conducted on a small group components. Proposed hypotheses regarding the psycho-
of pregnant women recruited before 14 weeks of ges- logical impact of exercise on mood include distraction,
tation. 26 All women had a significant history of mild self-efficacy, social interaction, 33 and improved body
hypertension, gestational hypertensive disorders, or image.34 Physiological mechanisms by which exercise may
a family history of hypertensive disorders and were improve mood include the release of monoamines and
therefore thought to be at significant risk for develop- endorphins.33 Improvements noted in women who engage
ing hypertension in their current pregnancy. Among in physical activity include increased vigor, decreased
women randomized to the exercise arm, there was a fatigue, less stress and anxiety, decreased symptoms of
strong trend toward lowered diastolic blood pressures, negative mood and depression, and improved self-image.35
though their results were not statistically significant. Wallace et al.36 found that pregnant women partici-
Other mechanisms by which exercise may reduce the pating in an aerobic exercise program during pregnancy
risk of hypertensive disorders in pregnancy, and specifi- had higher self-esteem and lower fatigue than sedentary
cally the risk of preeclampsia, include improving preg- women. Goodwin et al.37 found that women who exer-
nancy-induced dyslipidemia, decreasing concentrations cised during pregnancy reported better feelings of overall
666 Chapter 54 Exercise in Pregnancy
well-being and had fewer symptoms of somatic discom- augmentation, operative vaginal delivery, and cesarean
fort, anxiety, and insomnia. These results were echoed by delivery. A case-control study by Hall and Kaufman dem-
Marquez-Sterling et al., who demonstrated improvement onstrated a lower incidence of cesarean delivery and a
in energy levels and body satisfaction in a small group of shorter peripartum hospitalization course in women who
previously sedentary pregnant women randomized to an participated in a conditioning program over the course
exercise program and compared to controls that remained of their pregnancy.48 Clapp compared the onset, course,
sedentary.38 Similarly, pregnant adolescents participating and outcome of labor among women who continued
in a six-week aerobic exercise program reported signifi- their pre-pregnancy exercise regimen throughout gesta-
cantly less depressive symptoms and an increase in self- tion with those who discontinued their exercise routine
esteem compared to controls.39 Given the prevalence of before the end of the first trimester. Results indicated a
symptoms associated with depression and anxiety in preg- lower incidence of operative vaginal delivery and cesarean
nancy and the negative impact that these symptoms may delivery as well as a shorter active phase of labor among
have on pregnancy outcome, an exercise regimen may be the women who delivered vaginally.49 A randomized con-
a helpful tool in the maintenance of emotional well-being. trolled trial looking at the effect of water aerobics in preg-
Exercise during pregnancy has also been associated with nancy did not find a difference in the duration of labor or
improved mood postpartum and therefore may play an type of delivery; however, it found that women who par-
important role in preventing postpartum depression.15,40 ticipated in the exercise group were significantly less likely
to request analgesia. 50 This was true after controlling for
parity and level of education as well.
54.5 IMPROVEMENT IN
MUSCULOSKELETAL PAIN 54.7 OTHER BENEFITS
Studies indicate that 50–90% of women experience some
Women who are active during pregnancy may report less
degree of musculoskeletal discomfort during pregnancy,
nausea, heartburn, leg cramps, varicose veins, constipa-
most commonly low back and pelvic girdle pain.15,41
tion, and insomnia.43,50
Proposed mechanisms for pregnancy-associated muscu-
loskeletal pain include a change in weight distribution
and posture as well as hormonal influence on joint lax-
ity.42 Musculoskeletal discomfort tends to worsen over the 54.8 RISKS OF EXERCISE
course of the pregnancy and has been linked to disability,
functional impairment, and missed work.31
IN PREGNANCY
A regular exercise program before pregnancy and dur- With regard to the risks of exercise in pregnancy, there are
ing early pregnancy likely reduces the risk of back pain dur- many conflicting studies and most are limited in design
ing pregnancy.43,44 Sternfeld et al. found that women who and quality. Concerns regarding exercise in pregnancy
exercised more during early pregnancy had statistically are generally related to the risk of spontaneous abortion
fewer discomforts later in pregnancy, and those symptoms (SAB), fetal distress, low birth weight, preterm delivery,
were inversely proportional to the level of exercise women and maternal injury. Physiological mechanisms hypothe-
performed.44 In women who already have low back pain sized to mediate a potentially detrimental effect of mater-
associated with pregnancy, exercises to strengthen core nal exercise on embryonic and fetal health include the
abdominal and back muscles are likely of benefit. Sitting following:
pelvic tilt exercises and aquatic exercises have both been
shown to decrease the incidence and severity of low back 1. Reduction of placental blood flow secondary to
pain experienced in pregnancy.45,46 Yoga is also thought to redirection toward working skeletal muscles.51,52
play a role in improving back pain as well,47 possibly sec- 2. Rise in core body temperature/hyperthermia53,54
ondary to improvement in core strength. Beddoe et al. 31 3. Release of hormones (adrenaline, noradrenaline)
analyzed the effect of a seven-week mindfulness-based stimulating uterine contractility55,56
yoga intervention on several variables, one of which was 4. Hypoglycemia57
pain. They found women in the second trimester experi-
enced fewer hours of pain and less pain interference with
activity from baseline to post-intervention.
54.9 SPONTANEOUS ABORTION
The current literature yields mixed results when evaluat-
54.6 LOWERED RATES OF ing the risk of SAB in relation to a woman’s physical activ-
INTERVENTION DURING THE ity level. Hjollund et al. 58 followed a cohort of women
planning their first pregnancy in order to assess the rela-
TIME OF LABOR AND DELIVERY tionship between physical strain and SAB. Women were
recruited between 1992 and 1994 and followed from the
Though the evidence is of limited quality, some studies time of termination of contraception until pregnancy was
suggest that less medical intervention is required during achieved for a maximum of six menstrual cycles. Women
labor in women who exercised routinely during preg- recorded their level of daily physical strain in a structured
nancy. These interventions may include analgesia, labor diary, and pregnancy outcomes were analyzed with a SAB
54.11 Low Birth Weight 667
being defined as pregnancy loss prior to 28 weeks of ges- during the second and third trimesters and were matched
54
tation in this study. They found an increased risk of SAB with sedentary controls. At three different time points,
among women who reported high physical strain during both the study group and the controls were asked to per-
the time of implantation of the embryo as calculated based form on a cycle ergometer. Maternal heart rate, blood
on menstrual cycle length. No clear effect was seen at any pressure, and temperature were monitored, as was the
other time point. Madsen et al.59 found similar results FHR. While the most common response was a rise in
from a study within the Danish National Birth Cohort in FHR baseline by approximately 10–20 bpm during exer-
that women who exercised, high-impact exercises in par- cise, there were three incidences of fetal bradycardia (one
ticular, had an increased risk of SAB prior to 18 weeks after 10 min of exercise and two following cessation of
of gestation as compared to sedentary controls. Caution exercise). All FHRs normalized, and none were associ-
must be made when interpreting these results, given the ated with adverse pregnancy outcomes. Of note, there
potential bias that results from largely retrospective data were no differences in the FHR response between condi-
collection and confounders such as chronic medical condi- tioned and sedentary women.67 Manders et al. described
tions that were not accounted for in the results. similar FHR findings and added that fetal body move-
Other studies have found substantially different ments were decreased immediately following cessation
results. For example, Clapp.60 followed exercise perfor- of exercise whereas fetal breathing movements were
mance before and during pregnancy in 47 recreational increased during this time frame.68 Winn et al., on the
runners, 40 aerobic dancers, and 28 controls. In this group other hand, found a decrease in the total duration and
of women, SAB occurred in 19% of pregnancies and was frequency of fetal breathing and fetal body movement
not statistically different among the groups, and he there- following acute maternal exercise.69 Neither Manders
fore concluded that exercise in the preconceptional period nor Winn reported adverse pregnancy outcomes associ-
and early pregnancy does not appreciably alter early preg- ated with these findings.
nancy outcomes. In one large prospective study with 158 With regard to pregnancy outcomes, Clapp found
active women and 83 matched sedentary controls, there that women who continued to exercise regularly through-
was no association between exercise and the risk of infer- out pregnancy were actually less likely to have clinical
tility, SAB, or other adverse pregnancy outcomes.61 Also, evidence of fetal distress as indicated by the presence of
Latka et al.62 reported a lower risk of chromosomally nor- meconium, abnormal FHR tracing, or low APGAR score
mal SAB among women who participated in leisure-time at the time of labor and delivery.49 Rose et al. showed no
exercise. difference in the rate of fetal or neonatal death among
In summary, the data are quite limited in both the women who reported moderate or vigorous activity lev-
number and the quality of studies examining the relation- els during the second trimesters compared to women who
ship between physical activity and risk of SAB. At this reported light activity.70 It is important to recognize that
point, the benefits of exercise in pregnancy as mentioned neither FHR monitoring nor ultrasound is a perfect mea-
earlier likely far outweigh the risk of early pregnancy loss, sure of fetal oxygenation or acid–base status. While tran-
if there is any risk at all. sient abnormalities in fetal testing have been associated
with maternal exercise, there are no differences in fetal
morbidity or mortality.49,67,71,72 in pregnancy outcomes.
54.10 FETAL DISTRESS
Studies of animal models have demonstrated that maternal 54.11 LOW BIRTH WEIGHT
exercise may reduce uterine blood flow secondary to redis-
tribution toward maternal skeletal muscle and thus may Exercise leads to a redistribution of blood flow toward
result in relative fetal hypoxia.52 Fetal heart rate (FHR) skeletal muscle, and splanchnic blood flow (which includes
monitoring is a noninvasive method for determining fetal uterine blood flow) may decrease substantially. With high-
well-being, with specific patterns recognized to be associ- intensity exercise, oxygen and glucose are shunted to skel-
ated with fetal hypoxia.63 For this reason, it is frequently etal muscles and away from the placenta and developing
used in studies attempting to evaluate the risk of fetal dis- fetus.65 There has been concern that this redistribution
tress associated with maternal exercise. The most com- may lead to a decrease in birth weight or intrauterine
mon response to maternal exercise is a rise in FHR, which growth restriction, but studies are inconsistent. Recent lit-
returns to baseline after cessation of exercise53,64 and is erature suggests that the timing, volume, and intensity of
likely a response to a slight drop in oxygenation secondary exercise likely impact placental and fetal growth.73,74
to increased maternal consumption,63 release of maternal Though the majority of the data regarding the effects
catecholamines, and an increase in maternal core body of exercise on birth weight stem from retrospective cohort
temperature.64 Less common and more concerning are the studies, two recent prospective randomized studies have
few reports of transient bradycardia occurring with or fol- been conducted to evaluate the relationship between exer-
lowing exercise.65 Another technique used to assess fetal cise and fetoplacental growth. In the first, women who
status is ultrasonography with attention to fetal move- did not exercise regularly were randomly assigned at eight
ments and breathing, as these are thought to be markers weeks of gestation either to no exercise or to weight-bear-
of fetal well-being.66 ing exercise three to five times per week for the remainder
Webb et al.67 sought to evaluate the effects of acute of the pregnancy.73 The mid-trimester placental growth
and chronic maternal exercise on FHR. In this study, a rate was faster and the birth weights were increased sig-
group of women took part in a conditioning program nificantly (3.75 vs. 3.49 kg) in the exercise group.
668 Chapter 54 Exercise in Pregnancy
A follow-up study aimed to further determine the effect groups at 9%. Labor did begin an average of five days
of the timing and the volume of exercise on placental and earlier in the exercise group, which was statistically sig-
fetal growth during pregnancy. Clapp et al. randomly nificant,49 but may be clinically irrelevant, as this did not
assigned women at eight weeks of gestation who exer- result in preterm delivery or adverse outcomes.
cised regularly to one of three exercise regimens for the Juhl et al. 56 in contrast, reported a reduced risk of
remainder of the pregnancy.74 The first group increased preterm birth among women who engaged in some form
their volume of exercise in the third trimester, the second of exercise during pregnancy as compared to sedentary
maintained a moderate exercise regimen throughout the women. The association was not affected by the type of
pregnancy, and the third decreased their exercise volume exercise, and no dose-response relationship was found.56
in the third trimester. Women who maintained a moder- Important things to consider in the interpretation of these
ate exercise regimen or increased their exercise volume in results include the reliance on patient self-report and the
the third trimester had significantly slower fetoplacental possibility that the women who were exercising may have
growth than women who decreased their exercise vol- been at a lower baseline risk of preterm birth, resulting
ume in the third trimester. While infants of women who in a healthy exerciser effect. 56 Randomization helps to
maintained or increased their exercise volume in the third eliminate these biases, and recently two randomized con-
trimester weighed less than those who decreased their trolled trials designed to evaluate the association between
physical activity (3.39 vs. 3.81kg), there was no increased exercise and gestational age at the time of delivery were
risk of intrauterine growth restriction or birth weight clas- published.
sified as small for gestational age.74 Barakat et al.82 randomized previously sedentary
In summary, exercise in early pregnancy seems to pro- women with singleton pregnancies to a control group or
mote placental growth and development,73,74 which may an exercise group. The exercise program consisted of light
account for the finding that many women who start or resistance and toning exercises three days a week for 35
maintain exercise regimens during pregnancy actually min between 12 and 39 weeks. The mean gestational age
have increased mean birth weights when compared to less at delivery did not differ between the two groups, and
active or sedentary controls.75–77 Vigorous and high-vol- there was no significant difference in the percentage of
ume activity later in pregnancy does appear to be associ- women with preterm delivery.82 Cavalcante et al.79 simi-
ated with a small decrease in mean birth weight,8,49,74,78 larly randomized low-risk sedentary pregnant women to
which some believe to be the result of a loss of fat mass in a water aerobics group or a sedentary control group, and
the fetuses of endurance exercisers, while others feel this they reported no difference in the rate of preterm delivery
may be related to gestational age at delivery (addressed between the two groups.
in the following text) or maternal weight gain.78 In either Based on the limited available data, there is not an
case, there does not appear to be an increase in intrauter- increased risk of preterm delivery associated with exer-
ine growth restriction or SGA infants among women who cise during pregnancy. These studies do not address the
exercise during pregnancy.79,80 effects of exercise on preterm birth in women who have an
increased underlying risk for preterm labor. Thus, caution
should be used when counseling these women with regard
54.12 PRETERM DELIVERY to exercise during the course of their gestation.
of her fetus at risk. In these situations, the risks will far prescription should include recommendations for inten-
54
outweigh the exercise-related benefits. Of note, a his- sity, duration, frequency, and type of exercise, and should
tory of sedentary lifestyle was previously described as be tailored to patients on an individual basis.
a relative or even absolute contraindication to exercise
in pregnancy, as there was thought to be the potential
for harm. There are now studies to show that this is 54.16.1 Intensity of Training
unlikely, and when done appropriately, beginning an
exercise regimen in pregnancy is safe even for previously No safe upper limit of exercise in pregnancy has been
inactive women.79 established, though many studies demonstrate that physi-
cally fit women may participate in vigorous activity with-
out compromising the pregnancy.64 Methods to monitor
54.15 RECOMMENDATIONS FOR exercise intensity, including heart rate monitoring, Borg’s
rate of perceived exertion, and the “talk” test,88 may all
EXERCISE IN PREGNANCY be helpful in achieving a safe level of exercise. The goal is
for healthy women to achieve regular moderate-intensity
The most recent ACOG committee opinion on exercise exercise.
during pregnancy and the postpartum period was pub- Cardiovascular adaptations in pregnancy include an
lished in 2015. At that time, it was recommended that in increased resting heart rate and a decreased maximal
the absence of contraindications, pregnant women should heart rate, which results in reduced heart rate reserve and
engage in regular, moderate-intensity physical activity for a lowered slope of heart rate response to increasing work.89
30 min on most, if not all, days of the week. 2 More recently, Thus, heart rate alone may be an inaccurate reflection of
the 2008 physical activity guidelines for Americans the intensity of aerobic exercise. It has been proposed that
were published by the Centers for Disease Control and during pregnancy, the target heart rate range represents
Prevention, which recommends the following:85 about 60–80% of aerobic capacity.89 Davies et al. pro-
pose that the target heart rate range for pregnant women
1. Healthy women should get at least 150 min/week under 20 years old is 140–155 bpm, 20–29 years old is
of moderate-intensity aerobic activity during and 135–150 bpm, 30–39 years old is 130–145, and over 40
after their pregnancy. This may be broken down to years old is 125–140 bpm.90 The literature suggests that
30 min/day, 5 days/week and furthermore can be the target heart rate should also be adjusted according to
done in 10 min segments of exercise. BMI, because overweight and obese pregnant women may
2. For previously inactive women without medical con- be exercising at a higher intensity (%VO2) than intended
traindication to exercise, it is reasonable to begin a for a given heart rate.91 Borg’s rate of perceived exer-
moderate-intensity exercise regimen. tion is a 15-point scale from 6 to 20. A target range of
3. For healthy women who regularly perform vigor- 12–14, which corresponds with moderate to somewhat
ous-intensity aerobic activity, they may continue to hard intensity, is suggested to be appropriate during preg-
do so during pregnancy so long as they stay healthy nancy.88 The “talk test” refers to exercising mothers being
and are followed closely by a health care provider. able to carry on a conversation while exercising. 53,88 One
4. While pregnant, women should not partake in activ- should be able to hold a conversation during moderate-
ities that involve lying directly on one’s back or that intensity exercise. It is likely a combination of the earlier
increase the risk of falling or abdominal trauma. methods that allows for the determination of the appro-
priate intensity of exercise.
In the United States, only 16% of pregnant women
comply with the physical activity recommendations com-
pared with 26% of nonpregnant women.86 Even healthy, 54.17 DURATION/FREQUENCY
otherwise active women tend to decrease physical activ-
ity in pregnancy.87 Given the proven benefits of exercise The current recommendation for exercise in pregnancy
in pregnancy, it is important to educate and encourage is for 150 min of exercise per week,85 and it is generally
women to participate in moderate physical activity during suggested that this be spread over the course of the week
the course of their gestation. on most, if not all, days (rather than performed in long
but infrequent sessions). During exercise, glucose levels
decrease, and temperature increases with time.57 Blood
54.16 EXERCISE PRESCRIPTION glucose decreases at a faster rate and to a significantly
lower level post-exercise in pregnant women compared to
When counseling a patient regarding an appropriate exer- nonpregnant women. After 45 min of continuous exercise
cise regimen, there are several factors to consider: the wom- at 50–60% of maximal oxygen consumption, the blood
an’s age, weight, pre-pregnancy or current fitness level, glucose in pregnant women may fall substantially, which
medical history, and obstetric history. Contraindications could adversely impact the fetus. 57 It is therefore impor-
should be ruled out or at least weighed against the poten- tant to balance caloric intake with output, and perhaps
tial benefits in pregnancy that exercise may confer (e.g., limiting exercise sessions to 45 min or less may be advis-
weight management, glucose control, reduction in the able.89 Core body temperature also rises but when exer-
risk of hypertensive disorders, psychological benefits, cise is self-paced, body temperature tends to stay within
and improvement in musculoskeletal pain). An exercise safe limits. 57 In order to avoid complications such as
670 Chapter 54 Exercise in Pregnancy
hyperthermia, women should exercise in a thermoneutral is considered to be particularly dangerous during preg-
environment or in controlled environmental conditions nancy secondary to the risk of fetal decompression sick-
and pay careful attention to hydration and subjective feel- ness because the fetal pulmonary circulation is unable to
ings of heat stress.89 filter bubble formation. Therefore, such activity should be
avoided during pregnancy.93
CLINICAL APPLICATIONS22
Excessive weight gain and physical activity are recognized as independent risk factors for maternal obesity and gestational diabetes.
Regular physical activity during uncomplicated pregnancy has not been substantiated to cause miscarriage, poor fetal growth, maternal
musculoskeletal injury, or preterm delivery.
Aerobic exercise in pregnancy has been stratified by absolute and relative contraindications:
Absolute Contraindications Relative Contraindications
Bleeding persistently in second or third trimester Anemia
Cerclage or cervical insufficiency BMI below 12
Gestational hypertension or preeclampsia Chronic bronchitis
Hemodynamically significant heart disease Extreme morbid obesity
Multiple gestation at risk of preterm labor Heavy smoker
Placenta previa after 26 weeks gestation IUGR in current pregnancy
Premature labor Orthopedic limitations
Restrictive lung disease Poorly controlled hypertension
Ruptured membranes Poorly controlled hyperthyroidism
Severe anemia Poorly controlled type 1 diabetes
Poorly controlled seizure disorder
Sedentary lifestyle prior to pregnancy
Unevaluated maternal cardiac arrhythmia
References 671
REFERENCES
1. American College of Obstetricians
and Gynecologists (ACOG). Technical
recreational physical activity before and
during pregnancy. Am J Epidemiol 2004;
of depressive symptoms, body image
satisfaction, and exercise behavior. Ann
54
Bulletin: Exercise During Pregnancy and 159: 663–670. Behav Med 2008; 36(1): 54–63.
the Postnatal Period. Washington, DC: 19. Tobias DK, Zhang C, van Dam RM, 35. Dishman RK. Physical activity and men-
ACOG, 1985. Bowers K, Hu FB. Physical activity before tal health. In: Encyclopedia of Mental
2. ACOG Committee Obstetric Practice. and during pregnancy and risk of gesta- Health, Vol. 3. Friedman HS (Ed.).
ACOG Committee Opinion: Exercise tional diabetes mellitus: A meta-analysis. San Diego, CA: Academic Press, 1998:
during pregnancy and the postpartum Diabetes Care 2011; 34(1): 223–229. 171–188.
period. Number 650. December 2015, 20. Jovanic-Peterson L, Durak EP, Peterson 36. Wallace AM, Boyer DB, Bad A, Holm
reaffirmed 2017. CM. Randomized trial of diet vs diet plus K. Aerobic exercise, maternal self-
3. Institute of Medicine. Brief Report: Weight cardiovascular conditioning on glucose esteem, and physical discomforts during
Gain During Pregnancy: Reexamining the levels in gestational diabetes. Am J pregnancy. J Nurse Midwifery 1986; 31:
Guidelines, Washington, DC: National Obstet Gynecol 1989; 161: 415–419. 255–262.
Acadamies Press, 2009. 21. Garcia-Patterson A, Martin E, Ubeda 37. Goodwin A, Astbury J, McMeeken J.
4. Stuebe AM, Oken E, Gillman MW. J, Maria M, DeLeiva A, Corcoy R. Body image and psychological well being
Associations of diet and physical activity Evaluation of light exercise in the treat- in pregnancy. A comparison of exercisers
during pregnancy with risk for excessive ment of gestational diabetes. Diabetes and non-exercisers. Aust NZ J Obstet
gestational weight gain. Am J Obstet Care 2001; 24: 2006–2007. Gynaecol 2000; 40: 442–447.
Gynecol 2009; 201(1): 58.e1–58.e8. 22. Bung P, Bung C, Artal R, Khodogiuan 38. Marquez-Sterling S, Perry AC, Kaplan
5. Crane M, White J, Murphy P, Burrage N, Fallenstein F, Spatling L. Therapeutic TA, Halberstein RA, Signorile JF.
L, Hutchens D. The effect of gestational exercise for insulin-requiring GDM. Physical and psychological changes with
weight gain by body mass index on Results from a randomized prospective vigorous exercise in sedentary primi-
maternal and neonatal outcomes. J Obstet longitudinal study. J Perinat Med 1993; gravidae. Med Sci Sports Exerc 2000; 32:
Gynaecol Can 2009; 31(1): 28–35. 21: 125–137. 58–62.
6. Kiel DW, Dodson EA, Artal R et al. 23. ACOG Practice Bulletin Number 33. 39. Koniak-Griffin D. Aerobic exercise,
Gestational weight gain and pregnancy Diagnosis and management of preeclamp- psychological well-being, and physi-
outcomes in obese women: How much is sia and eclampsia. Int J Gynecol Obstet cal discomforts during adolescent preg-
enough? Obstet Gynecol 2007; 110: 1–7. 2002; 77: 67–75. nancy. Res Nurs Health 1994; 14(4):
7. Savitz DA, Stein CR, Siega-Riz AM, 24. Gifford RW. Report of the national 253–263.
Herring AH. Gestational weight gain and high blood pressure education program 40. Nordhagen IH, Sundgot-Borgen J.
birth outcome in relation to prepregnancy working group on high blood pressure in Physical activity among pregnant women
body mass index and ethnicity. Ann pregnancy. Am J Obstet Gynecol 2000; in relation to pregnancy related com-
Epidemiol 2011; 21(2): 78–85. 183: S1–S22. plaints and score of depression. Tidsskr
8. Clapp JF, Little KD. Effect of recreational 25. Gavard JA, Artal R. Effect of exercise on Nor Laegeforen 2002; 122: 470–474.
exercise on pregnancy weight gain and pregnancy outcome. Clin Obstet Gynecol 41. Wang SM, Zinno PD, Fermo L et al.
subcutaneous fat deposition. Med Sci 2008; 51(2): 467–480. Complementary and alternative medicine
Sports Exerc 1995; 27(2): 170–177. 26. Yeo S, Steele NM, Chang MC, Leclaire for low back pain in pregnancy: A cross
9. Gore SA, Brown DM, Smith DS. The role SM, Ronis DL, Hayashi R. Effect of exer- sectional survey. J Altern Complement
of postpartum weight retention in obesity cise on blood pressure in pregnant women Med 2005; 104: 65–70.
among women: A review of the evidence. with high risk of gestational hypertensive 42. MacEvilly M, Buggy D. Back pain and
Ann Behav Med 2003; 26(2): 149–159. disorders. J Reprod Med 2000; 45(4): pregnancy: A review. Pain 1996; 64(3):
10. Polley BA, Wing RR, Sims CF. 293–298. 405–414.
Randomized controlled trial to prevent 27. Sorensen TK, Williams MA, Lee IM et 43. Ostgaard HC, Zetherstrom G, Roos-
excessive weight gain in pregnant women. al. Recreational physical activity during Hansson E et al. Reduction of back and
Int J Obes 2002; 26: 1494–1502. pregnancy and risk of preeclampsia. posterior pelvic pain in pregnancy. Spine
11. Scholl TO, Hediger ML, Schall JI, Ances Hypertension 2003; 41: 1273–1280. 1994; 19: 894–900.
IG, Smith WK. Gestational weight gain, 28. Marcoux S, Brisson J, Fabia J. The effect 44. Sternfeld B, Quesenberry JR, Eskenazi B,
pregnancy outcome, and postpartum of leisure time physical activity on the Newman LA. Exercise during pregnancy
weight retention. Obstet Gynecol 1995; risk of preeclampsia and gestational and pregnancy outcome. Med Sci Sports
86: 423–427. hypertension. J Epidemiol Commun Exerc 1995; 27(5): 634–640.
12. Rooney BL, Schauberger CW. Excess Health 1989; 43(2): 147–152. 45. Borg-Stein J, Dugan SA, Gruber J.
pregnancy weight gain and long term 29. Bennett HA, Einarson A, Taddio A, Musculoskeletal aspects of pregnancy.
obesity: One decade later. Obstet Koren G, Einarson TR. Prevalence of Am J Phys Med Rehabil 2005; 84:
Gynecol 2002; 100: 245–252. depression during pregnancy: A system- 180–192.
13. American Diabetes Association. atic review. Obstet Gynecol 2004; 103: 46. Kihlstrand M, Stenman B, Nilsson S,
Gestational diabetes mellitus. Diabetes 698–709. Axelsson O. Water-gymnastics reduced
Care 2004; 27(Suppl 1): S88–S90. 30. O’Hara M, Swain A. Rates and risk of the intensity of back/low back pain in
14. Pridjian G, Benjamin TD. Update on postnatal depression: A meta-analysis. Int pregnant women. Acta Obstet Gynecol
gestational diabetes. Obstet Gynecol Clin Rev Psychol 1996; 8: 37–54. Scand 1999; 78: 180–185.
North Am 2010; 37: 255–267. 31. Beddoe AE, Yang CPP, Kennedy HP, 47. Williams KA, Petronis J, Smith D,
15. Pivarnik JM, Chambliss HO, Clapp JF et Wiss SJ, Lee KA. The effects of mind- Goodrich D, Wu J, Ravi N. Effect of
al. Special communications, Roundtable fulness-based yoga during pregnancy Iyengar yoga therapy for chronic low
consensus statement. Impact of physical on maternal psychosocial and physical back pain. Pain 2005; 115: 107–117.
activity during pregnancy and postpar- distress. JOGNN 2009; 38: 310–319. 48. Hall DC, Kaufmann DA. Effects of
tum on chronic disease risk. Med Sci 32. Grote NK, Bridge JA, Gavin AR, Melville aerobic and strength conditioning on
Sports Exerc 2006; 38: 989–1006. JL, Iyengar S, Katon WJ. A meta-analysis pregnancy outcomes. Am J Obstet
16. Devlin JT. Effects of exercise on insulin of depression during pregnancy and the Gynecol 1987; 157: 1199–1203.
sensitivity in humans. Diabetes Care risk of preterm birth, low birth weight, 49. Clapp JF. The course of labor follow-
1992; 15: 1690–1693. and intrauterine growth restriction. Arch ing endurance exercise during preg-
17. Dempsey JC, Butler CL, Sorensen TK Gen Psychiatry 2010; 67(10): 1012–1024. nancy. Am J Obstet Gynecol 1990; 163:
et al. A case-control s