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Observations on multivitamins.



Introduction

This is the first of a series of columns to assist healthcare practitioners and a growing number of interested consumers in understanding the basic concepts of the use of dietary supplements, or "nutraceuticals." In the title of these teaching columns, the word "therapeutics" is an oxymoron, given the US Dietary Supplement and Health Education Act of 1994 (DSHEA). This legislation requires that all dietary supplements carry the disclaimer "These statements have not been approved by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease."

[ILLUSTRATION OMITTED]

This disclaimer represents a major enigma in modern medicine. Many health-care practitioners or recipients increasingly use nutritional supplements, botanicals, and herbs to prevent or treat disease. In fact, the mainstay of several increasingly popular traditional medical treatments, such as naturopathic medicine or Ayurveda, is the use of natural medicine and, often, the avoidance of pharmaceuticals. In essence, these "traditional" methodologies may not be perceived as conforming to "usual and customary" standards of medical care in the US.

Surveys have indicated that consumers often purchase dietary supplements with a view to wellness promotion or disease management. This circumstance highlights the problems associated with the 'legislation" of medical practice. This kind of legislation has been identified as interfering with freedom of health care, and it affects the increasing self-reliance among patients in taking control of their own health-care needs. In fact, the modern concept of the Patients' Bill of Rights emphasizes the patient's ownership of wellness promotion and the patient's importance as the decision-maker in a well-developed healer/client relationship.

The past two decades have witnessed a major shift in medical treatment paradigms, where consumer lobbies have demanded simpler and gentler ways of health promotion. This situation is perceived by many as a potential, viable alternative to allopathic Allopathic
Pertaining to conventional medical treatment of disease symptoms that uses substances or techniques to oppose or suppress the symptoms.

Mentioned in: Traditional Chinese Medicine
 interventions, despite arguments to the contrary. Of course, these circumstances have led to a residual dichotomy in medical practice. There has been the modern emergence of alternative medicine on the one hand, somewhat pitched against conventional medicine on the other.

This harsh interface of differing opinion between the alternative and the conventional has softened over the past decade. This has resulted in attempts to take a "politically correct" position under the umbrella of "integrative medicine." There seems to be a raging debate on the evidence base, or lack thereof, that supports nonconventional medical practice, but patients own their own treatment decisions. This responsibility must be complemented by education, in order that the patient may make an informed judgment about his own disease management or prevention strategies.

In medical emergencies, natural medicine may have relatively little to offer. However, natural therapeutics may star in the realm of prevention and the management of common "functional disease" or "disorders." Therefore, the author of this column does not turn his back on allopathic medicine, but some conventional medical strategies have been shown to possess disadvantages or limitations. Most notable is the observation that US citizens are the most medicated individuals in the world per capita, but their general level of health is ranked below that of more than 40 other countries.

The objective of these columns on natural medicine is to provide basic information on how dietary supplements could be applied as complementary adjuncts in disease prevention or management. However, all of the author's comments in these writings must recruit the protection of "freedom of speech," because only pharmaceuticals and accepted surgical interventions are considered usual and customary standards of medical care in the US. (1) Many US citizens are appealing for greater freedom in health-care choices. This preamble is relevant to all subsequent columns where the therapeutic potential of natural substances may be discussed to a variable degree. Manufacturers and purveyors of dietary supplements are governed by strict regulations that do not permit "treatment claims." (1)

"Vitamin Therapies": Assessing Vitamin Needs

There are few people who doubt the benefit of supplementing the standard American diet (SAD) with essential vitamins and selected minerals. (1) Vitamins are a group of naturally occurring substances that are essential for the maintenance of all body structures and functions. Vitamins cannot be made by the human body, with the notable exception of vitamin D. There has been much recent research that shows that the correct dosages of vitamins in the diet can improve health and well-being in many ways. While dietary supplements have been labeled as "not to be used for the prevention or treatment of diseases," the exceptions should arguably be vitamins and minerals, especially when they are prescribed by a physician. (1) Vitamins and minerals have been shown to variably reduce the chances of developing many diseases, when used correctly, and they are known to promote health and well-being, most notably in states of deficiency. (1)

Food scientists are correct in their assertion that vitamins and minerals are best obtained from the diet. However, much processed food in Western societies, and in urban areas in third-world countries, has been manipulated to a degree that it has been robbed of many vitamins and minerals. There is a new problem emerging in potential vitamin and mineral deficiencies. This problem is related to the modern global epidemic of obesity. (2) Individuals who are trying to control their weight may often reduce the amount of food they eat. If they are reducing the intake of processed food, which may already be deficient in vitamins, they are putting themselves at risk of deficiencies. (3)

It is known that excessive calorie intake in the diet is one major cause for obesity, but much food is manufactured to be inexpensive with high calorie content. I am not suggesting that people are walking around with obvious signs of vitamin deficiency, but it must be clearly understood that marginal deficiency of several vitamins or minerals is quite common, especially in the elderly or in the large segment of the population that relies heavily upon "fast," processed, or "junk" foods.

In recent times, many physicians or other health-care providers may have changed their opinions about the need for vitamin or mineral supplements. There are many examples of population studies that show intakes of essential vitamins to be often below recommended daily intakes or values (RDI, RDV). Consumers must understand that the concept of the RDI was generated from assessments of vitamin intake that would prevent nutrient deficiencies. This does not necessarily mean that the RDI of a vitamin is enough for optimal health or the promotion of well-being. This has led to the suggestion that there may be optimal levels of intake of vitamins that are higher than the RDI. In addition, there are some circumstances where physicians use vitamins in higher dosages for therapeutic effects. High doses of vitamins should not be self-administered, especially if the vitamin is known to be toxic in larger amounts (A, D or K). (1)

The author believes that it is no longer possible to rely upon the average Western diet or SAD as a means of achieving optimal vitamin or mineral intake. (1) There are glaring examples of these circumstances. For example, many elderly people do not have enough vitamin D to maintain healthy bones, teeth, and other body structures, even though it can be synthesized by the body through exposure to sunlight. Furthermore, there are many references concerning the inability of individuals to receive a necessary amount of vitamins C or E from dietary sources. Many Americans are strangers to fruit and vegetables, and even daily dietary intakes of vitamin C may be inadequate in many people. (4) Only a limited segment of the population obtains the five servings of fruit and vegetables per day recommended by the obsolete USDA USDA,
n.pr See United States Department of Agriculture.
 Food Pyramid.

There are many circumstances in which the author believes that vitamin supplementation is absolutely necessary. These include calorie-controlled dieting and acute or chronic illness, or the presence of risk factors for illness, where the need for extra vitamins may be mandatory. Excessive urination in diabetes flushes out vitamins and essential minerals (e.g., magnesium and zinc), which must be then taken in the diet in greater amounts. (1)

Western society is constantly "on the go," and so nutritional challenges are made worse by the lack of time that people have to shop for well-balanced food substances and prepare their own meals. This basic information about nutrition provides a compelling argument for every person to consider his daily needs of essential vitamins and minerals.

New Horizons for the Use of Vitamins

Many scientists and health-care providers believe in taking enough vitamins to help ensure health and well-being. (4-15) Therefore, the modern use of vitamins has more to do with the promotion of wellness than merely avoiding vitamin deficiencies. (1-15) Scientists who have proposed and modified RDIs of vitamins have been quite frank with their opinion that it is not easy to determine ideal dosages. There is a growing medical view that these dosages are likely to be much higher than the standard recommendations or values that currently prevail in medical thought.

Vitamin needs change dramatically with age, disease status, environmental conditions and health status, to name a few circumstances. (1) Adequate vitamin or mineral intake cannot be effective in promoting health without positive lifestyle changes, such as the use of a balanced, nutrient-dense diet that is somewhat restricted in saturated fat, simple sugar, and animal protein. Modern dietary recommendations for health must stress the importance of increasing dietary fiber intake (about 25 g or more/day), with a more liberal use of healthy fats, such as omega-3 fatty acids, found in fish oil. (2)

Much concern continues to be expressed about the adverse effects of taking too many vitamins. The author thinks that this fear has been somewhat overestimated, because there are relatively few reports of toxicity from the use of vitamin supplements. However, a general rule is that the fat-soluble vitamins A, D, E, and K are not to be taken in high dosages without medical supervision. (1) Consumers become confused when studies are reported that allege negative outcomes from taking larger dosages of a single vitamin. In recent times, this situation has arisen with the use of vitamin E. (12), (13)

Many studies that focus on the single use of a nutritional substance are able to be criticized by their construction, which may not result in a conclusion that can be generally applied to the population. (1) The author believes that this was the case in the recent reports of the dangers of using higher dosages of vitamin E in patients with heart disease. That said, vitamin E is an antioxidant vitamin, and the dietary supplement industry may have been overpromoting the use of antioxidants as single agents, which in high dosages may cause unwanted actions such as "pro-oxidant effects."

Some scientists have suggested that vitamin supplementation can be tailored to a patient's individual needs. Unfortunately, this commendable approach is very difficult to achieve by self-management. (1) The background presented here for vitamin usage means that there is a compromise to be achieved between the RDI of vitamins and the avoidance of adverse effects of certain types of vitamin excess.

Naturopathic physicians and other practitioners of natural medicine may in general tailor vitamin needs to their patients so that they can achieve well-being beyond simple health. This approach is not often found in conventional medicine. Many drugs are known to deplete certain vitamins or minerals, and the act of adding supplements with pharmaceutical prescriptions is often overlooked. The population must be made more aware of drug-induced nutrient depletions (e.g., vitamin B12 depletion by potent antisecretory antisecretory /an·ti·se·cre·to·ry/ (-se-kre´tah-re)
1. secretoinhibitory; inhibiting or diminishing secretion.

2. an agent that so acts, as certain drugs that inhibit or diminish gastric secretions.
 drugs).

An Overview of the Health Benefits of Vitamins

There are many accounts of the actions of individual vitamins on body structures and functions. A brief overview of the health benefits of vitamins is given in Table 1. (16-26) All practicing clinicians must have a working knowledge of the actions of essential vitamins. Recent research has identified many previously ignored functions of vitamins.
Table 1: Actions of Vitamins "At a Glance." (All functions are not
described.)

Vitamin                                 General actions

Vitamin A, alpha, beta,            maintains epithelial tissue,
gamma-carotene                     critical in bone and tooth
                                   development, supports night vision,
                                   and is toxic in large dosages

Vitamin D, calciferol              a prohormone, essential to support
                                   teeth and bones; a major role in
                                   absorption and metabolism of calcium
                                   and phosphorous, and toxic in large
                                   dosages

Vitamin E, tocopherols             a principal antioxidant that
                                   supports structure of unsaturated
                                   fatty acids and vitamin A;
                                   anti-hemolytic actions with support
                                   of reproductive function,
                                   maintenance of epithelium and
                                   eicosanoid metabolism

Vitamin K, phylloquinone and       provides support for normal blood
menaquinone                        clotting functions; toxic in large
                                   dosages

Thiamine                           provides support for carbon dioxide
                                   removal from alpha-keto acids during
                                   carbohydrate oxidation, maintenance
                                   of digestive function, and nervous
                                   system function

Riboflavin                         acts as enzyme in tissue
                                   respiration, transports hydrogen
                                   ions, coenzyme forms flavin
                                   mononucleotide (FMN) and flavin
                                   adenine dinucleotide (FAD)

Niacin, nicotinic acid and         supports amino acid and carbohydrate
nicotinamide                       metabolism, promotes tissue
                                   respiration and fat synthesis, part
                                   of enzyme system

Vitamin B6, pyridoxine, pyridoxal  supports amino acid breakdown,
and pyridoxamine                   converts tryptophan to niacin,
                                   produces unsaturated fatty acids
                                   from essential fatty acids

Folate                             supports red blood cell growth,
                                   promotes production of nucleic acid,
                                   acts as coenzyme tetrahydrofolic
                                   acid

Vitamin B12                        promotes production of
                                   nucleoproteins and nucleic acids,
                                   supports folate, nervous tissue, and
                                   single-carbon fragment metabolism

Pantothenic acid                   part of coenzyme A, promotes
                                   metabolic function

Biotin                             supports enzyme function,
                                   particularly breakdown of fatty
                                   acids and amino acids

Vitamin C, ascorbic acid           classic antioxidant with special
                                   role in maintenance of intracellular
                                   cement substances, preservation of
                                   capillary structure, wound healing,
                                   allergic reactions, and facilitation
                                   of iron absorption; important role
                                   in hydroxylation and support of
                                   immune function


Vitamin A is present in the body in many different chemical forms. (16), (17) There are retinoids, which are "formed-types" of vitamin A, and a series of naturally occurring compounds called carotenoids that can be converted variably into vitamin A itself. Vitamin A plays a major role in supporting eye function, body linings, normal bone growth, immune functions, and reproduction. Vitamin A or beta-carotene may reduce the risk of cancer in some circumstances, but opinions are divided. Excessive amounts of vitamin A should be avoided, especially during pregnancy (due to teratogenicity ter·a·to·ge·nic·i·ty
n.
The capability of producing fetal malformation.


teratogenicity, (terˈ·
).

Vitamin D is probably best not referred to as a vitamin, because, unlike other vitamins, it can be manufactured in the body. It occurs in chemical forms called calciferols. The natural, active form is D3, which has many "hormonal actions" in the body. Vitamin D is best known for its ability to increase calcium and phosphorus absorption, and it has an important role in the formation of bones and teeth. Also, it supports the production of insulin, promotes healthy immune function, and has a role in cancer prevention. Excessive amounts are not recommended because of potential toxicity; but adverse effects are only seen at high dosages, taken continuously (> about 50,000 IU/day, depending upon the context).

Vitamin E occurs in several forms called tocopherols and tocotrienols. There is evidence that naturally originating vitamin E is more effective than synthetic vitamin E. Vitamin E is a classic antioxidant vitamin, and it plays a major role in protecting cell membranes against damage (antioxidant effects). (19), (20) It works in concert with vitamins A and C as a classic antioxidant, and it supports reproductive function. Whether or not vitamin E is toxic in high dosages remains arguable, but continuously taking more than 400 IU per day should be done only under medical supervision.

Vitamin K is the classic vitamin utilized by the body in blood clotting. It is not often deficient in the diet and can be synthesized by bacteria in the colon. (21)

The B vitamins include niacin (B3), pyridoxine pyridoxine: see coenzyme; vitamin.  (B6), cobalamin cobalamin: see coenzyme; vitamin.  (B12), thiamin thiamin
 or vitamin B1

Organic compound, part of the vitamin B complex, necessary in carbohydrate metabolism. It carries out these functions in its active form, as a component of the coenzyme thiamin pyrophosphate.
 (B1), riboflavin riboflavin: see coenzyme; vitamin.
riboflavin
 or vitamin B2

Yellow, water-soluble organic compound, abundant in whey and egg white. It has a complex structure incorporating three rings.
 (B2), pantothenic acid, biotin biotin: see vitamin; coenzyme.
biotin

Organic compound, part of the vitamin B complex, essential for growth and well-being in animals and some microorganisms.
, and folic acid. (22-25) All B vitamins are water soluble, and they serve many basic functions, including blood formation, support of central nervous system (CNS See Continuous net settlement.

CNS

See continuous net settlement (CNS).
) function, support of general body chemistry, genetic functions, and other important activities. (22-25) In general, B vitamins do not tend to cause adverse effects, even in relatively high doses. An exception is niacin, which can cause liver damage when used in gram amounts over a significant period of time. Crystalline niacin is less likely to damage the liver than "sustained-release" niacin. Niacin is valuable in detoxification programs that use sauna treatments and exercise.

Vitamin C requires little introduction. It is essential for the health of supporting tissues in the body, blood vessel functions, wound healing, and the production of body hormones or messenger substances. Vitamin C is a powerful antioxidant. Much evidence implies that it may protect against the common cold, prevent certain types of cancer, promote cardiovascular health, support memory, prevent cataract formation, and exert antiallergic effects. Vitamin C also has documented antiaging properties. (4)

What are the Best Vitamin Supplements?

Simply stated, one "gets what one pays for" when purchasing a vitamin supplement. Cheaper types are often presented in pressed, hard tablets that are difficult to swallow, and their contents are often poorly absorbed. (1) Some are so poorly absorbed that they may be passed in the stool in an intact form. Clearly, vitamin supplements are best administered in capsules, and vegetable capsules may be preferred because of concerns about bovine gelatin as a possible source of mad cow disease mad cow disease: see prion.
mad cow disease
 or bovine spongiform encephalopathy (BSE)

Fatal neurodegenerative disease of cattle. Symptoms include behavioral changes (e.g.
. Vegetable capsules are more expensive than regular gelatin capsules, but they are advantageous.

Many people are confused about the ideal amounts of vitamins to take on a daily basis. The amounts of several vitamins in advanced formulae often exceed RDI, but they will not produce toxic effects in average use. Superior vitamin supplements are distinguished by the addition of several other vital nutrients that are not able to be classified as vitamins per se, but have other potential health benefits by acting as cofactors. (1) Many of the benefits of these valueadded nutrients will be discussed in future columns. These include green tea extract, turmeric or curcuminoids, choline choline: see vitamin.
choline

Organic compound related to vitamins in its activity. It is important in metabolism as a component of the lipids that make up cell membranes and of acetylcholine.
, inositol inositol (ĭnō`sĭtōl): see vitamin.
Inositol

The generic name for hexahydroxycyclohexanes, which are classified as carbohydrates.
, PABA PABA
n.
Para-aminobenzoic acid; a crystalline para form of aminobenzoic acid that is part of the vitamin B complex, is required by many organisms for the formation of folic acids, and is widely used in sunscreens to absorb ultraviolet light.
, grape seed extract Grape seed extract contains chemicals known as polyphenols, (including the subclass of proanthocyanidins), which are recognized to be effective polyphenol antioxidants. , lutein lutein /lu·te·in/ (-in)
1. a lipochrome from the corpus luteum, fat cells, and egg yolk.

2. any lipochrome.


lu·te·in
n.
1.
, and lycopene. Small amounts of black pepper are sometimes added to multivitamin formulations for antioxidant functions and the alleged promotion of better vitamin absorption.

New Trends in Vitamin Supplementation

New trends in vitamin supplementation have been influenced by more detailed knowledge of the function of vitamins that are summarized in the following short paragraphs. Much of the information is found in quick reference sources (for example, Present Knowledge in Nutrition, Ziegler EE and Filer LJ, eds., 1996; and The Nutrient Bible, Osiecki H, 2006).

* Vitamin A (retinol retinol: see Vitamin A under vitamin. , retinal, retinoic acid, precursor -beta-carotene) supports retinoid receptor pathways for vision, sensory input, attention, concentration, and language processing. It is a classic lipid antioxidant that activates B and T lymphocytes: it enhances phagocyte phagocyte (făg`əsīt'): see blood.  function and antibody production. It plays a role in steroid synthesis, bone growth, and white cell differentiation, and it may induce apoptosis. It increases iron utilization and maintains tight junctions between cells with enhanced cellular adhesion, thereby stabilizing mucosal barriers for defense. It is important for membrane integrity and structure of myelin sheath. It protects against squamous cancer and promotes the synthesis of mucopolysaccharide. It is necessary for visual purple synthesis. It is a specific stimulator of neurotrophic factor synthesis.

* Vitamin B1 (co-carboxylase, active form--thiamine pyrophosphate pyrophosphate /py·ro·phos·phate/ (-fos´fat) a salt of pyrophosphoric acid.

py·ro·phos·phate
n. Abbr. PP
A salt or ester of pyrophosphoric acid.
 [TPP TPP thiamine pyrophosphate.
Thiamine pyrophosphate (TPP)
The coenzyme containing thiamine that is essential in converting glucose to energy.

Mentioned in: Beriberi


TPP

1. total plasma protein.

2.
]) is a cofactor cofactor

An atom, organic molecule, or molecular group that is necessary for the catalytic activity (see catalysis) of many enzymes. A cofactor may be tightly bound to the protein portion of an enzyme and thus be an integral part of its functional structure, or it may
 in two dozen enzyme systems, necessary for conversion of alpha-keto acids to acyl ac·yl
n.
A organic radical having the general formula RCO, derived from the removal of a hydroxyl group from an organic acid.



acyl

1. an organic radical derived from a fatty acid by removal of the hydroxyl group.

2.
 ions, carboxylic acid, and aldehydes. It has a role in the hexose hexose /hex·ose/ (hek´sos) a monosaccharide containing six carbon atoms in a molecule.

hex·ose
n.
 monophosphate shunt. It mimics acetylcholine (ACh) in the CNS and cardiac muscle. It regulates sugar metabolism and ion channels in cells, and may regulate appetite.

* Vitamin B2 (riboflavin, flavin adenine dinucleotide flavin adenine dinucleotide (FAD): see coenzyme.  [FAD] [active form]) is a coenzyme in respiratory systems and a component of flavoproteins with specific importance in Krebs cycle. It maintains the structure of mucosal surfaces and myelin, with a role in red cell production. It may exert a role in the reduction of brain swelling following stroke or injury and plays a pivotal role in fetal development.

* Vitamin B3 (niacin, nicotinic acid, niacinamide, nicotinamide adenine dinucleotide nicotinamide adenine dinucleotide and nicotinamide adenine dinucleotide phosphate: see coenzyme.
Nicotinamide adenine dinucleotide (NAD) 
 [NAD NAD: see coenzyme. ] [active form]--coenzyme I, nicotinamide adenine dinucleotide phosphate [NADP NADP: see coenzyme. ]--coenzyme P)--has indirect functions as an electron carrier in cellular respiratory activity, and it is involved in oxidation of fats and carbohydrates. It functions as part of biochemical complexes that act with hydrogen donation; for example, fatty acid and steroid synthesis. It has well defined antineuritic activity, lowers blood cholesterol, maintains skin and digestive structure, and has a role in energy production and stimulation of DNA repair. It plays role as nicotinamide nicotinamide (nĭk'ətĭn`əmīd): see vitamin.  in altering the activity of several interleukins and tumor necrosis factor tumor necrosis factor
n. Abbr. TNF
A protein that is produced in the presence of an endotoxin, especially by monocytes and macrophages, is able to attack and destroy tumor cells, and exacerbates chronic inflammatory diseases.
 alpha (TNF TNF
abbr.
tumor necrosis factor


TNF,
n an abbreviation for tumor
necrosis
f
).

* Vitamin B5 (pantothenic acid) supports immune function and steroid hormone production, and is a constituent of coenzyme A. It has major functions in the synthesis of cholesterol, corticosteroids, antibodies and acetylcholine. It alters uric acid production.

* Vitamin B6 (pyridoxine, co-decarboxylase hydrochloride, pyridoxal-5-phosphate [P-5-P] [active form] and pyridoxamine phosphate) has anti-aging potential by inhibiting the production of advanced glycation end products (AGEs). It plays a significant role in carbohydrate and lipid metabolism. It facilitates neurotransmitter synthesis and assists in synthesis of eicosanoids and prostaglandins. It supports nervous system function and alters transcription responses that control the actions of sex hormones. Pyridoxyl 5 phosphate is a natural angiogenesis inhibitor that downregulates RNA RNA: see nucleic acid.
RNA
 in full ribonucleic acid

One of the two main types of nucleic acid (the other being DNA), which functions in cellular protein synthesis in all living cells and replaces DNA as the carrier of genetic
 and DNA polymerase activity.

* Vitamin B12 (cobalamin, cyanocobalamin cyanocobalamin: see coenzyme; vitamin. , methylcobalamin, adenosyl-cobalamin) supports structure and function of bone marrow and epithelial tissues. Principal role in synthesis of nucleic acids, proteins and major activity in blood cell formation. Important in methyl group transfer and required for support of myelination of nervous tissue. Methylcobalamin assists in the synthesis of choline containing phospholipids and it is an obligatory factor in folate metabolism. The formation of succinyl coenzyme A is dependent on adenosylcobalamin, a factor in lipid formation in the CNS. Clear metabolic roles in the biochemistry of fats, proteins, and carbohydrates.

* Beta-carotene (belongs to a family of compounds known as carotenoids) is a vitamin A precursor with antioxidant function and immune-stimulating activity. It quenches singlet oxygen and supports structure and functions of mucus membranes and the respiratory tract.

* Biotin (also called vitamin H, co-enzyme R) is involved in carbon dioxide transfer; that is, carboxylation carboxylation /car·box·y·la·tion/ (kahr-bok?si-la´shun) the addition of carbon dioxide or bicarbonate to form a carboxyl group, as to pyruvate to form oxaloacetate.

car·box·yl·a·tion
n.
 reactions with effects on deamination. It maintains cutaneous health, bone marrow, and gonadal gonadal

pertaining to or arising from a gonad. See also testicular, ovarian.


gonadal cords
cords formed by epithelial cells which migrate from the mesonephric tubules in the embryo to the gonadal ridge and establish the indifferent
 structure and function. It may reduce atherosclerotic lesions; and it modifies genomic expressions, for example, glucokinase. It is an important cofactor to several enzymes, including acetyl CoA carboxylase acetyl CoA carboxylase

a biotin-containing enzyme which participates in the synthesis of fatty acids by catalyzing the carboxylation reaction in which acetyl-CoA is converted to malonyl-CoA.
 and other carboxylases. It increases intracellular GMP.

Folic Acid (folacin folacin: see vitamin. , pteroyl-mono-glutamic acid, vitamin B9) has a major role in DNA repair, nitric oxide production, purine and pyrimidine metabolism, and metabolic conversion of tyrosine and histidine histidine (hĭs`tĭdēn), organic compound, one of the 22 α-amino acids commonly found in animal proteins. Only the l-stereoisomer appears in mammalian protein. . It may inhibit genomic expression of chromosomal mutations and has a specific role in synthesis of choline and neurotransmitters, for example, serotonin. It is best recognized as pivotal in maturation of blood cells. It has important effects in the differentiation of the CNS during embryonic development (role in prevention of neural tube defects).

* Vitamin C (ascorbic acid) is a classic antioxidant required to support connective tissue, bone, and teeth. It has a role in detoxification and possesses "antihistaminic antihistaminic /an·ti·his·ta·min·ic/ (-his-tah-min´ik)
1. counteracting the effect of histamine.

2. antihistamine.


an·ti·his·ta·min·ic
adj.
" properties. It facilitates excretion of heavy metals, inhibits phosphodiesterase, and promotes wound healing. It protects against nitrosamine ni·tros·a·mine
n.
Any of a class of organic compounds present in various foods and other products and found to be carcinogenic and mutagenic in laboratory animals.
 formation in the stomach and inhibits carcinogens, such as benzopyrene ben·zo·py·rene
n.
A yellow, crystalline, aromatic hydrocarbon that is a carcinogen found in coal tar and cigarette smoke.
. It may reduce metastatic malignancy. It is involved in hydroxylation of cholesterol and improves specific aspects of immune function. Putative cancer protective effects remain underexplored.

* Vitamin D (1,25-dihydroxycholecalciferol [1,25-(OH)2D3]) [calcitrol or vitamin D hormone Vitamin D hormone
Vitamin D is a vitamin that also acts as a hormone. Vitamin D hormone acts with parathyroid hormone to regulate calcium levels in the blood and to supply appropriate amounts of calcium to all cells.

Mentioned in: Hypercalcemia
], vitamin D2 [ergocalciferol ergocalciferol /er·go·cal·cif·er·ol/ (er?go-kal-sif´er-ol) vitamin D; a sterol occurring in fungi and some fish oils or synthesized from ergosterol, with similar activity and metabolism to those of cholecalciferol; used as a dietary ], vitamin D3 [cholecalciferol cholecalciferol /cho·le·cal·ci·fer·ol/ (ko?le-kal-sif´er-ol) vitamin D; a hormone synthesized in the skin on irradiation of 7-dehydrocholesterol or obtained from the diet; it is activated when metabolized to 1,25-dihydroxycholecalciferol. ] [prohormone] is recognized as pivotal factor in calcium and phosphate regulation. It is distinguished by antiproliferative effects, recorded in several cancers, such as breast, colon, melanoma, and osteosarcoma osteosarcoma /os·teo·sar·co·ma/ (os?te-o-sahr-ko´mah) a malignant primary neoplasm of bone composed of a malignant connective tissue stroma with evidence of malignant osteoid, bone, or cartilage formation; it is subclassified as . It is an apoptosis-inducer. It is involved in blood clotting, muscle function, differentiation of immune cells, and promotion of neurotrophic factor synthesis, and promotes mineralization of bone and teeth. It is neuroprotective in states of ischemia. Complex immune functions include inhibition of cell-mediated immunity, reduction of specific interleukin levels, and assistance in the conversion of monocytes to macrophages.

* Vitamin E (tocopherols--there are eight naturally occurring compounds that can be divided into two classes--tocopherols and tocotrienols) is a classic lipophylic cellular antioxidant with notable effects on fertility and gestation. It has defined actions on retention of cognitive function in the elderly and is obligatory for actions of superoxide dismutase (SOD). It has specific effects on immunity including enhanced T-helper cell function. It inhibits platelet aggregation and adhesion of monocytes. It has a principal role in maintaining integrity of lipid membranes by direct trapping of peroxyl radicals. It has an important role in modulation of phospholipase phospholipase /phos·pho·lip·ase/ (-lip´as) any of four enzymes (phospholipase A to D) that catalyze the hydrolysis of specific ester bonds in phospholipids.

phos·pho·lip·ase
n.
, lipooxygenase, and cyclo-oxygenase with major effects on the expression of inflammation. Tocopherols have other defined effects on gene expression, angiogenesis, growth factor signaling, mitochondrial mitochondrial

pertaining to mitochondria.


mitochondrial RNAs
a unique set of tRNAs, mRNAs, rRNAs, transcribed from mitochondrial DNA by a mitochondrial-specific RNA polymerase, that account for about 4% of the total cell RNA that
 function, inflammation, etc. Tocotreinols inhibit lipid peroxidation, decrease blood cholesterol, and are antiangiogenic, antioxidant, etc.

* Vitamin K ([phylloquinoneK 1], menadione menadione /men·a·di·one/ (men?ah-di´on) vitamin K3.
1. a synthetic fat-soluble vitamin that can be converted in the body to active vitamin K.

2.
 [[kappa]3], menaquinone menaquinone /men·a·quin·one/ (men?ah-kwin´on) vitamin K2; any of a series of compounds having vitamin K activity and structurally similar to phytonadione (vitamin K1) but having a different side chain; synthesized by the intestinal flora.  [[kappa]2], phylloquinone Phylloquinone
An alternate name for vitamin K1.

Mentioned in: Vitamin K Deficiency


phylloquinone

see phytomenadione.
 [2-Me-3 phytyl-1-4 napthoquinone] sourced from plants, menaquinone [2-M3-3-polyisoprenyl-1-4-naptoquinone] bacterial source) plays a major role in calcium metabolism, blood clotting, and sphingolipid metabolism, but is best known for its role in blood clotting. It inhibits apoptosis in neurons. It is important in the synthesis of surfactants in the lung. It promotes the synthesis of proteins C and S, which inhibit clot formation, and promotes production of prothrombin prothrombin

Carbohydrate-protein compound in plasma essential to coagulation. In response to bleeding, a complex series of clotting-factor interactions leads to its conversion by thromboplastin to thrombin, which transforms fibrinogen in plasma into fibrin.
 with Factors II, IX, VII and X, involved in clot lysis.

The trend of using large doses of vitamins continues. Megadosages are generally defined as more than ten times the RDA. While some indications for the use of large doses of vitamins appear to have been defined, opinions differ on the value of such treatments. In general, the author reiterates that it is prudent to have a health-care practitioner supervise the use of high dosages of vitamins. (1)

Examples of the therapeutic use of certain vitamins in high dosage includes treatment of acne and other skin disorders with vitamin A and its derivatives; but toxicity, including an increased risk of birth defects, can occur. High-dosage vitamin therapy can pose special problems in individuals with underlying disease. In this context, excessive vitamin A administration in individuals with renal failure may cause bone resorption with hypercalcemia Hypercalcemia Definition

Hypercalcemia is an abnormally high level of calcium in the blood, usually more than 10.5 milligrams per deciliter of blood.
. (17) In general, fat-soluble vitamins tend to have greater toxicity than water-soluble vitamins.

However, megadosages of water-soluble vitamins are not devoid of side effect profiles. For example, in the B vitamins, large doses of nicotinic acid used in the management of lowering blood cholesterol may cause flushing with skin irritation and significant metabolic consequences, including a decrease in glucose tolerance and hyperuricemia hyperuricemia /hy·per·uri·ce·mia/ (-u?ri-se´me-ah) uricemia; an excess of uric acid in the blood.hyperurice´mic

hy·per·u·ri·ce·mi·a
n.
An unusually high concentration of uric acid in the blood.
. Abnormal liver function with clinical consequences similar to hepatitis and aggravation of acid peptic disease may also occur. Toxicity appears to be more overt when controlled-release preparations with niacin are used. In another case, administration of folic acid to an individual who is deficient in vitamin B12 may precipitate serious CNS side effects. (27)

In brief, one may see a clear distinction between the physiological and the pharmaceutical effects of vitamin intake, where the dosage appears to be critical in the clinical outcome. It seems clear that the harmony of body chemistry works is complex and requires a well-balanced interaction of many vital nutrients. All nutritional agents require ancillary help by others. This means that vitamins and other vital nutrients act in concert or as dependent cofactors in biochemical reactions.

These circumstances are well recognized with the increasing definition of other substances that have been considered to be essential nutrients for humans. That said, the "vitamin status" of many of these other substances may not have been clearly defined or established. A large body of experimental research, most notably in animals, implies that substances such as coenzyme Q10, para-aminobezoic acid, inositol, bioflavanoids, choline, lipoic acid, and L-carnitine have "vitamin-like activity." (27)

Nature provides an abundance of phytochemicals that may act in concert with essential vitamins or other nutrients. (1) Therefore, modern concepts in integrative medicine have now started to favor the use of complex mixtures of vitamins, phytochemicals, and minerals found in powdered preparations of berries, fruits, vegetables, and green plant life. (3) This approach is considered to provide more optimal nutritional insurance than the regular notion of "popping the multivitamin pill" alone. (1), (3)

There are major constituents of the diet that are essential for human health because several nutrients are not able to be synthesized by the body. Perhaps a key example is found in fatty acids of the omega-3 and omega-6 series. Omega-3 fatty acids are found in their active form in fish and certain algae algae (ăl`jē) [plural of Lat. alga=seaweed], a large and diverse group of primarily aquatic plantlike organisms. These organisms were previously classified as a primitive subkingdom of the plant kingdom, the thallophytes (plants that . Omega-6 fatty acids are overabundant in many Western diets, and supplementation is seldom required in general nutritional practice. There is believed to be a widespread deficiency of omega-3 fatty acids or a gross disturbance of the ratio of dietary intake of omega-6 to omega-3 fatty acids, such that many physicians in integrative medicine are routinely using omega-3 fatty acids in the same manner in which they utilize multivitamin supplements. (28)

The therapeutic benefits of omega-3 fatty acids are legion, and high dosages of active omega-3 fatty acids (eicosapentanioic acid [EPA] and docosahexanoic acid [DHA]) are often required to achieve an optimum therapeutic outcome in certain disease states--for example, chronic inflammatory disorders and depression. The notion that precursor omega-3 fatty acids are good sources of active EPA and DHA has been repeatedly challenged because the conversion of these precursors to active moieties is often impaired by disease or dietary selections, and this conversion is quite incomplete in many individuals under normal circumstances. (28)

The recognition of the need for high-dose fish oil administration to deliver high concentrations of EPA and DHA has implications for compliance with fish oil supplements. Evidence has emerged that enteric coated fish oil capsules may provide improved bioavailability of active omega-3 fatty acids (EPA/DHA) with improved patient tolerance. (1), (2), (28) These days, spontaneous decomposition of fish oil liquids and questionable absorption of EPA/DHA from standard gel capsules are seen as quite disadvantageous in a therapeutic setting.

Are Multivitamins a Health Risk?

Different opinions exist on the safety and effectiveness of dietary supplements. Airing these views can cause confusion, but it is necessary for consumers to reach an informed decision. In May 2006, the National Institutes of Health (NIH) held its "State-of-the-Science Conference on Multivitamin/Mineral Supplements and Chronic Disease Prevention." The members of this expert panel proposed that multivitamins may pose some "theoretical" health risks, especially in circumstances of self-medication.

Protests to the conclusions of the NIH panel emerged rapidly. For example, the National Nutritional Food Association (NNFA or NPA, a US body representing the dietary supplement industry) labeled the NIH panel as irresponsible and uninformed in its process of "theorizing" on the risks of multivitamins.

All medical interventions pose risks, and this is why the good practice of medicine always involves an assessment of risks versus benefits. In the case of multivitamins, it is clear that only a small proportion of the estimated 100 million users of vitamins have adverse reactions. Such reactions are infrequent and, in many cases, minor or rapidly reversible. Data produced by the American Association of Poison Control imply that only four percent of all adverse reactions to prescription or over-the-counter products can be linked to vitamin usage (NNFA, NPA 2006).

The NIH panel expressed concerns about lack of regulatory authority on supplement sales and the need for more research to assess supplement benefits, or lack thereof. One major problem is the unwillingness of some scientists to accept benefits of nutritional factors described in observational or population studies. If one waited for conclusive, clinical data on supplement usage, one might wait forever! Economic rewards in medical care rest most often with drugs. Dietary supplements do not fit the economic models of patented drugs, and there is little incentive and limited financial backing for dietary supplement research.

Some Important Therapeutic Concepts

There are several antagonists of the synthesis, metabolism, or actions of vitamins, where competitive biochemical activity occurs because of the resemblance of an "antivitamin" to the active vitamin molecule. Good examples of vitamin antagonists include isonicotinic acid hydrazide hy·dra·zide  
n.
An acyl derivative of hydrazine.



hydrazide  

A compound formed by combining hydrazine with an acyl compound. Hydrazides are important in the manufacture of certain medicines.
 (antagonist of pyridoxine), aminopterin aminopterin: see metabolite.  (folate antagonist), dicumarol (vitamin K antagonist), and avidin av·i·din
n.
A protein, found in uncooked egg white, that binds to and inactivates biotin and which, when present in abundance, can result in a deficiency of biotin.
 (interferes with biotin absorption). (27)

Arguments prevail about dietary factors that are considered arguably to be vitamins, but the presence of such nutrients provides strong support for the obligatory use of dietary supplements in certain circumstances. For example, choline is required in large amounts during growth and development, and it has demonstrable "vitamin-like" activity in experimental animals. (27), (29) While choline presents itself in the diet in phosphatide molecules, the ability of the body to synthesize choline from ethanolamine ethanolamine /eth·a·nol·amine/ (eth?ah-nol´ah-men) monoethanolamine.

ethanolamine oleate
 and methyl groups is sometimes subject to compromise, or it may be inadequate to meet needs.

Another example of obligatory requirements for supplements includes circumstances where vitamin loss may be excessive; for example, diabetes mellitus. (1) In this context, an important vitaminlike substance is myo-inositol. This nutrient is associated with high urinary loss in patients with diabetes, and there may be coincidental reduced levels of this form of inositol in membranes of the nervous system, perhaps providing one explanation for diabetic neuropathy. (27) These circumstances present one of many reasons why individuals with diabetes may benefit from routine vitamin supplementation, especially with water soluble-vitamins. (1)

Conclusion

Almost every medical practitioner believes in the benefits of vitamin supplementation of the standard American diet. Vitamins are essential substances in the diet that exert major controls over the chemistry of life. (30) Modern research demonstrates that certain vitamins have disease-prevention and even treatment capabilities when taken in the correct amounts or forms. The concept of recommended daily intakes has been challenged as it becomes clear that some nutrients assist in preventing several chronic diseases only in higher dosage ranges. Some vitamins may slow some of the physical deterioration that occurs with aging. (1), (30)

The author believes that several groups of people at risk must take daily vitamins. These include aerobic exercisers, smokers, prescription--drug users, people with diabetes mellitus, individuals with many chronic diseases, and especially the elderly. Pharmaceuticals remain an underestimated cause of nutritional depletion, which can be largely corrected by dietary supplementation with a well-formulated multivitamin product. (1)

Chev. Professor, Dr. Stephen Holt, MD, LLD (Hon.) ChB., PhD, DNM, FRCP FRCP Fellow of the Royal College of Physicians.

FRCP
abbr.
Fellow of the Royal College of Physicians
 (C), MRCP MRCP Member of Royal College of Physicians.

MRCP
abbr.
Member of the Royal College of Physicians
 (UK), FACP FACP Fellow of the American College of Physicians.

FACP
abbr.
1. Fellow of the American College of Physicians

2. Fellow of the American College of Prosthodontists
, FACG, FACN, FACAM, Knight of Grace and Lieutenant Grand Hospitaller of the Holy Order of St. John There are several orders of chivalry called the Order of Saint John, which claim as their origins the Knights Hospitaller Christian crusading order. These are the:
  • Sovereign Military Order of Malta, based in Rome
, is a best-selling author, physician, and pioneer of integrative medicine. He is the founder of the Holt Institute of Medicine (www.hiom.org), which is affiliated with the World University of Natural Medicine (www.wunm.org). He holds the academic rank of Distinguished Professor of Medicine and is the chairman of the New York Department of Integrative Medicine. Therapeutic content may be found in "Conversations in Integrative Medicine," a series of ten-minute module webinars, by specific request (973-256-4660).

Notes

(1.) Holt S. A Primer of Natural Therapeutics: A Certification Program for Dietary Supplement Counselors. Little Falls, NJ: Wellness Publishing; 2008.

(2.) Holt S. Metabolic syndrome, syndrome X: Syndrome Y, Z. ... Townsend Letter. May 2007;91-92, 97-103.

(3.) Holt S, Gengo L, MacConchie C. Natural approaches to clinical trauma and medical procedure recovery. Townsend Letter. Dec 2007;98-103.

(4.) Block G. Vitamin C and cancer prevention: the epidemiologic evidence. Am J Clin Nutr. 1991;53:270S-282S.

(5.) Blot WJ, Li JY, Taylor PR, et al. Nutrition intervention trials in Linxian, China; supplementation with specific vitamin/mineral combinations, cancer incidence, and disease-specific mortality in the general population. J Natl Cancer Inst. 1993;85:1483-1492.

(6.) Chapuy MC, Arlot ME, Duboeuf F, et al. Vitamin D3 and calcium to prevent hip fractures in elderly women. NEJM. 1992;327:1637-1642.

(7.) National Academy of Sciences, Institute of Medicine, Food and Nutrition Food and Nutrition
See also cheese; dining; milk.

accubation

Rare. the act or habit of reclining at meals.

alimentology

Medicine. thescience of nutrition.

allotriophagy

Pathology.
 Board. Dietary Reference Intakes for Calcium, Phosphorus, Magnesium, Vitamin D, and Fluoride. Washington, DC: National Academy Press, 1997.

(8.) Duchateau J, Delepresse G, Vrijens R, et al. Beneficial effects of oral zinc supplementation on the immune response of old people. Am J Med. 1981;70:1001-1004.

(9.) Enstrom JE, Kanim LE, Klein MA. Vitamin C intake and mortality among a sample of the US population. Epidemiology. 1992;3:194-202.

(10.) Harlan WR, Hull AL, Schmouder RL, et al. Blood pressure and nutrition in adults: the National Health and Nutrition Examination Survey. Am J Epidemiol. 1984;120:17-28.

(11.) MRC Vitamin Study Research Group. Prevention of neural tube defects: results of the Medical Research Council Vitamin Study. Lancet. 1991;338:131-137.

(12.) Rimm EB, Stampfer MJ, Ascherio A, et al. Vitamin E consumption and the risk of coronary heart disease coronary heart disease: see coronary artery disease.
coronary heart disease
 or ischemic heart disease

Progressive reduction of blood supply to the heart muscle due to narrowing or blocking of a coronary artery (see atherosclerosis).
 in men. NEJM. 1993;328:1450-1456.

(13.) Stampfer MJ, Hennekens CH, Manson JE, et al. Vitamin E consumption and the risk of coronary heart disease in women. NEJM. 1993;328:1444-1449.

(14.) Ubbink JB, Vermaak WJ, van der Merwe A, et al. Vitamin B12, vitamin B6, and folate nutritional status in men with hyperhomocysteinemia. Am J Clin Nutr. 1993;57:47-53.

(15.) Willett WC, Polk BF, Morris JS, et al. Prediagnostic serum selenium and risk of cancer. Lancet. 1983;2:130-134.

(16.) Goldberg J. Vitamin A and eyesight, Am J Epidemiol. 1988;128:700.

(17.) Canfield LM, Krinsky NI, Olson JA, eds. Carotenoids in human health. Ann N Y Acad Sci. 1994;691:1-300.

(18.) DeLuca H. Vitamin D and its metabolites. In: Shils, ME, Young VR, eds. Modern Nutrition in Health and Disease. 7th ed. Philadelphia: Lea and Febiger; 1988.

(19.) Lloyd JK. The importance of vitamin E in human nutrition. Acta Paediatr Scand. 1990; 79:6.

(20.) Murphy SP et al. Vitamin E intakes and sources in the United States. Am J Clin Nutr. 1990;52:361.

(21.) Suttie JW. Vitamin K. In: Ziegler EE, Filer LJ, eds. Present Knowledge in Nutrition. Washington, DC: ILSI Press; 1996.

(22.) Haas RH. Thiamin and the brain. Annu Rev Nutr. 1988;8:483.

(23.) Bender DA. Vitamin B6 requirements and recommendations. Eur J Clin Nutr. 1989;43:289.

(24.) Merrill AH, Henderson JM. Diseases associated with defects in vitamin B6 metabolism or utilization. Annu Rev Nutr. 1987;7:137.

(25.) Butterworth CE, Tamura T. Folic acid safety and toxicity: a brief review. Am J Clin Nutr. 1989;50:353.

(26.) Clementz GL. The spectrum of vitamin B12 deficiency vitamin B12 deficiency Megalobalstic anemia, see there . Am Fam Physician. 1990;41(1);150.

(27.) Mock DM. Biotin. In: Ziegler EE, Filer LJ, eds. Present Knowledge in Nutrition. Washington, DC: ILSI Press; 1996.

(28.) Holt S. Combat Syndrome X, Y and Z. ... Little Falls, NJ: Wellness Publishing; 2002 and Holt S, Wright J, Taylor TV. Nutritional Factors for Syndrome X. Little Falls, NJ: Wellness Publishing; 2003.

(29.) McMahon KE. Choline, an essential nutrient? Nutr Today. 1987;22(2):18.

(30.) Osiecki H. The Nutrient Bible. 7th ed. Queensland, Australia: Bio Concepts Publishing; 2008.

by Stephen Holt, MD *

* Stephen Holt, MD, Distinguished Professor of Medicine; Chairman, New York Department of Integrative Medicine, NYCPM, NY; Founder, Holt Institute of Medicine (www.hiom.org); Lieutenant Grand Hospitaller, Holy Order of St. John.
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Date:Feb 1, 2009
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