Professional Documents
Culture Documents
Vitamin Basics
Vitamin Basics
Edited by
Dr. Volker Spitzer, Global Science Manager, DSM Nutritional Products Ltd.
With a foreword by
Prof. Dr. Florian Schweigert, President of the German Society for Applied
Vitamin Research, Potsdam.
Designed by
graphic art studio, Grenzach-Wyhlen, Germany
Printed in Germany
Burger Druck, Waldkirch, Germany
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discoveries that DSM then links to customers’ needs, extending the range
of offering and creating new business opportunities.
Quality management: Products and services
In 1991, DSM Nutritional Products introduced quality DSM Nutritional Products is the leading supplier of
management based on Good Manufacturing Principles vitamins, carotenoids and fine chemicals to the food
(GMP) and all the relevant International Standards and pharmaceutical industries with a very strong global
Organization ISO (9000) quality standards. Since 1 marketing and sales base. The company provides the
January 2002, the company has had a uniform and following products:
group-wide certification based on the new international
standard ISO 9001:2000. This means that all production Carotenoids
units, premix plants, distribution centers and the entire b-Carotene
global marketing organization are covered by the certifi- CaroCare ® (b-Carotene – Natural Source)
cate. All processes are designed to anticipate customer Apocarotenal
requirements and market trends. Apocarotenoic Ester
Canthaxanthin
You can find more information on Lutein
www.dsmnutritionalproducts.com redivivo™ (Lycopene)
OPTISHARP™ (Zeaxanthin)
Nutraceuticals
ALL-Q ® (Coenzyme Q10)
TEAVIGO™ (EGCG)
BONISTEIN™ (Genistein)
LAFTI ® (Probiotics)
HIDROX ® (Olive Polyphenols)
Other ingredients
Citric Acid
Dextromethorphan Hydrobromide (DMH)
Tretinoin
Micronutrient blends
Contents
Foreword 4
Introduction 5
Vitamin A 11
Beta-carotene 17
Vitamin D 23
Vitamin E 29
Vitamin K 35
Vitamin C 40
Vitamin B 1 47
Vitamin B 2 53
Vitamin B 6 59
Vitamin B 12 65
Niacin 71
Vitamin B 5 76
Folic Acid 81
Biotin 87
References 93
Index 94
2
Foreword
While plants and micro organism have the capability to visible in the history of vitamin D research. In the late
produce the vitamins necessary for the metabolism 1970’s, research established vitamin D as a hormone
themselves, humans and animals have unfortunately essential in bone metabolism. Based on such findings,
lost this ability during evolution. Because of the lack of vitamins are no longer classified into groups defined
specific enzymes for synthesis, vitamins became essen- simply by their physical-chemical properties – such as
tial nutrients for them. It was recognized more than water-soluble and fat-soluble vitamins. More appro-
3500 years ago that vitamins are essential food ingre- priately, vitamins are now classified according to their
dients for maintaining health and well-being. The first biological function in the body; vitamins with coenzyme
records related to the use of specific food items, as we functions, vitamins with hormone-like properties and
know today contain information on specific vitamins, vitamins with antioxidants properties. But as expected
such as vitamin A in liver, to prevent specific diseases the borderlines between these groups can not clearly be
such as night blindness. Only 3000 years later specific defined and needs readjustment with the rapid progress
conditions of deficiency were recorded that could be in research.
attributed to the deficiency of selected nutrients. Well
known examples are scurvy (vitamin C deficiency), In developing countries chronic, diet-related diseases
beriberi (vitamin B 1 ) and rickets (vitamin D). It took are still an important public health problem but in the
another 400 years until we ware able to attribute these affluent societies, the prevention of degenerative
disease conditions to specific active substances in our diseases and also acute vitamin deficiencies might be of
diet named then vitamins. Although we now know that concern. Regarding the continuing debate of optimal
vitamins are not a uniform group of chemical sub- vitamin levels and tolerable upper intake levels (UL) a
stances like proteins, carbohydrates and lipids, we still valid knowledge-base of the daily expanding scientific
use the term to describe the whole group. evidence is necessary. This includes for example the
definition of populations at risk, the problem of appro-
Since the beginning of the last century our knowledge priate biomarkers that not only reflect the dietary intake
on the biological function of vitamins on the molecular but also the local status in specific tissues at risk of
and cellular level has increased significantly. This deficiency as well as environmental factors that influ-
research is reflected by 20 Noble Prize winners between ence status and need for certain vitamins.
1928 and 1967. Despite intensive research efforts no
additional vitamins have been added to the list of 13 The following chapters of this book will contribute to the
vitamins accumulated between 1897 and 1941. better understanding of the important role of vitamins
not only in preventing specific deficiencies but also
While in the past, scientist have basically been concern- maintaining and improving human health and well-being
ed with the role of vitamins in preventing vitamin related by summarizing the actual knowledge-base for the in-
disease and their biochemical functions, today it is dividual vitamins.
recognized that vitamins have an important role in
health and well-being beyond the mere prevention of Prof. Dr. Florian J. Schweigert
deficiency. This aspect of vitamins is based on the President of the German Society for Applied Vitamin
observation that vitamins are not only coenzymes in Research (GVF)
metabolic processes but also act as potent antioxidants Professor for Nutrition, University of Potsdam
and have hormone-like functions. The later is clearly Potsdam, Germany
3
Introduction
Vitamins are essential organic nutrients required in very small amounts for
normal metabolism, growth and physical well-being. Most vitamins are not
made in the body, or only in insufficient amounts, and are mainly obtained
through food. When their intake is inadequate, vitamin deficiency disorders
are the consequence. Vitamins are present in food in minute quantities
compared to the macronutrients protein, carbohydrates and fat. The aver-
age adult in industrialised countries eats about 600g of food per day on a -
dry-weight basis, of which less than 1 gram consists of vitamins.
No single food contains all of the vitamins and, therefore, a balanced and
varied diet is necessary for an adequate intake. Each of the 13 vitamins
known today has specific functions in the body, which makes every one of
them unique and irreplaceable. Vitamins are essential for life!
1. The empirical healing of di- any new vitamin is quite unlikely, 5. The accumulation of reports
seases, now associated with vit- although efforts are still of health benefits beyond
amin deficiency, through con- continuing in that quest. Many of preventing deficiencies and excit-
sumption of particular foods. An the researchers involved in this ing new biochemical functions of
example is the use of liver to treat golden age of the vitamins vitamins ushered in a fifth period,
night blindness (vitamin A defi- received a Nobel prize in reco- starting with the report in 1955 of
ciency) by the Egyptians (Papyrus gnition of their great achie- the cholesterol-lowering effect of
Ebers 1550-1570 BC), Assyrians, vements (Table 2). niacin (1). This is now a well
Chinese, Japanese, Greeks, accepted effect of the vitamin,
Romans, Persians and Arabs. 4. During the era of discovery, a which has nothing at all to do with
fourth period began which was its classical coenzyme role, and is
2. The second phase was charac- concerned with the biochemical a clear health effect beyond pre-
terised by the ability to induce a functions, establishment of venting the deficiency disease
deficiency disease in animals, dietary requirements and pellagra.
which started with the classical commercial production. In the
studies of Lunin and Eijkman early 1930s it was realised that Finally, work on the biochemical
around 1890. The ability to pro- riboflavin (vitamin B 2 ) was part of function of vitamins in the last three
duce deficiency diseases, such as the “yellow enzyme”, which in decades has considerably expanded
beriberi in animals, led to time led to the elucidation of the our concept of how vitamins func-
Hopkins’ concept that small role of the B-vitamins as coen- tion in the body and has helped pro-
amounts of “accessory growth zymes. The subsequent identifi- vide a chemical basis for the in vivo
factors” are necessary for growth cation of most of the B-vitamins observation of their health effects
and life, and the coining of the as coenzymes remained a central (Table 3).
term “vitamine” in 1912 by the theme, defining their function for
Polish-American scientist, Funk. many decades. The first com-
mercial synthesis of vitamin C by
3. The third phase consisted in Reichstein in 1933 was the start
seven decades of exciting of a successful industrial effort
research involving the discovery, that led to the availability of
isolation, structure elucidation relatively inexpensive vitamins for
and synthesis of all the vitamins, research and use in animal
and culminating in the synthesis feedstuffs, for the fortification of
of vitamin B 12 in 1972. Most sci- food products, and for supple-
entists think that the discovery of ments.
5
*Research ongoing
Dietary Reference The primary goal of having these • Estimated Average Requirement
new dietary reference values was (EAR) – the amount of a nutrient
Intakes not only to prevent nutrient deficien- that is estimated to meet the
cies, but also to reduce the risk of requirement of half of all healthy
From 1941 until 1989, RDAs chronic diseases such as osteo- individuals in a given age and
(Recommended Dietary Allowances) porosis, cancer, and cardiovascular gender group. This value is based
were established and used to evalu- disease. on a thorough review of the scien-
ate and plan menus to meet the tific literature.
nutrient requirements of certain The first report, Dietary Reference
groups. They were also used in Intakes for Calcium, Phosphorus, • Recommended Dietary Allowance
other applications such as interpre- Magnesium, Vitamin D and Fluoride, (RDA) – the average daily dietary
ting food consumption records of was published in 1997. Since then, intake of a nutrient that is sufficient
populations, establishing standards three additional vitamin related to meet the requirement of nearly
for food assistance programs, reports have been released, all (97-98%) healthy persons. This
establishing guidelines for nutrition addressing folate and other B vit- is the number to be used as a goal
labelling, etc. amins, dietary antioxidants (vitamins for individuals. It is calculated from
C, E, selenium and the carotenoids), the EAR.
The primary goal of RDAs was to and the micronutrients (vitamins A,
prevent diseases caused by nutrient K, and trace elements such as iron, • Adequate Intake (AI) – only estab-
deficiencies. iodine, etc). The DRIs are a compre- lished when an EAR (and thus an
hensive scientific source primarily for RDA) cannot be determined
In the early 1990s, the Food and nutrition scientists (see References). because the data are not clear-cut
Nutrition Board (FNB), the Institute They are used by health authorities enough; a nutrient has either an
of Medicine, the National Academy in many countries as a basis for RDA or an AI. The AI is based on
of Sciences (USA), with the involve- decisions regarding nutritional infor- experimental data or determined
ment of Health Canada, undertook mation on micronutrients. by estimating the amount of a
the task of revising the RDAs, and a There are four types of DRI reference nutrient eaten by a group of
new family of nutrient reference val- values: the Estimated Average healthy people and assuming that
ues was born – the Dietary Requirement (EAR), the Recom- the amount they consume is ade-
Reference Intakes (DRIs). mended Dietary Allowance (RDA), the quate to promote health.
Adequate Intake (AI) and the Tolerable
Upper Intake Level (UL).
7
• Tolerable Upper Intake Level (UL) also been suggested that marginal Antioxidant
– the highest continuing daily deficiencies are linked to behaviour-
intake of a nutrient that is likely to al and physiological changes. Vitamins
pose no risks of adverse health Extensive surveys have revealed that
effects for almost all individuals. As more than 60% of the elderly have Vitamin C, vitamin E and caro-
intake increases above the UL, the deficient dietary intake of vitamin D, tenoids, such as beta-carotene, are
risk of adverse effects increases. E and folate. Other vitamins – critical micronutrients with antioxidant
Consistently consuming a nutrient not just for the elderly – include properties. Antioxidants are sub-
at the upper level should not cause thiamin (B 1 ), panthothenic acid, and stances that prevent oxidation or
adverse effects. Intake levels at the biotin. chemical reactions involving oxygen.
UL can be interpreted as a ‘war-
ning flag’, not as reason for alarm. Many individuals have health As the atmosphere changed from
problems, habits, or living situations being anaerobic to aerobic, oxygen
in which chronic or periodic intake became available in energy pro-
of vitamins should exceed the duction for living organisms, but it
Certain groups at ordinary requirement. High-risk- also carried a price. When energy is
risk of vitamin groups include: produced, unstable oxygen species
known as free radicals are formed.
deficiencies • the elderly Free radicals are also produced at
• adolescents other sites in the metabolism (e.g.,
With the advent of vitamin fortifica- • young or pregnant and lactating by activated phagocytes as part of
tion in the manufacturing of flour, women the immune defence), and through
cereals and other foods, specific • alcoholics exogenous sources such as expo-
vitamin deficiency diseases such as • cigarette smokers sure to cigarette smoke, environ-
scurvy, beriberi, rickets and pellagra • vegetarians mental pollutants and ultraviolet
have become rare in most industri- • people fasting or on dietary light. Free radicals are atoms or mo-
alised countries. However, in many intervention lecules that have an unpaired elec-
African, Asian and Latin American • laxative abusers tron which makes them very reac-
countries, chronic, diet-related di- • users of contraceptives and tive. They have the potential to dam-
seases continue to be a major health analgesics and other medications age DNA, proteins, carbohydrates,
problem. In these countries there is for chronic disease lipids and cell membranes. In addi-
a need to eliminate frank vitamin A, • people with specific disorders of tion to free radicals, there is another
C and B-complex deficiencies, as the gastrointestinal tract. highly reactive compound that is a
well as other micronutrient deficien- potent generator of free radicals: it is
cies (iodine, iron, selenium, zinc and However, marginal deficiencies are called singlet oxygen. This molecule
calcium). not only limited to those groups is unique in that it contains a pair of
listed. The gradual change in the electrons but exists in an unstable
However, even in highly industri- way we live has influenced our diets configuration and is very reactive.
alised countries, numerous large and has altered our habitual intake
government nutrition surveys of the of vitamins and minerals. Hectic The body has an elaborate antioxi-
population indicate that marginal lifestyles, reduced physical activity dant defence system that works to
vitamin deficiencies with unspecific and an increase in fast and conve- neutralise free radicals and other
symptoms, like fatigue and frequent nience food have all played a signifi- highly reactive species. The major
headaches, are probably not rare. cant role. As a result, a significant biological antioxidants are enzymes
They are difficult for the individual to proportion of the population fails to (superoxide dismutase, catalase and
detect and are largely ignored. reach recommended intake levels. glutathione peroxidase) as well as
Marginal vitamin deficiency is a non-enzymatic scavengers (such as
“state of gradual vitamin depletion in uric acid, CoQ10, glutathione, thiols
which there is evidence of personal in proteins) and the antioxidant
lack of well-being associated with vitamins (beta-carotene, vitamin C
impairment of certain biochemical and E).
reactions”. Studies have found that
many people have nutritional defi- Each of the antioxidant nutrients has
ciencies which do not show up in a specific characteristics, and they
routine physical examination. It has often work synergistically to
8
strengthen the overall antioxidant Vitamin C, a water-soluble antioxi- attention on the part of researchers,
capability of the body. dant, interacts with free radicals in health/nutrition professionals, and
the aqueous compartment of cells. government policymakers, as well as
Vitamin E is the principal fat-soluble Additionally, vitamin C is considered the general public.
antioxidant in the body and is the most important antioxidant in
responsible for protecting the extra-cellular fluids. Vitamin C has
polyunsaturated fatty acids in cell the ability to regenerate vitamin E References
membranes from oxidation by free after it has neutralised free radicals
radicals. Vitamin E exhibits a sparing and terminated chain reactions. http://riley.nal.usda.gov/nal_display/index.php?inf
effect on beta-carotene by pro- o_center=4&tax_level=3&tax_subject=256&topic_
tecting the conjugated double bonds The balance of free radical produc- id=1342&level3_id=5141
from being oxidised. Exposure to tion and the level of antioxidant
increased oxygen levels, such as defences have important disease Dietary Reference Intakes for Calcium, Phos-
reperfusion, results in free radical- and health implications. If there are phorus, Magnesium, Vitamin D, and Fluoride
mediated tissue damage. However, too many free radicals produced, (1997) National Academy of Sciences. Institute of
due to the capability of vitamin E to and too few antioxidants, to a condi- Medicine. Food and Nutrition Board.
work at higher oxygen pressures, tion of “oxidative stress” develops
free radicals are scavenged and which can lead to chronic injury. Dietary Reference Intakes for Thiamin, Riboflavin,
tissue injury is minimised. Niacin, Vitamin B 6, Folate, Vitamin B12,
It has therefore been suggested that Pantothenic Acid, Biotin, and Choline (1998)
Beta-carotene also has antioxidant oxidative stress might play a role in National Academy of Sciences. Institute of
properties and is one of the most the development of a number of Medicine. Food and Nutrition Board.
powerful quenchers of singlet oxy- diseases:
gen. It can dissipate the energy of Dietary Reference Intakes for Vitamin C, Vitamin E,
singlet oxygen, thus preventing this • cancer Selenium, and Carotenoids (2000) National
active molecule from generating free • atherosclerosis Academy of Sciences. Institute of Medicine. Food
radicals. • cardiovascular diseases and Nutrition Board.
• cataracts
• age-related macular degeneration Dietary Reference Intakes for Vitamin A, Vitamin K,
• Alzheimer’s disease Arsenic, Boron, Chromium, Copper, Iodine, Iron,
• immune dysfunction Manganese, Molybdenum, Nickel, Silicon,
• rheumatoid arthritis Vanadium, and Zinc (2001) National Academy of
Sciences. Institute of Medicine. Food and Nutrition
Oxidative stress also plays a role Board.
in the aging process.
Vitamins continue
to fascinate, and
have become the
focus of renewed
9
Vitamin A
Synonyms
Retinol, axerophthol
Chemistry
Retinol and its related compounds consist of four isoprenoid units joined
head to tail and contain five conjugated double bonds. They naturally occur
as alcohol (retinol), as aldehyde (retinal) or as acid (retinoic acid).
CH3
*The Dietary Reference Intakes (DRIs) are actually Allowances (RDAs). The RDA was established as
a set of four reference values: Estimated Average a nutritional norm for planning and assessing
Requirements (EAR), Recommended Dietary dietary intake, and represents intake levels of
Allowances (RDA), Adequate Intakes (AI), and essential nutrients considered to meet adequately
Tolerable Upper Intake Levels, (UL) that have the known needs of practically all healthy people
Child suffering from corneal scar replaced the 1989 Recommended Dietary
13
History
Although it has been known since ancient Egyptian times that certain foods,
such as liver, would cure night blindness, vitamin A per se was not identi-
fied until 1913. Its chemical structure was defined by Paul Karrer in 1931.
Professor Karrer received a Nobel Prize for his work because this was the
first time that a vitamin’s structure had been determined.
1931 Karrer isolates practically pure retinol from the liver oil of a
species of mackerel. Karrer and Kuhn isolate active carotenoids.
1997 UNICEF, the World Health Organisation (WHO), and the govern-
ments of countries including Canada, the United States and the
United Kingdom, as well as national governments in countries
where vitamin deficiency is widespread, launch a global cam-
paign to distribute high-dose vitamin A capsules to malnourished
children.
Otto Isler
15
Beta-carotene
Chemistry
Beta-carotene is a terpene. It is made up of eight isoprene units, which are
cyclised at each end. The long chain of conjugated double bonds is respon-
sible for the orange colour of beta-carotene.
History
1907 Willstatter and Mieg establish the molecular formula for carotene,
a molecule consisting of 40 carbon and 56 hydrogen atoms.
1982 Krinsky and Deneke show the interaction between oxygen and
oxyradicals using carotenoids.
2004 Results from the French SU.VI.MAX study indicate that a com-
bination of antioxidant vitamins (C, E and beta-carotene) and
minerals lowers total cancer incidence and all-cause mortality in
men.
Paul Karrer
Otto Isler
21
Vitamin D
Synonyms
Calciferol; antirachitic factor; “sunshine” vitamin
Chemistry
Vitamin D is a generic term and indicates a molecule of the general struc-
ture shown for rings A, B, C, and D with differing side chain structures. The
A, B, C, and D ring structure is derived from the cyclopentanoperhydro-
phenanthrene ring structure for steroids. Technically, vitamin D is classified
as a seco-steroid. Seco-steroids are those in which one of the rings has
Vitamin D crystals in polarised light been broken; in vitamin D, the 9,10 carbon-carbon bond of ring B is broken.
H3C H CH3
CH3
H CH3
H
CH2
H
OH
Molecular formula of vitamin D3 (cholecalciferol)
22
Recommended Safety
Dietary Allowance Hypervitaminosis D is a potentially
serious problem as it can cause
(RDA) permanent kidney damage, growth
retardation, calcification of soft
Establishing an RDA for vitamin D is tissues and death. Mild symptoms of
difficult because vitamin D can be intoxication are nausea, weakness,
endogenously produced in the body constipation and irritability. In gener-
through exposure to sunlight. al, the toxic dose for adults is
Healthy people regularly exposed to around 1.25 mg (50,000 IU) per day.
the sun have no dietary requirement However, certain individuals have an
for vitamin D, under appropriate increased sensitivity to vitamin D
conditions. As this is rarely the case and present with toxic symptoms
in temperate zones, however, a after 50 µg (2,000 IU) per day.
dietary supply is needed. Hypervitaminosis D is not associated
In 1997, the Food and Nutrition with overexposure to the sun
Board based adequate intake levels because a regulating mechanism
(AI) on the assumption that no vita- prevents overproduction of vitamin Supplements and
min D is produced by UV light in the D.
skin. An AI of 5 µg (200 IU)/day is food fortification
recommended for infants, children The Food and Nutrition Board (FNB)
and adults (ages 19-50 years). For and the EU Scientific Committee on Monopreparations of vitamin D and
the elderly, higher intakes are rec- Food have set the tolerable upper related compounds are available as
ommended to maintain normal calci- intake level (UL) for vitamin D at 50 tablets, capsules, oily solutions and
um metabolism and maximise bone µg/day for adolescents and adults. injections. Vitamin D is also incorpo-
health. In other countries, adult rec- rated in combinations with vitamin A,
ommendations range from 2.5 µg calcium, and in multivitamins.
(100 IU) to 10 µg (400 IU). In many countries, milk and milk
products, margarine and vegetable
oils fortified with vitamin D serve as
a major dietary source of the vita-
min.
Current recommendations in the USA
RDA* Industrial
Infants 5 µg (AI)
Children 1-18 years 5 µg (AI) production
Males 19-50 years 5 µg (AI)
Females 19-50 years 5 µg (AI) Cholecalciferol is produced com-
Males 51- 70 years 10 µg (AI) mercially by the action of ultraviolet
Females 51-70 years 10 µg (AI) light on 7-dehydrocholesterol, which
is obtained from cholesterol by vari-
Males . 70 years 15 µg (AI)
ous methods. Ergocalciferol is pro-
Females . 70 years 15 µg (AI)
duced in a similar manner from
Pregnancy 5 µg (AI) ergosterol, which is extracted from
Lactation 5 µg (AI) yeast. Starting material for the pro-
duction of caIcitriol is the cholesterol
*The Dietary Reference Intakes (DRIs) are actually Allowances (RDAs). The RDA was established as derivative pregnenolone.
a set of four reference values: Estimated Average a nutritional norm for planning and assessing
Requirements (EAR), Recommended Dietary dietary intake, and represents intake levels of
Allowances (RDA), Adequate Intakes (AI), and essential nutrients considered to meet adequately
Tolerable Upper Intake Levels, (UL) that have the known needs of practically all healthy people
replaced the 1989 Recommended Dietary
25
History
1984 The same group presents evidence that calcitriol has a regulato-
ry role in immune function.
1989 Baker and associates show that the vitamin D receptor belongs
to the steroid-receptor gene family.
Elmer V. McCollum
Adolf Windaus
27
Vitamin E
Synonyms
Tocopherol
Chemistry
A group of compounds composed of a substituted chromanol ring with a
C 16 side chain saturated in tocopherols, with 3 double bonds in
tocotrienols.
Introduction
Deficiency prophylactic role of vitamin E in pro- not easily be acquired even with the
tecting against exogenous pollutants best nutritional intentions, yet most
Because depletion of vitamin E tis- and lowering the risk of cancer and research studies show that optimal
sue stores takes a very long time, no of cataracts. intake levels associated with health
overt clinical deficiency symptoms Vitamin E in combination with vita- benefits tend to be high. Vitamin E
have been noted in otherwise min C may protect the body from intake should also be adapted to
healthy adults. Symptoms of vitamin oxidative stress caused by extreme that of PUFA, which influences the
E deficiency are seen in patients sports (e.g. ultra marathon running). requirement for this vitamin. The EC
with fat malabsorption syndromes or A role of vitamin E supplementation Scientific Committee on Foods (SCF)
liver disease, in individuals with in the treatment of neurodegenera- has suggested a consumption ratio
genetic defects affecting the a-toco- tive diseases (Alzheimer´s disease, of 0.4 mg a-TE per gram of PUFA.
pherol transfer protein and in new- amyotrophic lateral sclerosis) is also
born infants, particularly premature under investigation.
infants.
Vitamin E deficiency results in neuro- Safety
logical symptoms (neuropathy),
myopathy (muscle weakness) and Recommended Vitamin E has low toxicity. After
pigmented retinopathy. Early diag- Dietary Allowance reviewing more than 300 scientific
nostic signs are leakage of muscle studies, the US-based Institute of
enzymes, increased plasma levels of (RDA) Medicine (IOM) concluded that vita-
lipid peroxidation products and min E is safe for chronic use even at
increased haemolysis of erythro- The recommended daily intake of doses of up to 1000 mg per day. A
cytes (red blood cells). In premature vitamin E varies according to age, recently published meta-analysis
infants, vitamin E deficiency is asso- sex and criteria applied in individual suggested that taking more than
ciated with haemolytic anaemia, countries. In the USA, the RDA for 400 IU of vitamin E per day brought
intraventricular haemorrhage and adults is 15 mg RRR- a-toco- a weekly increase in the risk of all-
retrolental fibroplasia. pherol/day (FNB, 2000). In Europe, cause mortality. However, much of
adult recommendations range from the research was done in patients at
4 to 15 mg a-TE/day for men and high risk of a chronic disease and
from 3 to 12 mg a-TE/day for these findings may not be generalis-
Disease women. able to healthy adults. Many human
prevention and The RDA for vitamin E of 15 mg can- long-term studies with higher doses
therapeutic use
Current recommendations in the USA
of vitamin E have not reported any Vitamin E has been used topically as Industrial
adverse effects, and it has been an anti-inflammatory agent, to
concluded that vitamin E intakes of enhance skin moisturisation and to production
up to 1600 IU (1073 mg RRR- a- prevent cell damage by UV light.
tocopherol) are safe for most adults. In pharmaceutical products toco- Vitamin E derived from natural
The Antioxidant Panel of the Food pherol is used, for example, to sta- sources is obtained by molecular
and Nutrition Board (FNB, 2000) has bilise syrups, aromatic components, distillation and, in most cases,
set the UL (tolerable upper intake and vitamin A or provitamin A com- subsequent methylation and esterifi-
level) for adults at 1000 mg/day of ponents. cation of edible vegetable oil prod-
any form of supplemental a-toco- a-Tocopherol is used as an antioxi- ucts. Synthetic vitamin E is pro-
pherol. In 2003 the EC Scientific dant in plastics, technical oils and duced from fossil plant material by
Committee on Foods (SCF) estab- greases, and in the purified, so- condensation of trimethylhydro-
lished the UL of 300 mg a-TE for called white oils, employed in cos- quinone with isophytol.
adults. Also in 2003, the UK Expert metics and pharmaceuticals.
group on Vitamins and Minerals
(EVM; 2003) set the UL at 540 mg
a-TE for supplemental vitamin E.
Pharmacologic doses of vitamin E
may increase the risk of bleeding in
patients treated with anticoagulants.
Patients on anticoagulant therapy or
those anticipating surgery should
avoid high levels of vitamin E.
Supplements,
food fortifica-
tions and other
applications
Vitamin E is available in
soft gelatine capsules, or as
chewable or effervescent
tablets, and is found in most
multivitamin supplements.
The most common fortified
foods are soft drinks and
cereals.
History
1911 Hart and coworkers publish the first report of a suspected “anti-
sterility factor” in animals.
1945 Dam and coworkers discover peroxides in the fat tissue of ani-
mals fed on vitamin E-deficient diets. The first antioxidant theory
of vitamin E activity is proposed.
1980 Walton and Packer propose that vitamin E may prevent the
generation of potentially carcinogenic oxidative products of
unsaturated fatty acids.
2004 Barella and coworkers demonstrate that vitamin E regulates gene Paul Karrer
expression in the liver and the testes of rats.
33
Vitamin K
Synonyms
Phylloquinone, menaquinone
Chemistry
Compounds with vitamin K activity are 3-substituted 2-methyl-1,4-naphtho-
quinones. Phylloquinone contains a phytyl group, whereas menaquinones
contain a polyisoprenyl side chain with 6 to 13 isoprenyl units at the 3-posi-
tion.
thesis of vitamin K. During opera- Recently, studies with cancer cell Safety
tions in which bleeding is expected lines and animal studies have indi-
to be a problem, for example, in gall- cated that a combination of vitamin
bladder surgery, vitamin K 1 is admin- C and vitamin K 3 has antitumor Even when large amounts of vitamin
istered. activity and inhibits the development K 1 and K 2 are ingested over an
Anticoagulants inhibit vitamin K of metastases. extended period, toxic manifesta-
recycling, which can be corrected tions have not been observed.
rapidly and effectively by the admin- Therefore, the major health authori-
istration of vitamin K 1 . ties have not established a tolerable
Vitamin K 1 is often given to mothers Recommended upper level of intake (UL) for vitamin
before delivery and to newborn K. Allergic reactions have been
infants to protect against intracranial
Daily Allowance reported, however. Furthermore,
haemorrhage. (RDA) administered menadione (K 3 ) has
A putative role of vitamin K in osteo- been known to cause haemolytic
porosis has been investigated since The US Food and Nutrition Board of anaemia, jaundice and kernicterus (a
vitamin K-dependent proteins have the Institute of Medicine (2001) has grave form of jaundice in the new-
been discovered in bone. However, established an adequate intake (AI) born) and is no longer used for treat-
further investigations are required to level for adults based on reported ment of vitamin K deficiency.
resolve whether vitamin K is a signif- dietary intakes of vitamin K in appar-
icant etiological component of ently healthy population groups.
osteoporosis. A role for vitamin K in Other health authorities have come
the development of atherosclerosis to similar conclusions. Supplements, food
is also under discussion, but studies fortification and
supporting this hypothesis are limit-
ed and future research is recom- other applications
mended.
History
1943 Dam receives half of the Nobel prize for his discovery of vitamin
K, the blood coagulation factor.
1943 Doisy receives half of the Nobel prize for his discovery of the
chemical nature of vitamin K.
Carl P. H. Dam
Edward A. Doisy
38
Vitamin C
Synonyms
Ascorbic acid, hexuronic acid, anti-scorbutic vitamin
Chemistry
L-ascorbic acid (2,3-endiol-L-gulonic acid-g-lactone), dehydro-L-ascorbic
acid (2-oxo-L-gulonic acid- g-lactone).
Introduction for blood cholesterol levels and gall- bage, spinach and tomatoes is also
stones. In addition, vitamin C plays of importance. Depending on the
an important role in the synthesis of season, one medium-sized glass of
Vitamin C is water-soluble, and several important peptide hormones freshly pressed orange juice (i.e. 100
probably the most famous of all the and neurotransmitters and carnitine. g) yields from 15 to 35 mg vitamin C.
vitamins. Even before its discovery Finally, vitamin C is also a crucial
in 1932, physicians recognised that factor in the eye's ability to deal with
there must be a compound in citrus oxidative stress, and can delay the
fruits preventing scurvy, a disease progression of advanced age-related Absorption and
that killed as many as 2 million macular degeneration (AMD) and
sailors between 1500 and 1800. vision-loss in combination with other
body stores
Later researchers discovered that antioxidant vitamins and zinc.
man, other primates and the guinea Intestinal absorption of vitamin C
pig depend on external sources to depends on the amount of dietary
cover their vitamin C requirements. Main functions in a nutshell: intake, decreasing with increasing
Most other animals are able to syn- • Immune stimulation intake levels. At an intake of 30 to
thesise vitamin C from glucose and • Anti-allergic 180 milligrams, about 70% to 90% is
galactose in their body. • Antioxidant absorbed; about 50% of a single
• “Cement” for connective tissues dose of 1 to 1.5 grams is absorbed;
• Wound healing and only 16% of a single dose of 12
• Teeth and gum health grams is absorbed. Up to about 500
Functions • Aids iron absorption milligrams are absorbed via a sodi-
• Eye health um-dependent active transport
The most prominent role of vitamin C process, while at higher doses sim-
is its immune stimulating effect, ple diffusion occurs.
which is important for the defence
against infections such as common The storage capacity of water-solu-
colds. It also acts as an inhibitor of Dietary sources ble vitamins is generally low com-
histamine, a compound that is pared to that of fat-soluble ones.
released during allergic reactions. As Vitamin C is widely distributed in Humans have an average tissue
a powerful antioxidant it can neu- fruits and vegetables. Citrus fruits, store of vitamin C of 20 mg/kg body
tralise harmful free radicals and aids blackcurrants, peppers, green veg- weight. The highest concentration is
in neutralising pollutants and toxins. etables (e.g. broccoli, Brussels found in the pituitary gland (400
Thus it is able to prevent the forma- sprouts), and fruits like strawberries, mg/kg); other tissues of high con-
tion of potentially carcinogenic guava, mango and kiwi are particu- centration are the adrenal glands,
nitrosamines in the stomach (due to larly rich sources. On a quantity liver, brain and white blood cells
consumption of nitrite-containing basis, the intake of potatoes, cab- (leukocytes).
foods, such as smoked meat).
Importantly, vitamin C is also able to
regenerate other antioxidants such
as vitamin E. Vitamin C is required Vitamin C content of foods Measurement
for the synthesis of collagen, the
intercellular “cement” substance Food Vitamin C Vitamin C can be measured in the
which gives structure to muscles, (mg/100g) blood plasma and other body tis-
vascular tissues, bones, tendons sues by various techniques. Also
Acerolas 1600
and ligaments. Due to these func- dipstick tests for estimation of vita-
tions vitamin C, especially in combi- Blackcurrants 200 min C levels in the urine are avail-
nation with zinc, is important for the Peppers 138 able. Less satisfying, however, is the
healing of wounds. Vitamin C con- Broccoli 115 evaluation of the analytical data con-
tributes to the health of teeth and Fennel 95 cerning the true reflection of the
gums, preventing haemorrhaging Kiwis 71 body status. Threshold values are
and bleeding. It also improves the difficult to define and the subject of
Strawberries 64
absorption of iron from the diet, and controversial discussion. Typical
Oranges 49
is needed for the metabolism of bile blood plasma levels are in the range
acids, which may have implications (Souci, Fachmann, Kraut) of 20 to 100 µmol/L.
40
Negative interactions
Due to toxic compounds in
smoke, the vitamin C require-
ment for smokers is about 35
mg/day higher than for non-
smokers. Also several pharma-
cologically active compounds,
among them some anti-depres-
41
Disease plaque, as this helps to prevent the ment in severity of colds after vita-
oxidation of LDL cholesterol (the min C supplementation may be due
prevention and “bad” cholesterol), especially in to the antihistaminic action of mega
combination with vitamin E. Some doses of vitamin C.
therapeutic use data has shown that vitamin C may
also boost blood levels of HDL cho- Wound healing
Dozens of prospective studies sug- lesterol (the “good” cholesterol), During a postoperative period, or
gest that vitamin C plays a role in which is also considered positive for during healing of superficial wounds,
preventing a variety of diseases. It is the prevention of heart diseases. supplemental vitamin C contributes
also used to treat certain diseases in The risk of stroke may be reduced to the prevention of infections and
orthomolecular medicine. As this by an adequate intake of vitamin C promotes skin repair.
nutrient is important for a variety of through fruits, vegetables and sup-
diseases, only a selection of them plements. However, due to the Blood pressure
are presented here in detail. inconsistency of the data and its Several studies have shown a blood
lack of specificity to vitamin C, the pressure lowering effect of vitamin C
Cardiovascular diseases (CVD) interpretation of these results is diffi- supplementation at about 500 mg
(heart disease and stroke) cult. per day due to improved dilation of
The data for the CVD protective ben- blood vessels.
efits of vitamin C are inconsistent. Cancer
While some studies have failed to The role of vitamin C in cancer pre-
find significant reductions in the risk vention has been studied extensive-
of coronary heart disease (CHD), ly, and until now no beneficial effect Recommended
numerous prospective cohort stud- has been shown for breast, prostate, Dietary Allowance
ies have found inverse associations or lung cancer. However, a number
between dietary vitamin C intake or of studies have associated higher (RDA)
vitamin C plasma levels and CVD intakes of vitamin C with decreased
risk. Vitamin C may protect coronary incidence of cancers of the upper
arteries by reducing the build-up of digestive tract, cervix, ovary, blad- The recommended daily intake of
der, and colon. Studies finding sig- vitamin C varies according to age,
nificant cancer risk reduction by sex, risk group and criteria applied
dietary intake recommended at least in individual countries. The RDAs in
5 servings of fruits and vegetables the USA for vitamin C were recently
per day. Five servings of most fruits revised upwards to 90 mg/day for
and vegetables provide more than men and 75 mg/day for women,
200 mg vitamin C per day. Just sig- based on pharmacokinetic data. For
nificant cancer risk reductions were smokers, these RDAs are increased
found in people consuming at least by an additional 35 mg/day. Higher
80 to 110 mg of vitamin C daily. amounts of vitamin C are also rec-
ommended for pregnant (85 mg/day)
Common cold and lactating women (120 mg/day).
Numerous studies have shown a The RDAs are in a similar range in
general lack of effect of other countries. Recent evidence
prophylactic vitamin sets the estimate for the mainte-
C supplementation nance of optimal health in the region
on the incidence of of 100 mg daily.
common cold, but
they do show a
moderate benefit in
terms of the duration
and severity of
episodes in some
groups, especially those
who are exposed to sub-
stantial physical and/or
cold stress. The improve-
42
Industrial
production
The synthesis of ascorbic acid was
achieved by Reichstein in 1933, and
Current recommendations in the USA this was followed by industrial pro-
duction five years later by Hoffman
Dietary Reference Intakes* La Roche Ltd. (the vitamin division of
Infants , 6 months 40mg (Adequate Intake, AI) which is now DSM Nutritional
Infants 7-12 months 50mg (AI) Products Ltd.). Today synthetic vita-
Children 1-3 years 15mg min C, identical to that occurring in
nature, is produced from glucose on
Children 4-8 years 25mg
an industrial scale by chemical and
Children 9-13 years 45mg
biotechnological synthesis.
Males 14-18 years 75mg
Females 14-18 years 65mg
Males . 19 years 90mg
Females . 19 years 75mg
Pregnancy , 18 years 80mg
Pregnancy . 19 years 85mg
Lactation , 18 years 115mg
Lactation . 19 years 120mg
*The Dietary Reference Intakes (DRIs) are actually Allowances (RDAs). The RDA was established as
a set of four reference values: Estimated Average a nutritional norm for planning and assessing
Requirements (EAR), Recommended Dietary dietary intake, and represents intake levels of
Allowances (RDA), Adequate Intakes (AI), and essential nutrients considered to meet adequately
Tolerable Upper Intake Levels, (UL) that have the known needs of practically all healthy people
replaced the 1989 Recommended Dietary
43
History
Ca.
400 BC Hippocrates describes the symptoms of scurvy.
Albert Szent-Györgyi
Vitamin B1
Synonyms
Thiamin, thiamine, antiberiberi factor, aneurine, antineuritic factor, nerve
vitamin.
Chemistry
Pyrimidine and thiazole moiety linked by a methylene bridge – phosphory-
lated forms: thiamin monophosphate (TMP), thiamin diphosphate (TDP),
thiamin triphosphate (TTP).
N N
+ CH3
NH2
CI
Molecular formula of vitamin B1-chloride
46
Absorption and
Functions
Dietary sources body stores
The main functions of thiamin are
connected to its role as a coenzyme Thiamin is found in most foods, but Gastrointestinal absorption of nutri-
in the form of thiamin pyrophoshate mostly in small amounts. The best tional thiamin occurs in the lumen of
(TPP). Coenzymes are 'helper mole- source of thiamin is dried brewer’s the small intestine (mainly the
cules' which activate enzymes, the yeast. Other good sources include jejunum) by means of a sodium and
proteins that control the thousands meat (especially pork and ham prod- energy dependent active transport
of biochemical processes occurring ucts), some species of fish (eel, mechanism. For thiamin levels high-
in the body. TPP acts as a “helper tuna), whole grain cereals and er than 2 µmol/L, passive diffusion
molecule” in about 25 enzymatic bread, nuts, pulses, dried legumes plays an additional role. Thiamin
reactions and plays an essential role and potatoes. Concerning cereal occurs in the human body as free
in the production of energy from grains, the thiamin-rich bran is thiamin and its phosphorylated
food in the carbohydrate metabolism removed during the milling of wheat
as well as in the links between car- to produce white flour, and during
bohydrate, protein and fat metabo- the polishing of brown rice to pro-
lism. It is one of the key compounds duce white rice. As a consequence,
for several reactions in the break- enriched and fortified grain-products
down of glucose to energy. are common today.
Furthermore, TPP is coenzyme for
the metabolism of branched-chain
keto acids that are derived from
branched-chain amino acids.
*The Dietary Reference Intakes (DRIs) are actually Allowances (RDAs). The RDA was established as
a set of four reference values: Estimated Average a nutritional norm for planning and assessing
Requirements (EAR), Recommended Dietary dietary intake, and represents intake levels of
Allowances (RDA), Adequate Intakes (AI), and essential nutrients considered to meet adequately
Tolerable Upper Intake Levels, (UL) that have the known needs of practically all healthy people
replaced the 1989 Recommended Dietary
49
Safety
Thiamin has been found to be well Industrial
tolerated in healthy people, even at production
very high oral doses (up to 200
mg/day). Due to its very broad
safety margin for oral administration Chemical synthesis of thiamin is a
and long history of safe use, none of complicated process, involving
the official regulatory authorities has some 15-17 different steps.
defined a safe upper limit for this Although commercial production of
vitamin. The only reaction found in thiamin was first accomplished in
humans is of the hypersensitivity 1937, the production did not
type. In the vast majority of cases develop on a broad scale until the
these have occurred after injection 1950s, when demand rose sharply
of thiamin in patients with a history because of food fortification.
50
History
1897 Dutch medical officers Eijkman and Grijns show that the symp-
toms of beriberi can be reproduced in chickens fed on polished
rice, and that these symptoms can be prevented or cured by Christian Eijkman
feeding them rice bran.
1912 Funk isolates the antiberiberi factor from rice bran extracts and
calls it a 'vitamine' - an amine essential for life. The name finds
ready acceptance and helps to focus attention on the new con-
cept of deficiency diseases.
1926 Jansen and Donath isolate antiberiberi factor from rice bran.
1943 Williams and coworkers, and Foltz and colleagues carry out
dietary studies that document widespread thiamin deficiency in
the United States.
Robert R. Williams
51
Vitamin B2
Synonyms
Riboflavin, riboflavine, vitamin B 2 , lactoflavin, ovoflavin
Chemistry
7,8-dimethyl-10-(1-D-ribityl)isoalloxazin - different redox states: flavochinon
(Fl ox ), flavosemichinon (Fl-H), flavohydrochinon (Fl red H 2 ).
Coenzyme Form(s): FMN (flavin mononucleotide, riboflavin monophos-
phate), FAD (flavin adenine dinucleotide, riboflavin adenosine diphosphate).
Deficiency
Overt clinical symptoms of riboflavin
deficiency are rarely seen in devel-
oped countries. However, the sub-
clinical stage of deficiency, charac-
terised by a change in biochemical
indices, is common. Riboflavin defi-
ciency rarely occurs in isolation but
usually in combination with deficien-
cies of other B-complex vitamins,
because flavoproteins are also
involved in the metabolism of other
54
B-complex vitamins. Along with Groups at risk of deficiency by chronic alcoholism and chronic
other B-vitamins, low vitamin B 2 sta- Individuals who have inadequate stress. During pregnancy and lacta-
tus has been associated with food intake are at risk of deficiency, tion riboflavin requirement is
unfavourably increased plasma particularly children from low socio- increased.
homocysteine levels. The absorption economic backgrounds in develop-
of iron, zinc and calcium is impaired ing countries, elderly people with
in riboflavin deficiency. poor diets, chronic ‘dieters’, and
people who exclude milk products Disease
Clinically, vitamin B 2 -defiency affects from their diet (vegans). Riboflavin
many organs and tissues. Most deficiency may also occur as a result
prevention and
prominent are the effects on the of: therapeutic use
skin, mucosa and eyes: • trauma, including burns and
• glossitis (magenta tongue, geo- surgery
graphical tongue) • chronic disorders (e.g. rheumatic Eye-related diseases
• cheilosis, angular stomatitis (fis- fever, tuberculosis, subacute Oxidative damage of lens proteins by
sures at the corners of the mouth) bacterial endocarditis, diabetes, light may lead to the development of
• sore throat hypothyroidism, liver cirrhosis) age-related cataracts. Riboflavin defi-
• burning of the lips, mouth, and • intestinal malabsorption, e.g. ciency leads to decreased glu-
tongue morbus crohn, sprue, lactose tathione reductase activity, which can
• inflamed mucous membranes intolerance result in cataracts. Therefore,
• pruritus (itching) • chronic medication (tranquillisers, riboflavin is used in combination with
• seborrheic dermatitis (moist scaly oral-contraceptives, thyroid hor- other antioxidants, like vitamin C and
skin inflammation) mones, fibre-based laxatives, carotenoids, in disease prevention for
• corneal vascularisation associated antibiotics) age-related cataracts. Riboflavin has
with sensitivity to bright light, • high physical activity been used to treat corneal ulcers,
impaired vision, itching and a feel- • phototherapy for newborns during photophobia and noninfective con-
ing of grittiness in the eyes icterus junctivitis in patients without any typ-
The consequences of a low ical signs of deficiency, with benefi-
In severe long-term deficiency, dam- riboflavin intake may be aggravated cial results. Most cases of riboflavin
age to nerve tissue can cause deficiency respond to daily oral doses
depression and hysteria. of 5-10 mg.
Other symptoms are normocytic and
normochromic anaemia, and periph-
eral neuropathy of the extremities Current recommendations in the USA
(tingling, coldness and pain). Low
intracellular levels of flavin coen- RDA*
zymes could effect mitochondrial Infants , 6 months 0.3mg (Adequate Intake, AI)
function, oxidative stress and blood Infants 7-12 months 0.4mg (AI)
vessel dilation, which have been
Children 1-3 years 0.5mg
associated with pre-eclampsia dur-
Children 4-8 years 0.6mg
ing pregnancy.
Children 9-13 years 0.9mg
Males . 14 years 1.3mg
Females 14-18 years 1.0mg
Females . 19 years 1.1mg
Pregnancy 1.4mg
Lactation 1.6mg
*The Dietary Reference Intakes (DRIs) are actually Allowances (RDAs). The RDA was established as
a set of four reference values: Estimated Average a nutritional norm for planning and assessing
Requirements (EAR), Recommended Dietary dietary intake, and represents intake levels of
Allowances (RDA), Adequate Intakes (AI), and essential nutrients considered to meet adequately
Tolerable Upper Intake Levels, (UL) that have the known needs of practically all healthy people
replaced the 1989 Recommended Dietary
55
History
1941 Sebrell and coworkers demonstrate clinical signs of riboflavin Otto Heinrich Warburg
deficiency in human feeding experiments.
Richard Kuhn
Paul Karrer
57
Vitamin B6
Synonyms
Vitamin B 6 is composed of three forms (vitamers): pyridoxine or pyridoxol
(the alcohol), pyridoxal (the aldehyde) and pyridoxamine (the amine).
Chemistry
Pyridoxine (3-hydroxy-2-methylpyridine) is a basal compound of the group.
Substitution (R) is carried out on 5'-C. Pyridoxic acid is an inactive catabo-
lite of the compounds.
H3C N
R = CH2OH = Pyridoxine
R = CHO = Pyridoxal
R = CH2NH2 = Pyridoxamine
History
1945 Snell demonstrates that two other natural forms of the vitamin Joseph Goldberger
exist, namely pyridoxal and pyridoxamine.
Paul György
Vitamin B12
Synonyms
Cobalamin, antipernicious-anaemia factor, Castle’s extrinsic factor, or
animal protein factor.
Chemistry
The structure of vitamin B 12 is based on a corrin ring, which has two of the
pyrrole rings directly bonded. The central metal ion is Co (cobalt). Four of
the six coordinations are provided by the corrin ring nitrogens, and a fifth by
a dimethylbenzimidazole group. The sixth coordination partner varies, being
Cyanocobalamin crystals in polarised light a cyano group (-CN) (cyanocobalamin), a hydroxyl group (-OH) (hydroxo-
cobalamin), a methyl group (-CH3) (methylcobalamin) or a 5'-deoxyadeno-
syl group (5-deoxyadenosylcobalamin).
CH3
H2NOC–CH2–CH2
H3C CH2–CONH2
H2NOC–CH2
CH2–CH2–CONH2
CH3 CN
CH3 N N
+
Co N CH3
H N N
CH3 N
H2NOC–CH2 CH3
CH3
H3C
CH3 CH2–CH2–CONH2
CH3 O
HO
O
CH2CH2CONHCH2C O P O
CH2OH
H O
A number of anticonvulsants – phe- damage to the nervous system by vegetarian mothers. Strict vege-
nobarbitone, primidone, phenytoin remains. It is therefore essential to tarians are urged to use a vitamin
and ethylphenacemide – can alter diagnose the deficiency accurately B 12 supplement.
the metabolism of cobalamins in the before starting therapy. The Food
cerebrospinal fluid and lead to neu- and Nutrition Board advises adults
ropsychic disturbances. Several to limit their folic acid intake Pernicious anaemia:
substituted amide, lactone and lac- (through supplements and fortifica- Pernicious anaemia is the classi-
tam analogues of cyanocobalamin tion) to 1 mg per day. cal symptom of B 12 deficiency,
compete with binding sites on intrin- but it is actually the end-stage of
sic factor and lead to depressed Cause of deficiency is not usually an autoimmune inflammation of
absorption of the vitamin. Nitrous insufficient dietary intake but lack of the stomach, resulting in destruc-
oxide (anaesthetic) also interferes intrinsic factor secretion. Without tion of stomach cells by the
with cobalamin metabolism. intrinsic factor, absorption is not body’s own antibodies. Anaemia
possible and a severe and persistent is a condition in which red blood
deficiency develops that cannot be cells do not provide adequate
prevented by the usual dietary oxygen to body tissues.
Deficiency intakes of vitamin B 12 . This occurs in Pernicious anaemia is a type of
people with: megaloblastic anaemia.
Clinical cobalamin deficiency due to
dietary insufficiency is rare in • pernicious anaemia (a hereditary Gastric atrophy:
younger people, but occurs more autoimmune disease that chiefly Gastric atrophy is a chronic
frequently in older people. Vitamin affects persons post middle age), inflammation of the stomach
B 12 deficiency affects 10-15% of • food-bound vitamin B 12 malabsorp- resulting in decreased stomach
individuals over the age of 60. tion, reported in patients on long- acid production. Because this is
term treatment with certain drugs, necessary for the release of vita-
Deficiency of vitamin B 12 leads to and in elderly patients with gastric min B 12 from the proteins in food,
defective DNA synthesis in cells, atrophy. vitamin B 12 absorption is reduced.
which affects the growth and repair • after gastrectomy
of all cells. Tissues most affected are • after ingestion of corrosive agents
those with the greatest rate of cell with destruction of gastric mucosa.
turnover, e.g. those of the • lesions of the small bowel (blind
haematopoietic system. This can loops, stenoses, strictures, diver- Disease
lead to megaloblastic anaemia ticula). Bacterial overgrowth may prevention and
(characterised by large and imma- lead to competitive utilisation of
ture red blood cells) and neuropathy, available vitamin. Impaired absorp- therapeutic use
with numerous symptoms including: tion also occurs in patients with
glossitis, weakness, loss of appetite, small intestinal defects (e.g. sprue,
loss of taste and smell, impotence, celiac disease, ileitis, ileal resec- Pernicious anaemia
irritability, memory impairment, mild tion) and those with inborn errors of Patients with lack of intrinsic factor
depression, hallucination, breath- cobalamin metabolism, secretion of secretion can be effectively treated
lessness (dyspnea) on exertion, tin- biologically abnormal intrinsic fac- using oral vitamin B 12 but require
gling and numbness (paraesthesia). tor, or Zollinger-Ellison syndrome. lifetime vitamin B 12 therapy. When
Vitamin B 12 deficiency can also lead • pancreatic insufficiency used alone, oral doses of at least
to hyperhomocysteinaemia, a possi- • in alcoholics vitamin B 12 intake 150 µg/day are necessary, although
ble risk factor for occlusive vascular and absorption are reduced, while single weekly oral doses of 1000 µg
disease. elimination is increased have proved satisfactory in some
• AIDS also brings an increased risk cases. Combinations of vitamin B 12
The symptoms of vitamin B 12 defi- of deficiency and intrinsic factor may be given,
ciency are similar to those of folic but as a variable number of patients
acid deficiency, the major difference The risk of nutritional deficiency is become refractory to intrinsic factor
being only that vitamin B 12 deficien- increased in vegans; a high intake of after prolonged treatment, parenter-
cy is associated with spinal cord fibre has been shown to aggravate a al therapy with cyanocobalamin or
degeneration. If folic acid is used to precarious vitamin balance. There hydroxocobalamin is preferred.
treat vitamin B 12 deficiency, anaemia have also been reports of vitamin
may be alleviated but the risk of B 12 deficiency in infants breast-fed
67
History
1824 The first case of pernicious anaemia and its possible relation to
disorders of the digestive system is described by Combe.
1926 Minot and Murphy report that a diet of large quantities of raw Georg Richard Minot
liver to patients with pernicious anaemia restores the normal level
of red blood cells. Liver concentrates are developed and studies
on the presumed active principle(s) (“antipernicious anaemia
factor”) are initiated.
1929 Castle postulates that two factors are involved in the control of
pernicious anaemia: an “extrinisic factor” in food and an
“intrinsic factor” in normal gastric secretion. Simultaneous
administration of these factors causes red blood cell formation
which alleviates pernicious anaemia.
1934 Whipple, Minot and Murphy are awarded the Nobel prize for
medicine for their work in the treatment of pernicious anaemia.
William Parry Murphy
1948 Rickes and associates (USA) and Smith and Parker (England),
working separately, isolate a crystalline red pigment which they
name vitamin B 12 .
Synonyms
Vitamin B 3 , vitamin B 4 , PP factor (pellagra-preventative factor)
Chemistry
Nicotinic acid (pyridine-3-carboxylic acid), nicotinamide (pyridine-3 carbox-
amide)
N N
Nicotinic Acid Nicotinic Amide
RDA*
Infants , 6 months 2mg (AI)
Infants 7-12 months 4mg (AI)
Children 1-3 years 6mg
Children 4-8 years 8mg
Children 9-13 years 12mg
Males . 14 years 16mg
Females . 14 years 14mg
Pregnancy 18mg
Lactation 17mg
*The Dietary Reference Intakes (DRIs) are actually Allowances (RDAs). The RDA was established as
a set of four reference values: Estimated Average a nutritional norm for planning and assessing
Requirements (EAR), Recommended Dietary dietary intake, and represents intake levels of
Allowances (RDA), Adequate Intakes (AI), and essential nutrients considered to meet adequately
Tolerable Upper Intake Levels, (UL) that have the known needs of practically all healthy people
replaced the 1989 Recommended Dietary
73
History
1755 The disease pellagra is first described by Thiery who calls the
disease “mal de la rosa”.
1955 Altschul and associates report that high doses of nicotinic acid
reduce serum cholesterol in man.
1961 Turner and Hughes demonstrate that the main absorbed form of
niacin is the amide.
1979 Shepperd and colleagues report that high doses of nicotinic acid
lower both serum cholesterol and triglycerides.
Conrad Elvehjem
1980 Bredehorst and colleagues show that niacin status affects the
extent of ADP-ribosylation of proteins.
Tom Spies
74
Pantothenic Acid
Synonyms
Vitamin B 5 , antidermatosis vitamin, chick antidermatitis factor, chick
antipellagra factor
Chemistry
Pantothenic acid is composed of beta-alanine and 2,4-dihydroxy-3,3-
dimethyIbutyric acid (pantoic acid), acid amide-linked. Pantetheine consists
of pantothenic acid linked to a ß-mercaptoethylamine group.
CH3 H O H
History
1931 Williams and Truesdail separate an acid fraction from “bios”, the
growth factor for yeast discovered in 1901 by Wildiers.
1965 Pugh and Wakil identify the acyl carrier protein as an additional
active form of pantothenic acid.
Tadeusz Reichstein
79
Folic Acid
Synonyms
Folacin, vitamin B C , vitamin B 9 , Lactobacillus casei factor
Chemistry
Folic acid consists of a pteridine ring system, p-aminobenzoic acid and one
molecule of glutamic acid (chemical name: pteroylglutamic acid). Naturally
occurring folates are pteroylpolyglutamic acids with two to eight glutamic
acid groups.
folate deficiency, as are patients with effective in decreasing the risk of Recommended
renal failure who require regular neural tube defects and other birth
haemodialysis. Acute folate defi- defects than folic acid alone. Dietary Allowance
ciences have been reported to occur Numerous studies have shown that
within a relatively short time in even moderately elevated levels of
(RDA)
patients undergoing intensive care, homocysteine in the blood increase
especially those on total parenteral the risk of atherosclerosis. Folic acid In the USA the recommendations of
nutrition. has been shown to decrease homo- the Food and Nutrition Board (1998)
cysteine levels. Several randomised are expressed as DFEs. This organi-
placebo-controlled trials are sation recommends a daily intake of
presently being conducted to estab- 400 µg of DFE for adult females and
Disease lish whether folic acid supplementa- males. To cover increased needs
tion reduces the risk of cardiovascu- during pregnancy and lactation, it
prevention and lar diseases by lowering homocys- recommends 600 µg/day and 500
therapeutic use teine blood levels. µg/day respectively. In Europe, the
A number of different observational RDA varies between 200-400
studies have found poor folate sta- µg/day for adults in different coun-
In situations where there is a high tus to be associated with increased tries.
risk of folate deficiency, oral folic cancer risk. There is evidence that
acid supplementation is recom- folate plays a role in preventing col- Dietary Folate Equivalents (DFE)
mended, usually in a multivitamin orectal cancer. The results of two have been introduced because of
preparation containing 400-500 µg large epidemiological investigations the different bioavailability of
of folic acid. suggest that increased folate intake folates and folic acid.
In acute cases of megaloblastic may reduce breast cancer risk asso-
anaemia, treatment often has to be ciated with regular alcohol con- 1 µg DFE = 1 µg of food folate
started before a diagnosis of the sumption. = 0.5 µg of folic acid
cause (vitamin B 12 or folate deficien- Low folate levels have also been taken on an empty
cy) has been made. To avoid compli- associated with Alzheimer´s disease, stomach
cations that may arise by treating a dementia and depression. = 0.6 µg of folic acid
B 12 deficiency with folic acid in such from fortified food or
circumstances (see below), both as a supplement
folic acid and vitamin B 12 need to be taken with meals
administered until a specific diagno-
sis is available.
It has been demonstrated that peri-
conceptional (before and during the Current recommendations in the USA
first 28 days after conception) sup-
plementation of women with folic RDA*
acid can decrease the risk of neural RDA listed as dietary folate
tube defects (malformations of the Infants , 6 months 65 µg (AI)
brain and spinal cord, causing anen-
Infants 7-12 months 80 µg (AI)
cephaly or spina bifida). Therefore, a
daily intake of 400 µg folic acid in Children 1-3 years 150 µg
addition to a healthy diet 8 weeks Children 4-8 years 200 µg
prior to and during the first 12 weeks Children 9-13 years 300 µg
after conception is recommended. Adults . 14 years 400 µg
There is evidence that adequate Pregnancy 600 µg
folate status may also prevent the
Lactation 500 µg
incidence of other birth defects,
including cleft lip and palate, certain *The Dietary Reference Intakes (DRIs) are actually Allowances (RDAs). The RDA was established as
heart defects and limb malforma- a set of four reference values: Estimated Average a nutritional norm for planning and assessing
tions. Requirements (EAR), Recommended Dietary dietary intake, and represents intake levels of
Results from intervention studies Allowances (RDA), Adequate Intakes (AI), and essential nutrients considered to meet adequately
have shown that a multivitamin sup- Tolerable Upper Intake Levels, (UL) that have the known needs of practically all healthy people
plement containing folic acid is more replaced the 1989 Recommended Dietary
83
Industrial
production
Folic acid is manufactured on a
large scale by chemical synthesis.
Various processes are known. Most
synthesised folic acid is used in ani-
mal feed.
84
History
1931 Wills in India observes the effect of liver and yeast extracts on tropical
macrocytic anaemia and concludes that this disorder must be due to a
dietary deficiency. She recognises that yeast contains a curative agent
equal in potency to that of liver.
1938 Day and coworkers find an antianaemia factor for monkeys in yeast and
designate it “vitamin M.” Around the same time, Stokstad and Manning
discover a growth factor for chicks, which they call “Factor U”.
1939 Hogan and Parrott identify an antianaemia factor for chicks in liver
extracts, which they name “Vitamin BC”.
1941 Mitchell and colleagues suggest the name “folic acid” (folium, Latin for
leaf) for the factor responsible for growth stimulation of Streptococcus
lactis, which they isolate from spinach and suspect of having vitamin-like
properties for animals.
1945 Angier and coworkers report the synthesis of a compound identical to the
L. casei factor isolated from liver. They later describe the chemical struc-
tures of the basic and related compounds.
Esmond Emerson Snell
1945 Spies demonstrates that folic acid cures megaloblastic anaemia during
pregnancy.
1962 Herbert consumes a folate-deficient diet for several months and records
his development of deficiency symptoms. His findings set the criteria for
the diagnosis of folate deficiency. In the same year, Herbert estimates the
folic acid requirements for adults, which still serve as a basis for many
RDAs.
1991 Wald establishes that folic acid supplementation reduces risk of neural
tube defects by 70% among women who have already given birth to a
child with such birth defects.
Robert B. Angier
1992 Butterworth finds that higher than normal serum levels of folic acid are
associated with decreased risk of cervical cancer in women infected with
human papillomavirus. Also, Czeizel demonstrates that first-time occur-
rence of neural tube defects may be largely eliminated with a multivitamin
containing folic acid taken in the periconceptional period.
1993 The US Public Health Service recommends that all women of childbearing
potential consume 0.4 mg (400 µg) of folate daily in order to reduce the risk
of foetal malformations such as spina bifida and other neural tube defects.
1998 Fortification of all enriched cereal grains (e.g., enriched bread, pasta, flour,
rice and breakfast cereals) with folic acid becomes mandatory in the USA
and in Canada. In Hungary, wheat flour is fortified with folic acid.
Tom Spies
2000 Fortification of wheat flour with folic acid is established in Chile.
85
Biotin
Synonyms
Vitamin H (“Haar und Haut”, German words for “hair and skin”), vitamin B 8
and co-enzyme R.
Chemistry
Biotin has a bicyclic ring structure. One ring contains a ureido group and the
other contains a heterocyclic sulphur atom and a valeric acid side-group.
(Hexahydro-2-oxo-1H-thieno [3,4-d]imidazole-4-pentanoic acid). Bio-
logically active analogues: biocytin (e-N-biotinyl-L-lysine), oxybiotin (S sub-
Biotin crystals in polarised light stituted with O).
O
H H
N N
H H
H
S COOH
Molecular formula of biotin
86
Disease
Interactions Deficiency prevention and
therapeutic use
Negative interactions Human biotin deficiency is extremely
Raw egg whites contain avidin, a rare. This is probably due to the fact There is no direct evidence that mar-
glycoprotein that strongly binds with that biotin is synthesised by benefi- ginal biotin deficiency causes birth
biotin and prevents its absorption. cial bacteria in the human intestinal defects in humans, but an adequate
Thus, the ingestion of large quanti- tract. Potential deficiency symptoms biotin intake/supplementation during
ties of raw egg white over a long include anorexia, nausea, vomiting, pregnancy is advisable.
period can result in a biotin deficien- glossitis, depression, dry scaly der- Biotin is used clinically to treat the
cy. It has also been reported that matitis, conjunctivitis and ataxia, biotin-responsive inborn errors of
antibiotics which damage the intes- and after long-lasting, severe biotin metabolism, holocarboxylase syn-
tinal flora (thus decreasing bacterial deficiency, loss of hair colour and thetase deficiency and biotinidase
synthesis) can reduce biotin levels. hair loss (alopecia). Signs of biotin deficiency.
Interactions with certain anticonvul- deficiency in humans have been Large doses of biotin may be given
sant drugs and alcohol have also demonstrated in volunteers consum- to babies with a condition called
been reported, as they may inhibit ing a biotin-deficient diet together infantile seborrhea or to patients
intestinal carrier-mediated transport with large amounts of raw egg white. with genetic abnormalities in biotin
of biotin. Pantothenic acid ingested After 3-4 weeks they developed a metabolism. A large number of
in large amounts competes with fine dry scaly desquamating der- reports have shown a beneficial
biotin for intestinal and cellular matitis, frequently around the eyes, effect of biotin in infant seborrheic
uptake because of their similar nose, and mouth. After ten weeks on dermatitis and Leiner's disease (a
structures. the diet, they were fatigued, generalised form of seborrheic der-
depressed and sleepy, with nausea matitis).
and loss of appetite. Muscular pains, Biotin supplements are sometimes
hyperesthesia and paresthesia given to help reduce blood sugar in
occurred, without reflex changes or diabetes patients. People with type
other objective signs of neuropathy. 2 diabetes often have low levels of
Volunteers also developed anaemia biotin. Some patients with diabetes
and hypercholesterolaemia. Liver may have an abnormality in the
biopsies in sudden infant death biotin-dependent enzyme pyruvate
syndrome babies reveal low biotin carboxylase, which can lead to dys-
levels. Most of the affected infants function of the nervous system.
were bottle-fed. The main benefit of biotin as a
88
dietary supplement is in strengthen- and thus an RDA, for biotin. Instead mg per day without objectionable
ing hair and nails. Biotin supple- an Adequate Intake level (AI) has effects. Due to the lack of reports of
ments may improve thin or splitting been defined. The AI for biotin adverse effects, no major regulatory
toenails or fingernails and improve assumes that current average authorities have established a toler-
hair health. Uncomable hair syn- intakes of biotin (35 µg to 60 µg/day) able upper level of intake (UL) for
drome in children also improves with are meeting the dietary requirement. biotin.
biotin supplementation, as do cer- An estimation of the safe and ade-
tain skin disorders, such as “cradle quate daily dietary intake for biotin
cap”. Biotin has also been used to was made for the first time in 1980
combat premature graying of hair, by the Food and Nutrition Board of Supplements and
though it is likely to be useful only the United States National Research
for those with a low biotin status. In Council. The present recommenda-
food fortification
orthomolecular medicine biotin is tions in the USA are 20-30 µg daily
used to treat hair loss, but scientific for adults and children over 11 Biotin, usually either in the form of
evidence is not conclusive. years, and 5-12 µg daily for infants crystalline D-biotin or brewer’s
Biotin has been used for people in and younger children. France and yeast, is added to many dietary sup-
weight loss programs to help them South Africa recommend a daily plements, infant milk formulas and
metabolise fat more efficiently. intake of up to 300 µg, and baby foods, as well as various
Singapore up to 400 µg biotin. dietetic products. As a supplement,
Others, including the Federal biotin is often included in combina-
Republic of Germany, assume that tions of the B vitamins. Mono-
Recommended diet and intestinal synthesis provide preparations of biotin are available in
Dietary Allowance sufficient amounts. some countries as oral and par-
enteral formulations.
(RDA) Therapeutic doses of biotin for
patients with a biotin deficiency
Safety range between 5 and 20 mg daily.
In 1998 the Food and Nutrition Seborrheic dermatitis and Leiner's
Board of the Institute of Medicine No known toxicity has been associ- disease in infants respond to daily
felt the existing scientific evidence ated with biotin. Biotin has been doses of 5 mg. Patients with bio-
was insufficient to calculate an EAR, administered in doses as high as 40 tinidase deficiency require life-long
RDA*
Infants , 6 months 5 µg (Adequate Intake, AI)
Infants 7-12 months 6 µg (AI)
Children 1-3 years 8 µg (AI)
Children 4-8 years 12 µg (AI)
Children 9-13 years 20 µg (AI)
Children 14-18 years 25 µg (AI)
Adults . 19 years 30 µg (AI)
Pregnancy 30 µg (AI)
Lactation 35 µg (AI)
*The Dietary Reference Intakes (DRIs) are actually Allowances (RDAs). The RDA was established as
a set of four reference values: Estimated Average a nutritional norm for planning and assessing
Requirements (EAR), Recommended Dietary dietary intake, and represents intake levels of
Allowances (RDA), Adequate Intakes (AI), and essential nutrients considered to meet adequately
Tolerable Upper Intake Levels, (UL) that have the known needs of practically all healthy people
replaced the 1989 Recommended Dietary
89
History
1927 Boas confirms the findings of dermatosis and hair loss in rats fed
with raw egg white. She shows that this egg white injury can be
cured by a “protective factor X” found in the liver. Paul György
1931 György also discovers this factor in the liver and calls it vitamin H
(from Haut, the German word for skin).
1935 Kögl and Tönnis extract a crystalline growth factor from dried egg
yolk and suggest the name ‘biotin’.
1940 György and his associates conclude that biotin, vitamin H and
coenzyme R are identical. They also succeed in isolating biotin
from the liver. Fritz Kögl
1942 Kögl and his group in Europe and du Vigneaud and his associates
in the USA establish the structure of biotin.
1981 Burri and her colleagues show that the early infantile form of
multiple carboxylase deficiency is due to a mutation affecting
holocarboxylase synthetase activity.
References
Dietary Reference Intakes for Cal- Expert Group on Vitamins and
cium, Phosphorus, Magnesium, Minerals. Safe upper levels for vita-
Vitamin D, and Fluoride (1997) mins and minerals, Food Standards
National Academy of Sciences. Agency, United Kingdom, 2003.
Institute of Medicine. Food and http://www.foodstandards.gov.uk/m
Nutrition Board. ultimedia/pdfs/vitmin2003.pdf
Index
Vitamin A history 16 measurement 19
immune function 12 negative interactions 19
acne 14 industrial production 15 provitamin A 18
axerophthol 11 introduction 12 RDA 20
beta-carotene 18 measurement 13 RE (retinol equivalent) 19
bone mineral density 15 mortality 14 safety 20
carotenoids 11, 13, 18 negative interactions 13 skin 19
chylomicrons 13 positive interactions 13 stability 19
cornea 12, 14 pregnancy 14 supplements and food
differentiation 12 prevention of vitamin A fortification 20
embryonic development 12 deficiency 14 carotenodermia 20
enterocytes 13 RDA 14 cholestyramine 19
epithelial cells 12 RE (retinol equivalent) 13 colestipol 19
erythropoiesis 13 safety 15 dioxygenase 18
follicular hyperkeratosis 14 stability 13 free radicals 18
gene expression 12 supplements and food HPLC (high performance liquid
hormone 12 fortification 15 chromatography) 19
hypervitaminosis A 15 UL 15 lipids 18
immune system 12 vision 12 omeprazole 19
iron 13 vitamin A activity 13 orlistat 19
killer cells 13 vitamin A content of foods 11 prostaglandin synthesis 18
lymphocytes 13 vitamin E 13 provitamin A carotenoids 18, 19
malformations 14, 15 vitamin A analogues 14 singlet oxygen 18
measles 13, 14 xerophthalmia 14, 16 terpene 17
nuclear receptor proteins 12 zinc 13
opsin 12
phagocytes 13 Vitamin D
provitamin A 13 beta-carotene
psoriasis 14 alkaline phosphatase 25
reproduction 12 beta-carotene 17-22 anticonvulsant 25
retinal 12, 15 see also vitamin A antirachitic factor 23, 27
retinoic acid 12, 16 absorption and body stores 18 bone density 25
retinol 12, 13, 15, 16 antioxidant activity 18 calcidiol
retinol equivalent (RE) 13 beta-carotene content of foods 18 (25-hydroxycholecalciferol) 24
retinyl esters 11, 12 bioavailability 18 calcitriol (1,25-dihydroxy-
rhodopsin 12 cancer and cardiovascular cholecalciferol) 24, 27
rod cells 11-16 diseases 19 calcium 24, 25, 26
vitamin A 3–8 chemistry 17 cell proliferation 24
see also beta-carotene deficiency 19 cholecalciferol (vitamin D 3 ) 24
blindness 12 dietary sources 18 cholestyramine 25
bone health 15 disease prevention and corticosteroid hormones 25
cellular differentiation 12 therapeutic use 19 diabetes mellitus 25
chemistry 11 erythropoietic protoporphyria 20 differentiation 24, 27
deficiency 12 free radical chain reactions 18 ergocalciferol (vitamin D 2 ) 24
dietary sources 13 functions 18 hypervitaminosis D 26
disease prevention and history 21 hypovitaminosis D 25
therapeutic use 12 immune system 19 insulin secretion 24
functions 12 industrial production 20 laxatives 25
growth and development 12 introduction 18 mineral balance 24
93
Vitamin C anaemia 56
Vitamin B1 antibiotics 55
advanced age-related macular barbiturates 55
degeneration (AMD) 41 acetylcholin 48 calcium 56
anti-scorbutic vitamin 40 adrenalin 48 cataracts 56
ascorbic acid 40 aneurine see vitamin B 1 chlorpromazin 55
bioflavonoids 42 antineuritic factor see vitamin B 1 creatinine 55
carnitine 41 beriberi 48 depression 56
cholesterol 41, 43 carbohydrate metabolism 48, 49 FAD dependent erythrocyte
collagen 41 HPLC (high performance liquid glutathion reductase 55
galactose 41 chromatography) 50 flavin adenine dinucleotide (FAD) 53
gangrene 42 neurotransmitters 48 flavin mononucleotide
glucose 41, 42 pentose phosphate pathway 48 (FMN) 54, 55, 58
haemorrhages 42 serotonin 48 flavoproteins 54, 55
histamine 41 thiamin see vitamin B 1 homocysteine 56
neurotransmitters 41 thiamin diphosphate (TDP) 47 HPLC (high performance liquid
nitrosamines 41 thiamin monophosphate (TMP) 47 chromatography) 55
orthomolecular medicine 43 thiamin pyrophoshate (TPP) 48 iron 56
peptide hormones 41 thiamin triphosphate (TTP) 47 lactoflavin 53
petechiae 42 thiaminases 49 migraine 57
plaque 43 transketolase 48, 49 ouabain 55
scurvy 41, 42, 45 vitamin B 1 47-52 ovoflavin 53
stress 41 absorption and body stores 49 oxidation-reduction (redox)
vitamin C 40-46 antioxidant vitamins 49 reactions 54
absorption and body stores 41 arsenic 48 peripheral neuropathy 56
antioxidant 41 chemistry 48 probenecid 55
blood pressure 43 chronic alcoholism 50 respiratory chain 54
cancer 43 coenzyme 48 riboflavin see vitamin B 2
95
Biotin
antibiotics 89
avidin 88
avidin binding assay 88
biotin 87-92
absorption and body stores 88
biotin content of foods 88
chemistry 87
coenzyme 88
deficiency 89
dietary sources 88
disease prevention and
therapeutic use 89
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