Twenty-eight essential vitamins and minerals play key roles in the metabolism of protein, carbohydrate, and fat, as well as in the structure of the human body (eg, vitamin K in bone matrix, calcium in bone tissue). Many micronutrients are also important antioxidants (eg, vitamins C and E) or act as cofactors for antioxidant enzymes (eg, selenium in glutathione peroxidase). Several trace minerals, though not considered essential, are being studied for their roles in human nutrition. Examples include silicon for bone health1 and vanadium for stimulation of glucose transport.2
Although vitamin deficiency diseases (eg, pellagra) are not widespread, suboptimal micronutrient intake is common. Recent studies show that 10% to 75% of Americans take in less than the recommended dietary allowance (RDA) for many micronutrients (eg, zinc, folate, iron, vitamin B6 and B12), and between 5% and 50% of Americans consume less than half the RDA for many micronutrients.3 While what constitutes sufficient intake is controversial for some nutrients, it is clear that a surprisingly large number of people are undernourished for certain micronutrients, even as they are overly nourished with respect to macronutrients.
Insufficient micronutrient intake has short-term and long-term implications for disease risk. As an example, immune function is adversely affected by poor intakes of nearly every essential vitamin and mineral.4 Thus, diets lacking essential micronutrients may theoretically, at least, affect health over the short term by impairing resistance to viral or bacterial infection. Among longer term problems, a lack of nutrients required for DNA methylation and gene stability may increase the risk for certain cancers.3
The following sections address issues of greatest concern to clinicians: deficiency states, diet-drug interactions, and at-risk populations. Three reference tables are included at the end of this chapter: Table 1, Conditions That May Be Improved by Nutritional Supplements; Table 2, Vitamin Functions, Deficiency Diseases, Toxicity Symptoms, and Dietary Reference Intakes; and Table 3, Mineral Functions, Deficiency Diseases, Toxicity Symptoms, and Dietary Reference Intakes.
Antioxidants and Phytochemicals
Antioxidant vitamins (vitamins C and E), carotenoids, and minerals that are constituents of antioxidant enzymes (eg, zinc, magnesium, and manganese in superoxide dismutase; selenium in glutathione peroxidase) are essential for minimizing free-radical reactions and the resulting destruction of cellular structures. However, clinical trials indicate that simply adding supplemental antioxidant nutrients to a typical American diet does not reduce the risk for common diseases such as cardiovascular disease and cancer.30 Evidence suggests that a healthful overall diet is required-namely, a diet that is both low in factors that promote disease and high in antioxidant nutrients.
In addition, an increasing body of evidence indicates that the presence of nonvitamin, nonmineral antioxidants (eg, phytochemicals) in foods is responsible for the majority of antioxidant effects.31 In general, populations eating greater amounts of phytochemical-containing foods (eg, fruits, vegetables, whole grains) have a significantly lower mortality risk32 and a lower risk for cardiovascular disease, cancer, diabetes mellitus, hypertension, and arthritis.33,34 Population studies do not, however, typically isolate the effect of micronutrients, and they also involve significant macronutrient differences, compared with unmodified diets. Nevertheless, these studies suggest that any additional nutrients should be supplemental to, and not substituted for, a plant-based diet.
At-Risk Populations
Certain groups are likely to be deficient in micronutrients and to need dietary adjustments or supplementation. The following nutritional choices may result in poor or deficient intakes of essential nutrients:
Alcohol abuse. Lower blood concentrations of vitamins C and E, carotenoids, and selenium have been found in alcohol-dependent patients, compared with low-alcohol consumers.35,36 Alcohol abusers may miss B vitamins through poor food intake and may lose B vitamins due to the diuretic effect of alcohol; these (particularly thiamine) must be replaced in order to prevent neurologic sequelae, including Wernicke-Korsakoff syndrome.37 Folate intake may be especially important for alcohol consumers. For example, individuals who consume as little as one-half of a serving of alcohol per day appear to be at twice the risk for breast cancer when folate intakes are below recommendations (ie, at <335 μg/day), compared with those with higher intakes.38
A Western dietary pattern. Individuals who eat a Western diet based on animal products generally have reduced intakes of several micronutrients, compared with individuals following plant-based diets, although these reduced intakes may not represent frank deficiencies. Vitamin C deficiency has been found in individuals who eat meat-based diets and shun fruits and vegetables.9,39 In the European Investigation into Cancer and Nutrition study of 65,429 men and women, individuals avoiding meat and other animal products had much higher intakes of fiber, folate, and vitamins C and E, compared with omnivores.40 Other surveys of vegetarians also determined higher intake of vitamins C and E, in addition to potassium41 and dietary fiber,42 compared with omnivores. Pregnant vegetarian women had significantly lower risk for folate deficiency than omnivores.43
Smokers. Smokers often have poorer diets in general than nonsmoking individuals, and generally consume fewer fruits and vegetables and more saturated fat.44 Moreover, even after adjustment for differences in diet, smokers have significantly lower blood levels of several carotenoids and vitamin C.45
Inappropriately restricted diets. Nutritional deficiency can result from overly stringent dietary restrictions, particularly those that suggest elimination of the most nutrient-rich foods (eg, vegetables, fruits, and whole grains). Such diets may be practiced by individuals who are dealing with what they suspect are problematic reactions to foods46,47 and who do not seek alternative sources of essential nutrients. Individuals who consume low-carbohydrate, high-meat diets may have vitamin C intakes that are nearly 50% lower than those of persons eating more plant-based diets,48 and individuals eating Western diets also have relatively poor carotenoid intakes. According to the Institute of Medicine, current and international dietary guidelines call for obtaining at least 90% of vitamin A in the form of provitamin A carotenoids, and U.S. residents obtain less than 40%, with the balance coming from animal products.25 This results in lower blood levels of carotenoids, and these reduced levels are consistent with a greater risk in these people for many chronic diseases, compared with individuals eating recommended amounts (ie, > 5 servings/day) of fruits and vegetables.25
Elderly persons, particularly those in hospitals or long-term-care facilities, and individuals following unsupplemented vegan diets are at risk for deficiency of vitamins D and B12. With appropriate supplementation, a vegan diet has nutritional advantages, compared with unmodified diets.49 Alcohol-dependent individuals are at risk for folate, B6, B12, and thiamin deficiencies. Poor intakes and subclinical deficiencies in these and other groups, and the increased risk for chronic diseases that may follow have led to the suggestion that all adults take a multiple vitamin daily.50
Vitamin dependency disorders resulting from inborn errors of metabolism are rare, but they require lifelong treatment with certain vitamins. Examples of these include multiple carboxylase deficiencies that are biotin-responsive51 and pyridoxine-dependent seizures.52
Drug-Diet Interactions
Drug-diet interactions can cause increased needs for certain micronutrients. Electrolyte imbalances are probably the most common micronutrient deficiency states, and are often caused by medications.13
Folic acid deficiency may occur due to treatment with many anticonvulsants (eg, phenytoin, carbamazepine, phenobarbital, valproic acid), and may subsequently increase the risk for birth defects.53 Through an antagonizing effect on folate, these same drugs also significantly increase certain indicators of cardiovascular risk, such as homocysteine and possibly lipoprotein(a).54 Available data indicate that folic acid treatment can significantly reduce homocysteine in children on anticonvulsant medications.55 Additional studies are needed to test the initial observation that B-vitamin supplements (folate, pyridoxine, and riboflavin) reduce certain other cardiovascular risk factors, including von Willebrand factor and lipoprotein, that are elevated in adults on anticonvulsant treatment.56
Many side effects of methotrexate treatment (gastro-intestinal intolerance, stomatitis, alopecia, and cytopenia) are due to folate antagonism. However, it is thought that these effects may be avoided by combining a folate-rich diet with minimal folate supplementation (ie, multiple vitamins) and by reducing the dose of methotrexate if necessary.57 American College of Rheumatology guidelines indicate that supplementation with additional folic acid or folinic acid (Leucovorin) may prevent treatment side effects without compromising therapeutic efficacy.58 Although doses of 2.5 mg to 5.0 mg reduce the side effects of methotrexate without significantly altering effectiveness, higher amounts (eg, 15 mg) have resulted in worsening of rheumatoid arthritis (RA) symptoms.51
Vitamin B12 absorption decreases as a result of long-term acid suppression therapy (eg, proton pump inhibitors) and can exacerbate the already-declining absorption of this vitamin caused by atrophic gastritis.59 Long-term treatment with metformin also decreases B12 absorption,60 apparently as a result of inhibiting a calcium-dependent process that normally promotes ileal uptake of the B12-intrinsic factor complex. Preliminary data indicate that this effect is ameliorated by calcium supplementation.61
Hypokalemia frequently results from commonly used diuretics, amphotericin B, corticosteroids, antipseudomonal penicillins, and insulin, while hyperkalemia may result from heparin,13 as well as potassium-sparing diuretics and poor kidney function.62
Hypomagnesemia and thiamine deficiencies frequently result from treatment with diuretics, and the former can also occur due to administration of amphotericin B, aminoglycoside antibiotics, and cyclosporine.13,26 Cisplatin therapy may cause hypomagnesemia.63
Hypocalcemia may result from foscarnet by forming a complex with ionized calcium.13 It may also occur in patients given bisphosphonates who have unrecognized hypoparathyroidism, impaired renal function, or vitamin D deficiency.64
Sodium imbalances may occur due to the ubiquitous presence of sodium and phosphorus in foods; deficiencies of these electrolytes are less common. Hyponatremia, however, can occur from carbamazepine and thiazide diuretics, while hypernatremia can result from drugs that cause diarrhea (eg, lactulose).
Hypophosphatemia may result from the use of antacids or sucralfate.
Mineral Deficiencies
Iron. Deficiency of this mineral occurs with a frequency ranging from 2% of pubescent and adult males to 16% of menstruating females,16 and iron deficiency-related anemia is the most common cause of anemia in pregnancy.17 (See Iron Deficiency Anemia.)
Iron overload, although less common than iron deficiency, occurs in roughly 0.5% of Caucasians and results from hereditary hemochromatosis (HHC), an autosomal recessive disorder caused in most cases by the C282Y and H63D mutation in the HFE gene on chromosome 6p21.3.18 However, in spite of the frequency of this disorder, it is not by itself responsible for HHC-related diseases, such as diabetes and liver disease.19 Even in the absence of the gene for hemochromatosis, evidence shows that individuals in Western, meat-eating populations may have iron stores far in excess of those needed for health.20 These individuals may be at greater risk for heart disease, cancer, and diabetes, risks that appear to be greatest among elderly persons.21 Among elderly participants in the Framingham Heart Study, 13% had high iron stores, while approximately 3% were found to have iron deficiency.21
Calcium. Intakes of calcium at levels significantly below dietary reference intakes (DRI) are common in a large segment of the U.S. population. After 10 years of age, both males and females get, on average, roughly half the recommended intake.22 A significant body of evidence, however, indicates that a more moderate calcium intake may be adequate. While calcium intakes below 400 mg per day may reduce bone development, intakes above this level do not appear to correlate to bone mineral density or to reduce fracture risk. Other factors, particularly targeted physical activity, do appear to more precisely reflect bone density in this population.23 Data from the Nurses' Health Study do not support the hypothesis that a higher total calcium or dairy calcium intake in adults is protective against hip or forearm fracture.24
Concerns about high calcium intakes have arisen from studies indicating a higher risk of prostate cancer among men consuming more dairy products or calcium (see Prostate Cancer) and a higher risk of kidney stones under certain circumstances (see Kidney Stones).
Magnesium. Clinical deficiency of blood magnesium is rare in the general population, but it should be suspected in individuals with chronic diarrhea, patients with hypocalcemia or refractory hypokalemia, and those given certain medications (see below).25,26 Individuals developing or having hypomagnesemia may show neuromuscular hyperexcitability,25 and hypocalcemia is a sign of severe hypomagnesemia (< 1.0 mEq/L, 0.5 mmol/L).26 Hypomagnesemia occurs in up to 12% of hospitalized patients and in as many as 60% to 65% of Intensive Care Unit (ICU) patients.26 In the Third National Health and Nutrition Examination Survey (NHANES III), 68% of adults consumed less than the recommended daily allowance (RDA) for magnesium, and 19% consumed less than 50% of the RDA.27 Hypomagnesemia was found in 27% of healthy lean children and 55% of obese children in one study,28 and the condition occurs in 25% to 38% of individuals with diabetes.29 (See Diabetes.) Magnesium deficiency may result from poor intake of foods rich in this mineral, such as green vegetables, nuts, seeds, dried beans, and whole grains.
Micronutrients in Clinical Practice
Certain diseases or conditions increase nutrient needs. For example, diseases that cause malabsorption (chronic cholestasis, abetalipoproteinemia, celiac disease, and cystic fibrosis) result in vitamin E deficiency and the need for supplementation.65 Clinicians should encourage patients to obtain these nutrients primarily from foods, rather than supplements, due to the presence of other nutrients in whole foods and their potentially synergistic effects.66 For example, vitamin E supplements only contain alpha-tocopherol, but food sources of vitamin E include γ-tocopherol (a scavenger of reactive oxygen and nitrogen radicals and inhibitor of cyclooxygenase)67 and tocotrienols, which have both antioxidant and nonantioxidant benefits that alpha-tocopherol does not possess.68
Similarly, patients may be tempted to purchase dietary supplements containing carotenoids (eg, lutein/zeaxanthin) to prevent or treat certain eye diseases (see Cataract and Macular Degeneration ). Although some studies indicate a benefit for supplements, many have found a protective association with carotenoids in foods. The latter may be a preferable source, because macular pigment density increases to a greater degree (43%) when lutein is combined with other antioxidants, compared with lutein alone (36% increase).69 Emerging evidence also suggests that higher lutein intake is associated with progression of macular degeneration in the context of diets higher in easily peroxidized polyunsaturated fat (ie, linoleic acid).70 Until further data are available, lutein and other micronutrients should be obtained from food primarily, and in supplement form only if recommended by a physician.
Certain individuals may require nutrients in amounts that exceed RDAs for healthy adults. Such individuals may also benefit from supplementation with nonessential or conditionally essential micronutrients (eg, carnitine, coenzyme Q10).
The following three tables show the relationship between micronutrients and health: Table 1, Conditions That May Be Improved by Nutritional Supplements; Table 2, Vitamin Functions, Deficiency Diseases, Toxicity Symptoms, and Dietary Reference Intakes; and Table 3, Mineral Functions, Deficiency Diseases, Toxicity Symptoms, and Dietary Reference Intakes.
Vitamin Deficiency States
Vitamin B12. Vitamin B12 deficiency affects 10% to15% of individuals over age 60, mainly due to poor absorption.5 (See Megaloblastic Anemia.)
Vitamin C. Deficiency of vitamin C, which manifests as scurvy in its most severe form, is a condition most clinicians would presume to be long gone. Nevertheless, vitamin C deficiency or depletion was found in 5% to 17% of participants in the Third National Health and Nutrition Examination Survey6; in 30% of a sample of hospice patients7; in 68% of a population of hospitalized elderly patients8; and in individuals who eat meat-based diets and avoid fruits and vegetables.9 In smokers, the risk for vitamin C deficiency is roughly 4 times greater than in nonsmokers.6
Vitamin D. Soft and deformed bones characterize rickets, a vitamin D deficiency disease that affects infants and children. Although rickets is presumed to be an infrequent problem in the United States due to vitamin D fortification of milk, these efforts have not been entirely successful, and resurgence of this disease has occurred for a number of reasons. The natural source of vitamin D is sun exposure. However, life in urban areas or at extremes of latitude makes sunlight a less predictable source. Vitamin D is present in few foods, many of which people do not eat for reasons of preference or health (eg, oily fish, egg yolk). This has prompted the American Academy of Pediatrics to recommend 200 international units (IU) of supplemental vitamin D for infants, children, and adolescents ingesting less than 500 mL per day of vitamin D-fortified formula or milk.10
Intakes that are considered either deficient or insufficient have also been found in young women and elderly persons who lack sun exposure.11 These low intakes are a risk factor for autoimmune disease and some cancers.12 Certain drugs (eg, phenytoin, phenobarbital) can also decrease blood levels of vitamin D, resulting in both osteopenia and osteomalacia.13
Some evidence suggests that a "functional" vitamin D deficiency state may be caused by a high calcium intake due to dairy intake and calcium supplements, and may influence the risk for prostate cancer. Although higher calcium intake was not appreciably associated with total or nonadvanced prostate cancer, men with intakes of 1,500 to 1,999 mg per day of calcium had nearly double the risk for advanced and fatal prostate cancer. Men consuming 2,000 mg per day or more had a risk almost 2-and-a-half times greater, compared with men whose long-term calcium intakes were 500 to 749 mg per day. These risks have been attributed to elevated blood calcium concentrations that decrease production of the active form of vitamin D (calcitriol), which under normal circumstances inhibits cellular proliferation, promotes differentiation, and regulates the invasiveness, angiogenesis, and metastatic potential of prostate cancer cells.14
Considerable evidence suggests that certain subgroups (eg, elderly persons) do not meet vitamin D requirements due to lack of sun exposure.15 Multiple vitamin formulas typically contain 400 IU of vitamin D, an amount that meets or exceeds the requirement for all age groups except those over 70 years.
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Micronutrients in Health and Disease
Table 1: | ||
Disease | Nutrient(s) | Rationale |
Anemia, microcytic | Iron | Increased need in high-risk groups (eg, pregnant adolescents) |
Anemia, pernicious | Vitamin B12 | Elderly individuals, postgastrectomy patients |
Burn injury | Vitamins A, D & E; carotenoids; selenium, zinc, copper | Low blood levels; increases needed to support immune function |
Celiac sprue | Vitamins D, E & K; | Restricted diet increases risk for |
Congestive heart failure | Thiamine, magnesium | Loss due to diuretics may further compromise cardiac function |
Cystic fibrosis | Vitamins A, D, E, K & | Malabsorption, low blood levels; greater |
Eating disorders | Multivitamin/mineral, calcium, vitamin D | Poor intake; evidence of deficiency; reversal of osteoporosis in patients with anorexia nervosa |
End-stage kidney disease | B-vitamins, vitamin C | Losses due to |
Inflammatory bowel disease | Beta-carotene, vitamins C, D & E; selenium, zinc | Malabsorption |
Macular degeneration | C, E, beta-carotene; zinc, copper, lutein | Reduction of oxidative stress in the macula; some evidence of benefit in clinical trials |
Osteoporosis | Calcium, vitamin D | Elderly individuals; persons on long-term corticosteroid treatment |
Micronutrients in Health and Disease
Table 2: | ||||
Vitamin | Functions/Roles | Deficiency Symptoms | Toxicity Symptoms | Recommended Dietary Allowance |
Vitamin A | Bone growth, reproduction, cell division, immunity, cell differentiation | Clinical: Night blindness; total blindness (rare in the U.S.) | Birth defects, liver abnormalities, reduced bone mineral density; central nervous system disorders (eg, pseudotumor cerebri) | Adults: Age 19+: Infants/children: (*) Pregnancy: |
Vitamin D
| Maintenance of normal blood levels of calcium and phosphorus; promotes bone mineralization; regulates cell growth, differentiation, immune function | In children: rickets | Nausea, vomiting, poor appetite, constipation, weakness, and weight loss; mental status changes; hypercalcemia; calcinosis | Adults:(*) Infants /children: (*) |
Vitamin E | Antioxidant (protects cells against free radicals); plays role in immune function and in DNA repair; inhibits cell proliferation, platelet aggregation, and monocyte adhesion1 | Nerve degeneration in hands and feet | Can influence coagulation in some persons with drug-induced vitamin K deficiency; anti-platelet effect | Adults:19+ years: 15mg Pregnancy: 15mg |
Vitamin K | Coenzyme for synthesis of proteins involved in blood coagulation and bone metabolism | Increase in prothrombin time; in severe cases, hemorrhagic events | None currently known | Adults: 19+ years: (*) Infants/children: (*) Pregnancy/lactation: |
Sources: National Institutes of Health, Office of Dietary Supplements Web site (http://dietary-supplements.info.nih.gov/)
^see Azzi A Zingg, Nonantioxidant activities of vitamin E. Curr Med Chem. 2004;11:1113-1133.
Institute of Medicine. Dietary Reference Intakes for Vitamin A, Vitamin K, Arsenic, Boron, Chromium, Copper, Iodine, Iron, Manganese, Molybdenum, Nickel, Silicon, Vanadium, and Zinc. Washington, D.C.: National Academies Press, 2000.
Institute of Medicine, Dietary Reference Intakes for Vitamin C, Vitamin E, Selenium, and Carotenoids. Washington, D.C.:National Academies Press, 2000. IOM did not set an RDA for vitamins in this age group. Instead, an Adequate Intake (AI) is used. According to the Institute of Medicine, "The AI is a recommended average daily nutrient intake level, based on experimentally derived intake levels or approximations of observed mean nutrient intake by a group (or groups) of apparently healthy people that are assumed to be adequate. An AI is established when there is insufficient scientific evidence to determine an Estimated Average Requirement (EAR)."
Vitamin | Functions | Deficiency Symptoms | Toxicity Symptoms | Recommended Dietary |
Vitamin C | Antioxidant; biosynthesis of connective tissue components (collagen, elastin, fibronectin, proteoglycans, bone matrix, and elastin-associated fibrillin); carnitine, and neuro-transmitters | Scurvy (involves deterioration of elastic tissue); follicular hyperkeratosis, petechiae, ecchymoses, coiled hairs, inflamed and bleeding gums, perifollicular hemorrhages, joint effusions, arthralgia, and impaired wound healing; dyspnea, edema, Sjogren syndrome, weakness, fatigue, depression | Nausea, abdominal cramps, and diarrhea (from supplements) | Adults (> 19 years): Infants/children: (*) Pregnancy: Lactation: |
Thiamine | Coenzyme in the metabolism of carbohydrates and branched-chain amino acids | Anorexia; weight loss; mental changes such as apathy, decrease in short-term memory, confusion, and irritability; muscle weakness; cardiomegaly; beriberi (polyneuritis) | Oral forms: None currently known Parenteral: Pruritus (rare: 1% of patients); extremely rare anaphylactic reaction IOM conclusion: Even high-dose IV use is relatively safe | Adults (> 19 years): Infants/children: (*) Pregnancy/lactation: 1.4 mg |
Riboflavin (B2) | Coenzyme in numerous redox reactions | Ariboflavinosis; sore throat; hyperemia and edema of pharyngeal and oral mucous membranes; cheilosis; angular stomatitis; glossitis (magenta tongue); seborrheic dermatitis; normochromic, normocytic anemia | None currently known | Adults (ages 19+): Infants/children: (*) Pregnancy: 1.4mg |
Niacin (B3) | Coenzyme in numerous redox reactions | Pellagra (pigmented rash, vomiting, constipation or diarrhea, bright red tongue; neurological symptoms including depression, apathy, headache, fatigue, and loss of memory) | From nicotinamide: nausea, vomiting, and signs and symptoms of liver toxicity (at intakes of 3,000 mg/day); from nicotinic acid: same signs at 1,500 mg/day (most toxicity related to pharmacologic use); hepatotoxicity (at doses of 3-9 g/day); blurred vision, toxic amblyopia, macular edema (doses of 1.5-5g/day) | Adult males and males >age 14: 16mg Pregnancy: 18mg |
Panto- | Component of coenzyme A; cofactor and acyl group carrier for many enzymatic processes, and acyl carrier protein, a component of the fatty acid synthase complex | Extremely rare; irritability and restlessness; fatigue; apathy; malaise; sleep disturbances; gastro-intestinal complaints such as nausea, vomiting, and abdominal cramps; neurobiological symptoms such as numbness, paresthesias, muscle cramps, staggering gait | None currently known | Adults (ages 19+): 5.0mg Infants/children: (*) Pregnancy: 6.0mg |
Pyridoxine (B6) | Coenzyme in the metabolism of amino acids, glycogen, and sphingoid bases | Seborrheic dermatitis, microcytic anemia, epileptiform convulsions | Sensory neuropathy with high (>100 mg) supplementary intake | Adults: Infants/children: (*) Pregnancy: 1.9mg |
Folic acid | Coenzymes are involved in DNA synthesis; amino acid interconversions; single-carbon metabolism; methylation reactions | Early sign: hypersegmented neutrophils | None in healthy individuals; may decrease phenytoin levels and trigger seizures in patients with seizure disorder (Neurology. 2005;64:1982); may precipitate or exacer-bate neuropathy in vitamin B12-deficient individuals | Adults (ages 19+): 400 µg Infants/children: (*) Pregnancy: 600 µg |
Vitamin B12 | Cofactor for methionine synthase and L-methyl-malonyl-CoA mutase; essential for normal blood formation and neurologic function | Pernicious anemia; neuro-logic manifestations (sensory disturbances in the extremities; motor disturbances, including abnormalities of gait); cognitive changes (loss of concentration; memory loss, disorientation and frank dementia); visual disturbances, insomnia, impotency, and impaired bowel and bladder control | None currently known | Adults (ages 19+): 2.4 µg Infants/children: (*) Pregnancy: 2.6 µg |
Source: Institute of Medicine. Dietary Reference Intakes for Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline (1998) and Institute of Medicine (IOM). Dietary Reference Intakes for Vitamin C, Vitamin E, Selenium, and Carotenoids. Washington, D.C.:National Academies Press, 2000. (*) IOM did not set an RDA for vitamins in this age group. Instead, an Adequate Intake (AI) is used. According to the Institute of Medicine, "The AI is a recommended average daily nutrient intake level, based on experimentally derived intake levels or approximations of observed mean nutrient intake by a group (or groups) of apparently healthy people that are assumed to be adequate. An AI is established when there is insufficient scientific evidence to determine an Estimated Average Requirement (EAR)."
Biotin | Coenzyme in bicarbonate-dependent carboxylation reactions (eg, acetyl-CoA carboxylase, pyruvate carboxylase) | Dermatitis, conjunctivitis, alopecia, and central nervous system abnormalities (depression, lethargy, hallucinations, and paresthesia of the extremities) | None currently known | Adults (ages 19+) (*): 30 µg Infants/children: (*) Pregnancy: 30 µg |
Choline | Synthesis and release of acetylcholine; precursor for the synthesis of cell membrane components (phospholipids and sphingomyelin), platelet activating factor, and betaine (important in metabolism of homocysteine) | Steatosis, liver damage | Fishy body odor, sweating, salivation, hypotension, mild hepatotoxicity | Men (ages 19+): 550mg Infants/children: (*) Pregnancy: 450 mg |
Micronutrients in Health and Disease
Table 3: | ||||
Mineral | Biochemical Role/Function | Deficiency Symptoms | Toxicity Symptoms | Recommended Dietary Allowance or AI (*) |
Calcium
| Component of teeth and bones; mediates vascular contraction and vaso-dilation, muscle contraction, nerve transmission, and glandular secretion | Reduced bone mass and osteoporosis | Hypercalcemia; increased risk for kidney stones (with supplements); milk-alkali syndrome; possible increase in risk for prostate cancer (see Prostate Cancer chapter) | Adults: (*) Infants/children: (*) Pregnancy/lactation:(*) |
Phosphorus (P)
| Component of most biological membranes and nucleotides and nucleic acids; buffering of acid or alkali excesses; temporary storage and transfer of the energy derived from metabolic fuels; activation of many catalytic proteins through phosphorylation | Anorexia, anemia, muscle weakness, bone pain, rickets and osteomalacia, general debility; may be seen in persons recovering from alcoholic bouts; in diabetic keto-acidosis; in refeeding with calorie-rich sources without paying attention to phosphorus needs; & with AL-containing antacids | Metastatic calcification, | Adults (ages 19+): 700 mg Infants/children: (*) Pregnancy/lactation: |
Magnesium | Required cofactor for over 300 enzymes, including ones involved in anaerobic and aerobic energy generation, glycolysis, and oxidative phosphorylation; DNA and RNA synthesis; activation of adenylate cyclase; sodium, potassium-ATPase activity; has a calcium channel-blocking effect | Hypocalcemia; neuro-muscular hyperexcitability & latent tetany; insulin resistance and impaired insulin secretion | GI disturbance (diarrhea, nausea, abdominal cram-ping, paralytic ileus); more likely to occur with impaired renal function | Adults: Pregnancy: Lactation: |
Source: Institute of Medicine. Dietary Reference Intakes for Calcium, Phosphorus, Magnesium, Vitamin D, and Fluoride. Washington, D.C.: National Academies Press, 1997.
* IOM did not set an RDA for vitamins in this age group. Instead, an Adequate Intake (AI) is used. According to the Institute of Medicine, "The AI is a recommended average daily nutrient intake level, based on experimentally derived intake levels or approximations of observed mean nutrient intake by a group (or groups) of apparently healthy people that are assumed to be adequate. An AI is established when there is insufficient scientific evidence to determine an Estimated Average Requirement (EAR)."
Mineral | Biochemical role/function | Deficiency symptoms | Toxicity symptoms | Recommended Dietary Allowance or AI (*) |
Potassium(K)
| Neural transmission; | Cardiac arrhythmias; muscle weakness; leg discomfort; extreme thirst; frequent urination; confusion; glucose intolerance, increased blood pressure, increased salt sensitivity, increased risk for kidney stones, increased bone turnover | Fatigue, wekness, tingling, numbness, or other unusual sensations; paralysis, palpitations, difficulty breathing; cardiac arrhythmias; GI distress | Adults & children: Infants/children: (*) Pregnancy:(*) 4,700 mg |
Sodium
| Maintenance of extra-cellular volume and plasma osmolality; is an important determinant of the membrane potential of cells and the active transport of molecules across cell membranes | Brain swelling, resulting in loss of appetite, nausea, vomiting, headache, mental status changes (confusion, irritability, fatigue, hallucinations); muscle weakness, convulsions | Elevated blood pressure; increased risk for cardiovascular disease and stroke; neuro-logic symptoms (confusion, coma, paralysis of the lung muscles) | Adults: 19-50 years: (*) 1,500 mg Infants/children: (*) Pregnancy:(*) 1,500 mg |
Chloride | Important component of gastric juice as hydrochloric acid | Hypochloremic metabolic alkalosis. In infants, hypochloremia results in growth failure, lethargy, irritability, anorexia, gastrointestinal symptoms, and weakness; may also result in hypokalemia, metabolic alkalosis, hematuria, hyper-aldosteronism, and increased plasma renin | Dehydration, fluid loss, hyper-natremia | Adults: Pregnancy: (*) 2,300mg |
Source: Institute of Medicine. Dietary Reference Intakes for Water, Potassium, Sodium, Chloride, and Sulfate. Washington, D.C.: National Academies Press, 2004.
Mineral | Biochemical Role/Function | Deficiency Symptoms | Toxicity Symptoms | Recommended Dietary Allowance or AI (*) |
Iron
| Component of enzymes necessary for oxidative metabolism; heme proteins (hemoglobin, myoglobin, cytochromes); participates in electron transfer | Impaired physical work performance, developmental delay, cognitive impairment, anemia | Fatigue, anorexia, dizziness, nausea, vomiting, headache, weight loss, shortness of breath
| Adults: Infants/children: Pregnancy: 27 mg |
Zinc | Component of enzymes (RNA polymerase, alkaline phosphatase); structural role for some enzymes and in protein folding; anti-oxidant function as part of zinc-copper SOD | Growth retardation, hair loss, diarrhea, delayed sexual maturation and impotence, eye and skin lesions, loss of appetite, delayed wound healing | GI symptoms (epigastric pain, nausea, vomiting, abdominal cramps, diarrhea); impaired immune response; reduced copper status | Adults (ages 19+): Infants/children: Pregnancy: Lactation: |
Copper | Component of metallo-enzymes (oxidases; eg, monoamine oxidase; lysyl oxidase used for collagen and elastin production; cytochrome c oxidase; dopamine β mono-oxygenase); part of zinc-copper SOD | Defects in connective tissue; anemia; immune and cardiac dysfunction | GI symptoms (abdominal pain, nausea, vomiting, cramps, diarrhea)
| Adults (ages 19+): 900 µg Infants/children: (*) Pregnancy: 1000 µg |
Chromium | Potentiation of insulin action; mobilize the glucose transporter, GLUT4, to the plasma membrane (Mol Endocrinol. 2006;20:857-870); enhances tyrosine phosphorylation of the insulin receptor (Biochemistry.2005;44:8167-8175) | Rare; found in patients on TPN prior to inclusion of Cr+3; symptoms included weight loss, neuropathy, and impaired glucose tolerance | None for Cr+3; Cr+6 is a known carcinogen when inhaled, and oral ingestion (20 mg/l) causes GI symptoms (abdominal pain, nausea, vomiting, diarrhea) | Adults: Infants/children: (*) Pregnancy: 30 µg |
Sources: Institute of Medicine. Dietary Reference Intakes for Vitamin A, Vitamin K, Arsenic, Boron, Chromium, Copper, Iodine, Iron, Manganese, Molybdenum, Nickel, Silicon, Vanadium, and Zinc. Washington, D.C.: National Academies Press, 2000;
National Institutes of Health, Office of Dietary Supplements Web site (http://dietary-supplements.info.nih.gov/)
Mineral | Biochemical role/function | Deficiency symptoms | Toxicity symptoms | Recommended Dietary Allowance or AI (*) |
Selenium
| Defense against oxidative stress, regulation of thyroid hormone action, and regulation of the redox status of vitamin C and other molecules, through | Keshan disease (cardiomyopathy in pediatric population); skeletal muscle disorders manifested by muscle pain, fatigue, proximal weakness, and serum creatine kinase (CK) elevation (Muscle Nerve.2003;27:662-668) | Selenosis (gastrointestinal upset, hair loss, white blotchy nails, garlic breath odor, fatigue, irritability, and mild nerve damage); hair and nail brittleness and loss
| Adults (ages 19+): 55 µg |
Iodine | Component of the thyroid hormones thyroxine (T4) and triiodothyronine (T3) | Mental retardation, hypothyroidism, goiter, cretinism, and varying degrees of other growth and developmental abnormalities | Burning of the mouth, throat, and stomach, abdominal pain, fever, nausea, vomiting, diarrhea, weak pulse, cardiac irritability, coma, cyanosis; thyroid enlargement (goiter) from increased TSH stimulation; increased risk of thyroid papillary cancer; iodermia; hyperthyroidism | Adults (ages 19+): 150 µg |
Manganese | Component of metallo-enzymes (arginase, manganese superoxide dismutase, pyruvate carboxylase) | Dermatitis, hypocholesterolemia | Neurotoxicity
| Adults (ages 19+): (*) Infants/children: (*) Pregnancy: (*) 2 mg |
Molybdenum | Component of sulfite oxidase, xanthine oxidase, aldehyde oxidase, enzymes involved in catabolism of sulfur-containing amino acids, purines, and pyridines | Rare; initially seen in patients on TPN, before addition of MO to standard TPN regimes; resulted in tachycardia, headache, night blindness, low serum uric acid | Reproductive effects as | Adults (ages 19+): 45 µg Infants/children: (*) Pregnancy/lactation: 50 µg |
Sources: Institute of Medicine. Dietary Reference Intakes for Vitamin A, Vitamin K, Arsenic, Boron, Chromium, Copper, Iodine, Iron, Manganese, Molybdenum, Nickel, Silicon, Vanadium, and Zinc. Washington, D.C.: National Academies Press, 2000;
National Institutes of Health, Office of Dietary Supplements Web site (http://dietary-supplements.info.nih.gov/)
