5. DETERMINE (13–15)
8.7 TRACE MINERALS
Studies of dietary intake and nutritional status of the trace minerals indicate that persons in later life are more vulnerable to deficiencies than are younger persons as a result of multiple physiological, psychological, and socioeconomic factors. Reasons for this include an increased prevalence of chronic diseases and medication use, e.g., diuretics, that may affect nutrient turnover in the former, physiologic changes with age that may influence absorption, distribution, and metabolism of the minerals, and psychological, e.g., loneliness, and socioeconomic conditions that may affect dietary choices and eating patterns. Brief discussions of the biologic importance of each of the minerals will be followed by presenting features and functional con- sequences of each trace mineral deficiency, along with how best to establish a diagnosis.
When available, Recommended Daily Allowances (RDAs) are provided for each of the trace minerals (Table 8.1). The RDA is defined as the intake that meets the nutrient need of 97–98% of the individuals in that group. Food sources providing the highest content of each mineral are listed. The quantity of each mineral in a typical once-daily multivitamin preparation for seniors is shown along with addi- tional sources of single element supplements. Also provided when available is a tolerable upper intake level defined as the maximum intake that is unlikely to produce adverse health effects in most (97–98%) individuals. More comprehensive reviews are available for those desiring additional information on the vast literature describing evidence for trace mineral deficiency and ranges of dietary intake of these minerals in population studies(18–20).
8.7.1 Zinc
Zinc is the intrinsic metal component or activating cofactor for over 70 important enzyme systems, including carbonic anhydrase, the alkaline phosphatases, the dehydrogenases, and the carboxypeptidases. It governs the rate of synthesis of the nucleoproteins (DNA and RNA polymerases are zinc-dependent enzymes) and other proteins, thereby influencing growth and the reparative processes. It is also an important regulator of the activity of various inflammatory cells (macrophages, polymorphonuclear leukocytes) thereby affecting the immune system, plays a role in certain endocrine functions (growth, sexual maturation), affects carbohydrate tolerance by decreasing the rate of insulin secretion in response to glucose admin- istration, and is an important regulator of bone repair.
Human zinc deficiency was first described in adolescent males (Iran, Egypt) receiving inadequate intakes of zinc and having excessive binding of ingested zinc to phytates (unleavened bread), fiber, and clay. These youths developed severe growth retardation (dwarfism), anemia, rough skin, apathy (general lethargy), and delayed sexual maturation that responded dramatically to zinc supplementa- tion. Similar manifestations of severe zinc deficiency have been seen in patients started on TPN and given no mineral supplements, and in certain disease states, especially those affecting GI absorption, e.g., regional enteritis (Crohn’s disease).
Potential manifestations of zinc deficiency include impaired taste and smell,
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anorexia, alopecia, dermatitis starting in the nasolabial folds and extending to the scrotum, perineum, and extensor aspects of the elbows, impaired wound healing, hypogonadism and sexual dysfunction, and immune dysfunction(19,20).
The Recommended Dietary Allowances (RDA) for adult males is 11 mg/day and for females 8 mg/day (21). While normal healthy elderly should be ingesting quantities near these amounts daily, only about two-thirds of the zinc ingested is normally absorbed through the GI tract. Zinc from meats is absorbed better than that from vegetables. Diets high in phytates (breads) interfere with absorption.
The normal plasma zinc concentration ranges from 80 to130mg/mL. Low plasma zinc concentrations can result either from redistribution of zinc due to acute infectious or inflammatory conditions (release of cytokines into the circulation), or from a true zinc deficiency state(19). Large population studies (NHANES II) have shown that 12% of men and women had plasma zinc levels below 70mg/mL, and were strikingly higher in the older populations, those in poor health, and/or those with low socioeconomic status(20).
A typical once-daily multivitamin preparation for seniors contains 15 mg of elemental zinc; however, zinc sulfate tablets containing 25 and 50 mg of elemental zinc are also available. The tolerable upper intake level has been established at 40 mg/day(19).
8.7.2 Copper
Copper is the metal component of a number of enzymes important in human metabolism. It is involved in such diverse enzymatic and metabolic activities as hemoglobin synthesis, bone and elastic tissue development, and the normal function of the central nervous system. The usual first manifestations of a copper deficiency in man are anemia unresponsive to iron supplements, leucopenia, and neutropenia.
Much less commonly seen are hypopigmentation, immune dysfunction, and skeletal abnormalities. Animals made severely deficient will develop central nervous system deficiencies (ataxia, mental deficiency), skeletal defects (osteoporosis with frac- tures), aortic rupture, and skin and hair (red) changes. Significant copper deficiency in adults does not appear to be common, unless the individual is on TPN without mineral supplements, or the patient has intestinal or malabsorptive disease. It is seen primarily in infants with GI disorders (diarrhea) on cow’s milk, and in children with a hereditary disorder (Mencke’s kinky hair syndrome) in which copper absorp- tion from the GI tract is defective.
Normal plasma copper concentrations range from 80 to 140mg/mL, but may be higher in acute infectious or inflammatory states. Wilson disease (hepatolenticular degeneration) is a rare, inherited inborn error of copper metabolism characterized by a low serum ceruloplasmin concentration (the major copper-binding protein in blood), usually low serum copper levels, but increased urinary copper and deposition of copper in vital organs (brain, liver, kidney, eyes) producing dysfunction in these systems.
The Recommended Dietary Allowance for older men and women is 900mg of elemental copper per day(19,21). Most once-daily multivitamin preparations for seniors contain 2 mg of elemental copper. Copper gluconate is also available in tablet form in dosages containing 3 mg of elemental copper. The tolerable upper intake level is 10 mg/day(19).
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8.7.3 Iron
About 70% of bodily stores of iron are found in hemoglobin and myoglobin, with most of the rest stored in a labile form (ferritin, hemosiderin) in the liver, spleen, and bone marrow to be used in the regeneration of hemoglobin in case of blood loss. A hypochromic, microcytic anemia (hemoglobin <12 g/dL) with decreased serum iron, normal to increased iron-binding capacity, and decreased serum transferrin levels, is the primary manifestation of iron deficiency. Other manifestations of iron deficiency (Plummer–Vinson syndrome) include listlessness, fatigue, palpitations, glossitis, stomatitis, and dysphagia caused by a post-cricoid stricture.
The range of normal serum iron concentration is 60–175 mg/dL in men and 50–170 mg/dL in women, the iron-binding capacity is 250–450 mg/dL in both genders, and serum transferrin is 200–400 mg/dL in both genders.
While many feel that post-menopausal females and males get enough iron in their diets to avoid a deficiency state, and that excess iron may actually have detrimental effects, RDAs for elemental iron have been established for both of these groups at 8 mg/day. While some once-daily multivitamin preparations for seniors include this amount of elemental iron in their preparations, many no longer contain any iron.
Oral ferrous sulfate tablets and capsules, both enteric-coated and extended release (commonly 325 mg of ferrous sulfate equals 65 mg elemental iron), are available for treatment of documented iron-deficiency anemia.
8.7.4 Selenium
Selenium is concerned with growth, muscle function, the integrity of the liver, and fertility in ways that are poorly understood. A number of animal disease models with deficiencies of both vitamin E and selenium can be cured by administration of one or the other showing the interacting biochemical roles of these two agents.
Selenium is the metal component of glutathione peroxidase; both this and vitamin E act as antioxidants in the detoxification of peroxides and free radicals that have their most damaging effects on cell membranes in blood, liver, and other tissues.
Selenium-deficient animals develop hair loss, growth retardation, and reproductive failure. Selenium deficiency has been implicated in Keshan disease, an endemic cardiomyopathy found in selenium-deficient areas of China. While selenium sup- plements will prevent the disease, they will not cure it once established. Selenium deficiency is not likely to occur in free-living, healthy individuals living in the United States; however, individuals in poor health may be at risk. A number of animal and human studies suggest that selenium may play a role in protecting against the development of cancer(20).
Serum/plasma selenium levels can be quantified (normal 100–180 ng/mL).
The best sources of selenium are grains (bread) (depending on the selenium content of soil), seafood, liver, and meats. The RDAs for selenium have been established for both men and women at 55mg/day(19,21). The typical once-daily multivitamin preparations for seniors contain 20mg of elemental selenium. Ele- mental selenium is also available in tablet form at dosages of 50, 100, and 200mg.
The tolerable upper intake level for both men and women is 400mg/day. Symptoms
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associated with selenium toxicity include nausea and vomiting, hair loss, nail changes, irritability, fatigue, peripheral neuropathy, and changes in breath odor (garlic or sour milk).
8.7.5 Chromium
Chromium is an integral and active part of the glucose tolerance factor (GTF), a dinicotinic acid glutathione complex that increases the influx of glucose into cells in response to insulin. Because it is difficult to quantify levels of chromium in tissue and blood, chromium deficiency is best demonstrated by showing a response to chromium supplementation. A deficiency of chromium in animals produces an abnormal glucose tolerance (insulin resistance). Chromium deficiency has been reported in humans on long-term TPN and is characterized by impaired glucose tolerance (insulin resistance) not responsive to added exogenous insulin, decreased HDL lipoprotein cholesterol, increased LDL lipoprotein cholesterol, and periph- eral neuropathy or encephalopathy. All these are reversible with chromium supple- mentation. Diabetics tend to have low tissue stores of chromium and lose increased amounts in the urine. Investigators have speculated that there may be a subset of diabetics with glucose intolerance that will respond to chromium supplementation, but the evidence for this remains inconclusive. Chromium supplements have also been reported to be performance enhancing, but the data to support this claim is also very limited.
Processed meats, whole grains, and certain vegetables have high chromium concentrations. There is no RDA for chromium, but intakes adequate (AIs) to sustain nutritional status are felt to be 30mg/day in adult males and 20 mg/day in adult females(19,21). Once-daily multivitamin supplements for seniors commonly contain 150 mg of elemental chromium. Chromium capsules are available that contain 200mg of elemental chromium. Toxicity has not been reported.
8.7.6 Manganese
Manifestations of manganese deficiency in animals include impaired growth, skeletal abnormalities, reproductive dysfunction, ataxia, and alterations in lipid and carbohydrate metabolism. A single case study describes manganese deficiency in a human volunteer inadvertently deprived of this mineral during an experimental study, who developed hypocholesterolemia, weight loss, transient dermatitis, and reddening and slow growth of normally black hair and beard. All returned to normal with repletion.
Manganese is ubiquitous being more available in vegetarian than in non-vegetar- ian diets. Although no RDAs have been published, the Food and Nutrition Board identified Adequate Intakes as 2.3 mg/day for men and 1.8 mg/day for women (19,21)the levels easily obtained with the normal diet. The typical once-daily multi- vitamin for seniors contains 2 mg of manganese. Parenteral manganese is available for use in TPN solutions. The tolerable upper limit for manganese is 11 mg/day.
8.7.7 Molybdenum
Molybdenum is a cofactor of xanthine, sulfite, and aldehyde oxidases, and is a copper antagonist. Molybdenum deficiency in animals impairs the conversion of Chapter 8/ Hydration, Electrolyte, and Mineral Needs 153
hypoxanthine and xanthine to uric acid causing xanthine renal calculi. Apparent molybdenum deficiency developed in a patient on TPN characterized by an intol- erance to the sulfur-containing amino acids. She/he developed tachycardia, tachyp- nea, central scotomas, night blindness, irritability, and finally coma that cleared when the sulfur-containing amino acids were stopped. There was biochemical evidence of impaired conversion of sulfite and thiosulfite to sulfates by sulfite oxidase, and xanthine and hypoxanthine to uric acid by xanthine oxidase, both reactions normally facilitated by molybdenum-containing enzymes. Treatment with molybdenum reversed the sulfur-handling defect.
The RDAs for molybdenum are 45 mg/day for men and 34mg/day for women, both easily achievable with a normal diet. The typical once-daily multivitamin preparation for seniors contains 75mg. The tolerable upper intake level is 2 mg/day.
8.7.8 Other Trace Minerals
Although studies in animals depleting and replacing single trace minerals have convincingly shown that vanadium, nickel, silicon, boron, and tin are essential for normal growth and maturation, the evidence that clinically apparent deficiencies develop in man is non-existent(18). Once-daily multivitamin–mineral supplements for seniors, however, commonly contain 150mg of boron, 5mg of nickel, 2 mg of silicon, and 10mg of vanadium. Cobalt is essential as the metal cofactor in vitamin B12, but because it is such a commonly available nutrient and such small amounts are needed to meet demands, cobalt deficiency has not been reported in animals or man. Finally, there are five non-essential minerals (cadmium, lead, mercury, arsenic, and aluminum) that can accumulate acutely or chronically to produce toxicity(18).