John E. Morley, M.B., B.Ch.
CONTENTS
11.1 Arsenic ... 179
11.2 Boron ... 181
11.3 Chromium ... 181
11.4 Cobalt... 182
11.5 Copper... 182
11.6 Fluoride... 183
11.7 Iodine ... 183
11.8 Lead ... 183
11.9 Lithium... 184
11.10 Manganese ... 184
11.11 Molybdenum... 184
11.12 Nickel... 185
11.13 Selenium ... 185
11.14 Silicon ... 187
11.15 Tin ... 188
11.16 Vanadium ... 188
11.17 Zinc ... 188
11.18 Trace Element Interaction ... 190
11.19 Conclusion ... 190
References... 190
Trace elements play an important role in the maintenance of multiple enzyme reactions and are essential for the maintenance of tissue structure. Table 11.1 sum-marizes the major functions of the trace elements and the effects of aging on them.
11.1 ARSENIC
Arsenic has a biologic function in the metabolism of arginine and zinc.1 Arsenic deprivation retards growth in the presence of marginal zinc status. Arsenic also plays a role in the modulation of kidney arginase activity, alkaline phosphatase activity, and plasma levels of triglycerides, uric acid, and urea. Based on animal studies, the human arsenic requirement appears to be between 12 and 25 µg daily. The role of arsenic in human malnutrition has been extrapolated from animal studies. The effect of aging on arsenic has not been studied.
180 Geriatric Nutrition
TABLE 11.1 Functions of Trace Elements and the Effects of Aging on These Trace Elements Trace ElementFunctionEffect of Aging ArsenicUrea cycle, myocardial muscle function, triglyceride synthesisUnknown BoronBone structure, mineral metabolismUnknown ChromiumGlucose homeostasis, lipid metabolismDecrease CobaltVitamin B12, erythropoiesis, triglyceride synthesisNo change CopperCholesterol metabolism erythropoiesis, collagen, cross-linking, conversion of dopamine to norepinephrine, electron transport chain, coagulation factor VIncrease in serum; decrease in saliva, hair, and heart FluorideBone structure, tooth enamelIncrease to 60, then decline in skeleton IodineThyroid hormonesUnknown LeadToxicity leads to dementia, hypertension, and anemiaIncrease in serum after 45 LithiumEndocrine secretory functionUnknown ManganeseProtein and energy metabolism, mucopolysaccharides; Parkinsonism with excess intakeNo change in serum; reduced in kidney and heart MolybdenumUric acid production, oxidation of sulfite to sulfateUnknown NickelRNA and DNA structure, membrane stabilization, iron absorption and metabolism, pituitary functionIncrease in lung SeleniumConstituent of glutathione peroxidase, T and B cell function, muscle metabolismDecrease SiliconBone structure, connective tissue structureDecrease in aorta and skin TinInduces hemoxygenase and carbon monoxide productionIncrease in Alzheimer’s disease VanadiumCholesterol synthesis, catalysis of oxidation–reduction reactionsUnknown ZincImmune function, taste, oxidative metabolism, sexuality, skin integrityNone
Trace Elements 181
11.2 BORON
In Drosophilia, moderate levels of boron increase life span while higher levels decrease it.2 Boron appears to interact with cholecalciferol in the maintenance of bone structure.1 It also interacts with magnesium. In postmenopausal women on a low-magnesium diet, boron supplementation (3 mg/day) reduced the urinary excre-tion of calcium, magnesium, and phosphorus.3 Boron supplementation also resulted in an increase in serum testosterone and 17-estradiol in these women. A second study found that a low-boron diet was associated with hypercalcemia.4 Increasing boron intake failed to alter sex steroid hormone levels or urinary excretion of pyrrolidinium cross-link markers of bone turnover. These studies have led to the perhaps premature claim that boron supplementation may play a role in the preven-tion of calcium loss and bone demineralizapreven-tion in postmenopausal women.
11.3 CHROMIUM
Chromium is an essential trace element that may play a role in glucose homeostasis.5 Deficiency of chromium or its biologically active form, glucose tolerance factor (a dinicotinic acid–glutathionine complex), has been shown to result in glucose intol-erance.6 The glucose tolerance factor is poorly characterized. The richest sources of it are brewer’s yeast, liver, and kidney.
Hyperglycemia, which responds to chromium replacement, has been reported to occur in patients on total parenteral nutrition.7–9 However, the role of chromium in the hyperglycemia of aging remains controversial. Skeptics totally reject its role, whereas others embrace it wholeheartedly. One well-controlled study of 16 patients 65 years of age and older found that chromium in combination with nicotinic acid caused a 15% decrease in the integrated glucose area in response to a glucose load.10 Numerous studies continue to produce contradictory studies on the effect of chro-mium on diabetic control.11–15 A low-chromium diet was shown to produce deterio-ration in glucose tolerance in some subjects, and this was improved by chromium supplementation.16
Chromium deficiency has been associated with hypercholesterolemia in some but not all studies.5 Two of three studies have found an increase in high-density lipoprotein (HDL) cholesterol with chromium supplementation.17–19
Chromium deficiency in humans has been associated with weight loss, atoxia, and peripheral neuropathy, as well as with hyperglycemia in patients on total parenteral nutrition.
Tissue and serum chromium levels decline with age20–22 and may do so more dramatically in Western societies that eat refined foods and are somewhat deficient in chromium.23 There is increased urinary excretion of chromium with aging and in diabetics.24 The Recommended Daily Allowance (RDA) for chromium is between 50 and 200 µg.25 However, Bunker et al.26 reported that healthy volunteers ingesting 13.6 to 47.7 µg/day were able to maintain a positive chromium balance. In a study of institutionalized older individuals, the average chromium content of food offered (not eaten) was 52 µg/day.27 Urinary excretion of chromium increases with age.28
182 Geriatric Nutrition
11.4 COBALT
Cobalt tissue concentrations are unchanged with age.29 Cobalt is an essential portion of the vitamin B12 molecule. Cobalt therapy increases hemoglobin in anemic patients on dialysis.30 However, this response may be associated with an increase in tumor-igenesis. Cobalt therapy also increases triglyceride levels.31 High cobalt levels in beer have been associated with the development of a cardiomyopathy.32 Cobalt may reduce thyroid function when given in pharmacologic doses.33 Elevated cobalt levels can be found in both the blood and urine of patients with metallic hip replacements.34
11.5 COPPER
Copper is involved in iron absorption and mobilization. It acts as a catalyst in multiple enzymatic reactions, including the superoxidase dismutase reaction, the cross-linking of collagen, the lipyloxidase enzyme, the electron transport chain through cytochro-mic oxidase, coagulation factor V, and the conversion of dopamine to norepinephrine.
Copper deficiency is associated with hypercholesterolemia, perhaps through an increased rate of cholesterol release from the liver.35 Copper deficiency also leads to an impairment of glucose tolerance,36 and copper has been shown to act syner-gistically with insulin to drive the incorporation of glucose into fat cells.37 In humans, a weak association between serum copper levels and fasting blood glucose has been demonstrated.38,39 Klevay40 suggested that atherosclerosis is related to the rate of zinc to copper levels. However, the evidence that copper deficiency is associated with atherosclerosis is extremely weak. A recent study did demonstrate higher serum copper levels in persons who had a myocardial infarction than in age-matched controls.41 Systolic blood pressure is positively correlated with urinary copper excre-tion.42 Copper deficiency has been associated with anemia, neutropenia, and osteoporosis.36 Lower levels of serum copper were found in elderly patients with femoral neck fractures.43 In addition, it may cause muscle weakness and a bleeding tendency. Symptoms of congenital copper deficiency (Menkes syndrome) include arterial disease, abnormal hair, osteoporosis, cerebellar atoxia, and other brain dam-age. Copper deficiency in older individuals has usually been associated with total
TABLE 11.2
Possible Clinical Syndromes Associated with Copper Deficiency in Humans
Anemia and neutropenia Osteoporosis
Arterial disease Pigmentation loss Muscle weakness Bleeding tendency
Cardiomyopathy vs. atherosclerotic heart disease Brain degeneration
Impaired glucose tolerance Myelopathy
Trace Elements 183 parenteral nutrition. Symptoms in two patients on total parenteral nutrition with severe copper deficiency responded to copper supplementation.44
Serum copper levels tend to increase with aging,45 although there is no change in leukocyte copper levels.46 A recent study found an increase in serum copper levels in men but a decrease in women.47 In the locus coeruleus of the brain copper levels decrease.48
The increase in serum copper with advancing age is accompanied by an increase in ceruloplasmin.49 Ceruloplasmin in older persons is oxidatively modified, resulting in conformational changes around the copper-binding sites.50 In contrast, copper levels decrease in salivary sediment and hair with aging.51 Copper levels are also significantly reduced in the heart tissue of older subjects.52 Absorption of copper is similar in young and old men53 and women.49 Biologic half-life increases in men but not in women with advancing age.
Although older subjects ingest significantly lower amounts of copper than younger subjects, they appear to have no problem in maintaining metabolic balance.53 In the presence of type II diabetes mellitus, both copper and ceruloplasmin levels are elevated, and this elevation is more pronounced with advancing age.36
Overall, copper metabolism seems to be conserved with aging. The potential pathophysiologic role of copper deficiency in atherosclerosis and the hyperglycemia of aging warrants further study. The potential effects of mild copper deficiency are summarized in Table 11.2. Recently copper deficiency has been recognized to pro-duce a myelopathy similar to subacute combined degeneration.54
11.6 FLUORIDE
Fluoride plays a role in the hydroxyapatite of bone and tooth enamel. Circulating fluoride levels tend to rise after middle age because of the decrease in renal function and an increased release of fluoride from bone.55
Fluoride has been used in the therapy of osteoporosis to reduce the fracture rate.56 However, during the early course of fluoride therapy, microfractures may occur in the lower limbs, resulting in pain in the lower extremities. An increase in hip fractures has been reported in some patients receiving fluoride therapy. Fluoride therapy can cause exacerbations of rheumatoid arthritis as well as gastrointestinal bleeding and painful joints.
11.7 IODINE
Iodine is an integral part of the thyroid hormones. Iodine deficiency can lead to the development of goiter. There are no studies on iodine metabolism with advancing age.
11.8 LEAD
Animal studies have suggested that aging produces enhanced vulnerability to the behavioral effects of lead.57 Lead levels increase throughout life, with levels being higher in males than in females.58