Vitamins and Minerals
Although nutritional deficiency is often associated with poverty, it is essential to remember that ANYONE can suffer from nutritional disorders. Although diseases of dietary deficiency are not very common in our society, they still do occur and should not be ruled out by an examining physician simply on the basis of a patient's economic status.
Most of you are probably familiar with the basic functions of the vitamins and minerals which are covered in this goal and at least some of the diseases which can result from deficiencies of these nutrients. If this is the case, then much of the material presented will not be new. You should also be aware of the fact that "new" roles are being discovered for many of the vitamins, such as possible prevention of chemical carcinogenesis by Vitamin A or a role in the regulation of lipolysis for Vitamin C. It is not unlikely that RDA's for some nutrients will be altered as more is learned about their physiological functions or that new therapeutic uses will be found for certain of them.
The fat-soluble vitamins are A, D, E and K. Their absorption parallels the absorption of fat, they can be stored, and their functions are often related to structural activities.
Vitamin A. Requirements: Please note that the requirement for Vitamin A is given in retinol equivalents (RE). One retinol equivalent is equal to one microgram of retinol.
Sources: Please note that Vitamin A itself is found only in animal products (butter, eggs, whole milk, liver, some fish) but beta-carotene (a precursor of Vitamin A) is found in many plant foods, particularly pigmented fruits and vegetables--carrots, pumpkin, sweet potatoes, cantaloupe--and dark green leafy vegetables like spinach and broccoli. In the United States, Vitamin A is also added to foods such as margarine and low-fat milks.
Functions: Vitamin A aldehyde combines with opsin to form the visual pigment rhodopsin, which is essential to the eye's ability to adapt to changes in light. The vitamin also plays a role in the formation and maintenance of epithelial tissue, in growth, and in reproductive processes.
Deficiency: An early sign of Vitamin A deficiency is night blindness (inability to see well in dim light) due to deficiency of rhodopsin. Without Vitamin A, epithelial cells become dry and flat, gradually hardening to form keratin (a process called keratinization). This will lead to: 1) drying and hardening of the cornea (xerophthalmia), progressing to blindness if the deficiency is severe enough; 2) dry, scaly skin, development of follicular hyperkeratosis (small pustules or hardened, pigmented, papular eruptions appear around hair follicles); 3) drying of nasal passages, salivary glands and mouth, increasing the likelihood of infection; 4) drying and sloughing of gastrointestinal mucosa, affecting digestion and absorption; 5)breakdown of genitourinary epithelial tissue, increasing the incidence of urinary tract and vaginal infections; 6) improper development of teeth. Vitamin A deficiency is also associated with anemia, due possibly to impaired intestinal absorption of iron, or decreased uptake of iron into bone marrow. Vitamin A deficiency is particularly serious in children. Children with this deficiency grow poorly, are more anemic, have more infections and a higher mortality rate.
Anti-cancer effects: Retinoids (Vitamin A and its synthetic analogs) have been shown to delay or prevent the development of invasive malignancy in animals, by arresting or reversing the progression of premalignant cells. This effect apparently involves the enhancement of intrinsic physiological defense mechanisms which protect the organism against the development of clones of malignant cells. Synthetic retinoids have been developed, which are less toxic and target specific organ sites better than the natural retinoids. In a recent prospective study of 16,000 men, low retinol levels were found to be associated with an increased risk of cancer.
Excess: The ingestion of large amounts of Vitamin A causes toxicity, either acute or chronic, in animals and humans. A large single dose of Vitamin A will cause vomiting, nausea, headache, vertigo, drowsiness, malaise, muscular incoordination, and recurrent vomiting. A single lethal dose will cause deepening coma, convulsions, respiratory irregularities and finally death from respiratory failure or convulsions. Chronic hypervitaminosis A includes such manifestations as joint pain, thickening of long bones, loss of hair, jaundice and liver injury resulting in portal hypertension and ascites. The incidence of hypervitaminosis A may be increasing, due to increased popularity of "megavitamin" therapy, the use of Vitamin A in the treatment of skin conditions (e.g., acne) and recent publicity concerning its apparent anti-cancer effects. Recommended daily allowances for Vitamin A range from 400 R.E. (for young children) to 1200 R.E. (for lactating women). Normal adult U.S. diets contain 1500-2000 R.E. Acute toxic effects resulting from a single dose of 350,000 IU (70,000 R.E.) have been described but the dosage level for chronic toxicity is difficult to pinpoint. Chronic hypervitaminosis A has been reported in patients ingesting daily doses of 55,000 R.E. for 2 years, 41,000 R.E. for 8 years and 6200 R.E. for 30 years. Chronic toxicity may be the result of the total dose ingested rather than the usage rate; lower doses can thus produce toxicity over longer periods of time. Chronic toxicity is often misdiagnosed because its symptoms mimic alcoholic liver disease and some common dermatological disorders. There are some indications that hypervitaminosis A may be teratogenic in humans; teratogenicity has been conclusively demonstrated in a number of other species, and there are case reports of defects among children of women who used high-dose vitamin A supplements during early pregnancy. Using oral contraceptives elevates blood Vitamin A levels, but toxicity is not likely since the induced change in Vitamin A still falls within the normal range and is accompanied by a corresponding change in retinol binding protein (RBP). Hypervitaminosis A does NOT result from excessive ingestion of carotenoids, but individuals who routinely ingest large amounts of carotenoids may exhibit a yellow jaundice-like coloration of the skin, particularly in the palms of the hands, soles of the feet and nasolabial folds (unlike jaundice, the sclerae are clear).
Vitamin D. Requirements: Apparently the requirement for Vitamin D is normally met by its synthesis in the skin from the precursor 7-dehydrocholesterol, and the single most important factor determining Vitamin D status appears to be the extent of solar radiation of the skin. Inadequate skin exposure to sunlight, dark-pigmented skin, aging, use of sunscreens, and a northern geographical latitude may make some individuals susceptible to a deficiency. In the U.S. and other countries, various foods are fortified with Vitamin D to prevent such deficiencies, resulting in widespread consumption of excessive amounts of Vitamin D. Because of the toxic nature of Vitamin D (see below, Excess), there have been many calls to abolish or curtail vitamin D-fortification of foods. Vitamins are formally defined as trace dietary constituents required to effect normal functioning of a physiological process. Since under normal physiological circumstances, all mammals can generate adequate Vitamin D via ultraviolet photolysis, Vitamin D does not really fit the definition of a vitamin. Or, it is only a vitamin when the organism does not have access to sunlight or ultraviolet light. This "vitamin" might be more properly classified as a steroid hormone.
Sources: There are few natural food sources of Vitamin D; D2 and D3 are found in yeast and fish liver oils. Milk and margarine are two foods commonly fortified with Vitamin D. As stated above, sunlight may be considered the primary source of Vitamin D for most people, most of the time.
Functions: Vitamin D is the most important hormone regulating the mineral content of bone. It is a seco-steroid, similar in structure and mode of action to other steroid hormones such as estradiol, testosterone, hydrocortisone, aldosterone, etc. It has been recognized that there is an endocrine system (in the liver and kidney) for processing the prohormone, Vitamin D, into its hormonally active form. There are two major forms of vitamin D: D2 (ergocalciferol) and D3 (cholecalciferol or calciferol). There are 28 chemically characterized metabolites of Vitamin D including several which are biologically active and contribute to calcium and phosphorus metabolism. Receptors for 1,25-(OH)2D(1,25-dihydroxycalciferol), a biologically active metabolite, have been identified in many tissues, including intestine, kidney, cartilage, teeth, skin, muscle, bone, cerebellum, pancreas, parathyroid, placenta, ovary, testes and pituitary. In each of these tissues, 1,25-(OH)2D is capable of stimulating the production of a calcium-binding protein (CaBP). 1,25(OH)2D can stimulate intestinal absorption of calcium and phosphorus, mobilize bone calcium, and modulate parathyroid hormone secretion. Physiological roles of vitamin D are discussed in more detail in the Endocrine Block.
Deficiency: Vitamin D deficiency may be due to low dietary intake, insufficient exposure to sunlight, malabsorption syndromes, use of drugs (such as phenobarbital) which accelerate metabolism of the vitamin, certain liver diseases, or failure of formation of 1,25-(OH)2D (due usually to renal failure or renal tubular disorders). Because of the complexity of the functions of Vitamin D and its metabolites, deficiency can have widespread manifestations. While rickets (malformation of skeletal tissue in growing children) and osteomalacia (bone abnormality due to impaired mineralization in adults) are the classic manifestations of Vitamin D deficiency, it is clear that many tissues other than bone could be affected. However, since tissues other than bone appear to be more sensitive to Vitamin D and would therefore be induced at lower levels, defects in function of these tissues would probably be seen only in extreme cases of Vitamin D deficiency.
Excess: The symptoms of Vitamin D toxicity include calcification of soft tissues, such as lungs and kidneys, and bone fragility. Renal tissue is especially prone to calcify, affecting glomerular filtration and overall function. In the recent past, oversupplementation of infant formulas and foods with Vitamin D in Britain resulted in epidemic infantile hypercalcemia. The principal manifestations were supravalvular aortic stenosis syndrome (SASS) along with related arterial abnormalities, renal tubular acidosis and fibrocystic disease of the pancreas. Severe manifestations were familial, indicating that hyperreactivity to Vitamin D is genetic. To those with such a metabolic pattern, inadvertent consumption of excess Vitamin D is a particular risk. It should be noted that the risks and benefits of Vitamin D supplementation constitute a very controversial subject.
Vitamin E. Vitamin E is the generic name for a group of compounds with similar physiologic activity (tocopherols). In human nutrition, alpha-tocopherol is the most significant of these.
Sources: The richest sources of vitamin E are the vegetable oils. Other food sources include leafy vegetables, milk, eggs, meats, fish and cereals.
Function, Deficiency: Vitamin E oxidizes very slowly, making it a potent antioxidant. By interrupting the oxidation of the lipid component of cell membranes, the tocopherols protect the cell from oxidative damage. Vitamin E deficiency has been recognized as an enhancer of platelet aggregation as well as a factor in hemolytic anemia, retrolental fibroplasia, bronchopulmonary dysplasia and several syndromes found in premature infants. For full-term infants, breast milk (which contains 2-5 units of Vitamin E per liter) is sufficient; but because of their Vitamin E-deficient state, supplementation is particularly important for premature infants. Vitamin E therapy (supplementation) has been found to be beneficial in treating deficiencies caused by fat malabsorption and in easing intermittent calf pain when walking. Vitamin E has been reported to relieve chronic cystic mastitis in about 70% of cases and may protect against the formation of cancer-causing nitrosamines in the body. Recent studies have indicated that Vitamin E may prevent cortical cataracts in diabetic patients. Neonatal cholestasis is characterized by malabsorption of fat (and fat-soluble vitamins) because of impairment in bile flow into the small intestine. The resulting vitamin E deficiency, if it is untreated, may lead to degenerative neuromuscular syndrome in children with this disorder. Early vitamin E supplementation can reverse these symptoms. Several recent studies have shown that supplementation with vitamin E can significantly reduce the incidence of heart disease.
Excess: There is some evidence that tocopherol can accumulate continuously in adipose tissue. Nonetheless there is as yet no convincing evidence of Vitamin E toxicity.
Vitamin K. Requirements: The 1989 RDAs recommend a daily intake of 60-80 µg of Vitamin K for adults. This amount is intended to supplement synthesis of Vitamin K by intestinal bacteria, which is the most important source of the vitamin.
Sources: The main source of Vitamin K is bacterial synthesis in the colon. Dietary Vitamin K is found in most human foods in small amounts. Relatively rich sources are green leafy vegetables (cabbage, spinach, kale and cauliflower), with lesser amounts found in tomatoes, cheese, egg yolks and liver.
Functions: Vitamin K is required for the modification and activation of a number of important proteins, including but not limited to, coagulation factors II (prothrombin), VII, IX, and X. The specific action of Vitamin K is the post-translational carboxylation of glutamic acid residue on the Vitamin K-dependent proteins. This carboxylation, or conversion of glutamic acid to alpha-carboxyglutamic acid, creates effective calcium binding sites on these proteins, allowing them to be functional. For example, prothrombin requires calcium for its activation to thrombin, which in turn converts fibrinogen to fibrin.
Deficiency: Vitamin K deficiency produces a bleeding disorder associated with a prolonged prothrombin time (PT). Due to the widespread distribution of Vitamin K in plant and animal tissues, and the significant amounts contributed by bacterial synthesis, primary Vitamin K deficiency is uncommon in healthy persons. However, newborn infants are at particular risk because: 1) lipids do not easily cross the placenta and 2) the gut is sterile for the first few days of life. Prothrombin levels may decrease to a level as low as 30% in normal neonates; if they fall below 10%, hemorrhagic disease of the newborn will occur. Vitamin K deficiency may also be a problem for severely ill patients who are eating inadequately and receiving antibiotics. A recent study described the discovery of a coagulopathy due to Vitamin K deficiency in 42 hospitalized patients, most of whom were misdiagnosed.
Excess: Even when large amounts of Vitamin K are taken over prolonged periods, toxic effects have not been observed.
This objective is obviously quite similar to the previous one, except that it involves a different group of vitamins--the so-called B-vitamins. The "Vitamin B Complex" is a group of essential nutrients, all water-soluble, which are grouped together because of their functional interrelationships and their common distribution in certain foods (whole grains, nuts, beans, lean meats, milk, eggs, leafy green vegetables). Included are three vitamins originally discovered because of classic deficiency diseases (thiamin, riboflavin, niacin), three more recently discovered coenzyme factors (pyridoxine, pantothenic acid and biotin) and two factors necessary for blood formation (folate and cobalamin). They were originally thought to be one vitamin (Vitamin B) and as each was further identified it was also numbered (Vitamin B1, B2, B3, etc.). This nomenclature has gradually been replaced by the use of specific chemical names, although some of the older names (particularly B6/pyridoxine and B12/cobalamin) are still in general use. Most of the B-vitamins are involved in the intracellular metabolism of carbohydrates, fats and proteins, or in erythropoiesis (production of red blood cells.) A deficiency of B-vitamins will tend to be manifested in tissues with a high rate of metabolic activity and a high rate of cell turnover. Common symptoms include stomatitis, gastritis, hematological disorders and involvement of the nervous system.
It has generally been believed that water-soluble vitamins are non-toxic, that excesses are simply excreted in the urine. In fact, while water-soluble vitamins (B-complex and ascorbate) are less toxic than fat-soluble vitamins (A, D, E, and K), toxic effects have been demonstrated following the regular ingestion of very high doses (megadoses) of water-soluble vitamins. Five mechanisms have been proposed whereby water-soluble vitamins can cause toxic effects in humans: 1) direct toxic effects of vitamins or their metabolites; 2) withdrawal symptoms following the discontinuation of a megadose regime; 3) masking the symptoms or signs of concurrent disease; 4) interaction with drugs or other vitamins; 5) ingestion of megadoses of water-soluble vitamins packaged as vitamin supplements which also contain high doses of fat-soluble vitamins.
Thiamin (Vitamin B1). Requirements: The general requirements are given in the RDA table. Some other important factors which may influence thiamin requirements: a) in alcoholism, impaired utilization of thiamin is often compounded by a dietary deficiency; b) fevers and infections increase cellular energy requirements.
Sources: Thiamin is widely distributed, in both plant and animal foods. Particularly good sources include whole and enriched grains, legumes, pork, and liver.
Functions: Thiamin serves as a coenzyme (thiamin pyrophosphate or TPP) in key reactions that produce energy from glucose or convert glucose to fat for energy storage.
Deficiency: The classic disease resulting from thiamin deficiency in humans is called beriberi. There are broad clinical effects: a) GI system: anorexia, indigestion, constipation, gastric atony and achlorhydria are seen; muscle and secretory cells do not receive enough energy to perform their digestive functions. b) Nervous system: impairment of neuronal activity, mental confusion, diminished reflexes, apathy and fatigue; the CNS requires glucose as an energy source. In severe deficiency, lipogenesis is affected, with resulting degeneration of myelin sheaths, leading to nerve irritation, pain and paresthesia. Paralysis eventually results. c) Cardiovascular system: peripheral vasodilation, weakening of heart muscle, and retention of sodium and water leading to edema (so-called wet beriberi). The Wernicke-Korsakoff syndrome is a thiamin deficiency disease that occurs mainly in alcoholics. The acute phase of this disease (Wernicke's encephalopathy) responds to IV administration of high doses of thiamin. Wernicke's disease is characterized by nystagmus, ophthalmoplegia, ataxia of gait and mental confusion. Korsakoff's psychosis refers to a mental disorder characterized by impairment of retentive memory.
Subclinical thiamin deficiency is characterized by irritability, frequent headaches and unusual fatigue.
Excess: Thiamin appears to be harmless when taken orally; parenteral doses greater than 400 mg cause nausea, anorexia, lethargy, and mild ataxia.
Riboflavin (Vitamin B2). Sources: Riboflavin is contained in many foods of animal and vegetable origin. The richest sources are milk and its nonfat products. Other good sources are green vegetables, whole or enriched grains and organ meats.
Functions: Riboflavin is a coenzyme participating in oxidation-reduction reactions in numerous metabolic pathways and in energy production via the respiratory chain. The cell enzymes of which riboflavin is an important part are called flavoproteins.
Deficiency: Naturally occurring deficiency of riboflavin alone is probably never encountered in humans; rather it is accompanied by other nutritional deficiencies. Ariboflavinosis induced by feeding a riboflavin-deficient diet involves a combination of symptoms centering on tissue inflammation and breakdown, and poor wound healing. Lesions mostly involve the mouth, eyes, skin and genitalia. The most common lesions are angular stomatitis (fissures or cracks radiating from the corners of the mouth), cheilosis (painful cracks on the lips) and glossitis (inflammation of the tongue.)
Excess: Due largely to its low solubility and ready excretion, there have been no reports of toxicity from ingestion of excess riboflavin.
Niacin (Nicotinic Acid). Requirements: In the 1989 RDA tables, niacin allowances are listed as milligrams of niacin equivalents (NE) thereby recognizing the contribution of the precursor tryptophan to the niacin activity of the diet. On an average, 60 mg of tryptophan is considered equivalent to 1 mg niacin or niacin equivalent (NE).
Sources: Niacin is present in many foods of vegetable origin, and its amide form niacinamide (nicotinamide) in foods from animal sources. Particularly rich sources are lean meat (especially liver), whole or enriched grains, and legumes.
Functions: Niacin plays an important role in glycolysis and tissue respiration. Nicotinamide is contained in NAD and NADP, which are required by hundreds of enzymes, mostly dehydrogenases, which catalyze diverse chemical reactions. Nicotinic acid therapy is used in treatment of hyperlipidemia; it decreases serum loads of triglyceride and cholesterol.
Deficiency: The classical niacin deficiency disease is pellagra. Early signs include weakness, lassitude, anorexia and indigestion. Pellagra is a chronic wasting disease associated with dermatitis (bilateral and symmetrical, aggravated by sunlight, heat, trauma), dementia (encephalopathy characterized by confusion, disorientation, hallucination, loss of memory and eventually psychoses) and diarrhea (due to widespread inflammation of intestinal mucosa).
Excess: Because niacin may release histamine (causing the common side effect of flushing) caution should be exerted by individuals with peptic ulcer disease and asthma. Megadoses of niacin (3000 mg for several years) have been associated with hepatotoxic effects, increased incidence of gouty arthritis, and certain cardiac arrhythmias. Many patients taking 3 grams of niacin daily also develop a variety of dermatological problems, which usually disappear when niacin is discontinued. Gastrointestinal distress and mild elevations of liver enzymes have also been noted.
Pyridoxine (B6). Requirements: Several studies have indicated that Vitamin B6 intake is often below RDA levels, even in individuals consuming diets adequate for most nutrients. The RDA itself is determined for the majority of persons, who are healthy, largely sedentary and have no underlying medical conditions. Requirements may be very different for persons who perform heavy physical labor, who are pregnant, asthmatic or who have sickle cell anemia. For these reasons, supplementation is often desirable. Vitamin B6 supplementation may prevent recurrence of Chinese Restaurant Syndrome in susceptible individuals. Alterations in tryptophan metabolism due to pregnancy or use of oral contraceptives (specifically incorrect excretion of tryptophan metabolites such as xanthurenic acid and kynurenic acid) may be corrected by the administration of 20 mg pyridoxine per day.
Sources: It is widely distributed in foods of animal and vegetable origin. Particularly good sources include whole grains, seeds, milk, liver and kidney.
Functions: Pyridoxine is a coenzyme in nearly 100 enzymatic reactions, involving proteins, carbohydrates and lipids. These include synthesis of hemoglobin, synthesis of certain neurotransmitters (including serotonin and alpha-aminobutyric acid), active transport of amino acids, transamination, glycogenolysis, formation of sphingolipid precursors. It is also known to interact with certain steroid hormones (a possible application has been treatment of premenstrual syndrome with B6). There are indications that Vitamin B6 may be useful in treating nausea and vomiting of pregnancy, and some cases of carpal tunnel syndrome. It may also enhance cellular immune mechanisms.
Deficiency: From a list of metabolic activities in which it is involved (a partial list appears above), it is apparent that deficiency will be associated with widespread symptoms. These include anemia, neurological disturbances, dermatitis, cheilosis, glossitis, anorexia, weight loss, lassitude and general weakness. Pyridoxine deficiency leads to CNS demyelination and has been linked to incidence of multiple sclerosis, although the nature of this association remains unclear. Deficiency of vitamin B6 usually occurs in combination with deficiencies of other B-complex vitamins. Recent studies have shown that individuals with low levels of vitamin B6 have a greater chance of developing heart disease, due possibly to elevated levels of homocysteine.
Excess: Large doses of Vitamin B6 (2 grams daily for four months, or 5 grams daily for two months) have been shown to exert a toxic effect on the peripheral nervous system. Symptoms included unsteady gait, numbness of feet and hands, and occasional peroral numbness.
Pantothenic acid. Requirements: Since naturally occurring deficiency is unknown, an RDA has not been established for pantothenic acid. The estimated "safe and adequate" range for adults is 4 to 7 mg daily.
Sources: Pantothenic acid is widely distributed among foods, being especially abundant in animal tissues, whole grain cereals, and legumes. It may also be synthesized by intestinal bacteria, but amounts and availability are unknown.
Functions: Pantothenic acid is an essential constituent of coenzyme A and is therefore vital to metabolic reactions involving carbohydrate, fat and protein metabolism in all cells.
Deficiency: Experimentally induced deficiency produces such symptoms as tiredness, abdominal pain and cramps, nausea, flatulence, vomiting, and paresthesia of the hands and feet.
Excess: There has been no evidence of harmful effects with therapeutic doses of pantothenic acid (10-100 mg daily). Even with amounts as high as 10 to 20 grams of the calcium salt, the only reported problem was occasional diarrhea.
Biotin. Requirements: Since the amount needed is so small, and since most of the body's need is supplied by intestinal bacteria, an RDA for biotin has not been established. The estimate for adults is 30-100 µg per day.
Sources: Biotin is widely distributed, but bioavailability varies greatly. The best food sources are liver, egg yolk, cereals and yeast.
Functions: Biotin is a coenzyme required for the function of several essential carboxylases, including pyruvate carboxylase and acetyl CoA carboxylase.
Deficiency: Biotin deficiency can be induced by ingestion of large amounts of avidin, a biotin binding substance found in raw egg white. Symptoms include anorexia, nausea, vomiting, glossitis, pallor, mental depression and dermatitis.
Excess: There have been no reports of toxicity associated with intakes as high as 10 mg daily.
Folate (folic acid). Sources: Folates are present in nearly all natural foods. Leafy vegetables, yeast, legumes, asparagus, liver and some fruits are good sources of this vitamin. Recent regulations require the fortification of flour and other grain products with folacin.
Functions: Folates function metabolically as coenzymes that transport single carbon fragments from one compound to another in amino acid metabolism and nucleic acid synthesis. Folate is essential for formation of DNA, which is critical in governing maturation of erythrocytes. Maternal dietary supplementation of 4 mg folic acid daily has been shown to reduce the occurrence of neural tube defects in the offspring of high-risk women.
Deficiency: Deficiency leads to impaired cell division and alterations of protein synthesis, most noticeably in rapidly growing tissues. With inadequate folate, fewer erythrocytes are formed and those produced are larger and more fragile (megaloblastic anemia). Deficiency affects other tissues as well, but erythrocytes are particularly susceptible because of rapid proliferation. A daily 0.1 mg supplement is now recommended to combat anemia and other symptoms associated with oral contraceptive use.
Excess: Folate is not toxic to normal humans even in amounts much larger than therapeutic doses. There is, however, a danger in taking doses greater than 0.1 mg/day, in that the neurological manifestations of pernicious anemia may be masked.
Vitamin B12 (Cobalamin). Sources: The only natural source of vitamin B12 is synthesis by microorganisms. It is generally not found in plants except when they are contaminated by or contain microorganisms (as do the root nodules of certain legumes). The vitamin is widely distributed in foods of animal origin, with the richest sources being organ meats, bivalves (clams, oysters), nonfat dry milk, seafood and egg yolks. It is also added to some breakfast cereals.
Functions: Cobalamin is an essential coenzyme required for amino acid metabolism and for the formation of hemoglobin. It is essential for the function of all cells, but particularly those of the bone marrow, intestinal tract and gastrointestinal system.
Deficiency: Vitamin B12 deficiency results in macrocytic, megaloblastic anemia, neurological symptoms due to CNS demyelination, and other general symptoms such as weakness. Dietary deficiency is very rare; B12 deficiency is often due to inadequate absorption (usually lack of intrinsic factor--see module on gastric secretion.) Low serum B12 levels are not uncommon in the elderly.
Because of the limited distribution of this vitamin (i.e., to foods of animal origin), it would be well to insert here definitions of vegetarianism: Vegans (strict vegetarians) do not eat meat or any meat products (i.e., eggs, dairy products). Lacto-vegetarians eat dairy products, ovo-vegetarians eat eggs, and lacto-ovo-vegetarians eat both eggs and dairy products. Since Vitamin B12 is virtually not found in plant foods, one would expect most individuals who adhere to a strict (vegan) vegetarian diet to develop the symptoms of B12 deficiency. This is not the case, however. Megaloblastic anemia arising from uncomplicated dietary deficiency of B12 is extremely rare, and overt manifestations of B12 deficiency are the exception, rather than the rule, in adults who are vegans. Vitamin B12 stores in the human body exceed its daily requirement 1000-fold. So if an adult who has been an omnivore changes to a vegan diet, it would theoretically take several years for body stores of Vitamin B12 to be depleted. While serum B12 levels do fall to very low levels in vegans during the first 2-3 years of dietary restriction, they do not continue to fall thereafter. And although serum B12 levels in vegans may be quite low, symptoms of B12 deficiency do not usually develop. The reason for this is unknown. Perhaps there is increased intestinal synthesis of the vitamin in response to the restricted diet (herbivorous animals obtain their Vitamin B12 from bacterial synthesis in the rumen). While adult vegans do not appear to be very susceptible to the symptoms of Vitamin B12 deficiency, such may not be the case with young children, particularly breast-fed infants of vegan mothers.
Excess: Vitamin B12 is not toxic to humans, even when administered (by mouth or injection) in amounts much greater than therapeutic doses.
Requirements: Vitamin C has long been known as an antiscorbutic (anti-scurvy) factor, hence the name "ascorbic acid." Glucose is the natural precursor of ascorbic acid. Almost every animal species can make this conversion to produce the vitamin and therefore do not require an exogenous source of ascorbic acid. The few exceptions (including monkeys, guinea pigs, Indian fruit bats, the red-vented bulbul, and human beings) lack the enzyme for conversion of 1-gulonic acid to ascorbic acid. Scurvy (and possible other diseases or disorders of Vitamin C deficiency as yet undefined) can be thought of as a disease of genetic origin, an inborn error of metabolism.
The RDA for ascorbic acid (60 mg for adults) is equivalent to that amount needed to prevent scurvy, with some margin of reserve. Still unanswered is the question of whether this amount of ascorbic acid is also equivalent to the optimal amount for human health.
Infectious processes (particularly bacterial infections) deplete the limited tissue stores of ascorbic acid and necessitate additional intake. Just how large a therapeutic dose of Vitamin C may prevent infection is not known. However, if the ability of a 70-kg goat to synthesize endogenous ascorbate is compared with the RDA of a 70-kg human, there is a 300-fold difference (13,000 mg vs. 45 mg), perhaps implying that fairly large doses of Vitamin C might not be out of line. There is still much controversy concerning the use of massive doses of the vitamin in the prevention of the common cold. As yet there is not sufficient evidence to either substantiate or repudiate claims for the validity of such large doses. Most recent results seem to indicate a reduced severity of cold symptoms in response to a regimen of Vitamin C megadoses, but no effect has been shown with respect to actual incidence of colds. Fevers also deplete tissue stores of ascorbic acid and would require additional intake.
In general, any body stress (such as injury, illness, shock) tends to deplete body tissue "stores" of ascorbate. Normal physiological stress periods, such as growth and pregnancy, also require additional Vitamin C. Supplemental ascorbic acid is also needed by smokers and individuals taking oral contraceptives or aspirin on a regular basis.
Even more controversial than the use of Vitamin C to prevent colds, is the use of the vitamin in the prevention, or even the treatment of cancer. There is some evidence that increasing the intake of ascorbic acid might enhance the body's natural resistance to cancer. Further, it has been suggested that Vitamin C may prevent the formation of carcinogenic nitrosamines by reacting with nitrite within the stomach. Several clinical trials in the United States and Britain are currently being conducted to assess the value of Vitamin C in cancer treatment.
Sources: Vitamin C is less widely distributed than the other water-soluble vitamins. It is particularly abundant in citrus fruits and tomatoes: other good sources are potatoes, broccoli, berries, melon, peppers, brussel sprouts. Ascorbic acid is unstable and easily oxidized; it may be destroyed by oxygen, alkalis and high temperatures. Much of the Vitamin C content may be lost in the processing of food.
Functions: Ascorbic acid serves as a cofactor of hydroxylating enzymes which catalyze a number of important reactions, including: a) the formation and stabilization of collagen; b) the production of carnitine, which provides energy to cells, particularly to cardiac and skeletal muscle; c) the biosynthesis of epinephrine and norepinephrine; d) the degradation of cholesterol; e) the metabolism of tyrosine. Ascorbic acid also stimulates dietary iron absorption and is a powerful antioxidant. In general, Vitamin C is required for the building and maintenance of body tissues, including bone matrix, dentin, collagen and connective tissue, as well as maintaining the mechanical strength of blood vessels. Vitamin C may also play a number of other roles, which are currently being explored and defined. For example, Vitamin C has been shown in some studies to lower cholesterol, protect against periodontal disease, enhance blood ethanol clearance, diminish the impairment of motor coordination caused by acute alcohol consumption, enhance the bioavailability of trace minerals such as iron, and improve athletic performance (by lowering oxygen consumption and pulse rate during exercise, for example).
Deficiency: Marginal vitamin C deficiency is accompanied by loss of appetite, physical fatigue or weakness, reduced work capacity, impaired immune response, retarded wound healing and poor iron absorption. The classic deficiency disease is scurvy, the symptoms of which include easy bruising, poor wound healing, pinpoint hemorrhages of the skin, bone and joint hemorrhages, easy bone fracture, and gingivitis (soft bleeding gums with loosened teeth.)
Excess: Large doses of Vitamin C may be associated with diarrhea, increased lytic sensitivity of red blood cells, acidification of urine (which might precipitate oxalate), and increased urinary excretion of uric acid. These effects seem to be highly variable.
Iron. Sources and Requirements: Iron is widely distributed in the food supply: meat, eggs, legumes, enriched and whole grain cereals, and dark green vegetables are good dietary sources. Adequate iron supply is not necessarily guaranteed by simply ingesting foods which are rich in iron content. The amount of iron potentially available from foods depends not only on the amount of iron supplied but also the nature of that iron and the composition of the meal with which it is consumed. For example, infant cereals which are fortified with iron may not have the desired effect if they are eaten with milk, which interferes with iron absorption. Iron absorption will be discussed in more detail in a subsequent module. Please note the differences in iron requirements determined by age and sex. If you look at iron content of various foods (see Pennington), you can easily see that (unless liver is a regular part of the diet) it may be somewhat difficult for young children and pre-menopausal women to obtain the RDA of iron (10 mg and 15 mg, respectively) from their diets. Iron supplementation or use of iron-fortified foods may often be recommended.
Functions: About 70% of body iron is contained in hemoglobin, myoglobin, heme enzymes, cofactor and transport iron; almost all of the remaining 30% is stored in the liver, spleen and bone marrow as ferritin and hemosiderin. Iron is essential to all vertebrate forms of life, because it is a vital constituent of the heme portion of hemoglobin. In addition to this role in oxygen transport and utilization, iron is necessary for the function of a number of enzymes, including those involved in immune competence and cell division.
Deficiency: Iron deficiency results in hypochromic microcytic anemia, which is associated with tiredness, weakness, and dyspnea on exertion. Severe anemia may lead to tachycardia, palpitations and edema. Some of the other manifestations of iron deficiency include: increased risk of low birth weight, prematurity and perinatal mortality in infants born to iron-deficient mothers; slowed rate of growth in infants; behavioral changes and impairment of learning in children; skin and mucosal changes (including glossitis and angular stomatitis); gastritis; achlorhydria; fat malabsorption; acute GI bleeding; impaired work performance; increased susceptibility to infections (immune deficiency) and a number of behavioral changes. There is some concern that iron deficiency in early life may impair mental development. Most of these symptoms appear to occur independently of the anemia associated with iron deficiency.
Excess: Human beings have no mechanism for dealing with iron overload. Iron overload may occur: 1) through a genetic predisposition toward increased iron absorption (as in primary hemochromatosis); 2) through the ingestion of excess iron (medicinal or dietary) or 3) through transfusion therapy (most markedly in thalassemia patients). Primary hemochromatosis is a hereditary disease found in both sexes, but because iron accumulation may be partly offset by menstrual losses, the symptoms are seen mainly in men. Patients with this condition absorb an excess of 3 mg/day of iron, which leads to the accumulation of 15-50 grams of body iron over 25-50 years. Initially, iron is taken up and stored by macrophages. Toxic effects are not seen because the iron is isolated in ferritin granules. Eventually, however, these mechanisms are overwhelmed and iron is deposited in the parenchyma of the cells. Iron is deposited most heavily in the liver and pancreas, but also in cardiac muscle, skin, and in the pituitary, adrenal, thyroid, and parathyroid glands. Accumulated iron eventually causes tissue damage, particularly to the heart. Hepatic cirrhosis, pigmentation of the skin, arthropathy, cardiomyopathy, and endocrine abnormalities will result. Another cause of iron overload is through ingestion of excess iron. Ingestion iron overload has been documented in Sweden, where various foods have been enriched with iron for the past 30 years. In the U.S., iron fortification has been the focus of much controversy since 1970, when the FDA began to consider a proposal to increase four-fold the amount of iron added to flour. A long and hard campaign (led by physicians) to prevent the proposed fortification ended in 1978 when the FDA concluded that the "increases are not proven to be needed, safe or effective." Whatever the cause of iron overload, the condition is treated by the use of chelating agents. Tea and other tannin-containing beverages which interfere with iron absorption have also been suggested as therapeutic agents.
The danger of excessive ingestion of medicinal iron is constantly present with persons believing that the more iron taken, the better for their health. There are circumstances under which such an erroneous assumption could have undesirable, even fatal, effects. It has long been known that plasma iron concentrations are lowered (by about 2/3) in patients with infections or neoplasia, and that the intestinal absorption of iron is also depressed in such individuals. This metabolic shift in response to infection or disease is enhanced as the clinical condition intensifies and returns to normal as the condition improves. Its apparent effect is to deprive the invading organism or tissue of the iron needed for growth. Giving exogenous iron to patients with infection or neoplasia could therefore have very deleterious effects. For example: administration of iron to children with kwashiorkor (protein-calorie malnutrition) has been reported to increase fatalities from overwhelming bacterial sepsis.
Like bacteria or neoplastic cells, normal mammalian cells also need iron. However, iron must be made available to the host while being withheld from the invading organisms or cells. This requirement is met by the drastic reduction of free iron and the binding of available iron to proteins instead. Transferrin and lactoferrin are the high-affinity iron binding proteins which are largely responsible for the host's ability to sequester iron from microorganisms or neoplastic tissue. With the onset of fever or establishment of an infection, plasma transferrin level increases, and iron saturation of transferrin decreases (the hypoferremic response).
Thus, although "iron deficiency" creates metabolic problems and may change susceptibility to some diseases, it also has some advantages. Some examples: 1) There is a high incidence of severe hepatic amebiasis among young adult male Zulus; they have iron intakes of 35-215 mg/day due to ingestion of beer brewed in iron kettles. Although Zulu females are presumably exposed to similar numbers of amoeba, they consume much less beer and amebiasis is much less common. 2) Considering their primitive and unsanitary living conditions, the milk-drinking Masai are remarkably free from disease. On their normal milk diet (milk inhibits iron absorption), they maintain a mean hemoglobin value of 11.7 g/dl and have an amebiasis infection rate of less than 9%. When they were given supplemental iron for a year, hemoglobin values rose to 13.1, and the rate of amebiasis rose to 83%. 3) It has been proposed that the lower incidence of coronary artery disease in premenopausal women, and in athletes, may be due at least in part to the lower body iron levels in these two groups of individuals. 4) In 69 cases of infant botulism, 39 had been primarily breast fed and 30 primarily bottle fed, there were ten fatalities, all in the second group, and each of the ten had been fed formula with added iron. The relatively high concentration of lactoferrin in human milk may be an important contributor to lower incidence of infection in breast-fed infants. It is (pardon me) ironic that conventional wisdom deplores the low iron content of breast milk and recommends iron supplementation for breast-fed babies.
Calcium. Sources: Dairy products contribute most of the dietary calcium for the U.S. population Other good sources are green leafy vegetables, soft bones of fish (sardines, salmon), lime-processed tortillas, tofu, nuts and legumes. Antacid preparations and calcium supplements are also significant contributors. Some brands of specific foods, such as bread, orange juice, and cereals, are fortified with calcium.
Requirements: It has been said that few issues in nutrition have been as controversial as the adult requirement for calcium. The adult RDA for calcium (800 mg) may be, according to some authorities, a rather high figure, based on estimates of actual need. However, the high protein content and unfavorable calcium:phosphorus ratio of the typical U.S. diet, both of which increase urinary calcium excretion, lend support for this rather generous recommendation. A person consuming less than the usual U.S. intakes of protein and phosphorus can maintain calcium balance on intakes below the RDA for calcium, particularly if this individual also has greater exposure to sunlight and increased physical activity, which favors calcium retention. It has been suggested that normal people can adapt to calcium intakes as low as 150-200 mg/day, even during pregnancy and lactation. One problem inherent in the establishment of reasonable dietary allowances for calcium is the lack of a clearly defined calcium deficiency syndrome. Also, bioavailability is another factor which makes it difficult to determine precise requirements. Intestinal absorption of calcium, and the factors which affect it, are discussed in a subsequent module.
Functions: Throughout the life cycle, calcium is essential for growth, maintenance and reproduction. Calcium is also essential for development of teeth and bones, and imparts mechanical strength to these tissues. The small but essential amount of calcium outside bones and teeth (only 1% of total body calcium) is required for contraction and relaxation of muscle (including cardiac muscle), blood clotting, transmission of nerve impulses, activation of enzyme reactions, stimulation of hormone secretion and integrity of intracellular cement substances.
Deficiency: Calcium deficiency has been implicated in the etiology of several disease states, osteoporosis, hypertension and colorectal cancer among others. Recent studies have indicated that development of osteoporosis (the major bone disease of developed nations and one which is characterized by relatively low bone mass) is indeed linked to low dietary intake of calcium or at least to a calcium:phosphorus ratio of less than one. Other major risk factors for osteoporosis include age, race, initial bone density, peak adult bone mass and menopause; low body weight, smoking, alcohol intake, and degree of physical activity have been identified as contributing factors. Several investigators have suggested that prevention of osteoporosis should begin around age 35, when net bone loss begins. Excess phosphorus may be the single most important cause of bone loss in humans. A high phosphorus intake raises the serum level of phosphorus, which suppresses production of 1,25(OH)2D (see discussion of Vitamin D). This causes a decrease in intestinal calcium absorption. Bone loss may result when the calcium:phosphorus ratio falls below one. Because it is very difficult to maintain a calcium:phosphorus ratio greater than one in the diet, calcium supplementation has been suggested. Although it has been demonstrated that some individuals show improved bone density in response to calcium supplementation, even at a mean age of 70 years, most evidence indicates that massive amounts of calcium do not prevent bone loss in menopausal women. Even so, various authorities have suggested calcium RDA's of 1000 mg for the general population and 1500 mg for postmenopausal women and osteoporotics. There is no consensus as to the relative effectiveness of early calcium supplementation in preventing postmenopausal bone loss. Estrogen replacement therapy (which is not without its own drawbacks) is apparently much more effective. Regular physical activity, particularly weight bearing activities, can also help prevent osteoporosis by increasing bone mass. Because of the multifactorial etiology of osteoporosis and the fact that only calcium-deficient individuals will show increased bone mass in response to calcium supplementation, increased calcium intake cannot be expected to be equally beneficial in all persons. Osteoporosis usually goes unnoticed until it has reached an advanced stage. If affects about 20 million people in the U.S., and accounts for some 1.3 million fractures annually, as well as an annual cost in excess of 6 billion dollars. Recent studies have indicated that a lack of calcium, rather than excess of sodium, may cause hypertension, at least in some individuals. If there is a relationship between calcium and blood pressure, it is a complex one, almost certainly involving interaction with other ions, such as sodium and potassium. This is still a very controversial area and, as yet, no dietary recommendations have been made. Low serum calcium causes tetany, which is characterized by muscular pain and spastic contractions.
Excess: No adverse effects have been observed in healthy adults consuming up to 2500 mg per day, but high intakes may produce constipation and increase risk of urinary stone formation in susceptible individuals. Intestinal absorption of iron and zinc may be inhibited. Ingestion of very large amounts may cause hypercalcinuria, hypercalcemia and deterioration of renal function.
Phosphorus. Sources: Phosphorus is present in nearly all foods, with animal foods (milk, meat, poultry, fish) and cereal grains the major contributors. Meat contains 15 to 20 times more phosphorus than calcium. Eggs, grains, nuts and legumes contain twice as much phosphorus as calcium. Only milk, natural cheeses, green leafy vegetables and bone contain more calcium than phosphorus (see discussion of calcium:phosphorus ratio above.) Phosphates are also found in processed foods, especially in soft drinks.
Requirements: The precise requirement for phosphorus is unknown. The RDA standard is the same as that of calcium for all ages except for the young infant, for whom the proportion of phosphorus is lower than that for calcium.
Functions: Most of the body's phosphorus (85%) is present in bone as an essential component of bone mineral; it also plays an essential role in the metabolism of carbohydrates, proteins and lipids. It is a modulator of enzyme activity, helps control acid-base balance (phosphate buffer system), and promotes glucose transport in gut and kidney. Energy for metabolic activity derives largely from the phosphate bonds of ATP, creatine phosphate and similar compounds.
Deficiency: Dietary phosphorus deficiency does not usually occur, except in small premature infants fed human milk exclusively, or in patients taking aluminum hydroxide (an antacid) for prolonged periods of time. Phosphorus deficiency results in bone loss and is characterized by weakness, anorexia, malaise and pain.
Excess: An excess of phosphorus will lower blood calcium level, which can result in increased neuroexcitability, tetany and convulsions.
Iodine. Sources: The environmental levels of iodine and their contribution to the daily intake vary widely throughout the United States. The iodine content of plant foods varies according to the iodine content of the soil in which they were grown. Iodine content of drinking water will also vary. Seafoods in general are good sources of iodine. Iodized salt is the major source of the mineral in areas with iodine-poor soil and water.
Requirements: The recommended allowances are given in the 1989 RDA tables.
Functions: Iodine is an essential component of thyroid hormone, which in turn stimulates cell oxidation and regulates basal metabolism in all cells of the body.
Deficiency: Endemic colloid goiter (enlargement of the thyroid gland) occurs in persons living in areas with iodine-poor soil and water. Insufficient iodine leads to low plasma levels of thyroid hormones, which in turn causes increased thyroid-stimulating hormone (TSH). The thyroid gland responds to increased TSH by increasing in size. The term "goiter" has been used for some time to describe the primary effect of iodine deficiency. While goiter is the most obvious feature, the more inclusive term "iodine deficiency disorder" (IDD) is now preferred. Iodine deficiency is particularly critical in children, since thyroid hormone is essential to normal growth and development. Maternal iodine deficiency during gestation can result in severe retardation of fetal brain maturation. Iodine deficiency in adults is characterized by suboptimal brain function, which is correctable by iodine supplementation.
Excess: Iodine doses of 1 mg per day will have a beneficial effect on hyperthyroid patients, by inhibiting thyroxine release. This effect is usually of short duration, however. In persons who are not hyperthyroid, large doses of iodide will inhibit thyroid hormone synthesis for a short period of time, after which most (but not all) individuals will "adapt" to the excess dose and thyroid hormone synthesis returns to normal. Individuals who do not adapt will eventually develop hypothyroidism and goiter. This condition is rapidly reversed when iodide is withdrawn. Endemic forms of iodide-induced goiter have been observed in areas where there is high dietary intake of iodine. Cases of iodide-induced hyperthyroidism have also been observed. More detailed information on iodine excess can be found in Shils, Olson & Shike, Modern Nutrition in Health and Disease.
Sodium. Sources: Over 90% of dietary sodium is taken in the form of sodium chloride, as a component of food or as table salt. The remainder is largely in the form of sodium bicarbonate and monosodium glutamate.
Requirements: The 10th edition of Recommended Dietary Allowances indicates a safe minimum intake of 500 mg/day. Because there is no known advantage in consuming large amounts of sodium and clear disadvantages for those susceptible to hypertension, a Food and Nutrition Board committee has recently recommended that daily intakes be limited to 2.4 g of sodium or less. Sodium needs can vary depending on age, environmental temperature and humidity and level of physical activity, among other variables.
Functions: Sodium, as the principal cation of the extracellular fluid, is the primary regulator of extracellular fluid volume. Sodium is also involved in the regulation of osmolarity, acid-base balance, and the membrane potential of cells.
Deficiency: Sodium deficiency resulting from low dietary intake does not normally occur because of the body's ability to conserve sodium. Excessive and prolonged sweating from any cause may lead to the symptoms and signs of salt depletion, including giddiness, exhaustion, cramps and vomiting.
Excess: Chronic overconsumption of sodium chloride has been linked to hypertension in sensitive individuals. The full expression of salt sensitivity apparently depends on high dietary intakes of both sodium and chloride.
Potassium. Sources: Potassium is widely distributed in all foods, since it is an essential component of all living cells. Processing tends to decrease potassium (while increasing sodium), so the richest dietary sources are unprocessed foods. Considerable amounts are provided by legumes, whole grains, oranges, bananas, leafy green vegetables, broccoli, potatoes and meats.
Requirements: Minimum potassium intakes of 1.6 to 2.0 grams per day are recommended for adults.
Functions: Potassium is the principal intracellular cation; as such, it balances with extracellular sodium to maintain normal osmotic pressures and water balance. It also works with sodium and hydrogen to maintain acid-base balance. Extracellular potassium, although only present in small amounts, contributes to the transmission of nerve impulses, control of muscle contractility and maintenance of normal blood pressure.
Deficiency: Under normal circumstances, dietary deficiency of potassium does not occur. Potassium deficiency is usually a result of excessive losses (through vomiting, diarrhea, laxative abuse, diuretics). Deficiency symptoms include weakness and paralysis (due to increased resting membrane potential), anorexia, nausea, listlessness, apprehension, drowsiness and irrational behavior. Severe hypokalemia can result in cardiac dysrhythmias that are potentially fatal.
Excess: Acute hyperkalemia (from doses in the range of 18 grams per day for an adult) can prove fatal because it can cause cardiac arrest.
Magnesium. Sources: All unprocessed foods contain magnesium, but in widely varying amounts. The highest concentrations are found in nuts, legumes and unmilled grains. Other good sources are green vegetables and bananas.
Requirements: As seen in the RDA table (1989), the recommended daily allowance for magnesium is 280-350 mg for adults.
Functions: About 40% of the magnesium in the adult human body is in the muscles and soft tissues, 1% in the extracellular fluid, and the remainder in the skeleton (it is an essential component of bone). Magnesium (as Mg-ATP) is essential for all biosynthetic processes, glycolysis, cyclic AMP formation, energy-dependent membrane transport and transmission of the genetic code. More than 300 enzymes are known to be activated by magnesium. Extracellular magnesium is critical to the maintenance of electrical potentials of nerve and muscle membranes and transmission of impulses across nerve-muscle junctions.
Deficiency: Magnesium depletion may be due to intestinal malabsorption, excessive vomiting/diarrhea, uncontrolled diabetes, alcoholism/general malnutrition, renal dysfunction, or iatrogenic causes (particularly, treatment with diuretics or digitalis). Purely dietary magnesium deficiency has not been reported in humans consuming natural diets. Magnesium deficiency is marked by anorexia, nausea, muscle weakness, cardiac arrhythmias, coronary spasm, hypocalcemia, hypokalemia, irritability, and mental derangement.
Excess: In cases of excessive magnesium ingestion or injection, the kidney is capable of rapidly excreting the excess ion. However, hypermagnesemia may develop when magnesium-containing drugs (such as antacids) are administered to individuals with renal insufficiency. Early symptoms include nausea, vomiting and hypotension. As the condition worsens, bradycardia, cutaneous vasodilation, ECG changes, hyporeflexia and CNS depression will follow. Central depression appears at magnesium levels above 8 mEq/L and pronounced anesthesia occurs at 20 mEq/L.
Zinc. Sources: Zinc is widely distributed in a variety of foods, but is particularly abundant in animal products, which provide 70% of the zinc consumed by most people in the U.S. Its distribution approximates that of iron. Meat, liver, eggs and seafood are good sources of available zinc, while the zinc in whole grain products is somewhat less bioavailable.
Requirements: Recommended dietary allowances for zinc (1989) are 12-15 mg/day for adults, with increases recommended during pregnancy and lactation. The total body content of zinc in the adult is 2-3 grams, making it the second most abundant trace mineral, after iron. The RDA is seen as a conservative estimate, based on a diet with moderate contents of fiber and phytate (both of which reduce zinc absorption).
Functions: Zinc has a primary nutritional and biochemical role as an essential constituent of over 200 enzymes, including carbonic anhydrase, carboxypeptidase A, lactic dehydrogenase, and alkaline phosphatase. Thus zinc has a role in acid-base balance, protein and carbohydrate digestion, etc. Zinc also combines with insulin in the pancreas to form a compound which may be the storage form of that hormone and has been shown to be involved in maintaining structural integrity of membranes.
Deficiency: The signs and symptoms of zinc deficiency in humans include loss of appetite, skin changes, immunologic abnormalities, increased pregnancy complications, poor healing, and some neuropsychological impairment. Zinc deficiency in children results in stunted growth and arrested sexual development. It is also linked with acrodermatitis enteropathica, a rare inherited disorder that usually appears with weaning, or earlier in infants who are not breast-fed. Serum zinc concentrations are decreased below normal values in acute and chronic infections, and are restored upon recovery. They are also decreased in untreated pernicious anemia and myocardial infarction, as well as various malignancies. A consistent finding in zinc-deficient patients is loss of taste acuity, which is likely to exacerbate the growth retardation in children.
Excess: Compared to copper, lead, mercury and arsenic, zinc is relatively non-toxic. Signs and symptoms of toxicity are nausea, vomiting, abdominal cramps, diarrhea, and fever.
Selenium. Sources: Seafoods, kidney and liver are consistently good sources, while grains and other seeds are more variable.
Requirements: 55-70 µg daily for nonpregnant adults (see Table). Recommendations for requirements of children have been extrapolated from adult requirements.
Functions: Selenium is present at the active site of glutathione peroxidase, an enzyme that catalyzes the breakdown of hyperperoxides.
Deficiency: Low selenium status has been associated with Keshan disease, a cardiomyopathy affecting mostly young children and women of childbearing age. Patients receiving total parenteral nutrition (TPN) have exhibited muscular discomfort or weakness which responded well to selenium therapy; cardiomyopathy has also occurred in such patients.
Excess: Symptoms include nausea, abdominal pain, diarrhea, nail and hair changes, peripheral neuropathy, fatigue and irritability.
Other Minerals: Not covered in this discussion are several other minerals for which no RDA has been established but which probably (in some cases, definitely) play an essential role in human nutrition: copper, manganese, fluoride, ammonium, and molybdenum.