Lifestyle Medicine - 2019

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Lifestyle Medicine
Lifestyle Medicine
Third Edition
Edited by
James M. Rippe, MD
CRC Press
Taylor & Francis Group
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Boca Raton, FL 33487-2742
© 2019 by Taylor & Francis Group, LLC

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Library of Congress Cataloging‑ i n‑ P ublication Data
Names: Rippe, James M., editor.

Title: Lifestyle medicine / [edited by] James M. Rippe.
Other titles: Lifestyle medicine (Rippe)
Description: Third edition. | Boca Raton : Taylor & Francis, 2019. | Includes
bibliographical references.
Identifiers: LCCN 2018043101| ISBN 9781138708846 (hardback : alk. paper) |
ISBN 9781315201108 (General eISBN) | ISBN 9781351781008 (pdf) | ISBN
9781351780995 (epub) | ISBN 9781351780988 (mobi/kindle)
Subjects: | MESH: Primary Prevention | Health Promotion | Health Behavior |
Healthy Lifestyle
Classification: LCC RA427 | NLM WA 108 | DDC 610--dc23
LC record available at https://lccn.loc.gov/2018043101
Visit the Taylor & Francis Web site at

http://www.taylorandfrancis.com
and the CRC Press Web site at

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Dedication
To my beautiful wife, Stephanie Hart Rippe, and our wonderful children

Hart, Jaelin, Devon, and Jamie who make my life worth living.
Contents
Preface.............................................................................. xiii Chapter 10: Effects of an Active Lifestyle on Water
Acknowledgments........................................................... xvii Balance and Water Requirements................................... 135
About the Editor................................................................ xix Gethin H. Evans, BSc, PhD, Ronald J. Maughan, BSc,
Contributors...................................................................... xxi PhD, and Susan M. Shirreffs, BSc, PhD
Part I Lifestyle Management and Part III Physical Activity

Prevention of Cardiovascular Disease Edward M. Phillips, MD
James M. Rippe, MD
Chapter 11: Implementation of the Exercise
Chapter 1: The Rationale for Intervention to Reduce Prescription...................................................................... 147
the Risk of Cardiovascular Disease..................................... 3 Rachele M. Pojednic, PhD, EdM, Caroline R. Loveland,
James M. Rippe, MD and Theodore J. Angelopoulos MS, and Sarah Tierney Jones, BS
PhD, MPH
Chapter 12: What Physicians Need to Know, Do, and
Chapter 2: Lifestyle Strategies for Risk Factor Say to Promote Physical Activity..................................... 153
Reduction, Prevention and Treatment of Mary A. Kennedy, MS
Cardiovascular Disease..................................................... 19
James M. Rippe, MD and Theodore J. Angelopoulos, Chapter 13: Physical Fitness Evaluation.......................... 163
PhD, MPH Peter Kokkinos, PhD and Jonathan Myers, PhD
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 4: Clinical Strategies for Managing

Dyslipidemias..................................................................... 53 Part IV Behavioral Medicine
Ulf G. Bronas, PhD, ATC, FSVM, FAHA, Elizabeth Pegg Frates, MD
Mary Hannan, MSN, APN, AGACNP-BC, and
Arthur S. Leon, MS, MD, FACSM Chapter 15: Behavior Change.......................................... 193
Elizabeth Pegg Frates, MD and
Chapter 5: Lifestyle Management and Prevention of James E. Eubanks Jr., DC, MS
Hypertension...................................................................... 65
Ulf G. Bronas, PhD, ATC, FSVM, FAHA, Chapter 16: Applying Psychological Theories to
Mary Hannan, MSN, APN, AGACNP-BC, and Promote Healthy Lifestyles.............................................. 197
Arthur S. Leon, MS, MD, FACSM Maryam Gholami, PhD, Cassandra Herman, MS,
Matthew Cole Ainsworth, MPH, Dori Pekmezi, PhD,
Part II Nutritional Aspects of Lifestyle Medicine and Sarah Linke, PhD, MPH
James M. Rippe, MD
Chapter 17: Motivational Interviewing and Lifestyle
Change............................................................................. 207
Chapter 6: The Concept of Nutritional Status and Its
Peter Fifield, EdD, LCMHC, MLADC, Joji Suzuki, MD,
Measurement..................................................................... 77
Samantha Minski, PhD, and Jennifer Carty, PhD
Johanna T. Dwyer, DSc, RD and Regan L. Bailey, PhD,
RD, MPH, CPH
Chapter 18: Transtheoretical Model................................ 219
Chapter 7: Dietary Guidelines for Americans, James O. Prochaska, PhD and Janice M. Prochaska, PhD
2015–2020: National Nutrition Guidelines....................... 101
Elizabeth B. Rahavi, RDN, Jean M. Altman, MS, and Chapter 19: The Impact of Positive Psychology on
Eve E. Stoody, PhD Behavioral Change and Healthy Lifestyle Choices......... 229
Shelley H. Carson, PhD, Andrea Cook, PhD, Stephanie
Chapter 8: Nutrition and Cardiovascular Disease............111 Peabody, PsyD, Sandra Scheinbaum, PhD, and
James M. Rippe, MD Leslie Williamson, BA
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 46: Exercise, Aging, and Immunity.................... 563

Part XII Cardiovascular Rehabilitation and
Jeffrey A. Woods, PhD, Yi Sun, PhD, and Brandt D.
Pence, PhD
Secondary Prevention
Kathy Berra, MSN, NP-BC, FAANP,
FPCNA, FAHA, FAAN and
Part X Pulmonary Medicine Barry A. Franklin, PhD
Nicholas A. Smyrnios, MD, FACP, FCCP Chapter 60: Medication Dosing and Adherence in
Secondary Prevention..................................................... 735
Chapter 47: Respiratory Symptoms................................ 573
Ozlem Bilen, MD and Nanette K. Wenger, MD, MACC,
Jeremy B. Richards, MD and Richard M. Schwartzstein,
MACP, FAHA
MD
Chapter 61: Using Digital Health Technology to
Chapter 48: Asthma......................................................... 589
Promote Cardiovascular Disease Risk Reduction in
David E. Ciccolella, MD and Gilbert E. D’Alonzo, DO
Secondary Prevention......................................................741
Neil F. Gordon, MD, PhD, MPH, FACC, Richard D.
Chapter 49: Occupational and Environmental Lung
Salmon, DDS, MBA, Mandy K. Salmon, ChBE, and
Diseases........................................................................... 611
Prabakar Ponnusamy, MS
Sunkaru Touray, MBChB, MSc, Emil Tigas, MD, and
Nicholas A. Smyrnios, MD, FACP, FCCP
Chapter 62: Psychosocial Risk Factors as
Modulators of Cardiovascular Outcomes in
Chapter 50: Venous Thromboembolic Disease............... 621
Secondary Prevention..................................................... 751
Joseph Gallant, MD and Ryan Shipe, MD
Joel W. Hughes, PhD, FAACVPR and David Ede, Jr., BS
Chapter 51: Influenza....................................................... 631
Chapter 63: A Patient’s Perspective on the Keys
Gail Scully, MD, MPH
to Longevity 40 Years after Undergoing Coronary
Artery Bypass Surgery..................................................... 761
Chapter 52: Indoor Air Quality......................................... 639
Joseph C. Piscatella, BA
Anthony C. Campagna, MD, FCCP and Dhruv Desai, MD
Chapter 64: Lipid Management in Secondary
Prevention........................................................................ 767
Part XI Obstetrics and Gynecology Paul D. Thompson, MD and Antonio B. Fernandez, MD
Amanda McKinney, MD, FACLM, FACOG, CPE
Chapter 65: Complementary Effects of Lifestyle
Chapter 53: Antenatal Care—Nutrition and Lifestyle Modification on Cardioprotective Medications in
to Improve Conception and Pregnancy Outcomes......... 653 Primary/Secondary Prevention........................................ 771
Amanda McKinney, MD, FACLM, FACOG, CPE Xisui Shirley Chen, MD and Philip Greenland, MD
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 102: Health Promotion Introduction................ 1169

Dee W. Edington, PhD Part XIX Injury Prevention
David A. Sleet, PhD, FAAHB
Chapter 103: Health Promotion: History and
Emerging Trends.............................................................1171 Chapter 115: Injuries and Lifestyle Medicine................. 1293
Michael Parkinson, MD, MPH, FACPM David A. Sleet, PhD, FAAHB
xii Contents
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
Steven A. Adelman, MD Carissa M. Baker-Smith, MD, MS, MPH, FAAP,

Director of Massachusetts Physician Health Services FAHA
Clinical Associate Professor of Psychiatry Assistant Professor of Pediatrics
University of Massachusetts Medical School Division of Cardiology
Worcester, Massachusetts University of Maryland School of Medicine
Baltimore, Maryland
Matthew Cole Ainsworth, MPH
Doctoral Trainee Christie Mitchell Cobb, MD
Department of Health Behavior Partner
University of Alabama at Birmingham Little Rock Gynecology & Obstetrics
Birmingham, Alabama Little Rock, Arkansas
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
Theodore J. Angelopoulos, PhD, MPH Mark Berman, MD, FACLM

Professor & Chair Head of Health
Department of Rehabilitation and Movement Sciences Better Therapeutics, LLC
University of Vermont San Francisco, California
Burlington, Vermont
Kathy Berra, MSN, NP-BC, FAANP, FPCNA, FAHA,
Katherine R. Arlinghaus, MS, RD, LD FAAN
Department of Health and Human Performance Co-Director
University of Houston The LifeCare Company
Houston, Texas Nurse Practitioner
Cardiovascular Medicine and Coronary Interventions
Redwood City, CA
Regan L. Bailey, PhD, RD, MPH, CPH Stanford Prevention Research Center
Associate Professor of Nutrition Science Stanford University School of Medicine (Ret)
Purdue University Menlo Park, California
West Lafayette, Indiana
Ozlem Bilen, MD
Elizabeth A. Baker, PhD, MPH Cardiology Fellow
Professor and Chair, Behavioral Science and Health Department of Medicine
Education Division of Cardiology
Saint Louis University School of Public Health Emory University School of Medicine
St. Louis, Missouri Atlanta, Georgia
xxi
xxii Contributors
Kristin Bixel, MD Debora S. Bruno, MD, MS

Division of Gynecologic Oncology Assistant Professor of Medicine and Oncology
Department of Obstetrics and Gynecology Hematology/Oncology Division
Ohio State University Department of Medicine
Columbus, Ohio Case Western Reserve University
School of Medicine
Richard Boles, PhD MetroHealth Medical Center
Associate Professor, Pediatrics-Nutrition Cleveland, Ohio
University of Colorado School of Medicine
Aurora, Colorado Wayne N. Burton, MD, FACP, FACOEM
Former Global Corporate Medical Director
Heather R. Bowles, PhD American Express Company
Epidemiologist Chicago, Illinois
Biometry Research Group
Division of Cancer Prevention Andrew M. Busch, PhD
National Cancer Institute Hennepin Healthcare
Bethesda, Maryland University of Minnesota Medical School
St Paul, Minnesota
Allyson G. Box, BS
Graduate Student Anthony C. Campagna, MD, FCCP
Department of Kinesiology and Community Health PCCM Fellowship, Program Director
University of Illinois Urbana-Champaign Department of Pulmonary and Critical Care Medicine
Urbana, Illinois Lahey Hospital and Medical Center
Burlington, Massachusetts
Matthew J. Breiding, PhD, CDR, US
Public Health Service Karen Carlson, MD
Traumatic Brain Injury Team Lead Assistant Professor
Division of Unintentional Injury Prevention Obstetrics & Gynecology
National Center for Injury Prevention & Control University of Nebraska Medical College
Centers for Disease Control & Prevention Nebraska Medicine Obstetrics & Gynecology
Atlanta, Georgia Omaha, Nebraska
Shelley H. Carson, PhD

Jenna Brinks, MS, FAACVPR
Associate
Business Manager
Department of Psychology
Heart & Vascular Services
Lecturer in Extension
Beaumont Hospital
Harvard University
Royal Oak, Michigan
Cambridge, Massachusetts
Ulf G. Bronas, PhD, ATC, FSVM, FAHA Jennifer Carty, PhD
Associate Professor Behavioral Health Fellow
The University of Illinois at Chicago University of Massachusetts Medical School
College of Nursing Worcester, Massachusetts
Department of Biobehavioral Health Science
Chicago, Illinois
Paulette Chandler, MD, MPH
Assistant Professor of Medicine
Julie A. Brothers, MD Harvard Medical School
Assistant Professor of Pediatrics and Medical Director Division of Preventive Medicine
Lipid Heart Clinic Associate Epidemiologist and Associate Physician
The Perelman School of Medicine at the University of Phyllis Jen Center of Primary Care
Pennsylvania Brigham and Women’s Hospital
The Children’s Hospital of Philadelphia Boston, Massachusetts
Philadelphia, Pennsylvania
Chwen-Yuen Angie Chen, MD, FACP, FASAM
Austin L. Brown, MPH, PhD Primary Care and Population Health in the Department
Instructor of Medicine
Department of Pediatrics Hematology & Oncology Medical Director of Primary Care Chemical Dependency
Baylor College of Medicine Program
Houston, Texas Stanford University School of Medicine
Contributors xxiii
Xisui Shirley Chen, MD Andrea Cook, PhD

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
David E. Ciccolella, MD Sarah C. Couch, PhD, RD

Department of Thoracic Medicine and Surgery Professor and Vice Chair
Temple Lung Center Graduate Program Director
Louis Katz School of Medicine Department of Rehabilitation, Exercise and Nutrition
Temple University Sciences
Philadelphia, Pensylvannia University of Cincinnati
Cincinnati, Ohio
Joseph T. Ciccolo, PhD, CSCS
Assistant Professor of Movement Science and Kinesiology
Department of Biobehavioral Sciences Alex E. Crosby, MD, MPH
Teachers College Medical Epidemiologist
Columbia University Centers for Disease Control and Prevention (CDC)
New York, New York National Center for Injury Prevention and Control
(NCIPC)
Daniel B. Clarke, MBA Division of Violence Prevention (DVP)
Executive Chef Atlanta, Georgia
Spaulding Rehabilitation Hospital
Boston, MA Nina Crowley, PhD, RDN, LD
University of Massachusetts, Boston, MA (MBA) Surgery Program Coordinator Metabolic and Bariatric
The Culinary Institute of America Surgery
Hyde Park, New York Medical University of South Carolina
Charleston, South Carolina
Matthew M. Clark, PhD
Professor of Psychology
Chair for Research Gilbert E. D’Alonzo, DO
Department of Psychiatry and Psychology Department of Thoracic Medicine and Surgery
Mayo Clinic Temple Lung Center
Rochester, Minnesota Louis Katz School of Medicine
Temple University
Paul M. Coen, PhD Philadelphia, Pennsylvania
Translational Research Institute for Metabolism &
Diabetes Dana Dabelea, MD, PhD
AdventHealth Conrad M. Riley Professor of Epidemiology and
Orlando, Florida Pediatrics
Director
Lola A. Coke, PhD, ACNS-BC, CVRN-BC, FAHA,
Lifecourse Epidemiology of Adiposity and Diabetes
FPCNA, FAAN
(LEAD) Center
Associate Professor
Colorado School of Public Health
Johns Hopkins School of Nursing
University of Colorado Anschutz Medical Campus
Baltimore, Maryland
Aurora, Colorado
Katherine A. Collins, MS, CBDT
Graduate Student Researcher Stephen R. Daniels, MD, PhD
University of Pittsburgh Chair
Department of Health and Physical Activity Department of Pediatrics
Healthy Lifestyle Institute University of Colorado School of Medicine
Physical Activity and Weight Management Research Pediatrician-in-Chief
Center Children’s Hospital Colorado
Pittsburgh, Pennsylvania Aurora, Colorado
xxiv Contributors
Cindy D. Davis, PhD Patricia M. Dubbert, PhD

Director of Grants and Extramural Activities Associate Director for Research Training
Office of Dietary Supplements Professor (Retired)
National Institutes of Health South Central Veterans Affairs Mental Illness, Research,
Bethesda, Maryland Education, and Clinical Center
Department of Psychiatry
Paul G. Davis, PhD, ACSM-CEP University of Arkansas for Medical Science
Associate Professor Little Rock, Arkansas
Department of Kinesiology
The University of North Carolina at Greensboro Wesley D. Dudgeon, PhD
Greensboro, North Carolina Associate Professor and Chair
Department of Health and Human Performance
R. Sue Day, MS, PhD College of Charleston
Professor of Epidemiology Charleston, South Carolina
The University of Texas Health Science Center at
Houston (UTHealth) Beth Baughman DuPree, MD, FACS, ABOIM
School of Public Health Adjunct Assistant Professor
Department of Epidemiology, Human Genetics & University of Pennsylvania
Environmental Sciences Medical Director
Southwest Center for Occupational and Environmental Oncology Service Line Northern Arizona Healthcare
Health VP Holy Redeemer Health System
Michael & Susan Dell Center for Healthy Living Sedona, Arizona
Houston, Texas
Johanna T. Dwyer, DSc, RD
Eco J.C. De Geus, PhD
Senior Nutrition Scientist (contractor)
Professor
Office of Dietary Supplements NIH
Department of Biological Psychology
Bethesda, Maryland
Vrije Universiteit
Amsterdam, The Netherlands
David Ede, Jr., BS
Ann M. Dellinger, PhD, MPH Graduate Student
Division of Unintentional Injury Prevention Department of Psychological Sciences
National Center for Injury Prevention and Control Kent State University
Centers for Disease Control and Prevention Kent, Ohio
Atlanta, Georgia
Dee W. Edington, PhD
Marleen H.M. de Moor, PhD Professor Emeritus
Assistant Professor University of Michigan
Section of Clinical Child and Family Studies, Methods Principal, Edington Associates
Faculty of Behavioural and Movement Sciences Ann Arbor, Michigan
Vrije Universiteit Amsterdam
Amsterdam, The Netherlands Ingrid Edshteyn, DO, MPH
Associate Physician
Dhruv Desai, MD Department of Medicine
Fellow Center for Human Nutrition
Department of Pulmonary and Critical Care Medicine David Geffen School of Medicine at UCLA
Lahey Hospital and Medical Center Los Angeles, California
Burlington, Massachusetts
Saria El Haddad, MD
Nikhil V. Dhurandhar, PhD Instructor
Professor and Chair Harvard Medical School
Department of Nutritional Sciences Department of Psychiatry
Texas Tech University Brigham and Women’s Faulkner Hospital
Lubbock, Texas Boston, Massachusetts
Elizabeth A. Dodson, PhD, MPH Jane Ellery, PhD

Research Assistant Professor Project For Public Spaces
Brown School and Prevention Research Center in St. and
Louis School of Kinesiology
Washington University in St. Louis Ball State University
St. Louis, Missouri Muncie, Indiana
Contributors xxv
Peter J. Ellery, PhD, MLA John P. Foreyt, PhD

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
Joseph Gallant, MD George Guthrie, MD, MPH, CDE, CNS, FAAFP,

University of Massachusetts Medical School FACLM
Division of Pulmonary, Allergy, and Critical Care President
Medicine American College of Lifestyle Medicine
Worcester, Massachusetts Centre for Family Medicine
Florida Hospital Medical Group
Katharina Gaudlitz, M.Sc Florida Hospital Graduate Medical Education
Dr. rer. medic University of Central Florida
Zentrum fuer Angst- und Depressionsbehandlung Winter Park, Florida
Zuerich (ZADZ)
Switzerland Matthew Allen Haemer, MD, MPH
Associate Professor
University of Colorado School of Medicine
Maryam Gholami, PhD Department of Pediatrics
Department of Family Medicine and Public Health Section of Nutrition
University of California, San Diego Medical Director
La Jolla, California Lifestyle Medicine Level One Weight Management
Program
Samuel Gidding, MD Children’s Hospital Colorado
Chief Aurora, Colorado
Division of Pediatric Cardiology
Department Nemours Cardiac Center Kori Hahn, BS, MS
Alfred I. duPont Hospital for Children Master of Science Candidate
Wilmington, Delaware Department of Health and Human Performance
University of Tennessee at Chattanooga
Chattanooga, Tennessee
Neil F. Gordon, MD, PhD, MPH, FACC
INTERVENT International
Aaron F. Hajart, MS, ATC, FACNA
Savannah, Georgia
Assistant Dean, Clinical Strategy and Development
and
Office of Clinical Affairs
Centre for Exercise Science and Sports Medicine
Rutgers New Jersey Medical School
School of Therapeutic Sciences
Newark, New Jersey
University of the Witwatersrand
Johannesburg, South Africa
Sadia Haider, MD, MPH
Associate Professor
Wayne Gordon, PhD, ABPP/Cn Chief, Family Planning and Contraceptive Research
Jack Nash Professor and Vice Chair Department of Obstetrics and
Department of Rehabilitation Medicine Gynecology
Icahn School of Medicine at Mount Sinai University of Chicago Medicine
New York, New York The University of Chicago
Chicago, Illinois
Philip Greenland, MD
Harry W. Dingman Professor Kara C. Hamilton, PhD
Department of Preventive Medicine Assistant Professor, Department of Health and Human
Northwestern University Performance
Feinberg School of Medicine University of Tennessee at Chattanooga
Chicago, Illinois Chattanooga, Tennessee
Gregory A. Hand, PhD, MPH, FACSM, FESPM

Angela Grone, MD, FACOG
Professor
Obstetrician/Gynecologist
Department of Epidemiology
Beatrice Women’s & Children’s Clinic
Robert C. Byrd Health Sciences Center
Beatrice Community Hospital and Health Center
West Virginia University
Beatrice, Nebraska
Morgantown, West Virginia
Virginia F. Gurley, MD, MPH Mary Hannan, MSN, APN, AGACNP-BC

AxisPoint Health and HGS Healthcare PhD student
Lisle, Illinois Department of Biobehavioral Health Science
College of Nursing
University of Illinois at Chicago
Chicago, Illinois
Contributors xxvii
Deborah Hasin, PhD Jessica L. Hildebrandt, MS, RD

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
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
Director of Integrative Medicine
University of Tennessee at Chattanooga
Holy Redeemer Health System
Meadowbrook, Pennsylvania
Cassandra Herman, MS Jason R. Jaggers, PhD

Doctoral Trainee Assistant Professor
Department of Health Behavior Department of Health & Sport Sciences
University of Alabama at Birmingham University of Louisville
Birmingham, Alabama Louisville, Kentucky
xxviii Contributors
John M. Jakicic, PhD Christopher M. Kaipust, MPH

Distinguished Professor and Chair Predoctoral Fellow
Department of Health and Physical Activity The University of Texas Health Science Center at
Director Houston (UTHealth) School of Public Health Division
Healthy Lifestyle Institute of Epidemiology, Human Genetics, & Environmental
and Sciences
Director Southwest Center for Occupational and Environmental
Physical Activity and Weight Management Research Health
Center Michael & Susan Dell Center for Healthy Living
University of Pittsburgh Houston, Texas
Pittsburgh, Pennsylvania
Heidi J. Kalkwarf, PhD
Jo Marie Tran Janco, MD Professor
Clinical Fellow Department of Pediatrics
Department of Obstetrics, Gynecology, University of Cincinnati College of Medicine
and Reproductive Biology Division of Gastroenterology, Hepatology
Beth Israel Deaconess and Nutrition
Medical Center Cincinnati Children’s Hospital Medical Center
Harvard Medical School Cincinnati, Ohio
Nattinee Jitnarin, PhD Sandeep (Anu) Kaur, MS, RDN, RYT-500

Principal Investigator Nutritionist
National Development and Research Institutes, Inc. Nutritional Science Research Group
Institute for Biobehavioral Health Research Division of Cancer Prevention
Leawood, Kansas National Cancer Institute
National Institutes of Health
Sarah Tierney Jones, BS Rockville, Maryland
Exercise Physiologist
Simmons University Maureen K. Kayes, MS
Boston, Massachusetts Department of Kinesiology
University of Maryland
Stephanie-Marie L. Jones, MD College Park, Maryland
Clinical Fellow
Department of Obstetrics, Gynecology
Case H. Keltner, MPH
and Reproductive Biology
MD Candidate
Beth Israel Deaconess
Oregon Health & Science University School
Medical Center
of Medicine
Harvard Medical School
Portland, Oregon
Elizabeth A. Joy, MD, MPH, FACSM Elizabeth Kelley, MS, ACSM-RCEP

Medical Director Lab Manager
Community Health, Health Promotion & Wellness, Food Health and Human Performance
& Nutrition College of Charleston
Intermountain Healthcare Charleston, South Carolina
Salt Lake City, Utah
John Kelly, MD, MPH
Jill Landsbaugh Kaar, PhD Oak Haven Lifestyle Medicine Center
Assistant Professor American College of Lifestyle Medicine
Department of Pediatrics Preventive Medicine
University of Colorado Anschutz Medical Campus Loma Linda University, California
Aurora, Colorado
Mary A. Kennedy, MS
Sergey Kachur, MD Institute of Lifestyle Medicine
Assistant Professor of Medicine at the University of Harvard Medical School
Central Florida Boston, MA
Associate Program Director of the Internal Medicine and
Residency Program Exercise Medicine Research Institute
Department of Graduate Medical Education Edith Cowan University
Ocala Regional Medical Center Joondalup, Western Australia
Ocala, Florida Australia
Contributors xxix
Wesley C. Kephart, PhD Karen L. Lawson, MD, ABIHM, NBC-HWC

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
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
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
Ron Loeppke, MD, MPH, FACOEM, FACPM Sanchit Maruti, MD, MS

Vice Chairman Assistant Professor of Psychiatry
U.S Preventive Medicine, Inc. Larner College of Medicine at the University of Vermont
Jacksonville, Florida Attending Psychiatrist, Inpatient service
and
Elise Loiselle, RN, MSN, FNP-C Medical Director
Nurse Practitioner Addiction Treatment Program
Spaulding Rehabilitation Hospital University of Vermont Medical Center
Massachusetts General Hospital Burlington, Vermont
Director- Open Learning Academy
Matt M. Longjohn, MD MPH Executive Director- Institute for Human and Planetary
Adjunct Assistant Professor of Pediatrics Northwestern Health
University Feinberg School of Medicine; Senior Doane University
Director, Chronic Disease Prevention Programs, Crete, Nebraska
Activate America, YMCA of the USA
Robert G. McMurray, PhD
Caroline R. Loveland, MS Professor Emeritus
Graduate Assistant Departments of Nutrition and Exercise and Sport Science
Department of Nutrition University of North Carolina
Simmons University Chapel Hill, North Carolina
Jeffrey I. Mechanick, MD, FACP, FACE, FACN,
ECNU
Angela Lumba-Brown, MD Professor of Medicine
Clinical Assistant Professor; Medical Director, The Marie-Josee and Henry R.
Department of Emergency Medicine Kravis Center for Cardiovascular Health at Mount
Clinical Assistant Professor of Sinai Heart
Pediatrics and
Stanford University School of Medicine Director, Metabolic Support
Palo Alto, California Division of Cardiology, Endocrinology, Diabetes, and
Bone Disease
Emily Maddux, MS, MPH, RD, LDN Icahn School of Medicine at Mount Sinai
Lecturer, Nutrition/Dietetics New York, New York
University of Tennessee at Chattanooga Darshan Mehta, MD
Chattanooga, Tennessee Medical Director of Medical Education
Benson-Henry Institute for Mind Body Medicine
Melissa M. Markofski, PhD Massachusetts General Hospital
Assistant Professor and
Department of Health and Human Performance Associate Director of Education
University of Houston Osher Center for Integrative Medicine
Houston, Texas Instructor in Medicine
Brigham and Women’s Hospital
Irena Matanovic Boston, Massachusetts
Master of Clinical Psychology degree candidate
Harvard Extension School Richard V. Milani, MD
Boston, Massachusetts Chief Clinical Transformation Officer
Ochsner Health System
Ronald J. Maughan, BSc, PhD Vice-Chairman
Visiting Professor Department of Cardiovascular Diseases
School of Medicine John Ochsner Heart and Vascular Institute
St. Andrews University Ochsner Clinic Foundation
St. Andrews, UK New Orleans, Louisiana
Contributors xxxi
Jonathan R. Miller, PhD Neil Nedly, MD

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
Division of Endocrinology
Samantha Minski, PhD Northwestern University
Behavioral Health Fellow Feinberg School of Medicine
Department of Family Medicine and Community Health Chicago, Illinois
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
Magdalena Pasarica, MD, PhD

James M. Muchira, MSN, PhD candidate Associate Professor of Medicine
PhD Program in Nursing (Population Health Track) Director
College of Nursing and Health Sciences Internal/Family Medicine Clerkship
University of Massachusetts Boston and
Boston, Massachusetts Medical Director
KNIGHTS student-run free clinic
Eileen Stellefson Myers, MPH, RDN, LDN, CEDRD, Family Medicine Chair of Education FMIG Advisor
FADA, FAND University of Central Florida
Private Practice College of Medicine
Nashville, TN Orlando, Florida
David Paulk, PA-C, EdD, DFAAPA

Jonathan Myers, PhD Professor and Founding Director
Director MSPA Program
Exercise Research Laboratory Murphy Deming College of Health Sciences
Division of Cardiology Mary Baldwin University
VA Palo Alto Health Care System Fishersville, Virginia
Palo Alto California
Stephanie Peabody, PsyD
Academy of Brain Health and Performance
Harvard Extension School
Cambridge, Massachusetts
xxxii Contributors
Dori Pekmezi, PhD Prabakar Ponnusamy, MS

Associate Professor Chief Technical Officer
University of Alabama at Birmingham INTERVENT International
Department of Health Behavior Savannah, Georgia
School of Public Health
Birmingham, Alabama James O. Prochaska, PhD
Cancer Prevention Research Center
Clinical Psychology
Brandt D. Pence, PhD
The University of Rhode Island
Assistant Professor of Nutrition
Pro-Change Behavior Systems, Inc.
School of Health Studies
Prochaska Change Consultants
The University of Memphis
Kingston, Rhode Island
Memphis, Tennessee
Janice M. Prochaska, PhD
Steven J. Petruzzello, PhD The University of Rhode Island
Department of Kinesiology and Community Health Pro-Change Behavioral Systems, Inc.
University of Illinois Urbana-Champaign Prochaska Change Consultants
Urbana, Illinois Mill Valley, California
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
Emory University School of Medicine
University of Texas Southwestern Medical Center
Atlanta, Georgia
Dallas, Texas
Joseph C. Piscatella, BA Jeremy B. Richards, MD

Founder and President Assistant Professor of Medicine
Institute for Fitness and Health Division of Pulmonary, Critical Care, and Sleep
Gig Harbor, Washington Medicine
Beth Israel Deaconess Medical Center
Jennifer S. Pitts, PhD
Founder
Institute for Positive Organizational Health Marcie K. Richardson, MD
and Assistant Clinical Professor in Obstetrics, Gynecology,
Co-Founder and Reproductive Biology
Edington Associates Harvard Medical School
Cambria, California and
Obstetrician
Rachele M. Pojednic, PhD, EdM Harvard Vanguard Medical Associates/Atrius Health
Department of Nutrition Department of Obstetrics and Gynecology
Simmons University Beth Israel Deaconess Medical Center
Boston, Massachusetts Boston, Massachusetts
Contributors xxxiii
James M. Rippe, MD Robert Scales, PhD

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
Sharon Ross, PhD, MPH Alyssa B. Schultz, PhD

Program Director Research Scientist
Nutritional Sciences Research Group Global Health Management Research Core
Division of Cancer Prevention Ann Arbor, Michigan
National Cancer Institute
National Institutes of Health
Department of Health and Human Services Nienke Schutte, PhD
Rockville, Maryland Postdoctoral Researcher
Department of Biological Psychology
Mandy K. Salmon, ChBE Vrije Universiteit Amsterdam
Analyst Amsterdam, The Netherlands
INTERVENT International
Savannah, Georgia Richard M. Schwartzstein, MD
Ellen and Melvin Gordon Professor of Medicine
Richard D. Salmon, DDS, MBA Harvard Medical School
Chief Operations Officer Associate Chief
INTERVENT International Division of Pulmonary, Critical Care and Sleep Medicine
Savannah, Georgia Beth Israel Deaconess Medical Center
Nicholas J. SantaBarbara, MS
Doctoral Research Fellow
Department of Biobehavioral Science Andiara Schwingel, PhD
Teachers College Associate Professor
Columbia University Department of Kinesiology and Community Health
New York, New York University of Illinois at Urbana-Champaign
Champaign, Illinois
Kelly Sarmiento, MPH
Health Communications Specialist Gail Scully, MD, MPH
Traumatic Brain Injury Team Assistant Professor
Division of Unintentional Injury Prevention Department of Medicine
National Center for Injury Prevention & Control Division of Infectious Disease
Centers for Disease Control & Prevention University of Massachusetts Medical School
Atlanta, Georgia Worcester, Massachusetts
Katherine A. Sauder, PhD
Assistant Professor Ryan Shipe, MD
Pediatric Nutrition School of Medicine
University of Colorado School of Medicine University of St. Andrews
Aurora, Colorado St. Andrews, UK
xxxiv Contributors
Susan M. Shirreffs, BSc, PhD Lisa Staimez, PhD, MPH

School of Medicine Assistant Professor
University of St. Andrews Hubert Department of Global Health
St. Andrews, UK Rollins School of Public Health
Emory University
Dexter Shurney, MD, MBA, MPH Atlanta, Georgia
Senior Vice President/Chief Medical Officer
Zipongo, Inc. Barbara A. Stetson, PhD
and Associate Professor
Former Chief Medical Director Department of Psychological and Brain Sciences
Executive Director Global Health and Wellness University of Louisville
Cummins, Inc Louisville, Kentucky
and
President-elect Courtenay Stewart, DO
American College of Lifestyle Medicine Chief Resident Physician
San Francisco, California Department of Orthopaedic Surgery
Physical Medicine & Rehabilitation Division
Stanford Health Care
Stacey L. Simon, PhD
Stanford, California
Assistant Professor
Pulmonary Medicine
Deborah M. Stone, ScD, MSW, MPH
Children’s Hospital Colorado
Behavioral Scientist
University of Colorado Anschutz Medical Campus
Division of Violence Prevention (DVP)
Aurora, Colorado
Centers for Disease Control and Prevention (CDC)
Sara C. Slatkin, MD (NCIPC)
Internal Medicine Atlanta, Georgia
The Permanente Medical Group
Campbell, California P. Michael Stone, MD, MS, IFMCP
Ashland Comprehensive Family Medicine
David A. Sleet, PhD, FAAHB Ashland, Oregon
Consultant to the National Center for Injury Prevention
& Control Eve E. Stoody, PhD
Centers for Disease Control & Prevention Lead Nutritionist
Atlanta, Georgia Nutrition Guidance and Analysis
and Center for Nutrition Policy and Promotion
Scholar-in-Residence U.S. Department of Agriculture
Evidence-Based (EB) Medicine Alexandria, Virginia
Norcross, Georgia
Andreas Ströhle, MD
Jonas Sokolof, DO Leitender Oberarzt
Assistant Attending Physician Department of Psychiatry and Psychotherapy
Department of Neurology Charité – Universitätsmedizin Berlin
Rehabilitation Service Berlin, Germany
Memorial Sloan-Kettering Center
Assistant Professor of Clinical Rehabilitation Medicine Yi Sun, PhD
Weill Cornell Medical College Doctoral Student
New York, New York Department of Kinesiology and Community Health
Integrative Immunology and Behavior Program
University of Illinois at Urbana-Champaign
Urbana, Illinois
Professor of Medicine
Associate Chief, Division of Pulmonary, Allergy, and
Joji Suzuki, MD
Critical Care Medicine
Director
and
Division of Addiction Psychiatry
Medical Director, Medical Intensive Care Units
Assistant Professor of Psychiatry Harvard Medical
School
UMass Memorial Medical Center
Worcester, Massachusetts
Brigham and Women’s Hospital
Contributors xxxv
Charlotte A. Tate, PhD Margaret Loeper Vasquez, MS, RD, LDN

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
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
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
Matthijs D. van der Zee, MSc Sandra Weisser, MSEd, ATC

PhD Student Clinical Operations Manager
Department of Biological Psychology Office of Clinical Affairs
Vrije Universiteit New Jersey Medical School
Amsterdam, The Netherlands Rutgers
The State University of New Jersey
Newark, New Jersey
xxxvi Contributors
Nanette K. Wenger, MD, MACC, MACP, FAHA Emily Wu, MD

Professor of Medicine (Cardiology) Emeritus Child and Adolescent Psychiatry Fellow
Emory University School of Medicine Department of Psychiatry
Consultant Harvard Longwood Psychiatry Residency Training
Emory Heart and Vascular Center Program
Founding Consultant Harvard Medical School
Emory Women’s Heart Center Massachusetts General Hospital
Atlanta, Georgia Boston, Massachusetts
Gary B. Wilkerson, EdD, ATC Henry Xiang, MD, MPH, PhD

Graduate Athletic Training Program Professor of Medicine
Department of Health & Human Performance Department of Pediatrics
University of Tennessee at Chattanooga The Ohio State University College of Medicine
Chattanooga, Tennessee Director of Center for Pediatric Trauma Research
Director of Research Core
Risa Wilkerson, MA Center for Injury Research and Policy
Project Officer The Research Institute at Nationwide Children’s Hospital
Active Living by Design, North Carolina Institute for Columbus, Ohio
Public Health
University of North Carolina Gillings School of Global Merissa A. Yellman, MPH
Public Health Synergy America, Inc.
Chapel Hill, North Carolina Division of Unintentional Injury Prevention
Leslie Williamson, BA Centers for Disease Control and Prevention
Academy for Brain Health and Performance Atlanta, Georgia
Center for School Success
Lebanon, New Hampshire Patricia Zheng, MD
Assistant Professor
Ruth Wolever, PhD Department of Orthopaedic Surgery
Director of Vanderbilt Health Coaching: Practice, University of California – San Francisco
Research & Education San Francisco, California
Osher Center for Integrative Medicine
Associate Professor Physical Medicine & Rehabilitation Robert F. Zoeller Jr., PhD
and Department of Psychiatry Professor and Graduate Coordinator
Vanderbilt Schools of Medicine and Nursing Department of Exercise Science and Health Promotion
Nashville, Tennessee Florida Atlantic University
Boca Raton, Florida
Jeffrey A. Woods, PhD
Professor of Kinesiology
Department of Kinesiology and Community Health
Integrative Immunology and Behavior Program
Division of Nutritional Sciences
Carle-Illinois College of Medicine
University of Illinois at Urbana Champaign
Champaign, Illinois
I
PA RT
Lifestyle Management and Prevention

of Cardiovascular Disease
James M. Rippe, MD
1
1
CHAPTER
The Rationale for Intervention to Reduce

the Risk of Cardiovascular Disease
James M. Rippe, MD and Theodore J. Angelopoulos PhD, MPH
Key Points...................................................................................... 3 1.8.1 Age......................................................................... 11

1.1 Introduction............................................................................ 3 1.8.2 Gender.................................................................... 11
1.1.1 The Pathophysiology of Atherosclerosis......................... 4 1.8.3 Family History......................................................... 11
1.2 Understanding Risk Factors.................................................... 5 1.9 The Metabolic Syndrome and the Concept of Multiple
1.2.1 The Concept of Risk Factors.......................................... 5 Risk Factors........................................................................ 11
1.2.2 Relative Risk versus Absolute Risk................................ 5 1.10 Emerging Risk Factors........................................................ 12
1.2.3 Primary versus Secondary Prevention........................... 5 1.10.1 High Sensitivity C-Reactive Protein (hs-CRP)............ 12
1.3 Primordial Prevention and “Ideal” Cardiovascular Health......... 5 1.10.2 Other Markers of Inflammation................................ 12
1.4 Implementing Risk Factor Reduction Guidelines...................... 6 1.10.3 Hemostatic Factors.................................................. 12
1.5 The Scientific Basis for Risk Factor Reduction......................... 6 1.10.4 Homocysteine......................................................... 12
1.6 Evidence-Based Versus Risk-Based Strategies for 1.10.5 LDL Subclasses and Particle Size............................ 12
Prevention of Cardiovascular Disease..................................... 6 1.10.6 Lipoprotein (a)......................................................... 12
1.7 Modifiable Risk Factors........................................................... 6 1.11 Other Risk Factors.............................................................. 12
1.7.1 Tobacco Use.................................................................. 6 1.11.1 Levels of Antioxidants.............................................. 13
1.7.2 Dyslipidemias................................................................ 7 1.11.2 Alcohol.................................................................... 13
1.7.2.1 Elevated Low Density Lipoprotein 1.11.3 Stress and Type A Personality.................................. 13
Cholesterol and Hyperlipidemia�� 7 1.11.4 Depression.............................................................. 13
1.7.2.2 Low Levels of HDL Cholesterol......................... 7 1.12 Future Trends in Risk Factor Assessment............................ 13
1.7.2.3 Hypertriglyceridemia........................................ 7 1.12.1 Direct Plaque Imaging............................................. 13
1.7.3 Hypertension................................................................. 7 1.12.2 Genomic Approaches............................................... 13
1.7.4 Diabetes and Glucose Intolerance.................................. 8 1.12.3 New Risk Factor Scoring Systems........................... 14
1.7.5 Obesity.......................................................................... 9 1.12.4 Implementation of Risk Factor Reduction Strategies......14
1.7.6 Inactive Lifestyle........................................................... 9 1.13 Conclusions........................................................................ 14
1.7.7 Poor Nutritional Habits................................................. 10 Clinical Applications..................................................................... 14
1.8 Nonmodifiable Risk Factors.................................................. 11 References.................................................................................. 14
maintain proper weight, 2 do not smoke cigarettes, 3

KEY POINTS engage in regular physical activity, and4 follow
sound nutritional patterns.
• Cardiovascular Disease (CVD) remains the leading
• The American Heart Association (AHA) has recom-
cause of death and disability in the United States
mended an emphasis on “primordial prevention,”
and worldwide.
which means lowering the likelihood of developing
• Multiple risk factors increase the risk of CVD.
risk factors in the first place.
Many of these risk factors have a significant lifestyle
• Physician visits are an ideal opportunity to stress
component.
the importance of lifestyle habits and practices to
• There has been a significant decrease in CVD mortal-
reduce the risk of cardiovascular disease.
ity over the past four decades. Half of this decrease
is due to lower risk factors. Increases in several risk
factors, however, including obesity and diabetes,
threaten to wipe out gains in all other risk factors. 1.1 INTRODUCTION
• If individuals used the following four positive daily
lifestyle measures, the prevalence of CVD could be Cardiovascular disease (CVD) remains the leading cause
decreased over 80% and the prevalence of diabetes of death for both men and women in the United States
could be decreased over 90%. The measures are1 each year.1 Over 37% of all mortality in the United States
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.
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.
1.4 IMPLEMENTING RISK FACTOR 1.7.1 Tobacco Use

REDUCTION GUIDELINES Cigarette smoking is the leading preventable cause of
death from all causes in the United States and the single
Another welcome trend in the area of risk factor reduction
most prevalent modifiable risk factor for the develop-
comes from the Dietary Guidelines for Americans 2015, 50
ment of CVD.60 CVD causes 35–40% of smoking-related
Physical Activity Guidelines for Americans 2008,10,51 and
deaths and an additional 8% have been attributed to sec-
the American Heart Association Scientific Statement on
ondhand smoke exposure.61–63
Implementing Pediatric and Adult Nutrition Guidelines.52
Unfortunately, following many years of declines in
All three of these guidelines have emphasized real-world,
cigarette smoking prevalence in the United States, the
practical implementation of guidelines. This is an impor-
percentage of adults who smoke has recently stabilized at
tant and new emphasis from these three widely read and
about 19%.64 Rates of tobacco use are actually increasing
influential documents.
among adolescents, young adults, and women.13
The link between cigarette smoking and increased
risk of CVD has been established in multiple studies.
1.5 THE SCIENTIFIC BASIS FOR Individuals who consume 20 or more cigarettes per day
RISK FACTOR REDUCTION increase their risk for CVD by 2–3 times. Framingham
Study data demonstrated that cardiovascular mortality
Multiple observational and interventional studies, includ- increases 31% in women and 18% in men for each ten
ing the Framingham Study, 53 the Nurses Health Study, 54 cigarettes smoked per day.65 Multiple observational stud-
the U.S. Male Professional Follow-Up Trial, and the ies have also shown that smokeless tobacco and low tar
Women’s Health Initiative, 55 have all demonstrated the cigarettes do not reduce the risk of CVD.
link between risk factors and developing CVD as well as Numerous studies have demonstrated that smok-
the power of reducing risk factors to reduce the likelihood ing cessation improves longevity and reduces the risk of
of developing CVD. Results from these and other studies CVD.66 Thus, stopping cigarette smoking remains the sin-
form the basis for recommendations in the following sec- gle most important intervention in preventive cardiology
tions on specific risk factors. and lifestyle medicine. Smoking cessation yields signifi-
cant benefits in a relatively short period of time.67 In one
study comparing 1,282 cigarette smokers to 2,068 con-
1.6 EVIDENCE-BASED VERSUS trols, the risk of developing CVD among those individuals
stopping cigarette smoking approached the level of never
RISK-BASED STRATEGIES smokers within three years.66 In addition to contributing
FOR PREVENTION OF greatly to the risk of CVD, cigarette smoking also signifi-
cantly increases the likelihood of developing lung cancer
CARDIOVASCULAR DISEASE and chronic obstructive pulmonary disease.
Despite the important and powerful health benefits
As new evidence has become available over the last decade, of cigarette smoking cessation, the medical community
some have argued that guidelines for strategies to prevent has not been active enough in this area. The Centers for
cardiovascular disease should be based on clinical trial Disease Control and Prevention (CDC) estimates that only
1.7 Modifiable Risk Factors 7
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
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
1.7.5 Obesity Distribution of body fat is also strongly and indepen-
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.
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
TABLE 1.4 Classification of levels of physical activity

Classification of total weekly
amounts of aerobic physical Summary of
activity into four categories Range of moderate-intensity overall health
levels of physical activity minutes a week benefits Comment
Inactive No activity beyond baseline None Being inactive is unhealthy.
Low Activity beyond baseline but Some Low levels of activity are clearly preferable to an
fewer than 150 minutes a week inactive lifestyle.
Medium 150 minutes to 300 minutes a Substantial Activity at the high end of this range has
week additional and more extensive health benefits
than activity at the low end.
High More than 300 minutes a week Additional Current science does not allow researchers to
identify an upper limit of activity above which
there are no additional health benefits.
Source: 2008 Physical Activity Guidelines for Americans.

1.9 The Metabolic Syndrome and the Concept of Multiple Risk Factors 11
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
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
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
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2
CHAPTER
Lifestyle Strategies for Risk Factor

Reduction, Prevention and Treatment
of Cardiovascular Disease
James M. Rippe, MD and Theodore J. Angelopoulos, PhD, MPH
Key Points.................................................................................... 19 2.5.3 Physical Inactivity....................................................... 30

2.1 Predicting Risk..................................................................... 21 2.5.4 Moderate Alcohol Consumption................................... 31
2.2 Assessing Risk...................................................................... 21 2.6 Class 3 Interventions............................................................ 31
2.3 Classifying Interventions for Modifiable Risk Factors............. 21 2.6.1 Nutritional Counseling................................................. 31
2.4 Class 1 Interventions............................................................ 21 2.6.2 Psychological Risk Factors/Counseling........................ 31
2.4.1 Lifestyle Approach to Cigarette Smoking Cessation..... 21 2.7 Post Menopausal Estrogen Therapy...................................... 31
2.4.2 Lifestyle Approach to Management of Dyslipidemias.......24 2.8 Determinants of Behavior Change......................................... 32
2.4.3 Lifestyle Management of Hypertension....................... 26 2.9 Establishing A Lifestyle Medicine Emphasis in
2.4.4 Pharmaceutical Measures for Cardiac Protection........ 28 Clinical Practice.................................................................... 32
2.5 Class 2 Interventions............................................................ 28 2.10 Summary............................................................................ 32
2.5.1 Obesity Prevention and Management.......................... 28 Clinical Applications..................................................................... 32
2.5.2 Diabetes/Glucose Intolerance...................................... 29 References.................................................................................. 33
Lifestyle strategies can play a significant role in the

KEY POINTS reduction of risk factors for CVD as well as in preven-
tion and effective treatment of the disease. In Chapter 1,
• Lifestyle strategies play a significant role in reducing
“The Rationale for Intervention to Reduce the Risk of
risk factors for cardiovascular disease (CVD).
Cardiovascular Disease,” we focused on the rationale for
• Lifestyle interventions are key components of the
employing lifestyle strategies for risk factor reduction. The
American Heart Association’s strategic plan for
current chapter provides practical strategies for employing
2020 to lower the burden of cardiovascular disease
these modalities in clinical practice for the prevention and
in the United States.
treatment of CVD.
• Lifestyle strategies are a key component for both
Lifestyle interventions also represent an important
the prevention and treatment of metabolic diseases
strategy for physicians and other health care workers to
and are recognized as such by virtually every major
use in assisting patients to lower their risk factors. These
national, evidence-based guideline in metabolic
interventions are also helpful in preventing CVD and
diseases.
treating individuals with established CVD. The lifestyle-
• In addition to annual fasting lipid profile, high-
related strategies discussed here are particularly valuable
sensitivity CRP (hs-CRP) should be obtained, since
since they carry very little risk and may simultaneously
levels of hs-CRP are the equivalent risk of LDL
reduce multiple risk factors for CVD. Furthermore, the
cholesterol.
American Heart Association (AHA) has articulated a
• Assessment and counseling for factors for CVD
vision to pursue “primordial” risk factors, meaning the
should be a part of every health care visit.
prevention of risk factors in the first place. Lifestyle mea-
sures will be key components of this strategy.7
Cardiovascular disease (CVD) remains the leading killer
Lifestyle measures are already incorporated, either
of men and women in the United States.1 CVD also rep-
prior to or in conjunction with pharmaceutical therapy,
resents one of the quintessential lifestyle related diseases,
as key recommended early intervention steps in most of
since many of the risk factors for it, including cigarette
the major, evidence-based guidelines that are designed to
smoking, 2 elevated cholesterol, 3 high blood pressure,4
help patients lower the risk of CVD.3,4,8–15 Unfortunately,
obesity5 and an inactive lifestyle,6 have significant life-
many health care workers still do not properly emphasize
style-related components.
these measures in their daily clinical practices. In addition,
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
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.
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.
long-term smoking abstinence. These are bupropion

TABLE 2.2 Framework for risk factor reduction
hydrochloride,53 Varenicline, and five nicotine replacement
interventions. See text for details
therapies (nasal spray, gum, patch, inhaler, and lozenges).54
Class 1 Interventions The efficacy of smoking cessation programs ranges from
• Cigarette smoking cessation 6% for one year’s success with physician counseling alone,
• Management of dyslipidemias to 18% with self-help programs, to 20–40% with coun-
• Management of hypertension
seling plus pharmacologic intervention.55 All individuals
• Pharmaceutical measures for cardiac protection
who smoke should, of course, be counseled to cease this
Class 2 Interventions deadly habit. A particularly appropriate time to encourage
• Obesity prevention and management patients to make this effort is after a cardiac event or dis-
• Diabetes/glucose intolerance management
• Physical inactivity
covery of existing cardiovascular disease.
The Healthy People 2020 Initiative has established
Class 3 Interventions a goal for the United States of reducing the national
• Nutritional counseling
prevalence of cigarette smoking among adults to under
• Psychological risk factors/counseling
• No alcohol consumption 12%. Achieving this ambitious goal will require exten-
sive implementation of evidence-based tobacco control
Class 4
interventions. Some advances in tobacco control have
• Age
• Male gender occurred recently in the United States, including imple-
• Low socioeconomic status mentation of the 2009 Family Smoking Prevention and
• Family history of early onset CVD Tobacco Control Act, which granted the U.S. Food and
Drug Administration (FDA) authority to regulate the
manufacture, distribution, and marketing of tobacco
between men and women.47 The 1989 Surgeon General’s products.55 Other laws include the Children’s Health
Report showed that smoking doubles the risk of CVD and Insurance Reauthorization Act, the Prevent All Cigarette
increases CVD mortality by 50%.44 Both of these risks Trafficking Act, and the Patient Protection and Affordable
increase with age and the number of cigarette smoked. Care Act. These laws grant various federal agencies both
More than one million more deaths worldwide were authority and funding to regulate tobacco products and
attributable to tobacco in the year 2000 than in 1990.47 decrease access to tobacco among youth. In 2010, the
Tobacco use is estimated to be responsible for five million U.S. Department of Health and Human Services entered a
deaths worldwide per year.48 In the United States, ciga- National Strategic Plan for Tobacco Control, including 21
rette smoking peaked in 1955, reaching 55% of men. The Action Steps to accomplish this goal.
peak for women came ten years later with more than 33%
smoking. Since that time cigarette smoking has substan-
tially declined, but the rate of decline has slowed substan- 2.4.2 Lifestyle Approach to
tially in the past decade.
Currently in the United States, 19% of adults smoke.49
Management of Dyslipidemias
Slightly more of these individuals are men than women. Average cholesterol levels among adult men and women
Approximately 16.5 percent of women over the age of 18 in the United States have decreased to some degree since
smoke and approximately 21.6% of men over the age of the 1960 s but are still considered higher than good health
18 years old smoke.49 If individuals do not smoke ciga- requires. Agrarian societies have very low rates of CVD
rettes by the time they graduate from high school, it is and exhibit total and LDL cholesterol levels well below
highly unlikely that they will adopt this habit as adults. those accepted as normal in Western societies.
Smoking rates among high school seniors are slightly Currently, approximately 45% of all American adults
above 30%, with more female smokers than males. 50 still have cholesterol levels greater than 200 mg/dL, and
Smoking also tracks with socioeconomic status. Thirty- 16% have levels higher than 240 mg/dL. 56 In addition,
two percent of individuals living below the federal poverty both depressed HDL cholesterol levels and elevated tri-
line are smokers. glyceride levels often occur together and result from dif-
The U.S. Public Health Service has published clini- ferent metabolic pathways than are typically involved in
cal practice guidelines classifying tobacco dependency elevated LDL. These latter two lipid abnormalities are
as a chronic condition requiring repeated intervention.51 particularly associated with the metabolic syndrome.
These guidelines recommend that health care profession- Various organizations have listed somewhat different
als ask every patient about tobacco use at every clinic recommendations for cholesterol screenings. There is wide
visit. 52 Counseling and behavior therapies are based on agreement that all patients with currently existing CVD
the following: should be periodically screened for serum cholesterol lev-
els. The NCEP ATP-III Guidelines recommend that all
1. Securing social support adults older than 20 years should be routinely screened for
2. Providing problem solving skills serum cholesterol. 3 The American College of Physicians
3. Social support outside treatment (ACP) provides less aggressive screening recommenda-
tions with advice that men between the ages of 35 and 65
According to the U.S. Public Health Service guidelines, be screened and women between the ages of 45 and 65 be
which support a combination of counseling and pharma- screened.57 The USPSTF advocates screening women over
ceutical therapy, seven pharmacotherapies reliably increase the age of 45 and men over the age of 35. 52
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.
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
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
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
Figure 2.4 Trends in adult overweight and obesity ages 20 to 74 years.
Source: National Center for Health Statistics No permission needed.

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
Figure 2.5 Trends in Childhood Overweight.
Source: National Center for Health Statistics No permission needed.
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
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
2.8 DETERMINANTS OF BEHAVIOR publications have suggested ways that interested physi-

cians can incorporate more lifestyle medicine strategies
CHANGE into their daily practice of medicine.139–141
The evidence supporting lifestyle therapies for reduction
The belief that it is possible to change patient behavior of risk of CVD is diverse and powerful. Moreover, an empha-
provides the fundamental underpinnings to the concept sis on the linkages between daily lifestyle habits and practices
of utilizing lifestyle measures to help patients adopt posi- and the risk of CVD is incorporated in virtually all of the evi-
tive lifestyle behaviors to lower the risk of CVD or as an dence-based guidelines for treating CVD and its risk factors
adjunct to the treatment of established CVD. A detailed as well as reducing the risk of other metabolic diseases.3–15
review of the literature in this area is beyond the scope of The American Heart Association has also included positive
the current chapter. However, this literature has been very lifestyle measures as a fundamental component of its stra-
well summarized in a variety of other publications.136–138 tegic plan for 2020 for improving the cardiovascular health
A variety of theoretical constructs provides the foun- of the nation.7 Finally, the Accountable Care Organizations
dation for behavioral therapy.136–138 These include: provision of the recent Affordable Care Act outlines that
health care organizations and individual providers are man-
• Cognitive behavioral therapy (which assumes that dated to increase involvement in this area.142 The Guidelines
behavior is learned and can, therefore, be unlearned for Physical Activity 2008117 as well as the Dietary Guidelines
through cognitive and behavioral strategies) for Americans 2015,69 provide fundamental, evidence-based
• Social cognitive theory (this is based on the assump- approaches to lifestyle related issues and should be the foun-
tion that behavior is the result of interaction of per- dation for every health care worker’s increasing emphasis on
sonal and behavior factors as well as environmental these strategies in their daily practice.
influences) There has been a recent impetus on incorporating
• Transtheoretical theory (stages of change; based on models of Intensive Therapeutic Lifestyle Change (ITLC)
accurately placing an individual along the path of into the practice of medicine. Several recent publications
various stages of change).137 have provided guidance into the rationale for employing
these strategies as well as methods for including them and
Familiarity with these theoretical constructs, as well potential outcomes.143,144
as techniques of motivational interviewing, provides use-
ful underpinnings and a practical framework for incorpo-
rating lifestyle change messages in clinical practice.
2.10 SUMMARY
An extensive body of scientific literature supports the con-
2.9 ESTABLISHING A LIFESTYLE cept that positive lifestyle measures are highly effective in
MEDICINE EMPHASIS IN lowering multiple risk factors for CVD as well as serving
as components of therapy for individuals who already have
CLINICAL PRACTICE established CVD. These interventions carry the substantial
advantages of being low cost, carrying virtually no adverse
As already indicated, physicians can play a particularly side effects, and often simultaneously ameliorating multi-
powerful role by recommending and monitoring lifestyle- ple risk factors for CVD. The key imperative for physicians
related changes for reduction in the risk of CVD. While and other health care workers is to commit to learning
challenges remain, including lack of time, inadequate how to incorporate counseling concerning these lifestyle
reimbursement models, and so on, it is clear that health measures in clinical practice and establishing strategies to
care professionals need to move in this direction. Recent bring this valuable body of information to their patients.
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.
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3
CHAPTER
Physical Activity and Fitness in the

Prevention of Cardiovascular Disease
Robert F. Zoeller Jr., PhD
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
their knowledge of the benefits of exercise, only about

25% demonstrated adequate knowledge useful for patient
counseling.10
Healthcare professionals need to promote physical
activity with all of their patients. In that regard, an under-
standing of the health benefits associated with physi-
cal fitness and regular physical activity is fundamental.
This chapter reviews the evidence linking greater physical
activity and fitness with primary prevention of cardiovas-
cular and metabolic disease through effective risk factor
management. Recommendations for exercise are also pro-
vided both in general terms and for specific conditions.
Figure 3.1 Estimated Dose–Response Curve for the Relative

Risk of either CHD or CVD by Sample Percentages of
3.1 PHYSICAL FITNESS VS. Fitness and Physical Activity. Studies weighted by Person-
PHYSICAL ACTIVITY Years of Experience.
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
3.2.1 Adults of men engaging in moderate-to-vigorous activity three or
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
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
3.5.1 Resistance Exercise Training 3.7 DIABETES

and Blood Pressure The latest available data from NHANES estimates that
Resistance training is generally recommended as an 12.8% of Americans over the age of 19 have diabetes
adjunct to aerobic activity. On average, studies have mellitus (DM), of which > 90% are classified as Type II
reported three mmHg reductions in resting systolic and (T2DM).1 Insulin resistance often precedes the onset
DBP following progressive weight lifting programs.33,40 – 42 of T2DM and is prevalent in the prediabetic states of
Although this decrease may seem small, a three mmHg impaired fasting glucose (IFG) and impaired glucose tol-
reduction lowers the risk of CHD, stroke, and all-cause erance (IGT). Over 35% of Americans are classified as
mortality.33 Two to three days per week of total body resis- pre-diabetic, with IFG and/or IGT.1 This means that more
tance training is generally recommended.16,43– 45 However, than 47% of all adults have some degree of abnormal gly-
as with aerobic exercise, the “optimal” exercise prescrip- coregulation!1 The prevalence of CHD has been estimated
tion for strength training is not known. More specifically, to be as high as 55% in adult diabetics, and T2DM is
low-to-moderate intensity strength training (30–40% of a an independent risk factor for myocardial infarction and
one repetition maximum (1RM) for upper body exercises, CVD in both men and women. 51,52 T2DM is a predictor
and 50–60% 1RM for lower body exercises) is currently of ischemic stroke and heart failure, and DM increases
recommended by some for the prevention and manage- the overall CV risk in patients with preexisting heart
ment of high blood pressure30,45 Rezk et al.46 showed that failure.53,54 Compared to non-diabetics, mortality from
both single bouts of high- or low-intensity resistance exer- CHD has been reported to be twice as great in diabetic
cise lower SBP, but only low-intensity training lowered men and four to five times greater in diabetic women.55
DBP. Other studies reported that high-intensity resistance Cardiovascular disease is responsible for at least two-
training reduced neither SBP nor DBP, and actually raised thirds of deaths in adults with DM. 55
SBP in some individuals.47
The currently recommended strength training program
to optimize BP reduction is one to three sets of 10–15 3.7.1 The Metabolic Syndrome,
repetitions for each of the major muscle groups (thighs
[hamstrings and quadriceps], hips, back, chest, arms, and
CVD, and T2DM
abdominals), two to three days per week.33,45 The clustering of risk factors known as the metabolic
syndrome (see section below for definition and more
information) is predictive of both T2DM and CVD. It
3.6 HEART FAILURE is associated with a twofold increase in the risk for car-
diovascular events.56 Abdominal obesity, in particular, is
It’s estimated that some 5.7 million Americans suffer from an independent risk factor for insulin resistance57,58 and
heart failure (HF, also known as congestive heart failure).1 T2DM. 59 Much of the increased risk of CHD and CVD
The risk of developing HF increases with age; by the age of associated with T2DM can be attributed to the presence
40, both men and women have a one in five risk of devel- of the metabolic syndrome.60 One study reported ten-year
oping HF at some time in their lives.1 Both the incidence cardiovascular mortality to be 3.55 times greater in men
and prevalence of HF are particularly high in minorities, with metabolic syndrome compared to those without the
especially African-Americans.1 Heart failure occurs ear- condition.61
lier and mortality is higher in African-Americans than in Numerous studies have demonstrated an inverse rela-
Caucasians.1 tionship between physical activity and/or fitness and the
Surprisingly few studies have examined the relation- risk for developing T2DM.62–70 Men of low fitness have
ship between physical activity and primary prevention a two to three times greater risk of developing T2DM
of heart failure. Two large longitudinal studies exploring compared to those in the higher fitness categories.62,63
this association found that compared to sedentary indi- Similarly, physical activity shares an inverse relation-
viduals, those who engaged in regular vigorous exercise ship with the risk for T2DM in a dose-response manner.
had a 15–35% lower risk for developing heart failure.48,49 Even just daily walking for more than 30 minutes has
Vigorous activity was defined as activities “vigorous been shown to reduce the risk of developing T2DM by
enough to work up a sweat,”48 such as running, jogging, 20–45%.66,69–72 Brisk/faster walking was associated with
swimming, heavy gardening or competitive sports.”49 The a lower risk independent of time spent walking.66,69,70 In
reduction in risk was correlated with the frequency of an interventional trial involving 18 previously sedentary
vigorous exercise in a dose-response manner.48 Activity middle-aged men and women, six months of walking
of a moderate intensity, defined as > 4 hr/week of walk- (minimum of three days per week for 30 minutes) resulted
ing, cycling, or light gardening was associated with ~15% in improved insulin sensitivity.73 Sedentary behaviors such
reduction in risk. Pooled data from three large cohort as excessive television watching have been demonstrated
studies showed a strong and negative dose-response rela- to increase the risk for T2DM even after controlling for
tionship between LTPA and risk for heart failure. Those diet and physical activity levels. It has been estimated
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
3.9.1 The “Fitness vs. Fatness” debate 3.9.3 Physical Activity and

It is well established that both increased body fat and low
levels of physical activity and/or fitness are associated with
Sustained Weight Loss
increased mortality and with T2DM and CVD. However, Unfortunately, most studies do not support increasing
it is not precisely clear as to the relative importance of physical activity, either alone or in combination with a
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-intention 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).
The clustering of established risk factors for CVD and

T2DM has been recognized for decades.151–166 In 1988, 3.11.2 Current Prevalence Estimates
Gerald Reaven drew immense attention to risk fac- It is estimated that close to one billion people world-
tor clustering and CVD in his now famous “Banting wide have the metabolic syndrome.176 Global prevalence
Lecture” at the annual meeting of the American Diabetes estimates of the metabolic syndrome vary considerably,
Association.155 He described a constellation of risk fac- depending on the population under study, the definition
tors leading to development of T2DM and CVD which he applied, and the study design utilized. Using the NCEP
termed Syndrome X. Reaven postulated the etiology and definition, the age-adjusted prevalence for the metabolic
clinical course of three major related diseases—T2DM, syndrome in the United States is estimated to be 34.6%.
CVD, and hypertension, all having a common foundation These data also showed a 10% increase in the prevalence
of insulin resistance and hyperinsulinemia. However, at of the metabolic syndrome in U.S. adults, from 1988 to
that time, adiposity was not considered a major etiologi- 2002. With the metabolic syndrome becoming more com-
cal factor. mon in westernized societies,176 the prevalence and inci-
The metabolic syndrome has been recognized as dence are anticipated to increase in line with the prevalence
a global public health problem that is strongly linked and incidence of obesity176 and T2DM.177
as a seminal cause of CVD and T2DM, both of which
are responsible for premature mortality and morbidity
worldwide.167–169 The metabolic syndrome is character- 3.11.3 Physical Activity and Prevalence
ized by the clustering of specific cardiovascular risk fac-
tors, including insulin resistance (IR), central obesity,
of the Metabolic Syndrome
hypertension, and atherogenic dyslipidemia (specifically, The association between physical activity or inactivity
elevated triglycerides and low levels of high-density lipo- and prevalence of the metabolic syndrome is not clear, at
protein cholesterol (HDL-C).169–174 Also, depending on the least based on cross-sectional studies.178–186 In most stud-
medical society definition applied, microalbuminuria may ies, the initial analysis often shows a negative relationship
also be considered another risk factor.174 between physical activity level and the prevalence or risk
of metabolic syndrome, but this association typically dis-
appears after controlling for other factors such as gender,
3.11.1 Different Medical Society Definitions age, education, socioeconomic status, or other risk factors
(e.g., smoking).
of the Metabolic Syndrome Several longitudinal studies showed that increased
In establishing an official diagnosis for the meta- levels of physical activity, especially of vigorous inten-
bolic syndrome, the American Association of Clinical sity, were associated with significantly and dramatically
Endocrinologists (AACE) championed the creation of the reduced risk for developing the metabolic syndrome and
International Classification of Disease 9th revision (ICD-9) in a dose-response manner. Interventional studies are
Code 277.7 for the metabolic syndrome.173 Currently, fewer in number, but at least one study showed that 20
there are five working medical society definitions pro- weeks of vigorous exercise performed for 30 minutes three
posed for the diagnosis of the metabolic syndrome. times per week resulted in a decreased prevalence of the
Table 3.1 summarizes the various definitions published metabolic syndrome (16.9% to 11.8%) in 621 men and
by the following medical societies: (1) the World Health women aged 17 to 65 years.177 That is, of the 105 par-
Organization (WHO),174 (2) the European Group for the ticipants with the metabolic syndrome at baseline, 32 no
Study of Insulin Resistance (EGIR),172 (3) the American longer had the syndrome at the end of the study.
TABLE 3.1 Metabolic syndrome definitions issued by various medical societies
WHO1999 EGIR 1999 ACE/AACE 2003 IDF 2005 AHA/NHLBI 2005
Requisite Criteria IGT, IFG, type 2 diabetes, Insulin in top quartile of a
High risk ;BM1 > 25 kg/m or 2 WC ≥ 94 cm (men) and ≥ 80 cm N/A
insulin in top quartile of population WC > 102 cm (men) or > 88 cm (women), and population-
population (women) specific for ethnic groups b
Other Criteria Plus ≥ 2 of: Plus ≥ 2 of: Plus ≥ 2 of: Plus ≥ 2 of: Plus ≥ 2 of:
Glucose N/A ≥100 mg/dL, 2-hour post ≥100 mg/dL, 2-hour post ≥100 mg/dL, diabetes ≥100 mg/dL, diabetes or Rx
OGTT ≥ 140 mg/dL but not OGTT ≥ 140 mg/dL but not
diabetes diabetes
Obesity W:H ratio > 0.9 (men) or >.85 WC ≥ 94 cm (men) or ≥ 80 cm N/A N/A WC ≥ 102 cm (men) or ≥ 88 cm
(women); BMI > 30 kg/m2 (women) (women)
Lipids TG ≥ 150 mg/dL and/or TG > 180 mg/dL and/or TG > 150 mg/dL or HDL-C < 40 TG ≥ 150 mg/dL or Rx or TG ≥ 150 mg/dL or HDL-C < 40
HDL-C < 35 mg/dL (men) HDL-C < 39 mg/dL in men or mg/dL (men) or < 50 mg/dL HDL-C < 40 mg/dL (men) or < 50 mg/dL (men) or < 50 mg/dL
or < 39 mg/dL (women) women or Rx (women) mg/dL (women) or Rx (women) or Rx
Hypertension ≥140/90 mmHg or Rx ≥140/90 mmHg or Rx >130/85 mmHg or Rx ≥130/85 mmHg or Rx ≥130/85 mmHg or Rx
Other Microalbuminaria ACR ≥ 30
mg/g
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
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
3.11.4 Cardiorespiratory Fitness and 3.11.5 Muscular Strength and the

the Metabolic Syndrome
The relationship between cardiorespiratory fitness, as mea-
Metabolic Syndrome
Evidence from the Aerobics Center Longitudinal Study
3
sured by VO2max, and the metabolic syndrome has not been (ACLS) suggests that even after controlling for age,
studied as extensively as that with physical activity. However, examination date, smoking status, alcohol intake, num-
cardiorespiratory fitness can be more objectively measured ber of metabolic syndrome risk factors at baseline, family
and may be more predictive of the metabolic syndrome history of diabetes, hypertension, and early onset coro-
than physical activity, per se. Cardiorespiratory fitness has nary artery disease, men above the 75th percentile for
been shown to be predictive of the metabolic syndrome, muscular strength have a 24% lower risk for developing
with men of low fitness (VO2max < 29.1 ml . kg−1 . min−1) the metabolic syndrome compared to men in the low-
being almost seven times more likely to have metabolic est strength category.187 Others have also illustrated the
syndrome compared with those men with a VO2max ≥ 35.5 benefits of resistance training and increases in muscular
ml . kg−1 . min−1.181 Over a four-year period, and after con- strength on metabolic risk.188–192 Muscular fitness appears
trolling for age, BMI, socioeconomic status, presence of to add another level of protection against the metabolic
CVD, smoking, and alcohol consumption, the incidence of syndrome in men and may help with daily and long-term
metabolic syndrome was found to be 47% and 75% lower glycemic control. However, strength training is recom-
in middle-aged men with a VO2max of 29.0 -35.6 and ≥ 37.0 mended as an adjunct to regular aerobic exercise but not
ml . kg−1 . min−1, respectively, compared with those men the sole or primary form of activity to prevent or manage
whose VO2max was less than 28.9 ml . kg−1 . min−1. the metabolic syndrome.193
The relationship between aerobic fitness and the preva-
lence of the metabolic syndrome appears to hold for women
as well. Women with a VO2max of 11 METs or greater had 3.12 CONCLUSION
a prevalence of the metabolic syndrome that was one-third
to one-fourth that of women of lower fitness.186 Cardiovascular disease, in all its forms, represents the
The precise amount and intensity of physical activity greatest threat, by far, to health and longevity in the
required to prevent or reverse the clustering of risk factors United States and the world. The major risk factors for
known as the metabolic syndrome has yet to be definitely CVD are well known, and their prevention and/or man-
determined. While there is evidence to suggest that regu- agement are crucial in reducing the prevalence of CHD,
lar, moderate-intensity physical activity (such as walking stroke, hypertension, and heart failure. Greater physical
30 minutes on most, if not every, day of the week) may be activity and especially greater cardiovascular fitness have
preventive of the metabolic syndrome, other evidence sug- been shown to significantly reduce the risk of CVD. The
gests that activity of greater intensity may be required to reduction in risk is largely mediated via the risk factors
optimally minimize risk. Greater cardiorespiratory fitness as described in this chapter. As such, an appropriate and
has demonstrated an even stronger negative association individually prescribed program of regular physical activ-
with the metabolic syndrome. Attainment of higher levels ity or exercise should be a standard lifestyle intervention
of fitness requires more vigorous physical activity.11 for individuals of all ages and abilities.
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4
CHAPTER
Clinical Strategies for

Managing Dyslipidemias
Ulf G. Bronas, PhD, ATC, FSVM, FAHA, Mary Hannan, MSN, APN, AGACNP-BC,
and Arthur S. Leon, MS, MD, FACSM
Key Points.................................................................................... 53 4.7.1 Impact of Diet (see also chapter on Nutrition and

4.1 Background.......................................................................... 53 Cardiovascular Disease)�� 57
4.2 Elevated Total and LDL Cholesterol....................................... 53 4.8 Weight Management............................................................. 59
4.3 High Density Lipoprotein....................................................... 54 4.8.1 Exercise Effects (see also chapter on Physical
4.4 Triglycerides......................................................................... 54 Activity and Fitness in the Prevention of
4.5 Non-HDL Cholesterol and Apo B............................................ 55 Cardiovascular Disease)�� 60
4.6 Lipid Classification and Treatment Targets............................ 55 4.9 Conclusions and Recommendations...................................... 60
4.7 Role of Lifestyle in the Management of Dyslipidemia............ 57 References.................................................................................. 61
lipoprotein carriers contributes significantly to the patho-

KEY POINTS physiology of atherosclerosis and the development and
progression of coronary heart disease (CHD).
1. Dyslipidemia in the form of abnormalities in total
cholesterol, lipoprotein (LDL), triglycerides (TG),
and/or a reduced level of high-density lipoprotein
(HDL) is a significant risk factor for coronary heart 4.2 ELEVATED TOTAL AND
disease (CHD).
2. Treatment of dyslipidemia is initiated depending on LDL CHOLESTEROL
cholesterol levels and overall cardiovascular risk.
3. Lifestyle management is a cornerstone treatment for Large-scale, long-term, longitudinal, observational stud-
dyslipidemia, including diet, exercise, maintaining a ies,3–7 have demonstrated a continuous, positive association
healthy weight, avoidance of tobacco, and modera- of TC with cardiovascular disease (from > 180 mg/dl, a 2%
tion of alcohol. increase in CHD risk for every 1% increase), even in the
4. Pharmacologic therapy for dyslipidemia focuses pri- presence of other major risk factors.3 Other observational
marily on the utilization of HMG-CoA reductase studies have indicated that a concentration of apolipopro-
inhibitor or statin drug therapy, with the addition tein B100 (apoB100) is an even stronger predictor of CHD
or utilization of alternate medications depending on than LDL-C.8,9 There also have been a number of studies
patient comorbidities and lipid profiles. that have shown an association of lipoprotein (α) (Lp [α])
with increased risk of CHD.8,10,11 Randomized, controlled
clinical trials using cholesterol-lowering drugs such as
4.1 BACKGROUND HMG-coenzyme A reductase inhibitors (statins), choles-
terol absorption inhibitors, cholestyramine, niacin, and
Dyslipidemia is defined as elevated fasting blood levels fibrates, have all been successful in reducing CHD risk.10–13
of total cholesterol (TC), low-density lipoprotein (LDL), A landmark meta-analysis that included the results
triglycerides (TG), and/or a reduced level of high-density of large-scale placebo-controlled, statin trials involv-
lipoprotein (HDL), alone or in combination. A high preva- ing > 30,000 participants over an average of 5.4 years indi-
lence of dyslipidemia exists in the United States, particu- cated that statin use resulted in a mean reduction of 30% in
larly elevated total cholesterol and low-density lipoprotein initial or recurrent CHD events.13 Further analysis indicated
C (LDL-C).1 There is generally a strong environmental/life- that this CHD reduction was primarily related to a 28%
style contribution to dyslipidemia, with a polygenic mode reduction in LDL-C, with some benefits being derived from
of inheritance. Familial hypercholesterolemia, an inherited a 20% reduction in TG and an increase of 5% in HDL-C.
monogenic, autosomal dominant form, is much less com- In addition, it should be noted that statin drugs have pleio-
mon.2 Although lipids contribute to many vital functions tropic anti-atherosclerotic effects, contributing to the reduc-
in the body, an abnormal blood level of lipids and their tion in the development and progression of CHD.14,15
53
54 Chapter 4 Clinical Strategies for Managing Dyslipidemias
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
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
Niacin. ↓5–25% ↑15–35% ↓20–50% Low Risk <130 <160 NR

(e.g., sustained-release)
Cholesterol absorption ↓20% ↑5% ± of HLD, utilizing HLD level treatment targets for dif-
inhibitor (eczetimibe)
ferent groups of patients.48 Depending on level of risk of
↑ = Increase, ↓ = Decrease, ± Variable, if any, Adapted from Gotto.26 For more atherosclerotic cardiovascular disease, there are speci-
details and precautions in use of these lipid management drugs, the reader is fied treatment goals for LDL-C, non-HDL-C, and
referred to Bettridge and Morrell.38
Apolipoprotein-B levels (Table 4.3). The AACE/ACE
guidelines recommend the utilization of any one of the
use of non-statin therapies, including ezetimibe, PCSK9 following four risk assessment tools: Framingham, Multi-
inhibitors, or bile acid sequestrants, for patients with Ethnic Study of Atherosclerosis, Reynolds Risk Score,
clinical CHD with comorbidities and LDL 70–189 mg/ or the United Kingdom Prospective Diabetes Study.48
dL or LDL-C ≥ 190 who are already on a statin and have A patient is categorized based on risk factors: a patient
not had a 50% reduction in LDL-C.18 The guidelines also with no risk factors is considered “low risk” and those
emphasize the importance of clinician-patient discussion with “extreme risk” are patients with progressive ath-
on pharmacologic therapy and risk reduction when add- erosclerotic cardiovascular disease after achieving an
ing non-statin therapies.18 LDL < 70 mg/d, L, those with cardiovascular disease in
The American Association of Clinical Endocrinologists patients with DM, CKD, or familial hypercholesterolemia,
and American College of Endocrinology (AACE, ACE) or those with history of premature atherosclerotic cardio-
Practice Guidelines for Managing Dyslipidemia and vascular disease.48 These guidelines support lower goals
Prevention of CVD of 2017 provided clinicians with addi- than other guidelines, particularly in the “extreme risk”
tional considerations and criteria for the management group, and support the use of coronary artery calcium
4.7 Role of Lifestyle in the Management of Dyslipidemia 57
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
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.
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.
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5
CHAPTER
Lifestyle Management and

Prevention of Hypertension
Ulf G. Bronas, PhD, ATC, FSVM, FAHA, Mary Hannan, MSN, APN, AGACNP-BC,
and Arthur S. Leon, MS, MD, FACSM
Key Points.................................................................................... 65 5.5.1 Effect of Sodium Restriction........................................ 69

5.1 Background.......................................................................... 65 5.5.2 Effects of Increased Dietary Potassium Intake............. 69
5.2 Measurement of Blood Pressure........................................... 66 5.5.3 Effects of Alcohol Consumption................................... 69
5.3 Etiology of Hypertension and Relationship to 5.5.4 Effect of Omega-3 Polyunsaturated Fatty Acids........... 69
Cardiovascular Disease......................................................... 66 5.6 Weight Management............................................................. 69
5.4 Physical Activity, Exercise, and Hypertension......................... 67 5.6.1 Complementary Therapies.......................................... 70
5.5 Dietary Modifications in the Prevention and 5.7 Pharmacological Management of Hypertension..................... 71
Management of Hypertension............................................... 68 References.................................................................................. 71
The 2014 Evidence-Based Guideline for the Management

KEY POINTS of High Blood Pressure in Adults (JNC-8),6 highlights the
importance of the lifestyle management recommenda-
1. Hypertension affects 50% of the U.S. population,
tions of the 2013 Lifestyle Work Group, which includes:
and the cornerstone therapy is lifestyle management.
(1) Consuming a diet high in vegetables, fruits, and whole
2. Physical activity and exercise training can reduce
grains; includes low-fat dairy, poultry, fish, legumes, non-
blood pressure through a variety of beneficial physi-
tropical vegetable oils, and nuts; and limits sweets, sugar-
ological mechanisms.
sweetened beverages, and red meat, (2) Consuming no
3. Healthy diets that follow a pattern of a high dietary
more than 2400 mg of sodium per day, and (3) Engaging
intake of fruits, vegetables, and whole grains are
in aerobic physical activity three to four times per week,
associated with lower blood pressure levels.
lasting on average 40 minutes per session of moderate-to-
4. Weight loss and maintaining a healthy body weight
vigorous-intensity physical activity.7
through comprehensive lifestyle changes improves
The 2017 ACC/AHA Guideline for the Prevention,
blood pressure levels.
Detection, Evaluation, and Management of High Blood
5. Although pharmacotherapy is a mainstay for the
Pressure in Adults has established classifications and treat-
treatment of hypertension, guidelines recommend that
ment thresholds (Table 5.1).8 This guideline also advocates
lifestyle interventions should be prescribed in conjunc-
for non-pharmacologic interventions to prevent and treat
tion with medications for patients with hypertension.
hypertension consisting of: (1) Weight loss to ideal body
weight, (2) DASH dietary pattern, (3) Reduced intake of
sodium to less than 1500 mg per day, (4) Enhanced intake
5.1 BACKGROUND of dietary potassium, (5) Physical activity consisting of
120–150 minutes per week of aerobic, 90–150 minutes
Hypertension is a well-established major risk factor for per week of dynamic resistance, and three sessions per
cardiovascular disease (CVD) morbidity and mortality.1– 4 week of isometric resistance, and (6) Moderation in alco-
Despite the fact that major advances have been made in hol intake.8
our understanding of hypertension and pharmacological Ideal blood pressure treatment targets were investi-
therapy, hypertension continues to be poorly controlled in gated through the randomized, controlled Systolic Blood
the approximately 75 million U.S. adults diagnosed with Pressure Intervention Trial (SPRINT) study with over
the condition.5 Pharmacotherapy has traditionally served 9,000 adults with a mean age of 67.9, who at baseline had
as the primary treatment modality for hypertension. This a systolic BP over of 130–180 and increased risk of cardio-
is despite strong evidence of the benefit of lifestyle modi- vascular events.9 The researchers sought to compare the
fications to reduce the incidence of hypertension and to influence of intensive treatment to achieve blood pressure
reduce blood pressure levels in individuals with estab- targets of SBP < 120 mmHg compared to standard tar-
lished hypertension. gets of SBP > 140 mmHg.9 The SPRINT trial was stopped
65
66 Chapter 5 Lifestyle Management and Prevention of Hypertension
TABLE 5.1 Adapted from 2017 ACC/AHA: Categories of BP in adults

BP classification SBP DBP Lifestyle habits Drug treatment
Normal BP <120 mmHg <80 mmHg Promote None
Elevated BP 120–129 mmHg <80 mmHg Yes None
Stage 1 hypertension 130–139 mmHg 80–89 mmHg Yes May be Indicated*
Stage 2 hypertension >=140 mmHg >=90 mmHg Yes Indicated+
Adapted from Whelton et al. 2017.8

* =Initiate pharmacological treatment if clinical ASCVD or estimated 10 year CVD risk > 10%.
+ Consideration of two medications from two different classes.
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
peripheral vascular resistance is postulated to be mediated

TABLE 5.2 Dietary Approaches to Stop Hypertension
by several factors, including:
(DASH) dietary plan
• Improved vascular endothelial function and arterial Nutrient Percentage of total caloric intake
elasticity/compliance
Total fat (% of total Kcal): 25–35%
• Due to increased nitric oxide (NO) synthase
activity from exercise-induced laminar shear- Saturated fat: < 7%
stress and prolonged NO activity via reduced Trans fats: < 1%
oxidative deactivation of NO, and reduction of
collagen deposition the media of the arteries Monounsaturated fats: 15%
• Reduction in endothelial derived endothelin-1 Polyunsaturated fats: 10% or less
• Attenuation of alpha-adrenergic receptor responsive
and reduced sympathetic tone (with an Omega-6 to 3
ratio of 3 to 4 to 1)
• Reduction in peripheral vascular resistance
• Improved baroreceptor reflex sensitivity Cholesterol (% of total ≤ 200 mg/d
• Reduced circulating catecholamines51,64 –71 Kcal):
Protein (% of total Kcal): About 18%
The effects of exercise training on the R-A-A system
are less well known. There have been a few reports of an Carbohydrates (% of 50–60%
exercise training-induced reduction in renin activity51 and total Kcal):
angiotensin-II activity in normotensive persons, but not Dietary fiber (g/day): 31 g/day
in hypertensive persons. 52 There also is an exercise train-
Potassium (mg/day): 4700 mg/day
ing-induced improvement in insulin sensitivity, which
has been associated with increased renal sodium excre- Calcium (mg/day): 500 mg/day
tion. 52,72 In addition, exercise training-induced vascular Sodium (mg/day): 1500–2400 mg/day
adaptations also include an increase in skeletal muscle
precapillary and capillary vessel numbers (i.e., angio- Number of servings per day based on 2,000 Kcal diet
genesis), and adaptations in vascular structure, including Daily Servings per NIH
vascular remodeling (arteriogenesis) resulting in a larger servings* DASH
conduit artery lumen diameter, which further contributes recommendations+
to reduced vascular resistance. 52,73 Fruits: 7–8 4–5
The genetic impact on the exercise-induced reduction
in blood pressure is not well known, and the interactions Vegetables: 4–5 4–5
between genes and environment are complex. It is plausi- Grains: 4–5 6–8
ble that genes affecting NO synthase activity are involved
in the blood pressure response to exercise training, as Low-fat dairy products: 2–3 2–3
shown by the Health Risk Factors Exercise Training and Meats, poultry, fish: <2 6 or less
Genetics (HERITAGE) Family Study.74,75
Nuts, seeds, dry beans: 4–5 4–5 per week
Fats, oils: 2–3 2–3
5.5 DIETARY MODIFICATIONS IN THE Sweets: <5 per week 5 or less per week
PREVENTION AND MANAGEMENT Total effect of blood pressure reduction using the DASH diet is approximately 11/6
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
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
TABLE 5.3 Clinical applications/lifestyle modifications for management of hypertension

Modification Recommendation Blood pressure reduction
Weight reduction Maintain a BMI between 18.5–24.9 5–20 mm Hg per 10kg weight loss
Healthy diet Consume a diet rich in fruits,
vegetables, and whole grains; 8–14 mm Hg
moderate in fat-free or low-fat dairy products;
reduced saturated fat and cholesterol, such as the
DASH dietary pattern
Exercise Regular aerobic exercise 120–150 min/week 4–9 mm Hg
Or 60–90 min/daily for weight reduction and
maintenance
Dynamic resistance exercise 90–150min/week
Isometric resistance exercise 3 sessions/week
Reduced sodium/salt intake Lower salt intake as much as possible 2–8 mm Hg
(1.5 g/d of sodium or 3.8 g/d of sodium chloride
or at least 1000 mg reduction in current intake
Limit Alcohol Consumption No more than two drinks/day for men 2–4 mm Hg
No more than one drink/day for women
Increase potassium Increase intake to 3500–5000 mg/day (level of DASH diet) 2–5 mm Hg
Content from fruits, vegetables, and low-fat dairy products
Adapted from references.1,8,77
References 71
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.
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II
PA RT
Nutritional Aspects of Lifestyle Medicine

James M. Rippe, MD
75
6
CHAPTER
The Concept of Nutritional Status

and Its Measurement
Johanna T. Dwyer, DSc, RD and Regan L. Bailey, PhD, RD, MPH, CPH
Key Points.................................................................................... 77 6.5.1 Food Groups vs. Nutrients......................................... 89

6.1 Introduction.......................................................................... 77 6.5.2 Dietary Patterns........................................................ 89
6.2 Concept of Nutritional Status................................................ 78 6.5.3 The Dietary Guidelines for Americans....................... 90
6.2.1 Nutrient Requirements.............................................. 78 6.5.4 The Healthy Eating Index.......................................... 90
6.2.2 Special Nutrient Requirements.................................. 78 6.5.5 USDA Food Group Patterns....................................... 90
6.2.3 Bioactive Food Components...................................... 78 6.5.6 My Plate................................................................... 90
6.3 Measurement of Nutritional Status........................................ 79 6.6 Other Terms Used in Describing Diets and Foods.................. 90
6.3.1 Overview.................................................................. 79 6.6.1 Energy Density and Nutrient Density......................... 91
6.3.2 Malnutrition.............................................................. 80 6.6.2 Determining Nutrient Quality of Foods and Diets....... 91
6.3.3 Evaluating the Diet.................................................... 80 6.6.3 Nutrient-Rich Foods Index........................................ 92
6.3.4 Dietary Assessment Methods.................................... 81 6.7 Nutrient Information on Food Labels..................................... 92
6.3.5 Usual Diets and Total Intakes.................................... 81 6.7.1 The Nutrition Facts Label.......................................... 93
6.3.6 Acute or Very Short-Term Intakes.............................. 82 6.7.2 Label Claims............................................................ 94
6.3.7 Total Nutrient Intakes................................................ 82 6.7.3 Nutrient Claims........................................................ 94
6.3.8 Food and Supplement Databases.............................. 82 6.7.4 Health Claims........................................................... 94
6.3.9 Measurement Error in Dietary Assessment................ 82 6.7.5 Structure/Function Claims........................................ 94
6.3.10 Validity of Dietary Data.............................................. 83 6.7.6 Voluntary and Front of Package Labeling.................. 94
6.3.11 Biomarkers of Nutritional Status............................... 83 6.7.7 Facts Up Front.......................................................... 95
6.3.12 Issues Arising in Interpreting Biomarkers of 6.7.8 Heart Check............................................................. 95
Nutritional Status�� 85 6.7.9 Other Labeling Systems............................................ 95
6.4 Guidelines for Energy and Nutrient Intakes............................ 85 6.7.10 Supermarket Scoring Systems and Icons.................. 95
6.4.1 The Dietary Reference Intakes (DRI).......................... 85 6.8 Personalized Nutrition........................................................... 96
6.4.2 Criteria for Setting Dietary Reference Intake 6.8.1 Definition.................................................................. 96
Recommendations�� 86 6.8.2 Potential of Personalized Nutrition............................ 96
6.4.3 The DRI Framework for Chronic Disease Risk............ 87 6.8.3 What Is Available Today............................................ 96
6.4.4 Dietary Risk Assessment and Excessive Intakes........ 88 6.9 Conclusions.......................................................................... 97
6.4.5 Limitations of the DRI............................................... 88 Clinical Applications..................................................................... 97
6.4.6 The Challenges of Updating the DRI.......................... 88 References.................................................................................. 97
6.5 Guidelines for Dietary Intakes............................................... 89
until now has few practical applications of demon-

KEY POINTS strated utility in planning intakes.
• The Dietary Guidelines for Americans provide rec-
• Dietary status includes only intake. Nutritional sta-
ommendations for healthful food intake patterns.
tus assessment involves a combination of dietary
intake, biochemical and anthropometric measure-
ments, clinical observations, functional status, and
if available, genetics. 6.1 INTRODUCTION
• Dietary Reference Intakes provide standards for
nutrient and energy needs. Diet plays an important role in human growth, develop-
• Personalized nutrition that takes account of bio- ment, and myriad bodily functions, and is directly related
markers and genetic information is promising but to health. This chapter provides a background on the
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)
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).
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
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
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
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.
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
recommendations are altered accordingly. However, little 6.4.5 Limitations of the DRI

is known about whether some common medications affect
some nutrient requirements. Research is needed to clarify Much attention lately has also been devoted to urging that
their effects, particularly in elders with many diseases and “candidate nutrients” such as the flavonoids, lutein, and
medications. omega-3 fatty acids which are thought to be associated
with reduced risk for certain chronic diseases be included
as essential nutrients using the DRI process. Many of
them are being taken in relatively high doses by consum-
6.4.4 Dietary Risk Assessment ers. However, at present, evidence that these bioactive
and Excessive Intakes constituents of foods are essential nutrients is inconclu-
Risk assessment describes the relationships between expo- sive. Also, it is difficult to determine what recommended
sure to a nutrient and the likelihood that adverse health dietary intakes of bioactives should be. Safety issues are
effects will occur in the exposed population. Risk assess- of concern for some bioactives without a long history of
ments systematically evaluate the probability of adverse human use at the levels that are being suggested for their
health events occurring in humans from excess exposure purported beneficial health effects. Since some of the bio-
to an environmental agent such as a nutrient or food com- actives are xenobiotic compounds that are foreign to the
ponent. Risk-risk assessments involve both the risks of body, there is little reason to assume that they are required
taking too much of the nutrient and the risk of not tak- or that the shape of the dose-response curves for them is
ing enough of the nutrient or supplement.90 Such assess- similar to that of nutrients. The DRI model of a normal
ments are becoming increasingly common. A constant set (Gaussian) requirement distribution may be inappropri-
of scientific principles involving risk assessment is used ate. It is not clear that the DRI “risk-risk” U shaped model
to set the UL. The process involves identifying hazards, of dose response, with increasing signs of deficiency with
assessing dose-responses, intake assessment, character- decreasing levels of intake or increasing signs of toxicity
ization, and evaluation of risk. All evaluations and judg- with increasingly large intakes, applies to them. The shape
ments are explicit, and evidence is provided to document of the dose-response curves for these bioactives may be
the conclusions that are reached. Both qualitative and quite different. More research is needed on these constitu-
quantitative types of evidence are considered. ULs are ents to both determine their possible beneficial effects on
set by first reviewing the literature to determine levels at chronic disease risk and establish what the safe upper lev-
which no observed adverse effects (NOAEL) are noted, els of intake are for these constituents.
or at the lowest level of intake associated with observed DRIs are limited for the very old and the very young.
adverse effects. Then an uncertainty factor is applied to Reference standards for infants of less than 32 weeks
reduce the intake level from the lowest adverse effect level gestation or elders over 80 years are derived largely by
to ensure that even the most sensitive persons would not extrapolation. These gaps need to be filled with additional
be affected by the UL dose chosen. At present, for many research. Keeping the DRIs current with the evolving sci-
nutrients there is simply not enough evidence to develop a ence is described in the next section.
UL. The risk is expressed as the fraction of the exposed
population, if any, that has nutrient intakes in excess of
the estimated Uls.91 ULs are not always certain, fixed, and
6.4.6 The Challenges of Updating the DRI
unvarying values. For many nutrients, ULs are not avail- Time and money are insufficient to update all the 51 nutri-
able because data have not been collected on the adverse ents that have DRI simultaneously. Therefore, ways must
effects of taking large amounts of nutrients, or the data be found to determine which nutrients have the highest
on adverse events are anecdotal or so sparse that they can- priority and who should decide this. A method for scan-
not be relied upon. Thus lack of a UL does not mean that ning the literature that may be useful has been developed
there is no risk of adverse effects from high intake of the but has not been accepted by the federal government or by
nutrient; in fact, when data about adverse effects are very the National Academies.92 A more fundamental question
limited, extra caution may be warranted. The data that is who shall make this updating decision and how it will
exist are often scanty or drawn on studies to address other be made. At present the fundamental decision to update is
questions. More attention needs to be paid to getting bet- made by the federal government, and at least half and usu-
ter data for setting ULs. ally virtually all of the funding comes from it. However, this
Although concerns about excessive energy and alco- decision relies not only on scientific issues but on economic
hol intakes have been of concern for many years, since and policy priorities, and does not ensure that a periodic
the promulgation of the UL, excessive intakes of micro- updating process will ensue such as that now in place for
nutrients are now receiving greater attention. In part, this updating the Dietary Guidelines for Americans. This need
stems not only from estimates of the UL but also from the to have updated DRIs is a critical issue, since virtually all of
population’s widespread use of dietary supplements and the nutrition guidance of the federal government depends
fortification of the food supply, both of which are concen- on up-to-date information on nutrient requirements.
trated sources of nutrients. In response to these concerns, Most of the DRI were arrived at by the deliberations
the NHANES, monitors total nutrient intake from natu- and consensus of volunteer expert committees nearly 20
rally occurring foods, enriched/fortified foods, and dietary years ago. Since then, the standards for evidence-based
supplements. It also monitors biochemical indices of nutri- decisions are increasingly based on systematic reviews of
ent status and excess, when appropriate and available. the totality of the evidence available, with formal grading
6.5 Guidelines for Dietary Intakes 89
of evidence quality. The process of conducting a system- 6.5.2 Dietary Patterns

6
atic review takes a great deal of money and time, and can-
not be accomplished by a staff of volunteer experts. The Dietary guidance to consumers in the United States is based
federal government funded the systematic review of cal- on the Dietary Guidelines for Americans that focuses
cium and vitamin D that was the basis for the revised DRI more on foods or food groups or food patterns than on
in 2010, but none of the other nutrients has been studied nutrients. The Nutrition Evidence Library’s Technical
in this fashion. In the future it will be necessary to find Expert Collaborative on the Study of Dietary Patterns
an ongoing and reliable source to fund and conduct such defines dietary patterns as “the quantities, proportions,
systematic reviews. Consensus panels of experts working variety or combination of different foods, drinks, and
on a voluntary basis can then review the totality of the nutrients in diet, and the frequency with which they are
evidence. habitually consumed.”97 The dietary pattern approach
has advanced nutrition research by capturing overall food
consumption behaviors and dietary quality in relationship
to health. Although errors in assessing dietary intakes
6.5 GUIDELINES FOR are well recognized, some research suggests that energy-
DIETARY INTAKES underreporting does not substantially alter estimates of
dietary patterns derived in epidemiological studies.98,99
Human beings require nutrients; they do not require spe- Dietary pattern methods can broadly be classified into
cific foods, food groups, or dietary patterns to be healthy. groupings by their relationship to health outcomes: inde-
However, humans must eat foods to obtain these nutrients, pendent and dependent.100,101 Health outcome independent
and therefore they need guidance on food selection and methods are the most commonly used in the field of nutri-
overall diet, since it is the quality of the total diet rather tion today. The term independent means that in deriving
than the nutrient content of individual foods that deter- the diet pattern there is no consideration used for speci-
mines associations with health.93 The focus on individual fying an outcome—essentially it is a two-step process.101
foods and food groups that should be emphasized or lim- First the patterns are formed, and next the patterns are
ited arose in part due to epidemiological studies linking tested against a selected health outcome. Outcome inde-
specific foods and food groups with obesity and other pendent methods to classify the diet include indexes and
chronic diseases.94 While it is correct that all foods can scores, factor analysis, cluster analysis, and selective diets
fit in healthy diets, such statements should be accompa- (e.g., vegetarian or gluten-free). In the outcome dependent
nied by an emphasis on total energy intake. The frequency methods, the end point or a surrogate end point is used in
and amount of food consumption, total energy intake, the creation of the patterns—this is a newer approach, but
and physical activity must be considered in order to avoid it is one that will certainly gain traction in the field in the
dietary excess. That is, it is true that there are no “bad” future.101 This type of dietary pattern approach includes
foods, only “bad” total diets from the health standpoint. methods like classification and regression tree analysis and
Everyone can benefit from advice on choosing foods that reduced rank regression.100 Metabolomics is one emerging
provide a balanced diet, what portion sizes constitute a area for helping to classify total dietary patterns.102
serving, how to transition to healthier dietary patterns, and Epidemiological studies increasingly examine over-
how to identify food groups that are eaten in excess of all food patterns as opposed to single nutrients or foods
recommendations or in insufficient quantities. because they better explain the associations between diet
For individuals who have diet-related diseases and and health. Human beings eat foods in certain patterns, and
require therapeutic diets, food-exchange lists may also not nutrients; this means that interactions between nutrients
be useful. These include, for example, American Diabetes may occur, that causation is difficult to establish, and that
Association food-exchange lists for diabetes and the the effects of foods or meals consumed at different times
Academy of Nutrition and Dietetics food-exchange lists may have differing effects on metabolism. Because dietary
for weight management.95,96 exposures are highly interrelated, focusing on the role of
single nutrients or foods in relation to disease risk is fraught
with error even after making adjustments for intakes of
other nutrients or foods that might have effects.103 Overall
6.5.1 Food Groups vs. Nutrients dietary patterns may also have a more pronounced impact
Foods can be categorized into similar groups on the basis on non-communicable disease risk than do single nutrients,
of their content of nutrients and other bioactives. Such dietary ingredients, foods, or food groups, since they include
groupings can be useful, since they identify the foods that the interacting influences of nutrients, non-nutrient bioac-
are high and low in specific nutrients and make it easier tives, and energy intake.104,105 There has been some work
for consumers to choose wisely. Food groups form the recently evaluating dietary patterns in national survey data
basis of dietary or eating patterns because they focus on from Canada by applying the Healthy Eating Index 2010
foods, rather than nutrients. However, while the Dietary and the 2015 Dietary Guidelines for Americans as the stan-
Guidelines Advisory Committee 2015–2020 report high- dards of diet quality; however, these indices only include
lights the importance of overall dietary patterns, certain sodium in their scores. Nevertheless, the indices do seem to
nutrients are also singled out because of the risk of low be good markers of a micronutrient-dense diet.
(e.g., calcium) or high intakes (e.g., saturated [not total] There are now many recommended eating patterns
fat and added [not total] sugar). emanating from government and health professional
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.
6.5.3 The Dietary Guidelines for Americans 6.5.5 USDA Food Group Patterns

The Dietary Guidelines for Americans (DGA) are The USDA has designed a series of USDA Food Patterns
issued every five years by the federal government. They that conform to the recommendations of the Dietary
are informed by a panel of independent research scien- Guidelines for Americans and the Recommended Dietary
tists called the Dietary Guidelines Scientific Advisory Allowances (RDA) of the Dietary Reference Intakes.
Committee. The DGA4 are recommendations to help These are available on the World Wide Web for con-
guide individuals to make healthy dietary choices. The sumers to tailor to their age, sex, and physical activity
guidelines emphasize healthy eating, which involves not levels. The Food Patterns identify the amounts of rec-
only getting enough food but also balance, variety, and ommended foods from five major food groups (fruits,
moderation in consumption patterns to decrease diet- vegetables, grains, protein foods, and dairy) and their
related risks of chronic degenerative diseases subgroups (dark green vegetables, orange and red veg-
The DGA provide a rough guide to the types and etables, starchy vegetables, other vegetables, beans and
amounts of foods to eat. This most recent iteration focused peas, whole grains, enriched/refined grains, meat/poul-
on overall dietary (i.e., eating) patterns. The Web version try/eggs, nuts, seeds, soy products, seafood). The rec-
of the guidelines had a calculator that tailored the num- ommended amounts to consume from each food group
ber of servings suggested for healthy patients of different differ depending on an individual’s energy and nutrient
weights, sexes, ages, and lifecycle stages to help them to needs. The Patterns achieve nutritional adequacy with-
meet their needs while avoiding excess (http://www.super- out exceeding recommended energy intake and conform
tracker.usda.gov/default.asp x and www.ChooseMyPlate. to the 2015 Dietary Guidelines for Americans limits for
gov) this has now been discontinued. Examples of different sodium, saturated fat, and added sugars. The Patterns
meal patterns are provided in Table 6.5. provide only limited amounts of solid fats and added sug-
Historically, the Guidelines have been targeted to peo- ars for the calories left after the other goals have been
ple over the age of two years because of a lack of available met, since meeting nutrient needs from food alone within
data to set recommendations for those < 2 years. However, the energy constraints that are present, particularly if
the next iteration will include infants and young children people are very sedentary, provides very little room for
thanks to the B-24 Project, formally titled “Evaluating components that provide mostly calories.
the evidence base to support the inclusion of infants and
children from birth to 24 months of age in the Dietary
Guidelines for Americans (DGA)—the B-24 Project ini- 6.5.6 My Plate
tiated by the U.S. Departments of Health and Human USDA’s Choose My Plate graphic is a pictorial represen-
Services and U.S. Department of Agriculture.109 tation intended to emphasize the balance between food
energy (calories) and nutritional needs, and to encourage
increased intake of fruits and vegetables, whole grains,
6.5.4 The Healthy Eating Index and low-fat milk, with reduced intake of sodium and
high-calorie sugary drinks.
The Healthy Eating Index (HEI) is used to assess compli-
ance with the Dietary Guidelines, and so it is also updated
every five years when new guidelines are issued.110 The HEI
2015 is an index used to assist in rating the overall dietary
6.6 OTHER TERMS USED IN
quality (e.g., balance, variety, and adequacy) of intakes DESCRIBING DIETS AND FOODS
based on criteria derived from both the Dietary Reference
Intakes and the Dietary Guidelines for Americans. Note Many special terms are used in describing diets and specific
that the index does not focus on energy needs or the foods from the health standpoint. This section discusses a
caloric contributions of foods directly. Instead, the HEI few selected common descriptors beyond the dietary and
is a combination system based on points for intakes of eating patterns that were previously discussed.
6.6 Other Terms Used in Describing Diets and Foods 91
HEI–2015 Components & Scoring Standards

1
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.
2: Includes 100% fruit juice.
3: Includes all forms except juice.
4: Includes legumes (beans and peas).
5: Includes all milk products, such as fluid milk, yogurt, and cheese, and fortified soy beverages.
6: Includes legumes (beans and peas).
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.
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
Front-of-pack labels provide scores or logos to help
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.
6.7.1 The Nutrition Facts Label

The “Nutrition Facts” label provides information about
the energy and content of certain macro and micro nutri-
ents to emphasize and those to limit in foods by their
amounts in standardized portion sizes for almost all pro-
cessed foods. Dietary supplements sold directly to consum- Figure 6.3 The Supplement Facts Label.
ers that contain nutrients have a Supplement Facts label.
Both labels use a dietary standard known as a percent of
Nutrition Facts food labels were made because of changes
the Daily Value (DV) per serving, to provide a comparison
in the prevalence of diets in the population with intakes of
of the nutrient content with the DV, which is based on the
too little or too much of certain nutrients in the American
RDA (see section 4.1). Daily Values are presented as the
diet. For example, there is great concern about the prev-
percent of daily value (%DV) on the label to help consum-
alence of obesity in the United States, and some of the
ers to understand the nutrient information on the product
changes in food labels such as the bolded values for calories
label in the context of the total diet.
reflect these concerns. Some of the nutrients singled out
On the Nutrition Facts label, the nutrients are not pro-
on the food label with Daily Values are intended to guide
vided as nutrient density but as a “percent of DV” and
consumers about maximum intakes— such as sodium or
in absolute amounts per serving and calories per serving.
saturated fat. Others included are intended to help con-
The absolute amounts in grams for macronutrients and in
sumers meet a nutrient requirement—iron, calcium, vita-
milligrams or micrograms of vitamins and minerals, and
min D, and dietary fiber, for example, with the emphasis
calories, in addition to the %DV, are all presented on the
on nutrients of public health significance that fall short of
label. Figure 6.2 presents the new Nutrition Facts label,
recommendations in dietary surveys of Americans.
and Figure 6.3 shows the new Supplement Facts label,
The current shortfall nutrients that must be declared
both of which will shortly appear on nearly all foods and
on the Nutrient Facts label are calcium, vitamin D, potas-
dietary supplements. Many of the changes in the “new”
sium, and iron, for which population-based surveys such
as the National Health and Nutrition Examination Survey
(NHANES) find that the U.S. population is consuming
in inadequate amounts. Calcium and iron are already
required; vitamin D and potassium are newly required.
Mandatory labeling is not required after 2020 for vita-
min C or vitamin A because data indicate that deficiencies
of these nutrients in the United States are not common.
However, these vitamins are still allowed to be declared
on labels voluntarily Other nutrients with DVs on the label
are intended to guide consumers about maximum intake,
such as sodium, saturated fat, and sugars. Sodium contin-
ues to be required, and the new label format also requires
“Total Fat,” “Saturated Fat,” and “Trans Fat,” since these
are associated with chronic degenerative disease and are
consumed in excess by many Americans. “Sugars” include
both “added sugars” and sugars that are naturally occur-
ring in food. Added sugars are indented under “Sugars”
on the label. Although added sugars are not chemically
different from naturally occurring sugars, many foods
and beverages that are major sources of added sugars have
lower micronutrient densities compared to foods and bev-
erages that are major sources of naturally occurring sug-
ars, and for this reason they too are labeled. Americans,
on average, exceed the < 10% of total energy guideline for
Figure 6.2 The Nutrition Facts Label. added sugars. For example, among children two to eight
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
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 mining 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.
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7
CHAPTER
Dietary Guidelines for Americans,

2015–2020: National Nutrition Guidelines
Elizabeth B. Rahavi, RDN, Jean M. Altman, MS, and Eve E. Stoody, PhD
Key Points.................................................................................. 101 7.4 Implementation by Health Professionals.............................. 106

7.1 Introduction........................................................................ 101 7.4.1 Translating the Dietary Guidelines to Support
7.2 Background........................................................................ 102 Nutrition Education�� 108
7.3 Overview of the Dietary Guidelines for Americans, 7.4.1.1 M yPlate Consumer Messages�� 108
2015–2020........................................................................ 103 7.5 Aligning with the Dietary Guidelines: What Does This
7.3.1 The Guidelines.......................................................... 103 Mean in Practice?............................................................... 109
7.3.2 Key Recommendations............................................. 103 7.6 Looking Ahead to 2020—Expanding Guidance................... 109
7.3.3 Healthy Eating Patterns............................................. 104 7.7 Additional Resources...........................................................110
7.3.4 Estimated Calorie Needs per Day.............................. 104 Clinical Applications....................................................................110
7.3.5 Shifts Needed to Align with Healthy Eating Patterns.......105 References.................................................................................110
However, as infectious disease rates have dropped,

KEY POINTS the rates of noncommunicable diseases—specifically,
chronic diet-related diseases—have risen, due in part to
• Almost half of all American adults have one or
changes in lifestyle behaviors. A history of poor eating
more chronic diseases that may be related to a poor-
and physical activity patterns have a cumulative effect
quality eating pattern and physical inactivity. The
and have contributed to significant nutrition- and physi-
medical costs associated with these chronic diseases
cal activity-related health challenges that now face the
come at a high cost.
U.S. population. About half of all American adults—117
• The Dietary Guidelines for Americans is updated
million individuals—have one or more preventable
every five years and reflects the current body of
chronic diseases, many of which are related to poor-
science to provide advice on how Americans can
quality eating patterns and physical inactivity. These
improve their health by building healthy eating and
include cardiovascular disease, high blood pressure,
physical activity patterns.
type 2 diabetes, some cancers, and poor bone health.
• Most Americans are not meeting the Dietary
More than two-thirds of adults and nearly one-third of
Guidelines recommendations for fruits, vegetables,
children and youth are overweight or obese. These high
dairy, and whole grains and are over-consuming
rates of overweight, obesity, and chronic disease have
added sugars, saturated fat, and sodium.
persisted for more than two decades and come not only
• Comprehensive and coordinated system-wide
with increased health risks but also at high cost. In 2008,
strategies are necessary to improve the health of
the medical costs associated with obesity were estimated
Americans. Health professionals are vital to these
to be $147 billion. In 2012, the total estimated cost of
strategies and provide a uniquely influential role in
diagnosed diabetes was $245 billion, including $176 bil-
creating behavioral and systems change. The federal
lion in direct medical costs and $69 billion in decreased
government provides a number of free resources to
productivity.1
assist them in these efforts.
Table 7.1 describes the high rates of nutrition- and
physical activity-related chronic diseases and their related
risk factors. These diseases affect all ages—children, ado-
7.1 INTRODUCTION lescents, adults, and older adults—though rates vary by
several factors, including race/ethnicity, income status,
Over the past century, essential nutrient deficiencies and body weight status.
have dramatically decreased, many infectious diseases However, a large body of evidence now shows that
have been conquered, and the majority of the U.S. pop- healthy eating patterns and regular physical activity
ulation can now anticipate a long and productive life. can help people achieve and maintain good health and
101
102 Chapter 7 Dietary Guidelines for Americans, 2015–2020: National Nutrition Guidelines
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.
7.3 OVERVIEW OF THE DIETARY 7.3.2 Key Recommendations

GUIDELINES FOR AMERICANS, Key Recommendations provide further guidance on how
2015–2020 individuals can follow the five Guidelines. The Dietary
Guidelines’ Key Recommendations for healthy eating
The 2015–2020 Dietary Guidelines for Americans, 2015– patterns should be applied in their entirety, given the

2020 provides five overarching Guidelines that encourage interconnected relationship that each dietary component
healthy eating patterns, recognize that individuals will can have with others.
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.
7.3.3 Healthy Eating Patterns The components of healthy eating patterns recom-

mended were developed by integrating findings from
An eating pattern represents the totality of all foods systematic reviews of scientific research, food pattern mod-
and beverages consumed. Eating an appropriate mix of eling, and analyses of current intake of the U.S. population:
foods from the food groups and subgroups —within an
appropriate calorie level—is important to promote health. • Systematic reviews of scientific research examine rela-
Healthy eating patterns support a healthy body weight tionships between the overall diet and health outcomes.
and can help prevent and reduce the risk of chronic disease • Food pattern modeling assesses how well various
throughout periods of growth, development, and aging as combinations and amounts of foods meet nutrient
well as during pregnancy. needs and accommodate limits.
There are many ways to consume a healthy eating pat- • Analyses of current intakes identify areas of poten-
tern, and the evidence to support multiple approaches has tial public health concern.
expanded over time. At the core of this guidance is the
importance of consuming overall healthy eating patterns,
Together, these complementary approaches provide a
including vegetables, fruits, grains, dairy, protein foods,
robust evidence base for healthy eating patterns that both
and oils—eaten within an appropriate calorie level and
reduce risk of diet-related chronic disease and promote
in forms with limited amounts of saturated fats, added
nutrient adequacy.
sugars, and sodium. Examples of how to put this guidance
into practice are provided by the Healthy U.S.-Style Eating
Pattern and two variations, a healthy Mediterranean-Style
Eating Pattern and a Healthy Vegetarian Eating Pattern. 7.3.4 Estimated Calorie Needs per Day
Because calorie needs vary based on age, sex, height, The amount of calories a person needs each day varies
weight, and level of physical activity, the Patterns have been depending on a number of factors, including the person’s
developed at 12 different calorie levels. The 2,000-calorie age, sex, height, weight, and level of physical activity.
level of each Pattern is shown in Table 7.2. The additional Estimates range from 1,600 to 2,400 calories per day for
calorie levels can be found in Appendices 3 and 4 of the adult women and 2,000 to 3,000 calories per day for adult
2015–2020 Dietary Guidelines for Americans. men. Within each age and sex category, the low end of the
7.3 Overview of the Dietary Guidelines for Americans, 2015–2020 105
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.
Quantity equivalents for each food group are:

• Vegetables and fruits, 1 cup-equivalent is: 1 cup raw or cooked vegetable or fruit, 1 cup vegetable or fruit juice, 2 cups leafy salad greens, ½ cup dried fruit or
vegetable.
• Grains, 1 ounce-equivalent is: ½ cup cooked rice, pasta, or cereal; 1 ounce dry pasta or rice; 1 medium (1 ounce) slice bread; 1 ounce of ready-to-eat cereal (about 1 cup
of flaked cereal).
• Dairy, 1 cup-equivalent is: 1 cup milk, yogurt, or fortified soymilk; 1½ ounces natural cheese such as cheddar cheese or 2 ounces of processed cheese.
• Protein Foods, 1 ounce-equivalent is: 1 ounce lean meat, poultry, or seafood; 1 egg; ¼ cup cooked beans or tofu; 1 Tbsp peanut butter; ½ ounce nuts or seeds.
b Assumes food choices to meet food group recommendations are in nutrient-dense forms. Calories from added sugars, added refined starches, solid fats, alcohol, and/or
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
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.
Among nutrients, calcium, potassium, dietary fiber,

and vitamin D are considered nutrients of public health 7.4 IMPLEMENTATION BY
concern because low intakes are associated with health
concerns. For young children, women capable of becom- HEALTH PROFESSIONALS
ing pregnant, and women who are pregnant, low intake of
The Dietary Guidelines describe the characteristics of
iron also is of public health concern.
healthy eating and physical activity patterns, and it is
An underlying premise of the Dietary Guidelines is
clear that across all population groups, the vast majority
that nutritional needs should be met primarily from foods.
of people in the United States are not meeting these rec-
All forms of foods, including fresh, canned, dried, and
ommendations. In general, Americans are consuming too
frozen, can be included in healthy eating patterns. Foods
many calories, are not meeting food group and nutrient
in nutrient-dense forms contain essential vitamins and
recommendations, and are not getting adequate physical
minerals and also dietary fiber and other naturally occur-
activity. Crosscutting coordination and collaboration are
ring substances that may have positive health effects.
needed in a variety of sectors and settings in order to create
In some cases, fortified foods and dietary supplements
a new paradigm in which healthy lifestyle choices at home,
may be useful in providing one or more nutrients that
school, work, and in the community are easy, accessible,
otherwise may be consumed in less-than-recommended
affordable, and normative. Health professionals play an
amounts.
important and unique role as providers; however, they can
Current eating patterns can be moved toward health-
also serve as trusted educators, respected advocates, and
ier eating patterns by making shifts in food choices over
facilitators of change.
time. Making these shifts can help support a healthy
The Social-Ecological Model can help health profes-
body weight, meet nutrient needs, and lessen the risk
sionals understand how layers of influence intersect to
for chronic disease. “Shifts” in intake are highlighted
shape a person’s food and physical activity decisions. The
to emphasize the need to make substitutions—that is,
model below shows how various factors influence food
choosing nutrient-dense foods and beverages in place
and beverage intake, physical activity patterns, and ulti-
of less healthy choices—rather than increasing intake
mately health outcomes (Figure 7.1).
overall. Most individuals would benefit from shifting
Among the components of the Social-Ecological
food choices both within and across food groups. Some
Model, sectors and settings influence change at the popu-
needed shifts are minor and can be accomplished by mak-
lation level and have the potential to improve population
ing simple substitutions, while others will require greater
health. Sectors include systems, organizations and busi-
effort to accomplish. Example shifts that can help move
nesses, and industries. These sectors all have an impor-
Americans toward healthier eating patterns include the
tant role in helping individuals make healthy choices
following, but vary for each individual based on current
because they either influence the degree to which peo-
intakes:
ple have access to healthy food and/or opportunities to
be physically active, or they influence norms and values
• Shift to consume more vegetables. through effective health promotion and marketing strate-
• Shift to consume more fruits. gies. Settings, such as early care and education programs,
schools, worksites, community centers, and food retail
* Data source for Healthy Eating Index 2015 scores: What We Eat and food service establishments, determine what foods
in America, National Health and Nutrition Examination Survey are offered and what opportunities for physical activ-
(NHANES) 2013–2014. For more information on the HEI, see: ity are provided. In combination, sectors and settings
https://www.cnpp.usda.gov/healthyeatingindex. Accessed March
11, 2018.
† Data sources: What We Eat in America, NHANES 2007–2010 ‡ Solid fats are the fats found in meats, poultry, dairy products, hydro-
for average intakes by age-sex group. Healthy U.S.-Style Food genated vegetable oils, and some tropical oils. They contain more
Patterns, which vary based on age, sex, and activity level, for rec- saturated fatty acids and less mono- and polyunsaturated fatty acids
ommended intakes and limits. compared to oils. Solid fats are solid at room temperature.
7.4 Implementation by Health Professionals 107
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.
• Settings: Provide nutrition assistance programs that

support education and promotional activities tai-
lored to the needs of the community.
• Settings: Implement educational programs tai-
lored to individuals and change organization
practices, approaches, and/or policies to support
healthy food choices where food decisions are
being made, including at early care and education
programs, schools, worksites, and other commu-
nity settings.
• Settings: Encourage opportunities in the workplace
for regular physical activity through active commut-
ing, activity breaks, and walking meetings.
• Working with Individuals: Help individuals become
more aware of the foods and beverages that make up
their own or their family’s eating patterns and iden-
tify areas, such as modifying recipes and/or food
selections, where they can make shifts to align with
the Dietary Guidelines.
• Working with Individuals: Teach skills like garden-
ing, cooking, meal planning, and label reading that 7.4.1.1 MyPlate Consumer Messages
help support healthy eating patterns. Find your healthy eating style and maintain it for a life-
• Working with Individuals: Suggest ways that indi- time. This means: Everything you eat and drink over time
viduals can model healthy eating behaviors for matters. The right mix can help you be healthier now and
friends and family members. in the future.
• Make half your plate fruits and vegetables.

7.4.1 Translating the Dietary Guidelines • Focus on whole fruits.
to Support Nutrition Education • Vary your veggies.
• Make half your grains whole grains.
The Dietary Guidelines was developed and written for • Vary your protein routine.
a professional audience. Therefore, its translation into • Move to low-fat or fat-free milk or yogurt.
actionable consumer messages and resources is crucial to • Drink and eat less sodium, saturated fat, and added
help individuals, families, and communities achieve healthy sugars.
eating patterns. With the needs of health professionals in • Start with small changes to make healthier choices
mind, the USDA and HHS have developed a variety of you can enjoy.
tools that can help health professionals with disseminat-
ing food and nutrition messages based on the Dietary The Communicator’s Guide. The Communicator’s
Guidelines to the public. These resources include MyPlate, Guide† can help health professionals with customizing
the Communicator’s Guide, and the Dietary Guidelines nutrition education materials for a specific audience. It
Toolkit for Health Professionals. was developed to assist them with applying the Dietary
MyPlate. One way the USDA and other federal Guidelines to their nutrition education materials, recog-
agencies implement the Dietary Guidelines is through nizing that in certain cases existing nutrition education
MyPlate,* which serves as a visual reminder to build a resources may not be suitable for their specific audience.
healthy eating pattern by making healthy choices across The Communicator’s Guide is designed for the professional
the food groups. MyPlate is also used by profession- to start where they are based on their level of comfort with
als across multiple sectors and settings to help increase different topics. For example, it provides a summary of the
awareness about how to make healthy food and bever- Dietary Guidelines, including key points from the most
age choices over time. Created to be used in various set- recent edition if the user wants to learn more. If the user
tings and to be adaptable to support the needs of specific is looking for inspiration on how to translate the Dietary
population groups, the MyPlate symbol and its support- Guidelines into consumer messages, the site provides
ing consumer resources bring together key elements of overarching communication points along with MyPlate’s
healthy eating patterns. These key MyPlate consumer consumer-tested messages. If the user is new to nutrition
messages can be used in a variety of educational materi- communication, the site provides best practices for creat-
als for the public. ing nutrition education materials. The site also provides
* 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
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.
• 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
Nutrition and Cardiovascular Disease

James M. Rippe, MD
Key Points...................................................................................111 8.4.14 Chocolate................................................................118

8.1 Introduction.........................................................................111 8.5 Nutritional Supplements......................................................118
8.2 Background.........................................................................112 8.5.1 Salt and Sodium......................................................118
8.3 Dietary Patterns...................................................................112 8.5.2 Vitamin D.................................................................118
8.4 Individual Food Items...........................................................114 8.5.3 Antioxidant Vitamins E and C....................................118
8.4.1 Fruits and Vegetables...............................................116 8.6 Aha Diet and Lifestyle Recommendations............................118
8.4.2 Whole Grains and Dietary Fiber................................116 8.6.1 Consume an Overall Healthy Diet.............................118
8.4.3 Fish.........................................................................116 8.6.2 Aim for a Healthy Body Weight.................................118
8.4.4 Nuts........................................................................116 8.6.3 Aim for a Desirable Lipid Profile...............................119
8.4.5 Meat........................................................................116 8.6.4 Aim for a Normal Blood Pressure.............................119
8.4.6 Dairy Products.........................................................116 8.6.5 Be Physically Active.................................................119
8.4.7 Soy..........................................................................117 8.6.6 Avoid Use and Exposure to Tobacco Products...........119
8.4.8 Sugar Sweetened Beverages (SSBs)........................117 8.7 Specific AHA Nutrition and Lifestyle Recommendations........119
8.4.9 Alcohol....................................................................117 8.8 Implementing Heart Healthy Nutrition Plans........................ 120
8.4.10 Coffee and Caffeine.................................................117 8.9 Conclusions........................................................................ 120
8.4.11 Tea..........................................................................117 Clinical Applications................................................................... 120
8.4.12 Eggs........................................................................117 References................................................................................ 120
8.4.13 Garlic.......................................................................117
not thousands, of studies to support the concept that daily

KEY POINTS lifestyle practices and habits exert profound effects on
the likelihood of developing CVD. While many lifestyle
• Cardiovascular disease (CVD) remains the leading
practices are associated with positive benefits both in pre-
killer of both men and women in the United States,
vention and treatment of CVD, nutrition clearly plays a
resulting in over 37% of annual mortality.
pivotal role. 2–5
• Nutritional practices play a pivotal role in the likeli-
Multiple studies have demonstrated that a diet con-
hood of developing CVD.
taining more fruits and vegetables, fish (particularly oily
• Dietary patterns that include increases in fruits and
fish), and whole grains and fiber—and also remaining in
vegetables, whole grains, seafood (particularly oily
caloric balance—lowers the risk of CVD.1–7 Other posi-
fish), legumes and nuts, and low- or non-fat dairy
tive lifestyle decisions such as maintaining a proper body
products, and that are lower in red meats and pro-
weight,8,9 engaging in at least 30 minutes per day of physi-
cessed meats, and low in sugar-sweetened beverages
cal activity,10 and avoiding smoking and tobacco products3
and refined grains have been repeatedly shown to
can also reduce the risk of CVD. These practices together
lower the risk of cardiovascular disease.
can reduce the risk of CVD over 80% and diabetes by
• Implementation of plant-based diets such as recom-
over 90% in both men and women. Indeed, participation
mended by the American Heart Association and
in only one of these activities on a regular basis can reduce
Dietary Guidelines for Americans will be a key
the risk of both CVD and diabetes by over 50%.11,12
mandate for clinicians in order to help their patients
Between 1980 and 2000, mortality rates from CVD
adopt healthier eating habits.
fell by 40%.13 Reductions in major lifestyle risk factors
such as increased physical activity, smoking cessation, and
8.1 INTRODUCTION better control of cholesterol and blood pressure accounted
for approximately half of these reductions. Unfortunately,
Cardiovascular disease (CVD) is the largest source of mor- obesity and diabetes have moved in the opposite direction
bidity and mortality in the United States and elsewhere and have the potential to wipe out all the gains achieved
in the developed world.1 CVD accounts for over 37% of by other lifestyle-related risk factors unless these nega-
all mortality in the United States. There are hundreds, if tive trends can be reversed.13 Nutritional factors play a
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
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
TABLE 8.1 (http://bloodpressureplan.com/download-free-dash-diet-cookbook-with-weekly-meal-plan-to-lower-b

lood-pressure-naturally/?utm_source=adwords&utm_medium=search&utm_term=exact&utm_content=1&utm_campa
ign=dash&gclid=CN-os8ng0dMCFZV XDQodC8sPQQ) 8
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
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
and other health-related organizations. Importantly, these

recommendations place heart-healthy nutritional prac-
8.9 CONCLUSIONS
tices in the context of an overall positive lifestyle, includ- Overwhelming evidence exists to support the concept that
ing physical activity and weight management. It should be nutritional practices strongly interact with the likelihood
noted that these practices will lower total CVD risk, even of developing CVD. Recent guidelines related to nutri-
if individual CVD risk factors are not decreased. These tional practices have placed them in the overall context
recommendations are also consistent with the Heart- of positive lifestyle habits and practices. Lifestyle medi-
Healthy Dietary Patterns and overall approach to lower- cine offers a promising framework for impacting on both
ing the risk of heart disease, which has previously been nutritional practices and other lifestyle factors which
described in this chapter. The following AHA nutrition affect the risk of developing CVD. Evidence-based guide-
and lifestyle factors have been recommended: lines from the Dietary Guidelines for Americans 2015–
2020, the American College of Cardiology, the American
• Balance caloric intake and physical activity to Heart Association Nutrition Guidelines, and the AHA
achieve and maintain healthy body weight. 2020 Strategic Plan all emphasize that dietary patterns
• Consume a diet rich in vegetables and fruits. that include fruits and vegetables, whole grains, seafood,
• Choose whole grain, high-fiber foods. legumes and nuts, and that also include non-fat dairy
• Consume fish, especially oily fish, at least twice a products and alcohol (among adults) and are lower in red
week. meats and processed meats, and lower in sugar-sweetened
• Limit intake of saturated fats, trans fats, and dietary beverages and refined grains all support reduced risk of
cholesterol. CVD. While these patterns may be achieved in many dif-
• Minimize intake of beverages and foods with added ferent ways, it is important that they be tailored to indi-
sugars. viduals’ cultural, biological, and medical needs.
• Choose and prepare foods with little or no salt. Implementation of the guidelines from these scientific
• If you consume alcohol, do so in moderation. bodies remains the key challenge which will require the
• When eating foods prepared outside the home, fol- recognition of multiple factors to interact with both indi-
low AHA guidelines. vidual and population-wide nutritional choices. A detailed
and sophisticated understanding of not only the emerging
science in nutrition and CVD but also behavioral medi-
8.8 IMPLEMENTING HEART cine will be essential to accomplish the goal of helping
individuals reduce their risk of heart disease through
HEALTHY NUTRITION PLANS nutritional and other lifestyle practices.
A recent emphasis at the American Heart Association and
other health-oriented associations has been on implement- CLINICAL APPLICATIONS
ing strategies to help individuals consume a more heart-
healthy diet. The AHA issued a Scientific Statement in • Plant-based diets from the American Heart
2009 entitled “Implementing American Heart Association Association, the American College of Cardiology,
Pediatric and Adult Nutrition Guidelines”.16 While this and the Dietary Guidelines for Americans are con-
Statement emphasized the complexity of factors that sistent with each other, so any of these can be fol-
impact on nutritional choices, it also offered a multilevel lowed to lower the risk of heart disease.
framework to impact on these factors. This framework • The DASH diet has been shown to effectively lower
started with individual factors which were then placed blood pressure in individuals with hypertension.
more broadly in family factors, environmental factors, the • Nutrition plays a key role in lowering the risk of
micro environmental, and finally, the macro environmental cardiovascular disease and should be placed in the
factors. Each of these interacting domains contain multiple context of an overall healthy approach to lowering
influencers. Specific results related to these interactive fac- the risk of CVD, including increased physical activ-
tors are beyond the scope of this chapter. Readers should ity, weight management, and avoidance of tobacco
refer to this Scientific Statement for more detail.16 products.
In order to positively impact on multiple factors that • Clinicians should routinely recommend that indi-
influence heart-healthy nutrition, proven models of behav- viduals follow diets that are high in fruits and vege-
ioral medicine will be required to help individuals adopt tables, whole grains, seafood (particularly oily fish),
positive behavior, in general, and in the area of nutrition, legumes and nuts, and non-fat dairy products, and
in particular. Models of behavior change are beyond the that are lower in red meats, processed meats, sugar-
scope of this chapter, but are found in Chapter 15–25 in sweetened beverages, and refined grains to support
this textbook. reduction in risk of CVD.
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9
CHAPTER
Optimal Nutrition Guidance for Older Adults

Alice H. Lichtenstein, DSc
Key Points.................................................................................. 125 9.4.3 Vision, Dexterity, and Mobility.................................... 129

9.1 Introduction........................................................................ 125 9.4.4 Social Factors........................................................... 129
9.2 Current Recommendations................................................. 125 9.5 Physiological Changes of Concern in Older Adults............... 130
9.3 Nutrients of Concern........................................................... 127 9.5.1 Dentition and Associated Senses.............................. 130
9.3.1 Vitamin D.................................................................. 127 9.5.2 Cardiovascular Disease............................................. 130
9.3.2 Calcium.................................................................... 127 9.5.3 Osteoporosis............................................................. 130
9.3.3 Potassium................................................................. 127 9.5.4 Glucose Intolerance/Type 2 Diabetes........................ 130
9.3.4 Fiber......................................................................... 127 9.5.5 Hypertension............................................................ 130
9.3.5 Sodium..................................................................... 127 9.5.6 Immune Function...................................................... 130
9.3.6 Saturated Fat............................................................ 128 9.5.7 Cancer...................................................................... 130
9.3.7 Added Sugar............................................................. 128 9.6 Conclusions........................................................................ 131
9.4 Special Dietary Considerations for Older Adults................... 128 Clinical Applications................................................................... 131
9.4.1 Organ Systems......................................................... 128 References................................................................................ 131
9.4.2 Taste and Smell........................................................ 129
physical and cognitive function with advancing years.

KEY POINTS Evidence suggests that within a population, older adults
who score in the higher categories for diet quality1–4 and
• Diet quality is directly related to optimal physical
physical activity measures5,6 have the best survival rates.
and cognitive function in older adults.
• Nutrient requirements either stay the same or
increase with advancing years, whereas energy
requirements decline, increasing the importance of 9.2 CURRENT RECOMMENDATIONS
making nutrient-dense food choices.
The revamp of the recommended dietary allowances
• Changes in sensory perception and the onset of
(RDA) by the Food and Nutrition Board of the Institute of
chronic diseases may necessitate added attention to
Medicine starting in the early 1990 s brought about more
diet composition in older adults.
precise recommendations for individuals above the age of
• Alterations in social environments and living situations
50 years.7–14 The current recommendations, termed dietary
make it important to monitor the ability and desire to
reference intakes (DRI), include guidance for adults in
obtain, prepare, and consume a high-quality diet.
categories of 31–50 years, 51–70 years, and greater than
70 years.15 No further distinction is made for individuals
aged 70 years and above. This lack of more precise guid-
9.1 INTRODUCTION ance for those over 70 years is likely a consequence of
limited information from the older-aged groups.15
In 2015, approximately 46 million individuals living in the DRIs for most nutrients, including vitamin A, vitamin C,
United States were over the age of 65 years. This number vitamin E, vitamin K, thiamin, riboflavin, niacin, folate,
is expected to double to approximately 98 million by the vitamin B12, pantothenic acid, biotin, choline, chromium,
year 2060, representing about 24% of the total population copper, fluoride, iron, magnesium, manganese, molyb-
(Figure 9.1). Accompanying this increase, the older popu- denum, phosphorus, selenium, and zinc, do not differ
lation is expected to become more racially and ethnically between adults above and below the age of 50 years. The
diverse. They are also expected to work longer and attain nutrient recommendations for three nutrients, vitamin D,
a higher level of education than prior generations. Current calcium, and vitamin B6, are higher for older adults. The
trends suggest a higher proportion of older adults than DRIs for vitamin D increased from 600 IU/day for females
previously will be dealing with the challenges of obesity. and males between 51 and 70 years of age to 800 IU/day
Accompanying this shift in the demographic makeup for both females and males above 70 years of age.16 The
of the U.S. population is an ever-increasing need for spe- DRIs for calcium increased from 1200 and 1000 mg/day
cific nutrition guidance to achieve and maintain optimal for females and males, respectively, between 51 and 70
125
126 Chapter 9 Optimal Nutrition Guidance for Older Adults
Figure 9.1 Projected Number of U.S. Residents 65 Years and Older.
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
Figure 9.2 MyPlate for Older Adults.

9.3 Nutrients of Concern 127
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.
However, high amounts of dietary sodium are associated

TABLE 9.1 Potential biologic changes contributing to
with hypertension.34 Major sources of dietary sodium
altered nutrient status in older adults
come from commercially prepared foods, with only a
small percent coming from salt added at the table. 39 There System Change
has been a dramatic increase in the availability of reduced-
Digestive system ↓ Hydrochloric acid secretion
sodium products available. Everyone, particularly older
adults, should be encouraged to take notice and choose ↓ Digestive juice secretion (pancreas and
those products. small intestine)
↓ Absorptive capacity (malabsorption)
↓ Muscles tone large intestine
9.3.6 Saturated Fat (↓ gastrointestinal motility)
Higher intakes of saturated fat relative to unsaturated fat, ↑ Chronic blood loss due to ulcers and
both monounsaturated and polyunsaturated, are associ- hemorrhoids
ated with higher risk of developing cardiovascular disease.
Liver ↓ Hepatic and biliary function
Major sources of dietary saturated fat are fats of animal
origin and tropical oils. Animal fats include meat and as ↓ Rate detoxification
indicated earlier, dairy fat. Tropical oils include palm, palm Heart ↓ Cardiac output
kernel, and coconut. Intake can be minimized by choosing
lean cuts of meat and limiting both frequency and portion ↓ Strength and flexibility of blood vessels
size. Low- and fat-free dairy products are readily available. Kidneys ↓ Blood flow
Ingredient labels can be used to determine whether com-
mercially prepared foods contain tropical oils. ↓ Glomerular filtration
Senses ↓ Acuity vision and hearing
↓ Taste (loss taste buds, mainly salt
9.3.7 Added Sugar and sweet)
High levels of added sugar intake have been associated ↓ Smell
with increased risk of developing obesity, heart disease,
and type 2 diabetes.39,45 Approximately 47% of added Skin ↓ Synthesis vitamin D
sugar in the diet comes from sugar-sweetened bever- Body composition ↓ Lean muscle mass
ages, 31% comes from snacks and sweets, and the bal-
↑ Fat mass
ance comes from a combination of other food categories,
both obvious and less obvious. 39 The introduction of ↓ Mobility
added sugars as a mandatory requirement of the revised ↓ Dexterity
Nutrition Facts labels make it easier for individuals to
compare items within categories so they can choose items Immune system ↓ T cell-mediated function
with less added sugar. ↑ Susceptibility to infection and malignancy
Pharmacokinetics ↑P
rescription and nonprescription drug use
9.4 SPECIAL DIETARY ↑ Chronic drug therapy
CONSIDERATIONS FOR ↓ Capacity to metabolize drugs
OLDER ADULTS Mouth ↓ Salivary secretion

↑ Altered bite pattern due to tooth loss
The area of maintaining optimal nutrient status in older
adults must be considered in terms of physiological fac-
tors and psychological factors. Special attention to both
of these factors is critical for ensuring optimal health secretion.46 The resulting hypochlorhydria causes a decline
outcomes. in the bioavailability of vitamin B12 . As previously noted,
due to the diminished capacity to synthesize endogenous
vitamin D, older adults may be at a compromised status
for vitamin D and, as a result, for calcium. Impairments
9.4.1 Organ Systems or decreases in the function of the heart, blood vessels,
The way the body handles nutrients can change with and kidneys can stress the normal demands on everyday
advancing age. These changes are mostly due to changes life. Changes in body composition (decreased lean muscle
in the functioning of organ systems, which can ultimately mass and increased fat mass) result in decreased basal
impact health outcomes (Table 9.1). Interestingly, few metabolic rates, energy needs, and capacity for physical
adverse nutritional consequences resulting from advanc- activity.47 Increased use of prescription and nonprescrip-
ing years have been noted that are independent of ancillary tion medications, chronic drug therapy, and decreased
biological changes. These exceptions include vitamin B12 , capacity of the liver to metabolize drugs can compromise
vitamin D, and calcium. With increasing years, many indi- nutrient utilization. These factors should be evaluated on
viduals experience a decline in gastric hydrochloric acid a regular basis by the health care provider.
9.4 Special Dietary Considerations for Older Adults 129
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
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.
9.5.1 Dentition and Associated Senses 9.5.4 Glucose Intolerance/Type 2 Diabetes

Salivary secretions decrease with increasing age. Changes The incidences of glucose intolerance and type 2 diabe-
in bite pattern from partial or complete extraction/loss of tes mellitus increase with age.64,65 The increased inci-
teeth are common. Poorly fitted dentures can make eat- dence has been strongly associated with weight gain in
ing painful and unpleasant. The prevalence of root canals later years. Lifestyle interventions have been shown to be
is higher in older than younger adults. 53,54 Increased inci- efficacious in preventing or delaying the onset of type 2
dence of tooth disease in older adults has been related, in diabetes mellitus.66–68 These include regular daily physical
part, to high levels of sugar consumption.55 Any one or activity, weight loss, and dietary modification consistent
a combination of these factors can restrict the type and with that advocated for the prevention and treatment of
variety of foods consumed. For example, chewing and cardiovascular disease.
swallowing fibrous foods may be difficult due to poor den-
tition, resulting in a shift toward highly processed foods
or juices that are low in fiber content. 56 It is critical when
evaluating dietary intakes of older adults to consider pos-
9.5.5 Hypertension
sible concerns regarding food textures and preparation The incidence of hypertension increases with age.57 This
methods and to assess dentition. increase is associated with changes in the vasculature and
kidneys and is exacerbated by weight gain. A number of
clinical trials have demonstrated clear benefits of dietary
9.5.2 Cardiovascular Disease modification to treat hypertension in older adults. The
DASH (Dietary Approaches to Stop Hypertension) dietary
The rate of cardiovascular disease increases with age, espe- pattern, rich in vegetables, fruits, and fat-free and low-fat
cially after menopause in females.57 Higher saturated fat dairy products, decreases blood pressure in a wide range
coupled with lower polyunsaturated fat intake has consis- of individuals. Further coupling this dietary pattern with
tently been associated with higher rates of cardiovascular sodium restriction has been shown to further decrease
disease.58–60 The American Heart Association/American blood pressure.43
College of Cardiology33 and the 2015–2020 Dietary
Guidelines for Americans39 recommend dietary patterns
that are rich in vegetables and fruits, whole grains, legumes
(beans), fat-free and low-fat dairy products, fish, and lean
9.5.6 Immune Function
meat. No specific recommendations for dietary change are The most commonly associated age-related change in the
made for adults as they age. The response to these recom- immune response is cell-mediated function.69,70 Limited
mendations in terms of plasma lipids appears consistent data suggest vitamin E supplementation may be benefi-
for both genders and all adult age groups.32 cial in decreasing the incidence of respiratory infections in
older adults living in residential settings.71
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.
• 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.
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10
CHAPTER
Effects of an Active Lifestyle on Water

Balance and Water Requirements
Gethin H. Evans, BSc, PhD, Ronald J. Maughan, BSc, PhD, and Susan M. Shirreffs, BSc, PhD
Key Points.................................................................................. 135 10.6 Implications for Drinking Strategies.................................. 139

10.1 Introduction...................................................................... 135 10.7 Hydration as Part of a Healthy Lifestyle............................. 139
10.2 Water Balance.................................................................. 135 10.8 Conclusion.........................................................................141
10.3 Sweating, Water Balance and Water Turnover................... 136 Clinical Applications....................................................................141
10.4 Hydration Status and Performance.................................... 137 References.................................................................................141
10.5 Hydration for Recreational Activity (RPE, Energy Balance)......138
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
activated in response to decreases in blood volume with

aldosterone acting on the collecting ducts of the kidney
to increase sodium reabsorption which, in turn, leads to
water reabsorption and the production of small volumes of
concentrated urine. ANP is secreted from the right atrium
in response to increases in blood pressure and leads to an
increase in urine volume.
Thirst and habit are major drivers of fluid intake.
Thirst is triggered by a complex interaction between phys-
iological, psychological, and behavioral factors.4 Changes
in plasma osmolality and blood volume are thought to
play important roles in the thirst response, so the same
Figure 10.1 Approximate Distribution of Water between the
factors that regulate water loss are involved in water
Main Body Water Compartments. intake. Animal models have suggested that substances
such as angiotensin 2, bradykinin, and serotonin may also
be involved in thirst response. Genetic factors may also
are continuous, so water balance fluctuates throughout account for some individual variation in thirst response,
the course of a day. Over a 24-hour period, water balance although the picture is not entirely clear. 5,6 Generally,
is generally maintained without conscious attention to thirst is considered to be a poor indicator of short-term
intake. Avenues of water intake include fluid consumed as deviations in body water, given observations that unlim-
drink, in the water content of ingested food, and a small ited access to drinks after periods of fluid restriction tends
amount generated by oxidative metabolism (Table 10.1). not to fully restore water losses7 and rapid fluid ingestion
For sedentary individuals in temperate environments, in these circumstances appears to alleviate the perception
daily water turnover is typically about 2–3 L, with the of thirst.8 The thirst response is considered, however, to
main avenue of loss via urine, with some additional losses be sufficient to restore body water levels over longer time
via respiration, transcutaneous loss, sweating, and fecal periods.
loss. Some individuals exercising in hot conditions may The European Food Safety Authority (EFSA) reports
lose this amount in an hour, as sweating is induced to limit that total (i.e., water from food and fluid) adequate daily
the rise of core temperature that occurs in these situations. water intake is 2.0 liters for an average adult female and 2.5
Urine production is regulated by a number of hor- liters for an average adult male.9 Different adequate total
mones in response to changes in intravascular vol- water intakes are reported by the Institute of Medicine in
ume and osmolality: these include arginine vasopressin the United States, with values reported as 2.7 liters and
(AVP), aldosterone, and atrial natriuretic peptide (ANP). 3.7 liters for adult females and males, respectively.10 The
Secretion of AVP from the posterior pituitary is induced values reported by these bodies are an average (or median)
by an increase in plasma osmolality and a decrease in volume consumed by healthy adults and are, therefore,
blood volume, increasing water reabsorption in the renal classed as adequate intakes rather than recommended
collecting ducts and the production of small volumes of intakes. Considerable variation in the volumes of water
concentrated urine. A one-mosm/kg increase in plasma consumed by healthy adults is observed. For physically
osmolality results in a 0.41 pmol/L increase in plasma active individuals who will lose greater volumes of water
AVP concentration 2 and a three-mosm/kg increase in via sweating, which is exacerbated in hot environments,
plasma osmolality results in a 250-mosm/kg increase in achieving the adequate intakes reported is not a guaran-
urine osmolality.3 A change in blood volume of 7–10% is tee that water intake is sufficient for that individual. It is
required for similar magnitudes of change in urine osmo- likely, however, that water intake throughout the day will
lality, making plasma osmolality the main determinant of match water losses due to a combination of habitual fluid
AVP release. 2 The renin-angiotensin aldosterone system is intake and the individual’s thirst response driving further
fluid intake.
TABLE 10.1 Estimates of Water Intake and Loss by

Various Routes in an Average Sedentary Male Living in a
Temperate Climate 10.3 SWEATING, WATER BALANCE
Water Intake Water Output AND WATER TURNOVER
Metabolism (400 mL) Urine (1400 mL)
Metabolic heat production at rest is approximately 60
Drinking (1500 mL) Respiration (320 mL) watts, but metabolic demand increases in a linear fashion
Food Ingestion (1000 mL) Skin Loss (530 mL) and can reach one kilowatt during moderately hard exer-
cise such as marathon running. This metabolic heat must
Sweat Loss (650 mL) be dissipated to avoid large increases in core temperature,
Water Loss in Feces (100 mL) and this is achieved largely by an increase in sweat rate.
There are many published reports of hydration status,
Total (3000 mL) Total (3000 mL)
sweat rates, and fluid intake in physically active individu-
Source: Data are collated from a variety of sources and can vary greatly from day to als. Most of these studies have focused on elite athletes
day within the same individual as well as between individuals. undertaking training sessions and/or matches in different
10.4 Hydration Status and Performance 137
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 condition 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
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
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.
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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
Implementation of the Exercise Prescription

Rachele M. Pojednic, PhD, EdM, Caroline R. Loveland, MS, and Sarah Tierney Jones, BS
Key Take Home Points................................................................ 147 11.1.2.2 Diabetes Prevention Program for

11.1 Introduction...................................................................... 147 Patients with Prediabetes�� 150
11.1.1 Exercise Professionals for Referral........................ 148 11.1.2.3 SilverSneakers and Enhance Fitness
11.1.1.1 Personal Trainer..................................... 148 for Older Adults�� 150
11.1.1.2 Exercise Physiologist.............................. 148 11.1.2.4 Park Rx and OutdoorsRx for Families...... 150
11.1.1.3 Physical Therapist.................................. 149 11.1.2.5 Exercise is Medicine............................... 151
11.1.1.4 Health Coach.......................................... 149 11.1.2.6 Summary............................................... 151
11.1.2 Successful Programs ............................................ 150 Clinical Applications................................................................... 151
11.1.2.1 Referral Guides...................................... 150 References................................................................................ 152
patterns. It will also outline the range of trained exercise

KEY TAKE HOME POINTS professionals and community programs that serve as the
providers ready to “ fi ll” the exercise prescription.
• Physician-directed exercise prescription is effective
Research shows that physicians generally view exercise
in helping patients make long-term lifestyle changes.
as an important component of a healthy lifestyle. A recent
• Exercise and physical activity referral networks are
survey7 investigated physicians’ current beliefs, attitudes,
not currently being utilized effectively, but success-
and practices regarding exercise prescription. Of the 340
ful strategies and programs have been identified and
physicians who responded, roughly half stated that they
can be used as models for the future.
believe that they play an important role in promoting
• Health care professionals can learn effective exer-
exercise to their patients and that specific recommenda-
cise and physical activity referral practices and
tions would be more effective than open-ended advice.
implement them in clinical practice.
However, the physicians also reported that only 20% or
• Personal trainers, exercise physiologists, physical
less of patients who would benefit most from increasing
therapists, and health coaches can be important
their physical activity level were provided with an exercise
members of a physician’ s referral network.
prescription.
In the same study, only 17% of physicians collaborated
with exercise professionals and fitness facilities, while
11.1 INTRODUCTION 65% of physicians who did not collaborate stated that they
believed this would not be possible in their community.7
Substantial evidence supports the efficacy of clinician-ini- Yet nearly 75% of physicians expressed interest in such a
tiated physical activity counseling, prescription, and refer- partnership if it were available to them. A similar study8
ral. Physicians, specifically, have begun to use physical surveyed health care providers working with patients with
activity vital signs and exercise prescription in their prac- diabetes in a Canadian teaching hospital and found that
tices.1 Yet, even with this increase in exercise counseling all clinician participants would appreciate assistance with
behavior, the CDC reports that only about one in three both learning the fitness facility referral guidelines and
adults were advised by a physician to engage in physical implementing the referral process in their practice.
activity. 2 While this is a significant increase from a decade It could be said that the systems for filling an exercise
earlier, in which only one-fifth of physicians discussed prescription remain elusive, which may be due in part to
physical activity with their patients, it is evident that several barriers perceived by both the physician and the
there are still numerous barriers to prescribing exercise in patient. While physicians clearly wish to promote physi-
health care settings. While research shows that exercise cal activity to their patients, it is evident that the refer-
prescription is effective in helping patients make long- ral process is not utilized effectively. Indeed, a recent
term lifestyle changes, 3 – 6 there is less certainty over how study7 found that 22% of physicians did not refer patients
prescriptions and referrals can be executed by physicians because they were not adequately informed about the
and other health care professionals. 5 This chapter will local exercise facilities available. Yet health care providers
outline the exercise prescription and referral process, with do consider their ability to refer patients to fitness facilities
specific focus on current physician attitudes and practice “ strong” or “ very strong.”8 Despite this perceived ability,
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
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
TABLE 11.1 Clinical referrals for physical activity

Physical activity
professional Target population Reason for referral
11
Personal Trainer Non-Specific Works with individuals to achieve their exercise goals. Conducts fitness evaluations and
creates performance programs for clients. Uses various assessments to design an
appropriate fitness plan. Promotes positive health behavior and motivates clients.
Exercise Non-Specific Helps diagnose and treat a number of diseases through exercise, either in a clinical or
Physiologist nonclinical setting. Works with individuals to provide exercise prescription based on health
history and physical assessment.
Physical Therapist Non-Specific Examines individuals and develops a plan using treatment techniques to improve the
ability to move, reduce pain, restore function, and prevent disability. Works with patients in
a preventative manner in order to prevent the loss of mobility before it occurs. Based on
various assessments and tests, PTs use the gathered information to design a plan of care.
Health Coach Non-Specific Works with individuals to facilitate healthy lifestyle changes like achieving adequate
physical activity, improved nutrition, smoking cessation, and stress reduction. Provides
guidance and personalized motivation to create behavior change strategies and goal
setting.
that takes a “ unique approach to ‘ fi lling’ outdoor play 11.1.2.6 Summary

prescriptions by removing cost and lack of experience as Physicians generally view exercise as an important com-
the biggest barriers for families who are new to the out- ponent of a healthy lifestyle and have begun to use physi-
doors and unfamiliar with their local urban parks and cal activity vital signs and exercise prescriptions in their
trails.” Upon guidance from a physician, families can practices. Still, data indicate only 20– 30% of physicians
register at http://www.outdoorsrx.org/ for access to the are actively prescribing physical activity, signaling room
state parks41 , weekly emails on local outdoor program- for improvement. Barriers do exist, including time, knowl-
ming, outdoor gear rewards, and outdoor trip planning. edge of programming, and professionals. However, these
OutdoorsRx has been implemented in community health impediments can be overcome with simple clinical strate-
centers serving ethnically diverse, low-income, urban gies and a robust referral network. Physical activity and
families and has been well received by clinicians and exercise professionals such as personal trainers, exercise
families. physiologists, physical therapists, and health coaches are
trained to work with patients to implement physical activ-
ity and exercise prescriptions. Moreover, there are several
11.1.2.5 Exercise is Medicine clinic-based strategies, such as referral guides and referral
Exercise is Medicine® (EIM) is a global health program to community-based programming, that can be utilized
designed to improve the health and well-being of patients to educate and encourage patients to “ fi ll” exercise pre-
through a prescription of physical activity, lifestyle scriptions. While writing the physical activity or exercise
changes, and education from physicians and health care prescription falls in the purview of the physician, practi-
providers.17 The goal of EIM is for clinicians to refer to cal execution relies on a robust network of systems and
EIM-credentialed professionals in medical fitness and professionals designed to support patient engagement and
general fitness settings, in order to work with patients to behavior change. Creating these networks is critical for
define realistic and attainable physical activity goals and the successful implementation and future of the use of
expectations. physician-directed exercise prescriptions.
Greenville Health System, in Greenville, SC, with part-
nerships from the local YMCA and the University of South
Carolina, Greenville, has instituted a model of Exercise is CLINICAL APPLICATIONS
Medicine® utilizing a multiphase, comprehensive 12-week
medically based program for adults experiencing at-risk • Physicians generally view exercise as an important
chronic health conditions such as hypertension, obe- component of a healthy lifestyle and have begun
sity, hyperlipidemia, or hypercholesterolemia (http:// to use physical activity vital signs and exercise pre-
eimgreenville.org/).42 Through EIM, participants learn scription in their practices.
how to reduce their risks and improve their overall health • Barriers to prescribing exercise exist, including time,
by adopting healthy behaviors that include exercise and knowledge of programming, and professionals.
movement. In order to ensure long-term success, upon • Barriers can be overcome with simple clinical strate-
completion of the 12-week program, participants are gies and a robust referral network.
encouraged to continue in EIM in the maintenance pro- • Clinic-based strategies can include referral guides
gram. There is an individual cost for the program, and it and referral to community-based programming that
is not covered by Medicaid. Although some YMCAs will can be utilized to educate and encourage patients to
help defray costs. “ fi ll” exercise prescriptions.
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12
CHAPTER
What Physicians Need to Know, Do,

and Say to Promote Physical Activity
Mary A. Kennedy, MS
Key Points.................................................................................. 153 12.2.2 Know the PA Guidelines........................................ 157

12.1 Physical Activity Promotion and the Healthcare Sector...... 153 12.2.3 Record PA as a Vital Sign...................................... 157
12.1.1 Emergence of the Chronic Disease Pandemic........ 153 12.2.4 Provide a Prescription........................................... 157
12.1.2 A Call to Action...................................................... 154 12.2.5 Provide Guidance on Filling the Prescription.......... 158
12.1.3 National Physical Activity Plans............................. 154 12.2.6 Refer to Experts.................................................... 158
12.1.4 Professional Organizations Set Expectations......... 154 12.3 Healthy Doctor, Healthy Patient......................................... 159
12.1.5 Unique Role of the Physician................................. 156 12.3.1 Be a Role Model.................................................... 159
12.1.6 Barriers to Implementation.................................... 156 12.4 Conclusion........................................................................ 159
12.2 Taking Action: Strategies to Incorporate PA Promotion Clinical Applications................................................................... 160
in Practice........................................................................ 156 Resources................................................................................. 160
12.2.1 Seek Out Continuing Education to Fill References................................................................................ 160
Knowledge Gaps�� 156
realize meaningful change and improve the health of our

KEY POINTS population.
The healthcare community has been identified as a sec-
• The healthcare sector has a vital role in reversing
tor of society necessary to influence and support physi-
the current pandemic of inactivity and burden of
cally active lifestyles.6,7 A call to action has been made
chronic disease.
for this community to adopt practices that allow for the
• Comprehensive strategies from multiple public
regular discussion and promotion of physical activity to
health and professional organizations have direc-
all patients. Physicians, in particular, play a crucial role
tives to guide the healthcare sector in this work.
in the success of this effort, though several barriers have
• Physicians have been identified as key influencers to
been identified that need to be overcome in order to suc-
engage patients in physical activity.
cessfully implement change.
• Several evidence-based resources are available to
This chapter aims to provide a framework for physi-
help physicians increase their knowledge about
cians to promote physical activity to their patients. It will
physical activity and provide appropriate guidance
review the support for the role of the healthcare sector
to their patients on the topic.
in PA promotion efforts; discuss the critical strategies a
clinician should employ in order to effectively implement
Physical activity (PA) is an essential component of overall
PA promotion into their practice; and highlight available
health.1,2 Over the past several decades, a strong evidence
tools and resources to assist providers in these efforts.
base has been built for its role in the prevention and treat-
ment of many chronic diseases, including cardiovascular
disease, type 2 diabetes, and certain types of cancer. 2 Yet
it remains a struggle to get people to engage in meaningful
12.1 PHYSICAL ACTIVITY PROMOTION
amounts of physical activity. Estimates suggest that more AND THE HEALTHCARE SECTOR
than 80% of adults in the United States do not meet the
current physical activity guidelines; that estimate remains 12.1.1 Emergence of the Chronic
consistent for adolescents. 3 This high level of physical
inactivity has been described as one of the biggest public
Disease Pandemic
health threats of the 21st century because of the result- Health promotion has been an area of focus for the health-
ing long-term health implications.4 The World Health care sector since the earliest days of medicine, though its
Organization (WHO) currently ranks physical inactivity level of priority has evolved over time. This evolution is
as the fourth leading cause of death worldwide. 5 Novel recounted in Dr. Jack Berryman’s 2010 paper, “Exercise is
solutions from multiple sectors of society are required to Medicine: A Historical Perspective”.8 Berryman describes
153
154 Chapter 12 What Physicians Need to Know, Do, and Say to Promote Physical Activity
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.
approach, informed by the available evidence, for assess-

TABLE 12.2 The exercise is medicine solution model
ing and prescribing PA in primary care and referring to
local networks of community-based PA resources”. 21 Step Module Activity
The EIM Solution aims to integrate physical activity into
1 Clinical Physical activity assessment
healthcare and link patients to evidence-based community
resources. 22 It is outlined in Table 12.2. As described in 2 Physical activity prescription/behavioral
the table, healthcare providers are the first point of con- counseling
tact, and their role is to assess and prescribe PA for their 3 Physical activity self-management or
patients, as well as refer them to exercise professionals/ referral
community programs. EIM recognized the need for tools
4 Community Development and training of a
to help inform and guide providers through these steps.
community-based PA referral network
Their “Healthcare Providers’ Action Guide” fills that gap.
It is a free resource that can be downloaded from the EIM 5 Active Health Clinical-community integration and
website (see the “Resources” section at the end of the chap- Technology utilization of Active health technology/
objective PA assessment
ter). 23 This guide offers step-by-step advice about how to
promote PA in a healthcare setting, assess a patient’s level Adapted from Lobelo F, Stoutenberg M, Hutber A. The exercise is medicine global
of PA, write a basic and advanced PA prescription, and health initiative: a 2014 update. Br J Sports Med. 2014:bjsports-2013-093080.
shows where to find qualified exercise professionals for

patient referrals. It also provides tools, such as sample fly-
12.2 TAKING ACTION: STRATEGIES
ers and PA prescription pads, to assist with implementa- TO INCORPORATE PA
tion efforts.
PROMOTION IN PRACTICE
12.1.5 Unique Role of the Physician 12.2.1 Seek Out Continuing Education
to Fill Knowledge Gaps
While the healthcare sector, as a whole, has been called
upon to promote physical activity among patients world- The current Western medical education system does not
wide, physicians are often a central focus of these ini- prioritize prevention and lifestyle modification, and as
tiatives because they have been recognized as having a a result, many of today’s practicing physicians did not
unique influence on patient behavior. Perhaps the most receive training regarding physical activity. The U.S.
important attribute of a physician is the level of respect Institute of Medicine brought this issue to light in their
and authority they command from patients. Several stud- 2004 report on improving medical education, noting that
ies have revealed that physicians are the most trusted PA was not effectively included in most medical school
source of PA information, and patients prefer to receive curricula. 35 Two subsequent systematic reviews supported
the initial advice regarding activity from their physician this finding. A 2012 systematic review of behavior change
as opposed to another healthcare provider, such as a dieti- counseling curricula in medical trainees included 109
cian, physical therapist, or nurse.24–26 A recent qualita- studies and found that PA was the least-addressed topic
tive study investigating pre-frail and frail older people’s of all health behaviors reviewed (i.e., smoking, nutrition,
perspectives on receiving advice about exercise revealed alcohol/drug use, exercise). 36 Additionally, a system-
that this preference, in part, comes from the belief that the atic review published in 2014 that focused specifically
primary care physician is the person most familiar with on physical activity counseling in medical school educa-
a patient’s medical conditions and is the primary referrer tion found very few programs in existence (n = 11) and
to healthcare services.25 Participants in this study consis- those that were included lacked consistency with regard
tently expressed they would exercise if their general prac- to teaching methods, program duration, and placement
titioner would tell them to do so. Additionally, evidence within the curriculum.37 The lack of consistent training
suggests a physician’s advice may have a “priming effect,” means the majority of today’s practicing physicians have
acting as a catalyst for change by making patients more not received adequate training in regard to physical activ-
aware of health information and programs and/or view- ity. As a result, many physicians do not feel confident in
ing that information as more relevant.27 Finally, physicians providing PA advice to their patients.38
have regular contact with their patients and are well posi- Several initiatives are working to address the lack of
tioned to provide this advice. Studies estimate 70–80% of PA training in medical education, and current medical
adults in developed countries report at least one physician students have expressed support for this change. 39 The
contact each year.28,29 Though the trend is moving in the Lifestyle Medicine Education Collaborative (LMEd) is one
right direction, there is still a long way to go. Data from example in the United States.40 The sole focus of LMEd
the CDC report that just 32% of adults who saw a physi- is to integrate lifestyle medicine education (including PA,
cian or other health professional in 2010 had been advised nutrition, behavior change, and self-care) into the curri-
regarding physical activity.30 Several studies also report cula of U.S. medical schools. It was created in 2013 and
this low rate of physician counseling.6,25,31 has reached more than half of all U.S. medical schools.
Medical schools interested in implementing lifestyle medi-
cine into their curriculum can connect with professionals
at LMEd to obtain support, mentorship, and resources.
12.1.6 Barriers to Implementation LMEd resources are appropriate for everyone involved in
Despite the clear need for physician involvement in PA medical schools, from deans to students. LMEd hosts a
promotion, there are well-documented barriers to partici- “Lifestyle Medicine” collection of peer-reviewed curricu-
pation. A lack of knowledge and confidence in the subject lar resources within the MedEdPORTAL maintained by
area, not enough time for the discussion, and disbelief that the Association of American Medical Colleges and a sec-
patients will follow through with the prescribed behav- ond collection within LMEd’s mentoring toolbox. LMEd
iors are three of the most commonly cited barriers. 25,32,33 uses a categorical assessment test of retired questions from
While these issues have merit, efforts are being made to the National Board of Medical Examiners to assess medi-
directly address and reduce these barriers. cal student knowledge about PA and other lifestyle issues
Physicians who are willing to make small, simple (e.g. nutrition, tobacco cessation, stress, sleep). These
changes to incorporate PA measurements and/or advice resources can be found in the “Resources” section at the
into their practice have the potential to make substantial end of this chapter.
impact. Increasing the number of patients who are physi- While efforts to create change in medical education
cally active can help prevent disease and prevent health- are evolving, today’s practicing physicians need to seek
care costs from becoming unsustainable. 34 The following out resources to educate themselves and build their con-
sections contain suggestions for incorporating evidence- fidence and competence to discuss PA with their patients.
based solutions into practice, while addressing some of the Continuing Medical Education (CME) courses offer a
barriers listed above. promising resource. Evidence supports the effectiveness of
12.2 Taking Action: Strategies to Incorporate PA Promotion in Practice 157
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
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
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/
American College of Preventive Medicine

CLINICAL APPLICATIONS • Annual Meeting, CMEs,
+
Residence Program:
http://www.acpm.org/
1. CME opportunities from professional organizations
offer opportunities to learn best practices and stay American College of Sports Medicine: Exercise is Medicine
abreast of advances in the field (see the “Resources”
section). These resources can assist clinicians in • Healthcare Providers Action Guide: http: //www
meeting the directive set forth by multiple public .exer c isei s medi c ine. o rg/s u ppor t _pag e .php / heal
health and professional organizations to incorpo- thcare-providers/
rate PA counseling into usual care.
2. Physicians are just one part of the solution. A systems Institute of Lifestyle Medicine
approach can assist in streamlining the prescription • Online + Live CMEs: http://www.instituteoflifestyl
process and overcoming the common barriers of emedicine.org/
lack of time and knowledge. Train staff (e.g., nurses,
MAs) to collect PA data as part of usual care, update Lifestyle Medicine Education Collaborative
EMRs to store and prominently display PA-related
data, and refer patients to exercise professionals to • Curricular Resources + Webinars: http://lifestyle-
fill their prescription. medicineeducation.org/
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13
CHAPTER
Physical Fitness Evaluation

Peter Kokkinos, PhD and Jonathan Myers, PhD
Key Take Home Points................................................................ 163 13.11 Muscular Fitness............................................................ 170

13.1 Definition of Physical Fitness.......................................... 163 13.12 Muscular Strength.......................................................... 170
13.2 Aerobic and Anaerobic Fitness........................................ 163 13.13 Muscular Endurance....................................................... 171
13.3 Determining Exercise Capacity: Direct Method-Open 13.14 Tests of Anaerobic Power................................................ 171
Circuit Spirometry........................................................... 164 13.15 Body Composition........................................................... 171
13.4 Determining Aerobic Fitness by Standardized Tests 13.15.1 Definition, Assessment, and Classification of
using Indirect Methods................................................... 164 Overweight and Obesity�� 171
13.5 Protocols........................................................................ 166 13.15.2 Hydrodensiometry or Underwater Weighing.........171
13.6 Cycle Ergometer Protocols.............................................. 168 13.15.3 Other Methods.................................................. 173
13.7 Ramp Testing.................................................................. 168 13.16 Waist Circumference....................................................... 173
13.8 Submaximal Testing....................................................... 169 13.17 Skinfold Assessment........................................................174
13.9 Walk Tests for Cardiorespiratory Fitness Assessment........ 169 References.................................................................................174
13.10 Non-Exercise Test Estimates of Cardiorespiratory
Fitness............................................................................ 170
KEY TAKE HOME POINTS 13.1 DEFINITION OF PHYSICAL

• There are many components of fitness that are FITNESS
important to health, including cardiorespiratory
fitness, muscular strength, endurance, and body The Centers for Disease Control and Prevention (CDC)
composition. and the American College of Sports Medicine (ACSM)
• Various measures of fitness have important impli- define physical fitness as “a set of physical attributes that
cations for overall health, including one’s ability to people have or achieve that relates to the ability to per-
perform recreational or occupational activities, the form physical activity”.1,2 These attributes have impor-
determination of disability, injury prevention, and tant implications for overall health, including one’s ability
skeletal muscle, bone, and cardiovascular health. to perform recreational or occupational activities, the
• Cardiorespiratory fitness is most accurately deter- determination of disability, injury prevention, and skel-
mined directly by a maximal exercise test in which etal muscle, bone, and cardiovascular health. Moreover,
oxygen uptake is determined directly. higher fitness is strongly associated with better long-term
• Cardiorespiratory fitness can also be estimated indi- health outcomes. 3,4 Engaging in proper physical training
rectly from the external work rate achieved on a leads to an improvement in these physical attributes and
treadmill or cycle ergometer. physical fitness. The degree of improvement is determined
• While many exercise protocols are used for exercise by several factors, including training, diet, rest, psycho-
testing, guidelines recommend using individualized logical factors, and genetics.
tests in which work rate is gradually and evenly
incremented.
• When an exercise test is impractical or unavailable,
walking and strength tests can provide useful infor-
13.2 AEROBIC AND ANAEROBIC
mation on an individual’s functional capabilities FITNESS
and overall health.
• Overweight and obesity are increasing in prevalence The energy necessary to sustain life and perform work is
throughout the Western world. Estimates of body extracted by the cells in one of two ways: with the use of
composition can provide important health informa- oxygen and without oxygen. Historically, the utilization
tion beyond body weight and body mass index. of oxygen to extract energy has been referred to as aerobic
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 13.1 Fitness Metrics, Methods of Measurement, and Health Implications

Fitness Metric Method of Measurement Health Implications
Measured peak VO2 Cardiopulmonary exercise test Cardiopulmonary function, predictor of outcomes
Estimated exercise Maximum work rate on treadmill or cycle ergometer Cardiopulmonary function, predictor of outcomes
capacity
Muscular strength 1 repetition maximum (upper and lower body) Functional capabilities, ADLs, predictor of
outcomes/disability
Muscular endurance Push-ups, sit-ups, sit-to stand tests Stamina to maintain functional tasks, ADLs
Walking tests 6-minute walk, Cooper 12-minute, Rockport 1-mile, 1.5 Stamina to maintain functional tasks, predictor of
mile test outcomes
Body composition Body weight, BMI, underwater weighing, DEXA, skinfolds, Cardiometabolic risk (insulin resistance, lipid and
waist circumference and waist-to-hip ratio, Bod-pod, MRI, blood pressure abnormalities, inflammation)
bioelectrical impedance
DEXA- Dual X-ray absorptiometry; ADL – Activities of daily living.

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
* Walking and running speed equations were used.
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

Stage Minutes Speed (MPH) % Grade METS 13
Bruce Protocol
1 3 1.7 10 4.6
2 3 2.5 12 7.0
3 3 3.4 14 10.2
4 3 4.2 16 13.5
5 3 5.0 18 17.2
6 3 5.5 20 20.4
7 3 6.0 22 23.8
Modified Bruce
1 3 1.7 0 2.3
2 3 1.7 5 3.5
3 3 1.7 10 4.6
4 3 2.5 12 7.0
5 3 3.4 14 10.2
6 3 4.2 16 13.5
7 3 5.0 18 17.2
8 3 5.5 20 20.4
9 3 6.0 22 23.8
Balke-Ware
1 3 3.3 1 4.0
2 3 3.3 2 4.4
3 3 3.3 3 4.9
4 3 3.3 4 5.3
5 3 3.3 5 5.8
6 3 3.3 6 6.3
7 3 3.3 7 6.7
8 3 3.3 8 7.2
9 3 3.3 9 7.6
10 3 3.3 10 8.1
11 3 3.3 11 8.5
12 3 3.3 12 9.0
13 3 3.3 13 9.4
14 3 3.3 14 9.9
15 3 3.3 15 10.3
16 3 3.3 16 10.8
17 3 3.3 17 11.3
18 3 3.3 18 11.7
19 3 3.3 19 12.2
20 3 3.3 20 12.6
21 3 3.3 21 13.1
Continued
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
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
Percent body fat is then calculated by the two formulas as

13.15 BODY COMPOSITION follows:
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
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)
TABLE 13.4 Various Methods of Assessing Body Composition

Method/techniques Method of Assessment Advantages Disadvantages
Densitometry from Subject exhales fully all air. Then It is based on Archimedes’ Expensive and time-consuming.
Underwater Weighing he/she is submersed in water for Principle. This method Requires a laboratory equipped with a
only a few seconds. Weight is computes percentage body fat water tank trained personnel. It also
assessed underwater. from body density (body mass/ requires that individuals exhale forcefully
body volume). to reduce all possible air from lungs.
Then they are submersed in water for
several trials, each lasting several
seconds. This may not be tolerated well
by some subjects, who will either not
undergo the procedure or make it
difficult to obtain an accurate reading.
Dual-Energy Uses two low- energy distinct x-ray Quick, takes approximately 12 Expensive, requires trained personnel.
X-ray Absorptiometry beams that penetrate bone and soft minutes to complete and
(DXA) tissue areas to the depth of 30 cm. correlates very highly with
Computer software reconstructs the densitometry. Total body mass
attenuated beams and produces an or regional tissue mass can be
image of the tissues and quantify assessed.
muscle and fat mass.
Bod-Pod Relatively new procedure that uses Quick, takes approximately 3–5 Expensive. Claustrophobia may be an
an elliptical-shaped box that the minutes and has high issue with some participants.
subject sits in. It is based on air reproducibility. Does not require
displacement plethysmography any special skills by technician.
Magnetic Resonance Can distinguish between Very expensive, requires highly trained
Imaging (MRI) changes in muscle mass and technicians. Cost-prohibitive for large
fat. Good for studies designed cohort studies.
to assess changes in muscle
mass (i.e., resistance (weight)
training).
Bioelectrical Impedance A light current is introduced into Quick, relatively inexpensive. Tends to over-predict body fat. Requires
the individual. Body fat is estimated trained personnel and standardized
by opposition to current flow. conditions (hydration, environmental
temperature) that may not be possible in
all situations.
Skinfolds Requires a caliper that measures Relatively easy and inexpensive Skilled and experienced personnel are
body fat at standardized anatomical to perform (requires a caliper). required.
body sites. No special laboratory required
other than a room for some
privacy. Time requirements are
only a few minutes per subject,
thus allowing large numbers of
individuals to be processed.
BMI Weight and height are needed. The simplest and least It is only an index of body dimensions. It
expensive method, requiring does not measure body fat, but only
only the weight (kg) and height assumes that higher BMI translates to
(m) of the individual. higher body fat content. This may or may
not be true and can vary greatly for
different populations.
Waist circumference Measurements of waist and hip Simple, inexpensive, and Both waist circumference and the
and waist-hip ratio circumference. relatively quick to perform. waist-to-hip ratio are indices of body
composition. They do not measure body
fat. However, they both provide an index
of fat distribution.
13.16 Waist Circumference 173
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.
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
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14
CHAPTER
Exercise Prescription for Apparently Healthy

Individuals and for Special Populations
Paul G. Davis, PhD, ACSM-CEP
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
metabolic, or renal disease to participate in mod-

KEY TAKE-HOME POINTS erate-intensity physical activity and, if desired, to
gradually progress to vigorous-intensity physical
• Those who regularly practice physical activity carry
activity without prior medical clearance.
a lower risk of premature mortality and of contract-
ing several of the most prevalent chronic diseases,
including cardiovascular disease, type 2 diabetes, More now than ever, increasing one’s physical activ-
some cancers. Functional abilities are also likely to ity is recognized as an important means of improv-
be preserved to an older age. ing one’s health. Tables 14.1 and 14.2 list the currently
• It is recommended that adults participate in 150– documented health benefits of physical activity.1 Physical
300 minutes of moderate-intensity physical activity, activity is defined as “bodily movement that is produced
or 75–150 minutes of vigorous-intensity physical by the contraction of skeletal muscle and that substan-
activity, per week. Muscle-strengthening exercise tially increases energy expenditure”. 2 Exercise, on the
should also be practiced 2–3 days per week. Balance other hand, is a more strictly defined subset of physical
exercise should also be included for those who may activity that is “planned, structured, and repetitive bodily
be at risk of falling. movement done to improve or maintain one or more com-
• The above guidelines can be met through varying ponents of physical fitness” (e.g., cardiorespiratory endur-
combinations of frequency, intensity, and duration. ance, muscular strength). 2 Increases in both exercise
Enjoyable modes of physical activity should be cho- and overall physical activity can maintain and improve
sen in order to enhance adherence. health. Accordingly, this chapter will (1) review the cur-
• Everyone should be physically active. If the above rent recommendations for physical activity, (2) discuss
guidelines cannot be met due to disease or frailty, they prescription of both formal exercise and overall physical
should be attained to the best of a person’s ability. activity, and (3) discuss prudent alterations to the normal
• It is considered safe for persons not possessing and exercise prescription in some of the more prevalent clini-
without signs and symptoms of cardiovascular, cal populations.
177
178 Chapter 14 Exercise Prescription for Apparently Healthy Individuals and for Special Populations
TABLE 14.1 Documented health benefits of physical activity – General population*

Children
3 to <6 years of age Improved bone health and weight status
6 to 11 years of age Improved cognitive function (ages 6 to 13 years)
Improved cardiorespiratory and muscular fitness
Improved bone health
Improved cardiovascular risk factor status
Improved weight status or adiposity
Fewer symptoms of depression
Adults, All Ages
All-cause mortality Lower risk
Cardiometabolic conditions Lower cardiovascular incidence and mortality (including heart disease and stroke)
Lower incidence of hypertension
Lower incidence of type 2 diabetes
Cancer Lower incidence of bladder, breast, colon, endometrium, esophagus, kidney, stomach, and lung
cancers
Brain health Reduced risk of dementia
Improved cognitive function
Improved cognitive function following bouts of aerobic activity
Improved quality of life
Improved sleep
Reduced feelings of anxiety and depression in healthy people and in people with existing clinical
syndromes
Reduced incidence of depression
Weight status Reduced risk of excessive weight gain
Weight loss and the prevention of weight regain following initial weight loss when a sufficient dose
of moderate-to-vigorous physical activity is attained
An additive effect on weight loss when combined with moderate dietary restriction
Older Adults
Falls Reduced incidence of falls
Reduced incidence of fall-related injuries
Physical function Improved function in older adults with and without frailty
* 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.
14.1 PHYSICAL ACTIVITY A combination of moderate- and vigorous-intensity activ-

ity may also be employed. In addition, resistance training
RECOMMENDATIONS involving all major muscle groups is recommended at least
twice weekly. Additional recommendations for children,
In 2008, the U.S. Department of Health and Human the elderly, and other special populations are discussed
Services released its Physical Activity Guidelines for later in this chapter.
Americans. 3 The purpose of this document was both to Although the basic Physical Activity Guidelines are
summarize the scientific data related to physical activity likely to remain intact, the Advisory Committee did
published since the release of the 1996 Surgeon General’s describe findings that are novel relative to the 2008 report.
Report, Physical Activity and Health, 3 and to resolve Regarding the accumulation of moderate- to vigorous-
any confusion created through differing recommenda- intensity physical activity, there is no longer a premise that
tions released after the Surgeon General’s report. Updated only activity bouts of 10 minutes or longer are recognized
Guidelines are targeted for release in late 2018 and, in a as being beneficial to health. Newer evidence indicates that
recent report,1 the Guidelines Advisory Committee con- moderate to vigorous bouts of any time length that are
tinued to support the following: for adults aged 18 to 64, included in one’s weekly total lead to health benefits. In
a minimum of 150 weekly minutes of moderate-intensity addition, there is no threshold amount of physical activity
aerobic activity are recommended, with recognition that needed to produce health benefits. Although not optimal,
increasing benefits are likely to accrue through at least increasing a low level of physical activity to a volume that
300 minutes per week. Alternatively, 75 to 150 minutes is still below that recommended in the Guidelines will
of vigorous-intensity aerobic activity can be performed still yield some benefit. In fact, in lower-active individu-
to amass similar benefits (moderate- and vigorous-inten- als, replacing sedentary behavior (e.g., prolonged sitting)
sity aerobic activity are defined and discussed below). with light-intensity activity (e.g., standing, slow walking)
14.2 Exercise Prescription 179
life. For example, the ability to drive a car or cross a busy

TABLE 14.2 Documented health benefits of physical
14
street safely depends as much on skill-related as health-
activity – Individuals with preexisting medical conditions*
related fitness. Conversely, all of the health-related fitness
Breast cancer Reduced risk of all-cause and parameters are key elements of various athletic and recre-
breast cancer mortality ational activities. Therefore, while categorization of these
Colorectal cancer Reduced risk of all-cause and elements may be helpful in developing fitness goals and an
colorectal cancer mortality exercise plan, one should realize that training toward ele-
ments of both health-related and skill-related fitness may
Prostate cancer Reduced risk of prostate cancer
be prudent with some clients.
mortality
Osteoarthritis Decreased pain
Improved function and quality of life
14.2.2 Exercise Training Principles
Hypertension Reduced risk of progression of
cardiovascular disease Although goals and responses to physical activity and
Reduced risk of increased blood exercise training can vary considerably from person to
pressure over time person, three general principles should be considered
Type 2 diabetes Reduced risk of cardiovascular when developing an exercise plan: progressive overload,
mortality specificity, and reversibility.
Reduced progression of disease
indicators: hemoglobin A1c, blood
pressure, blood lipids, and body 14.2.2.1 Progressive Overload
mass index
Adaptations only occur in physiological systems when the
Multiple sclerosis Improved walking systems are stressed at levels to which they are unaccus-
Improved physical fitness tomed. In other words, for any physical fitness or health
Dementia Improved cognition parameter, a threshold of physical activity exists that a
person must exceed in order to experience improvement.
Some conditions with Improved cognition
This minimal amount of training needed depends upon
impaired executive
function (attention deficit both the baseline level of the variable to be changed and a
disorder, schizophrenia, person’s genetic capacity to experience positive changes in
multiple sclerosis, the targeted physiological system(s).
Parkinson’s disease, and Given a steady overload, physiological improvement
stroke) will level off or plateau after a given period of time. The
term progressive overload indicates that the training
* From 2018 Physical Activity Guidelines Advisory Committee. 2018 Physical
Activity Guidelines Advisory Committee Scientific Report. Washington, DC: U.S. stimulus must continue to increase in order for further
Department of Health and Human Services, 2018. Available at: https://health.gov/p improvement to be recognized. The overall training stim-
aguidelines/second-edition/report/pdf/PAG_Advisory_Committee_Report.pdf.
ulus can usually be augmented by increasing the intensity,
duration, and/or frequency of physical activity.
can result in lower risk of all-cause mortality, cardiovas- 14.2.2.2 Specificity

cular disease incidence and mortality, and type 2 diabetes
incidence.1 Overload will only result in an adaptation to the muscle
groups and physiological systems that are stressed in
training. Specificity of training applies to the motor units
14.2 EXERCISE PRESCRIPTION involved (e.g., muscles used, joint angle), speed of con-
traction, and the energy systems and primary substrates
used (e.g., aerobic versus anaerobic metabolism, fat versus
14.2.1 Physical Fitness Parameters carbohydrate). Unless a person is severely untrained (e.g.,
Physical Fitness is “the ability to carry out daily tasks frail elderly), strength training will do little to improve
with vigor and alertness, without undue fatigue and with cardiorespiratory endurance and vice versa. Furthermore,
ample energy to enjoy leisure-time pursuits and to meet although distance cycling and running are both aerobic
unforeseen emergencies”.4 Elements of physical fitness activities using the legs, the carryover from training in one
have traditionally been categorized as either health-related mode to performance improvement in the other is limited.
(cardiorespiratory endurance, muscular endurance, mus- Similarly, while squat training mainly improves quadri-
cular strength, body composition, flexibility) or skill- ceps strength, this improvement may not be recognized
related (agility, balance, coordination, speed, power, when testing with another exercise (e.g., leg extension)
reaction time). 5 Definitions of the various physical fitness that uses different motor unit recruitment and acces-
elements are listed in Table 14.3. The health-related fit- sory muscles. Therefore, in addition to training specifi-
ness components are certainly important in chronic dis- cally toward a person’s goals, assessment of improvement
ease prevention and rehabilitation. However, particularly should involve testing that is congruent with the training
among the elderly and those with certain musculoskeletal that has been employed. The more specific a person’s train-
diseases, maintenance of a certain level of skill-related fit- ing goals (e.g., athletic performance), the more important
ness is also critical to independent function and quality of these issues become.
TABLE 14.3 Health-related and skill-related physical fitness parameters*†

Health-Related Skill-Related
Cardiorespiratory endurance – the ability of the circulatory and respiratory Agility – the ability to rapidly change the position of the
systems to supply fuel during sustained physical activity and to eliminate entire body in space with speed and accuracy.
fatigue products after supplying fuel. Balance – the maintenance of equilibrium while stationary
Muscular endurance – the ability of muscle groups to exert external force or moving.
for many repetitions or successive exertions. Coordination – the ability to use the senses, such as sight
Muscular strength – the amount of external force that a muscle can exert. and hearing, together with body parts, in performing motor
Body composition – the relative amounts of muscle, fat, bone, and other tasks smoothly and accurately.
vital parts of the body. Speed – the ability to perform a movement within a short
Flexibility – the range of motion available at a joint. period of time.
Power – the rate at which one can perform work.
Reaction time – the time elapsed between stimulation and
the beginning of the reaction to it.
*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.
14.2.2.3 Reversibility regimen, possibly leading to better program compliance.

Just as the body adapts positively to increases in physi- For beginning exercisers, walking is generally a very good
cal activity, it adapts negatively to inactivity. The rate of activity to include since it requires little skill and results in
deconditioning varies depending on the previous training fewer overuse injuries than most other modalities.
level and how much it is curtailed. For example, casting
or extended bed rest can result in sharp, rapid declines in
strength and endurance performance. In a more practi- 14.2.2.6 Intensity of Exercise
cal sense, fitness levels tend to decline significantly after Improvement in VO2max can usually be attained by exer-
about two weeks of exercise cessation. Endurance training cising regularly at 50–85% of VO2reserve (VO2reserve =
of two to three days per week and resistance training of VO2max – VO2rest). Obviously, this range is wide; the most
at least once per week are generally necessary to maintain effective intensity will depend in part upon the duration
previously attained fitness levels. and frequency of exercise. Nevertheless, larger improve-
ments in VO2max typically occur with higher intensities.
However, higher volumes of exercise (to include intensity,
14.2.2.4 Cardiorespiratory Endurance Training duration, and frequency) are more likely to result in over-
Maximal oxygen consumption (VO2max) is the most training symptoms (e.g., fatigue, injury, decreased perfor-
accurate measure of cardiorespiratory fitness. Although mance, suppressed immune function). Exercise training at
some health benefits may be recognized with the practice 60–80% VO2reserve generally results in improved VO2max.
of moderate-intensity physical activity that is less likely However, the intensity threshold for improved VO2max
to improve VO2max,6 strong inverse relationships exist also depends upon baseline fitness level; low-fit, untrained
between VO2max and overall mortality and most major individuals often experience improvement in the light-
chronic diseases.7 As such, the American College of Sports to-moderate intensity range, while highly trained and fit
Medicine has traditionally recommended the following individuals might need to spend a considerable amount of
frequency, intensity, time, and type (FITT) of exercise for their training time above 80% VO2reserve in order to con-
the improvement of cardiorespiratory fitness.8 tinue to improve their cardiorespiratory fitness.8
As stated in this chapter’s introduction, the Physical
Activity Guidelines for Americans give recommendations
14.2.2.5 Type (Mode) of Exercise for both moderate- and vigorous-intensity physical activ-
Activities that overload the cardiorespiratory system are ity. In relative terms, moderate-intensity physical activ-
repetitive (rhythmic) in nature and involve larger muscle ity is defined as activity requiring 40–60% of VO2reserve,
groups. Examples include brisk walking, running, cycling, while vigorous-intensity physical activity is anything that
rowing, and exercising on an elliptical machine. Sports requires above 60% VO2reserve. While moderate-intensity
that constantly require intermittent bouts of vigorous physical activity may result in some fitness improvement
body movement, such as basketball, soccer, and tennis, for those starting at a low fitness level, the progressive
can also contribute to improved cardiorespiratory fitness. overload necessary to elicit and maintain improvement
Unless medical conditions dictate otherwise, the major- lies in the vigorous-intensity range for many people, espe-
ity of exercise should be weight-bearing in order to help cially those who are younger and/or more fit.
prevent osteoporosis. If a person’s VO2max has been measured or estimated
While specificity of training is very important for ath- through exercise testing,7 exercise intensity may be pre-
letes, persons training more for overall health and fitness scribed as a given percentage of VO2reserve. VO2reserve is
purposes will likely benefit from practicing a variety of calculated by subtracting the estimated value for VO2rest
exercise modes. Such practice will likely lead to fewer (1 MET = 3.5 mL.kg−1.min−1) from VO2max. VO2reserve is then
overuse injuries and will also add variety to the training multiplied by the target percentage, and VO2rest is then
14.2 Exercise Prescription 181
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
* MET values may be substituted for VO2 (1 MET = 3.5 mL.kg−1.min−1).

† When possible, use HRmax from maximal graded-exercise test instead of estimation.
# Alternatively, the formula “HRmax = 206.9 − (0.67xage)” may be used.
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
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
exercise in warmer environments and to emphasize fre-

TABLE 14.6 Absolute and relative contraindications to
14
quent fluid intake (every 15–20 minutes). Secondly, adult
aerobic exercise during pregnancy
formulas for maximal heart rate do not apply to children
and adolescents, who typically have maximal heart rates Absolute Contraindications
of approximately 200–205 bpm. For exercise prescription • Hemodynamically significant heart disease
purposes, however, RPE scales tend to work well with • Restrictive lung disease
• Incompetent cervix/cerclage
older children [>8 years old]. 20
• Multiple gestation at risk for premature labor
• Persistent second- or third-trimester bleeding
• Placenta previa after 26 weeks gestation
14.8 OLDER ADULTS • Premature labor during the current pregnancy
• Ruptured membranes
Among older adults, proper physical activity can increase • Preeclampsia/pregnancy-induced hypertension
and maintain physical function, improve and maintain Relative Contraindications
• Severe anemia
body composition, promote psychological and cognitive • Unevaluated maternal cardiac dysrhythmia
well-being, and assist in primary and secondary preven- • Chronic bronchitis
tion of chronic diseases. Keeping in mind that exercise • Poorly controlled type 1 diabetes
intensity is relative (e.g., a given walking speed may be • Extreme morbid obesity
considered light for one person and vigorous for another), • Extreme underweight (BMI <12)
the physical activity guidelines are essentially the same for • History of extremely sedentary lifestyle
• Intrauterine growth restriction in current pregnancy
adults over the age of 65 as they are for middle-aged and • Poorly controlled hypertension
younger adults.3 Frail persons, who may have difficulty • Orthopedic limitations
meeting the guidelines, should practice as much physical • Poorly controlled seizure disorder
activity as they can tolerate with the goal of safely advanc- • Poorly controlled hyperthyroidism
ing their physical activity into the range recommended for • Heavy smoker
the general population. Reprinted with permission from the American College of Obstetricians and
In addition to the same endurance and resistance exer- Gynecologists. ACOG committee opinion: exercise during pregnancy and the post-
cise advocated for the general population, older adults at partum period. International Journal of Gynecology and Obstetrics, 77:79-81, 2002.
risk for falling should add exercises 2–3 days per week
that focus on balance. While a wide variety of such activi-
TABLE 14.7 Warning signs to terminate exercise while
ties exist, the ones performed should focus on a person’s pregnant
particular needs. Examples include walking sideways and
backward, repetitively standing and sitting, standing with • Vaginal bleeding
eyes closed, tai chi, etc. Previously inactive seniors, in par- • Dyspnea prior to exertion
ticular, may benefit from the services of a properly creden- • Dizziness
• Headache
tialed personal trainer or exercise class in the beginning
• Chest pain
stages of an exercise program. • Muscle weakness
• Calf pain or swelling (need to rule out thrombophlebitis)
• Preterm labor
14.9 PREGNANCY AND POSTPARTUM • Decreased fetal movement
• Amniotic fluid leakage
Proper physical activity during pregnancy may help pre- Reprinted with permission from the American College of Obstetricians and
vent excessive weight gain, gestational diabetes, and preg- Gynecologists. ACOG committee opinion: exercise during pregnancy and the post-
partum period. International Journal of Gynecology and Obstetrics, 77:79-81, 2002.
nancy-induced hypertension. When proper precautions
are followed, very little risk is associated with exercise.
On average, women who exercise throughout pregnancy physical activity is safe for most previously active women,
may deliver a few days earlier and have babies that are fetal effects of severe hyperthermia or repeated bouts of
a few ounces lighter. However, there is no evidence that hypoglycemia that may result from more prolonged or
properly practiced exercise leads to preterm deliveries competitive exercise are unknown. Hence, competitive
or low birth-weight babies. Absolute (exercise under no training during pregnancy requires more precaution and
circumstances) and relative (exercise only when benefits close physician supervision. 21
outweigh risks) contraindications and warning signs to Due to potential decompression sickness, ACOG rec-
terminate exercise as published by the American College ommends that scuba diving not be practiced during preg-
of Obstetricians and Gynecologists (ACOG) are listed in nancy. In addition, women who plan to expose themselves
Tables 14.6 and 14.7, respectively. 21 to higher altitudes (>6000 feet) should be made aware of
The Physical Activity Guidelines for Americans3 rec- the signs of altitude sickness at which they should termi-
ommend that previously inactive women progress to at nate exercise, descend from the altitude, and seek medical
least 150 weekly minutes of moderate-intensity physical attention. Sports and other activities with the potential for
activity. In addition, within reason and in consultation contact or falling should be avoided, especially as the preg-
with their physician, women who are already practicing nancy progresses. Also, supine exercise can inhibit venous
vigorous-intensity aerobic activity may continue to do return and is contraindicated after the first trimester.
so during pregnancy as long as no warning signs (e.g., Women at risk or with a history of preterm delivery should
vaginal spotting) surface. Although vigorous-intensity reduce their physical activity during the third trimester.21
The American College of Sports Medicine advocates

TABLE 14.8 Criteria for electrocardiographic stress testing
resistance training during pregnancy to a point of moder-
before exercise training participation in diabetes patients
ate fatigue.8 Such training has been shown to reduce insu-
lin requirements in women with gestational diabetes.22,23 • Age >40 years, with or without cardiovascular disease risk
However, little research has been performed to determine factors other than diabetes
the effects of more intense resistance exercise, particularly • Age >30 years and
• Type 1 or 2 diabetes of >10 years in duration
practicing of the Valsalva maneuver (holding one’s breath
• Hypertension
during exertion) or prolonged or intense contractions • Cigarette smoking
involving the abdominal muscles. The ACSM recommends • Dyslipidemia
avoidance of the Valsalva maneuver after the first trimester.8 • Proliferative or preproliferative retinopathy
During the postpartum period, regularly practiced • Nephropathy including microalbuminuria
physical activity may reduce excessive weight gain and/or • Any of the following, regardless of age
lessen depressive symptoms. In lactating mothers, moder- • Known or suspected coronary artery disease,
cerebrovascular disease, and/or peripheral artery disease
ate-intensity exercise does not significantly affect breast • Autonomic neuropathy
milk content or volume or their infants’ weight gain. 24 In • Advanced nephropathy with renal failure
addition, a combined aerobic and resistance training pro-
gram was shown to decrease bone mineral loss in lactating Reprinted with permission from the American College of Sports Medicine and
American Diabetes Association. Joint Position Statement: Exercise and type 2 dia-
mothers. 25 betes. Medicine and Science in Sports and Exercise, 42:2282-2303, 2010.
Nearly all women without postpartum complications
are able to resume leisure-time physical activity by six
weeks following delivery, if not much sooner. However, may cause a diabetic patient to be oblivious to foot ulcer-
earlier physical activity should begin at a low intensity ations, which are more common due to microcirculatory
and duration and should progress gradually, particularly damage. Therefore, diabetic patients should always exer-
in women who deliver via caesarian section. cise with clean, dry socks and proper fitting footwear. In
addition, they should check their feet daily for blisters
and ulcerations. Non-weight-bearing exercises should be
14.10 DIABETES MELLITUS practiced in persons with foot injuries or open sores. 27
Thermoregulation can also be impaired in persons with
Both type 1 and type 2 diabetes mellitus are characterized advanced diabetes, so particular precaution (e.g., keeping
by abnormally high blood glucose levels. Since physical extremities warm, proper hydration) should be practiced
activity facilitates glucose uptake by skeletal muscle, it in cold and hot weather.
can serve as an important mechanism of managing glu- Due to the risk of intraocular hemorrhage, diabetic
cose concentration in either disease. In addition, through patients with retinopathies should be carefully screened
its effect on weight management, an adequate amount of before participating in exercise. High-impact activities
physical activity (combined with a prudent diet) may assist (including running) and high-intensity activities are not
in partial or, more rarely, full reversal of type 2 diabetes. recommended. In addition, although it can be very ben-
Proper physical activity can also improve one’s cardio- eficial in helping manage blood glucose, higher-intensity
vascular disease (CVD) risk profile. Exercise can also be resistance training that causes straining on the partici-
an effective means of preventing diabetes onset in people pant’s part is contraindicated due to high increases in
with impaired glucose tolerance. 26 blood pressure. 27
It is generally safe for persons with diabetes to partici- Maintenance of a proper blood glucose concentration
pate in light-to-moderate physical activity as long as they is important during and following exercise. As long as they
are asymptomatic and are at low risk (10-year Framingham are feeling well, persons with type 2 diabetes may exercise
risk of <10%) for cardiovascular disease.8,27 However, a with elevated glucose levels (>300 mg.dL −1). 26 However,
physical examination is recommended before engaging persons with type 1 diabetes should not exercise in this
in vigorous-intensity exercise. Recommended criteria for condition (or with glucose >250 mg.dl−1 and the presence
electrocardiographic stress testing before vigorous-inten- of ketone bodies), as this represents insulin deficiency and
sity exercise training are listed in Table 14.8. 27 Although exercise will likely exacerbate the hyperglycemia.
many persons with type 1 and 2 diabetes participate inde- Hypoglycemia is a more common incident during and
pendently in exercise and sports, it is recommended that following exercise. As such, proper balance and timing
novices begin training with a qualified exercise specialist, of exercise, diet, and medication is important. Due to
particularly when resistance training is involved, in order increased glucose uptake during exercise, insulin or insu-
to avoid injury and blood glucose abnormalities that are lin secretagogue doses may need to be decreased in both
more likely to occur in persons with diabetes. 27 type 1 and 2 diabetes patients, particularly in the hours
Chronic hyperglycemia can lead to neural, retinal, preceding exercise. Exercise should not be practiced dur-
and circulatory damage that can present special probing times of peak insulin uptake, and insulin injections
lems during and as a result of exercise in persons with during the hours before exercise should not be in the vicin-
more advanced diabetes. Silent ischemia may be present ity of the exercising muscles. To avoid nocturnal hypogly-
in persons with underlying CVD. In addition to having cemia, it is best not to exercise within a few hours before
proper screening for CVD, such patients need to be aware bedtime. However, if this must be done, a carbohydrate
of other warning signs of CVD (e.g., dizziness, unusual snack should be ingested before going to sleep. In addi-
shortness of breath). In addition, advanced neuropathy tion, carbohydrates (5–30 grams) should be consumed
14.11 Cancer 187
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
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/).
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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
Take Home Points...................................................................... 193 References................................................................................ 196

Clinical Applications................................................................... 196
convincing the patient to follow the doctor’s orders and

TAKE HOME POINTS advice. This is, at times, a necessary approach, especially
when managing acute medical conditions like myocar-
1. Behavior change is the foundational activity through
dial infarctions, strokes, sepsis, bacterial pneumonia,
which Lifestyle Medicine works.
and meningitis. However, with lifestyle changes, the best
2. Healthcare providers need to be versed in behav-
approach is a different approach, the coach approach.
ior change techniques that foster self-efficacy and
With the coach approach, the emphasis is on listening to
cultivate a therapeutic relationship to empower the
the patient rather than informing the patient, motivating
change process.
the patient rather than convincing the patient, and collab-
3. Four key theories outlining behavior change are the
orating with the patient rather than directing the patient.
Health Belief Model, the Transtheoretical Model of
It takes some time to adopt the coach approach after years
Change, the Social Cognitive Theory, and the Social
of practicing the expert approach, but it is worth it. In
Ecological Model of Change.
order to adopt this approach, the practitioner needs to
4. The overall approach to any behavior change
be familiar with and understand the process of behavior
includes goal setting, follow-up, self-monitoring,
change. This entire section of the textbook is devoted to
action planning, problem solving and social support.
this important topic.
“Knowledge is power,” said Sir Francis Bacon. However, There are many behavior change theories and tech-
knowledge alone is not powerful enough to instill lasting niques. There is also a plethora of research examining their
change. Patients need more than lectures from healthcare use. By reviewing the state of the current literature, lifestyle
providers to adopt healthy habits. The field of behavior medicine practitioners will be able to better understand
change has been an active one for decades, dominated by which techniques are most powerful and in which situa-
psychologists, psychiatrists, social workers, nurses, and tions they are most effective. Learning about the different
others at the front line of counseling patients. The entire theories is essential and practicing the different techniques
field is blossoming as more and more attention is being with patients will enable the practitioner to become pro-
given to the impact of lifestyle on health. Research in this ficient with them. The more familiar the practitioners are
area is on the rise, and the groundwork has been laid by with the concepts and the research, the more likely they are
academics and clinicians dedicated to helping people quit to adopt these behavior change strategies. Many lifestyle
unhealthy behaviors and adopt healthy ones, people like medicine specialists are going through their own process of
Dr. James Prochaska, who created the Transtheoretical change in the way they practice medicine and prevention.
Model of Change and Drs. Miller and Rollnick, who Most medical schools did not teach behavior change
described and continue to teach the process of motiva- in the past. Although the research on behavior change
tional interviewing. This Behavioral Medicine section of is more mainstream, teaching behavior change theo-
the textbook is an essential one for all lifestyle medicine ries and techniques is not yet a routine part of medical
practitioners. Patients might know the right amount of training. The Medical College Admission Test (MCAT)
exercise they need to improve their health. Also, they might test changed a few years ago and added a section on psy-
know that they need to eat more vegetables or quit smok- chology, which includes information on behavior change.
ing. But they might not do it without the aid of a health- When standardized tests like medical school entrance
care provider who is versed in behavior change techniques exams and board exams change, the courses and curricu-
that foster self-efficacy, who can tap into intrinsic motiva- lum in pre-med courses, medical school courses, and resi-
tion, and who can cultivate a therapeutic partnership that dencies will have to change as well. There is movement in
can serve to empower and fuel the change process. this direction, and it is gaining momentum.
As physicians and clinicians, we are trained in the The National Institutes of Health have been interested
expert approach. In the expert approach, we spend a in behavior change for years. Karen Glanz, PhD, MPH,
significant amount of time lecturing, informing, and from the University of Pennsylvania, has spent her career
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
Applying Psychological Theories

to Promote Healthy Lifestyles
Maryam Gholami, PhD, Cassandra Herman, MS, Matthew Cole Ainsworth, MPH,
Dori Pekmezi, PhD, and Sarah Linke, PhD, MPH
Key Points.................................................................................. 197 16.4 Ecological Level................................................................ 201

16.1 Individual Level................................................................. 198 16.4.1 Socioecological Model.......................................... 201
16.1.1 Health Belief Model............................................... 198 16.5 Theory-Based Healthy Lifestyle Intervention in
16.1.2 Theory of Reasoned Action, Theory of Planned Research and Practice...................................................... 202
Behavior, Integrated Behavior Model�� 198 16.6 Summary.......................................................................... 203
16.2 Transtheoretical Model...................................................... 200 Clinical Applications.................................................................. 204
16.3 Interpersonal Level........................................................... 200 References................................................................................ 204
16.3.1 Social Cognitive Theory......................................... 200
focus here on a select few that have consistently received

KEY POINTS attention in the health behavior literature, including the fol-
lowing: Health Belief Model (HBM), Theory of Reasoned
• Theories vary based on their focus on the primary
Action (TRA)/Theory of Planned Behavior (TPB),
force(s) influencing behavior change.
Integrated Behavior Model (IBM), Social Cognitive Theory
• The primary force(s) influencing behavior change
(SCT), Transtheoretical Model (TTM), and Socioecological
are: individual, interpersonal, and ecological.
Model (SEM). Later in this chapter, we discuss theory-
• The Socioecological Model is based on the con-
based lifestyle interventions that have been broadly used
cept that behavior has multiple levels of influences,
in both research and practice, either by implementing a full
including intrapersonal, interpersonal, organiza-
model or by using a subset of the most effective constructs.
tional, community, environmental, and policy.
Many of these theories share some similar or even iden-
• Health behavior change interventions are most
tical constructs, including the widely adopted concept of
effective when they target the key constructs of
self-efficacy, which was coined by the famous psychologist
behavior change.
Albert Bandura.4,5 This construct refers to confidence in
one’s abilities to successfully perform a particular behavior
The application of psychological theories and models (i.e., walk one mile) despite barriers such as bad weather
to health behavior change research, program develop- or a busy schedule. Most incorporate static individual dif-
ment, and policy has soared in popularity over the past ferences (e.g., demographic variables), dynamic individual
few decades. Desired outcomes are most likely achieved differences (e.g., mood/affect), and interpersonal factors
within the context of health behavior change programs (e.g., social support), but the degree to which each of these
that are based on an objective understanding of the tar- variables is highlighted varies widely from one theory or
get health behaviors and the variables that influence them; model to another. Although similarities among the models
theories and models enable researchers and other program and theories are clearly apparent, their differences set them
developers to organize these variables to achieve these out- apart from one another and make them more or less useful
comes.1 Theories and models provide structures for iden- as frameworks through which to understand and/or modify
tifying and examining problems, choosing or developing different types of health behaviors. For example, some are
appropriate interventions, and assessing results. They fall more applicable to one-time or short-term health behaviors
within the parameters of the current emphasis on employ- (e.g., HBM), while others are better suited for longer-term
ing evidence-based interventions in public health, behav- ones (e.g., TTM). An overarching characteristic that differ-
ioral medicine, and medicine fields.1 entiates models and theories is their relative focus on the
Comprehensive lists and descriptions of theories and primary force(s) influencing behavior change. Thus, we
models that have been utilized to guide health behavior organize the selected models and theories into three broader
research have been described extensively elsewhere.2,3 We levels: individual, interpersonal, and ecological.
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
Individual Perceptions Modifying Factors Likelihood of Action
Demographic variables (age,

Perceived benefits
sex, ethnicity etc.)
minus perceived
Sociopsychological variables
barriers
(personality, SES etc.)
Perceived Likelihood of
susceptibility and Perceived threat behavior or
perceived severity adherence
Cues to action
Figure 16.1 Health Belief Model.

16.1 Individual Level 199
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
Normative beliefs – Injunctive

others’ expectations norm
Intention to
perform behavior Behavior
Normative beliefs – Descriptive
others’ behaviors norm
Personal Agency
Control Perceived Environmental
beliefs control constraints
Efficacy Self- Habit

beliefs efficacy
Figure 16.2 Integrative Behavior Model.

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 coming 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
Personal Factors Environmental Factors

(cognitive, affective, (social support, convenience,
biological events) culture, policies)
Figure 16.3 Social Cognitive Theory.
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
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.
Figure 16.4 Socioecological Model.

16.6 Summary 203
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.
• 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.
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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
Key Learning Points................................................................... 207 17.3.2 Engaging.............................................................. 210

Clinical Application Take-Home Points........................................ 207 17.3.3 Focusing............................................................... 213
17.1 Introduction...................................................................... 207 17.3.4 Evoking................................................................. 213
17.2 What is Motivational Interviewing?.................................... 208 17.3.5 Planning............................................................... 215
17.2.1 Research and Evidence......................................... 209 17.4 Summary.......................................................................... 216
17.3 Four Processes................................................................. 210 References................................................................................ 216
17.3.1 Introduction.......................................................... 210
KEY LEARNING POINTS 17.1 INTRODUCTION

• Understand the key components of the spirit of The United States spends the most money per capita in
Motivational Interviewing and how it differs from the world on healthcare.1 Additionally, four of the top
more directive communication approaches. ten causes of death in the world (cardiac and respiratory
• Learn the meaning of and how to use OARS (open- disease, diabetes and stroke) are behaviorally related. 2
ended questions, affirmations, reflections, and sum- Because of this, lifestyle medicine has the potential to
maries) when engaging with your patients. fundamentally change healthcare. Clinicians are think-
• Understand the importance of ambivalence and how ing outside their typical prescribing habits and writing
to intentionally focus on increasing change talk more and more prescriptions for exercise and healthy
while minimizing sustain talk. food choices, which is providing savings in healthcare
costs. 3 This change, however, comes with a different
kind of cost: the cost of effort. Patients are faced with
CLINICAL APPLICATION hard decisions about how they live, including potentially
changing major components in their lives. Clinicians will
TAKE-HOME POINTS have to change the tools they use to treat patients, and
this will most definitely include tools of conversation
• Motivational Interviewing (MI) is a strengths-based regarding change.
approach that holds that clients have within them- Making a significant change at least once in a lifetime
selves the capabilities to make lifestyle changes is inevitable, and initiating that change can often be dif-
successfully. ficult—and may never be complete. Change is often very
• MI recognizes and accepts the fact that patients simple in theory yet difficult to implement in practice.
who need to make changes in their lives approach Think, for instance, about flossing. How many people
lifestyle changes at different levels of readiness to floss their teeth as often as recommended? Is this lack
change their behavior. of sufficient flossing due to low supply of floss, a lack of
• Ambivalence is the patient’s ability to see both the knowledge about the importance of flossing or even lack
reasons for and the reasons against change; it is a of time to floss? Perhaps not. Most likely it is due to a
normal behavior that should be expected when any- low intrinsic need or perceived importance of flossing. For
one considers making a change in their lives. years, clinicians, teachers, consultants, and others recom-
• Clinicians should focus their attention on creat- mending behavior change, relied on a “directive approach”
ing therapeutic rapport with the patient and then to change (i.e., telling folks what to do). While such an
increasing change talk and decreasing sustain talk. approach may be indicated in certain situations (e.g.,
207
208 Chapter 17 Motivational Interviewing and Lifestyle Change
severe acute illnesses or emergencies), this approach tends

to backfire when addressing other situations. Although
17.2 WHAT IS MOTIVATIONAL
not always conscious about being directive, clinicians INTERVIEWING?
have often held the view that “I, the expert have the key
to change, which I will impart unto you, when and if you To better understand MI, it is helpful to explore its ori-
are ready.” If behavior change did not result, patients were gins. The foundation for MI was set during a clinical
deemed to be unmotivated, uncaring, and non-compliant. trial comparing treatment approaches for individuals
Motivational Interviewing4 is one clinical tool that allows with problems drinking.8 As part of this trial, clinicians’
for a shift in how we “see” patients’ attempts at making empathic statements towards their patients were recorded
changes. With this change of view comes a change in lan- by supervisors. It was noted that these empathic state-
guage. Instead of being non-compliant, a patient is seen as ments had a stronger effect on drinking behavior than the
ambivalent about changing, and the role of clinicians is to interventions being evaluated and that these improvements
adopt a “guiding” or “directional approach” as opposed in drinking behavior were maintained up to 24 months
to the more directive approach mentioned above. Such a following the intervention.9 The importance and utility
guiding/directional approach provides hope that change of empathy were reinforced after Miller participated in a
is possible. Paradoxically, respecting a patient’s autonomy role-play process where he modeled his therapeutic style
and freedom to not change is sometimes what makes the for a group of psychologists. His audience’s questioning of
change possible. Miller’s approach to treating alcohol problems led him to
Motivational Interviewing was birthed in the addic- identify the framework that would later become MI.
tions field and is a therapeutic approach that pays specific Since then, MI has evolved into a clinical approach
attention to the language of change. This specific atten- aimed at increasing an individual’s motivation for behav-
tion to the language of change offers an alternative view ior change.10,11 This communication method is not the
to addressing treatment readiness—instead of waiting for combination of a set of techniques to apply at random.
the motivation and readiness to suddenly appear, clini- It requires a clinician to purposely listen for two types
cians can work on enhancing the motivation and readiness of language: change talk and sustain talk. Simply put,
to change. There is an inherent view with MI practitioners change talk refers to statements focused on why a person
that they, the practitioners, are only responsible for the should engage in the desired behavior, while sustain talk
interaction between themselves and the patient, not the refers to reasons why a person should continue their cur-
specific outcome. Realistically, this is rooted in the fun- rent behavior(s). Often change and sustain talk occur in
damental truism that clinicians can do very little to make the same sentence, and the clinician’s goal is to strategi-
our patients implement sustained behavior change unless cally evoke change talk while simultaneously minimizing
they, themselves, want to do so. Clinicians can, however, sustain talk during certain parts of the encounter.
assist them in increasing and strengthening their internal This natural process of seeing reasons to change, as
motivation and preparedness for the change. MI offers cli- well as reasons not to, is referred to as ambivalence.4 For
nicians a lens that is more helpful and is proven to reduce example, an obese individual with poorly controlled dia-
burnout.5 As Miller and Rollnick put it, MI “involves a betes may express interest in increasing their consump-
collaborative partnership with patients, a respectful evok- tion of fruits and vegetables to lose weight yet struggle
ing of their own motivation and wisdom and a radical to make healthy choices when presented with sweets and
acceptance recognizing that ultimately whether change junk foods at work. The difficulty implementing behavior
happens is each person’s own choice, an autonomy that change persists despite an individual having the knowledge
cannot be taken away no matter how much one might of why they should act differently. Furthermore, MI posits
wish to at times.”4 that a patient has the resources they need to increase their
Currently, Motivational Interviewing: Helping People motivation for change within themselves. Through MI,
Change is in its third edition. Numerous other supportive their ambivalence can be explored and ultimately resolved.
texts have also been written describing the use of MI in While exploring ambivalence, MI encourages clini-
myriad settings ranging from treatment of addictions and cians to resist the “righting reflex,” or the tendency to
chronic illness to multiple offender programs and school argue for the behavior changes they wish to see in the
systems. Since the first edition, MI has been cited in more patient.4 The desired effect of telling someone why they
than 25,000 articles and has been studied in over 200 ran- should change is for the patient to align with these rea-
domized clinical trials.4 Furthermore, there have been over sons. However, what tends to happen is that the patient
16 different books expounding on MI, ranging from treat- defends their choices, paradoxically strengthening their
ing addictions and psychological problems to managing rationale for not changing the behavior. People, in gen-
classroom behaviors and interactions with dental patients. eral, tend to more strongly align with their own thoughts
MI improved outcomes in 63% of the studies examined.6 and opinions. When they verbalize their own reasons for
A recent review on the effects of MI found it to be effective sustaining their behavior, they may more closely align
in improving a wide range of medical outcomes, includ- with these beliefs than they previously had.
ing blood pressure, cholesterol, HIV viral load, alcohol MI differs from other treatment approaches in that it
use, marijuana use, abstaining from tobacco, and adher- is necessary to understand and demonstrate the “spirit
ing to medical advice.6 Impressively, the effects of MI hold of MI” to effectively utilize it.4,11 The spirit of MI differs
regardless of the clinician’s background (e.g., nurse, men- from the techniques a clinician can employ as part of this
tal health clinician) as long as the clinician has sufficient approach. It is characterized by four key elements: part-
training and supervision.7 nership, compassion, evocation, and acceptance.
17.2 What is Motivational Interviewing? 209
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
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
TABLE 17.1 Examples of open-ended vs. closed-ended questions

Open-ended questions Closed-ended questions 17
What brings you in today? You’re here to talk about quitting smoking, right?
What is important to you about changing your diet? Is your diet important to you?
How do you manage your stress? Do you mind if I ask you a few questions about your health habits?
If you had to quit smoking, how would you do it? Do you want to try the nicotine patch?
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
TABLE 17.2 Additional examples of reflections

Type of reflection Example
Amplified “You were petrified.”
Double-Sided “Quitting will be hard and you realize the change will benefit your family.”
Affective “It upsets you to hear yourself say that.”
Metaphor “It feels like you are drowning.”
Continuing the sentence “… and you have been waiting to say that for a long time.”
Emphasizing personal choice “… and you know you are the only one who can make this change.”
Siding with the negative “… and then there is always the choice to change nothing.”
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.
Elicit Listen/Reflect Provide Listen/Reflect Elicit
Figure 17.1 Elicit-Provide-Elicit-Model.

17.3.3 Focusing to acknowledge their dual role of being the patient’s clini-
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 evoking 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
Not making a change
Figure 17.2 Decisional Balance Grid.

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
Not important at all extremely important
Figure 17.3 Importance Ruler.

When done in this manner, the patient will offer up • Defensiveness
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
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.
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18
CHAPTER
Transtheoretical Model
James O. Prochaska, PhD and Janice M. Prochaska, PhD
Key Take Home Points................................................................ 219 18.3.7 Principle 7............................................................ 223

18.1 Introduction...................................................................... 219 18.4 Critical Assumptions of the TTM........................................ 224
18.2 Stages of Change............................................................. 219 18.5 Increasing Impacts with Multiple Behavior Change
18.3 Principles and Processes of Change.................................. 221 Programs.......................................................................... 224
18.3.1 Principle 1............................................................ 221 18.6 Studies Challenging the Transtheoretical Model................ 225
18.3.2 Principle 2............................................................ 221 18.7 Multiple Domains of Well-Being: From Suffering or
18.3.3 Principle 3............................................................ 221 Struggling to Thriving........................................................ 225
18.3.4 Principle 4............................................................ 221 18.8 Conclusions...................................................................... 226
18.3.5 Principle 5............................................................ 221 References................................................................................ 227
18.3.6 Principle 6............................................................ 221
To have a significant and sustainable impact on attain-

KEY TAKE HOME POINTS ing these healthy behaviors, a model of behavior change
is needed to address the needs of entire populations, not
• The importance of a healthy lifestyle
just the minority who are motivated to take immediate
• Characteristics of people in each stage of change
action for better health. The Transtheoretical Model of
• The principles and processes to apply at each stage
Behavior Change (TTM) is founded on stages of change
• Increasing impacts with multiple behavior change
that categorize segments of populations based on where
• Challenges to the Transtheoretical Model (TTM)
they are in the process of change. Principles and processes
• How TTM can increase well-being
are applied to initiate movement through the stages of
• Multiple benefits of integrating TTM into practice
change. Interventions based on TTM principles can pro-
duce programs that are interactive and broadly applicable
for treatment of entire populations. The programs include
18.1 INTRODUCTION computer-tailored interventions (CTIs) delivered through
various modalities, such as counselor guidance, telephonic
Health risk behaviors, like smoking, inactivity, unhealthy coaching, the Internet, and texting.
diets, alcohol abuse, and ineffectively managed stress,
account for about 70% of a population’s morbidity, dis-
ability, mortality, reduced functioning and productivity, 18.2 STAGES OF CHANGE
and escalating health care costs. In contrast, a healthy
lifestyle, including abstinence from smoking, eating five The TTM postulates that change is a process that unfolds
servings of fruits and vegetables each day, adequate physi- over time through a series of stages: Precontemplation,
cal activity (e.g., walking 10,000 steps a day or doing Contemplation, Preparation, Action, Maintenance, and
150 minutes of moderate exercise a week), and striv- Termination.
ing to maintain a body mass index (BMI) of less than Precontemplation is a stage in which the individual does
25, is being shown to increase life expectancy up to 14 not intend to take action in the foreseeable future (usually
years.1–3 However, having a healthy lifestyle of 0 (smok- measured as the next six months). Individuals may be at
ing), 1–2 alcohol drinks per day, 5 (fruits and vegetables), this stage because they are uninformed or underinformed
10 (10,000 steps), 20 (20 minutes of stress management), about the consequences of a given behavior, or they may
and 25 (<25 BMI) has been an elusive goal for 97% of have tried to change a number of times and have become
the population (0–1-5–10, 20, 25).4 Why are these health demoralized about their ability to do so. Individuals in both
risk behaviors so critical to health and well-being? They categories tend to avoid reading, talking, or thinking about
represent fundamental functions of life: breathing, drink- their high-risk behaviors. In other theories, such individu-
ing, eating, moving, and feeling. If we breathe toxins, we als are characterized as “resistant” or “unmotivated” or
threaten our bodies. If we drink alcohol to toxic levels, “not ready” for health promotion programs. In fact, tra-
we do damage to our mind and bodies. If we don’t move ditional programs were not ready for such individuals and
enough, we don’t remove enough toxins from our bodies. were not motivated to match their needs.
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
To help motivate patients to progress from one stage to the

next, it is necessary to know the principles and processes 18.3.5 Principle 5
of change that can produce such progress.
The weak principle of progress holds that, to progress
from Contemplation to effective Action, the perceived
costs of changing must decrease by one-half SD.
18.3.1 Principle 1 Because the perceived benefits for changing must
The benefits of changing must increase if clients are to increase twice as much as the perceived costs decrease,
progress beyond Precontemplation. In a review of 12 stud- twice as much emphasis must be placed on the benefits
ies, all showed that the perceived benefits were higher in than the costs of changing. What is striking here is that
the Contemplation than in the Precontemplation stage.7 the authors and colleagues believe they have discovered
This pattern held true across 12 problem behaviors: use of mathematical principles for the degree to which positive
cocaine, smoking, delinquency, obesity, inconsistent con- motivations must increase and negative motivations must
dom use, unsafe sex, sedentary lifestyles, high-fat diets, decrease. In a recent meta-analysis of nearly 140 studies
sun exposure, radon testing, mammography screening, on 48 behaviors, the pros of changing increased by exactly
and physicians practicing behavioral medicine. 1.00 SD, whereas the cons decreased by 0.54 SD.9 Such
A technique that can be used involves asking a client principles can produce much more sensitive assessments
in the Precontemplation stage to describe all the benefits to guide interventions, giving coaches and clients feed-
of a change such as quitting smoking or starting to exer- back for when coaches’ efforts are producing progress and
cise. Most persons can list four or five. The coach can when they are failing. Together, they can modify methods
let the client know that there are eight to ten times that if movement is needed for the client to become adequately
number and challenge the patient to double or triple the prepared for the Action stage.
list for their next meeting. If the client’s list of benefits of
exercise begins to indicate many more motives, such as
a healthier heart, healthier lungs, more energy, healthier 18.3.6 Principle 6
immune system, better moods, less stress, better sex life,
and enhanced self-esteem, he or she will be more moti- It is important to match particular processes of change
vated to begin to seriously contemplate such a change. with specific stages of change. Table 18.1 presents the
empirical integration found between stages and the prin-
ciples and processes of change. Guided by this integration,
18.3.2 Principle 2 the following processes would be applied to clients across
the stages of change:
The “cons” of changing must decrease if clients are to
progress from Contemplation to Action. In 12 of 12 stud- 1.
Consciousness raising (get the facts) involves
ies, the authors and colleagues found that the perceived increased awareness of the causes, consequences,
costs of changing were lower in the Action stage than in and responses to a particular problem. Interventions
the Contemplation stage.8 that can increase awareness include observations,
confrontations, interpretations, feedback, and educa-
tion. Some techniques, such as confrontation, pose
18.3.3 Principle 3 considerable risk in terms of retention and are not
The relative weight assigned to benefits and costs must recommended as highly as motivational enhance-
cross over before a client will be prepared to take action. ment methods such as personal feedback about the
In 12 of 12 studies, the costs of changing were assessed current and long-term consequences of continu-
as higher than the rewards in the Precontemplation stage, ing the unhealthy behavior. Increasing the costs of
but in 11 of 12, the rewards were assessed as higher than not changing is the corollary of raising the benefits
TABLE 18.1 Integration of the stages, principles, and processes of change

Precontemplation Contemplation Preparation Action Maintenance
Consciousness
raising
Dramatic relief
Environmental
reevaluation
Self-reevaluation
Self-liberation
Reinforcement
management
Helping
relationships
Counter
conditioning
Stimulus
control
Pros of changing
increasing
Cons of changing
decreasing
Self-efficacy
increasing
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.
30 increase the theory’s impact on enhancing health. One

potential is for TTM to treat multiple behaviors in a popu-
lation since most populations have multiple behavior risks
and are at risk for both chronic disease and premature
20 death. Those multiple comorbid populations also account
Percentage
for a disproportionate percentage of health care costs.

One estimate is that about 60% of health care costs are
generated by about 15% of populations who have multiple
10
behavior risks and medical conditions.12
Historically, studies conducted on multiple behavior
changes have been limited by reliance on the action-ori-
0 ented treatment and the lack of applying the most promis-
Pretest 6 12 18 ing interventions, such as interactive and individualized
Assessment Periods TTM-tailored interventions.13 From a TTM perspective,
applying an action paradigm to multiple behaviors would
Action Manuals Stage Manuals indeed risk overwhelming populations, since Action is the
Computers+ Counselors+ most demanding stage and taking action on two or more
behaviors at once could be overwhelming. Furthermore,
among individuals with four health behavior risks, like
Figure 18.1 Point prevalence abstinence (%) for treatment smoking, diet, sun exposure, and sedentary lifestyles, less
groups pretest and at 6, 12 and 18 months.
than 10% of the population was ready to take action on
two or more behaviors.14 The same thing was true with
populations with diabetes who needed to change four
18.4 CRITICAL ASSUMPTIONS behaviors.15
OF THE TTM With a population of 1,277 overweight and obese
patients proactively recruited in the United States, we
The Transtheoretical Model is also based on critical applied our first strategy for multiple behavior change. We
assumptions about the nature of behavior change and call this the modular approach, where participants receive
population health interventions that can best facilitate a separate TTM computerized tailored intervention (CTI)
such change. The following are a set of assumptions that module for each of their risk behaviors related to healthy
drive transtheoretical theory, research, and practice: weight management. The treatment groups had significant
changes at 24 months on healthy eating, exercise, and
1. Behavior change is a process that unfolds over time emotional eating. This study was the first to report results
through a sequence of stages. Effective health pro- showing significant coaction in the TTM CTI group and
motion interventions need to match their help to significant changes in fruit and vegetable intake that were
individuals’ stages as they progress over time. not treated. Also, this study reported a mean of about 0.8
2. Stages can be both stable and subject to change, just behaviors changed per participant in the TTM group,
as chronic behavioral risk factors are both stable which was 60% greater than the 0.5 behaviors in the con-
and subject to change. Health initiatives can moti- trol group.16
vate change by enhancing the understanding of the One of the most exciting developments in our knowl-
pros and diminishing the value of the cons. edge of simultaneously changing multiple behaviors is the
3. The majority of at-risk populations is not prepared phenomena of coaction. Coaction is the increased prob-
for action and will not be served by traditional ability that if individuals take effective action on one
action-oriented prevention programs. Helping indi- behavior (like exercise), they are more likely to take action
viduals set realistic goals, like progressing to the on a secondary behavior (like diet). We have found that
next stage, will facilitate the change process. significant coaction typically occurs only in our TTM
4. Specific principles and processes of change need to treatment groups and not in control groups, suggesting it
be emphasized at specific stages for progress through is likely to be treatment-induced.16–18
the stages to occur. With a population of 1,400 employees in a major
medical setting, the authors and colleagues made avail-
These critical assumptions need to be taken into con- able online modular TTM CTIs for each of four behav-
sideration when developing health promotion interven- iors (smoking, inactivity, BMI > 25, and stress) and three
tions for behavior change that can facilitate progress Motivational Interviewing (MI) telephonic or in-person
through the stages. sessions. Employees chose which behaviors to target and
how much time and effort would be spent on any behav-
ior. At six months, both treatments outperformed the
18.5 INCREASING IMPACTS Health Risk Intervention (HRI) that included feedback on
the person’s stage for each risk and guidance on how they
WITH MULTIPLE BEHAVIOR could progress to the next stage.19
CHANGE PROGRAMS With a population of 1,800 students recruited from
eight high schools in four states, Mauriello et al. applied
One of the greatest challenges for the application of any a second-generation strategy with exercise as the primary
theory is to keep raising the bar, that is, to be able to behavior receiving three online sessions of fully tailored
18.7 Multiple Domains of Well-Being: From Suffering or Struggling to Thriving 225
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
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.
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Norfolk prospective population study. Prev. Med. 2000;32:39–46. els, methods and premature conclusions.
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1992;4:107–116. Multiple behavior interventions to pre- tus for self-changers. Addict. Behav.
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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-
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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.
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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.
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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
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34. Sun X, Prochaska JO, Velicer WF, by decreasing multiple health risk behav- facilitate engagement. In O’Donohue,
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a representative sample of quitters, Well-Being in the United States. International Publishing, 2017.
19
CHAPTER
The Impact of Positive Psychology

on Behavioral Change and
Healthy Lifestyle Choices
Shelley H. Carson, PhD, Andrea Cook, PhD, Stephanie Peabody, PsyD,
Sandra Scheinbaum, PhD, and Leslie Williamson, BA
Key Points.................................................................................. 229 19.3.2 Positive Psychology Technological Devices............ 234

19.1 Positive Psychology: A Brief Overview............................... 230 19.4 Incorporating Positive Psychology into the Lifestyle
19.1.1 The PERMA Model................................................. 230 Medicine Practice............................................................. 235
19.2 Positive Psychology and Positive Health............................ 231 19.4.1 Modeling Positive Psychology Principles............... 235
19.2.1 Positive Psychology Factors and 19.4.2 Having Positive Health Conversations with
Cardiovascular Disease�� 231 Patients�� 235
19.2.2 Positive Psychology Factors and Diabetes............. 232 19.4.3 Prescribing Positive Psychology Interventions....... 236
19.2.3 Positive Psychology Factors and Mortality............. 232 19.4.4 Incorporating a Health Coach Trained in Positive
19.2.4 Positive Psychology Factors and Additional Psychology Principles into Your Practice��236
Health Considerations�� 233 19.5 Conclusion........................................................................ 237
19.3 Positive Psychology Interventions..................................... 233 Summary of Clinical Application Points...................................... 237
19.3.1 PPIs and Moderating Factors................................. 234 References................................................................................ 237
Positive psychology is defined as the scientific study

KEY POINTS of the “conditions and processes that contribute to the
flourishing or optimal functioning of people, groups, and
• The goal of Positive Psychology, a science that
institutions.”2 Patients who seek healthcare services, from
focuses on human strengths, is to increase well-being
yearly checkups to treatment for serious illnesses such
and flourishing in individuals and groups. The link
as diabetes and cancer, can benefit from incorporating
between Positive Psychology and Positive Health is
positive psychology principles into their lives. As health-
the idea that subjective well-being is a “health asset”
care professionals, we can assist patients in improving
that protects against risk of physical illness.
their overall well-being by promoting positive psychol-
• A substantial and growing body of evidence con-
ogy tenets during office visits and throughout treatment
nects positive emotions, optimism, and subjec-
protocols. We can inquire about what is going right for
tive well-being with better health and longevity
them, and point out personal strengths that we observe in
outcomes.
them. There is a growing body of evidence indicating that
• Positive Psychology practices can influence health
positive psychology practices can influence health and
and wellness by encouraging patients’ use of their
wellness by encouraging patients’ use of their strengths to
strengths to manage stress and emotions, and to
manage stress and emotions, and to work toward healthy
work toward healthy habits and lifestyle changes.
habits and lifestyle changes. We can assist patients to tap
• Positive Psychology Interventions (PPIs), that can
into these practices to improve their comfort, treatment
be prescribed, have been developed and tested in
compliance, and resilience.
randomized controlled trials. PPIs have been dem-
In this chapter, we will examine the major tenets of
onstrated to be effective in improving positive emo-
positive psychology, review the evidence-based research
tions and well-being, and in reducing depressive
on how positive psychology factors impact a variety of
symptoms.
physical health issues, and offer suggestions on how posi-
“Treatment is not just fixing what is broken; it is nurtur- tive psychology principles and interventions can be incor-
ing what is best.”1 porated into any lifestyle medicine practice.
229
230 Chapter 19 The Impact of Positive Psychology on Behavioral Change and Healthy Lifestyle Choices
19.1 POSITIVE PSYCHOLOGY: TABLE 19.1 Seligman’s PERMA Model of Well-Being

A BRIEF OVERVIEW Positive Emotions Experiencing emotions such as love, joy,
gratitude, serenity, hope
The term “positive psychology” was first used by Abraham
Engagement Being completely absorbed in an activity
Maslow in his 1954 book Motivation and Personality.3
(state of flow)
Maslow and other psychologists of the humanist tradi-
tion, who believed in the self-actualization tendencies of Relationships Engaging in positive connections with
humans and the nobility of the human spirit, deeply influ- others
enced the field of positive psychology as it exists today. Meaning Believing in and serving something that is
However, as a structured discipline, positive psychology is bigger than yourself
very young; most scholars trace its beginnings to Martin
Accomplishment Achieving incremental steps toward
Seligman’s presidential address to the 1998 American identified goals
Psychological Convention in San Francisco. In that
address, Seligman argued that psychology had become a Source: Adapted from Seligman, M. Flourish: A visionary new understanding of
science focused primarily on improving symptoms of men- happiness and well-being 2011; New York: Free Press.
tal illness, while neglecting research into what constitutes

human flourishing and “what makes life worth living”.4 inspiration, and awe. In addition to increasing levels of
Although reducing suffering is a worthy goal, Seligman happiness and overall well-being, these positive emotions
suggested it was incomplete; he called for an additional have been found to predict emotion regulation skills and
new psychological science, one that would focus on to help individuals find meaning in personal struggles.8
human strengths and the prevention of symptoms, rather Positive emotions have a specific effect on cognition as
than just the repair of human weaknesses. well, broadening the scope of attention and awareness,
Along with Seligman, other influential founders of which, in turn, allows for exploration and discovery.
the discipline of positive psychology include Mihaly Over time, exploration and discovery build new skills and
Csikszentmihalyi, known most widely for his work on the resources within the individual. This broaden-and-build
state of flow—a state in which one is totally immersed theory of positive emotions9 suggests that positive emo-
and actively engaged in an ongoing activity; the late tions confer both short-term and long-term benefits to
Christopher Peterson, who conducted research on opti- human flourishing. Positive emotions are also associated
mism and character strengths; and Ed Diener, who con- with recovery from bereavement and from daily stress,10
tributed groundbreaking research in the area of subjective and have been shown to facilitate the physiological com-
well-being. 5 Other influential research included work on ponents of recovery from stress, a major contributor to
self-efficacy by Albert Bandura, self-determination theory long-term health.
by Edward Deci and Richard Ryan, and personal strengths Engagement. Much of the initial work on the impor-
by Donald Clifton. tance of engagement for human flourishing centers on the
Since 1998, scientific centers for the study of positive work of Mihaly Csikszentmihalyi11 and his research on
psychology have continued to proliferate and investigate the psychological state of flow. In this state, a person is
factors leading to optimal self-regulation, well-being, fully immersed in, energized by, and focused on a current
flourishing individuals, and thriving communities.4 challenging activity. Flow is a state of optimal experience
Simultaneously, the applied arm of positive psychology and engagement in which both self-conscious awareness
seeks to develop human strengths, optimism, and compe- and sense of time seem to disappear. The ability to expe-
tencies, thus improving well-being and self-regulation as rience flow is associated with increased performance in
well as buffering against disease. both school and work settings,12 and with psychological
resilience.13 Full engagement in current activities, or flow,
serves several functions in promoting well-being. First,
19.1.1 The PERMA Model it is a pleasurable end state in itself, increasing positive
The main goal of positive psychology, according to emotions; second, flow has been shown to act as a buf-
Seligman,6 is to increase well-being and flourishing in fer against mental illness and other negative health out-
individuals and groups. The major elements of well-being comes; and third, the state of flow provides motivation to
can be summed up in the PERMA model (see Table 19.1). continue challenging work, thus promoting the develop-
Each of the five elements of the PERMA model not only ment of competencies.11 The tendency to experience flow
contributes to overall well-being but is sought after for its has also been related to overall health-related quality of
own sake.6 As we shall see throughout this chapter, these life.14,15
elements not only contribute to well-being but measurably Relationships. Having healthy, positive relationships
contribute to lifestyle medicine outcome goals as well. with other people is one of the best predictors of well-
Positive Emotions. Work in the area of positive emo- being.16 A large body of research indicates that close rela-
tions (also called positive affect) and well-being has tionships also contribute to health and longevity.17 For
been spearheaded by Barbara Frederickson’s lab at the example, in a recent longitudinal study, positive relation-
University of North Carolina and by the late Alice Isen’s ships were found to be a protective factor for heart disease
lab at Cornell University. Frederickson7 has identified and among people with depression.18
conducted research on ten positive emotions: joy, hope, Meaning. In his iconic book Man’s Search for Meaning,
pride, love, gratitude, serenity, interest, amusement, Victor Frankl19 argued that our ability to find meaning in
19.2 Positive Psychology and Positive Health 231
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
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
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?”
• 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
TABLE 19.3 Examples of Prescriptions for Positive Psychology Interventions

Evidence for
Name Rx Effectiveness
Gratitude Letter Write and deliver in person a letter of appreciation to someone who has been kind to you but 59
and Visit whom you have never properly thanked.

Three Good Things Write down three good things that happen each day for one week, together with an explanation 59
for why each good thing happened.

Use Your Signature Take the survey at viacharacter.org. Use one of your top five character strengths (your “signature” 59,77
Strengths strengths) in a new and different way for a week.

Gratitude List Write down three new things (small or large) you are grateful for each night for two weeks. At 73–76
the end of each week, read your entire list.

Best Possible Self Imagine as vividly as possible that you have worked hard and been successful at accomplishing 76,78,79
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.
SUMMARY OF CLINICAL APPLICATION POINTS

1. Have Positive Health • During examinations, ask open-ended questions that focus on the patient’s strengths.
Conversations with • When patients speak, employ active listening:
Patients • Encourage patients to avoid social comparisons (including comparisons with themselves as they used to
be when they were younger) and to focus on their own current strengths.
• Remind patients to make mindful choices: every bite we eat, every activity we perform, every reaction to
an event we have, is a choice. It’s liberating to know we can mindfully choose so much about our lives!
• Engage in a short, realistic optimism process with patients.
2. Model Positive • Display positive emotions during interactions with patients and with other staff (contentment, hope,
Psychology Principles serenity, interest, amusement, inspiration) unless inappropriate to the situation.
• Express gratitude (for example, to staff) within earshot of patients for their positive work.
• Determine your own signature character strengths and use them on a regular basis in your work.
• Discuss the personal meaning of health in your own life (e.g., lifestyle challenges you may have struggled
with in the past and how you may have used positive psychology principles to help effect positive
lifestyle changes).
3. Prescribe Positive Just as exercise can be prescribed for its health-enhancing and disease-preventing effects, positive
Psychology psychology interventions (PPIs) can be prescribed for the same reasons (e.g., gratitude letter, three good
Interventions things journal, acts of kindness).
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20
CHAPTER
The Intention–Behavior Gap

Mark D. Faries, PhD and Wesley C. Kephart, PhD
Key Take-Home Points............................................................... 241 20.3.2.1 Introduction............................................ 245

20.1 Introduction...................................................................... 241 20.3.2.2 Review................................................... 245
20.1.1 What Is the Intention–Behavior Gap?..................... 242 20.3.2.3 Practical Application............................... 246
20.2 Intention in Practice.......................................................... 243 20.3.3 Capacity (Executive Function)................................ 246
20.2.1 What Is Intention?................................................. 243 20.3.3.1 Introduction............................................ 246
20.2.2 Intention in Practice.............................................. 243 20.3.3.2 Review................................................... 246
20.2.3 Intention Stability.................................................. 243 20.3.3.3 Practical Application............................... 247
20.2.4 When to Intend?.................................................... 243 20.3.4 Emotional Response............................................. 248
20.3 Solutions for the IBG......................................................... 244 20.3.4.1 Introduction............................................ 248
20.3.1 Action and Coping Planning................................... 244 20.3.4.2 Review................................................... 248
20.3.1.1 Introduction............................................ 244 20.3.4.3 Practical Application............................... 249
20.3.1.2 Review................................................... 244 20.4 Summary.......................................................................... 249
20.3.1.3 Practical Application............................... 245 Clinical Applications................................................................... 250
20.3.2 Self-Efficacy......................................................... 245 References................................................................................ 250
action and coping planning, building self-efficacy,

KEY TAKE-HOME POINTS or identifying anticipated affective responses (e.g.,
regret).
• Intention indicates how hard a patient is willing
• Understanding the intention–behavior gap allows
to try, or how much effort they are willing to put
for modification of lifestyle prescriptions and devel-
toward any given behavior.
opment of practice models that maximize lifestyle
• Intention, alone, is generally found to not be a reli-
adherence when lifestyle is the medicine.
able predictor of physical activity or dietary behav-
ior—even if intention is high (the intention–behavior
gap).
• Thus, the practitioner should consider the factors 20.1 INTRODUCTION
that have been shown to moderate or affect the
strength of the intention–behavior relationship, We have all experienced it. We intended to pick something
which include: up from the store but forgot. We have all intended to stop
• Action and Coping Planning: Forms of planning by the post office or give so-and-so a call but did not. We
that specify a critical condition linked to goal- claim this New Year’s Resolution is different. However,
directed responses (e.g., “if-then” statements), despite our good intentions, we fail to follow through.
and when an individual imagines a scenario Our patients can relate. They experience, as do many
that might hinder them performing an intended practitioners, the same phenomenon with lifestyle medi-
behavior (e.g., barriers), respectively. cine prescriptions, such as a healthy diet or a physically
• Self-efficacy: A personal expectation or judg- active lifestyle. There are two common scenarios:
ment regarding one’s competence to accomplish
a specific task in a particular context. 1. The patient has no intention to adopt the lifestyle
• Capacity (Executive Function): A concept that prescription, or
describes the neurocognitive faculties of higher- 2. The patient has intention to adopt the lifestyle pre-
order supervisory abilities to direct cognitive scription but does not follow through with it.
functions toward a goal.
• Emotional Response: The affective reaction to Both scenarios of non-compliance can be frustrating
some type of internal or external stimuli. to the patients and the practitioners, who truly desire the
• The practitioner and healthcare team can play a key best for their patients. This chapter hinges on the realiza-
role in helping bridge the intention–behavior gap tion that lifestyle medicine only works if patients take their
with their patients by improving the utilization of medicine. As a result, practitioners are very interested in
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,
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
Preaction Maintenance Recovery

Self-Efficacy Self-Efficacy Self-Efficacy
Action
Outcome Planning Action,
Intention
Expectancies Coping Behavior
Planning
Risk
Motivational Volitional
Perception Phase Phase
Figure 20.1 Health Action Process Approach Model.31

20.3 Solutions for the IBG 245
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
could not fully transform their intentions into

TABLE 20.1 Example context-specific self-efficacy
action. On the contrary, the text message remind-
assessment for physical activity (pa)
ers in the augmented intervention group might have
Please rate your confidence to participate in regular PA assisted sedentary individuals to strengthen the con-
over the next 6 months when: fidence to become more active. Importantly, there is
Not at all Very robust evidence that self-efficacy is a prerequisite for
confident confident successful behavior change throughout a variety of
health-related domains, including physical activity.42
A little tired 1 2 3 4 5
In a bad mood or feeling 1 2 3 4 5 Thus, the practitioner should consider the common
depressed determinants of perceived self-efficacy in their patients43
Doing it by yourself 1 2 3 4 5 as well as novel methods or technology to enhance patient
self-efficacy.
It becomes boring 1 2 3 4 5 Planning is another key factor that can be facilitated
There are no noticeable 1 2 3 4 5 in practice, but it hinges, at least in part, on self-efficacy.
improvements in fitness In other words, proper planning can help patients connect
Having other demands 1 2 3 4 5
intention to behavior if they feel confident in their abilities
to be physically active or eat healthfully across various
Feeling stiff or sore 1 2 3 4 5 contexts, especially when faced with certain barriers or
There is bad weather 1 2 3 4 5 when resuming healthy behavior following a break from
it. In summary, “self-efficacious individuals are optimis-
When a little ill 1 2 3 4 5 tic about their capability to resume an exercise regimen
From 35 after a break, which might help them enact their plans.
Therefore, self-efficacious people might be more likely
to translate their intentions into action. In other words,
action plans do not convert intentions into behavior if a
with action planning (i.e., specific plans outlining actions person harbors self-doubts.”44 These findings also high-
to meet particular goals) led to similar increases in FV light (1) the need to ensure each type of self-efficacy in
consumption.39 Interestingly, Richert and colleagues inves- patients, and (2) the importance of understanding predic-
tigated the outcome of FV intake following a planning tors in theoretically based path models (e.g., working left
intervention in 411 employees.40 The effectiveness of the to right in the HAPA model).
planning intervention was found to be contingent on self-
efficacy. In other words, those with low self-efficacy did
not benefit from the planning. Similarly, Luszczynska & 20.3.3 Capacity (Executive Function)
Schwarzer examined the influence of self-efficacy on inten-
tion and subsequent breast self-examination.41 They first 20.3.3.1 Introduction
found that planning mediated the relationship between Self-regulation of behaviors, especially those behaviors
intention and behavior. Preactional self-efficacy had a posi- that have been ingrained over time, can be quite diffi-
tive effect on both their intention to conduct and their plan- cult—even for those who might have the utmost intent to
ning for conducting a breast self-examination, but not the follow a prescription. This paradox highlights an impor-
actual behavior. However, their maintenance self-efficacy, tant need for an adequate capacity of our brains to control
which was assessed 12–15 weeks later, had a weak but and manage our thoughts, attitudes, and behaviors. This
positive effect on actual breast self-examination behavior. capacity that is a foundation for self-regulatory abilities
is collectively known as the executive functions (EF). EF
is a concept that describes the neurocognitive faculties of
20.3.2.3 Practical Application
higher-order supervisory abilities to direct cognitive func-
Currently the evidence for self-efficacy to bridge the IBG tions toward a goal.45 When disassembled, the aspects of
is generally supportive, yet still somewhat speculative, EF generally include attentional control, response inhibi-
despite the growing literature in support of the impor- tion, planning and problem solving, working memory,
tance of self-efficacy in health behavior. Interventions and cognitive flexibility (see Table 20.2). Put simply, EF
to reduce the IBG continue to arise, some of which lend appears to be the capacity for an individual to control
potential support to the importance of self-efficacy. For their actions and thus is a theoretically pertinent attribute
example, when brief text messages were sent to partici- to help bridge the IBG.
pants to remind them of their action plans, in addition to
a standard psychoeducational intervention, self-efficacy
increased slightly, while the psychoeducational inter- 20.3.3.2 Review
vention alone resulted in a significant decrease in self- Firstly, the EF capacity of an individual might determine the
efficacy.42 The authors conclude with considerations for strength of the connection between intention and behavior.
application, suggesting For example, Hall and colleagues investigated the relation-
ship of attentional/inhibitory control and intention for vig-
that individuals in the standard intervention group orous PA and FV intake.51 This EF was assessed with a
became discouraged by the experience that they computerized Go/No Go task, which requires participants
20.3 Solutions for the IBG 247
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
with a simpler food log to self-monitor food intake if a

TABLE 20.3 Normative values (number of digits recalled)
more complex version might be too difficult. However, if
for forward/reverse digit span task of working memory
a patient is quite strong in planning, then a more detailed
Age (years) logging plan might be suitable. At this time, such indi-
vidualized prescriptions are speculative. Nevertheless, as
Order Recited 21–30 31–40 41–50 50+
the research continues to provide insight into EF and its
Forward 5 5 5 4 role in the IBG, the practitioner can incorporate EF into
Reverse 4.5 4 4 4 clinical practice when appropriate.
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.
Recreated from Brewer, DeFrank, and Gilkey79

20.4 Summary 249
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
prescriptions. This chapter provided initial insight into • Self-Efficacy

how the practitioner and healthcare team can play a key • The practitioner should consider the common
role in helping bridge the intention–behavior gap with determinants of perceived self-efficacy in their
their patients, such as the use of action and coping plan- patients. This can be done by using peer models,
ning, building self-efficacy, or identifying anticipated giving frequent and focused feedback, and also
affective responses (e.g., regret). An awareness and better encouraging accurate attributions.
understanding of the intention–behavior gap allows for • Capacity
modification of lifestyle prescriptions and development of • Test the individuals EF and determine where they
practice models that maximize lifestyle adherence when fall on the spectrum. Individuals with lower EF
lifestyle is the medicine. may require more guidance and planning than
those with higher EF scores. If EF is a constraint,
then it is imperative to configure an individual-
CLINICAL APPLICATIONS ized plan, where EF is not a limiting factor.
• Emotional Response
• Action and Coping Planning • Practitioners should consider assessing and high-
• Instruct the patient to write down how they lighting perceived regret, in particular, within
plan to exercise, where they plan to exercise, their patient interventions.
and when they plan to exercise. This can also be • The practitioner might ask the patient about
done in regard to more healthful dietary choices. their anticipated expectancies and feelings sur-
• Assist the patient in formulating coping plans to rounding the lifestyle prescription. The prescrip-
help clarify, specifically, how they will deal/cope tion can then be modified to encourage positive
with upcoming problems. Such as how to still feelings, feelings of self-efficacy, or even antici-
exercise on a rainy day. pated regret, depending on the specific behavior.
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21
CHAPTER
Cognitive and Behavioral Approaches to

Enhancing Physical Activity Participation
and Decreasing Sedentary Behavior
Barbara A. Stetson, PhD and Patricia M. Dubbert, PhD
Key Points.................................................................................. 253 21.4 Physical Activity Interventions in Racial /Ethnic

21.1 Introduction...................................................................... 253 Underserved Samples........................................................ 261
21.1.1 Overview of Current Physical Activity Guidelines........255 21.5 Community-Wide PA Interventions.................................... 262
21.1.2 Overview of Effective Physical Activity 21.6 Environmental Factors in PA............................................. 262
Interventions�� 256 21.7 Maximizing Real-World Translation—Effective PA
21.2 Emerging Technologies for Physical Activity Monitoring Intervention Dissemination............................................... 263
and Interventions.............................................................. 256 21.7.1 Dissemination of Effective Physical Activity
21.2.1 Activity Monitoring................................................ 257 Interventions through Counseling for Preventive Care
21.2.2 Computer and Web-Based Interventions............... 257 in Clinical Settings............................................................ 264
21.2.3 Mobile Phones and Devices.................................. 258 21.8 Conclusion........................................................................ 265
21.3 Expanding the Targets of Activity Promotion: Assessing Clinical Applications................................................................... 265
and Targeting SB.............................................................. 259 References................................................................................ 266
KEY POINTS 21.1 INTRODUCTION

• There are now many physical activity intervention Physical activity (PA) research has led to many develop-
studies, including excellent systematic reviews and ments in the understanding of the benefits of activity in
meta-analyses published in the past five years. prevention, risk reduction, and improvements in health.
• Development of behavior change coding taxonomies Regular PA can play a major role in weight control, risk
has facilitated systematic evaluations of the use and reduction for cardiovascular disease and diabetes and pre-
effectiveness of behavior change techniques in physi- diabetes, and some cancers. Regular activity also helps to
cal activity interventions. strengthen bones and muscles, improve functional status
• Rapidly expanding access to technology for monitor- and reduce fall risks, improve mental health and mood,
ing physical activity has increased the use of mobile and may increase longevity.1 The evidence base for these
apps and wearable devices to promote physical benefits has led to the development of guidelines for pro-
activity and provide objective data about behavior. moting activity and efforts to understand the optimal
• Accumulating evidence on the health risks of seden- types of PA and PA doses, delivery methods, and reach
tary behavior has led to an increase in assessment and dissemination in real-world settings. Recent advances
and intervention studies using sedentary behavior as in the study of sedentary behavior (SB) have led to a rap-
the primary outcome. idly growing evidence base on the health risks of inac-
• The substantial evidence base now available on tivity, 2 development of a Network of SB researchers and
effective approaches to enhancing physical activity stakeholders, 3 and consensus statements on terminology
has led to increasing emphasis on translational dis- and methodology.4 Recommendations for PA interven-
semination studies and community programs in a tions and research have increasingly incorporated SB as a
variety of settings. target of behavior change and some major health organi-
• Evidence-based resources for enhancing physical zations now also include reducing inactivity in their posi-
activity have been developed and disseminated for tion statements (see Table 21.1).
health providers for use in preventive counseling in Numerous recent systematic reviews and meta-anal-
clinical settings and for individuals in the commu- yses have led to increasingly specific understanding of
nity for self-paced behavior change. optimal approaches for promotion of PA behavior change
253
254 Chapter 21 Enhancing Physical Activity
TABLE 21.1 Guidelines for Healthy Physical Activity

Organization Guidelines for Adult Physical Activity (PA)
U.S. Department of Health and Physical Activity Guidelines for Americans
Human Services78 For Health Benefits
Adults need to do two types of physical activity each week to improve health—aerobic AND muscle-
strengthening activities.
Aerobic Activities
Aerobic activity should be performed for at least 10 minutes at a time and should preferably be
spread throughout the week.
For substantial health benefits, at least 2 hours and 30 minutes (150 minutes) of moderate-intensity
aerobic activity each week
OR
1 hour and 15 minutes (75 minutes) of vigorous-intensity aerobic activity each week
OR
a mix of moderate- and vigorous-intensity aerobic activity that is equivalent.
Muscle-Strengthening Activities
Muscle-strengthening should be done 2 or more days a week.
All major muscle groups should be worked (legs, hips, back, abdomen, chest, shoulders, arms).
Exercises for each muscle group should be repeated 8 to 12 times per set. As exercises become
easier, weight should be increased or another set performed.
For Greater Health Benefits
Adults should do 5 hours (300 minutes) of moderate-intensity aerobic activity each week
OR
2 hours and 30 minutes (150 minutes) of vigorous intensity a week
OR
a mix of moderate- and vigorous-intensity aerobic activity that is equivalent.
*Note: Updated Guidelines are scheduled to be available in Fall, 2018 (https://health.gov/paguidelin
es/second-edition/)
American Heart Association79 For Overall Cardiovascular Health:
At least 30 minutes of moderate-intensity aerobic activity at least 5 days per week for a total of 150
minutes
OR
At least 25 minutes of vigorous aerobic activity at least 3 days per week for a total of 75 minutes, or a
combination of moderate- and vigorous-intensity aerobic activity
AND
Moderate- to high-intensity muscle-strengthening activity at least 2 days per week for additional
health benefits.
For Lowering Blood Pressure and Cholesterol:
An average 40 minutes of moderate- to vigorous-intensity aerobic activity 3 or 4 times per week.
American Diabetes Association 80 For Reducing Sedentary Time:
All adults, and particularly those with type 2 diabetes, should decrease the amount of time spent in
daily sedentary behavior.
Prolonged sitting should be interrupted with bouts of light activity every 30 minutes for blood glucose
benefits, at least in adults with type 2 diabetes.
The above two recommendations are additional to, and not a replacement for, increased structured
exercise and incidental movement.
For PA and Type 2 Diabetes:
Daily exercise, or at least not allowing more than 2 days to elapse between exercise sessions, is
recommended to enhance insulin action.
Adults with type 2 diabetes should ideally perform both aerobic and resistance exercise training for
optimal glycemic and health outcomes.
Structured lifestyle interventions that include at least 150 min/week of PA and dietary changes
resulting in weight loss of 5%–7% are recommended to prevent or delay the onset of type 2 diabetes
in populations at high risk and with prediabetes.
Promoting the Adoption and Maintenance of PA
Targeted behavior change strategies should be used to increase PA in adults with type 2 diabetes.
When using step counters, adults with type 2 diabetes should initially set tolerable targets for steps/
day before progressing toward higher goals.
For adults with type 2 diabetes, internet-delivered interventions for PA promotion may be used to
improve outcomes.
For managing PA with health complications in diabetes, see details in position statement.
Continued
21.1 Introduction 255
TABLE 21.1 Guidelines for Healthy Physical Activity (Continued)

Organization Guidelines for Adult Physical Activity (PA) 21
American College of Sports Cardiorespiratory PA
Medicine 81 Adults should get at least 150 minutes of moderate-intensity exercise per week.
Exercise recommendations can be met through 30–60 minutes of moderate-intensity exercise (5 days
per week) or 20–60 minutes of vigorous-intensity exercise (3 days per week).
One continuous session and multiple shorter sessions (of at least 10 minutes) are both acceptable to
accumulate desired amount of daily exercise.
Gradual progression of exercise time, frequency, and intensity is recommended for best adherence
and least injury risk.
People unable to meet these minimums can still benefit from some activity.
Resistance Exercise
Adults should train each major muscle group 2 or 3 days each week using a variety of exercises and
equipment.
Very light or light intensity is best for older persons or previously sedentary adults starting exercise.
2 to 4 sets of each exercise will help adults improve strength and power.
For each exercise, 8–12 repetitions improve strength and power, 10–15 repetitions improve strength in
middle-age and older persons starting exercise, and 15–20 repetitions improve muscular endurance.
Adults should wait at least 48 hours between resistance training sessions.
Flexibility Exercise
Adults should do flexibility exercises at least 2 or 3 days each week to improve range of motion.
Each stretch should be held for 10–30 seconds to the point of tightness or slight discomfort.
Repeat each stretch 2 to 4 times, accumulating 60 seconds per stretch.
Static, dynamic, ballistic, and PNF stretches are all effective.
Flexibility exercise is most effective when the muscle is warm. Try light aerobic activity or a hot bath
to warm the muscles before stretching.
Neuromotor Exercise
Neuromotor exercise (sometimes called “functional fitness training”) is recommended for 2 or 3 days
per week. Exercises should involve motor skills (balance, agility, coordination, and gait),
proprioceptive exercise training and multifaceted activities (e.g. tai chi and yoga) to improve physical
function and prevent falls in older adults.
20–30 minutes per day is appropriate for neuromotor exercise.
In addition to outlining basic recommendations and their scientific reasoning, the position
stand also clarifies these new points:
Pedometers, step-counting devices used to measure PA, are not an accurate measure of exercise
quality and should not be used as the sole measure of PA.
Though exercise protects against heart disease, it is still possible for active adults to develop heart
problems. All adults must be able to recognize the warning signs of heart disease, and all health care
providers should ask patients about these symptoms.
Sedentary behavior—sitting for long periods of time—is distinct from PA and has been shown to be a
health risk in itself. Meeting the guidelines for PA does not make up for a sedentary lifestyle.
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
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
21.2.1 Activity Monitoring than that indicated by a commercial tracker for healthy
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
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.
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
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
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
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.
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22
CHAPTER
Enhancing the Nutrition Prescription

Using Behavioral Approaches
Jonas Sokolof, DO, Margaret Loeper Vasquez, MS, RD, LDN, Jenny Sunghyun Lee, PhD, MPH,
CHES, CWP, CHWC, BCLM, Daniel B. Clarke, MBA, and P. Michael Stone, MD, MS, IFMCP
Key Points.................................................................................. 269 22.3 Effective Counseling Techniques for the Nutritional

22.1 Educating Patients on Nutrition Basics, Laying the Prescription...................................................................... 273
Foundation....................................................................... 270 22.4 Nutrition Counseling and Education in the Group
22.1.1 Nutrition, a Snapshot............................................ 270 Medical Visit Model........................................................... 274
22.1.2 Whole Foods you Recognize.................................. 271 22.5 Practical Culinary Skills to Ease Behavioral Change.......... 276
22.1.3 Portion Control...................................................... 271 Clinical Applications................................................................... 279
22.1.4 Nutrients for Wellness........................................... 272 References................................................................................ 279
22.2 Cultural Sensitivity and Nutrition....................................... 272
prevention of disease is diet. It is clear that suboptimal

KEY POINTS nutrition plays a direct role in the development and
propagation of chronic diseases such as obesity, diabetes,
• The nutrition prescription is one of the most impor-
hypertension, cancer, and cardiovascular disease. 2 The
tant components of lifestyle intervention.
eighth edition of the Dietary Guidelines for Americans
• Empowering patients with basic nutrition knowl-
2015–2020 (hereinafter Dietary Guidelines), made
edge can help with nutrition prescription adherence.
available to the American public in 2015, emphasizes a
• When prescribing nutritional lifestyle interven-
dietary pattern rich in a variety of whole grains, fruits,
tion, it is important for the practitioner to take
and vegetables while simultaneously limiting consump-
into account the various cultural and social factors
tion of added sugars, saturated fat, and sodium. 3 These
involved in dietary habits.
guidelines were derived from scientific data that support
• A coaching approach built on a solid coach-client
a whole food, mostly plant-based diet as the overall pat-
relationship can promote positive behavioral change
tern of eating involved in health promotion. The evidence
as it relates to nutrition.
continues to accumulate on how a diet that is lower on
• Group medical visits can be a cost-efficient and pro-
the food chain can dictate the health of a population.4
ductive tool to implement nutritional prescription
The U.S. Preventive Services Task Force (USPTSF) recom-
within a lifestyle medicine program.
mends that nutrition counseling be intensive and focused
• In order to effectively comply with a nutrition
on behavioral interventions. A good nutrition prescription
prescription, it is vital for patients to possess fun-
increases both the intensity and ability to apply a focused
damental culinary skills so they can prepare health-
behavioral intervention. Based on the latest Dietary
promoting meals at home.
Guidelines and scientific evidence, most would agree that
Recent studies have shown that most patients suffering from the overall dietary pattern recommended for health pro-
chronic medical conditions do not follow lifestyle recom- motion would be one that is plant-centric. Furthermore,
mendations (e.g., tobacco cessation, healthy eating, exercise) emphasis should be placed on eating whole foods in the
despite the fact that doing so could significantly alter the “pure” form as opposed to foods that have been pro-
underlying disease process in a positive manner.1 Adopting cessed. However, possessing knowledge on the most
healthy behaviors centered on optimal diet, sufficient physi- health-promoting dietary pattern is meaningless without
cal activity, and reduction or elimination of substance use tools in place or a mechanism to put this knowledge into
thus becomes vital in the overall treatment of many chronic action. Dietary habits are largely controlled by the com-
diseases. Therefore, when considering the lifestyle medicine plex interaction of human behavior, cultural practices,
prescription, emphasis on changing a patient’s behavior and societal norms. Therefore, in order for clinicians to
becomes a key component in the treatment plan. effectively intervene from a nutritional perspective, they
Perhaps the most important modifiable lifestyle fac- must also know how to help change human behavior.
tor involved in the overall maintenance of health and Such behavior can be both learned and acquired and can
269
270 Chapter 22 Enhancing the Nutrition Prescription Using Behavioral Approaches
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.
TABLE 22.1 Sample progression towards whole foods

Current example Step towards Whole food
“Juice” or Soda 100% Juice Piece of fruit
Box cereal Low-sugar whole wheat cereal Oatmeal or quinoa
Frozen chicken wings Low ingredient whole meat chicken tender Homemade breaded chicken breast
Frozen stir-fry veggies Frozen stir-fry veggies, no sauce packet Raw sliced veggies
Hydrogenated nut butters Natural nut butters Raw nuts
Ramen-style noodles Rice noodles with soy sauce Rice or whole wheat noodles with veggies and
edamame
Size of the plate: This matters! People tend to fill the

plate. Choose a dessert plate rather than a dinner plate for
22.2 CULTURAL SENSITIVITY
meals. AND NUTRITION
Divide the plate: Half of the plate should be filled with
vegetables and/or fruits, a quarter with protein, and a Health is not simply the biochemical state of an absence of
quarter with whole grains. disease or illness. It also embodies quality of life, includ-
Measure: Use measuring cups/spoons for a week. See ing meaningfulness, joy, connection with others, happi-
how much you are actually serving yourself. Can you ness, fulfillment, and well-being. Health also includes a
decrease it by one tablespoon? One-quarter cup? After a person’s goals and circumstances as well as cultural val-
week you will have an idea of what serving sizes look like ues, traditions, and practice.15,16 Similarly, the molecules
on your plates and in your bowls. that constitute food provide the nutrients and energy nec-
Serve and put away: Serve yourself the appropriate essary to sustain life and promote health and healing at
portion and put the rest back into the refrigerator or pan- a biochemical level. However, food encompasses more
try. You will be less likely to serve yourself seconds when than biochemical entities and entails social and cultural
it is not in front of you. relevance as well. What people eat and how they eat are
Pre-portioned items: Purchase items already portioned determined by more than nutrients and provider recom-
(fruit cups, yogurts, string cheese) so you can grab and go! mendations but is developed by cultural traditions, social
Eat at the table: Turn off the screens and pay attention status, preferences, power, and more.
to what you are eating, who you are eating with, and how In past decades, health care professionals have endorsed
you are feeling the importance of nutritional intake when promoting
Cook!: When you are in charge (versus eating out), you healthful diets and lifestyles for their patients. Further, the
know what the ingredients are and you know how much advent of genome sequencing has resulted in personalized
you’ve served yourself. medicine based on a person’s genotype. This includes the
Split it!: When you do eat out, ask the server to pack- field of nutrigenomics, which encompasses the epigenetic
age half the entrée before bringing it to the table or split effects of food or how nutrients trigger changes in genome
an entrée with your friend. expression.17 Thus, one’s genotype could be used to deter-
mine a unique diet regimen for optimal health, disease
prevention, and therapy. Further, studies have shown indi-
viduals have reported dietary recommendations based on
22.1.4 Nutrients for Wellness genetics to be more understandable and useful compared
When one embarks on changing their behavior related to general dietary advice from their primary care providers
to nutrition in a more healthful direction, there are some (PCPs).18 This novel field may be useful to improve patient
nutrients that can help. Most Americans are not only jug- compliance with provider recommendations and subse-
gling their weight but also the comorbidities that accom- quently health maintenance. However, despite the intrigue
pany obesity as more than one-third of U.S. adults are of nutrigenomics, the relationship of a person’s environ-
obese.9 The bottom line when thinking about healthful ment and culture with their diet cannot be forgotten by
eating, modifying behaviors to increase health, or tak- PCPs. Providers need to inquire about the intricacies of
ing small steps in that direction is that the food has to patients’ eating habits, schedule, and lifestyle to help coun-
taste good. Processed foods do this largely by adding salt, sel them on best lifestyle practices.19 This also includes how
fat, and sugar.10 There are ways to make food not only food is prepared; finances or food budgets; troubles with
taste good without this formula but also provide some mastication, swallowing, or digestion; allergies or food-
potentially beneficial influence on those obesity-specific intolerances; and dietary needs and preferences.
comorbidities. Today, there exists a plethora of cultures and people
One of the obvious ways to improve flavor and nutrient with different eating habits, steps in food preparation, and
composition of a dish is to remove or drastically reduce identities in food. Eating is an intimate act one chooses,
the salt added and replace it with herbs and spices. Basil, performs, and practices based on various factors (e.g.,
oregano, and rosemary are all wonderful spices that can beliefs, attitudes, needs, preferences, traditions, circum-
jazz up a dish. A paste can be made with herbs and olive stances, environment) to sustain, promote, and celebrate
oil that can be used as a spread instead of butter, mar- life. The food one chooses to eat reflects their identity.
garine, or mayonnaise. Tumeric has been shown to have That is, the food choices an individual makes may reveal
anti-inflammatory effects,10,11 and a pinch can be added to their social class, educational background, knowledge
scrambled eggs, roasted veggies, rice, soup, and smooth- of food, and health and fitness goals. For instance, the
ies.12 Cinnamon is a wonderful addition to warm cereal, person eating a low-fat and high-protein diet has differ-
smoothies, and baked items, and has been shown to have ent physique goals or preferences than the person eating
antioxidant properties as well as wound-healing proper- a vegan diet or one who eats fast food daily. While these
ties.13 More studies are needed on these spices’ effects in people may have different fitness goals or understanding
humans, as often they are eaten in small quantities.14 This of what foods are healthy and nutritious, there may be
leads back to the moderation and balance message. The other health and cultural disparities present. These indi-
only way to attain a strong healthy body is to consume a viduals, for example, may have access to different food
diet of moderate portions of balanced fruits, vegetables, items due to living in a health desert or to financial bur-
lean proteins, complex carbohydrates, and a variety of col- dens. Similarly, food is linked to power. In general, pur-
orful herbs and spices for additional flavor and hydration. chasing or acquiring healthy and safe foods (e.g. organic
22.3 Effective Counseling Techniques for the Nutritional Prescription 273
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
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
The format and implementation are straightforward in

Table 22.3 and continues to have the benefits previously
22.5 PRACTICAL CULINARY
outlined in Table 22.2. The results have been improved SKILLS TO EASE
nutrition education, biomarkers, and therapeutic lifestyle
changes. The programs have increased the frequency of BEHAVIORAL CHANGE
delegated nutrition education and nutritionist evaluation
visits for all of the chronic conditions frequently seen in 1. Basic tools and kitchen setup
the clinic (see Table 22.3). • Tools and equipment with pictures. The pantry
The topics or focus of the groups can range from review of a healthy kitchen should include good vine-
of underlying general issues (inflammation), specific labo- gars, spices, and fresh herbs, olive oil and other
ratory or imaging related to a chronic process (lipids, healthy oils, no- or reduced-salt canned products,
advanced lipids, or carotid ultrasound carotid intima- real food salt substitutes, and assorted whole
media thickness). The groups can be diagnosis-specific grains When using salt, use it as a finisher and
(hypertension, high cholesterol, rheumatoid arthritis) or preferably a flake sea salt (fleur de sel) so you do
they can be a series about the same topic (pain, cardio- not have to use as much.
metabolic syndrome) (see Table 22.4). 2. Basic culinary skills
Conclusion: The introduction of the nutrition educa- • How to hold a knife/sharpen, and properly cook
tor, nutritionist, nutrition counselor, or health education vegetables.
specialist into the primary care clinic is essential for the • Cooking techniques—braising, roasting, grill-
patient-centered medical home, the primary care clini- ing, steaming, and sauté.
cian, and the desire for improved health and chronic
disease outcome. It is important to evaluate your clinic Braising is cooking a food, usually meat, by searing in
population, demographic, level of desire, and the extent some form of fat (corn oil or olive oil) and then simmering
of using this tool.36 But at the end of the day, this addition at a low temperature in a small amount of liquid or stock
empowers all involved and generates hope and expecta- usually half submerging the protein item in a covered ves-
tions because of the positive changes that occur. 37 This is sel. The cooking liquid is reduced throughout the cooking
a reimbursable process that is geared to the strength of all process and is used as a base for the sauce for the item.
members of the clinic and health-caring team with posi- Roasting is cooking by dry heat such as an oven, con-
tive results. vection oven, or open fire.
TABLE 22.3 Outline of a common routine process

Routine process in an insurance-based (medicaid/medicare/private) primary care practice
1. Define the Group topic, Series of Topics for the Shared Medical Visit.
2. Schedule on a repeating basis, or the series on a repeated basis.
3. Identify the patient group to be reached and inform them of the opportunity.
4. Agree to the education flow between the provider (a short review 5–15 minutes) and a Nutrition Educator or Health Education
Specialist.
5. Have the conference room or education space scheduled available.
6. Prepare the materials for handouts or presentation.
7. Have a review of systems form/or questionnaire that the patient fills out on arrival. This is targeted so the responses can be placed
in the paper or electronic medical record to fulfill the review of systems/or history component.
8. Clinician and/or nutritionist review the chart prior to the group medical visit. Identify any laboratory or studies related to the visit
focus that might be pertinent.
9. After reviewing the chart, fill out the beginnings of a plan to be given following the visit.
10. Have the group arrive 15–20 minutes prior to the starting point so vitals can be collected and forms/questionnaires completed and
name tags given.
11. Have adequate staff to take the vital signs (e.g., when we have 8–10 participants, there are two staff to collect vitals and usher the
patients through the pre-group process).
12. Start the Group medical visit with introductions and reminders of confidentiality. No personal information will be shared unless you
desire it to be shared, and the clinician will review your plan separately.
13. After the introductory remarks by the lead clinician, they leave the room and the Nutritionist or Health Educator takes over the
presentation or discussion.
14. The medical assistant or nurse ushers one client and/or partner-spouse to meet with the clinician in a 10–15-minute visit.
15. The clinician completes the focused physical exam.
16. The client returns to the group and the other participants review for the returning individual what was shared while they were out.
17. That process continues until all have been seen.
18. The nutritionist educator provides discussion or education that pertains to the topic, identifying the interrelationship of nutrition with
the other modifiable lifestyle factors when appropriate.
19. Offer food or healthy snacks which highlight nutrients and bioactives that are topic-specific and copies of the recipes provided.
20. At the end of the session, follow-up instructions are given and evaluations by the participants are completed
21. Provider/Nutritionist/Office staff debrief (5–10 minutes) follows.
22. Provider/Nutritionists note completed, Billing using the provider cpt codes
Total Time in Office 2:15 minutes or shorter, depending on process.
22.5 Practical Culinary Skills to Ease Behavioral Change 277
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.
• Basic Vinaigrette Pasta Dough Basic Formula:

1.5 quarts of oil (favorite extra virgin olive oil)
16 fl. oz. of vinegar (whatever vinegar you prefer) Durum Flour .5 lb.
1 tsp. of Dijon mustard Semolina Flour .5 lb.
Salt, pepper, and other seasonings such as fresh
herbs, as desired. Eggs, whole 4 ea.
1. Combine the vinegar and desired seasonings. Oil 1–2 Tbsp.
2. Slowly whisk in all oil until an emulsification
is formed. If it’s ever too thick, just very slowly Water 1–2 Tbsp.
add cold water to adjust. Season with salt and Salt pinch
pepper.
3. Serve immediately or store up to 7 days.
Soft Polenta or Farina Grits (Cream of Wheat) (By
4. This can also be done in a blender or with
Volume)
a hand blender using the same steps and
ingredients.
Stock 5.5 parts
Grains Cornmeal 1 part
Method
Rinse rice, drain well before cooking pilaf (with Uncle
Ben’s, no need to rinse) Hominy Grits (By Weight) To hold shape
Par-boiled or Carolina rice Basic Formula (By volume!)
Stock 4 parts
Stock, seasoned 1.75 or 2 parts Hominy grits 1 part
Rice 1 part
Healthy substitutions
Jasmine rice: Rinse, drain well, use 1.5 parts water or
1 whole egg = 2 egg whites
stock
1 cup of heavy cream = 1 cup of evaporated milk
Brown rice Basic Formula (By Volume)
1 cup of mayonnaise = .5 cup of mayonnaise and .5 cup
Stock, seasoned 2.25 or 2.5 parts
of low-fat yogurt.
1 cup of sour cream = 1 cup of low-fat yogurt plus 2
Brown Rice 1 part Tbsp. of buttermilk or fresh lemon juice.
3. Meal/menu planning
Wild Rice Basic Formula (By volume) Map out a menu weekly, before grocery shopping.
Try to incorporate local CSA/Farmers markets
Stock, seasoned 3 parts if accessible by location or monetarily feasible.
Use these incomplete protein combinations as sub-
Rice 1 part stitutes for animal proteins: grains and legumes,
lentils and brown rice, whole wheat pasta and
Risotto: (By Volume) beans, tortillas and beans, tofu and brown rice,
and hummus and whole wheat pita. These can
Stock, seasoned 3 parts be used for snacks, sides, or entrees.
Some guidelines for developing principles of healthy
Arborio rice 1 part
cooking should include sourcing and selecting
nutrient-dense ingredients; always incorporating
* Added in 3 stages a variety of plant-based ingredients into every
Cous Cous: (By Volume) meal; and trying to always make your own stocks,
sauces, and vinaigrette dressings. This way, you
Stock 1.25–1.5 parts can control all ingredients that you consume.
Cous Cous 1 part
4. Easy recipes for the hesitant cook
• Under 30-minute meals that are healthy and
Olive oil to coat grains good for you
• Ability to cook in batches, allowing you to have
* Coat grains with oil. Pour hot stock over grains, enough for another meal
cover, let sit 5 minutes. Fork through to separate grains. • Learning how to cook with alternative ingredi-
Firm Polenta or Farina Grits (Cream of Wheat) (By ents that are healthy yet have lots of flavor
Volume) To hold shape • Spices, seasonings, and herbs
• The use of “good” condiments that add flavor
and not salt or sugar
Stock 5 parts
In conclusion, more and more doctors are using the
Cornmeal 1 part
kitchen as the first defense for someone to becoming
References 279
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.
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23
CHAPTER
Behavioral Approaches to Manage Stress

Elise Loiselle, RN, MSN, FNP-C, Darshan Mehta, MD, and Jacqueline Proszynski, BS
Key Points.................................................................................. 281 23.3.2.2 Tai Chi................................................... 289

23.1 The Stress Response and Relaxation Responses............... 281 23.3.3 Gratitude.............................................................. 290
23.1.1 Physiological Response........................................ 281 23.3.3.1 Practicing Gratitude............................... 291
23.1.2 Biochemical Response......................................... 282 23.3.4 Building a Positive Perspective............................. 291
23.2 Building Resilience........................................................... 282 23.3.5 Adaptive Coping Strategies................................... 291
23.3 Mind-Body Therapies........................................................ 284 23.3.5.1 Teaching Patients to Change their Mind...... 291
23.3.1 Meditation............................................................ 286 23.3.6 Other Lifestyle Modifications................................ 292
23.3.1.1 Breath Awareness................................. 286 23.3.6.1 Nutrition and Stress............................... 292
23.3.1.2 Body Scan............................................. 286 23.3.6.2 Sleep and Stress................................... 293
23.3.1.3 Guided Imagery..................................... 288 23.4 The Role of Technology in Stress Management................. 293
23.3.1.4 Contemplation and Prayer..................... 289 23.5 Summary.......................................................................... 294
23.3.1.5 Loving Kindness.................................... 289 Clinic Applications..................................................................... 294
23.3.2 Movement............................................................ 289 References................................................................................ 294
23.3.2.1 Yoga...................................................... 289
environmental factors.1 Over time, with continued stress,

KEY POINTS the brain initiates a cascade of both physiological and
behavioral responses, leading to an increase in allostatic
• The stress response and the relaxation response are
load (Figure 23.1). 2 This is characterized by a cascade
innate protective and adaptive responses that initi-
of immune, endocrine, and neural mediators, leading to
ate physiological and biochemical reactions in the
a systemic effect on organ systems, 2,3 as illustrated in
body. The stress response can become harmful with
Figure 23.2.
prolonged exposure, but the relaxation response can
The relaxation response is a wakeful hypometabolic
help reverse the effects of allostatic load.
physiologic state that is believed to be voluntarily elicited
• Building resilience, practicing Mind-Body Therapies
by many mind-body practices, and counteracts the nega-
(MBTs) and making positive behavioral modifica-
tive effects of the stress response. Figure 23.3 summarizes
tions can all help counteract the stress response,
the physiological correlates of both the stress and relax-
elicit the benefits of the relaxation response, and
ation response processes.4
improve coping with perceived stress.
• Teaching patients to implement MBTs can help
improve their adaptation to stress and is an essential
treatment option for patients of all ages and health 23.1.1 Physiological Response
states. The stress response is characterized by increased oxy-
gen utilization, increased glucose uptake, and increased
respiratory rate. 3 Through activation of the body’s sympa-
23.1 THE STRESS RESPONSE AND thetic nervous system, there is bronchodilation and vaso-
constriction leading to increased cardiac output, blood
RELAXATION RESPONSES pressure, heart rate, and total peripheral resistance.3–9
Oxygen-rich blood is shunted to essential organs. 3–9 by
Stress is defined as the association between the patient and the vascular system.
their environment that requires resources.1 The stress response The relaxation response is characterized by decreased
is the physiological response to stress through activation of respiratory rate, decreased oxygen consumption, and car-
changes from the cellular to the behavioral domains.1 bon dioxide elimination.3–9 In addition, there is a reduc-
A patient’s perception of stress is influenced by tion in cardiac output, with lower heart rates and blood
their genetic predispositions, life experiences, and pressure as well as increased heart rate variability.8,10–14
281
282 Chapter 23 Behavioral Approaches to Manage Stress
Figure 23.1 Moving from Allostasis to Allostatic Load.
(Adapted from: The Stress Response and Development of Allostatic Load from McEwen(1998), New England Journal of
Medicine (2)).
23.1.2 Biochemical Response The relaxation response, also known as a wakeful

hypometabolic physiological state, is the opposite of the
The stress response is characterized by a cascade of bio- stress response.6 It elicits HPA changes, impacting the
chemical changes. Corticotrophin-releasing hormone release of cortisol from the adrenal cortex.11,17–21 It also
(CRH) release triggers two pathways—the Sympatho- increases nitric oxide in the vasculature.4,22 Nitric oxide is
Adreno-Medullary Axis (SAM) and the Hypothalamus- an important biomarker that plays a role in vasodilation
Pituitary-Adreno Axes (HPA).3–6,15 The SAM axis is and decreasing blood pressure.3,4 The relaxation response
rapid-acting, causing the adrenal medulla to distribute the also has immune system benefits, showing an increase in
powerful catecholamines epinephrine and norepineph- lymphocytes, 23 natural killer cell activity and prolifera-
rine, which activate the “fight or flight” response. This, tion, 24–26 and serum IgA levels. 27 In one study, eight weeks
in turn, triggers the organ systems to respond by increas- of relaxation response training changed the expression of
ing heart rate, respiratory rate, oxygen consumption, more than 1,500 genes in subjects compared to their pre-
and blood pressure.3–6,15 CRH also signals the anterior practice genetic makeup.4
pituitary gland to secrete adrenocorticotropic hormone
(ACTH). This signals the adrenal cortex to release the
stress hormone cortisol. The flow of cortisol initiates glu-
cose production in the liver, elevating the body’s glucose 23.2 BUILDING RESILIENCE
levels, which is necessary to yield adenosine triphosphate
(ATP)3–6,15 for utilization by cells.16 The stress response Resilience is a dynamic trait that reflects an individual’s
also triggers the immune system to release pro-inflamma- ability to cultivate adaptive behaviors, thereby counteract-
tory cytokines, including interleukin-1 and tumor necrosis ing the negative effects of stress and returning to a state
factor-alpha. of well-being. 28,29
23.2 Building Resilience 283
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
Figure 23.3 Physiological Changes from Stress Response.

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
Stress Appraisal & Coping Eliciting

Relaxation
DISTAL OUTCOME
Response
R
Cognitive
Decreasing
Physical Behavior Stress
Reactivity
RESILIENCY
Emotion
Increasing
Connectedness
to Self & Others
Growth Enhancement
Positivity STATE
Acceptance Empathy
Appreciation
TREATMENT APPROACHES
Figure 23.4 Building Resiliency.59

23.3 Mind-Body Therapies 285
TABLE 23.1 Conditions Treated with Mind Body Therapies

Health Condition MBT Studied Intervention Effects Recent Studies 23
Anxiety Disorders MBSR Improvements in symptom severity, stress Hoge et al. (2013). Randomized
Yoga reactivity, and coping. controlled trial of mindfulness
meditation for generalized anxiety
disorder: effects on anxiety and
stress reactivity.140
Atrial Fibrillation Yoga Improvements in arrhythmia burden, heart rate, Lakkireddy et al. (2013). Effect of
Meditation blood pressure, anxiety and depression scores, yoga on arrhythmia burden, anxiety,
and several domains of quality of life. depression, and quality of life in
paroxysmal atrial fibrillation: the
YOGA My Heart Study.141
Breast Cancer Yoga Moderate-quality evidence supports the Cramer et al. (2017). Yoga for
Meditation recommendation of yoga and meditation as improving health-related quality of
supportive interventions for improving life, mental health, and cancer-related
health-related quality of life and reducing symptoms in women diagnosed with
fatigue and sleep disturbances when breast cancer.142
compared with no therapy; also shown to
reduce depression, anxiety, and fatigue.
Cardiovascular Disease Meditation Decreases in blood triglycerides, blood Khobragade et al. (2016). Meditation
Tai Chi pressure, and increases in quality of life and as primary intervention strategy in
Qigong physical functioning. prevention of cardiovascular
diseases.143
Depression Yoga Short-term improvements in symptom severity Streeter et al. (2017). Treatment of
MBCT with yoga practice. major depressive disorder with
Iyengar yoga and coherent breathing:
A randomized controlled dosing
study.144
Diabetes Yoga Improved fasting glucose, blood sugar lipid Gainey et al. (2016). Effects of
profile, postprandial blood sugar, and Buddhist walking meditation on
glycosylated hemoglobin. glycemic control and vascular
function in patients with type 2
diabetes.145
Eating Disorders Mindful Meditation Effectively decreases binge eating and Pacanowski et al. (2017). Yoga in the
emotional eating in populations engaging in treatment of eating disorders within a
this behavior. residential program: A randomized
controlled trial.146
Fibromyalgia MBSR Increased quality of life and decreased reports Del Rosso and Maddali-Bongi (2016).
Tai Chi of pain, anxiety, depression, and somatic Mind-body therapies in rehabilitation
complaints. of patients with rheumatic diseases.91
Hypertension Yoga Reductions in systolic and diastolic blood Cramer (2016). The efficacy and
Meditation pressure. safety of yoga in managing
hypertension.75
Inflammatory Bowel 9-week relaxation Decreased pain catastrophizing, symptom Kuo et al. (2015). Genomic and
Disease response mind- severity, trait anxiety, and improved quality of clinical effects associated with a
body group life. relaxation response mind-body
intervention intervention in patients with irritable
bowel syndrome and inflammatory
bowel disease.147
Insomnia MBCT Improvements in patient-reported sleep quality, Shallcross and Visvanathan (2016).
Meditation sleep disturbance, and mood. Mindfulness-Based Cognitive
Therapy for Insomnia.148
Irritable Bowel Yoga Decreased bowel symptoms, IBS severity, and Sharma, Saito, and Amit (2014).
Syndrome anxiety. Significant improvements in quality of Mind-Body Medicine and Irritable
life, global improvement, and physical Bowel Syndrome: A Randomized
functioning. Control Trial Using Stress Reduction
and Resiliency Training.149
Continued
TABLE 23.1 Conditions Treated with Mind Body Therapies (Continued)

Health Condition MBT Studied Intervention Effects Recent Studies
Lower Back Pain Yoga Practice moderately associated with alleviation Morone et al. (2016). A mind-body
MBSR of pain. program for older adults with chronic
Tai Chi low back pain: A randomized clinical
trial.150
Lung Cancer Yoga Reduced anxiety, mood disturbance, sleep Deng et al. (2013). Complementary
MBSR disturbance, fatigue, chronic or acute pain, therapies and integrative medicine in
chemotherapy-induced nausea and vomiting in lung cancer: diagnosis and
lung cancer patients experiencing the management of lung cancer: American
symptoms, and improved quality of life. College of Chest Physicians evidence-
based clinical practice guidelines.151
Migraine/Headache Yoga Significant reductions in monthly headache Millstine et al. (2017). Complementary
Meditation frequency and headache intensity, and and integrative medicine in the
Biofeedback improved daily functioning. management of headache.152
Multiple Sclerosis Tai Chi Helps to improve balance, coordination and Burschka et al. (2014). Mindfulness-
Yoga fatigue, and to lessen depressive symptoms. based interventions in multiple
Mindful Meditation sclerosis: Beneficial effects of Tai Chi
on balance, coordination, fatigue and
depression.153
Osteoarthritis Mindfulness Improved disease-specific symptoms of pain, Lee, Harvey, Price, Morgan, Morgan
training stiffness, pain coping, and knee extensor and Wang (2017). Mindfulness is
MBSR strength. associated with psychological health
Tai Chi and moderates pain in knee
osteoarthritis.154
Post-Traumatic Stress Biofeedback Reductions in anxiety, depression, and anger, Colgan et al. (2016). The body scan
Disorder MBSR and increases in pain tolerance, self-esteem, and mindful breathing among veterans
Yoga energy levels, ability to relax, and ability to with PTSD: Type of intervention
cope with stressful situations. moderates the relationship between
changes in mindfulness and post-
treatment depression.155
Substance Use Yoga May aid in short-term detoxification and Nakamura et al. (2015). Investigating
Disorders long-term management of substance use via impacts of incorporating an adjuvant
stress reductions, increased coping skills, and mind-body intervention method into
additional prosocial support networks. treatment as usual at a community-
based substance abuse treatment
facility: A pilot randomized controlled
study.156
Thyroid Disease Various MBTs As adjunctive therapies, eased side effects, Rosen, Gardiner, and Lee (2013).
such as weight gain, constipation, and fatigue. Effectiveness of mindfulness-based
interventions on physiological and
psychological complications in adults
with diabetes: A systematic review.157
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
Figure 23.5 Example Techniques for Eliciting the Relaxation Response.59
Figure 23.6 Tips for Developing a Practice. Figure 23.7 Breath Awareness.
Stress Reduction (MBSR), Stress Management and

Resiliency Training (SMART), yoga, Buddhism, and
Hinduism. Chronic pain patients noticed significant
reduction in pain with a ten-minute body scan interven-
tion.67 Progressive muscle relaxation is another tool to
help identify the difference between tension and relax-
ation throughout the body. These practice techniques are
prescribed in Figures 23.8 and 23.9.
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.
Figure 23.8 Body Scan. Figure 23.10 Guided Imagery.

23.3.1.4 Contemplation and Prayer 23.3.2 Movement

Another way to elicit the relaxation response is contem-
plation and prayer. The major health benefits associated
Traditions from the present-day countries of China and
India have attested to the powerful interplay between
23
with prayer are increased sensation of relaxation and feel- the mind and body for thousands of years. Yoga and
ings of peace.71 Many patients may resonate more with the tai chi, for example, are two modalities that are highly
idea of prayer than meditating. Prayer and contemplation associated with well-being, reduced perceived stress,
have been practiced in almost every religious tradition for increased physical fitness, and a host of positive health
several thousand years. Maintaining focus on a main idea, outcomes.73,74 There is little safety concern for practicing
experience, or feeling, the mind is focused on an intention yoga and tai chi when taught by a certified instructor, yet
or positive outcome and must remain still, with its atten- types of stroke, minor musculoskeletal aches and pains,
tion on the intention. Figure 23.11 provides an example as well as pain from nerve damage, are rare possible side
activity to guide patients through this practice. effects.75,76 As with all movement-based practices, it is
advised that women who are pregnant and people with
23.3.1.5 Loving Kindness certain medical conditions, such as high blood pressure,
glaucoma, and sciatica, should modify or avoid cer-
Loving Kindness Meditation is a practice that helps bring tain postures, especially when starting a yoga or tai chi
more kindness, peace, and love into the mind-set and routine.
life of the patient practicing. Patients who use this tech-
nique showed more positive emotions, decreased depres-
sion, more mindfulness use, increased social supports, 23.3.2.1 Yoga
and decreased symptoms in diseases.72 Overall, patients Yoga is a moving meditation, coupling breath with vari-
are more satisfied with life when they practice Loving ous body postures, that elicits the relaxation response. Its
Kindness. The practice allows patients to bring more com- origins date back between 5000 BC to 300 AD in a collec-
passion, empathy, and kindness into their daily lives. In tion of classical writings that serve as the primary text for
practice, it again deactivates the stress response. Teach yogic practice, known as the yoga sutras.77 Initially a rem-
the patient to sit in quiet stillness and send out feelings of edy based on spiritual practice used in India to relieve suf-
love, kindness, compassion, and well-being towards oth- fering,78 yoga was later introduced into clinical settings in
ers. This can be done towards themselves, friends, fami- the early 20th century near Mumbai.79 Today, it is among
lies, strangers, collective groups, even the world. The idea the most popular MBTs and has shown steady increases
is to promote these positive feelings and emotions towards in use over the past 14 years. In 2012, 9.5% of American
others, in turn promoting a sense of personal well-being adults practiced yoga, up from 6.1% in 2007 and 5.1%
and overall compassion for others. in 2002, with prevalence rates of 13.2% for lifetime use
and 8.9% for 12-month use.80 Yoga use throughout all
age and minority groups has increased as well.80,81
Extensive evidence suggests yoga may be particu-
larly beneficial for those suffering from lower back pain,
migraine, anxiety, depression, hypertension, and some
gastrointestinal conditions.74,78 It has also been shown to
reduce fatigue associated with multiple sclerosis, help to
better manage epileptic seizures, and help cancer patients
cope with their diagnosis and treatment side effects.82–85
These effects are in part due to the relaxing, anti-inflam-
matory properties of the practice.82–85 Thus, beginning
regular practice may help alleviate symptom intensity and
severity directly through physical movement, as well as
indirectly though psychological mechanisms.68 There are
many styles of yoga, ranging from low-intensity restorative
and hatha practices to high-intensity vinyasa or ashtanga,
each with its own benefits and limitations.78,86 Yet all
forms traditionally place emphasis on isometric exercise
and stretching than on aerobic fitness.78 It is important
to review the differences between styles to make a recom-
mendation best suited for the patient’s health status and
treatment goals. However, given the diversity of styles, it is
likely that almost anybody can benefit from yoga practice.
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
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
Figure 23.12 Tai Chi as a Multicomponent System.89

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
23.3.5.1 Teaching Patients to Change their Mind

Cognitive reappraisal is a mechanism of change used in
many psychotherapeutic interventions, including CBT,
MBSR, SMART, and mindfulness-based cognitive ther-
Figure 23.13 Tips for Gratitude Practice. apy (MBCT). These four therapies require formal training
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
Figure 23.14 Cognitive Reappraisal.

Figure 23.15 Mindful Eating.
impulsive eating and increases enjoyment of food. It is also
related to a preference for healthier food choices, espe- of sleep greatly impacts health. Working with your patient
cially for stressed individuals.127,128 Figure 23.15 provides to establish a consistent sleep schedule will improve the
an example of prescribing mindful eating. quality of their sleep and subsequent health.132 Propose
shutting off harsh lighting a few hours before the targeted
bedtime and using “nightshift” settings or decreasing
23.3.6.2 Sleep and Stress brightness on electronic devices to reduce alterations in
Sleep is often sacrificed for the sake of time when sched- the body’s circadian rhythm. Suggest incorporating more
ules become overwhelming. Yet this creates a harmful movement throughout the day and engage in calming
cycle: lack of sleep may contribute to a rise in stress, while activities at night such as reading or drawing. Beginning
a rise in stress can affect sleep. Stress may alter sleep pat- a meditation practice may also be of benefit, especially
terns by increasing or decreasing the number of hours a for individuals trying to overcome insomnia and chronic
person sleeps or feels that they need, resulting in nega- sleep loss.130
tive consequences on cognitive and physical functioning.
The literature consistently finds that sleep disturbance and
deprivation are associated with diseases of inflammation, 23.4 THE ROLE OF TECHNOLOGY
increased levels of the stress hormone cortisol, metabolic
disruptions, and all-cause mortality.129,130 IN STRESS MANAGEMENT
Technology can be a great tool to help patients elicit the
23.3.6.2.1 Teaching Patients to Sleep Better relaxation response. There are many smartphone appli-
Discuss good sleep hygiene habits to ensure the patient is cations, online websites, computer programs, audio
getting the necessary amount of sleep per night for ade- recordings and videos, that can help patients develop a
quate mental and physical restoration. Lack of rest may practice. Self-guided, online, asynchronous computer
lead to mood abnormalities, decreased cognitive function- courses showed significant decrease of stress and anxiety,
ing, weight gain, suppressed immune system, and exac- as well as increasing cognitive attention in recent stud-
erbation of preexisting conditions.131,132 The Centers for ies. 53 Researchers are studying mobile apps and video
Disease Control and Prevention (CDC) lists specific rec- conferencing for treatment of stress, anxiety and depres-
ommendations for hours of sleep for different age groups. sion, 38,53,135,136 as well as chronic pain.137 Virtual reality
Adults are encouraged to sleep at least seven hours, while programs are also being utilized as an educational tool
teens need 8–10, and school-aged children need 9–12 to elicit the relaxation response. These programs have a
hours per night. Toddlers and infants required the most at significant psychological benefit of lowered depression,
11–17 hours per 24-hour period.133,134 Yet the regularity anxiety and perceived stress, as well as increased skin
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.
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24
CHAPTER
Health Coaching and Behavior Change

Karen L. Lawson, MD, ABIHM, NBC-HWC, Margaret Moore, MBA, ACC,
Matthew M. Clark, PhD, Sara Link, MS, NBC-HWC, and Ruth Wolever, PhD
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
are threatened or disrupted. Health and Wellness Coaches

KEY POINTS provide the opportunity and support for individuals to
actively choose—and change—their health narratives.
• Despite awareness that lifestyle behaviors—such as
Our contemporary healthcare system is built around
a nutritional diet and regular exercise—play a criti-
diagnosis—what is broken and how we fix the illness, limit
cally important role in achieving health, individuals
the pain, or minimize the damage caused by the illness.
struggle to achieve these things on their own.
The patient is often depersonalized, and care is prescribed
• Information alone does not readily result in signifi-
according to the diagnosis. Prevention is a secondary pro-
cant or sustainable health behavior changes. People
cess, one which screens for problems that already exist,
need reliable support, encouragement, empower-
but of which we are as yet unaware. As healthcare con-
ment, and accountability—which health and well-
sumers, we receive expert advice and therapeutic proce-
ness coaches can provide.
dures, are prescribed pharmaceuticals, are operated on,
• An individual’s beliefs and perspectives about their
and are informed of statistical prognoses. If fortunate, we
health challenges and capacity to heal impact their
may receive education about the illness or intervention, or
quality of life and clinical course. Health coaching
have help navigating the complexities of the disease-care
can be a path to more empowered and positive beliefs.
system, given our disorder or condition. However, true
prevention through supporting positive health habits—
such as eating well, not smoking, exercising, managing
24.1 INTRODUCTION stress, cultivating positive relationships, or having qual-
ity sleep—is rarely part of our financed medical system.
Life stories. We all have them. They are our sanctuaries, This is true even though such practices are responsible
our sources of strength, and also, unfortunately, at times for at least 40% of our health outcomes,1 and research
our prisons. In them, we play heroes or victims, are whole shows that sustaining four primary health behaviors (not
or damaged, heal or suffer. Stories can provide hope and using tobacco, being physically active, moderating alco-
guide us in growing or foster despair. Most importantly, hol intake, and consuming five servings a day of fruit and
we have the power to choose whether we are author, edi- vegetables) predicts a fourfold difference in total mortal-
tor, or witness to this narrative. While the choice is ours, ity. 2 Patient- or relationship-centered care endeavors to
most of us need companionship along the way to have empower the individual and acknowledge the importance
healthy and productive lives. This need is especially great of the relationship between patient and provider. These
in times of upheaval, whenever our health and well-being relationships, however, are filtered through reductionistic
299
300 Chapter 24 Health Coaching and Behavior Change
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)
Figure 24.1 Illness–Wellness Continuum.

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).
Counseling in Medicine Health Coaching

Medical model Learning/Development Model
Diagnosable illness in paradigm of Desirable goals & achievement in
pathology paradigm of possibility
Focus on fixing a problem Focus on optimal performance
Non-judgmental partner supports
Expert provides information
exploration of health priorities
“How” questions with present/future
“Why” questions with present/past focus
focus
Restore to level of functioning Move to optimal behavior
Figure 24.2 Health Coaching Is Not Counseling or Therapy.

24.2 Health and Wellness Coaching (HWC)—as a Field and a Profession 303
% of those studies with

Element
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
Self-discovery 63% of 188 trials
Accountability 81% of 159
Content Education 91% of 233 trials
Relationship-based 78% of 154 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
Allied Health Professionals

19.8%
Registered Dietitions 11%
Mental Health Providers

20.5%
Other 0.8%
Medical Professionals: Nurses

41.9%
Medical
Professionals: Physicians 6%
9.9% of these identi ied themselves as professional coaches of some kind, 6.4% as
Figure 24.4 Distribution of Professions.

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,
40%
Self-employed or independent
35%
contractors
30%
Employed Medical outpatient
25%
20% Employed in employer health

and wellness
15%
Employed by coaching
services contractors
10%
5% Employed in Academic,
government, military and
community-based facilities
0%
Distribution of Practicing Health Coaches
Figure 24.5 2014 Survey of Practicing Health and Wellness Coaches.35,33
health and wellness coaches may serve as salaried team

members as part of Medical Homes or Accountable Care
24.4 EVALUATION AND
Organizations (ACOs) (personal correspondence, Paul RESEARCH IN HEALTH AND
Erickson, MD, Medical Director, North Point Health and
Wellness Center, Minneapolis, MN.) WELLNESS COACHING
At both the U.S. federal and state government levels,
the persistence of the fee-for-service model is very limiting 24.4.1 Current Evidence Base
to the economic case for population health investment in Research from Europe, Australia, and the United States
areas of disease prevention through lifestyle medicine and is converging to demonstrate that HWC is an effective
coaching. Fee-for-service provides no financial incentives approach for many health behaviors that can lead to posi-
to reduce future costs by investing in the prevention of tive outcomes for many health conditions. The first review
diseases that emerge from years or decades of unhealthy of the HWC literature was published in 2003 in Australia.63
lifestyles. Effective strategies to engage patients in healthy Between 2009 and 2017, seven reviews of the HWC litera-
lifestyles for long-term health have not yet been confirmed ture were published worldwide. 56,64,32,65,66,67,68,52
or consistently implemented, though it is the authors’ In 2017, a compendium of peer-reviewed, data based
premise that HWC may be just what is needed to achieve literature was compiled using a standardized, evidence-
such ends. The Accountable Care Act, launched in 2010, based definition of HWC and a systematic review process
added reimbursement codes for annual wellness visits, of relevant literature databases after 1989.52 The authors
and CMS added reimbursement codes for obesity coun- included literature on interventions wherein the health
seling in 2011. The CDC’s Diabetes Prevention Program coach was a trained healthcare professional who was also
involves training of lay lifestyle coaches to deliver a six- trained in and used behavior change theory and coach-
month group diabetes education program in communities; ing processes within a patient-clinician relationship with
approximately 1,400 programs and 7,000 lay coaches are a single coach and wherein the intervention consisted of
in place today.62 at least three sessions. Goals were at least partially deter-
The implementation of a prevention/wellness focus in mined by the patients, and progress was monitored. These
primary care practices is limited by many challenges: new criteria allowed for inclusion of 219 articles, 150 of which
regulations and technologies leading to increased over- were data based, with about half of these (n = 72) being
heads and reduced profits, provider burnout, and a dearth RCTs. The remainder were expert opinion or review-style
of expertise to effectively help patients engage in healthy articles. The articles were organized by clinical category/
lifestyles. One promising trend is the new American Board patient group (e.g., wellness, cardiovascular disease, dia-
of Lifestyle Medicine, which launched a lifestyle medicine betes, cancer). The wellness category included the most
board specialty. The first cohort in 2017 consists of more studies40 but also the most varied populations, ranging
than 200 physicians determined to integrate healthy life- from healthy adults to those at elevated risk for various
style education and coaching into primary care. There is conditions to those with fibromyalgia, multiple sclerosis,
now a fresh opportunity in evolving healthcare reform to glaucoma, and other conditions. The two largest popula-
develop an economic model for disease prevention and life- tions studied were patients who had diabetes and patients
style medicine, and for implementing a shift in current medi- who had obesity, with 32 and 31 studies of each, respec-
cal practice via HWC, specifically as it relates to “self-care.” tively. While cancer studies were the least represented,
24.5 Health and Wellness Coaching—Practical Nuts and Bolts 307
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,
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.
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25
CHAPTER
Digital Health Technology

for Behavior Change
Jeffrey Krauss, MD, DipABLM, Patricia Zheng, MD,
Courtenay Stewart, DO, and Mark Berman, MD, FACLM
Key Point....................................................................................311 25.5.2 Considerations for Implementation....................... 318

25.1 Introduction.......................................................................311 25.6 Section 5: Digital Therapeutics.......................................... 319
25.2 Section 1: Text Messaging................................................ 313 25.6.1 Outcomes............................................................. 319
25.2.1 Outcomes............................................................. 314 25.7 Section 6: Emerging Technologies..................................... 320
25.2.2 Considerations for Implementation....................... 314 25.7.1 Multiomics........................................................... 320
25.3 Section 2: Mobile (Smartphone and Tablet) Applications.......315 25.7.2 Virtual and Augmented Reality.............................. 320
25.3.1 Outcomes............................................................. 315 25.7.3 Assistive Mobility Devices..................................... 321
25.3.2 Considerations for Implementation....................... 316 25.7.4 Novel Sensors and Form Factors.......................... 321
25.4 Section 3: Wearables, Sensors, and Devices..................... 316 25.7.5 Big Data and Machine Learning............................ 321
25.4.1 Outcomes............................................................. 317 25.8 Conclusion........................................................................ 321
25.4.2 Considerations for Implementation....................... 317 Clinical Takeaways..................................................................... 322
25.5 Section 4: Social Media.................................................... 318 References................................................................................ 322
25.5.1 Outcomes............................................................. 318
behavior change process would be neglecting important

KEY POINT levers for change.
Digital health refers to a diverse set of technologies,
• A growing body of evidence supports the use of digi-
including mobile health (mHealth), health information
tal health technologies to promote healthy behavior
technology (IT), wearable devices, telehealth and telemedi-
change, however clinical success depends on multi-
cine, and personalized medicine.8 While formal definitions
ple implementation considerations described in this
vary, digital health can be broadly seen as the convergence
chapter.
of the digital and genomic revolutions with health, health-
care, living, and society.9 The field has emerged from the
massive growth in mobile connectivity and bandwidth,
25.1 INTRODUCTION social networking, computing power, data storage, sensor
technologies, imaging, and sequencing speed, which some
Lifestyle medicine stresses the importance of simple, pow- predict will lead to a “creative destruction” of medicine as
erful behaviors to prevent and treat disease. Compared we know it.10,11
with much of modern biomedicine, one of the strengths of Multiple measures reflect the recent growth in digi-
lifestyle medicine is that healthy behaviors do not funda- tal health. In 2016, there were approximately 165,000
mentally require the use of advanced technology. Indeed, health-related applications (“apps”) for Apple or Android
many behavior change strategies and lifestyle medicine smartphones, with an estimated 1.7 billion downloads by
programs have demonstrated remarkable success in pro- 2017.12 Thousands of start-up companies have emerged in
moting healthy behaviors without the use of technology.1–4 the space, and venture capital investment has grown by
Nevertheless, behavior change is notoriously diffi- over 30% annually from 2011 to 2016, with over $4 bil-
cult to achieve, and digital health tools offer significant lion invested in 2016.13 Given this rapid growth, digital
potential to enhance the effectiveness of interventions. health has become a new focus of the U.S. Food and Drug
Furthermore, digital technologies have become tightly Administration (FDA), which is now working on a Digital
integrated into daily behavior in modern society. With the Health Innovation Plan to encourage safe and effective
average American adult spending two to three hours per innovation.14
day on a smartphone, 5,6 engaging in 76 separate phone This chapter will focus on those digital health tech-
sessions per day,6 and spending an additional 4.3 hours nologies with the greatest potential to promote healthy
on the Internet,7 failure to utilize digital health tools in the behavior change in the areas of physical activity, healthy
311
312 Chapter 25 Digital Health Technology for Behavior Change
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
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
emergency or high-risk texts from patients. Most 25.3 SECTION 2: MOBILE

25
studies have used some degree of bidirectional com-
munication, 31 but the literature is mixed regarding (SMARTPHONE AND
its benefits.37,38,50
• Tailoring and personalization – Message content TABLET) APPLICATIONS
or frequency may be targeted to subgroups of users
As stated earlier, a mobile application (“app”) is a com-
or even tailored to individual users. While this can
puter program designed to run on a mobile device such as a
make programs more complex, difficult to design,
smartphone or tablet. These devices first debuted with the
and potentially more expensive, most reviews have
Blackberry in 2002 and were then followed by the iPhone
reported benefit, since messages are more likely to
in 2007 and smartphones that run on the Google Android
catch a user’s attention, be read and remembered,
operating system in 2008.64 Smartphones are now the
discussed with others, perceived as interesting, and
most commonly owned computing devices worldwide,65
be personally relevant. 27 Benefits seen in text mes-
though ownership is far higher in advanced nations than
saging reviews include higher readership, higher
in developing ones.66 Seventy-seven percent of Americans
message recall, perceptions of higher personal rel-
currently own smartphones, compared to 35% in 2011,
evance, greater behavior change, and greater medi-
reflecting the increasing utilization of digital information
cation adherence.31,38,46,51–54
on the go, rather than in front of a computer. While the
• Data security, confidentiality, and privacy – Each
ownership rate is only 42% among Americans 65 and
country has its own laws and regulations for collect-
older, the rate jumps to 74% among those aged 54–64
ing, storing, or transmitting personal health infor-
years old,67 suggesting that smartphones will become
mation (e.g., HIPAA in the United States). Designers
increasingly prevalent as the population ages. With regard
should generally state in the terms and conditions
to smartphone usage, the average American uses his or her
that text messaging is not secure, and that the user
phone for well over two hours per day, 5,6 and far higher
agrees to the risk. In general, however, U.S. and
rates are found in countries as diverse as Brazil, Thailand,
European agencies have not regulated applications
and Saudi Arabia. The high degree of worldwide preva-
aimed at behavior change and medication adher-
lence and interactivity makes mobile applications useful
ence, and security or privacy concerns have not
tools for lifestyle interventions.
prevented programs from being developed by gov-
As noted earlier, approximately 165,000 health-related
ernmental agencies themselves.32
applications existed in 2016 for Apple or Android smart-
phones,12 with the most popular apps focused on healthy
Once a text messaging program has been designed, the eating and physical activity.68,69 Research interest in these
importance of testing cannot be overemphasized, as it pro- applications for health improvement is growing exponen-
vides critical information regarding intervention accept- tially. In 2000, the annual number of published English
ability and effectiveness. 27 Messages should ideally be articles in the medical literature with the search term
pretested with the target audience to assess content, and “mobile application” was only 121 compared with 1,338
then a brief pilot test (e.g. two-four weeks) with actual in 2017. Some of these studies assess lifestyle applications
participants using their actual devices can be valuable for directed at patients primarily, while others are aimed at
assessing the perception of the messages in their actual clinicians.70
delivery context. Once pretesting is completed, experts
recommend a brief pilot test (e.g., two to four weeks) with
actual participants using their actual devices.
Fortunately, numerous resources are available to
25.3.1 Outcomes
assist with development of text messaging programs. The evidence base for mobile application interventions is
The National Cancer Institute’s (NCI) Making Health growing but still is in its early stages. Small and mostly
Communication Programs Work provides useful informa- observational studies have shown that mobile interven-
tion on program planning and design, and Pew Research tions can be successful in encouraging positive lifestyle
Center’s Internet and American Life Project provides data changes and monitoring treatment compliance. However,
on technology use in various U.S. population segments.55,56 there are also negative studies, and retrospective reviews
Guidelines and specific tools for developing programs are combining available trials do not always show a benefit
available through the World Health Organization’s Be of adopting mobile-based interventions. Furthermore, the
He@lthy, Be Mobile program, 57 the U.S. Dept of Health rapid advancement and adoption of mobile technology
and Human Services41 and its Text4Health Task Force, 58 have rendered many research findings out of date shortly
the Johns Hopkins Global mHealth Initiative, 59 the after their publication.
University of Colorado’s Text Messaging in Healthcare Weight management: Among healthy behaviors
Research Toolkit,60 and the PATH Mobile Messaging encouraged by mobile applications, weight management is
Toolkit.61 Specific text messaging platforms are now being one of the most frequently studied.71 A study of 70 adults
researched62 and may be available to the public, and nonrandomized to receive standard treatment with or without
profit organizations offer text messaging programs for a personal digital assistant (PDA) to self-monitor diet and
underserved populations.63 Numerous for-profit compa- physical activity showed that the PDA group lost on aver-
nies offer technical tools for text messaging that are easy age 3.6 kg more over 12 months. 24 However, in a larger
to find through Internet searches. randomized controlled trial of 212 patients, the use of a
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
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
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
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.
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V
PA RT
Women’ s Health
Paulette Chandler, MD, MPH
329
26
CHAPTER
Breast Health: Lifestyle Modification

for Risk Reduction
Beth Baughman DuPree, MD, FACS, ABOIM and Jodi Hutchinson, PA-C
Key Take-Home Points............................................................... 331 26.10.4 Nutrition............................................................. 336

26.1 Introduction...................................................................... 331 26.10.5 Exercise and Recreational Activity...................... 336
26.2 Epidemiology.................................................................... 331 26.10.6 Stress Reduction................................................ 336
26.2.1 Genetics............................................................... 332 26.10.7 Important Vitamins, Antioxidants, and Minerals.......337
26.3 Risk Assessment.............................................................. 332 26.10.8 Vitamin A............................................................ 337
26.4 Protective Life Choices..................................................... 332 26.10.8.1 Retinol and β-Carotene...................... 337
26.5 Epigenetics....................................................................... 332 26.10.9 Vitamin D............................................................ 337
26.6 Hormone Therapy............................................................. 333 26.10.10 CoQ10.............................................................. 337
26.7 Screening......................................................................... 333 26.10.11 Folate............................................................... 337
26.8 Prevention........................................................................ 334 26.10.12 Vitamin E and Vitamin C.................................... 337
26.9 Risk Factors...................................................................... 334 26.10.13 Zinc.................................................................. 338
26.9.1 Alcohol................................................................. 334 26.10.14 Selenium.......................................................... 338
26.10 Obesity........................................................................... 334 26.10.15 The Future of Breast Cancer Prevention............ 338
26.10.1 Clean Eating....................................................... 335 Clinical Applications................................................................... 338
26.10.2 Sleep.................................................................. 335 References................................................................................ 338
26.10.3 Lifestyle Evaluation and Modifications................ 336
use, the rising prevalence of obesity, and increased detec-

KEY TAKE-HOME POINTS tion through screening.3
Women who were treated for an estrogen-receptor-
• Regular physical activity reduces the risk of breast
positive breast cancer and exhibited poor lifestyle choices
cancer across the lifespan.
(smoked, were obese, and drank more than seven alco-
• Avoidance of alcohol and tobacco across the lifes-
holic beverages per week) were 7.2 times more likely to
pan reduces the risk of breast cancer.
develop a contra-lateral breast cancer than matched coun-
• A plant-based diet rich in fruits and vegetables
terparts who never smoked, were not obese, and drank
and maintaining a body mass index (BMI) <26%
less then seven cocktails per week.4 This data leads us to
reduces the risk of breast cancer.
believe that lifestyle choices and changes can significantly
• Breastfeeding our children and practicing stress
impact the risk not only of a woman who has had breast
management techniques such as meditation and
cancer but all women.
mindfulness reduce the risk of breast cancer.
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
lives in the world. Nearly half of the total cases diagnosed

and approximately 60% of the breast cancer deaths
26.3 RISK ASSESSMENT
occur in economically developed countries of North Carriers of the BRCA I or II gene mutation have a 56–87%
America, Western and Northern Europe, New Zealand chance of developing breast cancer and a 27–44% risk of
and Australia, and the high-risk regions. The lowest-risk developing ovarian cancer by the age of 70. Breast cancer
regions are Sub-Saharan Africa and Asia. An increased risk programs consider that, in addition to the BRCA I
incidence is observed in countries as they become and II genes, there are other genes that create a predis-
“Westernized” and adopt a less plant-based diet.6 One position to breast cancer. The woman’s family history is
prominent factor is that women living in industrialized used to calculate the likelihood of her carrying an adverse
nations often delay childbearing until their fourth and gene, which in turn affects her likelihood of developing
sometimes fifth decade of life. This delay allows breast breast cancer. The latest risk program, the International
cells to continue to be influenced by the cyclic estrogen Breast Cancer Intervention Study (IBIS),9 incorporates
and exogenous estrogen (e.g. oral contraceptives) as well mammographic density, age at first child, and benign
as environmental toxins and can increase a woman’s disease combined with familial risk. Breast cancer risk
breast cancer risk later in life. assessment models tend to underestimate a woman’s risk;
therefore, it is important to discuss a woman’s personal
risk with a healthcare professional to determine her indi-
26.2.1 Genetics vidual risk.
Seventy-five percent of all breast cancer occurs in women
who have no family history. Many women are under the
mistaken impression that they are not at significant risk 26.4 PROTECTIVE LIFE CHOICES
if they have no family members with breast cancer. About
one-third of postmenopausal breast cancers are thought to The final phase of total breast development occurs after
be caused by modifiable behavioral factors, such as post- completion of a woman’s first full-term pregnancy.
menopausal obesity, physical inactivity, use of combined A woman who delays childbirth until she is 30 has
estrogen and progestin menopausal hormones, alcohol approximately the same risk of developing breast can-
consumption, diet, and limited breastfeeding of children.7 cer as a woman who is nulliparous. The more children
Women who have a family history of breast and/or ovarian that you have at a younger age, the less likely you are to
cancer on her maternal or paternal family tree are at a high develop breast cancer.
risk for developing breast cancer and need to clearly under- A major protective effect of pregnancy as it relates to
stand their lifetime risk to make positive lifestyle changes breast cancer risk is breastfeeding. Women who themselves
early on in their lives. Only about 4–6% of all breast can- breastfed their infants cumulatively over their lifetime for
cers occur because of a known genetic mutation. 12–24 months had a 66% reduction in breast cancer. There
There is an ongoing discovery of cancer-causing muta- is a direct relationship between the duration of breastfeed-
tions in genes, which increases cancer risk. A study of over ing and decreased risk. Women who were breastfed when
35,000 women with breast cancer tested with a 25-gene they were infants were found to have a decreased inci-
panel of hereditary cancer genes demonstrated that panel dence of premenopausal breast cancer in a meta-analysis.10
testing increased the number of women identified as car- Young women who were at high risk due to family his-
rying a pathologic variant (PV) in this cohort compared tory were found to have a decreased incidence of breast
with BRCA I and II testing alone.8 Furthermore, the pro- cancer when they breastfed.11 Studies from Brigham and
portion of women identified who carried a PV in this Women’s Hospital support these findings of breast cancer
cohort did not decrease between ages 40 and 59. Today’s risk reduction from breastfeeding.12 If a young woman
advanced gene panel testing combined with genetic coun- becomes aware of the impact of her life choices while she is
seling will assess risk levels and improve patient surveil- young, she could choose to have her children at a younger
lance and personalized risk-reduction strategies. age, breastfeed her children, avoid exogenous estrogen,
Risk factors for carrying a breast and ovarian cancer and maintain a healthy BMI with diet, exercise, and stress
gene include: management.
• Breast cancer diagnosed before age 50

• Ovarian cancer at any age 26.5 EPIGENETICS
• Two primary breast cancers in an individual
• Both breast and ovarian cancer in an individual Is it possible that DNA is controlled by the environment
• Male breast cancer at any age and not by biology? For decades, the focus has been on the
• Two or more breast cancers in a family, one under DNA as a blueprint for bodily function, but epigenetics
age 50 reveals two mechanisms, nature and nurture, for passing
• Women of Ashkenazi Jewish descent with breast or on hereditary information. One human cell is capable of
ovarian cancer at any age respiration, digestion, reproduction, and elimination. The
• A previously identified BRCA mutation in the family nucleus of the cell contains the chromosomal contents,
• Prostate cancer half of which is made up of DNA and half which is made
• Pancreatic cancer up of regulatory proteins, but if we remove it, the cell will
26.7 Screening 333
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.
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
stimulate estrogen or androgen pathways and cause epi-
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
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.
26.10.13 Zinc Genetics aside, there are many modifications that can

greatly impact the global risk of breast cancer. Remember
Zinc, a trace mineral which is vital for the functioning of that epigenetic control is the signal from the environment
numerous cellular processes and critical for growth, may that activates the gene’s expression. Early detection is
play an important role in cancer etiology and outcome.81 important to help prevent death from breast cancer but
Immune function of many cells is impaired by low levels does not address how to reduce the risk of ever getting
of zinc which gives credence to the theoretical anti-cancer breast cancer.
benefit.82 Zinc is found in shellfish, grass-fed beef, lamb, If we, as a society, are going to decrease the overall inci-
chicken, toasted wheat germ, pumpkin seeds, sesame seeds, dence of breast cancer, we need to create positive changes
cashews, lentils, garbanzo beans, green peas, spinach, and in our lives. We need to encourage plant-based nutrition,
shiitake mushrooms. regular physical activity, mindfulness-based stress reduc-
tion, maintenance of a BMI < 26%, and breastfeeding our
26.10.14 Selenium children. Knowledge is power!
Selenium helps to produce selenoproteins, which are

important antioxidant enzymes that prevent cell dam-
age from free radicals.83,84 The Nurses’ Health Study, a CLINICAL APPLICATIONS
prospective analysis, previously had found no associa- • Encourage lifestyle modification
tion with selenium levels and breast cancer risk where • Early childbearing and breastfeeding
the selenium concentrations were assessed through nail • Avoiding alcohol prior to the first successful
clippings.85 McConnell et al. identified a statistically sig- pregnancy
nificant inverse relationship between dietary selenium • Minimize alcohol consumption through life
concentrations in the blood and the incidence of human • Maintain BMI < 26%
breast cancer. Furthermore, low selenium levels were iden- • Exercise 30–40 min per day, 5x per week
tified in women with breast cancer.86 • Nutrition – eat clean, predominantly plant-based
• Sleep hygiene
26.10.15 The Future of Breast • Stress management
• Encourage breast imaging screening based on indi-
Cancer Prevention vidual guidelines
Despite advances in the screening and treatment of breast • Clinical evaluation of any breast masses, nipple dis-
cancer, the incidence of breast cancer is on the rise. charge, abnormal lymph nodes, or skin changes.
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27
CHAPTER
Sports and Physical Activity

for Women and Girls
Elizabeth A. Joy, MD, MPH, FACSM
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
and methodical physical exercise save it and preserve it.”

KEY TAKE-HOME POINTS No truer words were ever spoken, and they were spoken
by Plato, centuries ago. The human body is made to move.
• Regular physical activity is associated with improve-
Starting with a simple roll at six months of age, progressing
ments in health across the female lifespan.
to a crawl, walk, and run, humans need to move not only
• Participation in sports and physical activity during
to function and survive but to thrive!
adolescence is strongly associated with adult physi-
As the evidence for the impact of regular physical
cal activity levels.
activity, exercise, and sports on human health and well-
• Low energy availability is the foundation of the
being expands and solidifies, the role of healthcare pro-
female athlete triad, which also includes menstrual
viders in promoting active lifestyles becomes increasingly
dysfunction and low bone mineral density, increas-
important – and this is important for every person at every
ing the risk of bone stress injuries in active females.
age. Physical activity is essential to normal human devel-
• The risk of developing type 2 diabetes and demen-
opment, function, and quality of life.
tia, two of the most common diseases of sedentary
The Physical Activity Guidelines for Americans (PAGA)
lifestyle and aging, can be significantly mitigated
is the definitive guide to physical activity recommendations
through regular physical activity and enhanced car-
across the age spectrum. The very first PAGA was pub-
diorespiratory fitness.
lished in 2008 and will be updated in 2018.1 The guidelines
serve to inform medical, public health, and health fitness
27.1 INTRODUCTION professionals (among others) on promoting and sustaining
physical activity for all. Each age group (children, adoles-
The importance of regular physical activity for health has cents, adults, and older adults) has unique needs, benefits,
been understood for centuries. “Lack of activity destroys and challenges related to physical activity. In the health-
the good condition of every human being, while movement care domain, understanding these guidelines will inform
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.
TABLE 27.1 Key guidelines for children and adolescents

Children and adolescents should do 60 minutes (1 hour) or more of physical activity daily.
• Aerobic: Most of the 60 or more minutes a day should be either moderate- or vigorous-intensity aerobic physical activity and should
include vigorous-intensity physical activity at least three days a week.
• Muscle-strengthening: As part of their 60 or more minutes of daily physical activity, children and adolescents should include
muscle-strengthening physical activity on at least three days of the week.
• Bone-strengthening: As part of their 60 or more minutes of daily physical activity, children and adolescents should include
bone-strengthening physical activity on at least three days of the week.
27.3 Benefits and Risks of Physical Activity and Competitive Sports for Adolescent Females 343
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
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
Figure 27.1 Spectrum of the Female Athlete Triad.27

27.4 Reproductive Health in Active and Athletic Females 345
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
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.
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
KEY CLINICAL MESSAGES

Population Message
Girls School-based physical activity represents the greatest opportunity for children to meet recommended levels of
physical activity. Physicians should assess physical activity at all well child visits, and encourage parents to regularly
provide opportunities for children and (and their families) to be physically active.
Adolescents Active adolescent females may be at risk for the female athlete triad. Screening should be performed during the
preparticipation physical evaluation. Early identification and intervention are associated with the best clinical
outcomes. Multidisciplinary team care (physician, sports dietitian, mental health professional) is warranted for those
with eating disorders and likely those with disordered eating.
Adults Physical activity should be assessed as a vital sign at each clinical encounter. Those with less than 150 minutes per
week of moderate-intensity activity and those not performing muscle strength training activities two times per week
should be advised and prescribed physical activity to improve health and prevent and manage disease.
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program with exercise, nutrition, and 2017;66:521–526.
VI
PA RT
Endocrinology and Metabolism

Jeffrey I. Mechanick, MD, FACP, FACE, FACN, ECNU
353
28
CHAPTER
Impact of Lifestyle Medicine on

Dysglycemia-Based Chronic Disease
Michael A. Via, MD and Jeffrey I. Mechanick, MD, FACP, FACE, FACN, ECNU
Key Points.................................................................................. 355 28.2.9 Systemic Inflammation....................................... 360

28.1 Introduction...................................................................... 355 28.2.10 Endocrine Disruptors.......................................... 361
28.2 Metabolic Components of Dysglycemia............................. 356 28.2.11 Artificial Sweeteners........................................... 361
28.2.1 Carbohydrate Metabolism..................................... 356 28.3 Dietary Patterns................................................................ 361
28.2.2 Dietary Carbohydrates – Starch, Fiber, and Sugar...... 357 28.3.1 Mediterranean Diets........................................... 361
28.2.3 Fructose............................................................... 357 28.3.2 The New Nordic Diet........................................... 362
28.2.4 Lipid Metabolism.................................................. 358 28.3.3 The Ornish Diet.................................................. 362
28.2.5 Omega-3 Fatty Acids............................................ 358 28.4 Physical Activity................................................................ 362
28.2.6 Antioxidants......................................................... 358 28.5 Conclusion........................................................................ 363
28.2.7 Plant Polyphenols................................................. 359 Clinical Applications................................................................... 363
28.2.8 Advanced Glycated End Products.......................... 360 References................................................................................ 363
harbor elements of insulin resistance and pancreatic β-cell

KEY POINTS dysfunction, producing specific states, such as polycystic
ovary syndrome (PCOS), metabolic syndrome (MetS),
• Dysglycemia-based chronic disease describes a spec-
and type 2 diabetes (T2D). In this context, the term dys-
trum of metabolic risk, to biochemical risk (predi-
glycemia describes any pathophysiological state with a
abetes), to early asymptomatic type 2 diabetes, to
primary or secondary disturbance in glucose regulation
late type 2 diabetes with complications, particularly
(Table 28.1). Dysglycemia-based chronic disease (DBCD)
cardiovascular events, reflecting varying degrees
refers to the multitude of chronic disease states that result
of pancreatic ß-cell dysfunction, insulin resistance,
from dysglycemia, especially those with cardiometabolic
inflammation, and organ dysfunction. Metabolic
risks factors. Another way of viewing DBCD is along a
syndrome, insulin resistance syndrome, and poly-
spectrum beginning with molecular or genetic risk for
cystic ovary syndrome also fall within this dysgly-
T2D, to demonstrable biochemical risk for T2D (“pre-
cemia spectrum.
diabetes”), to early asymptomatic and uncomplicated
• The role of early diagnosis and intervention for
T2D, to later symptomatic T2D with diabetes-related
patients with dysglycemia, primarily through
complications. This new perspective advances the clinical
screening and lifestyle medicine in the prediabetes
imperative to diagnose DBCD as early as possible so that
stage, is evidence-based and should be systemati-
effective preventive strategies, consisting primarily of life-
cally implemented to prevent downstream morbid-
style interventions, can be implemented. In addition, the
ity and mortality.
use of DBCD terminology can simplify health messaging
• Core lifestyle medicine interventions for patients
to patients by bundling recommendations about disease
with dysglycemia include healthy dietary patterns
prevention with disease treatment.
and plenty of physical activity.
Far beyond the observed impairment to insulin sig-
naling, DBCD, or more specifically, insulin resistance,
encompasses systemic metabolic dysfunction that affects a
28.1 INTRODUCTION wide array of energy regulatory hormonal and biochemi-
cal pathways. These include reduced release and activity
The metabolic regulation and internal control of how of glucagon peptide-1 (GLP1), improper postprandial
energy modulates biochemical processes are achieved hepatic glucose release mediated by inappropriate gluca-
through complex interactions of substrate-, humoral-, and gon activity during meals, leptin resistance, reduced adipo-
hormonal-level signals. Dysfunctional activity of this con- nectin activity, reduced ghrelin levels, unmasked pancreatic
trol network confers pathological consequences leading β-cell dysfunction resulting in impaired and delayed insu-
to various clinical syndromes. Many of these syndromes lin release, low-grade systemic inflammation, generalized
355
356 Chapter 28 Impact of Lifestyle Medicine on Dysglycemia-Based Chronic Disease
Current controversies in the definition for MetS should

TABLE 28.1 Measures of dysglycemia and insulin
not lessen the importance of dysglycemia and insulin
sensitivity.*
resistance as the main drivers of metabolic dysfunction in
Metric Description modern populations. Elevations in serum glucose concen-
trations (fasting serum glucose > 100 mg/dl), hypertension
Hyperinsulinemic-Euglycemic Measured response to constant
Clamp blood insulin and glucose (systolic blood pressure > 130 mm Hg, diastolic > 85 mm
concentrations Hg), increased abdominal girth (waist circumference > 102
cm in males, >88 cm in females), elevated circulating tri-
Hyperglycemic Clamp Rate of glucose disposal during
glycerides (>150 mg/dl), reduced circulating high-density
steady-state hyperglycemic
conditions lipoprotein (HDL) levels (<40 mg/dl in males, <50 mg/
dl in females) all result from systemic insulin resistance,
Intravenous Glucose Systemic response to either directly, indirectly, or both.8 For simplicity, we will
Tolerance Test (IVGTT) intravenous glucose load consider MetS in individuals with at least three of these
Oral Glucose Tolerance Test Systemic response to oral five components. The aggregate risk conferred by MetS
(OGTT) glucose load to each patient is greater than the sum of each individual
Mixed Meal Tolerance Test Systemic response to a mixed
component, and the difference (aggregate minus sum of
meal the components) is considered as residual risk. While each
MetS component can be addressed pharmacologically, it
Homeostasis Model Calculation based on fasting is intensive lifestyle intervention that specifically targets
Assessment (HOMA IR) serum insulin and glucose
concentration
residual risk.9
Insulin resistance leading to dysglycemia is also a fun-
Quantitative Insulin Calculation based on fasting damental component and causative factor in PCOS. A 27%
Sensitivity Check Index serum insulin and glucose reduction of insulin sensitivity is observed in women with
(QUICKI) concentration
PCOS, independent of body mass index.10 Decreased
Matsuda Index Total change in both serum expression of insulin receptors in visceral adipocytes is
insulin and glucose levels observed in PCOS as well as pancreatic β-cell dysfunc-
following OGTT tion.11,12 By addressing insulin resistance in patients with
Disposition Index (Insulin Sensitivity) x (First PCOS, many symptoms improve or resolve.13
Phase Insulin Response) In patients with T2D, insulin resistance is present for
years prior to diagnosis. This earlier DBCD stage of predi-
* See reference.108
abetes, in which MetS or PCOS generally reside, exposes
an important window for intensive lifestyle interventions
endoplasmic reticulum stress leading to protein misfold- that reduces both the risk of T2D, associated complica-
ing, and reduced clearance of advanced glycated end tions, and most importantly, cardiovascular disease.14
products.1,2 Impairment within each of these pathways Similarly, the gradual onset and chronic nature of MetS,
contributes to reduced metabolic efficiency and increases hepatosteatosis, and PCOS allow for intensive lifestyle
the risk of atherosclerotic vascular disease, degenerative interventions to mitigate complications or possibly resolve
disease, cardiomyocyte dysfunction, reduced function and the risk. Although pharmacological and surgical interven-
quality of life, potentially increased risk of malignancy in tions are available, the high prevalence rate and risk for
some cases, and increased overall risk of mortality. DBCD among modern populations mandate successful
Insulin activity exerts multiple cellular effects that implementation of intensive lifestyle changes.
stimulate growth and metabolism. Aside from impaired
cellular glucose uptake, resistance to insulin also directly
leads to reduced lipoprotein lipase activity and altered 28.2 METABOLIC COMPONENTS
triglyceride metabolism, reduced endothelial nitric oxide
synthase activity and increased secretion of endothelin-1 OF DYSGLYCEMIA
associated with vasoconstriction and elevated blood pres-
sure, increased oxidative free radical species production, Insulin resistance exerts many effects on the control of
impaired energy metabolism and contractility of cardio- metabolism in DBCD and consequently alters the effi-
myocytes, reduced capillary recruitment within skeletal ciency of substrate utilization. The impact of lifestyle
muscle, and impaired hypothalamic regulation of energy medicine on DBCD is better understood by parsing out
metabolism. 3,4 the relevant pathophysiology.
In recent decades, the prevalence of specific DBCD
states has increased significantly, paralleling trends in
obesity. Approximately 10% of the U.S. population is 28.2.1 Carbohydrate Metabolism
diagnosed with T2D, and 22–30% may be diagnosed In normal physiology, serum glucose concentration is
with MetS, depending on diagnostic criteria.5 PCOS is kept within a specific range during times of fasting, influx
present in approximately 7–10% of reproductive-age (e.g., food consumption), utilization (e.g., physical activ-
women.6 Among all of these conditions, hepatosteatosis ity), or stress (e.g., critical illness). This glycemic stability
is present among 50–75% of patients with dysglycemia, is achieved through a network of cellular/substrate-level,
which can lead to nonalcoholic steatohepatitis, and even- humoral, and hormonal regulatory mechanisms result-
tually cirrhosis.7 ing in “glucose allostasis,”15 with many vulnerable
28.2 Metabolic Components of Dysglycemia 357
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
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
TABLE 28.2 Examples of polyphenol compounds that affect glucose metabolism.*

Compound Source Metabolic effect
Chlorogenic acid Coffee Improved glycemic clearance
Curcumin Turmeric Reduce inflammation, antioxidant
Epigallocatechin gallate Grapes, tea, legumes Enhanced insulin secretion
Flavanols Cocoa powder Inhibition of dipeptidyl peptidase-4
Hydroxytyrosol and Oleuropein Olives Improved glucose levels, reduced insulin resistance,
improved β-cell function
Nagamine Sweet Potatoes Enhanced GLP-1 production
Naringin and Hesperidin Citrus Reduced glycemia
Procyanidin Cacao liquor Increased GLP-1 and insulin production
Quercetin Onions, fennel, cilantro, capers, Reduced glycemia, inhibition of α-glycosidase
and dill
Syringic acid Mangoes Enhanced insulin secretion
* See reference.109
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
TABLE 28.3 Classes of endocrine disrupting compounds.

Compound Source Metabolic effect
Organotins Wood preservatives Adipocyte growth, associated with obesity
Phthalates Plastics, vinyl, cosmetics Visceral fat accumulation, associated with obesity, inhibition of PPARα*
and PPARγ*
DDT, methoxychlor Pesticides Associated with obesity
Polybrominated diphenol esters Flame retardants Associated with obesity, impaired lipid metabolism
Saccharine, aspartame Artificial sweeteners Induce insulin resistance via altered gut microbiota, possibly activate
nutrient sensing receptors eliciting inappropriate insulin release
* Abbreviations: PPARα – Peroxisome Proliferator-Activated Receptor α; PPARγ – Peroxisome Proliferator-Activated Receptor γ.

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.
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29
CHAPTER
Lifestyle Medicine and the

Management of Prediabetes
Karla I. Galaviz, PhD, MSc, Lisa Staimez, PhD, MPH, Lawrence S. Phillips, MD,
and Mary Beth Weber, PhD, MPH
Key Points.................................................................................. 367 29.4.2 Weight Loss.......................................................... 373

29.1 The Burden of Prediabetes................................................ 367 29.4.3 Changes in Insulin Secretion and Action............... 374
29.2 The Role of Lifestyle Factors in the Development of 29.4.4 Physical Activity and Diet Behavior Change........... 374
Prediabetes...................................................................... 369 29.5 Preventing and Managing Prediabetes in the Real World........376
29.3 Lifestyle Interventions for Prediabetes Prevention and 29.6 Conclusions...................................................................... 377
Treatment......................................................................... 371 Clinical Applications................................................................... 377
29.4 Components of Effective Lifestyle Interventions Programs...... 373 References................................................................................ 377
29.4.1 Intervention Modality............................................ 373
physical activity can prevent or reverse prediabetes.

KEY POINTS Moreover, this evidence supports the use of screening or
aggressive case finding tools for early detection of this per-
• Prediabetes is a physiological state created by
vasive medical condition.
molecular/genetic risk, insulin resistance, ß-cell
Prediabetes is diagnosed when there is impaired fasting
defects, and abnormal glycemic status (fasting and/
glucose (IFG), impaired glucose tolerance (IGT) or both.
or postprandial) that is associated with not only an
The American Diabetes Association defines IFG as fasting
increased risk for type 2 diabetes but also diabetes-
plasma glucose (FPG) levels of 100–125 mg/dL (5.6–6.9
related complications.
mmol/L) and IGT as two-hour plasma glucose levels of
• Prediabetes is diagnosed by fasting plasma glucose
140–199 mg/dL (7.8–11.0 mmol/L) after an oral glucose
100–125 mg/dl, two-hour post-challenge plasma
tolerance test.1 The World Health Organization has a dif-
glucose 140–199 mg/dl, or hemoglobin A1c 5.7–
ferent definition for IFG, corresponding to FPG values of
6.4%, according to screening and aggressive case
110–125 mg/dL (6.1–6.9 mmol/L). 2 IFG reflects primarily
finding strategies. On a population scale, awareness
hepatic insulin resistance and impaired early-phase insu-
of the risk for prediabetes and consequent adverse
lin secretion, while IGT reflects muscle insulin resistance
health impacts should be improved.
with impaired late-phase insulin secretion. 3 These patho-
• Prediabetes should be detected and managed early
physiologic characteristics have led to the distinction of
to minimize the morbidity associated with this dys-
two main prediabetes phenotypes, isolated IFG and iso-
glycemic state. Lifestyle medicine interventions, that
lated IGT, and individuals may present with either or both
promote healthy dietary patterns, healthy weights
of these conditions (i.e., impaired glucose metabolism).
and body composition, and regular physical activ-
Glycated hemoglobin (hemoglobin A1c; A1C), a measure
ity, are critical.
of the amount of red blood cells covalently bonded to a
glucose molecule, reflects chronic hyperglycemia over a
three-month period (the life span of a hemoglobin). A1C
29.1 THE BURDEN OF PREDIABETES values between 5.7–6.4% (39–47 mmol/mol) are also
recommended by the American Diabetes Association to
Prediabetes is a state of hyperglycemia where blood glu- define prediabetes (Figure 29.1).1
cose levels are higher than normal but lower than diabetes A debate exists on whether a prediabetes diagnosis
thresholds. Prediabetes is an economically costly dis- should be used. Experts opposing the use of a prediabetes
ease and a major contributor to morbidity and mortality diagnosis argue that it leads to unnecessary use of glucose
worldwide. Fortunately, there is compelling evidence that management drugs (typically used in diabetes to control
lifestyle interventions that focus on achieving and main- blood sugar) to prevent or delay the condition, trans-
taining a healthy weight among high body mass index forming people with prediabetes essentially into those
populations, improving dietary patterns, and increasing with “diabetes.” They also argue that using a prediabetes
367
368 Chapter 29 Lifestyle Medicine and the Management of Prediabetes
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.
Adapted from Kahn et al., Nature 2006.48

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.
Adapted from Weber et al., 2010.153

29.3 Lifestyle Interventions for Prediabetes Prevention and Treatment 371
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
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.
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
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.
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30
CHAPTER
Lifestyle Therapies for the

Management of Diabetes
Marion J. Franz, MS, RD, CDE
Key Points.................................................................................. 383 30.4.1.1 Medical Nutrition Therapy...................... 387

30.1 Introduction...................................................................... 383 30.4.1.2 Physical Activity..................................... 388
30.2 Diagnosis of Diabetes....................................................... 384 30.4.1.3 Education/Counseling and Support......... 389
30.3 Type 1 Diabetes................................................................ 384 30.4.1.4 Psychosocial Care.................................. 389
30.3.1 Treatment of Type 1 Diabetes: Insulin and 30.5 Gestational Diabetes......................................................... 389
Blood Glucose Monitoring�� 385 30.5.1 Lifestyle Interventions for Gestational Diabetes.........390
30.3.2 Lifestyle Interventions for Type 1 Diabetes............ 385 30.5.1.1 Medical Nutrition Therapy...................... 390
30.3.2.1 Medical Nutrition Therapy (MNT)............ 385 30.5.1.2 Physical Activity..................................... 391
30.3.2.2 Physical Activity/Exercise....................... 385 30.5.1.3 Education/Counseling and Support......... 391
30.3.2.3 Education/Counseling and Support......... 387 30.5.1.4 Psychosocial Care.................................. 391
30.3.2.4 Psychosocial Care.................................. 387 30.6 Summary.......................................................................... 391
30.4 Type 2 Diabetes................................................................ 387 Clinical Applications................................................................... 391
30.4.1 Lifestyle Interventions for Type 2 Diabetes............ 387 References ................................................................................ 392
have diabetes and another 84.1 million have prediabetes

KEY POINTS (33.9% of adults). This total includes the nearly 1 in 4
adults, or 7.2 million Americans who do not know they
• Medical Nutrition Therapy provided by a registered
have diabetes. In people age 65 years or older, 25.2% have
dietitian nutritionist is a critical evidence-based
diabetes, and among children and adolescents younger
intervention for patients with diabetes. Eating Plans
than 20 years, approximately 193,000 have diagnosed
for patients with diabetes should be individualized,
type 1 diabetes (T1D) or type 2 diabetes mellitis (T2D). Of
emphasize a variety of nutrient-dense foods with
interest, disease numbers appear to be holding steady— in
appropriate portion sizes, and developed with the
2012, it was estimated that 29.1 million people, or 9.3%
patient to optimize implementation and success.
of the population, had diabetes. Fortunately, the rates of
• Specific evidence-based physical activity recommen-
diabetes-related complications in the United States have
dations consisting of moderate to vigorous cardiore-
declined substantially in the past two decades; however, the
spiratory fitness and strength training activities are
large burden of diabetes persists because of the continued
available and should be individualized and imple-
prevalence of the disease.2 It is reported worldwide that
mented for all patients with diabetes.
the number of adults with diabetes has increased from 108
• Diabetes Self-Management Education and Support
million in 1980 to 422 million in 2014, with the number
(DSMES) as well as psychosocial care should be pro-
of adults affected increasing the fastest in low-income and
vided for all patients with diabetes as part of a col-
middle-income countries.3
laborative, patient-centered approach.
In no other disease than diabetes does the role of life-
style therapies (e.g., medical nutrition therapy (MNT),
physical activity, and/or education/counseling and sup-
30.1 INTRODUCTION port) play a more important role in both prevention and
management.4,5 Multiple studies have shown that lifestyle
In the United States (U.S.) and worldwide, the preva- interventions implemented in individuals with prediabetes
lence of diabetes has increased dramatically since the late can effectively prevent or delay T2D— in some studies— up
1990s. The Centers for Disease Control and Prevention to 15 to 20 years.6 Diabetes is known to be a progressive
(CDC) reported that as of 2015 more than 100 million disease, and although lifestyle interventions are effective
U.S. adults were living with diabetes or prediabetes.1 Of throughout the disease process, they have their greatest
these, 30.3 million U.S. residents (9.4% of the population) impact earlier in the course of the disease.7
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).
TABLE 30.1 Criteria for the diagnosis of diabetes*

Fasting plasma glucose ≥ 126 mg/dL (7.0 mmol/L). Fasting is defined as no caloric intake for at least 8 h.a
OR
2-h plasma glucose ≥ 200 mg/dL (11.1 mmol/L) with oral glucose tolerance test (OGTT). The test should be performed using a glucose
load containing the equivalent of 75 g anhydrous glucose dissolved in water.a
OR
A1C ≥ 6.5% (48 mmol/mol). This test should be performed in a laboratory using a method that is NGSP (www.ngsp.org)-approved and
standardized to the Diabetes Control and Complications Trial (DCCT) assay.a
OR
In a patient with classic symptoms of hyperglycemia or hyperglycemic crisis, a random plasma glucose ≥ 200 mg/dL (11.1 mmol/L).
* See references.8,12
In the absence of unequivocal hyperglycemia, results should be confirmed by repeat testing.
a
30.3 Type 1 Diabetes 385
Autoimmune markers include autoantibodies to glu- insulin-to-carbohydrate ratios contributed to significant
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)
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.
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
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
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
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
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.
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31
CHAPTER
Implementing Nutritional Lifestyle

Treatment Programs in Type 2 Diabetes
George Guthrie, MD, MPH, CDE, CNS, FAAFP, FACLM
Key Points.................................................................................. 393 31.4.4 Increased Vegetable Intake................................... 399

31.1 Introduction and Context................................................... 393 31.4.5 Grain Intake.......................................................... 399
31.2 Primary Prevention........................................................... 394 31.4.6 High Fiber Diet..................................................... 400
31.3 Secondary and Tertiary Prevention: Can Pathology be 31.4.7 Low Protein Diet................................................... 400
Reversed?........................................................................ 395 31.4.8 Hydration and Sodium Intake................................ 401
31.4 Lifestyle Programs for Type 2 Diabetes............................. 396 31.4.9 Meal Timing and Intermittent Fasting.................... 401
31.4.1 Low Fat Eating Patterns........................................ 396 31.5 Summary.......................................................................... 403
31.4.2 100% Plant-Based Eating Patterns....................... 396 Clinical Applications................................................................... 403
31.4.3 Increased Fruit..................................................... 399 References................................................................................ 404
In this chapter, the implementation of best principles in

KEY POINTS type 2 diabetes (T2D) care will be examined through the
lens of clinical narratives to curate experiential and evi-
1. There is credible evidence that a significant portion
dentiary information, and then present an expert array of
of the underlying pathophysiology of type 2 diabetes
how-to guidelines on program building, particularly for
is reversible by making appropriate behavioral and
secondary and tertiary nutritional prevention strategies.
lifestyle changes; therefore, clinicians have an ethi-
Nathan Pritikin’s founded his longevity center in Santa
cal responsibility to guide implementation of effec-
Barbara in 1974, then moved it in 1978 to an old Santa
tive, evidence-based lifestyle medicine programs.
Monica, California beach-side hotel, repurposed for inten-
2. Calorie restriction and weight loss provide the foun-
sive lifestyle intervention. It is the source of data showing
dation of dietary interventions for type 2 diabetes.
significant improvement in lipids, weight, blood pressure,
The evidence also points to a dietary pattern high in
blood sugar, and hemoglobin A1c (A1C) with “treatment”
fruits, vegetables, whole grains, dietary fibers, and
(Figure 31.1). The exercise facilities on the beach level were
low in saturated fat and animal proteins, as highly
next to the boardwalk and surf in this immersive envi-
effective in type 2 diabetes.
ronment. The dining room served a minimally processed,
3. Other lifestyle factors are also evidence-based and
whole and plant-based meal presented in first-class style to
should be part of any programmatic lifestyle medi-
the “guests.” A little fish was being served in a vegetable
cine application for type 2 diabetes, such as hydra-
soup once a week so that the program would not be labeled
tion, meal timing, and increased physical activity.
“vegetarian,” as that had a negative connotation at the time.
Both the analyzed statistics and the stories of individual
31.1 INTRODUCTION AND CONTEXT “guests” were impressive but there was no randomization,
control group, or long-term follow-up. Later, R.J. Barnard
Strategies for applying structured lifestyle (nonpharma- of UCLA would formally report on the improvement of lipid
cological and nonsurgical) interventions to improve dys- parameters1 and glucose control measures2 seen in program
glycemic states must be relevant and then actionable as participants.3 Skeptics and purists responded by arguing
implementation tactics. These concrete actions must be that this was a self-selected group without a true control
suitable for adaptation to a variety of clinical scenarios so group, and consequently, the scientific community largely
that real-life clinical benefits can be observed, validated, ignored the results. Notwithstanding these criticisms, this
and replicated by others to create and nurture a success- proof-of-concept experience demonstrated that there are at
ful health care culture. This process translates best prin- least some people for which certain metabolic parameters
ciples from basic and clinical science into best practices can be improved, and, at least for a few, the beneficial effects
for different inpatient and outpatient settings, in order were considered stronger than the medication treatments
to improve chronic lifestyle-related disease management. available at the time.
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
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
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.
Figure 31.2 Homeostatic Model Assessment to Assess Pancreatic Beta-Cell Function.
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
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
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
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.
31.5 SUMMARY significant benefits when compared to the six-meal-a-day
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.
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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 inhibits 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
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VII
PA RT
Lifestyle Issues in the Prevention

and Treatment of Cancer
407
32
CHAPTER
Diet and Cancer Prevention

Key Points.................................................................................. 409 32.3.3 Carotenoids...........................................................412

32.1 Introduction...................................................................... 409 32.4 Dietary Fiber......................................................................412
32.2 Total Fruits and Vegetables............................................... 409 32.5 Meat Intake.......................................................................413
32.3 Specific Micronutrients and Phytochemicals......................410 32.6 Alcohol..............................................................................414
32.3.1 Garlic and Allium Vegetables..................................410 32.7 Summary and Conclusion..................................................415
32.3.2 Folate....................................................................411 References.................................................................................415
by 13% between 2004 and 2013.1 This positive trend is

KEY POINTS thought not to be a result of miraculous medical break-
throughs but rather a result of improvements in preven-
• Increase consumption of foods that have been shown
tion, early detection, and treatment of different causes
to decrease cancer risk including whole grains, veg-
of cancer. Altering what a person eats based on current
etables, fruits, and pulses such as beans.
guidelines represents a proactive, practical, and cost effec-
• Decrease consumption of foods associated with
tive approach to cancer prevention that is also likely to
increased cancer risk, including red meat such as beef,
promote overall good health since many of the recommen-
pork, and lamb, processed meat such as ham and
dations for cancer prevention are similar to those for the
bacon, alcoholic drinks, and salt-preserved foods.
prevention of other chronic diseases.
• Eat a healthy diet rather than relying on supple-
Evidence continues to accumulate that modifying
ments to protect against cancer.
dietary habits can reduce cancer risk and alter the bio-
logical behavior of tumors. The importance of diet was
emphasized more than a quarter-century ago when Doll
32.1 INTRODUCTION and Peto4 suggested that approximately 35% (10–70%) of
all cancers in the United States might be attributable to
“Cancer” is a generic term that represents more than 100 dietary factors. In 2007, similar conclusions were reached
diseases, each with a different etiology. Types of cancer by The World Cancer Research Fund/American Institute
are usually named for the organs or tissues where the can- of Cancer Research (WCRF/AICR) after evaluating over
cer originates, but they also may be described by the type 7,000 studies. Their report concluded that diet and physi-
of cell that formed them. In 2016, an estimated 1,685,210 cal activity were major determinants of cancer risk. 5
new cases of cancer were diagnosed in the United States On a global scale, this could represent over 3–4 million
and 595,690 people died from the disease. 1Worldwide, the cancer cases that could be prevented each year. 5 Since
number of new cancer cases is expected to rise by about 2007, WCRF/AICR has been performing an ongoing anal-
70% over the next two decades and approximately 70% ysis, known as the Continuous Update Project (CUP), of
of deaths will occur in low- and middle-income coun- all relevant papers from randomized controlled trials and
tries. 2 Cancer risk is influenced not only by genetic factors cohort studies published on the relationship between diet,
but also by environmental factors such as dietary habits. nutrition, physical activity, and weight and the risk for 17
While each type of cancer has unique features, they all cancers, as well as breast cancer survivorship.6
share one common characteristic, namely that they begin
when a single cell acquires genetic changes and loses con-
trol of its normal growth and replication processes.3 Most
cancers develop to the stage of being clinically identifiable 32.2 TOTAL FRUITS AND VEGETABLES
only years or decades after the initial cell damage.
Cancer is no longer being recognized as an inevitable Evidence that consumption of vegetables and fruits
consequence of aging. Only about 5–10% of cancers can provides protection against cancer comes principally
be classified as familial, and thus most are associated with from epidemiological, animal, and cell culture studies.
multiple environmental factors, including one’s eating Vegetables and fruits are usually low in energy density
behaviors. The National Cancer Institute has estimated and are high in fiber, vitamins, minerals, and other bio-
that in the United States, the overall cancer death rate fell active compounds (phytochemicals). Recommendations
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
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
that prolonged high-temperature cooking of meats results

in the greatest content. Epidemiologic and animal studies
32.6 ALCOHOL
have linked HCA with cancers of the colorectum, breast, Alcohol is the common term for ethanol or ethyl alco-
prostate, lung, and pancreas. 56 Polymorphisms in specific hol, a chemical substance found in beer, wine, and liquor.
genes associated with metabolism or detoxification of Ethanol has been classified by the International Agency
HCA (e.g. CYP1A1, CYP1A2, GSTM1, and NAT2) may for Cancer Research (IARC) as a human carcinogen. The
explain variations in genetic susceptibility among indi- WCRF/AICR panel judged that there is convincing evi-
viduals. 57 In view of the possible role of HCA in human dence that alcoholic drinks increase mouth, pharynx, and
carcinogenesis, minimizing exposure seems prudent, i.e. larynx, esophagus, colorectum (men), and breast cancer. 5
avoiding overheating and overcooking. Alcoholic drinks are probably also a cause of liver cancer,
Nitrites and nitrates are often used as preservatives in and of colorectal cancer in women. 5 Recently, it was sug-
meats and other “cured” products. These additives are not gested that alcohol consumption appears to cause 8% of
carcinogenic in experimental animals; however, nitrate new cancer cases in France66 and binge drinking (>1 d/
can interact with dietary substances, such as amines or week) has been associated with a 22% increased risk of
amides, to produce N-nitroso compounds (nitrosamines cancer mortality in the United States.67 Numerous stud-
and nitrosoamides), which are potent carcinogens in ani- ies have examined the association between alcohol con-
mals and probably humans58 Epidemiologic studies have sumption and the risk of other cancers, such as cancers of
demonstrated a direct relationship between nitrosamine the pancreas, ovary, prostate, stomach, uterus, and blad-
exposure and cancer of the stomach, esophagus, naso- der. For these cancers, either no association with alco-
pharynx, urinary bladder, liver, and brain. 58 When 14 hol use has been found or the evidence for an association
volunteers consumed a high red meat diet (325 g) com- is inconsistent. In contrast, for two cancers—renal cell
pared to an isocaloric high fish diet (375 g), there were (kidney) and non-Hodgkin lymphoma (NHL), multiple
significantly higher nitroso compounds excreted in the studies have shown that increased alcohol consumption is
feces (9 μmol/d vs. 1.7 μmol/d, respectively). 59 Several associated with a decreased risk of cancer.68,69 However,
naturally occurring foods and their constituents, includ- the mechanisms by which alcohol consumption would
ing tea, garlic, and cruciferous vegetables, may inhibit the decrease the risk of either renal cell cancer or NHL are
formation of endogenous nitrosamines.60 This reduction not understood. The amount of alcohol someone con-
in carcinogen formation may contribute to the generally sumes over time, not the type of alcoholic beverage, seems
protective effect of fruit and vegetables on cancer risk to be the most important factor in influencing cancer risk.
since vitamin C may reduce their formation while other Researchers have identified multiple potential mecha-
compounds such as allyl sulfur may reduce their bioacti- nisms whereby alcohol may contribute to an increased
vation to agents that bind to DNA and thereby lead to the risk of cancer. First, ethanol in alcoholic drinks is mainly
initiation phase of cancer. oxidized in the liver by alcohol dehydrogenase (ADH) to
Heme iron from animal sources is better absorbed than acetaldehyde. Acetaldehyde is the most toxic metabolite
iron from plant sources; thus, animal food is important of alcohol metabolism, a probable human carcinogen, and
in minimizing this nutritional deficiency. However, heme particularly damaging to cells. In experimental animals,
promotes the formation of N-nitroso compounds. In addi- acetaldehyde is a mutagen and carcinogen that causes
tion, excess heme iron in the colon may irritate the mucosa DNA damage.70 Acetaldehyde is subsequently metabo-
and alter the normal rates of proliferation/exfoliation, cir- lized to acetate, mainly by the enzyme aldehyde dehydro-
cumstances that increase the risk for the development of genase 2 (ALDH2). Second, generation of reactive oxygen
colon cancer.61 There is also evidence that heme iron in species during ethanol metabolism can damage DNA,
meat may foster the generation of free radicals through lipids, and proteins and can activate signaling molecules
the Fenton reaction.62 Multiple factors may influence the involved in inflammation and angiogenesis. Third, the
amount of free iron and thus free radicals, including the intake of ethanol not only causes mucosal damage but
formation of iron binding and transport proteins.63 also changes the composition of enteric bacteria, which
In a large, prospective study of meat consumption and disrupts the intestinal epithelial barrier. Fourth, chronic
colorectal cancer risk, meat derived increases in heme iron, alcohol consumption can result in decreased absorption of
nitrate/nitrite, and heterocyclic amines were all associated a variety of nutrients associated with cancer risk, includ-
with increased risk of colon cancer.64 Nevertheless, it is ing folate, which may provoke aberrant DNA methylation
important to remember that meat can be a valuable source profiles, thereby influencing cancer-related gene expres-
of many nutrients, including protein, iron, zinc, selenium, sion. Finally, alcohol may increase blood levels of estrogen
and vitamins B6, and B12 . Iron deficiency is the most com- which has been linked to breast cancer risk.
mon and widespread nutritional deficiency in the world. Polymorphisms in ethanol- and acetaldehyde-metab-
Therefore, it is important to limit red meat consumption olizing enzymes, especially ADH and ALDH, have been
rather than to avoid it. The WCRF recommends that pop- closely associated with ethnic and individual differences
ulation average consumption of red meat be no more than in susceptibility to alcohol-related cancers. For exam-
300 g (11 oz.) a week, very little of which is processed. ple, many individuals of Chinese, Korean, and Japanese
Their personal recommendation is that individuals limit descent carry a version of the gene for ADH that codes for
their intake to less than 500 g (18 oz.) a week.65 Also, it a “superactive” form of the enzyme. As a result, they have a
is important to consider the entire diet and, thus, interac- quicker conversion of ethanol to acetaldehyde and a higher
tions among different food groups; for example, fruit and risk of pancreatic cancer.71 In addition, a genetic variant in
vegetables decreasing the formation of nitrosamines. ALDH2 that codes for a defective form of the enzyme with
References 415
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.
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33
CHAPTER
Lifestyle Approaches Targeting

Obesity to Reduce Cancer Risk,
Progression, and Recurrence
Debora S. Bruno, MD, MS and Nathan A. Berger, MD
Key Points...................................................................................419 33.4.1.7 Follow Cancer Screening Guidelines...... 425

33.1 Introduction.......................................................................419 33.4.2 Guidelines for Secondary Prevention in Cancer
33.2 Mechanisms of Obesity Impact on Cancer........................ 420 Survivors�� 425
33.3 Strategies to Disrupt the Obesity–Cancer Linkage............. 422 33.4.2.1 Secondary Prevention of Cancers.......... 425
33.4 Lifestyle Recommendations to Disrupt the Obesity– 33.4.2.2 Avoid Weight Gain After Cancer
Cancer Linkage................................................................ 423 Diagnosis�� 425
33.4.1 Recommendations for Lifestyle Modifications 33.4.2.3 Use Exercise as a Tool to Decrease
for Primary Cancer Prevention�� 423 Obesity�� 425
33.4.1.1 Achieve and Maintain a Lean Weight 33.4.2.4 Use Exercise to Increase Cancer
Across Life Span�� 423 Survival Odds�� 425
33.4.1.2 Avoid High-calorie Foods and 33.4.2.5 Make Dietary Changes to Achieve
Sugary Drinks�� 423 Weight Loss�� 425
33.4.1.3 Prioritize Healthy Eating Patterns—Rich 33.4.2.6 Invest in Sleep Hygiene......................... 426
in Whole Foods, Plant-based Elements��423 33.4.3 Type 2 Diabetes Mellitus and Cancer Risk............. 426
33.4.1.4 Physical Activity..................................... 424 33.4.4 Special Considerations......................................... 427
33.4.1.5 Maintain Good Sleep Hygiene................ 424 33.5 Conclusions...................................................................... 427
33.4.1.6 Lose Weight If You Are Overweight References................................................................................ 427
or Obese�� 424
million obese adults and 110 million obese children.3,4

KEY POINTS These figures are alarming in that overweight and obesity
are associated with increased risk for many health prob-
• Overweight and obesity are accompanied by
lems including heart disease, stroke, type 2 diabetes mel-
increased risk and worse prognosis for multiple
litus, musculo-skeletal disorders, cancer, and many others.5
malignancies; individuals who are overweight or
Thus, obesity and its consequences are replacing infec-
obese should follow standard cancer screening
tious diseases as major causes of morbidity and mortality.
guidelines.
Further cause for alarm is the cost of obesity-associated
• For individuals who are overweight or obese, inten-
diseases, which, in the United States, was estimated at $147
tional weight loss lowers cancer risk and improves
billion annually or an increase per individual of $1,429 per
survival.
year above average healthcare costs.6
• Patients with cancer should avoid excess weight gain
The terms “overweight” and “obesity” are used to
and, if already overweight or obese, should lose
describe the condition where an individual carries more
weight to improve prognosis.
weight, usually as fat mass, than the average normal per-
son of the same height and gender. These weight compari-
sons are commonly expressed using the term “body mass
33.1 INTRODUCTION index” (BMI), calculated as weight in kilograms divided
by height in meters squared (BMI = weight (kg) ÷[height
Obesity is a major health problem in the United States, (m)]2). BMI can be easily determined using readily avail-
where it is now considered the major public health chal- able websites.7 Individuals with a BMI less than 18.5 kg/
lenge of our time.1,2 On a global basis, obesity has m2 are considered underweight and may be subject to
reached pandemic proportions with an estimated 640 unique health problems associated with malnutrition and
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, proof 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
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
33.4 LIFESTYLE RECOMMENDATIONS developing many diseases, such as type 2 diabetes mel-
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
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
33.4.2 Guidelines for Secondary The authors recommend that following a diagnosis of

Prevention in Cancer Survivors cancer all the aforementioned strategies to control weight
and obtain/keep lean body weight are developed and/or
Cancer survivorship is, by definition, life after a diagnosis strengthened (Table 33.2). Some other considerations spe-
of cancer. From the time of diagnosis and onwards, treat- cific to cancer survivorship include:
ment goals should not only focus on a cure or lengthening
survival, but also decreasing and treating complications
related to therapy, surveying for progression or recurrence 33.4.2.3 Use Exercise as a Tool to Decrease Obesity
of the original cancer, as well as preventing and detect- Different forms of exercise activity have been studied in can-
ing new primary cancers. With improvement in screen- cer survivors to combat side effects from treatment.142,143
ing and treatment of different types of malignancies, the While in the recent past, oncology patients were fre-
number of cancer survivors has increased substantially quently told to rest and conserve energy, currently they
over the past decades. Currently, there are more than 15.5 are told to be as active as possible. It is best to combine
million survivors in the U.S.134 and many face substantial and diversify aerobic, resistance, and mindfulness-based
challenges not only in recovering and living with sequelae exercise to achieve maximal health benefits and fight side
from their diagnosis and treatment but also working on effects. There is no single exercise prescription that fits all
instituting and maintaining lifestyle modifications that cases, and the type and level of activity should be tailored
can lead to improved health outcomes. In this section, we to individual needs and limitations.
focus on the impact of obesity in cancer survivorship and Both aerobic and resistance training exercise can
potential strategies to address this health problem. improve cancer-related fatigue,144–147 a highly prevalent
symptom that often persists after cancer-directed therapy
is complete.148 Positive effects of physical activity seem
33.4.2.1 Secondary Prevention of Cancers to be dose-related, with moderate- or vigorous-intensity
Obesity is a risk factor for cancer recurrence after ini- exercise displaying a more pronounced impact.149
tial diagnosis and treatment, and can lead to worse
outcomes.135–137 Obese cancer survivors are more likely
33.4.2.4 Use Exercise to Increase
to develop complications from cancer treatment,138–140
including lymphedema and post-operative complications. Cancer Survival Odds
They are also more likely to develop new primary malig- The biological reasons for the protective effects of exercise
nancies.141 Therefore, following an initial cancer diagno- may be more complex than simply weight management.
sis, obesity should be aggressively treated as a risk factor For instance, there is evidence that exercise can modu-
that needs to be controlled as much as tobacco use. late circulating levels of growth factors such as IGF-1150
and insulin,151 as well as endogenous hormones such as
estradiol.152 For a detailed review on exercise for cancer
33.4.2.2 Avoid Weight Gain After Cancer Diagnosis prevention, refer to the chapter on Physical Activity and
Many interventions aiming to control and treat can- Cancer Risk.
cers can lead to deleterious weight gain. The etiology of
weight gain following cancer diagnosis is multifactorial.
It includes:
33.4.2.5 Make Dietary Changes to
Achieve Weight Loss
• Use of medications to prevent nausea and reactions Two clinical studies in breast cancer survivors have
to chemotherapy that are notorious for inducing addressed the impact of dietary intervention on breast
increased appetite and weight gain (corticosteroids) cancer recurrence and overall survival. The Women’s
• Development of fatigue as a cancer symptom or a Healthy Eating and Living (WHEL) study looked at the
side effect of the treatments provided (chemotherapy, effects on breast cancer outcomes and overall survival of
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.
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34
CHAPTER
Physical Activity and the Prevention

and Treatment of Cancer
Case H. Keltner, MPH and Heather R. Bowles, PhD
Key Points.................................................................................. 431 34.3.2 Physical Activity Guidelines for Cancer

34.1 Global Cancer Burden....................................................... 431 Populations�� 434
34.2 Physical Activity and Cancer Prevention............................ 431 34.3.3 Summary of Physical Activity Guidelines
34.2.1 Overview.............................................................. 431 Adherence�� 435
34.2.2 The Role of Physical Activity in Primary Cancer 34.4 Physical Activity Behavior Change..................................... 435
Prevention�� 432 34.4.1 Barriers to Physical Activity for Healthy
34.2.3 The Role of Physical Activity in Secondary Populations�� 435
Cancer Prevention�� 433 34.4.2 Barriers to Physical Activity for Cancer
34.2.4 The Role of Physical Activity in Tertiary Cancer Populations�� 436
Prevention�� 433 34.5 Strategies for Physical Activity Interventions..................... 436
34.3 Defining “ Health-Enhancing” Physical Activity.................. 433 34.6 Limitations of Physical Activity and Cancer Research........ 437
34.3.1 Physical Activity Guidelines for Healthy 34.7 Conclusion........................................................................ 437
Populations�� 434 References................................................................................ 437
new cancer cases are projected to be diagnosed in the United

KEY POINTS States alone in 2017.3 As of 2016, over 15.5 million living
Americans, approximately 4.8% of the population, had been
• Research is continuing to affirm the role of physical
diagnosed with cancer at some point during their lives.3,4
activity in primary, secondary, and tertiary cancer
The human and fiscal toll of cancer has risen sharply
prevention.
since the turn of the century. Between 2005 and 2015,
• More cancers are being linked to physical inactivity.
the number of new cancer cases increased by 33% glob-
• Multiple guidelines have been released that can
ally, with age-standardized incidence rates for all cancer
help clinicians prescribe physical activity to patients
types increasing in 174 countries during that time period.5
according to their cancer status.
Direct medical costs for cancer in 2014 surpassed $87.7
• Various barriers often stand between patients and
billion in the United States, with 58% of costs stemming
their ability or desire to engage in physical activity.
from the office-based provider or hospital outpatient vis-
• Offering tailored patient counseling and using digi-
its, and 27% due to inpatient hospital services. 3 Some esti-
tal technologies can help increase patient adherence
mates suggest that the direct fiscal toll of cancer could
to a physical activity regimen.
double by 2020.6 As incidence rises and the cost of care
• Best practices in physical activity, and the biological
mounts, healthcare providers must develop strategies for
mechanisms linking inactivity with heightened can-
delivering efficacious, cost-effective preventive care.
cer risk, must continue to be evaluated.
34.1 GLOBAL CANCER BURDEN 34.2 PHYSICAL ACTIVITY AND

In recent decades, pronounced epidemiological transitions
CANCER PREVENTION
have been marked by rising rates of chronic illnesses. Non-
communicable diseases (NCDs) contribute to 70% of deaths
34.2.1 Overview
globally, and cancer comprises a sizeable portion of this Clinicians and researchers alike have embraced main-
growing burden.1 Cancer poses a ubiquitous public health tenance of a healthy lifestyle as a component of oncol-
threat throughout the world. Nearly one in six deaths is ogy, and lifestyle issues have been scrutinized in greater
attributable to cancer, which equates to 8.8 million deaths breadth and depth in recent years. Physical activity plays
annually.2 Over the next twenty years, global cancer inci- a key role in the lifestyle– cancer nexus. Although spe-
dence is expected to rise by 70%,2 and nearly 1.69 million cific biological mechanisms linking physical activity and
431
432 Chapter 34 Physical Activity and the Prevention and Treatment of Cancer
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
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 physical 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
TABLE 34.1 Clinical recommendations for physical activity
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
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.
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35
CHAPTER
Nutrition Therapy for the Cancer Patient

Sandeep (Anu) Kaur, MS, RDN, RYT-500 and Elaine Trujillo, MS, RDN
Key Points.................................................................................. 441 35.6 Complementary and Restorative Therapeutic

35.1 Introduction...................................................................... 441 Treatment of Cancer......................................................... 446
35.2 Malnutrition and Cancer Cachexia..................................... 441 35.6.1 Special and Alternative Diets—Metabolic
35.3 Metabolic Alterations in Cancer......................................... 442 Therapy vs. Dietary Approaches�� 447
35.3.1 Altered Carbohydrate Metabolism......................... 442 35.6.2 Metabolic Dietary Therapies................................. 448
35.3.2 Altered Fat Metabolism......................................... 442 35.6.3 Fasting Diet.......................................................... 448
35.4 Nutrition Screening........................................................... 443 35.6.4 The Ketogenic Diet............................................... 449
35.4.1 Nutrient Needs..................................................... 444 35.7 Conclusion........................................................................ 449
35.5 Cancer Treatment and Side Effect Management................ 444 Acknowledgments..................................................................... 449
35.5.1 Chemotherapy and Radiation Therapy.................. 444 References................................................................................ 450
35.5.2 Lifestyle Strategies When Eating During Treatment......444
weight loss of approximately 83% and 87%, respectively.1

KEY POINTS Cancer and/or cancer treatment often leads to symptoms
that hinder dietary intake and digestion, which may result
• Cachexia is a weight loss of >5% or a weight loss
in a host of side effects such as, anorexia, nausea, vom-
of >2% in individuals already showing depletion or
iting, diarrhea, constipation, stomatitis, mucositis, dys-
sarcopenia.
phagia, and alterations in taste and smell. 2 Many patients
• Early detection of malnutrition, anorexia, sarcope-
also experience emotional distress with a cancer diag-
nia and cancer cachexia are critical for appropriate
nosis and often during cancer treatment. In addition to
treatment and quality of life for cancer patients.
addressing nutritional intake and symptom management,
• The Nutrition Care Process is a systematic approach
Complementary and Alternative Medicine (CAM) may
to providing high-quality nutrition care and con-
be useful in managing behavior-related factors such as
sists of nutritional assessment, nutritional diagno-
depression, fatigue, pain, and stress. 2,3
sis, intervention that will be directed to the root
cause of the nutrition problem, and monitoring and
evaluation.
• Special diets and metabolic therapies such as fasting 35.2 MALNUTRITION AND
and the Ketogenic Diet remain controversial in can-
cer care and more research is needed before recom-
CANCER CACHEXIA
mending them in clinical practice. Malnutrition and weight loss commonly occur in can-
• A multidisciplinary approach with a combination cer patients undergoing treatments,4–6 and up to 80% of
of diet modification, physical activity, and mind- cancer patients receiving multimodal therapy experience
body modalities improve quality of life for cancer unintentional weight loss. Compared to weight stable
patients. patients, individuals with weight loss experience lower
doses of treatment, more severe dose-limiting toxicities,
and overall poorer outcomes and survival.7 Malnutrition
35.1 INTRODUCTION may result from anorexia (loss of appetite), sarcopenia
(skeletal muscle loss), dehydration, or cancer cachexia,
There is increasing recognition of the importance of nutri- which, unlike the aforementioned conditions, cannot
tion and lifestyle strategies in managing cancer treatment always be reversed. 5 Depending on the neoplasia, a large
and quality of life (QOL). The metabolic response to can- percentage, approximately 50% to 80%, of advanced can-
cer is varied and certain tumors cause more nutritional cer patients experience cachexia during the progression of
alterations than others. Solid tumors such as lung, pancre- their disease,4,8–11 and cachexia is responsible for an esti-
atic, head and neck, and gastrointestinal (GI) cancers are mated 20% of total deaths in cancer patients.12–14
associated with poor nutritional status and weight loss. The word “cachexia” originates from the Greek kakos
GI and pancreatic cancers have the highest prevalence of and hexia, meaning “bad condition”.4,15 In 2011, an
441
442 Chapter 35 Nutrition Therapy for the Cancer Patient
international consensus defined cachexia as a multifac-

torial syndrome of ongoing loss of skeletal muscle mass,
35.3 METABOLIC ALTERATIONS
with or without loss of fat mass, that cannot be fully IN CANCER
reversed by conventional nutritional support and leads to
progressive functional impairment. The agreed diagnostic Weight loss, anorexia, and metabolic dysfunction are
criterion for cachexia is weight loss > 5%, or weight loss > associated with higher resting energy expenditure (REE)27
2% in individuals already showing depletion according to and play a role in the progression of cancer cachexia. The
current bodyweight and height (body mass index [BMI] < REE in cancer patients is strongly determined by the type
20 kg/m 2) or sarcopenia. 3 Cancer cachexia results in sys- of tumor. Certain cancers, such as esophageal, gastric,
temic inflammation induced by tumor and host-derived pancreatic, and non-small cell lung cancers, have been
factors and causes unintentional loss of lean muscle mass found to increase energy expenditure. However, there is
and adipose fat tissue.3,6,12,16,17 contradicting data and, in some cases, the REE in gas-
Clinically, cachexia has three different stages: pre- tric and colorectal cancer patients remained similar to an
cachexia, cachexia and refractory cachexia. Pre-cachexia individual’s normal metabolism.12,28 An estimated average
is marked with loss of appetite, impaired glucose toler- caloric deficit in an advanced cancer patient experiencing
ance, and involuntary weight loss (≤5% usual body weight weight loss is 200 kcal per day29 and 250–400 kcals/d in
during the last six months), and is an early clinical indica- those patients with cancer cachexia.30
tion of wasting.18 Cachexia is characterized by ongoing Although the underlying mechanisms of cachexia are
skeletal muscle mass loss and negative energy and protein not well understood, systemic inflammation is thought to
balance.3 Active catabolism is present during refractory occur. C-reactive protein (CRP), an acute-phase protein,
cachexia and is manifested with decreased performance has been implicated in muscle wasting31 and is often used
scores, loss of subcutaneous fat (e.g. orbital, triceps, fat to assess general inflammation and pro-inflammatory cyto-
overlying the ribs), 3,19,20 muscle wasting, and an inability kine activity.32 Both tumor cells and individuals’ immune
to maintain weight. cells secrete inflammatory cytokines, such as TNF-α, the
Typically, an individual who presents with cachexia first identified mediator of cachexia, 27 and IL-1. Both
is thought to be underweight and wasted;10 however, an TNF-α and IL-1 have been shown to break down protein
unintentional weight loss of >5% is difficult to detect in isolated skeletal muscle, in addition to impacting appe-
in individuals who are overweight or obese. Sarcopenic tite and continuing the cycle of inflammation.12,33,34
obesity, which occurs in individuals who are overweight Inflammatory markers, along with dietary intake and
or obese and have high fat mass yet have low skeletal weight loss, may be predictive of cancer outcomes. A CRP
muscle mass, is often overlooked in cancer patients and level of 10 mg/l or higher when combined with a reduced
can go unrecognized without nutrition assessment.4,21 food intake of <1500 kcal/day and weight loss of ≥10%
Sarcopenic obesity is estimated to exist in about 40% of has been shown to predict functionality and cancer prog-
overweight or obese patients with advanced pancreatic nosis.35 The Academy of Nutrition and Dietetics recom-
cancer, has been associated with poorer functional status mends assessing markers of inflammation such as elevated
in patients with solid tumors of the respiratory or GI tract CRP and other signs of wasting to help determine the
compared with obese patients who did not have sarco- acuteness of weight loss in cancer patients.19,36
penia, and is an independent risk factor for accelerated
mortality.10,20,22,23
Sarcopenia has become evident through techniques 35.3.1 Altered Carbohydrate Metabolism
such as computerized tomography (CT), which can detect
Cori and Cori37 first observed carbohydrate metabolism
differences in visceral and subcutaneous adipose tissue. 24
changes with cancer via increased rate of tumor glycolysis
Although BMI is a simple and affordable screening tool
in vivo and tumor tissue uptake of glucose, which has been
for obesity and is a strong predictor of overall mortality
estimated to account for 300 kcal per day energy loss. 22,27
both above and below the optimum of 22.5 to 25 kg/m 2 ,
This energy imbalance may be attributable to uncoupling
it does not consistently correlate with adiposity. For exam-
protein (UCP) upregulation and to the Cori cycle recy-
ple, BMI may underestimate body fatness in those indi-
cling tumor-derived lactate to the liver. 26,38,39 A decrease
viduals, such as the elderly, who have increased adipose
in hepatic glycogen stores does not limit endogenous glu-
tissue distribution and decreased skeletal muscle mass,
cose production and/or utilization in cachectic patients. 27
whereas BMI may overestimate body fatness in those with
Although studies on glucose metabolism in cachectic
increased skeletal muscle mass and decreased adipose tis-
patients are nominal, recent genetic studies with fruit flies
sue, such as in athletes. Regular body composition assess-
have revealed a tumor-secreted factor, ImpL2/IGFBP,40,41
ments to evaluate skeletal muscle and fat tissue depletion
which is an insulin-binding protein and antagonist of
by CT image analysis, dual-energy X-ray absorptiometry
insulin/insulin-like growth factors. This tumor-secreted
(DEXA), or Magnetic Resonance Imaging (MRI) may
factor may be responsible for the wasting phenotypes in
help guide clinical interventions.4,25 Body composition
organs far from the transplanted tumors. 27,42
tools provide fundamental data for cancer patients with
a wide range of BMIs and ensures a more accurate assess-
ment of nutritional status by revealing atrophy of skeletal
muscle mass and adipose tissue.12,26 However, more non-
35.3.2 Altered Fat Metabolism
invasive and accessible tools to detect skeletal muscle atro- In addition to alterations in carbohydrate metabolism, can-
phy are needed in the clinical setting.6 cer causes changes to lipid metabolism. Das and colleagues 43
35.4 Nutrition Screening 443
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,
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
35.5 CANCER TREATMENT AND

35.4.1 Nutrient Needs SIDE EFFECT MANAGEMENT
Both over- and underfeeding of a cancer patient can be det-
rimental. Underfeeding can potentially result in malnutri- Anti-cancer therapies such as chemotherapy, hormone
tion and sarcopenia and overfeeding can result in increased therapy, radiation therapy, biotherapy, and surgery88 can
carbon dioxide production, hyperglycemia, azotemia, impact nutritional status and may cause anorexia, poor
hypertriglyceridemia, electrolyte imbalances, immunosup- appetite, delayed gastric emptying, early satiety, and other
pression, and alterations in hydration, hepatic steatosis, GI discomforts (e.g. nausea, vomiting, and diarrhea).74
and possible respiratory failure.22 In addition to protein, Depending on the anti-cancer treatment, early satiety and
adequate energy from fat and carbohydrate intake is essen- decreased desire to eat, change in smell or taste of food,
tial to allow protein to be utilized for its necessary functions and other nutrition impact symptoms may occur for can-
and preserve lean muscle mass. The recommended protein cer patients, and managing the symptoms may prevent a
intake for a cancer patient is 1.0–1.5 g/kg per day;76 yet, decline in nutritional status.12 Table 35.1 provides dietary
the typical cancer patient’s protein intake is 0.7–1.0 g/kg.77 suggestions for managing symptoms during treatment.
Catabolic cancer patients have additional increased pro-
tein needs ranging from 1.2–2.0 g/kg per day with 1.5 g/kg
often recommended for metabolically stressed individuals. 35.5.1 Chemotherapy and
Micronutrients play a critical role in metabolic reac-
tions. Decreased nutrition intake and urinary losses can
Radiation Therapy
lead to deficiencies of vitamin A, B, and C, along with zinc, Chemotherapy, whether a single antineoplastic agent or a
iron, and selenium.73,78 Preexisting vitamin and mineral combination of agents, is a common approach to cancer
deficiencies are often seen with hospitalized individuals, treatment and impacts individuals differently depending
and surgery may further decrease certain micronutrients.78 on their personal health, the dose given, and length of
The inflammatory process and protein catabolism can the chemotherapy treatment. Although all chemotherapy
further aggravate micronutrient deficiencies and impact agents have the goal of cancer cell death, they differ in
biochemical processes, and enzyme functions resulting in their mechanism to interfere with cell division and gener-
altered immunity, possible organ dysfunction, and muscle ally worsen cancer cachexia.12
weakness.73,79 Dietary supplements in the form of a mul- The effects from radiation are impacted by the loca-
tivitamin/mineral supplement may be considered if less tion of the tumor. For example, with head and neck
than two-thirds of a patient’s food intake is consumed.80 cancer, patients may experience extreme mucositis, dry
Micronutrient supplementation above the Dietary mouth, and poor appetite. And in those patients who are
Reference Intake does not guarantee increase in serum lev- malnourished prior to radiation, there may be a decreased
els and excessive dietary supplements may be harmful.78 tolerance to the treatment. In a review of six studies evalu-
A therapeutic component of nutrition support for ating the relationship between nutrition status and radia-
adult cancer patients losing weight includes oral nutrition tion treatment tolerance, positive associations between
supplementation and immune-enhancing nutrition (IEN) nutrition status and either reduced treatment interrup-
support with formulas that have at least two of the fol- tions, unplanned hospital admissions, treatment toxicity,
lowing ingredients: arginine, omega-3 fatty acids, gluta- PG-SGA score, and QOL occurred. 52,63–66,89
mine, and/or ribonucleic acid.74 Studies using IEN show
improved body weight, including lean muscle mass, and
improved performance ability, and decreased inflamma- 35.5.2 Lifestyle Strategies When
tion. In a meta-analysis of 27 randomized controlled trials
(RCTs), Song et al (2015)81 found IEN to be a promising
Eating During Treatment
option for managing perioperative care in GI malignan- Cancer treatment experience can be influenced by being
cies. Additionally, there is strong evidence that medical prepared as much as possible with meal planning and eat-
food supplements such as fish oil, which contains 0.27g ing healthful appealing foods that may diminish side effects.
to 6.0 g of eicosapentaenoic acid (EPA) per day, can result Being aware of food preferences is an important part in
in weight stabilization or possible weight gain along with meal planning and can improve QOL.65 See Table 35.2 for
preservation of muscle mass.82–86 lifestyle strategies when eating during treatment.
35.5 Cancer Treatment and Side Effect Management 445
TABLE 35.1 Managing side effects during treatment134,135

Symptoms Suggestions 35
Altered sense of • Rinse mouth or brush teeth before eating.
taste or smell • Season foods with fruit marinades for meats, or use lemon, herbs and spices, pickles or hot sauce if
tolerated.
• Try sugar free lemon drops, gum, or mints to improve mouth taste.
• For foods that have an off taste, try fruity or salty flavors.
• For metallic tastes, try spices or seasonings such as onion, garlic or onion powder or add a little sweetener,
agave nectar or maple syrup or a nut butter (peanut butter, almond butter).
• For too salty, bitter or acid tastes, choose food naturally sweet rather than salty or acidic. Use low sodium
products. Also, try 1/4 teaspoon of lemon juice to get rid of the salt taste.
• For too sweet, add 6 drops of lemon or lime juice and add until the sweetness is muted.
• For general muted tastes, add a spritz of lemon juice, but focus on adding more sea salt until the flavor
becomes present.
• For bitter or strange tasting meats, add a sweetener such as a fruit-based marinade or sweet and sour
sauces to meats or choose meat alternative protein sources, i.e. eggs, tofu, dairy, or beans.
Constipation • Focus on adequate hydration: aim for 64 ounces (8 cups) of fluid a day and a slow increase to 25–35 grams
of fiber/day as tolerated.
• Try a hot beverage, hot cereal, or high fiber food to stimulate bowel movements.
• Incorporate probiotics such as yogurt, miso soup, and/or other supplements that help facilitate bowel
movements.
• Engage in light activity and/or stretching to improve bowel regularity.
• Discuss medications that affect bowel function or stool softeners with a health professional as needed.
• Schedule adequate bathroom time to facilitate bowel movements.
Diarrhea • Identify problem foods and decrease consumption.
• Try a low-fat, low-fiber and/or lactose-free diet, avoiding gas producing foods, caffeine, and alcohol.
• Try bulking agents, pectin, or soluble fiber foods (applesauce, banana, oatmeal, potatoes, rice).
• Avoid sorbitol or other sugar-alcohol containing products (e.g. sugarless gum and candy).
Fatigue • Encourage use of easy to prepare meals, snacks, prepared foods, and energy-dense foods.
• Keep non-perishable snacks at bedside (e.g. trail mix, nuts).
• Eat small, frequent meals and snacks.
• Eat well when appetite is best, i.e. breakfast.
• Limit duties or chores as much as possible.
• Try to apply energy-saving strategies to your activities.
• Encourage light activity/movement.
• Consider a physical therapy consult for strengthening.
• Be evaluated for anemia as a cause of lack of energy and consider the use of a multi-vitamin and mineral
supplement if medically appropriate.
Loss of appetite • Eat small, frequent meals of calorie-dense foods and fluids.
• Eat in pleasant surroundings, avoiding stress or conflict at meal time.
• Eat by the clock rather than waiting for appetite or hunger cues.
• Consume smoothies or medical beverages when eating is too tiring.
• Engage in light physical activity even for just 10 minutes to stimulate appetite.
• Use easy to prepare and serve foods to preserve energy.
Nausea and • Eat 5–6 small meals/day that include lean protein choices like fish, chicken, beans, tofu.
vomiting • Limit exposure to smells by avoiding food preparation areas.
• Consider eating cool, light foods with little odor.
• Avoid greasy, high fat foods.
• Consume liquids between meals, rather than with meals.
• Avoid/limit strong smelling lotions, perfumes, soaps, and air fresheners.
• Rest with head elevated for 30 minutes after eating.
• Consider using complementary therapies such as ginger tea, ginger ale, 0.5–1 gram ginger extract.
Oral Candidiasis, • Choose foods lower in acidity and avoid tomato products, citrus juice, and pickled foods.
Mucositis/ • Choose foods that are less spicy, stay away from chili, chili powder, curry, cloves, black pepper, hot sauce,
Esophagitis, cold ginger, curry, red pepper flakes, and other strong spices.
sores, inflammation • Choose foods softer in texture, with added moistness, sauce, or gravy.
in the mouth or • Choose cream soups, mashed cauliflower and/or potatoes, yogurt, eggs, tofu, and pudding.
esophagus • Serve foods cool or at room temperature.
• Prepare smoothies with low acid fruits like melons, bananas, or peaches and add yogurt, milk, or silken tofu.
• For pain in mouth—sip one tablespoon honey dissolved in one cup of warm water and avoid carbonated
drinks.
• Consume ice chips or frozen ice pop.
Continued
TABLE 35.1 Managing side effects during treatment134,135 (Continued)

Symptoms Suggestions
Early satiety • Choose calorie dense foods or medical nutrition beverages.
• Maximize intake when most hungry.
• Eat, small, frequent meals and snacks which include protein sources such as eggs, cod, legumes, and seeds
throughout the day.
• Consume liquids between meals rather than with meals.
• Engage in light physical activity to help move food through the GI tract.
Xerostomia, dry • Alternate bites and sips at meals.
mouth, or reduced • Add broth, gravies, and sauces to meals and dunk dry food in liquids.
saliva • Sip liquids throughout the day; aim for 8–10 cups/day.
• Chew on carrots or celery.
• Swish and spit using club soda or carbonated water.
• Use a humidifier at home to moisten air.
• Practice good oral hygiene.
• Suck on hard candy, frozen grapes, or melon balls.
• Avoid alcohol and alcohol containing mouthwashes.
TABLE 35.2 Lifestyle strategies when eating during treatment135

Suggestions
General • Plan meals ahead, i.e. month, week, and day.
Approaches • Plan to eat 5–6 small meals/day that have protein and are nutrient-dense with vitamins, minerals, and
phytonutrients.
• Engage in light physical activity to stimulate appetite, if possible.
• Maximize quality and quantity of food intake when most hungry.
Specific Two Days Before Chemotherapy
Approaches • Eat as well as possible to give your body “the extra boost and hopefully minimize side effects.” Also, avoid
favorite foods to minimize developing a food aversion associated with nausea/vomiting during chemotherapy.
Lastly, avoid greasy, fried, or high-fat foods.
During the Week of Treatment (Chemotherapy or Radiation)
• Try eating something every hour or so, EVEN if not hungry. Nausea is worse if the stomach is empty.
• Bare Minimum Menu if no appetite—try to consume homemade broths, 2 servings of Smoothies with protein
powder, 2 cups of healing tea, e.g. ginger tea.
• If any sort of appetite, try easy to digest nourishing soups that are full of vitamins, minerals, and phytonutrients.
Be sure to add veggies when possible and protein-building foods.
• If hungry, eat well! Add in protein-building foods, such as chicken and rice, eggs as in egg salad to poached
eggs. Continue with tonics and elixirs, i.e. ginger lemonade and mango coconut smoothies. Anytime foods may
include oatmeal, hummus, quinoa pilaf.
A Week After Chemotherapy
• When taste buds are back, add favorite foods that jump-start the appetite.
Between Treatments
• When appetite is normal, focus on plant-based foods that offer phytonutrients, i.e. cancer fighting nutrients.
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
TABLE 35.3 Popular cancer diets: Non-evidence based136

Diet Nutrient Composition Diet Philosophy Comments/Concerns
Alkaline • 80% plant based and low-sugar • Alkaline foods can improve health • May be low in calories, protein,
fruits and prevent cancer calcium, and vitamin D
• 20% acid forming foods, i.e. • Requires large amounts of fluid
grains, meat, eggs, dairy, coffee, intake, >2 quarts, day and the
sugar, and alcohol avoidance of certain food
combinations or eating at specific
times
Budwig • Primarily vegetarian or vegan • Combination of cottage cheese • May be limited in protein, calcium,
• Avoids hydrogenated oils, trans and flaxseed oil, which is high in and calories
fat, animal fat, dairy, and polyunsaturated fatty acids,
processed foods would improve cellular
• Multiple daily servings of functioning
flaxseed oil and cottage cheese
Gerson • Strict metabolic diet that • The diet detoxifies the body and • Severe nutritional deficiencies and
emphasizes fresh fruit and stimulates the metabolism so that malnutrition, dehydration, colitis
vegetable juice the body can heal itself • Excessive use of coffee enemas
• Typically, 3 vegetarian meals and • By increasing potassium in the can lead to sepsis, electrolyte
snacks with 15–20 lbs juice/day cells and decreasing sodium deficiencies, dehydration, colitis,
to be consumed as 1 cup ideally through the diet, the body will and possibly death
every hour for 13 hours detox and build up the immune
• Limit whole grains for 6 weeks system
Gonzales • Diets vary and can range from • Cancer is related to • Flu-like symptoms, low-grade fever,
Therapy nearly vegetarian to requiring red environmental toxins and muscle aches, skin rashes,
meat 2–3 times/day processed foods. Pancreatic misbalances of electrolytes
• Organic foods, fresh vegetable enzymes help eliminate toxins
juice, and avoid refined foods and help normal cells repair
• Daily coffee enemas, vitamin/ damaged cells
mineral supplements, extracts of
animal organs
Macrobiotic • Vegetarian, whole-foods • Live in harmony with nature by • Weight loss, anemia, potential
• 40% from whole grains, eating a simple, healthy diet and protein inadequacies
20%-30% from vegetables, avoiding foods containing toxins • Possible deficiencies in zinc,
5%-10% from beans, including calcium, and vitamins B12 and D
soy products
Raw Food • Mostly or all uncooked and • Cooked foods lead to cancer • Weight loss
unprocessed foods • Unprocessed foods and fewer • Deficiencies in protein, calcium,
• No meat, dairy, and eggs added ingredients preserve iron, zinc, vitamins B12, and D
• Calcium and vitamins B12 and D enzymes in food and provide
supplements recommended health benefits
Vegan • Plant-based diet • Excludes dairy, eggs, and all • Weight loss, deficiency of zing,
• If seeds, nuts, legumes, and animal products with a strict calcium, vitamins B12, and D
cereal-grain products are adherence to plant products • Vitamin D may need to be
included in appropriate amounts, supplemented if there is inadequate
can meet protein requirements exposure to ultraviolet light from
the sun or if insufficient vitamin D
from fortified foods
TABLE 35.4 Clinical application table

Recommendations for nutritional therapy for cancer patients
• The screening tools validated for use with oncology patients include the Patient Generated-Subjective Global Assessment
(PG-SGA), the Malnutrition Screening Tool (MST), the Malnutrition Screening Tool for Cancer Patients (MSTC), and the Malnutrition
Universal Screening Tool (MUST).50,55,56
• Regular body composition assessments to evaluate skeletal muscle and fat tissue depletion by CT image analysis, dual-energy
X-ray absorptiometry (DEXA), or Magnetic Resonance Imaging (MRI) may help guide clinical interventions.4,25,137
• A CRP level of 10 mg/l or higher when combined with a reduced food intake of <1500 kcal/day and weight loss of ≥10% has been
shown to predict functionality and cancer prognosis.35
• The Nutrition Care Process is a systematic approach to providing high-quality nutrition care and consists of nutritional assessment,
nutritional diagnosis, and intervention that will be directed to the root cause of the nutrition problem, monitoring, and evaluation.2
• A key benefit to Medical Nutrition Therapy is identifying malnutrition and cachexia early in cancer patients and offering nutrition
support via enteral feeding, parenteral feeding, and/or managing nutrition impact symptoms. Nutrition intervention is most
successful when cancer patients’ nutritional needs are met by considering the increased energy expenditure resulting from the
tumor itself, or the individual’s response to the tumor, along with factors such as stress, anxiety, or depression, which gravely impact
nutrition and often minimize a cancer patient’s food intake.4,73,74
• The recommended protein intake for a cancer patient is 1.0–1.5 g/kg per day. Catabolic cancer patients have additional increased
protein needs ranging from 1.2–2.0 g/kg per day with 1.5 g/kg often recommended for metabolically stressed individuals.12,79
• Dietary supplements in the form of a multivitamin/mineral supplement may be considered if less than two-thirds of a patient’s food
intake is consumed.80
• The limited data on fasting and the Ketogenic Diet show some beneficial effects, however, are not yet conclusive.133
• Depending on the anti-cancer treatment, early satiety and decreased desire to eat, change in smell or taste of food, and other
nutrition impact symptoms may occur for cancer patients and managing the symptoms may prevent a decline in nutritional
status.12,138
(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
35.6.2 Metabolic Dietary Therapies 35.6.3 Fasting Diet

Within the last few decades, a greater understanding Fasting has been a practice for cultural and spiritual rea-
regarding the molecular mechanisms of cancer has been sons for centuries,114 and it has long been established that
gained. The metabolic dysfunction of cancer has been dietary and caloric restrictions bring about health ben-
linked to the metabolic syndrome, which is characterized efits.115 In 1914, Payton Rous first observed116 that tumor
by elevated insulin levels (insulin resistance), insulin-like growth was reduced with limited food and caloric intake.
growth factor-1 (IGF-1), elevated levels of the hormone In mice models, cycles of fasting augment the efficacy of
leptin and decreased amounts of the hormone adiponec- chemotherapy and suggests that short-term or intermit-
tin, and elevated inflammatory cytokines.104 Although tent fasting may be beneficial if done close to or during
there is no evidence that high simple sugar diets directly chemotherapy.117 Pre-clinical studies also indicate that
increase cancer progression, high simple sugar intake is fasting protects non-cancerous cells, reduces some side
linked to higher levels of insulin and growth factors that effects of cytotoxic therapy, and simultaneously makes
may influence cancer cell proliferation and increase the cancer cells more receptive to cancer treatments, such as
risk of other chronic diseases.105,106 chemotherapy.117–120
Even though the role of specific genes and cancer Most of the animal and human observational studies
metabolic signaling pathways are not fully understood in that link energy restriction to reduced rates of carcinogen-
cancer progression, there is an emerging interest in meta- esis involved continuous energy restriction. However, there
bolic therapies.107 The Warburg effect, first described by is an increasing focus on intermittent energy restriction
Warburg and colleagues,108 is the observation that cancer (IER) or intermittent fasting (IF), which comprises periods
cells inefficiently use the glycolytic pathway to derive ade- of marked energy restriction or total fasting interspersed
nosine triphosphate (ATP) for energy,107,109 The Warburg with periods of normal eating.121 Although the effect of
effect108 is suspected to be due to mitochondrial respira- IEF or IF on cancer rates in humans is uncertain, there is
tion malfunction110 or possibly the hypoxic state, which is evidence on cancer risk biomarkers that are thought to
often present in solid tumors and causes the cancer cells to mediate the links between adiposity and energy intake and
Acknowledgments 449
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.
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VIII
PA RT
Obesity and Weight Management

John P. Foreyt, PhD
453
36
CHAPTER
Epidemiology of Adult Obesity

R. Sue Day, MS, PhD, Nattinee Jitnarin, PhD, Michelle L. Vidoni, MPH, PhD,
Christopher M. Kaipust, MPH, and Austin L. Brown, MPH, PhD
Key Points.................................................................................. 455 36.3.2 Global Obesity Trends........................................... 460

36.1 Obesity and Adiposity....................................................... 455 36.4 Potential Causes of Obesity............................................... 461
36.2 Measurement of Adiposity................................................ 456 36.4.1 Energy Imbalance................................................. 461
36.2.1 Densitometry........................................................ 456 36.4.2 Genetics and Epigenetics...................................... 462
36.2.2 Dual-Energy X-Ray Absorptiometry (DEXA)........... 456 36.4.3 Infections............................................................. 462
36.2.3 Anthropometric Measurements............................. 456 36.4.4 Smoking............................................................... 463
36.2.3.1 Body Mass index (BMI).......................... 456 36.4.5 Sleep.................................................................... 463
36.2.3.2 Waist Circumference (WC)..................... 457 36.4.6 Gut Microbiota...................................................... 463
36.2.3.3 Waist-to-Hip Ratio (WHR)....................... 457 36.4.7 Other Factors....................................................... 463
36.2.3.4 Waist-to-Height Ratio (WHtR) or 36.5 Health Consequences of Obesity....................................... 463
Waist-Stature Ratio (WSR)�� 457 36.6 Economic Costs of Obesity in the U.S................................ 463
36.2.3.5 Skinfolds............................................... 458 36.6.1 Direct costs.......................................................... 464
36.2.3.6 Sagitta Abdominal Diameter (SAD)......... 458 36.6.2 Indirect costs........................................................ 464
36.2.4 Bioelectrical Impedance (BIA)............................... 458 36.6.2.1 Presenteeism and Absenteeism............. 464
36.2.5 Computed Tomography (CT).................................. 458 36.6.2.2 Disability and Premature Mortality......... 465
36.2.6 Ultrasound Technique (UT).................................... 458 36.7 Summary.......................................................................... 466
36.3 Prevalence of Obesity....................................................... 458 Clinical Applications................................................................... 466
36.3.1 U.S. Obesity Trends............................................... 459 References................................................................................ 466
of excess deaths due to obesity (BMI ≥ 30.0 kg/m 2)

KEY POINTS in 2000 in the United States, relative to the reference
BMI category of 18.5 kg/m 2 to < 25.0 kg/m 2 , indicate
• Obesity is pandemic, one of most significant public
over 111,000 deaths in those less than 70 years of age, 3,4
health problems in the world.
and 2.8 million deaths worldwide are attributable to the
• Multiple measures of adiposity exist and can be used
disease. 5 Sadly, obesity is one of the leading preventable
together in clinical and research settings.
causes of death and disease globally, yet the rates across
• Every age, gender, race, and smoking status group is
the globe continue to increase.
experiencing obesity.
• Obesity researchers may benefit from a systems
approach to study the multiple potential risk factors.
• Obesity is a risk factor for mortality and numerous 36.1 OBESITY AND ADIPOSITY
comorbidities.
• Over 30% of the world population is overweight or Clinically, obesity is a condition characterized by the
obese with a global economic impact from direct accumulation of excess adipose tissue. Therefore, stan-
and indirect costs estimated to be $2.0 trillion. dards to define and classify obesity require the assessment
of total body adiposity. However, the quantitative deter-
Obesity is pandemic, representing one of the most signifi- mination of body fat composition remains difficult and
cant public health issues for the world in recent history. costly to obtain. Techniques such as dual-energy X-ray
Current estimates suggest 2.1 billion people in the world absorptiometry (DEXA) and bioelectrical impedance pos-
are overweight or obese.1 Obesity significantly contributes sess the ability to quantify total body fat. However, these
to both worldwide morbidity and mortality. In 2013 obe- techniques require the use of specialized equipment by
sity was recognized by the American Medical Association qualified technicians. Thus, these methods remain largely
as a disease, and research supports that obesity increases restricted to small-scale research purposes because the
the risk for many chronic diseases including cardiovascu- high cost and burden of data collection make their use
lar disease, cancer, type 2 diabetes, chronic kidney disease, in large-scale research or clinical practice unrealistic. For
and many musculoskeletal conditions. 2 Mortality due to practical reasons, researchers and clinicians often rely on
obesity is challenging to measure, but estimated numbers proxy measurements to approximate adiposity.
455
456 Chapter 36 Epidemiology of Adult Obesity
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
tissue and central adiposity than are BMI and waist-to-hip

TABLE 36.1 Classification of overweight and obesity by
36
ratio.46–48 In addition, WC is highly correlated with cardio-
BMI levels and public health action points31,36
vascular and diabetes risk factors and all-cause mortality
Public Health and is considered to be a stronger predictor of obesity-
Action Points related risk factors than BMI.6,49–51 WC is measured with
WHO Classification BMI (kg/m2) BMI (kg/m2) a non-elastic tape at the superior border of iliac crest,6 the
Underweight <18.5 – mid-abdomen or mid-point between iliac crest and low-
est rib,6 umbilicus level,52 or at the narrowest point of the
Normal 18.5–24.9 23.0 waist,53 to the nearest 0.1 cm. A WC of >102 cm (or >40
Overweight/Pre-obese 25.0–29.9 27.5 inches) in men and >88 cm (or >35 inches) in women is
considered as abdominal obesity, while men with a WC
Obese Class I 30.0–34.9 32.5
94–102 cm and women with a WC 80–88 cm are classified
Obese Class II 35.0–39.9 37.5 as overweight (Table 36.2).54 The combination of classifica-
Obese Class III ≥40.0 –
tion of overweight or obese and a large WC is proposed to
carry additional risk for numerous comorbidities.6,55 WC
correlates with MRI measures of intra-abdominal fat in
non-obese women ranging r = 0.49–0.77 and among men
Organization (WHO) and International Obesity Task r = 0.77–0.90.29 WC is a comparable measure of abdominal
Force (IOTF) recommend the use of BMI to define and fat mass to DEXA for men but not for women.29,56
classify obesity. International standards to classify BMI
consider an individual with a BMI between 25 kg/m² and
29.9 kg/m² overweight and any person with a BMI ≥ 30.0 36.2.3.3 Waist-to-Hip Ratio (WHR)
kg/m² obese.31–36 (Table 36.1) These BMI guidelines are
based on numerous longitudinal cohort studies showing WHR is an alternative anthropometric measure for
increased mortality risk as BMI increases beyond 25 kg/m². abdominal obesity, additional to WC. WHR is obtained
The BMI guidelines are based on the assumption that by dividing the waist circumference by the hip circumfer-
body fatness is increased as weight increases in relation to ence. For hip measuring, the tape is placed at the maxi-
height37; they do not consider fat content and inadequately mum extension of the buttocks.31 Classification of obesity
distinguish between lean and fat tissues. 38,39 Moreover, is: men with a WHR > 1.00 and women with a WHR
BMI does not provide information on the distribution of > 0.85; and classification of overweight is: men with a
fat mass.36 Thus, BMI may overestimate fat mass in indi- WHR = 0.90–1.00 and women with WHR = 0.80–0.85
viduals with high levels of lean (muscle) mass (e.g. ath- Table 36.2).31 Because WHR provides additional informa-
letes) and underestimate fat mass in individuals with low tion related to hip circumference, gluteofemoral muscle
levels of lean mass (e.g. the elderly).6,40,41 mass, and bone structure, WHR might be a better pre-
The correlation between BMI and percent body fat dictor of risk factors for cardiovascular disease as hip
can vary between gender, age, and ethnic groups.42 For circumference is inversely related to the development of
example, non-Hispanic blacks generally have a lower per- insulin resistance, dyslipidemia, cardiovascular disease,
centage of body fat for a given BMI compared to other hypertension, and death. 31,57,58 WHR and DEXA mea-
ethnic groups.43,44 Therefore, the health risk correspond- sures of abdominal visceral fat had the same correlation
ing to a given BMI category may differ among gender, age, with MRI measures in men (r = 0.80), but WHR was not
and ethnic groups.36,42,45 An expert consultation by WHO as good a measure among women as DEXA when using
amended the guidance in 2004 and identified potential the MRI as the standard measure (r = 0.19). 29
public health action points (Table 36.1) to further aid
countries’ identification of individuals at increased risk for
obesity related comorbidities.36
36.2.3.4 Waist-to-Height Ratio (WHtR) or
Waist-Stature Ratio (WSR)
WHtR is another alternative method for measuring body
36.2.3.2 Waist Circumference (WC) fat distribution and abdominal obesity. The WHtR is cal-
Waist circumference is used for measuring the fat located culated by dividing waist circumference by height. The
in the central region of the body (intra-abdominal fat). classification for central obesity is proposed to be the
WC is more strongly associated with visceral adipose same for both genders (WHtR = 0.5): classification for
TABLE 36.2 Classification of overweight and obesity by anthropometric measures

Anthropometric measure Overweight Obese
Male Female Male Female
Waist circumference 54 94–102 cm 80–88 cm >102 cm >88 cm
Waist-to-hip ratio 31 0.9–1.0 0.8–0.85 >1.0 >0.85
Skinfolds (sum of biceps, triceps, subscapular, and – – >25.0 >30.0
supra-iliac)6
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 caring, 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).
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
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
in different experimental models, though Adenovirus-36 36.4.6 Gut Microbiota

36
(Ad36) is the most studied.135 Although the adipogenic-
ity action of Ad36 is not well understood, the in vitro The microbiota, or the “forgotten organ,” plays a sig-
and in vivo studies collectively suggest that the virus nificant role in health, including involvement in energy
infects preadipocytes and stem cells. Ad36 increases harvest and storage, metabolic functions, and immune
adipogenic commitment in stem cells, preadipocyte rep- system signaling to promote immune cell maturation and
lication, adipogenic differentiation, and lipid accumu- normal development of immune functions.167 The bacte-
lation in rodent and human cells.136–138 Ad36 strongly rial divisions bacteroidetes and firmicutes dominate the
up-regulates glucose uptake by adipocytes and adipose gut microbiota with lower bacteroidetes and increased fir-
tissue.137,139 Thus, it appears Ad36 increases not only adi- micutes associated with obesity. The change in levels of
pocyte cell number but glucose and lipid uptake by these the divisions of microbiota leads to an increased capacity
cells, which may collectively contribute to increased adi- for harvesting energy from food and produces low-level
posity. Infections can affect metabolism and adipose tis- inflammation, which is associated with obesity.167 The
sue can impact inflammation, a factor associated with exact complex mechanisms leading to obesity are still
obesity. In meta-analyses of the relationship in humans, being explored, and imbalanced gut microbiota should be
persons exposed to Ad36 had a two-fold increased risk explored further in future obesity mechanistic research.
of being obese.140 –142 Ad36, first identified in 1980, coin-
cided with the early recognition of the rising prevalence
of obesity.143 36.4.7 Other Factors
Other putative factors being explored in association with
obesity risk include endocrine disruptors, pharmaceuti-
36.4.4 Smoking cal agents, cranial radiotherapy, and ambient temperature
Smokers consistently have been shown to weigh less control.105,135,168 Each of these requires more investigation
than non-smokers. The physiologic response to nicotine to establish mechanisms and experimental evidence in
includes appetite suppression and alteration in thermo- animals and humans.
genic responses.105,144,145 A systematic review and meta-
analysis on smoking cessation provide evidence of weight
gain following cessation.146 Those who quit smoking 36.5 HEALTH CONSEQUENCES
reported gaining an average of 4.1 kg over five years com-
pared to those continuing to smoke at 2.6 kg. In addi- OF OBESITY
tion, the differences in weight gain between these two
groups ranged from 2.6 to 5.3 kg.147–149 Several possible Obesity is associated with increased overall mortality and
predictors of weight gain among smokers who quit, such is a significant risk factor for developing numerous comor-
as daily cigarette consumption before quitting and base- bidities.31,169–172 Obesity is associated with increased risk
line BMI, have been proposed but findings have not been of type 2 diabetes, cardiovascular diseases, numerous
consistent150,151 The molecular mechanism for this weight cancers, asthma, chronic back pain, sleep apnea, gout,
change is not well described.144,145 Current smoking preva- osteoarthritis, pulmonary embolism, breathing problems,
lence in U.S. adults has declined from 20.9% in 2005 to gallbladder disease, pregnancy complications, menstrual
15.1% in 2015 while the prevalence of obesity increased irregularities, stress incontinence, and psychological dis-
significantly.100 Thus, the decreasing prevalence of smok- orders. 2,33,173–175 There is a positive trend associated with
ers may be associated with the rise in prevalence of overweight gain and disease risk with even small weight gains
weight and obesity. of 10–12 pounds associated with increased risk. 33 Certain
comorbidities have a higher prevalence among different
racial groups; however, the increased risks associated with
36.4.5 Sleep being obese appear to be consistent globally.
Evidence from animal and human studies supports an

inverse relationship between amount of sleep and obe-
sity. Several endocrine changes associated with lack of
36.6 ECONOMIC COSTS OF
sleep include decreased glucose tolerance, leptin and OBESITY IN THE U.S.
thyroid-stimulating hormone, and increased ghrelin
levels.105,152 Each of these has a role in obesity develop- The economic costs associated with obesity in the work-
ment stimulating food intake and energy storage.152–161 place have continued to increase over the last several
As much as 30% of adults and 69% of teens do not get decades in the United States101 and worldwide. In 2014,
the recommended hours of sleep.162 Insufficient sleep is a the global prevalence of overweight or obese was more
public health epidemic.162 Reports suggest hours of sleep than 2.1 billion people, or 30% of the global population.
have declined in adults and children over the last 20 The global economic impact of obesity alone was esti-
years.163,164 Large cohort studies support an inverse rela- mated to be $2.0 trillion, or 2.8% of the global domestic
tionship between sleep duration and prospective weight product.176
gain.165 Sleep deprivation as a risk factor for obesity The economic costs related to obesity have been esti-
should be considered in the systems approach to curbing mated based on the direct health care costs associated with
the obesity epidemic.166 treating comorbid diseases (e.g. hypertension, diabetes,
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.
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.
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37
CHAPTER
Exercise Management for the Obese Patient

John M. Jakicic, PhD, Renee J. Rogers, PhD, and Katherine A. Collins, MS, CBDT
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
approximately 70%, 36%, and 16%, respectively. 2 These

KEY POINTS prevalence rates are of significant public health concern
because of the association between excess body weight
• Physical activity contributes to the prevention of
and many chronic diseases that include cardiovascular
weight gain and incidence of obesity, and it is an
disease, diabetes, some forms of cancer, musculoskeletal
important lifestyle behavior to facilitate long-term
disorders, and others.3,4 Thus, public health approaches
weight loss maintenance. Thus, health-care provid-
and interventions are needed to prevent overweight and
ers and health-fitness professionals need to work
obesity, and to reduce body weight in adults who are
closely with patients to counsel them on the appro-
already classified as overweight or obese. The cornerstone
priate aspects of physical activity that can impact
of these approaches are lifestyle factors that contribute to
body weight regulation.
optimal energy balance to prevent weight gain, and energy
• Despite the current emphasis on reducing seden-
imbalance that results in an energy deficit to promote
tary behavior to improve health, with regard to
weight loss. One of the key lifestyle factors that has been
body weight regulation, it appears that the greatest
implicated for these prevention and treatment efforts is
impact results from moving from sedentary or low
physical activity.
amounts of physical activity to sufficient amounts of
moderate-to-vigorous physical activity.
• Physical activity is an important lifestyle behavior
even when the patient is receiving other medical-based 37.2 EFFECT OF PHYSICAL
forms of treatment for obesity (e.g. bariatric surgery).
• Independent of body weight and obesity status,
ACTIVITY ON PREVENTION
physical activity contributes to a variety of health OF WEIGHT GAIN
benefits, which justifies its importance as a key life-
style behavior for health. Given the high prevalence of overweight and obesity in
adults, much of the clinical emphasis is typically on effec-
tive treatments for weight loss. However, from a public
37.1 INTRODUCTION health perspective, it is also important to consider effective
approaches to prevent weight gain in an effort to reduce
Overweight and obesity are significant public health prob- the onset of overweight and obesity. There is evidence that
lems in the United States and other countries throughout physical activity may be an important lifestyle behavior
the world.1 Within the United States, the prevalence of that can contribute to these prevention efforts. 5
overweight (body mass index [BMI] > 25 kg/m 2), obesity There is evidence to support the influence of physical
(BMI > 30 kg/m 2), and severe obesity (BMI > 35 kg/m 2) is activity on the prevention of weight gain. For example,
473
474 Chapter 37 Exercise Management for the Obese Patient
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 structure, 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
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
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.
37.5.1 Effects on Mortality 37.5.2.1 Blood Pressure

An interesting observation is that the association between It is commonly accepted that hypertension is a primary
higher levels of cardiorespiratory fitness and reduced risk risk factor for cardiovascular disease. However, the com-
of mortality is present even when data are adjusted for bined influence of fitness and fatness on blood pressure
37.6 Summary and Clinical Applications 479
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.
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51. Goodpaster BH, DeLany JP, Otto 66. Bouchard C, Tremblay A, Nadeau A, 81. Blair SN, Kohl III H, Paffenbarger RS,
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JE, et al. Effects of diet and physical Long-term exercise training and constant Physical fitness and all-cause mortality.
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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
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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.
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Cardiorespiratory fitness, body composi- outcomes in overweight or obese people AM, Priest EL, Rodarte RQ, Saunders
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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
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J, Froelicher VF. Fitness and fatness as 92. Chen J, Das S, Barlow CE, Grundy S, 97. Van Gaal LF, Mertens IL, DeBlock
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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
Key Points.................................................................................. 483 38.5 Determining Eating Environment and Readiness For

38.1 Introduction...................................................................... 483 Intervention...................................................................... 485
38.2 Medical Assessment......................................................... 483 38.6 Dietary Intervention.......................................................... 486
38.3 Nutrition Assessment........................................................ 484 38.7 Intensity of Intervention.................................................... 487
38.4 Dietary Assessment.......................................................... 484 38.8 Conclusions...................................................................... 488
38.4.1 Determining Energy Expenditure........................... 484 Clinical Applications................................................................... 488
38.4.2 Determining Energy Intake................................... 485 References................................................................................ 488
weight loss or sufficient energy to prevent further weight

KEY POINTS gain, and provide enjoyment of eating while supporting
healthy and sustainable eating patterns. This chapter will
• Diet plays a critical role in the prevention and treat-
focus on the assessment, diagnosis, intervention, monitor-
ment of obesity.
ing, and evaluation of overweight and obesity.
• Decreased energy intake is a key strategy for
weight loss; however, it is important for energy to
be reduced in a manner that still provides essential
nutrients to maintain optimal nutritional status and 38.2 MEDICAL ASSESSMENT
is sustainable for patients.
• There is no universally ideal diet composition for Accurate assessment of weight status requires an office
weight loss or weight maintenance. The diet most environment sensitive to the unique needs of patients with
likely to aid in successful weight loss is one that will obesity. This includes having appropriately sized furniture,
help a patient achieve an energy deficit and one that equipment, gowns, and scales that can weigh patients of
a patient is able to adhere to for the long term. all sizes. The assessment of overweight or obesity involves
• Registered Dietitians are uniquely poised to help annual measurement of anthropometrics including height,
patients select the dietary approach most appropri- weight, and calculation of body mass index (BMI; calcu-
ate for the patient through the assessment, monitor- lated as kg/m2) to classify overweight and obesity using
ing, and evaluation of the patient’s eating habits, current classification methods. Weight and height are mea-
environment, and level of readiness for intervention. sured with the patient wearing light clothing or an exami-
nation gown and no shoes. Patients identified as having
overweight (BMI 2009; 25 kg/m2) or obesity (BMI>30
38.1 INTRODUCTION kg/m2), should be referred to a Registered Dietitian
Nutritionist (RDN) for medical nutrition therapy (MNT).3
The dietary management of people with overweight and Measuring waist circumference in patients with
obesity remains one of today’s greatest healthcare chal- BMI≤35 kg/m 2 is recommended to provide additional
lenges. Rates of obesity and associated health conditions and information about other medical conditions associated
healthcare costs continue to burden society. Obesity has been with obesity, such as cardiovascular risk (>88 cm or >35
described as a chronic, relapsing disease process that is rarely, in for women; >102 cm or >40 in for men).4 A medical his-
if ever, cured.1 While larger weight loss confers greater ben- tory and an examination should query for cardiovascular
efits, modest weight loss of 5–10% has been associated with risk factors like high blood pressure, hyperlipidemia, and
significant improvements in cardiovascular risk factors.2 hyperglycemia. The measurement of blood pressure, lip-
The role of diet in producing successful outcomes for ids, and glucose to assess for cardiovascular risk enables
the prevention and treatment of obesity is to provide essen- treatment to be matched to risk profile.4 As lifestyle
tial nutrients to achieve and maintain an optimal nutri- changes and modest, sustained weight loss of 3–5% body
tional status, produce an energy deficit to yield a reasonable weight can produce clinically meaningful health benefits,
483
484 Chapter 38 Dietary Management of Overweight and Obesity
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
38.3 NUTRITION ASSESSMENT 38.4.1 Determining Energy Expenditure

Medical nutrition therapy by the Registered Dietitian Resting metabolic rate (RMR; can be substituted for
Nutritionist (RDN) will include a comprehensive nutrition REE) should be measured through indirect calorimetry
assessment to obtain, verify, and interpret data needed to whenever possible.3 Although reasonably priced, hand-
identify nutrition-related problems, their causes, and sig- held medical devices enable measurement of RMR (REE)
nificance. It is an ongoing, nonlinear, and dynamic pro- in the primary care setting, there are still times when mea-
cess that involves data collection and continual analysis surement is not possible. The Mifflin-St. Jeor Equation
of the patient’s status compared to specified criteria.7 The (MSJE) is the most accurate predictive formula available
RDN should assess food- and nutrition-related history, for adults, and has been found to predict RMR within
anthropometric measurements, biochemical data, medical 10% of measured in most individuals.3,10,11 Online and
tests and procedures, nutrition-focused physical findings, mobile applications utilizing the MSJE make calculation
and client history in order to individualize the comprehen- of energy needs particularly convenient and accessible.
sive weight management treatment.8 However, the simplified MSJE for males and females11 are
Assessment of food and nutrition-related history includes provided below:
asking questions about beliefs and attitudes, including food
preferences and motivation, food environment, access to
fruits and vegetables, dietary behaviors, eating out, screen For females, REE = 10 × weight (kg ) + 6.25 × height (cm )

time, past dieting history, food allergies, medications,
−5 × age ( y ) − 161
dietary supplements, and physical activity. Understanding
the patient’s weight history, family medical and health his-
tory, social history, living situation and socioeconomic status For males, REE = 10 × weight (kg ) + 6.25 × height (cm )
are all factors to consider in a thorough assessment. Weight
history includes questions about highest and lowest adult –5 × age ( y ) + 5
body weight, usual body weight (within the last six months)
and, finally, the preferred body weight. Consideration of To complete the estimation of TEE, PAL must be esti-
individual factors such as eating disorders, pregnancy, and mated. Assess the patient’s current activity level and apply
if a patient is receiving treatment for other health condi- the appropriate activity factor of REE × 1.2 (sedentary), ×
tions that impact diet (e.g. chemotherapy, management of 1.4 (low active to moderate), and× 1.6 (active). Subsequent
diabetes, renal disease) are part of determining appropriate- adjustments for intentional activity or exercise (such as
ness of a weight management plan. The nutrition-focused walking, biking, dancing, or exercise routines, etc.) are
physical assessment9 is an examination of the body and added as individuals engage in these activities and can be
physical function to help determine nutritional status, signs adjusted per day or averaged per week.
of malnutrition, and nutrient deficiencies. Findings from Although the role of physical activity will be discussed
body composition testing can further help individualize the in more detail in other chapters, the assessment of energy
dietary intervention for weight loss. expenditure is a natural opportunity for the RDN to assess
a patient’s physical activity and sedentary behaviors. As
a modifiable component of energy expenditure, physical
38.4 DIETARY ASSESSMENT activity plays a critical role in long-term weight manage-
ment. For an energy deficit to occur, physical activity has
The first step in dietary assessment for weight manage- to increase and/or TEI must decrease. While difficult to
ment is to determine a patient’s energy needs. To maintain lose weight through increased physical activity alone,
38.5 Determining Eating Environment and Readiness For Intervention 485
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
TABLE 38.1 Dietary intake assessment methods

Method Strengths Limitations
Food Record/Food Diary • Doesn’t rely on patient memory • Patient intake may change as a result
Patients are asked to prospectively • Can be completed in advance of dietetic visit of keeping a food record
record intake for a specified period of • Portion sizes can be measured at time of • Requires patient to be literate,
time consumption numerate, and have portion size
• Data can be entered into dietary analysis knowledge
program • High patient burden, time consuming
• Records of multiple days provide valid • Relies on self-reported information
measure of usual intake for most nutrients
24-hr Recall • Unlikely to modify behavior • Dependent on patient memory
Patients are retrospectively asked • Inexpensive • Relies on self-reported information
about intake from the past 24 hours • Low patient burden • Requires skilled interviewer
• No patient literacy requirement • High inter-interviewer variability
• Can be conducted in person or by telephone • Time consuming
• Data can be entered into dietary analysis • Not representative of usual intake
program
Food Frequency Questionnaire • Low patient burden • Requires patient to be literate and
Patients complete a survey that • Quick, inexpensive numerate
retrospectively queries how often • Easily standardized • Dependent on patient memory
certain foods/beverages were • Useful screening tool • Can be cognitively difficult for patient
consumed in a specified period of time because food lists are not
meal-based
• Doesn’t provide valid estimate of
total intake or meal patterns
Diet History • No patient literacy requirement • Dependent on patient memory
Patients are interviewed about their • Low patient burden • Requires skilled interviewer
usual eating habits • Enables assessment of meal patterning, usual • Time consuming
nutrient and food group intake in one
interview
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
38.8 CONCLUSIONS without judgment, even if they experience weight regain.

Like other chronic conditions, management of obesity will
A number of dietary approaches have produced weight be lifelong and will require change in approach by pro-
loss in the short term; however long-term maintenance vider and patient alike.
of weight loss remains a critical challenge. The patient’s
ability to adhere to a diet long-term is an important fac-
tor to consider when selecting the dietary intervention. CLINICAL APPLICATIONS
Successful selection of the dietary approach taken in MNT
depends on thorough assessment, monitoring, and evalua- • As energy balance and nutrition experts, Registered
tion of a patient’s eating behaviors, environment, and level Dietitians play a critical role in the prevention and
of readiness for intervention. Despite the critical role of treatment of obesity.
dietary intervention in the treatment of obesity, reimburse- • It is imperative that clinicians establish a trusting
ment for MNT weight management varies by state and and supportive relationship with patients under-
insurance provider. Future directions include continued going obesity treatment and that expectations for
progress in reimbursement for MNT for weight manage- weight loss are realistic.
ment by RDNs, consideration of “non-diet” approaches • Selection of dietary weight loss approaches should
for people with obesity (e.g. intuitive eating), counsel- be based on careful assessment and continual moni-
ing to modify behavior, and greater focus on preventing toring and evaluation of a patient’s anthropometric
weight regain after weight loss. It is critical that patients and clinical outcomes, as well as the patient’s eating
have a relationship with their healthcare team based in behaviors, environment, and level of readiness for
trust that the provider will continue to work with them, intervention.
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39
CHAPTER
Pharmacological Management
of the Patient with Obesity
Magdalena Pasarica, MD, PhD and Nikhil V. Dhurandhar, PhD
Key Points.................................................................................. 491 39.4.1 Special Considerations for Concurrent

39.1 Obesity: A Serious Condition............................................. 491 Pharmacotherapy�� 498
39.2 Obesity Treatment............................................................. 492 39.4.2 Who Should Receive Pharmacotherapy for
39.3 The FDA-Approved Obesity Drugs..................................... 492 Obesity�� 498
39.3.1 Drugs Approved for Short-term Use...................... 492 39.4.3 Special Consideration for FDA Indications and
39.3.1.1 Phentermine (Adipex, Ionamin, Lomaira)......492 the State Law�� 499
39.3.1.2 Diethylpropion (Tenuate)........................ 493 39.4.4 Deciding What Weight Loss Drug to Use and
39.3.1.3 Benzphetamine (Didrex)........................ 493 for How Long�� 500
39.3.1.4 Phendimetrazine (Bontril, Prelu-2)......... 493 39.4.5 Optimizing Weight Management During Long-
39.3.2 Drugs Approved for Long-Term Use...................... 494 term Continuity of Care�� 500
39.3.2.1 Orlistat (Xenical TM, Alli TM)....................... 494 39.5 Summary and Conclusions............................................... 501
39.3.2.2 Lorcaserin (Belviq TM, Belviq XR TM)......... 494 Clinical Applications................................................................... 501
39.3.2.3 Phentermine-Topiramate ER (Qsymia)..... 495 Acknowledgements................................................................... 501
39.3.2.4 Naltrexone ER-Bupropion SR (Contrave).......496 Potential Conflict of Interest....................................................... 501
39.3.2.5 Liraglutide (Saxenda)............................. 497 References................................................................................ 501
39.4 Clinical Considerations for Pharmacotherapy
Management of Obesity.................................................... 498
KEY POINTS 39.1 OBESITY: A SERIOUS CONDITION

• Obesity is a chronic disease that requires lifelong The prevalence of obesity continues to rise globally. Based
treatment. on the body mass index (BMI) calculated from measured
• Modest weight loss improves multiple comorbidities heights and weights, the 2013–2014 National Health and
associated with obesity. Nutrition Examination Survey (NHANES) noted the preva-
• The United States Food and Drug Administration lence of obesity (BMI of 30.0 kg/m2 or greater) and class
has approved six drugs with acceptable safety pro- III obesity (BMI of 40.0 kg/m2 or greater) in adults to be
files, for short-term and long-term weight loss. 37.7% and 7.7%, respectively.1 Previous NHANES surveys
• Use of pharmacologic treatment of obesity is indi- were conducted about every four years with at least one
cated as an adjunct to lifestyle changes in adults year between survey periods. Beginning in 1999, NHANES
with a body mass index at or above 30 kg/m 2 or became a continuous survey. There was a significant
at or above 27 kg/m 2 in the presence of at least one increase in obesity prevalence in adults from 1999–2000
weight-related comorbidity. to 2013–2014; however, the increase from 2011–2012
• Providers should get a comprehensive history of to 2013–2014 was not significant (National Health and
the patients with obesity, consider contributors for Nutrition Examination Survey January 2016. https://ww
obesity, including any drugs promoting weight gain w.cdc.gov/nchs/data/factsheets/factsheet_nhanes.htm). The
before starting pharmacological therapy. World Health Organization (WHO) estimates that over
• Selection of an obesity drug should be personal- 600 million adults had obesity in 2014 and the prevalence
ized to accommodate considerations for a patient’s of obesity more than doubled from 1980 to 2014 world-
past medical and social history, current medical and wide. Most importantly, WHO warns that in most coun-
mental health issues, and current medications. tries obesity kills more than underweight (http://www.who
• If response to an obesity drug is poor, or if it causes .int/mediacentre/factsheets/fs311/en/). Obesity prevalence is
non-tolerable side effects, then the drug should be estimated to increase up to 20% in adults by 2025.2
discontinued, and an alternative approach should be Obesity is linked with numerous medically significant
discussed with the patient. comorbidities such as diabetes mellitus, hypertension
491
492 Chapter 39 Pharmacological Management of the Patient with Obesity
(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 hyperin 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
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
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
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
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
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.
Phenermine-Topiramate Qsymia IV 6.6% (49) 18 and older.
Naltrexone-Buproprion Contrave None 4.8% (50) 18 and older.
Liraglutide Saxenda None 5.4% (56) 18 and older.
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 longtime 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
39.5 SUMMARY AND CONCLUSIONS behaviors, increasing compliance, and consequentially,
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.
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40
CHAPTER
Surgery for Severe Obesity

Robert F. Kushner, MD and Lisa A. Neff, PhD
Key Points.................................................................................. 505 40.7.6 Benefits of Physical Activity in Postoperative

40.1 Introduction...................................................................... 505 Bariatric Surgery Patients�� 510
40.2 Bariatric Surgical Procedures............................................ 506 40.7.7 Barriers to Physical Activity after Bariatric Surgery.....510
40.3 Importance of Lifestyle Intervention.................................. 507 40.7.8 Recommendations for Physical Activity after
40.4 Preparing the Patient for Surgery...................................... 507 Bariatric Surgery�� 510
40.5 Weight Loss Outcomes and Improvement in Obesity- 40.7.9 Behavioral/Psychological Care.............................511
Related Medical Conditions............................................... 507 40.7.10 Mood Disorders...................................................511
40.6 Lifestyle Interventions in the Postoperative Care of 40.7.11 Disordered Eating................................................511
Bariatric Surgical Patients................................................. 508 40.7.12 Alcohol Misuse....................................................511
40.7 Nutritional Care................................................................. 508 40.7.13 Psychological Counseling and Peer Support
40.7.1 Dietary Changes after Bariatric Surgery................ 508 in the Postoperative Period�� 512
40.7.2 Recommended Dietary Patterns and Eating 40.7.14 Comprehensive Lifestyle Interventions after
Behaviors�� 508 Bariatric Surgery�� 512
40.7.3 Prevention of Micronutrient Deficiencies after 40.7.15 Weight Regain following Bariatric Surgery.......... 513
Bariatric Surgery�� 508 40.8 Conclusion........................................................................ 513
40.7.4 Physical Activity.................................................... 510 Clinical Applications................................................................... 513
40.7.5 Physical Activity Levels after Bariatric Surgery.......510 References................................................................................ 513
non-Hispanic women, the most vulnerable subgroup.6

KEY POINTS According to the American Society for Metabolic and
Bariatric Surgery,7) 216,000 bariatric surgeries were per-
• Bariatric surgery is indicated for patients with a BMI
formed in the U.S. in 2016. Given the high prevalence rates
of ≥40 kg/m 2 or those with a BMI of ≥ 35 kg/m 2
for moderate-to-severe obesity and the increased availabil-
who have comorbid conditions.
ity of bariatric surgery, it is likely that healthcare profes-
• Mean weight loss at two to three years following a
sionals from all disciplines will encounter patients who
surgical procedure ranges from 20% to 34% of ini-
have undergone a bariatric surgical procedure. Similarly,
tial body weight, depending on the procedure.
primary care physicians will be expected to monitor and
• All patients who are considering weight loss surgery
manage their patients on a long-term basis. Many of the
should undergo a comprehensive assessment by a
weight loss surgeries—most notably the combined restric-
multidisciplinary team of healthcare providers that
tive-malabsorptive surgical procedure Roux-en-Y gastric
includes a physician or advanced practice provider,
bypass (RYGB), the malabsorptive biliopancreatic diver-
registered dietitian, and mental health professional.
sion (BPD), and biliopancreatic diversion with duodenal
• Continued attention to diet, physical activity, and
switch (BPDDS)—place patients at high risk for develop-
emotional health after bariatric surgery is essential
ment of both macro-and micronutrient deficiencies unless
to ensure optimal outcomes.
they are properly counseled and supplemented. Since most
of the deficiencies can be identified at a preclinical stage,
early identification and treatment will prevent or reduce
40.1 INTRODUCTION symptoms and deficiency syndromes. Although bariatric
surgery does not cure obesity, it is considered a signifi-
Various expert panels have endorsed bariatric surgery cant tool for weight loss and maintenance of weight loss.
as an acceptable weight loss option for patients with a As such, patients are at risk to experience weight regain
BMI of ≥ 40 kg/m2 (severe or class III obesity) or those several years following surgery. This chapter will review
with a BMI of ≥ 35 kg/m2 who have comorbid condi- the most commonly performed weight loss procedures, the
tions.1–5 Currently, overall age-adjusted U.S. population importance of preoperative and postoperative manage-
prevalence rates for those who are potentially eligible ment, identification and management of nutritional defi-
for bariatric surgery (BMI of ≥ 35 kg/m2) are 11.9% and ciencies that may occur following bariatric surgery, and
17.0% for men and women, respectively, and 29.2% for factors associated with weight regain.
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
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.
40.7.1 Dietary Changes after

Bariatric Surgery 40.7.2 Recommended Dietary Patterns
A variety of dietary changes occurs after bariatric surgery.
and Eating Behaviors
Most importantly, there is a significant and sustained As a result of the reductions in gastric capacity and caloric
reduction in caloric intake. Although portion sizes tend intake after surgery, patients must take care to ensure that
to increase gradually over time in postoperative patients, nutritional needs are met. Postoperative patients should be
caloric intake is typically still reduced by 25% or more for advised to consume small portions, have 4–6 small meals
years after surgery.40,41 A recent analysis of the Swedish daily, and ensure an adequate intake of lean protein (60–
Obese Subjects (SOS) study, a prospective, matched (non- 120 grams/day), fruits and vegetables (>5 servings/day),
randomized), intervention trial of bariatric surgery, dem- and whole grains.10,50 Patients should also eat slowly, chew
onstrated the importance of early caloric restriction.42 thoroughly, avoid fatty foods, sweets and sugar-sweetened
Study participants with greater reductions in energy and beverages, and avoid ingestion of liquids within 30 minutes
fat intake in the first six months after bariatric surgery of meals. Unfortunately, many postoperative patients fail to
maintained greater weight loss after 10 years. follow the recommended guidelines, particularly regarding
Food intolerances may occur and can lead to altera- fruit and vegetable consumption and avoidance of sweets
tions in dietary patterns after bariatric surgery. Lactose and caloric beverages.50 For this reason, clinicians should
intolerance can develop in patients who have undergone routinely assess patients’ dietary intake during postopera-
gastric bypass; as a result, nearly one-third of patients tive visits and reinforce recommended dietary goals.
report avoiding milk after this procedure.43 Dumping
syndrome occurs in up to 76% of patients after RYGB
and may lead patients to reduce their intake of concen- 40.7.3 Prevention of Micronutrient
trated sweets and fatty foods to avoid associated post-
prandial symptoms, such as abdominal cramping, nausea, Deficiencies after Bariatric Surgery
diarrhea, lightheadedness, sweating, and tachycardia.44 Patients who have undergone bariatric surgery should
Over 60% of patients report avoiding sweets and nearly be counseled that they are at risk for the development of
30% avoid fatty foods after RYGB surgery.43 Other food micronutrient deficiencies after surgery. After RYGB, the
intolerances include difficulty consuming whole meats, most common micronutrient deficiencies include those of
fresh fruits, and raw vegetables, presumably due to the vitamin B12, vitamin D, calcium, and iron.51,52 Folic acid
phenomenon referred to as “plugging,” when a food deficiency has also been reported but is largely preventable
becomes lodged in the gastric pouch.45,46 with regular use of a standard multivitamin preparation.51
40.7 Nutritional Care 509
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.
TABLE 40.1 Recommended micronutrient supplementation after bariatric surgery

Supplement Dose and frequency
Vitamin B1 (thiamine) a12 mg daily
Folate (Folic Acid) a400–800 µg daily
800–1000 µg daily for women of childbearing age

Calcium b 1200–1500 mg/day from all sources (after RYGB, SG, or LAGB)
b 1800–2400 mg/day from all sources (after BPD/DS)
Vitamin D (in calcium supplement or separate) 3000 IU/day
Elemental iron a18 mg daily for low risk patients
40–60 mg/day for menstruating females

Vitamin B12 350–500 µg/day orally
Or 500 µg every week intranasally
Or 1000 µg/month parenteral (IM or SQ)
Zinc a16–22 mg/d (after BDP/SD)
a8–22 mg/d (after RYGB)
a8–11 mg/d (after SG/LAGB)
Copper a2 mg/d (after BPD/DS or RYGB)

a1 mg/d (after SG or LAGB)
Vitamins A, E and K aVitamin A 5000 IU/D and vitamin K 90–120 µg/d (after LAGB)
aVitamin A 5000–10,000 IU/D and vitamin K 90–120 µg/d (after RYGB and SG)
aVitamin A 10,000 IU/D and vitamin K 300 µg/d (after DS)
aVitamin E 15 mg/d (after LAGB, SG, RYGB, and BPD/DS)
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.
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
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
outcomes has been largely disappointing. Multiple factors 40.8 CONCLUSION

40
appear to influence the varied outcome results, including
patient selection, timing and intensity of the intervention, Bariatric surgery is an effective and acceptable treatment
comprehensiveness of counseling provided, and selection for individuals with severe obesity who are at risk for or
of outcome measurements. Further studies will need to have complications associated with obesity. Several surgi-
be conducted to identify the most suitable targets and cal procedures are available with variable risk and weight
patients for intervention. loss outcomes. However, regardless of the procedure per-
formed, surgery is considered a tool that is adjunctive to
choosing a healthy, calorie-controlled diet and engag-
40.7.15 Weight Regain following ing in daily physical activity. For patients who undergo
restrictive-malabsorptive or malabsorptive operations,
Bariatric Surgery dietary supplementation is necessary to avoid nutritional
Although clinicians commonly see bariatric surgery deficiencies. Patients are at risk for weight regain follow-
patients regain some weight postoperatively, the prevalence ing surgery due to several biopsychosocial factors. In order
and incidence of weight regain has not been well-charac- to maximize successful outcomes, all patients should be
terized. Follow up data from the LABS study has continued monitored and managed by a multidisciplinary team of
to inform clinical care regarding various aspects of postop- healthcare providers knowledgeable in bariatric surgical
erative management, including postoperative weight loss care.
trajectories,104 behavioral variables, and three-year weight
change.105 The underlying factors that influence weight
regain following bariatric surgery are multifactorial and CLINICAL APPLICATIONS
include endocrine/metabolic alterations, anatomic surgi-
cal failure, dietary indiscretion, mental health issues, and • Bariatric surgery should be considered for patients
physical inactivity.106 The extent and significance of these with BMI of ≥ 40 kg/m 2 or those with a BMI of ≥
factors is currently uncertain and likely varies between 35 kg/m 2 who have comorbid conditions and have
individuals and the operative procedure performed. Using failed nonsurgical approaches.
cross-sectional data, weight regain has been estimated to • Preoperative assessment and postoperative manage-
occur in 20–35% of patients, depending on the proce- ment should be conducted by a multidisciplinary
dure performed and duration of time following surgery.47 team of health care providers with attention to
Table 40.3 provides a categorical list of potential etiolo- medical, dietary, physical activity and mental health
gies that should be explored with all patients who present aspects of care.
with weight regain. The physiological and behavioral (diet • Since obesity is considered a chronic disease,
and physical activity) causes are common to surgical and patients who undergo bariatric surgery require long-
nonsurgical patients. Depending on the patient’s age and term management, employing lifestyle behaviors
gender, a through history should be performed that reviews and strategies conducive to maintaining a healthy
all of these reasons followed by appropriate counseling. body weight.
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41
CHAPTER
Adiposity-based Chronic Disease

a New Diagnostic Term
Michael A. Via, MD and Jeffrey I. Mechanick, MD, FACP, FACE, FACN, ECNU
Key Points.................................................................................. 517 41.6.2 Antibiotic Use in Farming.................................... 522

41.1 Introduction...................................................................... 517 41.6.3 Endocrine Disruptors.......................................... 522
41.2 Consequences of ABCD.................................................... 518 41.7 Alcohol Moderation......................................................... 523
41.3 Intensive Lifestyle Intervention.......................................... 518 41.8 Mood.............................................................................. 523
41.4 Sleep Hygiene................................................................... 520 41.9 Community Engagement................................................ 523
41.5 Stress Reduction.............................................................. 521 41.10 Transculturization........................................................... 524
41.6 Antibiotic Use and the Microbiome.................................... 522 41.11 Conclusion...................................................................... 524
41.6.1 Antibiotic Use by Humans...................................... 522 References................................................................................ 524
dysfunction. For the purpose of clarity and communi-

KEY POINTS cation, the term adiposity refers to all sites of intracel-
lular fat deposition, constituting a full range of healthy
• Adiposity-based chronic disease (ABCD) is a
to unhealthy pathophysiological mechanisms. The term
novel diagnostic term that emphasizes dysfunc-
ABCD refers to the chronic disease state causally associ-
tional adipose tissue that is present in an unfavor-
ated with abnormalities of adiposity (Table 41.1). This is
able distribution and associated with metabolic
distinguished from the term “obesity,” which is currently
disease, cardiovascular risk, and a host of other
and strictly defined as having a body mass index (BMI)
comorbidities.
greater than a defined cutoff (e.g. 30 kg/m 2 or greater for
• An intensive lifestyle intervention can address
Caucasians). The clinical diagnosis of ABCD may be sup-
many of the risks associated with ABCD. This
ported by anthropometrics (e.g. BMI and waist circum-
includes healthy dietary patterns, physical activ-
ference), body composition technologies (e.g. bioelectrical
ity, sleep hygiene, stress reduction, and community
impedance and dual X-ray absorptiometry), and other
involvement.
imaging studies (e.g. computerized tomography, magnetic
• Other aspects of lifestyle may affect ABCD, includ-
resonance, and positron emission tomography), 3 as well as
ing minimal use of antibiotics, avoidance of endo-
serum markers of adipose function, including adipokines,
crine disruptor chemicals, and transculturalization.
triglycerides, and markers of inflammation (Table 41.2).4,5
Unfortunately, multiple and conflicting health mes-
saging about the definition and the causes of obesity, best
41.1 INTRODUCTION lifestyle practices, and unproven therapies only aggravate
confusion within the scientific literature,6,7 lay press,8 and
The physiologic role of intracellular fat deposition in the popular culture.9,10 Abnormal adiposity poses significant
regulation of energy metabolism allows for the classi- and irrefutable health risks, but sustainable lifestyle inter-
fication of adiposity-based chronic disease (ABCD) as a ventions, though logically sound and evidence based, are
distinct entity and diagnostic term, with opportunities very difficult to implement. This incongruence commonly
for research, clinical applications, and intensive lifestyle leads to therapeutic nihilism on the part of both healthcare
interventions.1 Fat deposition occurs in eutopic adipose professionals (HCP) and patients. To some degree, this
tissue (adipocytes) with various body distributions, as follows from the widely held belief that obesity is a per-
well as in ectopic sites (non-adipocytes, such as myocytes sonal choice rather than a bona fide chronic disease state
and hepatocytes). 2 Depending on the deposition loca- with hallmark biological and behavioral components.
tion, distribution, and function, intracellular fat directly Despite the classification of obesity as a disease several
and indirectly participates in energy metabolism through years ago, negative personal and societal connotations
intermediary metabolism and hormone receptor signal remain associated with the word “obesity.”1,6,7 Moreover,
transduction producing states of inflammation, insulin limitations in the use of BMI to predict adverse risk, espe-
resistance, abnormal food-seeking behavior, and organ cially among Asian populations,11 as well as acceptance of
517
518 Chapter 41 Adiposity-based Chronic Disease a New Diagnostic Term
modern global populations, and the limited access to other

TABLE 41.1 Defining characteristics of ABCDa
therapeutic options, an intensive lifestyle modification may
Adiposity be the only available option for the majority of patients
variable Metric with ABCD worldwide. Moreover, the effective imple-
mentation of structured lifestyle change for patients with
Increased mass Anthropometrics (e.g. weight, BMI)
ABCD promises to decrease the need for costlier medical
Body composition imaging and surgical interventions (quaternary prevention).
Abnormal Anthropometrics (e.g. WC, WHR) The premise of this chapter is that the decades-long
distribution trend of clinical inertia in obesity medicine, stigmatiza-
Body composition imaging tion, and skyrocketing obesity rates within many sub-
Abnormal function Adipokine/cytokine levels (e.g. populations in the United States and worldwide prompts
adiponectin, leptin) a call-for-action to optimize and formalize lifestyle inter-
ventions to mitigate ABCD risk factors and complications.
a ABCD is differentiated from obesity by the specific excessive distribution and
dysfunction of adipocytes. Abbreviations: ABCD – adiposity-based chronic dis-

ease; BMI – body mass index; WC – waist circumference; WHR – waist-to-hip ratio.
See references,4,5 and.129 41.2 CONSEQUENCES OF ABCD
The health consequences of ABCD are far-reaching and
TABLE 41.2 Selected energy and inflammation signal include metabolic, cardiovascular, orthopedic, gastro-
networks affected in ABCDa intestinal, psychiatric, and oncologic risk (Table 41.3).
Adipokines Change in ABCD Prediction of specific ABCD sequelae can be difficult.
Not all patients with ABCD develop each of the associ-
Adiponectin Reduced ated complications. Additionally, the degree of adipose
Leptin Elevated tissue accumulation may not correlate with the sever-
ity or the incidence of ABCD-associated complications,
Resistin Elevated
especially in conditions characterized by abnormalities
Visfatin Elevated in the distribution and function of adipose tissue. Some
Cytokines
authors propose the existence of a subset of patients with
“metabolically healthy” obesity (MHO), who are not at
Interleukin-1 Elevated increased risk for cardiovascular disease or type 2 diabe-
Interleukin-6 Elevated tes (T2D), despite the presence of a BMI above 30 kg/m 2
(highlighting the problem of defining obesity by a simple
Tumor necrosis factor-α Elevated arithmetical formula).13 Over time, patients with MHO
Other signal molecules still demonstrate increased rates of T2D, insulin resis-
tance, and cardiovascular disease.14,15 These patients with
Fibroblast growth factor-21 Elevated
MHO are also at risk for other ABCD-associated compli-
Glucagon-like peptide 1 Reduced cations (Table 41.3),16 consistent with a more complex net-
Ghrelin Elevated
working model that demonstrates emergent properties. 5
More significantly, many ABCD-associated complica-
Plasminogen activator inhibitor-1 Elevated tions instigate adverse lifestyle choices and create vicious
Mechanistic target of rapamycin Reduced cycles of abnormal adiposity. For example, orthopedic
injuries, cardiovascular atherosclerotic disease, or depres-
a ABCD – adiposity-based chronic disease. See reference.5 sion can prevent regular exercise and favor individual
preference for sedentary activity.17–19 Obstructive sleep
changing societal norms, may cast doubt on the urgency apnea disrupts healthy sleep hygiene. 20 Dysglycemia syn-
and severity of risk among patients with obesity.12 To dromes such as T2D, polycystic ovary syndrome (PCOS),
address these concerns, the concept of ABCD emphasizes and the metabolic syndrome affect hormonal control of
the unhealthy nature of adiposity extending well beyond energy homeostasis, which may render attempts at weight
simple BMI or body weight, which includes abnormal loss through lifestyle intervention more difficult. 21 In sev-
body fat distribution, anthropometrics, and adipocyte eral studies, patients with T2D achieved approximately
secretome patterns. Changes in production of adipokines, 50% of the weight loss that was sustained by patients
such as leptin, resistin, and adiponectin, are among the without T2D following identical dietary and exercise pro-
most notable alterations of adipocyte function.5 This tocols. 22,23 Similarly, women with PCOS demonstrate less
greater detail allows for more precise therapeutic interven- weight loss than obesity-matched women without PCOS. 24
tions, particularly structured lifestyle interventions, but
also requires a more robust diagnostic coding system for
reimbursement and economic incentive for ABCD tactics.
41.3 INTENSIVE LIFESTYLE
Following a laser-focused behavioral intervention to INTERVENTION
activate patients for change, an intensive lifestyle interven-
tion approach should be implemented for ABCD and con- All patients with ABCD should strive for a healthy life-
tinued even as pharmaceutical and procedural interventions style, avoiding or minimizing modern conveniences and
are delivered. Given the high prevalence rate of obesity in living practices that are detrimental to metabolic health.
41.3 Intensive Lifestyle Intervention 519
TABLE 41.3 ABCD-related conditionsa
Condition
Relative
risk ABCD component Reference
41
Abnormal
Adiposity Characteristic Adipocyte
Amount Adipose Distribution Function
Metabolic
Type 2 diabetes 7.7 ++++ ++++ ++++ 130
Polycystic ovary syndrome 1.5 + ++ ++ 131,132
Hepatosteatosis 1.9 ++ +++ ++ 133,134
Obstructive sleep apnea 3.6 +++ ++ ++ 135,136
Cardiovascular
Hypertension 2.0 ++ ++ + 130,137
Atherosclerotic disease 1.6 ++ ++ +++ 130,138
Arrhythmia 1.49 + +++ ++ 139,140
Orthopedic
Osteoarthritis 1.39 + + − 130,141
Tendon injuries 1.7 ++ ++ ++ 142,143
Gout 2.2 ++ + + 144,145
Gonadal function
Infertility (women) 1.2 + ++ ++ 146,147
Hypothalamic hypogonadism (men) 1.6 ++ +++ +++ 148
Gastrointestinal
Cholelithiasis 1.8 ++ + ++ 130,149
Psychiatric
Depression 2.0 ++ +++ +++ 150
Cancer
Obesity-related (esophageal, 1.5 ++ + + 130,151
colon, pancreatic, prostate, kidney,

liver, gall bladder)
a Relative risk compared to non-obese population.
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
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
TABLE 41.4 Effects of lifestyle intervention on components of ABCD

Intervention (Reference) Adipose amount Adipose distribution Adipose function
Dietary pattern28 Moderate Moderate Moderate
Physical activity6 Negligible Moderate Moderate
Sleep hygiene49,50 Strong Moderate Moderate
Stress reduction59,60,63 Mild Moderate Strong
Antibiotic use 74 Mild – –
Endocrine disruptors 85 Moderate Moderate Strong
Alcohol moderation 88–90 Moderate Negligible Moderate
Mood 93,95 Moderate NA Strong
Community engagement 113 Moderate NA Strong
NA: Sufficient data not available.

41.5 Stress Reduction 521
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
TABLE 41.5 Clinical application for lifestyle interventions

Intervention (Reference) Practical clinical application
Dietary pattern 28 Mediterranean, DASH, Ornish, New Nordic, or similar dietary pattern
Physical activity 6 Cardiovascular activity for 30 minutes 5x weekly
Resistance training 3–5x weekly
Sleep hygiene49,50 7–9 hours nightly sleep, regularly
Stress reduction 59,60,63 Mindfulness, low-impact exercise
Antibiotic use74 Minimal use of antibiotics
Endocrine disruptors 85 Avoidance, minimize exposure of environmental toxins
Alcohol moderation 88–90 0–9 alcoholic beverages per week for women, 0–14 for men
Mood 93,95 Cognitive behavioral therapy
Community engagement 113 Engagement in community outreach programs
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
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.
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42
CHAPTER
Future Directions in Obesity

and Weight Management
Theodore K. Kyle, RPh, MBA
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
Both Presidents George W. Bush and Barack Obama sup-

KEY POINTS ported vigorous initiatives to reduce the health impact of
obesity and overweight on public health.
• Significant barriers to effective obesity care are
And yet, as outgoing CDC Director Thomas Frieden
slowly falling away to make better outcomes
conceded in late 2016, progress against public health
possible.
goals to reduce obesity has fallen well short of expecta-
• Largely ineffective prevention programs narrowly
tions.1 Data from the National Health and Nutrition
focused on individual behaviors will be replaced by
Examination Survey for 2016 indicates that obesity prev-
more systematic, evidence-based strategies.
alence is at record high levels. 2 Despite best efforts from
• Advances in pharmacotherapy are progressing
public health policymakers, what had been an epidemic of
toward providing more targeted options with the
obesity in the United States and other developed countries
potential to deliver efficacy comparable to bariatric
has become a global pandemic.3 To date, no country has
surgery.
succeeded in reversing these trends.
• Research insights into diverse obesity phenotypes
These developments have unfolded within the context
promise advances in precision medicine for obesity.
of progress, albeit incomplete, in understanding the bio-
• Attention to long-term outcomes will pinpoint pat-
logical and behavioral drivers of obesity. In recent years,
terns of obesity care that will yield better health and
options for treatment have grown, especially with respect
longer lives.
to pharmacotherapy. A growing number of healthcare
providers are acquiring skills and credentials for provid-
ing evidence-based care for patients affected by obesity.
42.1 INTRODUCTION The evidence for benefits of obesity treatment, especially
for bariatric surgery, is growing steadily.
For more than four decades, experts in public health and Yet relatively few people are benefiting from this prog-
medicine have been calling attention to the health threat ress. Many primary care providers do not provide or even
of rising obesity prevalence. Pediatric health experts recommend effective forms of treatment for obesity. Many
expressed specific concerns about rising pediatric obesity patients are either unaware of treatment options that can
prevalence and the implication for the health of future improve their health, or they do not believe that such
generations as early as 1974. treatments are relevant to them.
To address these concerns, the Centers for Disease Future directions for progress in reducing the health
Control and Prevention established the Division of impact of obesity will depend upon three broad themes:
Nutrition, Physical Activity, and Obesity in 1997. In 2001, removing barriers to better outcomes, developing public
Surgeon General David Satcher issued a national call to health strategies that work, and research to provide better
action to prevent and decrease overweight and obesity. treatment options.
529
530 Chapter 42 Future Directions in Obesity and Weight Management
42.2 REMOVING BARRIERS American Academy of Pediatrics11 formally resolved to

work toward reducing the harm of weight bias in both pedi-
TO BETTER OUTCOMES atric, adolescent, and adult medicine. In parallel, popular
media is increasingly drawing attention to this problem,
Obesity is a chronic disease with growing prevalence characterizing it as fat shaming and thus unacceptable in
caused by complex interactions between biological, social, popular culture12 In combination with increasingly potent
economic, and environmental factors. And yet, consider- social movements favoring body positivity and feminism,
able evidence suggests that better outcomes for public and these developments provide reasons for encouragement.13
individual health are possible by implementing evidence- In fact, life might be considerably better for people
based prevention and treatment options that already exist. with obesity if all the energy that goes into concern troll-
Improved outcomes will require removing numerous sys- ing were redirected. Redirecting it to fight bias and fat
temic barriers that include deeply entrenched bias and shaming, as well as promote and support body positivity,
stigma, inadequate clinical resources for delivering effec- would do more to improve the lives of people affected.
tive obesity care, and payment systems that presently favor
treating the complications of obesity over preventing those
complications.
42.2.2 Inadequate Resources
for Obesity Care
42.2.1 Entrenched Bias and Stigma Although both healthcare providers and patients per-
Considerable research has shown that many policies and ceive obesity as a disease, clinical practice patterns do not
practices related to obesity serve to make life worse for reflect that perception.14 This might come from a lack of
people living with the disease.4 Recent research shows that appreciation for the biological basis for obesity and a false
children with excess weight and obesity face bias, stigma, perception that this disease results almost exclusively from
and bullying from a very early age. lifestyle and behavioral factors. Perhaps as a result, many
Using data from the TRAILS study, Kayla de la Haye physicians incorrectly believe that behavioral interven-
and colleagues examined the social networks of chil- tions are more effective than pharmacologic and surgical
dren with a mean age of 11.5 They looked at friendship therapies for obesity.15
nominations and dislike nominations for children by their For childhood obesity care, resources are especially
peers. They confirmed findings of prior research: heavier scarce. Approximately 5,000,000 children have severe
kids were less likely to be nominated for friends. But the obesity in the U.S. and yet fewer than 50 centers with class
researchers went further by examining social networks. 3 programs for obesity care exist to serve these children.16
They found that the heavier kids were more likely to nom- A recent conference of cross-sector stakeholders found
inate children as friends whom they dislike—further evi- that inadequate payment systems for childhood obesity
dence of the social isolation caused by weight bias. care present a significant barrier to the sustainability of
Similarly, researchers have documented that weight centers that can meet this need. Most of those centers
bias in children is every bit as harsh as racial bias seen operate at a financial loss.17
in adults.6 The high levels of implicit weight bias they One reason for this gap in clinical care is that most
found by themselves foster unhealthy eating behaviors healthcare providers have relatively little training for
and increased risk that childhood obesity will persist into delivering evidence-based obesity care. Unsurprisingly,
adulthood. Bullying is pervasive for children and adoles- they do not express high confidence in providing such
cents, and leads to poor health outcomes.7 care.18 Medical licensure examinations do not yet test
Screening children at school for obesity singles them prospective physicians for key competencies required to
out for stigma and bullying while offering no clinical care effectively treat obesity.19
that can help to reverse the condition. In a recent review, However, recent developments point to more health-
Thompson and Madsen could find no evidence for a ben- care professionals seeking training to provide obesity
efit for students regarding this policy and significant con- care. The American Board of Obesity Medicine reports
cerns about the potential for harm.8 that more than 2,000 physicians have now become board
Likewise, many other “awareness” campaigns serve certified in obesity medicine, making it one of the fast-
mainly to promote stigma while doing nothing to provide est growing fields of medical care. 20 Most of those diplo-
access to clinically effective care. Most adults and children mates come from primary care—family practice, internal
with excess weight experience daily reminders about their medicine, obstetrics, and gynecology. For a wide range of
weight status—even if they avoid the subject of obesity allied health professionals, the Commission on Dietetic
because it is so highly stigmatized. Among adults with Registration now offers board certification in obesity and
obesity, experiences of weight bias and discrimination are weight management.
common in employment, education, mass media, personal
relationships, and healthcare. They lead to poor psycho-
logical and physical health outcomes. Bias expressed by 42.2.3 Payment Systems that Favor
healthcare providers significantly impairs the quality of
care that people with obesity receive.9
Treating Obesity Complications
Rising awareness of the problems that weight bias and Perhaps one of the most important factors that impedes
fat shaming create offers reason for encouragement. In the delivery of evidence-based obesity care is payment
2017, both the American Medical Association10 and the systems that either deny or severely restrict coverage for
42.3 More Effective Public Health Strategies 531
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
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.
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IX
PA RT
Immunology and Infectious Disease

Gregory A. Hand, PhD, MPH, FACSM, FESPM
537
43
CHAPTER
Exercise, Inflammation, and

Respiratory Infection
Wesley D. Dudgeon, PhD, David C. Nieman, DrPH, FACSM,
and Elizabeth Kelley, MS, ACSM-RCEP
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
(WBC) and a variety of cytokines including interleukin-6

KEY POINTS (IL-6), IL-8, IL-10, IL-1 receptor antagonist (IL-1ra),
granulocyte colony stimulating factor (GCSF), monocyte
• Chronic exercise reduces systemic inflammation.
chemoattractant protein 1 (MCP-1), macrophage inflam-
• Weight reduction is key in reducing overall
matory protein 1 beta (MIP-1β), tumor necrosis factor-
inflammation.
alpha (TNF-α), and macrophage migration inhibitory
• Moderate exercise training reduces the risk of
factor (MIF). 2–4 C-reactive protein (CRP) is also elevated
URTIs.
following heavy exertion, but the increase is delayed in
• Moderate exercise improves immunosurveillance.
comparison to most cytokines. Despite regular increases
in these inflammation biomarkers during each intense
exercise bout, endurance athletes have lower levels when
43.1 INTRODUCTION measured during rest in contrast to overweight and unfit
adults. For example, mean CRP levels in long-distance
Exercise immunology is a relatively new area of scientific runners (rested state) typically fall below 0.5 mg/L in
endeavor, with the majority of papers published within comparison to 4.0 mg/L and higher in obese, postmeno-
the past 25 years.1 Most studies have focused on the acute pausal women. 3,5
and chronic effects of various exercise workloads on the The persistent increase in inflammation biomarkers is
immune system and immunosurveillance against patho- defined as chronic or systemic inflammation and is linked
gens. For the practicing physician, two areas of investiga- with multiple disorders and diseases including athero-
tion from exercise immunology have the greatest clinical sclerosis and cardiovascular disease (CVD), metabolic
and public health implications: (1) chronic anti-inflamma- syndrome, diabetes mellitus, sarcopenia, arthritis, osteo-
tory influence of exercise training and (2) reduction in risk porosis, chronic obstructive pulmonary disease, demen-
of upper respiratory tract infections (URTI) from regular, tia, depression, and various types of cancers.6–8 CRP is
moderate exercise training. the most frequently measured inflammatory biomarker,
and individuals with CRP values in the upper tertile of
the adult population (>3.0 mg/L) have a twofold increase
43.2 CHRONIC ANTI-INFLAMMATORY in CVD risk compared to those with CRP concentrations
below 1.0 mg/L.8 An elevated fasting IL-6 concentra-
INFLUENCE OF EXERCISE TRAINING tion is a significant component of the chronic low-grade
inflammation that underlies metabolic syndrome, CVD,
Acute inflammation is a normal response of the immune diabetes, and various cancers.9 Athletes typically have
system to infection and trauma. Intense and prolonged plasma IL-6 concentrations that fall below 1.0 pg/mL in
exercise similar to marathon race competition causes contrast to values above 2.0 pg/mL in older and obese
large but transient increases in total white blood cells individuals.3,9
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
TNF-α decreases, and insulin sensitivity improves.31,32
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
Figure 43.5 URTI incidence in three groups of elderly

women for 12 weeks: Highly conditioned, walkers, and
controls.
Figure 43.3 This one-year epidemiological study of 547
adults showed a 23% reduction in URTI risk in those
(From Nieman, D.C. et al., Med. Sci. Sports Exerc., 25, 823,
engaging in regular vs. irregular physical activity.
1993.) Physically inactive controls had the highest URTI inci-
dence during the fall cold season.
(From Matthews, C.E. et al., Med. Sci. Sports Exerc., 34, 1242,
2002.)
Figure 43.4 The number of URTI symptom days was

decreased by approximately half through a walking pro-
gram (five days/week, 45 min/session, for 15 weeks) by Figure 43.6 A one-year randomized study of 115 over-
previously sedentary, overweight adult women. weight, postmenopausal women showed that 166 min/
week (approximately four days/week) of moderate exer-
(From Nieman, D.C. et al., Int. J. Sports Med., 11, 467, 1990; cise lowered URTI risk compared to controls (stretching),
Nieman, D.C. et al., Med. Sci. Sports Exerc., 30, 679, 1998.) especially during the last three months.
(From Chubak, J. et al., Am. J. Med., 119, 937, 2006.)

of 36 women (mean age 35 years), subjects walked briskly
for 45 minutes, five days/week, and experienced one-half
the days with URTI symptoms (5.1 versus 10.8) during the and elderly44,45 women who exercised compared to the
15-week period compared to that of the sedentary control control group (Figure 43.5). With increased duration of
group (Figure 43.4).43 regular exercise, the risk of colds in the exercisers was
Studies comparing the effect of exercise vs. control more than three times less than that of the control group
(sedentary or calisthenics) groups on URTI risk indicated (Figure 43.6).46
that regular, moderate exercise, such as walking for 30 to Regular physical activity may lower rates of infection
40 minutes, four to five days per week.44–46 was effective for other types of diseases, but data are limited due to
in reducing the incidence of URTI in postmenopausal46 low disease prevalence. For example, women with a high
References 543
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.
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44
CHAPTER
Chronic Exercise and Immunity

Melissa M. Markofski, PhD, Paul M. Coen, PhD, and Michael G. Flynn, PhD
Key points.................................................................................. 547 44.4.2 Toll-like Receptors................................................ 550

44.1 Effect of Chronic Exercise on Leukocyte Number and 44.4.3 Excessive Training: URS or URTI?.......................... 550
Function........................................................................... 547 44.5 Moderate Training and Immunity....................................... 551
44.2 Effect of Chronic Exercise on Innate Immunity.................. 547 44.5.1 Exercise and Inflammation................................... 551
44.2.1 Monocytes and Tissue Macrophages.................... 547 44.5.2 Wound Healing..................................................... 551
44.2.2 Natural Killer Cells................................................ 548 44.5.3 Exercise and Efficacy of Vaccines......................... 552
44.2.3 Neutrophils........................................................... 548 44.6 Conclusion........................................................................ 552
44.3 Effect of Chronic Exercise on Adaptive Immunity............... 549 Clinical Applications................................................................... 552
44.3.1 T and B Lymphocytes........................................... 549 Acknowledgments..................................................................... 552
44.4 Excessive Training and Immunity...................................... 549 References................................................................................ 553
44.4.1 Th1/Th2 Balance.................................................. 549
stem cells, which are collectively responsible for mounting

KEY POINTS an immune response. A physically active or regularly exer-
cising person has a lower number of circulating leukocytes
• Acute exercise induces transient changes to circulat-
at rest, but it can be difficult to partition the specific effects
ing immune cells, and some of these changes may be
of exercise from the associated health benefits of regular
related to the fitness of the individual.
exercise.1–4 Furthermore, regular exercise and physical
• Exercise training may induce beneficial changes to
activity can alter phenotype and influence the function of
resting immune function.
specific subsets of leukocytes.5,6 These changes potentially
• Participation in regular exercise is encouraged for
mediate the systemic anti-inflammatory effects of chronic
prevention of many inflammation-related diseases,
exercise as evidenced by lower levels of circulating mark-
especially cardiometabolic diseases.
ers of inflammation (IL-6 and CRP). In this section, we
will summarize current literature to support regular exer-
Exercise training influences numerous aspects of host
cise eliciting changes in number, function and phenotype
defense and indices of immune function. The field of exer-
of the major leukocyte subsets.
cise and immune function continues to be an active area of
research, and there are documented potential changes in
immunity that are induced by regular exercise or strenu-
ous exercise training. The objective of this chapter is to 44.2 EFFECT OF CHRONIC EXERCISE
identify practical implications of chronic exercise that are
applicable to both fitness exercisers and athletes. The influ- ON INNATE IMMUNITY
ence of chronic exercise on innate and adaptive immunity
will be reviewed along with the effect of excessive exercise 44.2.1 Monocytes and Tissue
training on selected immune parameters and resistance to Macrophages
infection. We will also address the influence of moderate
exercise training on inflammation, wound healing, and Monocytes are circulating cells that have both innate and
the efficacy of vaccines. adaptive immune functions.7 Monocytes can respond to
infection or tissue damage by traveling to the lymph nodes
to become dendritic cells8 or migrating to the site of insult,
where they then differentiate into tissue-specific macro-
44.1 EFFECT OF CHRONIC phages (e.g. Kupfer cells in liver, macrophages in adipose
EXERCISE ON LEUKOCYTE tissue). Antigen presentation and subsequent cytokine
release help to coordinate the responses of the adaptive
NUMBER AND FUNCTION immune system. However, chronic low-grade activation of
the monocyte/macrophage lineage is thought to contribute
Leukocytes are circulating cells of the immune and lym- to the pathophysiology of obesity, insulin resistance,9 and
phatic systems derived from bone marrow hematopoietic development of atherosclerosis.10
547
548 Chapter 44 Chronic Exercise and Immunity
Several researchers highlighted the role of chronic 44.2.2 Natural Killer Cells

exercise-induced alterations in monocyte phenotype/
inflammatory response as a possible mechanism under- Natural killer cells are cytotoxic lymphocytes and a major
lying the anti-inflammatory effects of exercise. In both constituent of the innate immune system. They protect
cross-sectional and longitudinal training studies, subjects against certain tumors and virally infected cells by releas-
who regularly exercised had lower mitogen-stimulated, ing granules containing proteases and porins that induce
ex vivo whole blood production of inflammatory cyto- apoptosis in the target cell. Yan et al. reported that the
kines.11,12 The degree to which Toll-Like Receptor (TLR4) proportion of NK cells (CD16+CD56+) in isolated periph-
is expressed on circulating monocytes may be related to eral blood mononuclear cells was higher in older subjects
mitogen-stimulated cytokine production.13 This finding who exercised regularly than those who did not, 26 but the
may be significant, as monocyte/macrophage TLR4 acti- NK activity against K562 target cells was not different
vation is implicated in the pathophysiology of atheroscle- between these subject groups. Further, there were no dif-
rotic plaque development and peripheral tissue insulin ferences in either NK cell number or activity between exer-
resistance. Indeed, exercise training has elicited decreased cisers and non-exercisers in the young and middle-aged
monocyte TLR4 expression.13–15 Taken together, this groups. In another study, there were no differences in the
emerging evidence implies that regular exercise can reduce expression of NKG2D or NKG2A receptors, but young
expression and reactivity of the innate immune recep- athletes had a greater NK cell activation and degranu-
tor TLR4, an important factor in monocyte/macrophage lation in response to cells from the K562 and .221 cell
activation. lines, though not .221-AEH, when compared with young
Major populations of circulating monocytes are phe- non-athletes. 27
notypically classified based on cell surface expression The differences reported between studies may be
of CD14 and CD16. CD14++CD16− cells are classical attributable to differences between recreationally trained
monocytes, which make up the largest proportion of the individuals and athletes, and the length of time a person
circulating monocyte population.16 CD14+CD16+ mono- has engaged in habitual exercise. For example, endur-
cytes are non-classical “inflammatory” monocytes—a ance-trained older women had greater NK cell activity
subpopulation with a proclivity for production of pro- compared to sedentary older women, but 12 weeks of
inflammatory cytokines. CD14++CD16+ monocytes are moderate aerobic exercise did not alter NK cell activity
called intermediate monocytes, but a range of method- or number in the previously sedentary women. 28 Another
ologies employed in measuring this subpopulation makes factor to consider is infection history, as there is emerg-
it difficult to compare the influence of exercise on inter- ing evidence that latent infections may blunt NK cell
mediate monocytes. Circulating inflammatory monocyte mobilization in response to an exercise bout in trained
percentage is elevated in patients with subclinical athero- adults. 29
sclerosis and obesity.17 This is significant, as inflamma- The results of NK cell exercise/physical activity
tory monocytes adhere robustly to activated endothelial studies are varied, with exercise reported to suppress, 30
cells.18 and may be precursors to CD16+ macrophages increase, 31–34 or not change the cytotoxic activity or num-
found distributed throughout atherosclerotic lesions and ber of natural killers cell.11,35–38 Despite many published
adipose tissue.19,20 Regular exercise training can reduce studies in which the effect of exercise training on NK
the inflammatory monocyte population, 21,22 thus pro- cells has been examined, it appears that a consensus has
viding another potential mechanism by which exercise not been reached. Variables such as age of participants,
reduces inflammation. length of training, and infection history contribute to the
Adipose tissue macrophages are the most dominant reported variability of results. Furthermore, there may
immune cell in adipose tissue. There is evidence that be a need for a more specific NK subset classification,
adipose tissue macrophages in obese persons are more including differentiation status and activation/inhibitory
pro-inflammatory than in lean persons. 23 Furthermore, receptors.
activation of adipose tissue macrophages is associated with
obesity and peripheral tissue insulin resistance, 24 which
may be abated by regular exercise. Bruun et al. reported
44.2.3 Neutrophils
that a 15-week hypocaloric diet and exercise intervention Neutrophils are polymorphononuclear cells and are the
reduced macrophage-specific markers and inflammatory most abundant leukocyte subtype. Neutrophils are the
cytokines in adipose tissue. 25 These effects were concomi- first responders of the innate immune system and migrate
tant with improved insulin sensitivity. to the site of infection or injury within minutes. In ath-
There is strong evidence in support of the concept letes, resting circulating neutrophil number is similar to
that regular exercise can reduce monocyte/macrophage sedentary individuals. 39,40 However, an exercise train-
inflammation, possibly through modulation of TLR4 ing program lowered neutrophil number in overweight
expression and/or altering the phenotype of circulating women with multiple risk factors for cardiovascular dis-
monocyte subpopulations. However, more studies need ease.41 Furthermore, the decrease in neutrophil number
to be conducted to clarify the effect of regular exercise was correlated with improvements in insulin sensitivity.
on adipose tissue macrophage recruitment and activation. It may be that in the context of chronic inflammation,
This body of work is clinically important, as activation such as is evident with CVD, exercise training can impact
of the monocyte/macrophage lineage is implicated in the the neutrophil number. In athletes, however, it appears
pathophysiology of diseases such as diabetes and cardio- that regular intense exercise may reduce neutrophil
vascular disease. function. 28,42,43
44.4 Excessive Training and Immunity 549
44.3 EFFECT OF CHRONIC EXERCISE reference to the short-term condition “overreaching.”
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
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
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
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
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45
CHAPTER
HIV and Exercise

Jason R. Jaggers, PhD and Gregory A. Hand, PhD, MPH, FACSM, FESPM
Key Points.................................................................................. 555 45.5 Treating the Side Effects................................................... 558

45.1 Introduction...................................................................... 555 45.5.1 Treatment of HIV-related Symptoms...................... 558
45.2 HIV Epidemic.................................................................... 556 45.5.2 Exercise as Medicine for Managing Art Toxicities.......558
45.3 Virology and Infection....................................................... 556 45.5.3 Cardiorespiratory Fitness (VO2peak)......................... 559
45.3.1 Primary HIV Infection............................................ 556 45.5.4 Blood Lipids.......................................................... 559
45.3.2 Asymptomatic (Active Latency).............................. 556 45.5.5 Body Composition................................................. 559
45.3.3 Symptomatic........................................................ 556 45.5.6 Immune System.................................................... 559
45.4 Symptomatology of HIV Infection...................................... 556 45.5.7 Psychological Improvements with Exercise........... 560
45.4.1 Psychological Consequences................................ 556 45.5.8 Recommendations for Exercise............................. 560
45.4.2 Physical Consequences......................................... 557 45.6 Conclusion........................................................................ 560
45.4.3 Antiretroviral Therapy............................................ 557 Clinical applications................................................................... 561
45.4.4 Toxic Side Effects.................................................. 557 References................................................................................ 561
the spread of infection have quickly gone from a multi-pill

KEY POINTS daily routine to a single combo-pill. Many people can now
live decades longer and well into old age, but also must
• Investigations have continuously reported signifi-
be more health conscious to offset negative consequences
cant health improvements by modest changes in
from antiretroviral therapy (ART) side effects.
activity.
Although the advances in ART have increased life
• Future research is necessary to determine success-
expectancy, the treatment is not without consequence.
ful motivational- and behavioral-changing interven-
Early into treatment, chief complaints are often psycho-
tions aimed at increasing physical activity for this
logical in nature, which over time either subside or become
population.
more tolerable. However, studies have shown that there
• Routine physical activity has shown to reduce daily
are many physiological consequences, such as increased
stress and circulating cortisol in as little as three
lipids and risk for cardiovascular disease (CVD) and dia-
weeks among people living with HIV/AIDS.
betes.1–3 On top of medication related side effects, there is
• Light-to-moderate intensity levels are sufficient to
still an ongoing social stigmatization that comes with liv-
achieve short-term health benefits as long as the
ing with HIV. Even researchers still struggle to not only
individual stays consistent with their exercise plan.
recruit eligible participants for HIV specific studies but
• There is no evidence to indicate that exercise per-
maintain their participation throughout the study dura-
formed at low-, moderate-, or high-intensity will
tion. This, in turn, makes it more difficult to determine
negatively impact immune function or disease pro-
solid results due to a lack of longitudinal clinical trials
gression in HIV-infected individuals.
and interventions with large datasets.
Due to increased life expectancy and only slight reduc-
tions in new infections, we have also begun to experience
45.1 INTRODUCTION increased prevalence rates. Healthy lifestyle choices, such
as diet and exercise, have now become that much more
Living with HIV has become more of a management of important with this population. Exercise alone has shown
chronic conditions in recent years than the battle of oppor- to have positive impacts on health across all populations,
tunistic infections from a depleted immune system, as it regardless of disease or health status, on both psychologi-
was in the first two decades of the epidemic. Even faster cal and physiological outcomes. Research from our lab
have been the changes in patient symptomatology. With and others have also demonstrated significant improve-
rapid advances in medical science, the pharmacological ments to the health and quality of life for people living
regimens designed to block viral replication and prevent with HIV/AIDS (PLWHA).
555
556 Chapter 45 HIV and Exercise
45.2 HIV EPIDEMIC production. 5,8–10 The appearance of HIV antibodies

detected within plasma begins a period of clinical latency
Statistics reported by the Centers for Disease Control also referred to as seroconversion. With more advanced
(CDC) indicate that the number of new HIV cases reported measurement techniques, it has been shown that during
within the United States declined by 10% between 2010 this stage of clinical latency the virus is actually in a state
and 2014.4 The trend of new cases has varied between of active reproduction. Even though it appears to be in a
specific populations with higher incidence rates often state of inactivity, there is continued infection of nearby
observed among minority male populations and gay males cells and ongoing production of viral strands.
in their mid-20s and 30s. A large number of new cases
also derive from lower socioeconomic backgrounds. On a
global level there is even more concern for both prevention 45.3.3 Symptomatic
and treatment in underdeveloped countries.
The widespread use of ART has successfully increased
Different populations and cultures are plagued by more
the lifespan of PLWHA, with AIDS-related deaths declin-
negative health outcomes and life expectancy. Newborns
ing annually. Instead, PLWHA are more likely to reach
with HIV in third-world countries are a continuing prob-
a stage of “accelerated aging,” referring to the increased
lem, as well as the need for access to proper care and
risk of developing chronic disease(s) known to primar-
treatment. Even within the United States, the population
ily affect uninfected aging populations. Recent evidence
primarily affected by the HIV epidemic will vary depend-
indicates PLWHA are being diagnosed with and/or dying
ing on geographical location as well as access to adequate
from CVD, diabetes, and other metabolic disorders with
healthcare. More rural parts of the country may require
an early age of onset.1,2,11 This is mainly due to the toxic
patients to drive hours to the closest healthcare provider
effects of certain classes of antiretrovirals, which can be
able to serve their health needs. Regardless of location,
found in Table 45.1.
it’s imperative for all PLWHA to have access to specialists
and the medications necessary to maintain a non-detect-
able viral load to help reduce the spread of infection.
45.4 SYMPTOMATOLOGY
OF HIV INFECTION
45.3 VIROLOGY AND INFECTION
45.4.1 Psychological Consequences
45.3.1 Primary HIV Infection PLWHA are burdened with multiple psychosocial stress-
The stage known as primary HIV infection (PHI) is best ors at all stages of illness. Immediately upon diagnosis,
defined as the time between acute viral transmission lasting patients must face life-changing issues such as managing
anywhere from two to six weeks until the onset of antibody the illness, affording appropriate healthcare, and the daily
production.5 Current evidence indicates a massive CD4+ struggles that accompany living with the stigmatization of
cell depletion occurring at mucosal sites within two to three HIV. In addition to these personal stressors, various envi-
days following viral transmission. Using polymerase chain ronmental factors could potentially exacerbate the levels of
reaction (PCR) techniques, Piatak and colleagues indicated stress already experienced such as living in a lower socio-
that viral reproduction was capable of reaching 106 or 107 economic status, facing unemployment, reduced access to
viral particles/mL of plasma within the first two weeks of health care, and many others. The patients’ ability to cope
transmission.6,7 At the onset of viral infection, symptoms
generally appear anywhere within a few days to a couple of TABLE 45.1 Common antiretroviral side effects
weeks. The majority of persons newly infected (70%) expe-
rience mild forms of symptoms generally associated with Toxic side effect from ART Drug class(es)
common colds, the flu, or stomach viruses. Due to the ini- Decreased BMD All
tial symptoms being mild in nature and the fact the PHI is
short in duration, the initial infection often goes unnoticed Cardiac Conduction Impaired PI, NNRTI
until more severe symptoms appear, causing the person to Cardiovascular Disease PI, NRTI
seek medical attention. It is believed that the severity of the
Diabetes Mellitus PI, NRTI
initial symptoms and how the immune system reacts are
indications for disease progression. Dyslipidemia All
Gastrointestinal Disturbances PI, NRTI
Lactic Acidosis NRTI
45.3.2 Asymptomatic (Active Latency)
Lipodystrophy All
Following PHI, there is a sharp increase in viral load as
the virion is being disseminated throughout the entire Psychiatric Disturbances NRTI, NNRTI, INSTI
body and spreading the infection to nearby peripheral Neurological Disturbances All
and distal sites. Generally, within two to four weeks,
the sudden peak in viral load begins to regress, which is Key to Abbreviations: ART= antiretroviral therapy; BMD = bone mineral density;
INSTI = integrase strand transfer inhibitor; NNRTI = non-nucleoside reverse tran-
believed to be the result of the primary immune response scriptase inhibitor; NRTI = nucleoside reverse transcriptase inhibitor; PI = protease
involving cell-mediated immunity in addition to antibody inhibitor
45.4 Symptomatology of HIV Infection 557
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,
psychotropics, and ergot alkaloids (vasoconstrictors). It

TABLE 45.2 2010 Recommendations of the International
has also become evident that when an individual begins
AIDS Society—USA panel to initiating antiretroviral
therapy an ART regimen their risk of developing cardiovascular
disease or diabetes increases every year.
Measure Recommendation
Specific conditions ART is recommended
*Symptomatic HIV Disease
regardless of CD4 cell
count
45.5 TREATING THE SIDE EFFECTS
*Pregnant women 45.5.1 Treatment of HIV-related Symptoms
* HIV-1 RNA > 100,000 copies/ml Additional medications are generally prescribed for viral
*Rapid decline in CD4 cell count symptoms and treatment related side effects. Common
prescription medications taken in addition to ARTs may
*Active hepatitis B or C virus
coinfection
include appetite stimulants, psychoactive drugs, sopo-
rific agents, antidiabetic drugs, analgesics, antibiotics,
*Active or high risk for CVD biophosphonates, calcitonin, or hormone replacements.
*HIV-associated nephropathy Some of the more common antidepressants and anxiolyt-
ics may be prescribed among those beginning an ART
*Symptomatic PHI regimen to assist with maintenance of drug adherence.
*Risk for secondary HIV transmission Studies have consistently shown beneficial results in
adherence to ART when patients are treated with antide-
*Asymptomatic, CD4 cell count ART is recommended
pressants, as well.
<500 µL
The use of additional prescription medications in
*CD4 cell count < 350/µL response to disease and ART side effects has not always
*CD4 cell count 350–500 µL yielded beneficial results. Each ART can have different
interactions with other pharmaceuticals that could further
Key to Abbreviations: ART = antiretroviral therapy; CVD = cardiovascular disease; exacerbate symptoms or even prevent the ART’s primary
PHI = Primary HIV Infection mechanism of action from working, without the patient’s
knowledge. 23 For example, in the treatment of anxiety
lipodystrophy, and insulin resistance, thus creating a in which someone is taking a daily valium or Klonopin
metabolic syndrome. What was once a short-term muscle to treat their anxiety in addition to starting ART, the
wasting disease for people living with HIV that ended in mechanism responsible for inhibiting serotonin reuptake
death over a period of several months has evolved into a may no longer be effective due to specific antiretroviral
chronic metabolic disorder with primary causes of mor- mechanisms. In fact, there are some PI medications, such
tality no longer being AIDS-related. as ritonavir, that metabolize antianxiety or antidepres-
Symptoms and side effects from ART medica- sant medications completely. Because of the unpredictable
tions will vary depending upon specific antiretrovirals reactions that an antiretroviral may have on new prescrip-
included in the patient’s pharmacological regimen, as tions, or even over-the-counter medications, new treat-
well as the total number of antiretroviral medications ment strategies are imperative.
included. Table 45.1 provides a list of antiretrovirals cur- A complementary treatment that may help address
rently available, the toxic side effects, as well as other ART toxicities in viral-related side effects is exercise train-
drug interactions. For example, NRTIs are associated ing. Similar metabolic abnormalities within the general
with lactic acidosis, hepatic steatosis, and lipodystro- population respond positively to prescribed dosages of
phy. Evidence has shown lipodystrophy is more preva- routine exercise designed to increase fitness. These exer-
lent among individuals currently taking a combination cise-induced changes include decreases in total cholesterol
of NRTI and PI, both of which have known side effects and triglycerides, decreased fat mass, increased lean tissue
to stripping metabolic function and disrupting adipo- mass, decreased waist circumference, and increased insu-
cyte mitochondrial function. Other symptoms specific to lin sensitivity. 30–36
the type of an NRTI being taken included pancreatitis
nausea, diarrhea, headache, insomnia, peripheral neu-
ropathy, fatigue, malaise, anemia, and many others. The 45.5.2 Exercise as Medicine for
common side effects outlined in Table 45.1 are those that
directly inhibit exercise performance and or adherence.
Managing Art Toxicities
For a more extensive list of all symptoms and side effects In populations with a broad range of chronic diseases,
please refer to Bartlett et al. and the medical manage- there is a growing body of evidence showing that health
ment of HIV infection. benefits can be obtained by incorporating structured aer-
Further caution must be considered for the possibility obic and resistance exercise into an individual’s recov-
of drug interactions such as PI ritonavir, which has demon- ery and/or treatment plan. For those living with chronic
strated interactions with analgesics, cardiac medications, conditions, aerobic combined with resistance exercises
lipid-lowering agents, antimycobacterial, calcium channel can have positive effects in alleviating symptoms asso-
blockers, antihistamines, antidepressants, neuroleptics, ciated with the diseases and side effects of the medical
45.5 Treating the Side Effects 559
per week. This study also demonstrated that there were

TABLE 45.3 Summary of clinical exercise interventions:
45
additional cardiovascular adaptations such as a reduced
physiological and psychological changes
resting heart rate and a reduced heart rate at submaximal
Response to exercise workloads, which is a cardiovascular adaptation known
as training bradycardia. These findings have also been in
Psychological • ↓depressive symptoms47,50,63
• ↓anxiety51,57 agreement with others.42,43,50–52
• ↑mood state47,51,57,63,64
Physiological • ↑VO2peak41,45,48,51,65,66
• Sig. increases between 2.40–3.71 ml/kg/ 45.5.4 Blood Lipids
min43 Another variable of interest in regard to cardiovascu-
• ↑Strength49,65,67
lar disease risk is the blood lipid panel. Although not as
• ↓Fat mass and waist circumference28,44,47,49,63
• ↓Cortisol47,49 strong as CRF, evidence suggests a potential effect regard-
• ↑GH, IL-6, and sTNFrII49 ing improvements in blood lipids following routine exer-
• Acute increase post exercise cise. Thoni et al. and Grinspoon both showed increases
• Blood lipids44,54 in HDL cholesterol following light-to moderate-intensity
• Conflicting results aerobic exercise. 53,54 Thoni also reported decreases in cho-
Immunological • No change in CD4+51,65,66,68,69 lesterol and triglycerides. However, there is still limited
evidence to draw any formative conclusions regarding
Key: GH: Growth Hormone; IL-6: Interleukin-6; sTNFrII: Tumor Necrosis Factor blood lipids and exercise training. One of the common
side effects of ART includes increased blood lipids and
fat deposits. Future studies should look into the long-term
interventions. Only in the last few years has there been protective effects exercise may have in regard to normal-
an association established between HIV and increased izing blood lipids panels for PLWHA taking ART.
risk of chronic diseases such as CVD and diabetes.1,37– 40
As a result, there is limited evidence to make a definitive
statement as to whether or not exercise is a beneficial
alternative to pharmacological therapy for decreasing 45.5.5 Body Composition
the risk of CVD among PLWHA. Although limited, the As stated previously, an increase in central fat accumula-
data that are available suggest that even modest amounts tion is a common side effect of various ART regimens.
of routine exercise can yield both psychological and Additionally, it is well known that an increased waist cir-
physiological health improvements that are known to cumference is a strong indicator of CVD risk. Multiple
reduce the risk of CVD within the general population. investigations have reported significant improvements in
Table 45.3 provides an overview of the primary findings body composition by decreasing fat mass, waist circum-
that have been discussed in greater detail from previ- ference, and/or body mass index, as well as increasing lean
ous literature reviews.41– 43 Below is a general overview tissue mass (see Table 45.3). More recently Dudgeon et al.
of the main physiological benefits reported within the confirmed these findings by showing significant decreases
literature. in trunk fat and total fat while also increasing lean tissue
mass following a six-week combination aerobic and resis-
tance training intervention.49 Although still limited by the
45.5.3 Cardiorespiratory Fitness (VO2peak) small sample sizes, this evidence appears strong enough to
confirm that benefits in body composition (specifically fat
Most exercise-related interventions measure cardiore- mass and lean tissue mass) that are commonly observed
spiratory fitness (CRF) as a common practice prior to among general populations can be obtained by PLWHA.
any low- or moderate-intensity intervention. As a result,
there is substantial data consistently showing both func-
tional aerobic impairment (FAI) and training adaptations
which increased CRF in as little as six weeks.41,44–48 FAI
45.5.6 Immune System
is defined as a peak VO2 less than 25% of one’s age- In addition to the findings on physiological variables, no
predicted VO2peak. This aerobic impairment results in a significant changes in CD4+ cell count have been reported
reduced CRF level, which is known to be a significant in high- or moderate-intensity exercise groups.42,44,55
indicator of various chronic conditions and all-cause mor- Further, there have been no significant changes from base-
tality.30,31,33,34,36 Even before the introduction of ART, a line reported in CD8+ cell count, leukocytes, or lympho-
common consistency among exercise interventions has cytes following moderate- or high-intensity exercise.56
been significant FAI. Whether this is due to lifestyle fac- Recently it was shown that patients with dyslipidemia
tors or disease-related pathologies is not well understood. and lipodystrophy had no significant changes in immuno-
In a previous investigation from our lab, we have demon- logical variables after completing 12 weeks of moderate-
strated significant improvements in VO2peak and reductions intensity aerobic exercise, as well.52 Notably, there are no
in submaximal heart rate.45,49 Hand et al. shows evidence published reports of exercise-induced immunosuppression
of these findings which suggests that PLWHA can reverse in PLWHA who participated in physical activity regimens
any indications of FAI, even when meeting less than half designed to reduce the psychological or physiological
of the Surgeon General recommendations of 150 minutes symptomatology associated with HIV.
45.5.7 Psychological Improvements exercise program. Even though the majority of PLWHA

have a reduced aerobic capacity, most of the standard
with Exercise physical fitness tests are applicable to this population and
Early investigations conducted prior to widespread use of can be completed with little or no risk to the individual.
ART compared the effects of aerobic exercise on psycho- Table 45.4 outlines potential HIV-associated changes that
logical components, such as depression and anxiety. Eight may be observed during exercise testing and/or training
to twelve weeks of moderate-intensity aerobic exercise according to disease state.
completed twice weekly for 45–60 minutes have shown Ongoing investigations by Jaggers and colleagues have
significant reductions in anxiety and depression.57 Other been studying community-based approaches to facilitating
investigators reported significant improvements after only increases in daily physical activity. Recent results of a nine-
five weeks of aerobic exercise. Men who exercised for 45 month, home-based activity program used accelerometers
minutes a day, three days a week reduced anxiety and to assess changes in activity from baseline. As indicated in
depression upon learning of their seropositive status. 58 the results, the average number of total minutes of daily,
As most of these investigations were performed before moderate-intensity activity was approximately 90 min-
ART, the results are limited to symptoms specific to viral utes, suggesting that the majority of the participants were
progression and not treatment. Further, the majority of already meeting the physical activity recommendations.
the study’s demographics consisted of middle-class, het- However, when looking at step counts, the daily average
erosexual males. Due to the shift in patient demographics was only approximately 5,200 steps per day.47 It is pos-
and treatments, these findings lack generalizability with sible that, with such a deconditioned population, physi-
today’s predominantly impoverished minority seroposi- cal activity prescribed by total minutes, as indicated by
tive populations. It is unknown whether or not the virus, wearable activity monitors, may grossly overestimate the
or any ART medications, would inhibit specific exercise- amount of activity that is being achieved for health ben-
induced psychological improvements that are observed efits. Therefore, it may be a more realistic approach that
among other clinical and healthy populations. recommendations for deconditioned populations such as
In the era of widespread use of ART, there has only been this focus more on gradual increases in daily steps with
one investigation utilizing aerobic exercise as the primary the ultimate goal of 10,000 or more daily steps.
intervention for HIV-associated depressive symptoms.
Like those investigations previously discussed, reductions
in depressive symptoms and/or significant improvements
in quality of life were shown. 50 Findings from this study 45.6 CONCLUSION
suggest that 60 minutes of moderate intensity (60–80%
VO2peak) aerobic exercise conducted three days a week can Evidence would suggest that PLWHA, regardless of dis-
be used as a beneficial method for improving the psycho- ease status, can obtain similar short-term health benefits
logical disturbances experienced by PLWHA. from routine physical activity reported within general pop-
ulations. Research has shown significant improvements
following moderate levels of routine exercise in as little
as six weeks. It is also clear that across various popula-
45.5.8 Recommendations for Exercise tions routine moderate-intensity physical activity reduces
Current exercise training recommendations as described in the risk of chronic disease and that many of these condi-
ACSM’s Exercise Management for Persons with Chronic tions have been established as major causes of morbidity
Disease and Disabilities (4th edition) for PLWHA sug- and mortality among PLWHA. It is therefore imperative
gest a moderate-intensity aerobic and resistance training that healthcare professionals and researchers test various
regimen. 59 This includes accumulating a total of 150 min- approaches to help PLWHA adopt healthy lifestyle choices
utes of moderate-intensity physical activity a week, as well for the rest of their lives.60
as two days of full body resistance training at approxi- In regard to immunity, research among PLWHA has
mately 60% of one repetition maximum. Regardless of demonstrated that aerobic exercise performed at low-,
disease status, it is strongly recommended that anyone moderate-, or high-intensity does not negatively impact
living with HIV or AIDS receive medical clearance from immune function or disease progression at any stage of
their primary health care provider prior to beginning an HIV infection. 52,56,57,61,62 This clearly shows that aerobic
TABLE 45.4 HIV-associated changes to exercise testing

Disease status Response to exercise
Asymptomatic • Physiological parameters within normal limits (e.g. blood pressure, heart rate, VO2)
• Possible functional aerobic impairments due to sedentary lifestyle
Symptomatic • Reduced aerobic capacity and muscular strength
• Possibility of increased heart rate at rest and submaximal work rates
• Increased difficulty in adhering to exercise prescription
• ART related side effects
AIDS • Drastically reduced aerobic capacity and muscular strength
• Possible abnormal neuroendocrine responses at moderate- and/or high-intensity work rates
References 561
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.
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46
CHAPTER
Exercise, Aging, and Immunity

Jeffrey A. Woods, PhD, Yi Sun, PhD, and Brandt D. Pence, PhD
Key Points.................................................................................. 563 46.4 Aging and T Cell-Mediated Immunity................................. 565

46.1 Introduction...................................................................... 563 46.5 Effect of Exercise on T-cell Mediated Immunity in
46.2 Exercise and “Inflammaging”............................................ 563 the Aged........................................................................... 565
46.2.1 Exercise and Inflammaging: Prospective 46.6 Exercise and Humoral Immunity........................................ 566
Training Studies�� 564 46.6.1 Cross-Sectional Studies........................................ 566
46.3 Potential Mechanisms of Anti-inflammatory Effects of 46.6.2 Prospective Training Studies................................. 567
Exercise Training in the Aged............................................ 564 46.7 Conclusion........................................................................ 567
46.3.1 Adipose Tissue Modulation.................................... 564 Clinical Applications................................................................... 567
46.3.2 Cholinergic Anti-inflammatory Pathway................. 564 References................................................................................ 568
46.3.3 Gut Microbiota...................................................... 565
immune function in elderly including reductions in chronic

KEY POINTS low-level inflammation. 2
1. Aging is associated with immunosenescence and a
state of chronic, low-grade inflammation charac-
terized by elevated levels of circulating IL-6, CRP, 46.2 EXERCISE AND
and TNF-α, which may increase morbidity and
mortality.
“INFLAMMAGING”
2. Regular, moderate-intensity exercise training It is recognized that normal aging is associated with a state
may improve antibody and cell-mediated immune of chronic, low-grade inflammation characterized by ele-
responses and reduce the state of chronic inflamma- vated levels of circulating IL-6, C-reactive protein (CRP),
tion in older adults. and tumor necrosis factor (TNF)-α all of which may be
3. The mechanisms of the beneficial effect of exercise involved in the pathogenesis of numerous age-related dis-
training on immune system in the elderly are not eases. This state has been termed “inflammaging”.1 With
fully understood. It is hypothesized that this occurs these findings, therapies and interventions aimed at atten-
by adipose tissue modulation, stimulation of the uating age-induced, low-grade inflammation have come
parasympathetic nervous system, and perhaps alter- to the forefront of behavioral and biomedical research.
ation of the gut microbiome. Exercise may be one such therapy, as both epidemiologi-
cal and longitudinal data suggest increasing physical activ-
ity is an effective means of reducing systemic, low-level
46.1 INTRODUCTION inflammation and chronic inflammatory diseases in aged
individuals. Several large population cohorts such as the
Restoration of immunological function is important for Third National Health and Nutrition Examination Study
the improvement of quality of life of the elderly, as the (NHANES III), the Cardiovascular Health Study (CHS),
aging population is rapidly increasing throughout the and the Health ABC Study support this inverse relation-
world. Potential strategies have included grafting of cells ship, having reported negative correlations between physi-
and tissues, dietary manipulation, anti-oxidant supple- cal activity levels and circulating CRP (all), IL-6 (NHANES
mentation, thymic peptides, endocrine manipulation, and III), and TNF-α (NHANES III).3 Furthermore, this rela-
exercise.1 To date, there have been no widely used strate- tionship appears to occur in a dose-dependent manner, in
gies proven efficacious in restoring immune function in that the lowest levels of inflammatory biomarkers were
the aged. However, there is evidence that regular, moder- observed in elderly persons reporting the highest levels of
ate cardiovascular exercise is related to overall, improved physical activity.3
563
564 Chapter 46 Exercise, Aging, and Immunity
46.2.1 Exercise and Inflammaging: 46.3 POTENTIAL MECHANISMS

Prospective Training Studies OF ANTI-INFLAMMATORY
Given the quantity of cross-sectional evidence suggest-
ing a link between exercise and inflammation, several EFFECTS OF EXERCISE
researchers have conducted longitudinal studies investi-
gating whether exercise training reduces inflammation
TRAINING IN THE AGED
in aged adults. Our lab has published evidence that 10
months of aerobic exercise training (60–70% VO2max)
46.3.1 Adipose Tissue Modulation
was able to reduce serum CRP levels in older adults, with Visceral adipose tissue has become increasingly recog-
no reduction in CRP levels of a similar group that under- nized as a metabolically active organ capable of secreting
went only flexibility exercise.4 Additionally, we found inflammatory signals that can impact whole body physiol-
that reductions in trunk fat associated with cardiovas- ogy. Two recent reports indicate that normal aging leads
cular exercise were the best predictor of the reductions to a dysregulated state in visceral adipose characterized
in systemic inflammation, further supporting the cross- by exaggerated inflammation, and pinpoints adipose tis-
sectional data suggesting that adipose tissue accumula- sue as a primary source of inflammatory mediators during
tion may be at least partially responsible for the increases aging. Wu et al. found that visceral adipose tissue from
in basal inflammation seen in the elderly and other indi- 22- to 24-month-old C57BL/6JNIA mice had increased
viduals.4 In a similar study, Kohut et al. examined the gene expression of IL-1, TNF-α, IL-6, and COX-2 when
effects of 10 months of aerobic exercise (65–80% VO2max) compared to young counterparts.14 In another study, Starr
in elderly men and women compared to a flexibility con- et al. demonstrated that the exaggerated systemic IL-6
trol group. Results demonstrated that aerobic exercise response induced by intraperitoneal lipopolysaccharide
induced significant reductions in serum IL-6, CRP, and administration was highly related to increased expres-
IL-18, while both interventions were sufficient to cause a sion of IL-6 within visceral adipose depots of aged mice
decrease in serum TNF-α. 5 when compared to young controls.15 Accordingly, it has
Nicklas et al.6 reported that a 12-month exercise inter- been hypothesized that exercise training may attenuate
vention including aerobic, strength, balance and flexibility age-induced inflammation via a reduction in both visceral
exercises significantly reduced systemic concentrations of adipose tissue mass and inflammatory profile. Previous
IL-6, but not CRP, compared to the elderly individuals studies from our lab have demonstrated moderate-inten-
who received health education intervention. Additionally, sity exercise training reduces adipose tissue and systemic
the exercise training intervention lowered systemic IL-8 inflammation in obese mice.16,17 The biological mecha-
and IL-15, though the differences were not significant nisms responsible for the anti-inflammatory effects of
after various comparison adjustments.6 Martins et al. exercise within adipose tissue are not known, but could
reported that 16 weeks of both progressive aerobic train- be due to regulation of cellular hypoxia, oxidative stress,
ing and strength training decreased CPR levels in the adipocyte size, macrophage polarization, and energy
elderly.7,8 A 10-week exercise intervention reduced serum sensing pathways. Kawanishi et al. examined the effect
IL-6 and had improvements in perceived stress among of 16-week treadmill running on M1 and M2 macro-
10 older adults.9 In addition, an eight-week whole-body phages’ infiltration into adipose tissue in obese mice. They
vibration exercise program training decreased plasma have shown that exercise training significantly increased
CPR and TNF-α levels in elderly subjects.10 mRNA expression of CD163 in adipose tissue, which
It must be noted that while the presence of a chronic is a specific marker for M2 macrophage, and decreased
inflammatory disease is one of the primary causes of mor- CD11c mRNA expression, which is an M1 macrophage
tality in the aged population,11 a normal, innate immune marker, indicating phenotypic switching from M1 to
response is necessary to protect against infectious dis- the less inflammatory M2 macrophage in adipose tissue.
ease. To this extent, further studies must examine the Exercise training also inhibited TLR4 expression, which
hormetic role of exercise mode, intensity, and duration induces pro-inflammatory cytokine production.18
on maintaining the necessary balance between an ade-
quate inflammatory response and chronic inflammation
in older adults. 46.3.2 Cholinergic Anti-
The majority of the literature supports the anti-inflam-
matory effects of exercise observed in the above-cited inflammatory Pathway
studies; however, several longitudinal studies have failed Work from Kevin Tracey’s lab suggests that stimulation of
to detect reductions in inflammatory biomarkers follow- the parasympathetic nervous system, via the efferent vagus
ing exercise training intervention.12,13 A potential expla- nerve, inhibits pro-inflammatory cytokine production and
nation for the discrepancies between the studies could be protects against systemic inflammation.19 They referred to
attributed to differences in training intensity, duration, this pathway as the “cholinergic anti-inflammatory path-
modality, subject population, and initial inflammatory way,” and described it as a central homeostatic mechanism
profile. Moreover, we know little about the mechanisms by which the sympathetic division of the autonomic nervous
responsible for inflammaging and how exercise might system stimulates the inflammatory response through the
reduce it. Three potential mechanisms involve the roles release of epinephrine and norepinephrine, while the para-
of aging and exercise in regulating body fat, parasympa- sympathetic nervous system works reciprocally to suppress
thetic neural activity, and the gut microbiota. this release of pro-inflammatory cytokine.19 A primary
46.5 Effect of Exercise on T-cell Mediated Immunity in the Aged 565
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
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 intervention 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
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.
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X
PA RT
Pulmonary Medicine
571
47
CHAPTER
Respiratory Symptoms
Jeremy B. Richards, MD and Richard M. Schwartzstein, MD
Key Points.................................................................................. 573 47.4.1 Definition and Physiology...................................... 580

47.1 Introduction...................................................................... 573 47.4.2 Clinical Causes of Cough....................................... 581
47.2 Objective Assessment of Respiratory Symptoms............... 574 47.4.3 Acute Cough......................................................... 581
47.2.1 Objective Dyspnea Scales..................................... 574 47.4.4 Subacute and Chronic Cough with Clear
47.2.2 Pulmonary Function Tests..................................... 574 Chest X-Ray�� 581
47.2.2.1 Spirometry............................................. 574 47.4.5 Chronic Cough with an Abnormal Chest X-Ray...... 582
47.2.2.2 Lung Volume Testing.............................. 575 47.5 Hemoptysis....................................................................... 583
47.2.2.3 Diffusion Limitation of Carbon Monoxide.... 575 47.5.1 Definition and Physiology...................................... 583
47.2.2.4 Pulse Oximetry...................................... 575 47.5.2 Etiology................................................................. 583
47.3 Dyspnea........................................................................... 576 47.6 Wheezing.......................................................................... 584
47.3.1 Definition.............................................................. 576 47.6.1 Definition and Physiology...................................... 584
47.3.2 Physiology of Dyspnea.......................................... 576 47.6.2 Etiology................................................................. 584
47.3.3 Qualities of Dyspnea............................................. 577 47.7 Nocturnal Respiratory Symptoms: Snoring and Apnea....... 585
47.3.4 Essentials of the History........................................ 578 47.7.1 Definition and Physiology...................................... 585
47.3.4.1 Timing: Acute vs. Chronic Dyspnea......... 578 47.7.2 Etiology................................................................. 585
47.3.4.2 Timing: Night vs. Day............................. 579 47.7.3 Essentials of the History........................................ 586
47.3.4.3 Position.................................................. 579 47.8 Conclusion........................................................................ 587
47.3.5 Palliative Management.......................................... 580 Clinical Applications................................................................... 587
47.4 Cough............................................................................... 580 References................................................................................ 587
KEY POINTS 47.1 INTRODUCTION

• Dyspnea is the result of a complicated, multisys- Shortness of breath, cough, and wheezing are among the
tem pathophysiology that results in the sensation of most common symptoms experienced by patients seeking
breathlessness. medical care. As in most areas of medicine, the evaluation
• Understanding the pathophysiologic mechanisms of patients with respiratory symptoms largely depends on
that result in dyspnea can guide the clinical evalu- a comprehensive and insightful history obtained by the
ation and diagnostic testing in a patient with short- physician. Information offered spontaneously by patients
ness of breath. is the starting point in the evaluation of any problem,
• The history and physical exam are critical in identi- but knowledge of the pathophysiology and differential
fying causes of dyspnea and guide the appropriate- diagnoses underlying the symptoms allow the physician
ness and necessity of further diagnostic testing. to probe further, to determine which areas of the physi-
• For patients with a clear chest X-ray and who do cal examination require special attention, and ultimately
not smoke cigarettes or take an ACEI, upper airway to narrow if not eliminate the radiographic and labora-
cough syndrome (UACS), asthma, and GERD cause tory testing required to confirm the diagnosis. We must
the majority of cases of chronic cough. also remember that, as with pain, many patients do not
• Wheezing is caused by turbulent flow due to nar- spontaneously tell healthcare providers about breathing
rowing of intra- and/or extrathoracic airways; intra- discomfort, and it is important to directly inquire about
thoracic airway narrowing results in expiratory this symptom. Often there is confusion between respi-
wheezing, while extrathoracic narrowing causes ratory symptoms and signs. For example, patients are
inspiratory wheezing. described as being “short of breath” as part of the physi-
• Apnea is defined as cessation of breathing for ≥10 cal examination. In fact, symptoms can only be described
seconds, and hypopnea is defined as a reduction of by the patient. Physicians may speculate that a patient is
airflow for ≥10 seconds with a ≥4% decrease in oxy- experiencing respiratory discomfort based on observing
gen saturation. physical signs such as recruitment of accessory muscles
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
47.3 DYSPNEA physiology of cardiac dyspnea is less well understood, but

likely involves many of these mechanisms as well as others
unique to low cardiac output states.
47.3.1 Definition In the presence of increased mechanical load on the
The word dyspnea derives from the Greek term for dif- respiratory system, the motor cortex must increase the
ficult breathing, but has come to represent a more global neural signals it sends to ventilatory muscles to overcome
set of sensations that can be grouped as “breathing the load. These outgoing messages, or efferent signals, are
discomfort.” Dyspnea, or breathlessness, may be expe- associated with a simultaneous corollary discharge to the
rienced by healthy individuals when exercising to the sensory cortex that is hypothesized to provide the individ-
limits of their aerobic capacity, may represent primary ual with a sense of how much “effort” or “work” is being
pulmonary or cardiac disease, or may be a manifestation expended in the act of breathing.12 Dyspnea associated
of a severe metabolic acidosis. In a study of more than with muscle weakness (e.g. myasthenia gravis, Guillain-
1,000 randomly selected adults, investigators discovered Barre syndrome) is also attributable to this mechanism.
the presence of dyspnea in approximately 35% of adult Dyspnea results when the respiratory system does not
patients without known, underlying cardiopulmonary respond as expected for a given level of neural drive to
pathophysiology9; dyspnea is associated with increased breathe, and the larger the discrepancy, the more intense
morbidity and possibly mortality as compared to patients the dyspnea experienced. This discrepancy between respi-
without dyspnea.9–11 ratory center output and the mechanical response of the
Given the frequency with which physicians encoun- system has been termed efferent-afferent or neurome-
ter patients with dyspnea and the varied conditions that chanical dissociation.13–15
may lead to this symptom, having a clear understand- Conditions resulting in a reflexive or automatic
ing of the physiology and causes of dyspnea is critical increase in the neural output from the brainstem respi-
in making a correct diagnosis. A summary of common ratory control centers are also associated with breathing
cardiopulmonary conditions and the associated patho- discomfort, generally described as a sense of “air hun-
physiological mechanisms that cause dyspnea is outlined ger,” or an increased “urge to breathe.” Stimulation of
in Table 47.2. peripheral chemoreceptors by hypoxia and hypercapnia
and stimulation of central chemoreceptors by hypercapnia
and metabolic acidosis is thought to produce dyspnea by
47.3.2 Physiology of Dyspnea this mechanism. Interestingly, inducing either hypoxia or
hypercapnia in healthy volunteers results in similar lev-
Dyspnea associated with respiratory disorders appears
els of “air hunger” for each condition, demonstrating the
to arise due to a variety of physiologic mechanisms that
importance of the corollary discharge from the brainstem
involve stimulation of receptors in the upper airways,
in creating the sensation of dyspnea.16 Stimulation of pul-
lungs, and chest wall, as well as peripheral and cen-
monary mechano- or irritant receptors (e.g. from asthma
tral chemoreceptors (Figure 47.1). In addition, there are
or pulmonary embolism) may also result in an increase in
believed to be neural discharges, termed corollary dis-
ventilation and be responsible for part of the breathless-
charges, between the motor and sensory cortex that are
ness in these conditions.
activated when ventilation is consciously increased. The
Bronchoconstriction is associated with a sensation of
chest tightness,17–19 which is believed to arise from stimu-
TABLE 47.2 Relationship of possible mechanisms of lation of pulmonary receptors by bronchoconstriction.12
dyspnea to selected conditions Studies of the palliative effects of inhaled furosemide
demonstrate decreased dyspnea scores in subjects experi-
Asthma Increased sense of effort encing limited tidal volume excursion, acute hypercapnia,
Stimulation of irritant receptors in airways and resultant breathlessness. 20 The mechanism of action
Neuromuscular Increased sense of effort of inhaled furosemide likely involves stimulation of pul-
disease monary stretch receptors, thereby creating a sensation
COPD Increased sense of effort
that the lung is inflating more than it actually is, resulting
Hypoxia in a decreased sensation of breathlessness. In addition,
Hypercapnia there is likely a psychological effect of the therapeutic
Dynamic airway compression intervention of delivering an inhaled aerosol that contrib-
utes to an expectation of relief of dyspnea with inhaled
Pulmonary Stimulation of receptors in pulmonary
embolism vasculature or right atrium* furosemide. 21
Cardiac dyspnea may occur due to impaired systolic or
Congestive heart Stimulation of J-receptors in the lung diastolic function and resultant high left ventricular dia-
failure Stimulation of receptors in pulmonary
stolic pressure. This leads to increases in pulmonary capil-
vasculature*
Hypoxia lary wedge pressure and, in some instances, transudation
Stimulation of ergoreceptors* of fluid into the pulmonary interstitium and alveoli. As
Increased sense of effort due to reduced a result, the lung becomes less compliant, increasing the
compliance of lung with interstitial fluid respiratory system mechanical load, and hypoxia may
Deconditioning Stimulation of ergoreceptors* occur. Increased pulmonary vascular pressures and stim-
ulation of pulmonary receptors by interstitial fluid may
*Data in support of the listed mechanism are limited. also directly lead to respiratory discomfort. Furthermore,
47.3 Dyspnea 577
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.
low cardiac output states may lead to reduced blood flow

TABLE 47.3 Descriptors of dyspnea
to ventilatory muscles, resulting in muscle weakness and
fatigue. 22 Furthermore, congestive heart failure appears to 1. My breath does not go in all the way.
alter respiratory control mechanisms, leading to increased 2. My breathing requires effort.
levels of ventilation compared to control subjects for any 3. I feel that I am smothering.
given level of exercise. 23 Stimulation of the neural drive 4. I feel a hunger for more air.
5. My breathing is heavy.
to breathe may lead to dyspnea. Finally, there appear to
6. I cannot take a deep breath.
be receptors (ergoreceptors) in the peripheral muscles 7. I feel out of breath.
that are sensitive to increases in byproducts of anaerobic 8. My chest feels tight.
metabolism and may contribute to increased ventilation 9. My breathing requires more work.
and breathing discomfort associated with low cardiac 10. I feel that I am suffocating.
outputs. 24 11. I feel that my breath stops
12. I am gasping for breath.
13. My chest is constricted.
47.3.3 Qualities of Dyspnea 14. I feel that my breathing is rapid.
15. My breathing is shallow.
Do patients with CHF, COPD, pulmonary embolism, and 16. I feel that I am breathing more.
17. I cannot get enough air.
asthma all experience the same sensations of respiratory
18. My breath does not go out all the way.
discomfort? Can we differentiate distinct types of dyspnea 19. My breathing requires more concentration.
by the questions we ask patients? Studies demonstrate that
dyspnea, like pain, is actually multiple, qualitatively dis-
tinct sensations and that attention to the “language of dys-
pnea” can provide insights into a patient’s disease. From these and related studies, a language of dyspnea
Using a questionnaire (Table 47.3) derived from inter- has emerged (Table 47.4). Patients with bronchoconstric-
views with patients and studies in which normal subjects tion commonly describe a sensation of “chest tightness.”
were made breathless while performing a range of venti- Increased mechanical loads (typical of airway obstruc-
latory tasks, 25 various cardiopulmonary conditions asso- tion), interstitial disease, and chest wall abnormalities,
ciated with dyspnea could be characterized by a unique usually result in increased “effort of work” of breath-
set of verbal phrases.18 These findings were confirmed in ing. Neuromuscular weakness produces a sensation of
an investigation using a similar approach, but with an increased effort to breathe. Significant hyperinflation, as
expanded questionnaire.19 Responses offered by patients in severe COPD, may cause a sensation of an “inability
when asked to describe their breathing discomfort have to get a deep breath”. 26 In experimental conditions, acute
been shown to be reproducible over time. 21 hypercapnia produces a discomfort characterized as “air
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
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 47.6 Selected causes of cough stimulation

Anatomic location Mechanism of cough stimulation
Larynx Activation of epithelial irritant receptors
Trachea and large airways Activation of epithelial irritant receptors
Lung parenchyma Activation of stretch receptors
Activation of C fibers
Pleural space Activation of irritant receptors
Esophagus Reflex mechanism in response to reflux of gastric acid
Tympanic membrane Stimulation of irritant receptors in the external auditory canal
47.4 Cough 581
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
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
Although cough due to lower respiratory infections

TABLE 47.8 Etiologic categories for hemoptysis
47
usually presents acutely, there are indolent infections that
can present with a chronic cough and minimal systemic Pulmonary infections
symptoms. PCP pneumonia (i.e. pneumonia caused by
Neoplasms
Pneumocystis jerovici) in patients with acquired immu-
nodeficiency syndrome due to human immunodeficiency Collagen-vascular and immunologic lung diseases
virus is characterized by a nonproductive cough and dys- Cardiovascular diseases (including pulmonary vascular and
pnea on exertion over weeks to months. Similarly, early valvular diseases)
reactivation of Mycobacterium tuberculosis can present
with cough, fatigue, and mild weight loss. A chest X-ray Congenital or acquired vascular disease (arteriovenous
malformation)
usually provides evidence of the underlying infection.
Structural parenchymal disease (cavitary lesion)
47.5 HEMOPTYSIS Structural airway disease (bronchiectasis)

Infection (bacterial pneumonia, invasive fungal pneumonia)
47.5.1 Definition and Physiology Aspiration of foreign bodies
Hemoptysis refers to coughing or expectoration of blood Chest trauma with pulmonary contusion
or blood-tinged sputum. As a general principle, the term is
reserved for blood that originates in the lower respiratory
tract (i.e. below the larynx). However, it may be difficult on the presence or absence of additional symptoms beyond
to determine whether blood is coming from the lungs vs. hemoptysis itself.
the posterior nasopharynx or the gastrointestinal tract, Lower respiratory tract infections cause airway inflam-
especially if vomiting is associated with a paroxysm of mation, which can result in epithelial injury and bleeding.
cough. It is worth noting that the normal tracheobronchial This is most common with bacterial tracheobronchi-
tree should not bleed even in the presence of coagulopathy. tis, but it can also occur with bacterial pneumonias.
Thus, hemoptysis in the setting of anticoagulation should Typically, hemoptysis in the setting of an acute infection
be considered a pathologic finding. is small in volume (<50 mL) and resolves with improve-
The four major sources of blood in the lower respira- ment in the other symptoms (e.g. cough, fever, malaise).
tory tract are airways, pulmonary parenchyma, pulmo- Bronchiectasis and chronic bronchitis predispose patients
nary circulation, and bronchial circulation. Inflammation to acute infections and are associated with occasional epi-
or irritation of airway epithelium (e.g. with acute pulmo- sodes of blood-streaked sputum, typically in the presence
nary infections, chronic bronchitis, or foreign body aspi- of an acute infection. Bronchiectasis infrequently leads to
ration), usually results in small volume hemoptysis, often massive hemoptysis.
mixed with sputum. Bleeding from the pulmonary paren- Lung cancers, most commonly bronchogenic carci-
chyma occurs with pulmonary infarction or contusion. noma, are a common cause of hemoptysis. Lung cancer
In the presence of pulmonary AVMs or greatly elevated should be especially considered in patients over the age
pulmonary venous and/or capillary vascular pressures of 40 with a significant smoking history and more than
(e.g. from mitral stenosis) bleeding may occur as well. 10 days of hemoptysis.51 Patients with an extrathoracic
Finally, the bronchial circulation may result in hemoptysis malignancy that can metastasize to the lungs (e.g. breast
in patients with bronchiectasis or large intrapulmonary carcinoma or sarcoma) are at increased risk of hemoptysis
cavities. due to cancer. Bleeding due to cancer usually occurs in the
Massive hemoptysis is generally defined as production absence of other symptoms and presents as frank blood
of ≥600 mL of blood in 24 hours; however, the precise vol- without sputum.
ume qualifying as “massive” hemoptysis varies between Hemoptysis in association with joint symptoms, rashes,
authors and guidelines. Patients commonly overestimate dyspnea and/or renal dysfunction suggests collagen-vas-
the amount of blood they have expectorated because of cular disease as an etiology. Pulmonary-renal syndromes,
concomitant anxiety. Therefore, it is important to encour- (e.g. systemic lupus erythematosus, granulomatosis with
age the patient to be as explicit as possible when quantify- polyangiitis [previously referred to as Wegener’s granulo-
ing the amount of blood. One should show the patient, matosis], and Goodpasture syndrome) may present with
and witnesses to the episode, various-sized containers to hemoptysis as part of the symptom complex. In most
assist them in estimating the quantity expectorated. While cases, hemoptysis is not an isolated finding.
massive hemoptysis can occur from an endobronchial car- Pulmonary emboli, AVMs, pulmonary edema, and
cinoma, it is more commonly associated with erosions of mitral stenosis are cardiovascular causes of hemopty-
bronchial vessels in large intrapulmonary cavities or with sis. Pulmonary edema classically produces pink sputum
bronchiectasis. 50 and lung biopsy reveals hemosiderin-laden macrophages
consistent with pulmonary hemorrhage. Gross blood is
uncommon in CHF without concomitant coagulopathy.
47.5.2 Etiology Bleeding may occur as the first symptom of an AVM, and
There are 10 etiologic categories to be considered when massive hemoptysis has been reported.52 Hemoptysis from
evaluating a patient with hemoptysis (Table 47.8). pulmonary emboli or mitral stenosis usually occurs with
Determining the reason for a patient’s hemoptysis depends other symptoms such as dyspnea and chest discomfort.
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
TABLE 47.10 Epworth sleepiness scale

How likely are you to doze off or fall asleep in the following situations, in contrast to just feeling tired? This refers to your usual way of life
in recent times. Even if you have not done some of these things recently try to work out how they would have affected you. Use the
following scale to choose the most appropriate number for each situation:
0 = would never doze
1 = slight chance of dozing
2 = moderate chance of dozing
3 = high chance of dozing
Situation Chance of Dozing
Sitting and reading
Watching TV
Sitting, inactive in a public place (e.g. a theater or a meeting)
As a passenger in a car for an hour without a break
Lying down to rest in the afternoon when circumstances permit
Sitting and talking to someone
Sitting quietly after a lunch without alcohol
In a car, while stopped for a few minutes in the traffic
TABLE 47.11 Mechanisms of end-organ damage in the OSA syndrome

Pathophysiologic mechanism Systemic effects End-organ consequences
Increased sympathetic tone due to apneas/ Increased systemic vascular resistance Hypertension
hypopneas Cardiovascular disease
Cerebrovascular disease
Increased systemic inflammation due to Accelerated atherosclerosis Coronary artery disease
intermittent hypoxemia Cerebrovascular disease
Peripheral vascular disease
Systemic oxidative stress due to cyclical Atherosclerotic changes Cardiovascular disease
hypoxemia and reoxygenation Tissue ischemia Cerebrovascular disease
Endothelial dysfunction (uncertain Increased thrombogenesis Coronary artery disease
mechanism) Cerebrovascular disease
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.
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48
CHAPTER
Asthma
David E. Ciccolella, MD and Gilbert E. D’Alonzo, DO
Key Points.................................................................................. 589 48.5.7 Reslizumab......................................................... 597

48.1 Introduction...................................................................... 589 48.5.8 Benralizumab..................................................... 597
48.2 Clinical Features............................................................... 590 48.5.9 Bronchial Thermoplasty...................................... 597
48.3 Pathophysiology............................................................... 590 48.5.10 Quick-Relief Medications.................................... 598
48.3.1 Variable Airflow Obstruction.................................. 590 48.6 Management of Asthma according to Severity and
48.3.2 Airway Inflammation............................................. 590 Control Classification........................................................ 598
48.3.3 Airway Hyperresponsiveness................................. 591 48.6.1 Other Issues in Long-Term Asthma Management..... 600
48.3.4 Management........................................................ 591 48.6.2 Asthma Complications........................................ 600
48.3.5 Monitoring Disease Activity................................... 592 48.6.3 Allergy Testing and Immunotherapy.................... 601
48.4 Treatment......................................................................... 593 48.6.4 Exercise and Asthma.......................................... 602
48.4.1 Environmental Control........................................... 593 48.6.5 Occupational Asthma.......................................... 603
48.4.2 Indoor Allergens.................................................... 594 48.6.6 Obesity............................................................... 604
48.4.3 Outdoor Allergens................................................. 594 48.6.7 Stress................................................................. 604
48.5 Pharmacologic Therapy.................................................... 595 48.6.8 Food Hypersensitivity.......................................... 604
48.5.1 Chronic Controllers............................................... 595 48.6.9 Medication-Induced Asthma............................... 604
48.5.2 Long-Acting Beta-2 Agonist.................................. 596 48.6.10 Gastroesophageal Reflux.................................... 605
48.5.3 Long-Acting Muscarinic Antagonists..................... 596 48.6.11 Pregnancy and Asthma....................................... 605
48.5.4 Biologic Therapies................................................ 596 Clinical Applications................................................................... 606
48.5.5 Omalizumab......................................................... 596 References................................................................................ 606
48.5.6 Mepolizumab........................................................ 597
• To meet patient and family expectations for

KEY POINTS asthma care.
• To provide optimal pharmacotherapy with min-
• Asthma is an inflammatory disease of the airways
imal adversity.
characterized by intermittent symptoms, including
• A comprehensive asthma management plan includes
chest congestion, cough, and wheezing. These symp-
both environmental control and medication therapy.
toms are associated with airway responsiveness and
variable airflow obstruction.
• Airway narrowing leading to increased airway resis-
tance, and airflow obstruction in asthma occurs 48.1 INTRODUCTION
through three major mechanisms:
• Airway smooth muscle contraction. Asthma is an inflammatory disease of the airways char-
• Increased airway lumen debris. acterized by intermittent symptoms, including chest
• Airway wall thickening from inflammation, congestion, cough, and wheezing. These symptoms are
edema, and over time, fibrosis. associated with airway responsiveness and variable air-
• The goals of asthma therapy are as follows: flow obstruction.
• To prevent symptoms and help the patient In 2016, approximately 20.4 million adults repre-
achieve normal lung function and activity, espe- senting 8.3% of the population in the United States had
cially during exercise. asthma.1,2 Despite the constant development of new medi-
• To prevent exacerbation of asthma, no matter cations to treat asthma over the last decade, this disease
how mild. remains a large burden to the healthcare system, account-
• To minimize the need for emergency department ing for up to 6.2% of physician outpatient visits and emer-
visits or hospitalizations. gency department visits of 1.7 million. Asthma remains a
589
590 Chapter 48 Asthma
frequent cause of absenteeism from both school and work.

Most concerning is that approximately 3,615 deaths
48.3 PATHOPHYSIOLOGY
occurred in the United States in 2015, representing about
11 per million population. 3
48.3.1 Variable Airflow Obstruction
The prevention and treatment of asthma are highly Airway narrowing leading to increased airway resistance,
dependent upon a variety of interventions, both phar- and airflow obstruction in asthma occurs through three
macologic and non-pharmacologic. The daily habits and major mechanisms:
activities of patients with asthma play an important role
in disease management and prevention. Minor altera- • Airway smooth muscle contraction.
tions in lifestyle practices can make substantial differ- • Increased airway lumen debris.
ences in the long-term health of the asthmatic patient. • Airway wall thickening from inflammation, edema,
This chapter focuses on the traditional asthma topics and over time, fibrosis. 2
of pathogenesis, diagnosis, and treatment. In addition, the
environmental issues important to asthma are discussed. Damaged epithelial cells detach from the mucosal
Asthma symptom prevention and enhanced control of surface of the asthmatic airways. Airway wall thickening
disease are stressed, and the effects of exercise, occupa- occurs in patients with persistent asthma resulting from an
tion, stress, and pregnancy on asthma are discussed. unimpeded inflammatory process. The effects of inflam-
mation accumulate over time, leading to smooth muscle
hypertrophy, epithelial basement membrane thickening,
48.2 CLINICAL FEATURES connective tissue deposition, and proliferation and hyper-
trophy of mucus-producing glands). All of these factors
Clinical symptoms of asthma are dyspnea, cough, contribute to progressive airflow obstruction, which is fur-
chest congestion and tightness, and noticeable wheez- ther decreased by the presence of thick, tenacious mucus,
ing. Milder cases of asthma may only be recognized by ineffective mucociliary clearance, and edema in the walls of
a cough, which is worse at night, or dyspnea during or the bronchi, especially during an acute asthma exacerba-
following exertion. Many of the more severe attacks of tion. Episodic smooth muscle contraction further leads to
asthma begin with some or all of the symptoms above the variability of symptoms in asthma.
occurring for several days before the patient seeks medi-
cal help; however, a minority of patients have a rapid
onset of severe symptoms over just a few minutes or
hours. Very severe attacks may lead to respiratory failure
48.3.2 Airway Inflammation
requiring tracheal intubation and mechanical ventilation Multiple mechanisms produce airway inflammation,
to avoid death. and they involve a variety of interactions between pro-
An asthma patient may be able to identify a certain trig- inflammatory and inflammatory mediators. The asth-
ger that destabilizes his or her asthma. Often symptoms matic inflammatory cell matrix is made of eosinophils,
occur during exercise, viral infection, exposure to furry or activated T-helper type 2 lymphocytes, mast cells, neutro-
feathered animals, or exposure to environments laden with phils, macrophages (Figure 48.2). Both immune and non-
dust, mold, smoke, or other noxious fumes or chemicals. immune factors can activate the disease process. When an
Changes of weather, emotions such as laughing or crying, asthmatic is exposed to a specific activating allergen, the
and menses may destabilize the asthmatic patient. There release of a variety of mediators occurs via high-affinity
are certain patients who have attacks following the inges- immunoglobulin E (IgE) receptors, which are found on
tion of aspirin or other medications. Eczema, hay fever, bronchial mast cells, and low-affinity IgE receptors on
rose fever, or a family history of asthma is often associ- macrophages and eosinophils. Lymphocytes control these
ated with asthma, but their presence is not required for its processes. Both antibody-mediated and cell-mediated
diagnosis. immune systems are involved. There are increased levels
The asthmatic will often have a normal physical of pro-inflammatory cytokines such as IL-4, IL-5, IL-13.
examination when asthma is not active. However, when The chemical mediators from these activated cells can
patients are having asthma symptoms the physical exami- directly contract airway smooth muscle, stimulate mucus
nation often reveals an increase in respiratory rate with a secretion, enhance vascular permeability, and result in
prolonged expiratory time and wheezing. On forced expi- airway edema, all of which contribute to airflow obstruc-
ration, wheezing is accentuated and coughing generally tion. Furthermore, some mediators actually attract other
occurs. During more severe asthma attacks, the patient inflammatory cells and activate them, and these activated
will often use the accessory muscles of ventilation, their cells further damage the airway. Part of the inflammatory
chest appears to be hyperinflated, and they may be dia- reaction causes a disruption of airway epithelial cell wall
phoretic and not able to speak in full sentences. These integrity, which allows increased permeability to inhaled
clinical features of asthma have been used to develop allergens and other triggering substances and decreases
a clinical classification of asthma severity based on the mucociliary clearance of airway debris, enhances cholin-
frequency of these symptoms and nighttime awakenings, ergic-mediated airway hyperreactivity, and predisposes
interference with activities, lung function impairment, asthma patients to bacterial and viral infections. The
and the frequency of exacerbations (Figure 48.1). 2 loss of epithelial integrity exposes nerve endings, which
48.3 Pathophysiology 591
48
Figure 48.1 Classification of asthma severity.
(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
Inflammatory Stimuli 48.3.5 Monitoring Disease Activity

The goals of asthma therapy are as follows: (1) to prevent
symptoms and help the patient achieve normal lung func-
Cell Activation/Mediator Release: tion and activity, especially during exercise; (2) to prevent
exacerbation of asthma, no matter how mild, (3) to mini-
Eosinophils Mast cells Macrophages mize the need for emergency department visits or hospi-
T Lymphocytes Neutrophils talizations; (4) to meet patient and family expectations for
asthma care; and (5) to provide optimal pharmacotherapy
Bronchial Epithelial Cells with minimal adversity. 2
To ensure that these goals are met, periodic assessment
and ongoing monitoring of asthma daytime and noctur-
nal symptoms, short-acting beta agonist use for symptom
Asthmatic Inflammation
relief and symptom interference of daily activities, and
measurement of airflow obstruction by spirometry and
peak expiratory flow are recommended. 2 Both physician
Airway Hyperresponsiveness Airway Obstruction assessment and patient self-assessment are part of the
asthma monitoring process.
Measurements of airflow are known not to be
strongly related to asthma symptoms but provide a more
AsthmaSymptoms objective and additional measure to evaluate asthma
control. Spirometry is recommended at least every one
to two years and especially at initial assessment, after
Figure 48.2 Steps involved in the asthmatic inflammatory
treatment has stabilized symptoms and peak flow, and
cascade. These include the introduction of inflammatory stim-
uli to cell activation and mediator release, to asthmatic inflam-
during progressive or prolonged worsening of asthma. 2,5
mation and bronchial hyperresponsiveness, and finally clinical The patient performs spirometry by taking a deep breath
asthma. and forcefully exhaling air from the lungs through a
spirometer until all airflow has ceased.6,7 As shown in
Figure 48.4, airflow obstruction is shown by a decrease
Dose-response curves of methacholine challenge in the forced expiratory volumes, the forced vital capac-
pre-challenge ity (FVC), and the forced expiratory volume in one sec-
100 Normal control ond (FEV1) and a decreased FEV1/FVC ratio. The main
90 factors for determining normal ranges for these param-
PC22 - Provocation concentration eters are age, height, and gender. Abnormalities in these
80
producing 20% fall In FEV1 parameters are typically based on the appropriate refer-
70
ence population using 95% confidence intervals and not
Percent FEV1
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,
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
that may occur. 29 The immunotherapy should be directed

TABLE 48.1 Long-term control and quick-relief therapies
48
at a single or only a very few antigens. There is a pau-
for asthma
city of data support for use of multiple-allergen mixes.
The responses to therapy may be specific to the allergen Long-term control Quick-relief
extracts and regimens used and it has been recommended
Inhaled Corticosteroids Short-acting beta-2 agonists
to use those allergen extracts shown to have efficacy in
clinical trials.13 Finally, the optimal duration of allergen Cromolyn Systemic Corticosteroids
therapy is not clear but typically is three to five years, and Leukotriene Modifiers Ipratropium bromide
a recognizable favorable improvement in asthma should
occur early in treatment. Long-Acting Bronchodilators
• Long-acting beta-2 agonists
• Theophylline
48.5 PHARMACOLOGIC THERAPY • Tiotropium
Systemic Corticosteroids
The pharmacologic treatment of asthma includes two
Anti-IgE Therapy
broad categories of drugs: bronchodilators that relax
airway smooth tissues and anti-inflammatory drugs that • Omalizumab
reduce the influx of inflammatory cells and the release Anti-IL-5 Ab and –IL-5-Receptor Ab
of chemical mediators from these cells. Bronchodilators
include short- and long-acting beta-2 receptor agonists • Mepolizumab
• Reslizumab
(beta agonists), methylxanthines, and anticholinergics.
• Benralizumab*
Anti-inflammatory agents include glucocorticoids, cro-
molyn, leukotriene blockers, omalizumab, and anti-IL-5 Immunotherapy
monoclonal antibodies.
* IL-5 Receptor Ab.
In the chronic management of asthma, pharmacologic
therapy is given by the oral or inhalation route, but inha-
lation therapy seems to be the preferred because of the However, some patients with severe chronic disease may
higher concentration of medication directly delivered to require systemic corticosteroid therapy on a regular basis.
the lungs, often with greater efficacy and lower risk of Corticosteroids reduce airway inflammation and airway
adverse effects.30 The inhalation of medication can be per- hyperresponsiveness.32–35 Glucocorticoids also prevent
formed through a small-volume nebulizer or a metered- asthmatic exacerbations and bronchial wall remodeling,
dose inhaler. An inhaler is sometimes attached to a tube known to occur with chronic inflammation and to be
spacer device, in order to reduce certain oropharyngeal responsible for the development of fixed airflow obstruc-
adverse effects and, for some patients, enhance aerosol tion later in life. There are many different products and
drug delivery into the lungs. 2 delivery devices for the administration of inhaled cortico-
Medications are characterized into two general treat- steroids, and their inhalation doses vary. 2 The lowest daily
ment classes: long-term control medications, which are dose of an inhaled corticosteroid should be used in order
used to achieve and maintain control of chronic asthma, to control the disease.
and quick-relief medications, or relievers, which treat acute Leukotriene receptor blockers and synthesis inhibitors
symptoms during an asthma exacerbation (Table 48.1). 31 are another group of anti-inflammatory agents. These are
The most effective medications for long-term controller oral therapies that block or inhibit the production of leu-
therapy are those that have clearly demonstrated anti- kotrienes, which are by-products of the arachidonic acid-
inflammatory effects. metabolic pathways and are potent bronchoconstrictors
The U.S. National Asthma Education and Prevention and inflammatory stimulants in humans.36 Leukotrienes
Program (NAEPP 2007) Guidelines for Asthma recom- are released from a variety of inflammatory cells, such as
mend the use of these medications for asthmatics based lymphocytes, eosinophils, and mast cells, and not only
on severity using a step therapy approach from 1–6. induce bronchoconstriction but increase vascular perme-
There are also more recently updated Global Initiative for ability, mucous secretion, and other inflammatory cells.
Asthma guidelines in 2018 (GINA 2018) which use step When these additional cells enter the airway, they are acti-
therapy from 1–5. vated and release other powerful chemicals that propagate
the inflammatory state even further. 36
There are three agents currently being used in the
United States; they are montelukast and zafirlukast (which
48.5.1 Chronic Controllers are leukotriene receptor blockers) and zileuton, a 5-lipox-
Corticosteroids are the most potent and effective anti- ygenase inhibitor. Zileuton acts earlier in the arachidonic
inflammatory medications available for the manage- acid/leukotriene pathway and could have greater effects.
ment of asthma. The inhaled form of medication from Zileuton is taken twice a day and requires liver function
a metered-dose inhaler is used for the long-term control monitoring. Leukotriene-pathway agents improve lung
of asthma. Systemic corticosteroids, administered orally, function, diminish asthma symptoms, and reduce the
are used to gain control of asthma following a period of need for the use of short-acting inhaled rescue beta ago-
destabilization and are avoided for long-term control. nists.37–40 Their efficacy has been shown in patients with
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.
48.5.6 Mepolizumab 48.5.9 Bronchial Thermoplasty

Mepolizumab is a monoclonal antibody antagonist to The airways of chronic asthmatics are narrowed by
IL-5, the major cytokine involved in the production and increased wall thickness due to several mechanisms,
survival of eosinophils, that is used for the treatment of including airway smooth muscle hypertrophy. Bronchial
patients 12 years and older with severe persistent asthma thermoplasty targets the airway smooth muscle and can
with eosinophilia.76 Studies suggest that a blood eosin- be considered for uncontrolled severe persistent asthmat-
ophil count of 150 or more is important for efficacy.77 ics who are not candidates for either omalizumab or anti-
Mepolizumab 100 mg subcutaneously injected every four IL-5 therapies.85 Bronchial thermoplasty is a technique
weeks has a glucocorticoid-sparing effect and reduces that delivers radiofrequency wave generated heat to the
asthma exacerbations in general by 53% and reduces walls of airways (approximately 3–10 mm diameter) to
exacerbations requiring emergency department care or reduce airway smooth muscle hypertrophy and contrac-
inpatient hospitalization by 61%.78–80 Recommendations tility.85 The airways distal to the main stem bronchi are
from GINA 2018 guidelines indicate that it should be treated in a systematic manner during three separate
considered for severe persistent asthmatics in step 5 bronchoscopies of 30–60 minutes each, spaced about
(inadequately controlled on step 4 treatment high-dose three weeks apart. Bronchial thermoplasty compared to
inhaled corticosteroids and LABAs).13 Although the control appears to reduce severe exacerbations and ED
mechanism of action of mepolizumab is not fully under- visits but not hospitalizations, and has a controversial
stood, it reduces the production and survival of eosino- marginal improvement in the quality of life. Long-term
phils, ultimately reducing blood and sputum eosinophils, benefit and safety are unknown.85 In addition to being a
which may reduce airway inflammation.78 Mepolizumab poorly controlled (never smoker or greater than one year
may increase the risk for herpes zoster infection, and it is ex-smoker) asthmatic, there are several other criteria to
especially important to determine if the patient has had meet for bronchial thermoplasty, including FEV1 >60%
the chicken pox or the chicken pox vaccine. The safety of predicted since more severe asthmatics were excluded
of mepolizumab during pregnancy is unknown, and it is from the sham-controlled trial.13,86 Although bronchial
important to know if the patient is pregnant or planning thermoplasty may be of benefit in certain severe asth-
on becoming pregnant. There is a registry for women matics, further studies are needed on the long-term
who are on mepolizumab while pregnant. Mepolizumab efficacy and safety of bronchial thermoplasty in other
may cause allergic hypersensitivity reactions, including severe asthma populations.13 The European Respiratory
anaphylaxis. The most common side effects of mepoli- Society/American Thoracic Society (ERS/ATS) 2014
zumab include a headache, injection site reactions (pain, Task Force on severe asthma recommends that bronchial
redness, swelling, itching, or burning), back pain, and thermoplasty be done in an IRB-approved registry or
weakness/fatigue. clinical study.12
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
Figure 48.6 Classification of asthma control.
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.
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
TABLE 48.2 Referral to asthma specialist for consultation or co-management

1. Patient has had a life-threatening asthma exacerbation.
2. Patient has needed more than two bursts of oral corticosteroids in one year or required hospitalization.
48
3. Patient is not meeting the goals of asthma therapy after three to six months of treatment or is unresponsive to therapy.
4. Diagnosis unclear
5. Conditions complicating asthma or its diagnosis (e.g., sinusitis, nasal polyps, aspergillosis, severe rhinitis, VCD, GERD, COPD,
psychosocial problems).
6. Further diagnostic studies needed) is needed (e.g., allergy skin testing, rhinoscopy, complete pulmonary function studies,
provocative challenge, bronchoscopy).
7. Consideration for immunotherapy.
8. Patient requires step 4 care or higher, or even consider referral for step 3 care.
9. Patient education and guidance on complications of therapy, problems with adherence or allergen avoidance.
10. Confirmation of possible occupational or environmental inhalant or ingested substance contributing to asthma.
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
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, partic 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
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
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
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
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.
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49
CHAPTER
Occupational and Environmental

Lung Diseases
Sunkaru Touray, MBChB, MSc, Emil Tigas, MD, and Nicholas A. Smyrnios, MD, FACP, FCCP
Key Points.................................................................................. 611 49.2 Clinical Presentation and Diagnosis.................................. 615

49.1 Work-Related Asthma....................................................... 611 49.3 Treatment and Prevention................................................. 616
49.1.1 Epidemiology...................................................... 611 49.3.1 Coal Mine Dust Lung Disease................................ 616
49.1.2 Clinical Presentation and Diagnosis.................... 612 49.3.2 Epidemiology........................................................ 616
49.1.3 Prevention and Treatment................................... 612 49.4 Clinical Presentation and Diagnosis.................................. 616
49.1.4 Chronic Obstructive Pulmonary Disease.............. 612 49.5 Prevention and Treatment................................................. 616
49.1.5 Epidemiology...................................................... 612 49.5.1 High-Altitude Illnesses.......................................... 616
49.1.6 Clinical Presentation and Diagnosis.................... 612 49.5.2 Acute Mountain Sickness and High Altitude
49.1.7 Prevention and Treatment................................... 613 Cerebral Edema�� 617
49.1.8 Non-pharmacologic Therapy............................... 613 49.5.3 High Altitude Pulmonary Edema............................ 617
49.1.9 Pharmacologic Therapy...................................... 613 49.5.4 Prevention and Treatment..................................... 617
49.1.10 Asbestos-Related Lung Disease........................ 613 49.5.4.1 Controlled Ascent................................... 617
49.1.10.1 Epidemiology..................................... 614 49.5.4.2 Acetazolamide........................................ 617
49.1.11 Clinical Presentation and Diagnosis..................... 614 49.5.5 Hypersensitivity Pneumonitis................................ 618
49.1.12 Silicosis.............................................................. 614 49.5.6 Epidemiology........................................................ 618
49.1.13 Epidemiology...................................................... 614 49.6 Clinical Presentation and Diagnosis.................................. 618
49.1.14 Clinical Presentation and Diagnosis..................... 614 49.6.1 Treatment and Prevention..................................... 618
49.1.15 Prevention and Treatment................................... 615 Clinical Applications................................................................... 618
49.1.16 Berylliosis........................................................... 615 References ................................................................................ 618
49.1.17 Epidemiology...................................................... 615
content. Treatment consists of descent, supplemen-

KEY POINTS tal oxygen, and occasionally medication.
• Work-related asthma is responsible for about
15– 20% of adult asthma and is associated with high
morbidity, disability, and costs.
• Chronic Obstructive Pulmonary Disease is a leading
49.1 WORK-RELATED ASTHMA
cause of morbidity and mortality globally, especially
among non-smokers with occupational exposure to
49.1.1 Epidemiology
noxious fumes from the combustion of biomass fuel. Asthma affects about 8% of the adult U.S. population,
• Silica, coal, asbestos, and beryllium are important and it is estimated that about 15– 20% of patients with
causes of occupational lung disease among work- asthma have work-related asthma (WRA).1 Work-related
ers in the mining, automotive, and construction asthma is a chronic inflammatory lung disease character-
industries. ized by the presence of reversible airway narrowing fol-
• Hypersensitivity pneumonitis is an immunologi- lowing exposure to airborne dust, gases, or fumes in the
cally mediated lung disease caused by exposure to a work environment. Work-exacerbated asthma (WEA) is
variety of inducing agents. The cornerstone of treat- a subset of WRA, which describes asthma that worsens
ment is avoidance of exposure and in some cases in individuals with a preexisting diagnosis of asthma
corticosteroids. occurring in the context of exposure to triggers in the
• High-altitude illness is a group of clinical syndromes work environment. 2 Work-related asthma is grouped into
that occur among travelers to altitudes above 2,500 Sensitizer-Induced Asthma (SIA) and Irritant-Induced
meters. It is caused by the physiologic responses to Asthma (IIA) based on the mechanism of disease.
a low barometric pressure at an altitude that results SIA is an immune-mediated inflammatory reaction
in a low inspired oxygen tension and arterial oxygen to compounds known to be sensitizers, of which there
611
612 Chapter 49 Occupational and Environmental Lung Diseases
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
Figure 49.1 GOLD COPD Assessment Tool.
Source : Global Initiative for Chronic Obstructive Lung Disease , © 2017

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
lavage effluent, requiring the exclusion of other potential 49.2 CLINICAL PRESENTATION

49
causes, including malignancy, pulmonary alveolar lipo-
proteinosis, and atypical infections such as Pneumocystis AND DIAGNOSIS
jirovecii and Norcardiosis. A diagnosis of silicosis can be
established on the basis of a documented history of sig- Acute exposure to beryllium presents with nonspecific
nificant silica exposure, consistent chest imaging findings respiratory symptoms, including a cough, rhinorrhea, and
of diffuse nodular and patchy consolidative opacities, and dyspnea. This is associated with a delayed hypersensitiv-
supportive BAL findings in the absence of other causes ity reaction resulting in chronic granulomatous inflamma-
(Figure 49.2). tion affecting the lungs, a condition known as beryllium
sensitization (BeS). About 8% of individuals with BeS,
may progress to chronic beryllium disease, characterized
49.1.15 Prevention and Treatment by progressive dyspnea, non-productive cough, fatigue,
and exercise intolerance as lung tissues are destroyed by
The Occupational Safety and Health Administration chronic granulomatous inflammation.38 Patients may have
(OSHA) recommends limiting exposure to silica using a constitutional symptoms, including fever, night sweats,
combination of respiratory protection, medical surveil- and weight loss. Physical examination findings are non-
lance, and good record-keeping. Half-face particulate specific, although bibasilar crackles and digital clubbing
respirators with N95 or better filters are considered appro- may be present. Extrapulmonary manifestations are rare
priate for silica at concentrations of 50 microgram/m3 or and include uveitis and cardiac conduction abnormalities.
fewer; powered respirators are recommended for expo- Chest x-ray has a low sensitivity for diagnosing beryl-
sures above this limit.37 liosis in the acute setting, as it may be normal in BeS and
early phases of CBD. Chest computed tomography has a
higher sensitivity and may demonstrate hilar adenopathy,
49.1.16 Berylliosis upper lobe predominant reticulonodular infiltration in a
peribronchovascular pattern that is indistinguishable from
Beryllium is a naturally occurring element that is extracted
sarcoidosis. It has been reported that about 6% of patients
from ores and processed into metal, oxides, alloys, and
undergoing diagnostic evaluation for a clinical suspicion
composite materials used in the aerospace, automotive,
of sarcoidosis were ultimately diagnosed with berylliosis,
and mining industries.38 Berylliosis manifests as two
highlighting the importance of a detailed occupational
clinical syndromes at opposite ends of a disease spectrum.
history to assess for exposure.39 – 41 Pleural effusion is an
Beryllium sensitization occurs in acutely exposed indi-
uncommon manifestation of BeS and CBD. Pulmonary
viduals, while chronic beryllium disease is an inflamma-
function tests may be normal in the early stages of the dis-
tory lung disease affecting individuals who are chronically
ease, while in advanced cases airflow obstruction, restric-
exposed to beryllium.
tion, or a mixed pattern on spirometry may be present.
A reduced diffusion capacity for carbon monoxide
(DLCO) may also be present in advanced cases.
49.1.17 Epidemiology The diagnosis of beryllium sensitization is made on the
It is estimated that about 134,000 current workers in gov- basis of a positive blood beryllium lymphocyte prolifera-
ernment and private industry are potentially exposed to tion test (BeLPT) in a patient with a history of beryllium
beryllium in the United States.38 exposure.
Figure 49.2 Touray Occupational Environmental Lung Disease Silicosis.

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
is characterized by changes in the heart rate, respiratory 49.5.4 Prevention and Treatment

49
rate, chemoreceptor sensitivity to hypoxia, and pulmo-
nary vasoconstriction. These act in concert to restore nor- 49.5.4.1 Controlled Ascent
mal oxygen levels in tissues, but when the rate of altitude Controlled exposure to hypobaric hypoxia remains the
change exceeds the body’ s homeostatic capacity, acute most effective non-pharmacologic means of preventing
hypoxemia ensues, resulting in distinct clinical syndromes HAI. Gradual ascent that allows for acclimatization is the
primarily affecting the lung and brain. most effective preventive strategy. The ideal rate of ascent
Risk factors for the development of HAI include pre- is variable, but it is generally recommended that at alti-
existing cardiopulmonary disease, heavy exertion at altitudes above 3,000 meters, daily ascent should not exceed
tude, low-altitude residence before ascent, and obesity.49 300– 500 meters above the previous night with a rest day
after every 1,000 meters (or every 2– 3 days).48 , 51
49.5.2 Acute Mountain Sickness and

High Altitude Cerebral Edema 49.5.4.2 Acetazolamide
Acute mountain sickness (AMS) is the most common pre- The use of acetazolamide, a carbonic anhydrase inhibi-
sentation of HAI that typically occurs about 6– 12 hours tor, has been shown to be effective in preventing HAI by
after ascent to altitudes above 2,500 meters (8,000 feet). inhibiting bicarbonate excretion in the kidneys, which
It is diagnosed when an unacclimatized traveler develops results in an increase in serum bicarbonate and a con-
a headache, with one of the following symptoms: nau- comitant increase in minute ventilation in response to
sea, anorexia, vomiting, insomnia, dizziness, or fatigue. elevated PCO2 . The benefit of acetazolamide for the pre-
It occurs in about 10– 40% of climbers at 3,000 meters, vention of AMS/HACE has been demonstrated in mul-
while more than 50% of climbers experienced symptoms tiple trials, and it remains the primary pharmacologic
at altitudes greater than 4,000 meters. 50 agent of choice. 52 , 53
High-altitude cerebral edema (HACE) is considered an In patients who develop AMS, rest and descent to a
end-stage form of acute mountain sickness and is charac- lower altitude are recommended. Given that AMS and
terized by the presence of ataxia and altered mental status HACE are considered two extremes of a continuum,
in an unacclimatized climber and can occur in the absence physicians must be vigilant to look out for symptoms of
of acute mountain sickness or pulmonary edema. HACE. The Lake Louise Scoring system is a screening
tool that can detect AMS/HACE in high-altitude climb-
ers. A score of 3– 5 is consistent with AMS, while a score
greater than 6 indicates severe AMS/HACE, and such
49.5.3 High Altitude Pulmonary Edema patients should be treated with acetazolamide. The rec-
High altitude pulmonary edema (HAPE) is a rare life- ommended dose is 125– 250 mg twice a day. Common side
threatening form of noncardiogenic pulmonary edema effects include paresthesia, loss of appetite, and nausea.
that develops two to four days following rapid ascent Because acetazolamide is sulfonamide, patients with sulfa
above 2,500 meters (8,000 feet). allergies should not take this medication (Table 49.1).
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
49.5.5 Hypersensitivity Pneumonitis Diagnosis of HP requires a high index of suspicion in a

patient presenting with the aforementioned clinical symp-
Hypersensitivity pneumonitis (formerly extrinsic allergic toms and diagnostic imaging. Once the diagnosis is con-
alveolitis) is an immune-mediated inflammatory disease sidered, a detailed history looking for potential exposure
of the lung that occurs due to exposure to an inducing to an HP-inducing antigen is crucial, although these are
agent called a hypersensitivity-pneumonitis inducer (HP identified in only about 50% of cases. 56 , 59 A detailed occu-
inducer). Exposure typically occurs in an occupational pational and social history should be obtained to identify
or recreational setting, which has given rise to an exten- any potential exposures in the work environment or dur-
sive list of diseases, including farmer’ s lung, bird fancier’ s ing recreational activities.62
lung, and hot-tub lung. It is characterized by a lympho- Pulmonary function tests and referral to a pulmonolo-
cytic inflammation of the lung due to the accumulation of gist are recommended for further diagnostic evaluation,
activated T-lymphocytes in the lung tissues. including bronchoscopy with bronchioalveolar lavage
and/or lung biopsy. Cases of HP are best managed with
a multidisciplinary team comprised of pulmonologists,
49.5.6 Epidemiology chest radiologists, and pathologists. Specific IgGs have
been employed as a screening tool, but these tests are per-
The incidence of HP is about one per 100,000 in the formed only in a few specialized centers.
United Kingdom, with a mean age of 57 and an almost
equal sex distribution. Incidence in the United States is
unknown. 54 In the United States, identified risk factors
are quite extensive and include bird and hot-tub exposure, 49.6.1 Treatment and Prevention
contaminated humidifiers, and exposure to mold or fungi The cornerstone of HP treatment involves identification
in plants and water systems.55 , 56 Lung fibrosis on chest of the offending antigen and avoidance. However, given
CT has been associated with poorer outcomes with about that an inducing agent remains unidentified in half of
25% of patients with fibrotic HP dying or requiring lung patients with HP, consideration of treatment with inflam-
transplantation during a five-year follow-up period. 57 matory suppression agents in symptomatic patients may
be indicated. Prednisone has been used in this scenario,
while mycophenolate and azathioprine have been used as
49.6 CLINICAL PRESENTATION second-line agents.
AND DIAGNOSIS
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.
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50
CHAPTER
Venous Thromboembolic Disease

Joseph Gallant, MD and Ryan Shipe, MD
Key Points.................................................................................. 621 50.5.4 Diagnosis.............................................................. 625

50.1 VTE Introduction/Overview................................................ 621 50.5.5 Treatment............................................................. 626
50.2 Epidemiology.................................................................... 621 50.5.6 Massive PE........................................................... 626
50.3 Pathophysiology............................................................... 622 50.6 Distal DVT......................................................................... 627
50.4 Embolization to the Pulmonary Vasculature....................... 622 50.7 Isolated Subsegmental PE................................................. 627
50.5 Risk Factors...................................................................... 623 50.8 Malignancy-Associated Thromboembolism....................... 627
50.5.1 Immobility............................................................. 623 Clinical Applications................................................................... 627
50.5.2 Obesity................................................................. 623 References................................................................................ 627
50.5.3 Smoking............................................................... 624
This concept describes the observation that the presence

KEY POINTS of specific combinations of individual (and often relatively
weak) risk factors engenders an overall risk that is poten-
• Venous thromboembolism (VTE) is a common,
tially much greater than the sum of their individual con-
morbid, and costly disease process with a multitude
tributions.1 While it is true that many risk factors for the
of risk factors.
development of VTE have a non-modifiable genetic basis,
• Risk factors for the development of venous throm-
other risk factors may exist as a consequence of an other-
boembolic disease are commonly present in combi-
wise healthy or necessary risk exposure (such as OCP use
nation rather than isolation.
or surgical immobilization). The application of the prin-
• The role of modifiable risk factors for VTE such as
ciples of lifestyle medicine can further reduce the overall
immobility, obesity, and smoking is an area of grow-
risk of developing VTE due to their influence over several
ing interest.
important risk factors that are synergistic, common, and
• More study is needed to define the impact of modi-
modifiable. While the precise pathophysiological mecha-
fication of these risk factors with respect to VTE or
nisms underlying the interactions of these modifiable risk
VTE recurrence in individual patients.
factors are not fully understood, we do know that getting
adequate levels of physical activity, making smart nutri-
tional choices for maintenance of a healthy weight, and
50.1 VTE INTRODUCTION/ avoiding cigarette smoking will be increasingly important
OVERVIEW in the overall management of patients with DVT and sub-
sequent PE.
Venous thromboembolic disease (VTE) in the form of deep
venous thrombosis (DVT) and pulmonary embolism (PE)
is a common, costly, and morbid problem encountered by 50.2 EPIDEMIOLOGY
both generalists and specialists in a variety of medical and
surgical fields. As our understanding of the many risk fac- Accurately assessing the true incidence of VTE disease is
tors for the development of VTE has grown, and as our challenging due to the unknown number of asymptomatic
approach to diagnosis and treatment has become more DVT or PE cases that are suspected to occur each year.
complex, it has become necessary to adopt an increasingly Asymptomatic PE alone is believed to complicate up to
broad and multidisciplinary approach to management of 50% of all confirmed cases of DVT.2 Estimates suggest a
these patients. There is growing evidence that application combined incidence rate of one in 1,000 people per year,
of the principles of lifestyle medicine should become a cen- with the rate of diagnosis of PE being approximately half
tral component of comprehensive management of patients that of DVT (60 vs. 124/100,000).1,3 CDC data are in
with VTE. agreement, reporting 300,000 to 600,000 new cases of
Critically important to an understanding of the devel- VTE each year in the United States alone. As many as 80%
opment of VTE and the management of this patient popu- of these new cases of VTE will occur in the context of at
lation is the concept of risk factor synergy or interaction. least one, and often more than one, known risk factor.4
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
50.5 RISK FACTORS Immobility not related to airline travel is less well
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 addition, 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
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
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.
• Dabigatran, rivaroxaban, apixaban, and edoxaban

are all recommended over warfarin.
• Dabigatran (150 mg twice daily) and edoxaban (30
50.5.6 Massive PE
or 60 mg once daily) are preceded with a period of Hemodynamic instability acts as a critical branch point in
parenteral anticoagulant, usually a low-molecular- all recommended treatment algorithms. Patients at high
weight heparin, for 5–10 days. risk of death presenting with obstructive shock should be
• Rivaroxaban (15 mg BID × 21 days, then 20 mg considered for administration of thrombolytic therapies.74
daily, all with food) and apixaban (10 mg BID × 10 The potential benefit derived from thrombolysis is believed
References 627
to be a continuum, varying directly with the patient’s risk 50.7 ISOLATED SUBSEGMENTAL PE

50
of imminent death from their VTE episode and inversely
with their risk of major bleeding (most notably intracra- Isolated, asymptomatic, subsegmental pulmonary emboli
nial hemorrhage). The tipping point for potential benefit detected by highly sensitive modalities (multidetec-
is hard to identify, however, due to the dearth of data tor CT) do not require anticoagulation. These patients
precisely describing patient characteristics and outcomes can be managed with continued observation following
after receiving thrombolysis. A recent study attempted a negative ultrasound evaluation of the proximal legs.
to describe outcomes in “intermediate risk” patients (as This approach is based mostly on the expectation that a
defined by aggregate evidence of right ventricular dys- number of very small defects in the periphery on low or
function but in the absence of true shock). Although more intermediate risk scans will be false positives, with the
than 1,200 patients with acute PE and evidence of right likelihood of a true positive rising sharply in the context
ventricular strain were randomized to receive tenecteplase of a persistent underlying risk factor (see above).83,84 The
and heparin (versus heparin alone), no clear net benefit was presence of symptoms attributable to a clot or the pres-
identified due to the counterbalancing effect of increased ence of residual lower extremity thrombosis should push
bleeding (including intracranial bleeding).78 patients and clinicians towards therapy. It is important to
The technical method of thrombolytic delivery has also understand that the presence of both distal DVT and iso-
been an area of research interest, and it has been hypoth- lated subsegmental PE excludes those patients from each
esized that PA catheter-directed thrombolysis (CDT) (ver- of those groups and should prompt appropriate antico-
sus peripheral vein infusion) would carry a lower risk of agulant treatment.
serious bleeding. Data are currently limited to mostly small
trials with limited generalizability of results. Based on the
current body of evidence, catheter-directed thrombolysis
leads to resolution of clots faster than heparin alone and
50.8 MALIGNANCY-ASSOCIATED
is potentially associated with a lower risk of major bleed- THROMBOEMBOLISM
ing compared to systemic infusions.79,80 Catheter-directed
therapy and systemic thrombolysis, however, have not There is insufficient evidence to recommend the use of
been compared head-to-head in any trial to date. While DOACs in the treatment of malignancy associated VTE.
recommendations may change as more evidence accumu- LMWH remains the standard of care. This recommenda-
lates, current guidelines reflect this paucity of data and tion is based on an observed higher failure rate of warfa-
favor systemic therapy over CDT. rin in these patients.85 Although DOACs appear safe and
effective in this population, more study is needed to clarify
their role. Most up-to-date society guidelines have not yet
50.6 DISTAL DVT recommended DOACs for treatment of cancer-associated
VTE.71,82
Distal thrombosis of the extremities that have occurred
with or without a potentially modifiable risk factor does
not uniformly require anticoagulation. The decision to CLINICAL APPLICATIONS
treat these patients with anticoagulation should be based
on an evaluation of the patient’s symptoms, the risk of • Maintenance of a high clinical suspicion for DVT
adverse bleeding events, and risk of recurrence or pro- or PE must include an awareness of applicable
gression of clot conferred by their medical history. An risk factors, and a sedentary lifestyle, obesity,
approach to patients with distal DVT includes performing and smoking should be considered in the clinical
serial duplex ultrasounds of the lower extremities for a assessment.
period of two weeks off of anticoagulation. An absence • The keys to diagnosing pulmonary embolism (PE)
of symptoms or clot progression over this surveillance are the maintenance of high clinical suspicion, appli-
interval suggests that the patient is at low risk for embo- cation of serological testing in selected low-proba-
lization or clot propagation. Candidates most likely to bility patients, and CT with contrast in patients
benefit from such a treatment plan will have a good car- with high pre-test probability.
diopulmonary reserve, small distal clot, and no concur- • Direct oral anticoagulants have become the stan-
rent pulmonary embolism.81 Current guidelines recognize dard of care for most cases of DVT and hemody-
that shared decision making may result in a higher value namically stable PE.
being placed on definitive therapy rather than a period of • A number of special circumstances exist in the treat-
uncertainty, and this cohort of patients is likely at low risk ment of PE which require a tailored approach to
of serious bleeding events with anticoagulation.82 therapy.
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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
Key Points.................................................................................. 631 51.8.2 Avian Influenza................................................. 634

51.1 Definition.......................................................................... 631 51.9 Laboratory Diagnosis of Influenza................................... 634
51.2 History of Influenza........................................................... 631 51.10 Prevention...................................................................... 635
51.3 Virology of Influenza Virus................................................. 631 51.10.1 Vaccination....................................................... 635
51.4 Genetic Variation............................................................... 632 51.10.2 Chemoprophylaxis............................................ 635
51.5 Epidemiology of Influenza................................................. 632 51.10.2.1 Self-Care for Persons with Influenza......636
51.6 Economic Impact.............................................................. 633 51.11 Antiviral Therapy............................................................. 636
51.7 Pathophysiology of Influenza............................................. 633 51.12 Summary........................................................................ 637
51.8 Clinical Illness................................................................... 633 Clinical Applications................................................................... 637
51.8.1 Seasonal Influenza................................................ 633 References................................................................................ 637
“grippe” and epidemic catarrh. Influenza is commonly

KEY POINTS called “the flu”; however, the term “flu” is also frequently
used by the general public for other acute febrile illnesses.
• The influenza virus evolves via mutation and mix-
Acute gastrointestinal illnesses are often referred to as the
ing among and between humans and other animal
“stomach flu” despite the fact that they have no associa-
species.
tion with the influenza virus. Major influenza epidemics
• This evolution allows the influenza virus to escape
have occurred since at least the Middle Ages, but may
immune responses which are directed at a specific
have also occurred in earlier times. The high attack rate,
strain.
the nature of the epidemic curve, and the characteristic
• Currently it is estimated that more than 50,000 peo-
of frequent cough allow the identification of past epidem-
ple die in the United States each year from complica-
ics. The first influenza epidemic generally agreed upon by
tions of influenza.
medical historians took place in 1580, originating in Asia,
• Current vaccines are imperfect but are useful none-
spreading across Europe over a period of six months and
theless and are generally recommended.
eventually reaching the American continent1
• Current medications to treat influenza are recom-
mended for certain populations and for those hos-
pitalized with influenza, but efficacy is less than
desired. 51.3 VIROLOGY OF
• Ongoing research may lead to better therapeutics. INFLUENZA VIRUS
Influenza viruses are members of the family
51.1 DEFINITION Orthomyxoviridae. There are three types of influenza
virus: influenza A, influenza B, and influenza C. Influenza
Influenza is a contagious acute illness of the respiratory viruses have been divided into these three types on the
tract. The etiologic agent is the influenza virus. This basis of major antigenic differences in the nucleoprotein
common disease is the source of significant illness in the (NP) and matrix (M) protein antigens. Influenza A viruses
general population and can lead to death, especially in are the most virulent of the three influenza viruses and
persons at “high risk” for complications of influenza. are the etiologic agents of all known influenza pandem-
ics. Influenza B virus tends to cause milder disease than
influenza A. 2 Influenza C virus causes infection in humans
51.2 HISTORY OF INFLUENZA only infrequently, and its pattern of infection follows no
seasonal variation. All three types of virus exhibit a host-
The name “influenza” is derived from the Italian, and cell-derived lipid envelope and a genome of segmented,
arose from the notion that the disease was due to the negative sense single-stranded RNA. Influenza viral parti-
“influence” of the stars. Clinical illness due to influenza cles are variable in shape, from irregular spheres that mea-
virus has had many names over the years, including the sure 80–120 nm in diameter to long filamentous particles.
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.
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 vaccination, 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
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.
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.
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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):
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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
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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
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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):
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52
CHAPTER
Indoor Air Quality

Anthony C. Campagna, MD, FCCP and Dhruv Desai, MD
Key Points.................................................................................. 639 52.10 Mice............................................................................... 644

52.1 Introduction...................................................................... 639 52.11 Water Pipe Smoking (also known as Hookah).................. 644
52.2 Secondhand Smoke.......................................................... 639 52.12 Electronic Cigarettes....................................................... 645
52.3 Secondhand Smoke Exposure in Children......................... 641 52.13 Contamination of Home Showerheads, Dishwashers,
52.4 Radon............................................................................... 641 and CPAP Devices........................................................... 645
52.5 Carbon Monoxide.............................................................. 641 52.14 Smart Devices that Analyze Indoor Air Quality................. 646
52.6 Indoor Mold...................................................................... 642 52.15 Summary........................................................................ 646
52.7 Animal Dander.................................................................. 643 Clinical Applications................................................................... 646
52.8 Dust Mites........................................................................ 643 References................................................................................ 646
52.9 Cockroaches..................................................................... 644
secondhand smoke, radon levels, home water damage,

KEY POINTS heating and ventilation, renovation work, the presence of
a pool or hot tub, and hobbies, including arts and crafts
• Indoor smoking, elevated radon levels, and unde-
and model building. Also, activities such as do-it-yourself
tected elevated carbon monoxide levels present sig-
repair work, gardening, pet exposure, and wood or coal
nificant health hazards.
heater exposure should be discussed 2
• Humidity levels greater than 50% in your home can
promote dust mite and mold growth.
• Water pipe hookah and e-cigarette use pose consid-
erable risk to young adults. 52.2 SECONDHAND SMOKE
• Home appliances including CPAP devices need peri-
The awareness of smoking and its adverse effects is as wide-
odic cleaning because they can become contami-
spread today as at any time in history. Globally, smoking
nated with microbes.
remains a highly prevalent lifestyle choice. Secondhand
smoke exposure is a leading public health problem.
Approximately one nonsmoker dies from secondhand
52.1 INTRODUCTION smoke exposure for every eight smokers who die from
smoking3 Three publications serve as landmark summa-
Since humans take over 20,000 breaths daily, clean envi- ries of the effects of environmental tobacco smoke (ETS)
ronmental air is essential. The relationship between health on human health. The U.S. Surgeon General’s Report in
and air quality was recognized as far back as the fourth 19863 and a report of the National Research Council4
century BC by Hippocrates, the Father of Medicine. described the health risks associated with passive smok-
Indoor air quality is particularly important to humans ing. Lastly, the Environmental Protection Agency (EPA)
since we spend up to 90% of our time indoors.1 Outdoor released a report in 1992 that causally linked secondhand
and indoor air quality in the United States is regulated smoke exposure to lung cancer, 5 effectively classifying
by the federal government through the Environmental ETS as a group A carcinogen. While secondhand smoke
Protection Agency (EPA). In this chapter, we concentrate has been referred to as ETS in the past, the term “sec-
on indoor air quality and highlight the sources of poten- ondhand smoke” better captures the involuntary nature
tial morbidity of indoor air quality as it pertains to lung of the exposure. The 2006 Surgeon General’s report uses
health. the term “involuntary smoke” in the title because most
One of the most important tasks of the healthcare nonsmokers do not want to breathe tobacco smoke.
worker who is meeting a patient for the first time is taking Secondhand smoke is composed of a mixture of both
a comprehensive history of environmental exposures both a sidestream smoke, the smoke released from the burning
at work and in the home. The healthcare worker should end of a cigarette, and exhaled mainstream smoke, the
ask the patient about contemporary exposures as well as smoke exhaled by the smoker.6,7 During cigarette burn-
exposures in their childhood home or homes. 2 Household ing, there are over 4,000 chemical compounds created
factors which may affect respiratory health include which may be toxic and carcinogenic.8,9 The chemical
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
52.4 RADON 52.5 CARBON MONOXIDE

Radon-222 is a noble gas that is produced from the Carbon monoxide (CO), the by-product of the combus-
decay of uranium-238 and radium-226, which are natu- tion of carbonaceous fuels, is a colorless, odorless gas.
rally present in the earth’s rock and soil. It decays with Sources of CO include unvented kerosene heaters, gas
a half-life of 3.8 days. It can diffuse itself into the soil space heaters, leaking chimneys, furnaces, gas water
and air before decaying. The breakdown of radon-222 heaters, wood stoves, generators and other gas-powered
occurs by emission of an alpha particle which produces equipment, automobile exhaust, and tobacco smoke.40–42
radioactive progeny that include polonium-218 and polo- Approximately 15,000 emergency department visits and
nium-214.34,35 These are known as the “short-lived” 500 accidental deaths in the United States are attributed to
progeny, and they, in turn, break down into “long-lived” accidental exposure to CO inhalation.43,44 Mortality rates
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.
TABLE 52.3 Environmental dust mite control measures

• Use of impermeable mattress and pillow covers
• Minimize reservoirs by frequent vacuuming and removal of stuffed animals from bedrooms
• Remove carpeting from the bedroom
• Decreasing the indoor humidity to less than 50%
• Frequent washing approximately every two weeks of bedding in hot water
• Removal of upholstered furniture
• Avoidance of feathered and non-hypoallergenic pillows
• Routine use of insecticides or allergen-denaturing agents is not recommended
52.9 COCKROACHES 52.11 WATER PIPE SMOKING (ALSO

Cockroaches are a common occurrence in the urban envi- KNOWN AS HOOKAH)
ronment and play an important role in indoor air quality
and development of asthma in the inner city. While there Water pipe smoking is becoming an increasing trend
are over 3,500 different species known, the most common among young adults as a “safe” alternative to smoking.
species are the German species Blatella germanica and It is also known by other names, including Shisha and
American species Periplaneta americana. Antigenic par- Narghile. The concept is not a new one, with reports of its
ticles Bla g1 and Bla g2, similar to those produced by dust use dating back to the fifteenth century in both the Middle
mites, are found in the fecal particles as well as their secre- East and Europe.85 Due to recent laws limiting the use of
tions.74 High levels of cockroach infestations are seen in tobacco products within public buildings and restaurants,
densely populated areas, urban environments, inner-city Hookah bars have opened up, most within the last ten
communities, and areas of low socioeconomic status.75 years.85 Hookah bars are small cafés and clubs that rent
Conditions that favor cockroach infestation include food the use of hookahs and sell special hookah. These bars are
left uncovered, humid and warm conditions, poor sani- often located near universities and college campuses and
tation, and crowding.76 Inner-city children sensitized to market themselves directly to young adults aged 18–24.
cockroach antigen in high levels (>8U/g) were more likely One study found that one in five boys and one in six girls
to develop asthma, have higher asthma morbidity, and aged 18 had used water pipe tobacco in the past year.86
more office visits and hospitalizations due to asthma.77 Further smaller studies in college students show its use to
Matsui and colleagues outline a comprehensive review of be as high as 40%.86
disproportionate asthma mortality among inner-city resi- Smoking is done through direct heating of the tobacco
dents where approximately half of the homes have cock- with items such as burning embers or charcoal. The smoke
roach allergen levels more than >8U/g.78 is then filtered through a water medium that is some-
Several techniques have been recommended to reduce times flavored with artificial flavorings such as apple or
cockroach antigen exposure: controlling humidity, watermelon. The smoke is then drawn through a pipe to
improving indoor sanitation, and implementing both a mouthpiece to be inhaled. When combined with other
chemical and nonchemical extermination.76 Although a flavors, it is called shisha.85
difficult task, simple measures such as improving sanita- Although limited research has been done on the
tion and reducing overcrowding may have a significant health risks of water pipe use, the existing evidence indi-
impact on minimizing the development and severity of cates that water pipe smoking carries the same or similar
asthma in inner-city children. health risks as cigarette smoking. Links have been made
to many of the same adverse health effects, including
lung, oral, and bladder cancer, as well as coronary artery
52.10 MICE and heart disease.87,88 Despite knowing the risks, almost
90% of beginning Hookah smokers thought that ciga-
Mice and the allergens they release pose a significant rette smoking was more addictive.89 Trends suggest hoo-
health risk for both urban and rural indoor air quality. kah use is increasing worldwide. Analysis of mainstream
Mus m 1 and Mus m 2 are the major allergens found in smoke from water pipes found that it contains significant
mice dander, hair, and urine.79 These allergens are more amounts of nicotine, tar, and heavy metals.89,90 Analysis
commonly found in inner-city urban environments and of nicotine and cotinine, a chemical marker of nicotine
highest in rooms where food products are stored, includ- exposure, before and after water pipe use revealed that
ing the cafeteria or kitchen. Mice allergens were found in nicotine levels increased up to 250% and cotinine levels
95% of homes in a large study of inner-city children with to 120% with just one session of use lasting 40 minutes.90
asthma.80 The greatest predictor of high levels of mice Because water pipe smoking has a more prolonged inha-
allergen exposure was the presence of visible droppings.81 lation time and exposure than a conventional cigarette, it
The impact of these allergens was noted by Sheehan et has been estimated that one session can be equivalent to
al., where children with preexisting asthma in homes with smoking 100 cigarettes within that time.90 These results
high levels of mouse allergen had more missed school days may be complicated by the routine concurrent use of
due to asthma-related events.82 Exposure to mouse aller- cigarettes.
gen is associated with high rates of sensitization. Children Other risks are also seen with use of the heat sources
sensitized to mouse allergen were found to have increased that are used to light the tobacco, such as wood or char-
risk of developing asthma and have higher rates of asthma- coal. These substances when ignited alone put one at risk
related morbidity.83 Urban children with asthma in homes for exposure to smoke that contains heavy metals and
with a high bed mouse allergen concentration were shown carbon monoxide. These compounds are known to cause
to have an 87% higher probability of an asthma-related cancer and obstructive lung disease more commonly in
healthcare use.84 developing countries that use fire to cook. There is also
Overall, mice had a significant impact on the lung health a concern for transmission of infectious diseases such as
of the people exposed and sensitized to their allergen. The tuberculosis, hepatitis, and herpes, although this has not
most effective way to limit their impact is to prevent or been extensively studied.88
reduce the chance of exposure. The use of rodent-proof Continued research is needed to determine the abso-
construction, improved sanitation, and population control lute long-term health risks with water pipe smoking. The
using traps and chemicals may also reduce exposure. current evidence supports that both direct exposure and
52.13 Contamination of Home Showerheads, Dishwashers, and CPAP Devices 645
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
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.
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February 11, 2018). ww w.prnewswire.com /news-releases/
XI
PA RT
Obstetrics and Gynecology

651
53
CHAPTER
Antenatal Care—Nutrition and

Lifestyle to Improve Conception
and Pregnancy Outcomes
Key Points.................................................................................. 653 53.5 Preeclampsia.................................................................... 655

53.1 Introduction...................................................................... 653 53.6 Fetal Impacts of Maternal Lifestyle.................................... 656
53.2 Ovulatory Infertility........................................................... 653 53.7 Autism.............................................................................. 657
53.3 Pregnancy Outcomes........................................................ 654 53.8 Exercise in Pregnancy....................................................... 658
53.4 Maternal Mortality............................................................ 655 References................................................................................ 658
of conception during any month of unprotected inter-

KEY POINTS course is about 20% when a woman is 30 years old and
declines to only about 5% by age 40—with only 30% of
• Obesity and the Standard American Diet (SAD) are
all conceptions actually resulting in a live birth. 2,3 Data
contributing to 90% of ovulatory infertility.
from the CDC (2013–2014) tell us that 71% of adults age
• The causes of maternal mortality have shifted away
20 years and older are overweight or obese.4 This preva-
from non-preventable causes, such as hemorrhage,
lence is most certainly affecting the capacity for repro-
to diseases of lifestyle. Cardiovascular disease,
duction in various ways, including ability to conceive and
stroke, and hypertensive diseases of pregnancy com-
to maintain a pregnancy. Pregnancy outcomes are also
bined now cause 30% of maternal deaths.
being affected deleteriously by the obesity and diabetes
• Maternal diet and lifestyle behaviors can result
epidemics. Dietary patterns are directly affecting ovula-
in negative fetal impacts that include obesity and
tory infertility, male factor infertility, and maternal and
autism.
fetal complications. In this chapter, the impacts of lifestyle
on ovulatory infertility and maternal and fetal pregnancy
outcomes will be addressed.
53.1 INTRODUCTION
The live birth rate in the United States is at an all-time
low at 59.8 live births per 1000 women aged 15 to 44. In 53.2 OVULATORY INFERTILITY
2010 it was 64.1, and the previous historical nadir was in
1997 at 63.6.1 Several factors may be contributing, includ- Ovulatory infertility is directly related to polycystic ovar-
ing continued access to contraception, delaying childbear- ian syndrome (PCOS). PCOS gets its name from the
ing to older ages when fecundity is in decline, and a shift appearance of the ovary on ultrasound, but metaboli-
of cultural norms placing more importance on careers or cally, it is a constellation of obesity, insulin resistance, and
self-fulfillment rather than on the rearing of children. oligo, or anovulation that results in infertility, menstrual
There is, however, a compelling argument to be made dysfunction, and hirsutism.
that the obesity and diabetes epidemics might also be As women become obese, they become insulin resis-
factors in the declining birth rate. We have seen a steady tant, resulting in elevated levels of circulating insulin.
rise in diabetes and obesity since 1960 and then a dra- Insulin suppresses the synthesis of sex hormone binding
matic rise in both in the mid-1970s and early 1980s. At globulin (SHBG), which is crucial in binding free andro-
both extremes of the body fat/body mass index scale, gens. When SHBG synthesis is suppressed, free androgens
there are increases in infertility and declines in fecun- rise, resulting in infrequent ovulation. 5
dity. Maintaining a normal BMI helps retain reproductive It is prudent to think that the obesity crisis in this coun-
capacity, which is important because humans have one try is changing the rates of infertility and subfecundity.
of the lowest fecundity rates of all animals. The chance Population studies have shown that approximately 30%
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
53.4 MATERNAL MORTALITY delivery, regardless of gestational age. The clinical mani-
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
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 having 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
TABLE 53.1 Clinical applications

Pregnant patients and those trying to conceive should be counseled to:
• Reduce animal food consumption and avoid fish for at least one year and then throughout the pregnancy.
• Avoid processed food and highly refined carbohydrates.
• Supplement with B12 and folic acid for at least three months prior to conception.
• Avoid tobacco, alcohol, and other substances before conception and during pregnancy.
• Work to achieve 150 minutes of chronic, moderate physical activity before, during, and after pregnancy.
individuals have up to 230 times the levels of inflamma-

tory mediators, like interferon.96–98 Children with autism
53.8 EXERCISE IN PREGNANCY
tend to have higher activity in the mammalian target of Regular aerobic exercise during pregnancy has been shown
rapamycin or mTOR pathway that is involved in many cel- to improve or maintain physical fitness. Although the evi-
lular processes, including synaptic plasticity and immune dence is limited, some benefit to pregnancy outcomes has
function that can alter neurodevelopment.99 been shown, and there is no evidence of harm when not
Targeting maternal inflammation and oxidative stress contraindicated. Observational studies of women who
appears to be the key to prevention of these disorders. exercise during pregnancy have shown benefits such as
Some of these inflammatory responses are being mediated decreased gestational diabetes, cesarean and operative
by the intestinal flora, which is selected for based on diet. vaginal delivery, and postpartum recovery time, although
By eating a plant-based diet, humans select for more favor- evidence from randomized controlled trials is limited. In
able bacterial species that actually improve risk factors for those instances where women experience low-back pain,
a variety of metabolic diseases.100–103 Maternal diet and water exercise is an excellent alternative. Studies have
the maternal microbiome play crucial roles in what hap- shown that exercise during pregnancy can lower glucose
pens to the fetus and infant. A recent study revealed that levels in women with gestational diabetes or help prevent
an infant’s first meeting with microbes and its first intes- preeclampsia. However, exercise has shown only a modest
tinal colonization happens in the womb. It is now known decrease in overall weight gain (1–2 kg) in normal weight,
that there is a placental microbiome consistent with the overweight, and obese women. For healthy pregnant and
maternal oral microbial community. The next meeting postpartum women, the guidelines recommend at least
with microbes is during birth and then with breastfeed- 150 minutes per week of moderate-intensity aerobic activ-
ing. From the moment the placenta starts supplying the ity (i.e., equivalent to brisk walking). This activity should
infant with nutrients, the microbiome is being developed, be spread throughout the week and adjusted as medically
and that microbiome will determine the health status of indicated. Contact sports and activities with a high risk of
the infant.104 Another recent study revealed that a high- falling, such as skiing, should be avoided. Exercise is safe
fat diet in pregnancy and during breastfeeding causes a for all pregnant women except those with significant heart
microbial dysbiosis in the infant. This dysbiosis can only or lung disease, incompetent cervix, current premature
partially be corrected by a low-fat diet after weaning. The labor, or placenta previa after 26 weeks of pregnancy.106
authors provide evidence to support the theory that the Generally speaking, whatever level of activity was being
maternal diet contributes to establishment of the fetal undertaken prior to pregnancy can be continued, and for
microbiota, which, in turn, affects intestinal maintenance those who had not been as physically active as recom-
and metabolic health.104 This underscores the importance mended, exercise should be encouraged with a program
of maternal periconceptional, prenatal, and postnatal tailored to the individual’s current level of fitness. Please
nutrition. see Table 53.1.
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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
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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
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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
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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
Key Points.................................................................................. 663 54.10 Fetal Distress.................................................................. 667

54.1 Benefits of Exercise in Pregnancy................................... 663 54.11 Low Birth Weight............................................................ 667
54.1.1 Weight Management........................................... 663 54.12 Preterm Delivery............................................................. 668
54.2 Glycemic Control............................................................ 664 54.13 Maternal Injury............................................................... 668
54.3 Reduction of Risk of Hypertensive Disorders in 54.14 Contraindications to Exercise in Pregnancy..................... 668
Pregnancy...................................................................... 665 54.15 Recommendations for Exercise in Pregnancy.................. 669
54.4 Psychological Benefits.................................................... 665 54.16 Exercise Prescription...................................................... 669
54.5 Improvement in Musculoskeletal Pain............................. 666 54.16.1 Intensity of Training........................................... 669
54.6 Lowered Rates of Intervention during the Time of 54.17 Duration/Frequency........................................................ 669
Labor and Delivery.......................................................... 666 54.18 Types of Exercise............................................................ 670
54.7 Other Benefits................................................................ 666 54.19 Know When to Stop........................................................ 670
54.8 Risks of Exercise in Pregnancy....................................... 666 Clinical Applications................................................................... 670
54.9 Spontaneous Abortion..................................................... 666 References................................................................................ 671
done focusing on the safety, risks, and benefits of physi-

KEY POINTS cal activity in pregnancy. Currently, both the Centers for
Disease Control and Prevention and the American College
• Exercise decreases the risk of postpartum weight
of Obstetricians and Gynecologists (ACOG) encourage
retention.
regular physical activity during pregnancy, as the ben-
• Exercise prevents and treats gestational diabetes.
efits are thought to far outweigh the risks. 2 This chapter
• Current data suggests that exercise before pregnancy
will review the benefits and potential risks of exercise in
and during the first 20 weeks plays a protective role.
pregnancy, the contraindications to exercise in pregnancy,
• Exercise provides psychological and physiological
and the current recommendations for type, intensity, fre-
mechanisms to improve mood in pregnancy.
quency, and duration of activity in pregnancy.
• Pregnant women who exercise report decreased inci-
dence of musculoskeletal discomfort and complaints.
• Data does not support an increased risk of sponta-
neous abortion with exercise. 54.1 BENEFITS OF EXERCISE
• Exercise has not been found to increase IUGR or
SGA infants.
IN PREGNANCY
• Exercise does not increase the risk of preterm deliv-
ery and may actually be protective.
54.1.1 Weight Management
• Obstetricians should be familiar with absolute The population as a whole is heavier today than in previ-
and relative contraindications to aerobic exercise ous times. The fourth leading risk factor for early mortal-
in pregnancy and make recommendations that are ity worldwide is physical inactivity. 2 A greater percentage
individualized by intensity, duration, frequency, and of women are entering pregnancy overweight or obese,
type of exercise. and many are gaining significantly more weight during
• 150 minutes of exercise per week is recommended pregnancy than is recommended. 3 Excessive weight gain is
for healthy pregnant women. emerging as an important predictor of adverse pregnancy
outcomes. Independent of pre-pregnancy weight, women
The recommendations regarding exercise in pregnancy who gain excessively during the course of the pregnancy
have been in flux over the years. In 1985, the American are more likely to deliver by cesarean section, have an
College of Obstetricians and Gynecologists provided the unsuccessful trial of labor after cesarean section, develop
first guidelines for exercise during pregnancy based on the hypertension or preeclampsia, deliver preterm, have a
limited evidence available.1 Prior to this time, women were macrosomic or small-for-gestational-age (SGA) infant,
often told to avoid strenuous physical activity, stretching, retain excessive weight after delivery, and become over-
or bending for fear of pregnancy complications that might weight or obese later in life.4–7 The Institute of Medicine
result. Since that time, a great deal of research has been recently reexamined the guidelines for weight gain during
663
664 Chapter 54 Exercise in Pregnancy
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
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 conditioned 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.
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.
Preterm birth is defined as delivery prior to 37 weeks of

gestation and is associated with significant neonatal mor-
bidity and mortality, especially for infants born prior to
54.13 MATERNAL INJURY
32 weeks of gestation.81 Approximately 12.5% of deliver- Profound physical changes occur over the course of a preg-
ies in the United States are preterm, and this number has nancy. Postural changes include a significant increase in
been rising over the last two decades.81 Lifestyle-related lumbar lordosis and a forward tilt of the pelvis. Combined
risk factors for preterm birth include maternal stress, with pregnancy-associated weight gain and a shift in
smoking, and intensity and duration of work.81 An associ- the center of gravity forward, balance coordination and
ation between physically demanding occupations and the exercise tolerance can be greatly altered.65 Joint laxity
risk of preterm birth has been described in the literature. and mobilization are also increased secondary to the hor-
The relationship between exercise and the risk of preterm monal changes of pregnancy.84 Thus, pregnant women
delivery is questionable.82 engaging in exercise should take caution when performing
During exercise, catecholamine output increases sub- high-velocity or jerking movements as they may be more
stantially, which could, in turn, stimulate uterine activ- prone to joint injury.
ity.83 However, studies are conflicting on whether physical
exercise actually increases uterine contractility. 56 The
most recent literature suggests that exercise or leisure-
time physical activity does not increase the risk for pre-
54.14 CONTRAINDICATIONS
term delivery and may instead actually be protective. In TO EXERCISE IN PREGNANCY
a study published in 1990, Clapp compared birth weights
and labor courses among women who maintained exercise Understanding the absolute and relative contraindica-
at greater than or equal to 50% of preconception levels tions to exercise in pregnancy is essential when counsel-
with those who stopped exercising in the first trimester.49 ing a patient. Any factor that may compromise maternal
The incidence of preterm labor was equivalent in the two physiological reserve could put her health and the health
54.17 Duration/Frequency 669
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
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
54.18 TYPES OF EXERCISE

54.19 KNOW WHEN TO STOP
Most forms of exercise are safe during pregnancy, though
there are some that involve risks and should be avoided. There are a few basic principles that pregnant women
Women should avoid exercises that require them to lie flat should adhere to: stay cool, stay hydrated, stay nourished,
on their backs (especially after 16 weeks of gestation) or and know when to stop. It is important for women exer-
stand still for prolonged periods of time, as well as those cising during pregnancy to have a clear understanding
activities that place women at risk for injury or abdomi- of the signs and symptoms that should prompt them to
nal trauma.89,92 Reasonable activities to suggest for preg- stop exercising and contact a physician. Any symptoms
nant women include walking, jogging, stationary cycling, of excessive fatigue, chest pain, shortness of breath before
low-impact aerobics, swimming, and yoga. 2,89,92 Yoga and exertion, palpitations, dizziness, lightheadedness, diffi-
pilates should be modified to avoid positions that result in culty walking, vaginal bleeding, regular painful uterine
decreased venous return, hypotension, and environments contractions, or decreased fetal movement should prompt
of high heat and humidity. 2 Contact sports such as soccer, immediate cessation of exercise and medical assessment as
basketball, hockey, or football put one at risk for abdomi- soon as possible. 2,88
nal trauma, and it is generally thought best to avoid such For most women, the benefits of exercise far outweigh
activities. 2 Participation in skiing, snowboarding, gym- any potential risks, and clinicians should educate them-
nastics, and horseback riding comes with a significant risk selves so that they can provide evidence-based advice to
for falls and thus should be discouraged. 2 Scuba diving pregnant women.
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
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Lifestyle Medicine - 2019

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© 2019 by Taylor & Francis Group, LLC

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International Standard Book Number-13: 978-1-138-70884-6 (Hardback)

Library of Congress Cataloging‑ i n‑ P ublication Data

Names: Rippe, James M., editor.

Visit the Taylor & Francis Web site at

and the CRC Press Web site at

To my beautiful wife, Stephanie Hart Rippe, and our wonderful children

Part I Lifestyle Management and Part III Physical Activity

Chapter 4: Clinical Strategies for Managing

Chapter 46: Exercise, Aging, and Immunity.................... 563

Chapter 102: Health Promotion Introduction................ 1169

Steven A. Adelman, MD Carissa M. Baker-Smith, MD, MS, MPH, FAAP,

Theodore J. Angelopoulos, PhD, MPH Mark Berman, MD, FACLM

Kristin Bixel, MD Debora S. Bruno, MD, MS

Shelley H. Carson, PhD

Xisui Shirley Chen, MD Andrea Cook, PhD

David E. Ciccolella, MD Sarah C. Couch, PhD, RD

Cindy D. Davis, PhD Patricia M. Dubbert, PhD

Elizabeth A. Dodson, PhD, MPH Jane Ellery, PhD

Peter J. Ellery, PhD, MLA John P. Foreyt, PhD

Joseph Gallant, MD George Guthrie, MD, MPH, CDE, CNS, FAAFP,

Gregory A. Hand, PhD, MPH, FACSM, FESPM

Virginia F. Gurley, MD, MPH Mary Hannan, MSN, APN, AGACNP-BC

Deborah Hasin, PhD Jessica L. Hildebrandt, MS, RD

Cassandra Herman, MS Jason R. Jaggers, PhD

John M. Jakicic, PhD Christopher M. Kaipust, MPH

Nattinee Jitnarin, PhD Sandeep (Anu) Kaur, MS, RDN, RYT-500

Elizabeth A. Joy, MD, MPH, FACSM Elizabeth Kelley, MS, ACSM-RCEP

Wesley C. Kephart, PhD Karen L. Lawson, MD, ABIHM, NBC-HWC

Ron Loeppke, MD, MPH, FACOEM, FACPM Sanchit Maruti, MD, MS

Jonathan R. Miller, PhD Neil Nedly, MD

Magdalena Pasarica, MD, PhD

David Paulk, PA-C, EdD, DFAAPA

Dori Pekmezi, PhD Prabakar Ponnusamy, MS

Joseph C. Piscatella, BA Jeremy B. Richards, MD

James M. Rippe, MD Robert Scales, PhD

Sharon Ross, PhD, MPH Alyssa B. Schultz, PhD

Susan M. Shirreffs, BSc, PhD Lisa Staimez, PhD, MPH

Charlotte A. Tate, PhD Margaret Loeper Vasquez, MS, RD, LDN

Matthijs D. van der Zee, MSc Sandra Weisser, MSEd, ATC

Nanette K. Wenger, MD, MACC, MACP, FAHA Emily Wu, MD

Gary B. Wilkerson, EdD, ATC Henry Xiang, MD, MPH, PhD

Lifestyle Management and Prevention

The Rationale for Intervention to Reduce

Key Points...................................................................................... 3 1.8.1 Age......................................................................... 11

maintain proper weight, 2 do not smoke cigarettes, 3

1.4 IMPLEMENTING RISK FACTOR 1.7.1 Tobacco Use

1.7.5 Obesity Distribution of body fat is also strongly and indepen-

TABLE 1.4 Classification of levels of physical activity

Source: 2008 Physical Activity Guidelines for Americans.

Lifestyle Strategies for Risk Factor

Key Points.................................................................................... 19 2.5.3 Physical Inactivity....................................................... 30

Lifestyle strategies can play a significant role in the

long-term smoking abstinence. These are bupropion

Figure 2.4 Trends in adult overweight and obesity ages 20 to 74 years.

Source: National Center for Health Statistics No permission needed.

Figure 2.5 Trends in Childhood Overweight.

Source: National Center for Health Statistics No permission needed.

2.8 DETERMINANTS OF BEHAVIOR publications have suggested ways that interested physi-

Physical Activity and Fitness in the

Part I Lifestyle Management and Part III Physical Activity

1.4 IMPLEMENTING RISK FACTOR 1.7.1 Tobacco Use

1.7.5 Obesity Distribution of body fat is also strongly and indepen-

Key Points.................................................................................... 19 2.5.3 Physical Inactivity....................................................... 30

2.8 DETERMINANTS OF BEHAVIOR publications have suggested ways that interested physi-

3.2.1 Adults of men engaging in moderate-to-vigorous activity three or

3.5.1 Resistance Exercise Training 3.7 DIABETES

3.9.1 The “Fitness vs. Fatness” debate 3.9.3 Physical Activity and

3.11.4 Cardiorespiratory Fitness and 3.11.5 Muscular Strength and the

Key Points.................................................................................... 53 4.7.1 Impact of Diet (see also chapter on Nutrition and

recommendations are altered accordingly. However, little 6.4.5 Limitations of the DRI

of evidence quality. The process of conducting a system- 6.5.2 Dietary Patterns

6.5.3 The Dietary Guidelines for Americans 6.5.5 USDA Food Group Patterns

6.7.1 The Nutrition Facts Label

7.3 OVERVIEW OF THE DIETARY 7.3.2 Key Recommendations

7.3.3 Healthy Eating Patterns The components of healthy eating patterns recom-

TABLE 8.1 (http://bloodpressureplan.com/download-free-dash-diet-cookbook-with-weekly-meal-plan-to-lower-b

CONSIDERATIONS FOR ↓ Capacity to metabolize drugs

OLDER ADULTS Mouth ↓ Salivary secretion

9.5.1 Dentition and Associated Senses 9.5.4 Glucose Intolerance/Type 2 Diabetes

Key Take Home Points................................................................ 147 11.1.2.2 Diabetes Prevention Program for

that takes a “ unique approach to ‘ fi lling’ outdoor play 11.1.2.6 Summary