Vitamins are carbon-containing substances that are required for normal metabolism but are not synthesized in the body; they are obtained, therefore, from such outside sources as food and water or are administered orally or intravenously. Exceptions to this definition include vitamin D, which is synthesized in the body to a limited extent, and vitamin B(12), which is synthesized by bacterial flora in the intestinal tract. Vitamins and minerals function as "cofactors" in the metabolism of products in the body. Most aspects of bodily metabolism proceed with the aid of specific enzymes but if additional catalysts were not present, for example, the cofactor vitamins and minerals, the reactions would proceed so slowly that they would be ineffective. RDA Most authorities assume that all the human vitamin and mineral requirements have been discovered; it is possible, therefore, to predict accurately the vitamin and mineral requirements of humans for health and prevention of disease. In the United States a Food and Nutrition Board was established for the purpose of determining vitamin and mineral requirements. This board is composed of distinguished scientists and nutritionists and is under the auspices of the National Research Council of the National Academy of Sciences. Since 1940 the board has periodically prepared a brochure listing the "Recommended Dietary Allowances" (RDA) of vitamins and other nutrients, based on existing knowledge. These allowances are intended as a guide for nutritionists, institutional dietitians, and homemakers in planning food supplies and in the interpretation of food consumption levels. The RDA figures, however, are estimations based on the present state of knowledge of the needs of most human beings; particular requirements will be less or more, depending on numerous individual factors such as genetics, environmental influences, and presence or absence of disease processes. Supplements Dietary supplements of vitamins are often recommended by physicians when any of the following conditions are present: unusual diets obviously deficient in vitamins (insufficient intake); conditions or diseases causing poor intestinal absorption; and increased tissue requirements that occur in relatively healthy individuals during periods of growth, hard physical work, pregnancy, lactation, and menstruation. Some disorders, including hyperthyroidism, infectious diseases accompanied by fever, and tissue-wasting diseases, also cause increased tissue requirements. Multivitamin Preparations Two principal types of multivitamin preparations are available to the public and the medical profession: supplemental, or prophylactic, and therapeutic. Supplemental vitamins contain a range of one-half to one-and-a-half times the RDA requirements except for vitamin D, which should not exceed 400 international units (IU). These multivitamin preparations are designed to help prevent disease and to supplement the diet in cases of unusual stress and other such situations. Therapeutic multivitamin preparations are prescribed by physicians only for deficiency states and for the nutritional support of severe pathological conditions. Toxicity Most of the water-soluble vitamins ingested in excessive amounts are rapidly excreted in the urine and thus rarely cause toxicity. The fat-soluble vitamins, on the other hand, are stored in body fat and are capable of causing severe toxicity when taken in excessive amounts, as in the case of vitamins A and D. The amounts of vitamins A and D, however, that are sold "over the counter" are regulated by the \TFood and Drug Administration\t (FDA). FAT-SOLUBLE VITAMINS Vitamin A Vitamin A exists in a variety of forms, including retinol, which is currently considered the most active form. Carotene, a pigment in some plants (see \Tcarotenoid\t), can be converted in the human body to vitamin A. Vitamin A is also highly concentrated in fish-liver oils. The normal diet contains adequate amounts of vitamin A, and therefore supplements rarely need to be administered. Vitamin A has many important functions in the body that relate to membrane integrity, especially of epithelial cells and mucous membranes. It is also essential for bone growth, reproduction, and embryonic development. Vitamin A deficiency has long been known to result in \Tnight blindness\t, in which the ability of the eye to see in dim light is impaired. Hypervitaminosis A, which results from excessive intake over a long period of time, is most common in children. Symptoms consist of irritability, vomiting, loss of appetite, headache, dry skin, and scaling of skin. Intracranial pressure is increased, and characteristic bony changes are demonstrable on X-ray examination. An extremely high plasma level of vitamin A occurs in this disorder. Vitamin D The active forms of vitamin D are ergocalciferol vitamin D-2 and cholecalciferol vitamin D-3, both of which arise in the body from ingested precursors by exposure of the skin to ultraviolet light. Vitamin D primarily regulates calcium metabolism by determining the movement of calcium from intestines to blood and from blood to bone. It interacts with \Tparathyroid\t hormone and calcitonin (see \Thormone\t) in controlling calcium levels. In tropical countries, where exposure to sunlight is high, vitamin D deficiency is rare. It is much more common in northern regions. Ultraviolet irradiation of food products, a practice common in some countries, increases their vitamin D content. A deficiency of vitamin D results in failure to absorb calcium and phosphorus, causing faulty formation of bone. In children the syndrome is known as \Trickets\t and is manifested by deformities of the rib cage and skull and by bow legs as a consequence of long bones. Adult rickets, or osteomalacia, is characterized by generalized bone calcification and, eventually, gross bone deformities. Symptoms of hypervitaminosis D consist of weakness, fatigue, lassitude, headache, nausea, vomiting, and diarrhea. Urinary symptoms occur when calcium deposits build up in the kidneys. Vitamin E Vitamin E is chemically known as alpha tocopherol, the most active of a group of tocopherols. It is present in seed oils, especially wheat-germ oil. Few vitamins have been advocated for more diseases than has vitamin E, including such diverse disorders as coronary artery disease, muscular dystrophy, habitual abortion, and schizophrenia. No persuasive evidence, however, demonstrates that vitamin E has any therapeutic value in these or other diseases. Fortunately it is relatively nontoxic, and few adverse effects from excessive intake have been reported from its use in humans. Vitamin K Vitamin K is essential for synthesis by the liver of several factors necessary for the clotting of blood. Chemically, phylloquinone is the natural plant source of vitamin K, and a synthetic derivative, menadione, is used therapeutically. A wide variety of vegetables, egg yolk, liver, and fish oils contain this vitamin. Deficiency of vitamin K rarely occurs, and its human requirements have not been specified. It is never included in dietary vitamin preparations but is used medically in treating specific deficiencies that occur during anticoagulant therapy, in hemorrhagic disease of the newborn, and in hepatocellular disease. WATER-SOLUBLE VITAMINS With the exception of vitamin C (ascorbic acid), water-soluble vitamins belong mainly to what has been termed the B complex of vitamins. The better-known B vitamins are thiamine (B-1), riboflavin (B-2), niacin (B-3), pyridoxine (B-6), pantothenic acid, lecithin, choline, inositol, and para-aminobenzoic acid (PABA). Two other members are folic acid and cyanocobalamin (F-12). Yeast and liver are natural sources of most of these vitamins. Thiamine Thiamine, the first B vitamin to be identified chemically (1926), consists of a complex organic molecule containing a pyrimidine and a thiazole nucleus. In the body it functions as a \Tcoenzyme\t in the form of thiamine pyrophosphate and is important in carbohydrate intermediary metabolism. The symptoms of thiamine deficiency are known as \Tberiberi\t, a syndrome consisting primarily of peripheral neuritis marked by sensory and motor paralysis of the limbs and, finally, heart failure. People of Asia who acquired beriberi as a result of a diet of mainly polished rice could be cured by adding rice polishings, which are high in thiamine. Today, thiamine deficiency results from liver damage and most often occurs in nutritionally deficient alcoholics. Riboflavin Riboflavin (B-2) is a complex organic ring structure to which the sugar ribose is joined. In the body riboflavin is conjugated by phosphate to yield riboflavin 5'-phosphate (FMN) and by adenine dinucleotide to yield flavin adenine dinucleotide (FAD). Both serve as coenzymes for a wide variety of respiratory proteins (see \Tmetabolism\t). Riboflavin deficiency in humans is characterized by growth failure in children; nerve degradation, particularly of the eyes; sore throat; seborrheic dermatitis of the face and extremities; and anemia. The only established use of riboflavin is in the therapy or prevention of deficiency disease. Niacin Two forms of niacin exist: nicotinic acid and nicotinamide. Both are related to the tobacco alkaloid nicotine; in the body they are active as nicotinamide adenine dinucleotide (NAD) and nicotinamide adenine dinucleotide phosphate (NADP) which serve as coenzymes in conjunction with protein in tissue respiration and also as dehydrogenases. \Tpellagra\t, caused by niacin deficiency, is characterized by a cutaneous eruption, at first resembling sunburn because it affects the areas of the body exposed to sunlight. The tongue becomes red and swollen, with excessive salivary secretion, and diarrhea occurs along with nausea and vomiting. Later, central nervous system symptoms appear with headache, dizziness, insomnia, depression, and even overt psychosis with hallucinations and other mental disturbances. The only established use of niacin is in the treatment of pellagra. Because nicotinic acid in large doses lowers blood lipids, it has been extensively used in the therapy and prevention of arteriosclerotic vascular disease. Toxicity may occur in the form of liver damage, however, with prolonged large doses. Pyridoxine Pyridoxine, or vitamin B-6, is a substituted pyridine ring structure that exists in three forms, all of which may be converted in the body to pyridoxal-5-phosphate (PLP), the active coenzyme form. PLP functions in human metabolism in the conversion processes of amino acids, including decarboxylation, transamination, and racemization. Symptoms of deficiency in humans consist of seborrhealike skin lesions of the face; increased irritability; convulsive seizures, particularly in children; and neuritis resulting in degeneration of peripheral nerves. Pantothenic Acid Widely distributed in nature, pantothenic acid was first identified in 1933 as a factor necessary to cure certain skin lesions in chicks. Its role in human nutrition, however, has not been clearly delineated. Biochemically, pantothenic acid is converted to coenzyme A, which serves a vital role for a variety of reactions involving transfer of 2-carbon fragments (acetyl groups). It is also essential for the production of metabolic products crucial to all living organisms. Pantothenic acid has no specific therapeutic indications but is included in multivitamin preparations. Folic Acid Chemically, folic acid is pteroylglutamic acid, composed of a pterin, para-aminobenzoic acid, and glutamic acid moieties. In the body folic acid is converted to folinic acid (5-formyl-tetrahydrofolic acid), the coenzyme form, which accepts 1-carbon units important in the metabolism of many body compounds. Nucleic acid synthesis cannot take place without the presence of folic acid. Deficiency in humans results in various anemias and can be produced by antivitamins such as methotrexate, which is used in cancer chemotherapy. Folic acid is present in many common foods, for example, vegetables and liver, but can be destroyed by excessive cooking. Pure folic acid deficiency is relatively rare unless caused by an antivitamin, tropical sprue, or pregnancy. The only therapeutic use of folic acid is in treating the specific anemias caused by its deficiency, although it is included in multivitamin preparations. Cyanocobalamin (B-12) Vitamin B-12, isolated in 1948, is chemically the most complex of all the vitamins. It has a central ringed structure called a corrin nucleus, linked to an aminopropanol esterified by a nucleotide and also an atom of cobalt to which is attached a cyanide group. Few vitamins are as important metabolically as B-12, because it is involved in many of the synthetic steps required in the manufacture of nucleoproteins and proteins. Almost all organisms need this vitamin but only in very small amounts. Vitamin B-12 is present mainly in the liver, the kidneys, and the heart. In nature the source is believed to be solely that synthesized by microorganisms. The ability to absorb this vitamin depends on the production by the stomach of an intrinsic factor, a glycoprotein; cases of B-12 deficiency often involve patients with defective production of an intrinsic factor. The symptoms of deficiency are identical to the classical syndrome of pernicious anemia: ineffective manufacture of red blood cells; faulty myelin synthesis, leading to a paralyzing neuritis; and a failure to maintain the epithelium of the intestinal tract. Marked anemia and generalized debility eventually develop, which are always fatal unless treated. Cyanocobalamin has only one established use, the treatment of this deficiency disease, but it is included nevertheless in many multivitamin preparations. Ascorbic Acid (Vitamin C) Probably the first deficiency disease to be recognized was \Tscurvy\t, and as early as 1720 fresh vegetables or fruit were found to cure the disease. James Lind, a physician in the British navy, demonstrated in 1757 that consumption of oranges and lemons could prevent the disease. As a result of his work, and the scurvy-free voyages of Captain James \TCook\t, who adopted his principles, the British navy in 1804 made it compulsory to issue a ration of lemons or limes to sailors, who were from then on nicknamed "limeys." Chemically, ascorbic acid is a plant sugar in the acid form, hexuronic acid. In the body ascorbic acid is reduced to dehydroascorbic acid and is involved in oxidation-reduction reactions. Unlike vitamins of the B complex, it does not act as a cofactor. The symptoms of scurvy result from the fact that ascorbic acid is essential for the formation and maintenance of intercellular ground substance and collagen. The pathology affects mainly bone and blood vessels; teeth loosen because dentin is absorbed and the gums become spongy and bleed easily. In the skin and other tissues hemorrhages occur easily with the slightest trauma. Vitamin C is used to prevent and treat scurvy as well as a great variety of other disorders, including various dental problems. Controversy surrounds the practice of taking very large daily doses of vitamin C to prevent the common cold, because medical research has not supported this notion. Intake of very large amounts for long periods of time can also be harmful, even though vitamin C has relatively low toxicity. A sufficient daily intake of fresh orange juice provides enough vitamin C for most purposes. Biotin, Choline, Inositol, and PABA Biotin, a complex organic acid containing sulfur, is a coenzyme for several carboxylation reactions involving carbon dioxide fixation. It is synthesized by intestinal bacteria and is widespread in food products. A natural deficiency in humans is unknown, even in individuals on extremely deficient diets. Choline, a simple amino alcohol, is a component of lecithin and of acetylcholine, the latter of which is one of the most important neurotransmitters. Unlike most vitamins, choline can be synthesized in the body, provided that methionine intake is sufficient. It is present in large amounts in egg yolk, milk, and seafood. Human deficiency rarely occurs. Inositol is actually an isomer of glucose, which is the common sugar of human diets. It is a component of certain phospholipids. No coenzyme function has been established, but inositol promotes the growth of yeast. Para-aminobenzoic acid (PABA) deserves brief mention not because it is a human requirement but because it is an obligatory metabolite for most microorganisms and unicellular forms such as protozoa. Sulfonamides, the first successful group of modern chemotherapeutic agents against infections, act as antagonists to para-aminobenzoic acid. In order to survive, most microorganisms need to incorporate para-aminobenzoic acid into the molecule of folic acid. Sulfonamides prevent this, and thus they are inhibitory to the growth of bacteria. They are not harmful in this sense to mammals, because these higher forms cannot synthesize folic acid and obtain it preformed in the diet. MINERALS Unlike sodium and potassium, which are staple elements of the diet and are present in ample amounts in all food of vegetable and animal origin, certain minerals are additional dietary requirements. Although most are present in the average diet, these minerals may not always be ingested in quantities sufficient to satisfy metabolic needs, especially during growth, stress, trauma, and blood loss, and in some diseases. Calcium The body's requirements for calcium are generally met by eating or drinking dairy products, especially milk. Most calcium (90 percent) is stored in bone, with a constant exchange occurring among blood, tissue, and bone. The intake is balanced by losses in urine and feces. The blood levels of calcium and its intestinal absorption, deposition, or mobilization from bone are all controlled by a complex interplay of vitamin D, parathyroid hormone, and calcitonin. Contrary to some long-held beliefs, high intakes of protein and phosphorous do not lead to a loss of calcium. Besides promoting rigidity in bones, calcium regulates nervous excitability and muscle contraction; it is also important in maintaining the integrity of intracellular cement and cellular membranes. During periods of growth, pregnancy, and lactation, calcium intake needs to be supplemented. Diseases of calcium metabolism include vitamin D deficiency (rickets), hypervitaminosis D, hypoparathyroidism and hyperparathyroidism, and some forms of renal disease. Phosphorus Phosphorus plays an important role in the hemostasis of calcium and in reactions involving carbohydrates, lipids, and proteins. The chemical energy of the body is stored in "high energy phosphate" compounds. Elemental phosphorus is extremely poisonous, but phosphorus ingested as phosphates in the diet is not toxic. Iodine The one important function of iodine is associated with the synthesis of thyroxine and the function of the thyroid gland. Persons living in coastal regions usually receive an adequate supply of iodine because of the high content in seafood. In geographic regions located far inland, however, a lack of iodine in food is apt to occur, causing goiter. To protect an inland population from goiter, a small amount of iodine is often added by manufacturers of table salt (iodized salt). Elemental iodine is highly poisonous, and its only use in medicine is as an antiseptic. Iron Iron is a vital component of hemoglobin and also of certain respiratory enzymes. Foods high in iron content include meat (liver and heart), egg yolk, wheat germ, and most green vegetables. Increased requirements for iron occur during the growth period and pregnancy, and with excessive menses and other instances of blood loss. Ordinarily the average diet contains 10 to 15 mg a day, which is adequate for most people. Iron deficiency, resulting in anemia, can be treated by large amounts of iron in order to gain positive absorption. Magnesium Magnesium is an essential element in human metabolism and functions in the activities of muscles and nerves, protein synthesis, and many other reactions. Magnesium deficiency may occur in alcoholism, diabetes mellitus, pancreatitis, and renal diseases. Prolonged deficiency can cause changes in heart and skeletal muscle. Excessive retention of magnesium can occur in renal disease and results in muscle weakness and hypertension. Zinc Zinc serves as a cofactor of dehydrogenases and carbonic anhydrase. The average diet contains adequate amounts, and water from galvanized pipes may contribute an added increment. Losses of zinc from the body occur during such stress situations as surgical operations, and the replacement of zinc appears to hasten recovery. Overingestion of zinc or inhalation of its vapors, particularly common among foundry workers, can produce depression, malaise, vomiting, and headache. Fluorine and Trace Minerals Fluorine as fluoride is a requirement to bind calcium in bones, and fluoridation of the water supply is the most efficient method of providing this mineral. Microamounts of such elements as boron, chromium, chlorine, copper, manganese, molybdenum, selenium, silicon, sulfur, and vanadium are considered necessary to health; the minute amounts needed of these trace minerals, however, can be obtained in even the poorest diets. Joseph R. Dipalma Bibliography: Briggs, M. H., Vitamins in Human Biology and Medicine (1981); Consumer Guide, Complete Book of Vitamins and Minerals (1988); Dyke, S. F., The Chemistry of the Vitamins (1965); Kutsky, R. J., Handbook of Vitamins, Minerals and Hormones, 2d ed. (1981); Latour, John Paul, The ABCs of Vitamins, Minerals, and Natural Foods (1972); Lesser, Michael, Nutrition and Vitamin Therapy (1979); Levy, Joseph V., Vitamins; Their Use and Abuse (1976); Lewis, C. M., Basic and Family Nutrition, 2d ed. (1984); Passwater, Richard, A Beginner's Introduction to Vitamins (1983); Rennert, O. M., and Chan, Waiyee, eds., Metabolism of Trace Minerals in Man, 2 vols. (1984); Solomons, N. W., and Rosenberg, I. H., Absorption and Metabolism of Mineral Nutrients (1984); Spedding, V. A., Vitamins (1988).