The Vitamins

The vitamins are a disparate group of compounds; they have little in common either chemically or in their metabolic functions. Nutritionally, they form a cohesive group of organic compounds that are required in the diet in small amounts (micrograms or milligrams per day) for the maintenance of normal health and metabolic integrity. They are thus differentiated from the essential minerals and trace elements (which are inorganic) and from essential amino and fatty acids, which are required in larger amounts.

The discovery of the vitamins began with experiments performed by Hopkins at the beginning of the twentieth century; he fed rats on a defined diet providing the then known nutrients: fats, proteins, carbohydrates, and mineral salts. The animals failed to grow, but the addition of a small amount of milk to the diet both permitted the animals to maintain normal growth and restored growth to the animals that had previously been fed the defined diet. He suggested that milk contained one or more "accessory growth factors" -essential nutrients present in small amounts, because the addition of only a small amount of milk to the diet was sufficient to maintain normal growth and development.

The first of the accessory food factors to be isolated and identified was found to be chemically an amine; therefore, in 1912, Funk coined the term vitamine, from the Latin vita for "life" and amine, for the prominent chemical reactive group. Although subsequent accessory growth factors were not found to be amines, the name has been retained-with the loss of the final "-e" to avoid chemical confusion. The decision as to whether the word should correctly be pronounced "vitamin" or "veitamin" depends in large part on which system of Latin pronunciation one learned - the Oxford English Dictionary permits both.

During the first half of the twentieth century, vitamin deficiency diseases were common in developed and developing countries. At the beginning of the twenty-first century, they are generally rare, although vitamin A deficiency (Section 2.4) is a major public health problem throughout the developing world, and there is evidence of widespread subclinical deficiencies of vitamins B2 (Section 7.4) and B6 (Section 9.4). In addition, refugee and displaced populations (some 20 million people according to United Nations estimates in 2001) are at risk of multiple B vitamin deficiencies, because the cereal foods used in emergency rations are not usually fortified with micronutrients [Food and Agriculture Organization/World Health Organization (FAO/WHO, 2001)].


In addition to systematic chemical nomenclature, the vitamins have an apparently illogical system of accepted trivial names arising from the history of their discovery (Table 1.1). For several vitamins, a number of chemically related compounds show the same biological activity, because they are either converted to the same final active metabolite or have sufficient structural similarity to have the same activity.

Different chemical compounds that show the same biological activity are collectively known as vitamers. Where one or more compounds have biological activity, in addition to individual names there is also an approved generic descriptor to be used for all related compounds that show the same biological activity.

When it was realized that milk contained more than one accessory food factor, they were named A (which was lipid-soluble and found in the cream) and B (which was water-soluble and found in the whey). This division into fat- and water-soluble vitamins is still used, although there is little chemical or nutritional reason for this, apart from some similarities in dietary sources of fat-soluble or water-soluble vitamins. Water-soluble derivatives of vitamins A and K and fat-soluble derivatives of several of the B vitamins and vitamin C have been developed for therapeutic use and as food additives.

As the discovery of the vitamins progressed, it was realized that "Factor B" consisted of a number of chemically and physiologically distinct compounds. Before they were identified chemically, they were given a logical series of alphanumeric names: B1, B2, and so forth. As can be seen from Table 1.2, a number of compounds were assigned vitamin status, and were later shown either not to be vitamins, or to be compounds that had already been identified and given other names.


1.1 The Vitamins



Deficiency Disease



Visual pigments in the retina;

Night blindness,


regulation of gene expression and cell differentiation; (p-carotene is an antioxidant)

xerophthalmia; keratinization of skin



Maintenance of calcium balance; enhances intestinal absorption of Ca2+ and mobilizes bone mineral; regulation of gene expression and cell differentiation

Rickets = poor mineralization of bone; osteomalacia = bone demineralization



Antioxidant, especially in cell

Extremely rare - serious


membranes; roles in cell signaling

neurological dysfunction



Coenzyme in formation of

Impaired blood clotting,


7-carboxyglutamate in enzymes of blood clotting and bone matrix

hemorrhagic disease



Coenzyme in pyruvate and 2-oxo-glutarate dehydrogenases, and transketolase; regulates Cl-channel in nerve conduction

Peripheral nerve damage (beriberi) or central nervous system lesions (Wernicke-Korsakoff syndrome)



Coenzyme in oxidation and reduction reactions; prosthetic group of flavoproteins

Lesions of the corner of the mouth, lips, and tongue; sebhorreic dermatitis


Nicotinic acid

Coenzyme in oxidation and



reduction reactions, functional part of NAD and NADP; role in intracellular calcium regulation and cell signaling

dermatitis; depressive psychosis



Coenzyme in transamination

Disorders of amino acid


and decarboxylation of

metabolism, convulsions


amino acids and glycogen phosphorylase; modulation of steroid hormone action

Folic acid

Coenzyme in transfer of one-carbon fragments

Megaloblastic anemia


Table 1


1 (continued )


Deficiency Disease



Coenzyme in transfer of

Pernicious anemia =

one-carbon fragments

megaloblastic anemia with

and metabolism of folic

degeneration of the spinal




Functional part of coenzyme

Peripheral nerve damage


A and acyl carrier protein:

(nutritional melalgia or

fatty acid synthesis and

"burning foot syndrome")




Coenzyme in carboxylation

Impaired fat and

reactions in


gluconeogenesis and fatty

metabolism; dermatitis

acid synthesis; role in

regulation of cell cycle



Coenzyme in hydroxylation

Scurvy - impaired wound


of proline and lysine in

healing, loss of dental

collagen synthesis;

cement, subcutaneous

antioxidant; enhances


absorption of iron

NAD, nicotinamide adenine dinucleotide; NADP, nicotinamide adenine dinucleotide phosphate.

For a compound to be considered a vitamin, it must be shown to be a dietary essential. Its elimination from the diet must result in a more-or-less clearly defined deficiency disease, and restoration must cure or prevent that deficiency disease.

Demonstrating that a compound has pharmacological actions, and possibly cures a disease, does not classify that compound as a vitamin, even if it is a naturally occurring compound that is found in foods.

Equally, demonstrating that a compound has a physiological function as a coenzyme or hormone does not classify that compound as a vitamin. It is necessary to demonstrate that endogenous synthesis of the compound is inadequate to meet physiological requirements in the absence of a dietary source of the compound. Table 1.3 lists compounds that have clearly defined functions, but are not considered vitamins because they are not dietary essentials; endogenous synthesis normally meets requirements. However, there is some evidence that premature infants and patients maintained on long-term total parenteral nutrition may be unable to meet their requirements for carnitine (Section 14.1.2), choline (Section 14.2.2), and taurine (Section 14.5.3) unless they are provided in the diet, and these are sometimes regarded as

Table 1.2 Compounds that Were at One Time Assigned Vitamin Nomenclature, But Are Not Considered to Be Vitamins


Assigned to a compound that was probably pantothenic acid, also sometimes

used (incorrectly) for niacin


Later identified as a mixture of arginine, glycine, and cysteine, possibly also

riboflavin and vitamin B6


Assigned to what was later assumed to be either vitamin B6 or nicotinic acid; also

sometimes used for pantothenic acid


A factor that prevented digestive disturbance in pigeons (also called vitamin I)


Later identified as adenylic acid


Never assigned


A factor for feather growth in chickens, probably folic acid and thiamin


Later identified as a mixture of folic acid and thiamin

B 13

A growth factor in rats; orotic acid, intermediate in pyrimidine synthesis

B 14

An unidentified compound isolated from urine that increases bone marrow

proliferation in culture

B 15

Pangamic acid, reported to enhance oxygen uptake

B 16

Never assigned

B 17

Amygdalin (laetrile), a cyanogenic glycoside with no physiological function


Obsolete name for folic acid


Chicken antiperosis factor; can be replaced by choline and manganese salts


Carnitine, a growth factor for insects


A growth factor, probably biotin


Obsolete name for p-aminobenzoic acid (intermediate in folate synthesis); also

used at one time for pantothenic acid


A postulated antipneumonia factor (also called vitamin J)


Essential fatty acids (linoleic, linolenic, and arachidonic acids)


Obsolete name for riboflavin


"Gerovital," novocaine (procaine hydrochloride) promoted without evidence as

alleviating aging, not a vitamin


A factor that prevented digestive disturbance in pigeons (also called vitamin B7)


A postulated antipneumonia factor (also called vitamin C2)


Factor isolated from yeast that was claimed to promote lactation


Obsolete name for folic acid


Extracts from the brain and stomach, purported to have anticancer activity




Pellagra-preventing factor, obsolete name for niacin


Ubiquinone (also called Qi0)


Bacterial growth factor, probably folic acid


Bacterial growth factor, probably biotin


Growth factor in insects, and reported to increase protein uptake in rats, later

identified as a mixture of folic acid, vitamin Bi2, and nucleotides


Methylsulfonium salts of methionine


Bacterial growth factor, probably NAD


Bacterial growth factor, probably biotin


Bacterial growth factor, probably biotin


Probably vitamin B6

NAD, nicotinamide adenine dinucleotide.

Table 1.3 Marginal Compounds that Are Probably Not Dietary Essentials


Required for transport of fatty acids into mitochondria


Constituent of phospholipids; acetylcholine is a neurotransmitter


Constituent of phospholipids; inositol trisphosphate acts as second

messenger in transmembrane signaling


Coenzyme in redox reactions



Osmotic agent in retina and used for conjugation of bile acids; dietary

essential for cats


Redox coenzyme in mitochondrial electron transport chain

(coenzyme Q)

"marginal compounds," for which there is no evidence to estimate requirements.

The rigorous criteria outlined here would exclude niacin (Chapter 8) and vitamin D (Chapter 3) from the list of vitamins, because under normal conditions endogenous synthesis does indeed meet requirements. Nevertheless, they are considered to be vitamins, even if only on the grounds that each was discovered as the result of investigations into once common deficiency diseases, pellagra and rickets.

In addition to the marginal compounds listed in Table 1.3, there are a number of compounds present in foods of plant origin that are considered to be beneficial, in that they have actions that may prevent the development of atherosclerosis and some cancers, although there is no evidence that they are dietary essentials, and they are not generally considered as nutrients.

These compounds are listed in Table 1.4 and discussed in Section 14.7.

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