A moderately high intake compared to a low intake of zinc depresses magnesium balance and alters indices of bone turnover in postmenopausal women.

OBJECTIVES: To determine whether moderately high or low intakes of zinc adversely affect the copper status of postmenopausal women to result in unfavorable changes in calcium and magnesium metabolism and other indicators of bone turnover. DESIGN: After a 10-day equilibration period in which the diet provided 31.5 micromol (2 mg) Cu and 137.7 micromol (9 mg) Zn/8.4 MJ (2000 kcal), the subjects were randomly divided into two groups, with one group fed the basal diet supplemented to provide 15.7 micromol (1 mg) Cu/8.4 MJ, and the other group fed the same diet supplemented to provide 47.2 micromol (3 mg) Cu/8.4 MJ. After equilibration, both groups were fed the basal diet with no zinc supplemented (provided 45.9 micromol [3 mg] Zn/8.4 MJ) for 90 days; this was followed by another 10-day equilibration period before the basal diet was supplemented with zinc to provide 811 micromol (53 mg)/8.4 MJ for 90 days. SETTING: The metabolic unit of the Grand Forks Human Nutrition Research Center, Grand Forks, ND, USA. SUBJECTS: A total of 28 postmenopausal women recruited by advertisement throughout the United States of America. Among them, 25 women (64.9+6.7 y) completed the study; 21 as designed. RESULTS: The moderately high intake compared to the low intake of zinc increased the excretion of magnesium in the feces and urine, which resulted in a decreased magnesium balance. In the women fed low dietary copper, plasma osteocalcin was higher during the low-zinc than high-zinc dietary period. The urinary excretion of N-telopeptides was increased and the serum calcitonin concentration was decreased by high dietary zinc regardless of dietary copper. CONCLUSIONS: A moderately high intake of zinc (811 micromol/day; 53 mg/day) did not induce changes in copper metabolism that resulted in unfavorable changes in bone or mineral metabolism. However, low dietary zinc (45.9 micromol/day; 3 mg/day) apparently resulted in undesirable changes in circulating calcitonin and osteocalcin. As a moderately high intake of zinc decreased magnesium balance, further study of the possibility that a high intake of zinc is a health concern for individuals consuming less than the recommended amounts of magnesium is warranted.

Low dietary zinc alters indices of copper function and status in postmenopausal women.

OBJECTIVES: To better define the relationship between dietary zinc and copper for humans so that sound recommendations for intakes of these elements can be made. METHODS: A study was conducted to ascertain the effect of moderately excessive and deficient intakes of zinc on copper metabolism and use in humans fed low and luxuriant amounts of copper. Twenty-one postmenopausal women housed in a metabolic unit completed the study as designed. After a 10-d equilibration period in which they were fed a diet providing 31.5 micromol (2 mg) Cu and 91.8 micromol (9 mg) Zn/8.4 MJ (2000 kcal), the women were divided into two groups. One group was fed a diet containing 15.7 micromol (1 mg) Cu/8.4 MJ (2000 kcal), and the other group was fed a diet containing 47.2 micromol (3 mg) Cu/8.4 MJ (2000 kcal). After equilibration, both groups were fed the basal diet providing 45.9 micromol (3 mg) Zn/8.4 MJ (2000 kcal) for 90 d; this was followed by another 10-d equilibration period before dietary zinc was increased to 811 micromol (53 mg)/8.4 MJ (2000 kcal) for 90 d. RESULTS: The women were in positive copper balance only when the diet provided 47.2 micromol (3 mg) Cu and 811 micromol (53 mg) Zn/d. Immunoreactive ceruloplasmin concentrations and platelet cytochrome-c oxidase activity on a platelet number basis were significantly lower and the ratio between enzymatic and immunoreactive ceruloplasmin was significantly higher during low dietary than during high dietary zinc intake. Serum cholesterol was higher in subjects fed 15.7 micromol (1 mg) Cu/d than in those fed 47.2 micromol (3 mg) Cu/d. Total and low-density lipoprotein cholesterol concentrations decreased with zinc supplementation. Whole-blood glutathione concentration and erythrocyte glutathione peroxidase activity were lower during high than during low dietary zinc intake. CONCLUSIONS: The findings indicate that an inadequate intake of zinc (45.9 micromol/d; 3 mg/d) was more effective than a moderately high intake of zinc (811 micromol/d; 53 mg/d) in inducing changes associated with a decreased copper status in postmenopausal women. Furthermore, the findings indicate that copper status indicators might be useful in evaluating changes in zinc status in humans, and an intake of 15.7 micromol (1 mg)/d of copper may be inadequate for postmenopausal women.

Changes in dietary zinc and copper affect zinc-status indicators of postmenopausal women, notably, extracellular superoxide dismutase and amyloid precursor proteins.

BACKGROUND: Zinc is an essential trace element for human health and well-being; however, methods currently available for the assessment of zinc status in humans are unsatisfactory. OBJECTIVE: The objective was to critically evaluate the use of various indicators of zinc status in humans in a controlled metabolic ward study. DESIGN: Indicators of zinc status were measured in 25 healthy postmenopausal women aged 64.9 +/- 6.7 y. After a 10-d equilibration period, volunteers consumed a diet with either a low (1 mg/d; n = 12) or a high (3 mg/d; n = 13) copper content based on a total energy content of 8.4 MJ. They received the same amount of copper throughout the study. Both groups were fed the basal diet (3 mg Zn/d) with no zinc supplement for one 90-d period, and the diet supplemented with 50 mg Zn/d for another 90-d period. RESULTS: Zinc supplementation significantly increased (P < 0.0001) extracellular but not erythrocyte superoxide dismutase activity. This increase was more apparent when subjects were fed the low-copper diet. Zinc supplementation in combination with the low-copper diet significantly decreased (P < 0.01) amyloid precursor protein expression in platelets. Other indicators of zinc status that were significantly elevated after zinc supplementation were as follows: plasma zinc and free thyroxine concentrations and mononuclear 5'-nucleotidase activity. CONCLUSION: The measurement of serum extracellular superoxide dismutase activity may be useful as a marker for the functional assessment of zinc status in humans.

The interaction between dietary fructose and magnesium adversely affects macromineral homeostasis in men.

OBJECTIVE: Studies with rats have found that an interaction between fructose and magnesium affects macromineral metabolism; high dietary fructose significantly increased kidney calcification in both male and female rats, particularly when dietary magnesium was low. This study tests the hypothesis that an interaction between dietary fructose and magnesium adversely affects macromineral homeostasis in men. METHODS: Eleven men aged 22 to 40 years were fed a mixed, Western diet for four 42-day dietary periods in which dietary magnesium was either approximately 170 or 370 mg/day and dietary fructose was either 4% or 20% of energy. A decaffeinated beverage containing high fructose corn syrup replaced cornstarch, bread and rice in the low fructose diet to give the high fructose diet. RESULTS: High dietary fructose significantly (p<0.01) increased magnesium balance during both low and high dietary magnesium intakes. Ultrafilterable and ionized serum magnesium also apparently were related to magnesium and fructose intakes; they were higher when fructose was fed and when Mg intakes were high. High fructose depressed calcium balance: the effect tended to be more marked when dietary Mg was low. High dietary fructose also significantly (p<0.005) decreased phosphorous balance. Urinary phosphorous losses were significantly (p<0.001) higher when high dietary fructose was fed. High dietary fructose also increased the concentration of serum alkaline phosphatase (p<0.005). CONCLUSION: These findings indicate that dietary fructose adversely affects macromineral homeostasis in humans and suggest further studies to see if a high fructose diet coupled with low dietary magnesium and marginal calcium leads to bone loss.

Chromium supplementation and resistance training: effects on body composition, strength, and trace element status of men.

The effects of 8 wk of daily chromium supplementation (3.3-3.5 mumol as chromium chloride or chromium picolinate) or placebo (0.1 mumol Cr) and weight training were examined in 36 men in a double-blind design. Strength, mesomorphy, fat-free mass, and muscle mass increased with resistance training independently of chromium supplementation (P < 0.0001). Protein, magnesium, zinc, copper, and iron intakes equalled or exceeded the recommended dietary allowance (RDA) or estimated safe and adequate daily dietary intake (ESADDI) during training and did not change significantly from pretraining intakes (P > 0.05). Chromium supplementation increased the serum chromium concentration and urinary chromium excretion without a difference as a result of the chemical form of chromium (P < 0.05). Resistance training was associated with a significant decrease (P < 0.05) in serum ferritin, total-iron-binding capacity, transferrin saturation, the ratio of enzymatic to immunoreactive ceruloplasmin, and plasma copper, independently of chromium supplementation. However, transferrin saturation was decreased more with chromium picolinate supplementation (24%) than with chromium chloride or placebo (10-13%). Compared with pretraining values, urinary magnesium excretion increased (P < 0.05) and urinary zinc output tended to decrease during the first 4 wk of resistance training and then returned to baseline values for the final 4 wk, which suggests an adaptation in mineral excretion in response to weight training. These findings suggest that routine chromium supplementation has no beneficial effects on body- composition change or strength gain in men. Whether chromium supplementation of individuals with diminished chromium nutriture facilitates propitious changes in body structure and function remains to be determined.

Effects of a diet low in copper on copper-status indicators in postmenopausal women.

To study the effects of low copper intake in older individuals, 12 postmenopausal women, aged 63.1 +/- 8.8 y, were fed a diet containing 9 micromol (0.57 mg) Cu/d for 105 d, followed by a copper-repletion period of 35 d during which the diet was supplemented with 31.5 micromol (2.0 mg) Cu/d. Plasma copper and ceruloplasmin did not change significantly during copper depletion but ceruloplasmin decreased during copper repletion. Erythrocyte superoxide dismutase activity dropped significantly during low copper intake from 3450 to 2600 U/g hemoglobin, but did not increase during copper repletion. Platelet cytochrome c oxidase activity changed significantly (P<0.0001) from 1740 to 810 U/g protein during copper depletion, then increased to 1000 U/g protein during copper repletion. Erythrocyte glutathione peroxidase activity responded similarly. Clotting factor VIII activity increased significantly during copper depletion, then dropped during copper repletion. Low copper intakes did not induce the changes in serum cholesterol and hematology generally found in copper-deficient animal models. These results indicate that a paradigm shift may be needed in evaluating copper status in adult humans. Sensitive indicators of copper include functional activities of platelet cytochrome c oxidase, platelet copper, glutathione peroxidase, and clotting factor VIII. Plasma copper, ceruloplasmin, and cholesterol are relatively insensitive indicators. Also, the recovery from mild copper depletion may require more aggressive intervention tha 2 mg Cu/d for 35 d.

Response of various indices of iron status to acute iron depletion produced in menstruating women by low iron intake and phlebotomy.

We investigated response sensitivities of indices of iron status to controlled iron depletion and repletion in 11 premenopausal women. The women were depleted of storage iron (as reflected by serum ferritin) through a combination of a low-iron diet and phlebotomy. They then consumed a diet containing 13.7 mg of iron per 2000 kcal, supplemented with either ascorbic acid or placebo (for 5 1/2 weeks) and a daily 50-mg iron supplement (for the subsequent 17 days). The relative sensitivities of different indices for detecting iron depletion were as follows: ferritin greater than % transferrin saturation greater than plasma iron greater than hemoglobin greater than hematocrit greater than zinc protoporphyrin (ZnPP) and erythrocyte protoporphyrin (EP). Ascorbic acid treatment during repletion, before iron supplementation, significantly (P less than 0.05) affected changes in hemoglobin, ZnPP, ZnPP/heme, and EP/heme. Changes in heme synthesis evidently do not occur until iron stores are depleted and, conversely, during iron repletion hematopoiesis must be satisfied before iron stores, as reflected by ferritin, increase. Thus, the use of only one index of iron status is of limited value for detecting iron depletion.

Effects of dietary copper on human autonomic cardiovascular function.

Heart rate and blood pressure responses during supine rest, orthostasis, and sustained handgrip exercise at 30% maximal voluntary contraction were determined in eight healthy women aged 18-36 years who consumed diets varying in copper and ascorbic acid content. Copper retention and plasma copper concentration were not affected by diet. Enzymatic, but not immunoreactive, ceruloplasmin was lower (p less than 0.05) after the low copper and high ascorbic acid diet periods. Diet had no effect on resting supine heart rates, orthostatic responses in heart rate and blood pressure, or standing resting blood pressure. Systolic and diastolic blood pressures were increased significantly (p less than 0.05) during the handgrip test at the end of the low copper and ascorbic acid supplementation periods. Also, the ratio of enzymatic to immunoreactive ceruloplasmin decreased significantly during these dietary treatments. The mean arterial blood pressure at the end of the handgrip test was negatively (p less than 0.0004) correlated with the ceruloplasmin ratios. These findings indicate a functional alteration in human blood pressure regulation during mild copper depletion.

Ethanol metabolism in postmenopausal women fed a diet marginal in zinc.

Five postmenopausal women aged 50-63 y were fed a diet of mixed Western foods that supplied an average of 2.6 mg zinc/d for 6 mo. Plasma zinc did not change significantly during Zn depletion but increased slightly when Zn was fed. Zn content of blood cellular components and activities of Zn-containing enzymes were not affected by Zn intake. Ethanol tolerance tests performed at the end of control, middle of depletion, end of depletion, and end of repletion showed a change in ethanol metabolism at the end of the low-Zn intake period that was corrected within 1 mo with Zn supplementation. These data suggest that there are homeostatic mechanisms that maintain circulating levels of Zn. Zn and activity of Zn enzymes in tissues may be decreased before changes in circulating Zn levels are seen. Functional indices of Zn biochemistry, such as ethanol metabolism, may be more sensitive indicators of Zn stores and nutriture than circulating Zn.

Comparison of dietary histories and seven-day food records in a nutritional assessment of older adults.

Dietary histories and seven-day food records were obtained for 54 apparently healthy older adults. The two dietary methods correlated for most nutrients, but mean differences were significant for several nutrients. Intakes below recommended levels occurred most frequently for energy, calcium, and zinc. Biochemical evidence of thiamin and riboflavin deficiency was unexpectedly frequent. Using food records, dietary iron correlated with serum ferritin. Using dietary histories, dietary protein correlated with serum albumin, and dietary zinc correlated with plasma zinc. Using either dietary method, plasma ascorbate was associated positively with both dietary ascorbate and ascorbate supplements, and negatively with cigarette smoking. Use of thiamin- or folate-containing supplements was associated with improved biochemical status for the respective vitamin. Though neither dietary histories nor food records give precise intake data for individuals, either method may be useful for epidemiologic studies with appropriate sample sizes.

Changes in plasma zinc content after exercise in men fed a low-zinc diet.

For 30 days five healthy men aged 23-57 yr consumed a diet adequate in zinc (8.6 mg/day); they ate a low-zinc diet (3.6 mg/day) for the next 120 days and then received a zinc-supplemented (33.6 mg/day) diet for 30 days. Copper intake was constant at 1.8 mg/day. Aerobic capacity was determined periodically during each diet period. Relative zinc balance (% of control) declined during depletion (r = -0.28, P less than 0.009). Pre- and postexercise zinc concentrations decreased when dietary zinc was restricted (r = -0.61, P less than 0.0001 and r = -0.78, P less than 0.0001) and increased with supplementation (r = 0.61, P less than 0.008 and r = 0.76, P less than 0.0003, respectively). Both plasma zinc and hematocrit increased (P less than 0.01) after maximal exercise. To minimize the effect of hemoconcentration during exercise, the van Beaumont quotient (J. Appl. Physiol. 34: 102-106, 1973) was calculated using pre- and postexercise hematocrit and plasma zinc. The initial quotient of 1.8 +/- 1.8% (mean +/- SE) declined (P less than 0.05) to -7.4 +/- 2.3% during depletion. With zinc repletion, the quotient increased to 6.9 +/- 3.6%, which was greater (P less than 0.05) than the quotient in depletion but similar to the initial quotient. The quotient was a strong predictor (r = 0.71, P less than 0.0005) of the change in relative zinc balance during zinc depletion. In contrast, no changes were found in plasma copper content. These data suggest that zinc mobilization from tissues is impaired during zinc depletion, and they validate the use of the van Beaumont quotient as an index of change in body zinc stores.

Effect of oral folic acid supplements on zinc, copper, and iron absorption and excretion.

Effects of folic acid supplements on zinc excretion patterns were seen during studies of mild zinc deficiency in men. During these studies eight men were fed diets containing 150 micrograms of folacin (by analysis) per day. Four of the men were supplemented with 400 micrograms of pteroylglutamic acid (folic acid) every other day. All of the men were fed diets containing about 3.5 mg/Zn per day which were supplemented with 4.0 mg/Zn day for 4 wk and unsupplemented for 16 wk, then supplemented with 30.0 mg/Zn day for 4 wk. Their body weights were kept constant by adjustments of energy intakes and expenditures. Duplicate diets, stools, and urines were analyzed for zinc, copper, and iron. Fecal zinc was significantly (p less than 0.001) higher in the group that received folic acid supplements during the initial control and low zinc intake periods. No significant differences were seen during the period of high zinc intake. During all dietary periods urinary zinc excretion was reduced by about 50% by folic acid supplementation. No apparent changes occurred in iron or copper excretion. These data indicate that supplemental folate influences zinc homeostasis, perhaps through formation of an insoluble chelate and impairment of absorption.

Effect of consuming fiber from corn bran, soy hulls, or apple powder on glucose tolerance and plasma lipids in type II diabetes.

The effects of consuming corn bran, soy hulls, or apple powder on glucose and lipid metabolism were investigated in two studies of persons with type II diabetes. Fiber sources, completely or partially added to bread, were incorporated into subjects' self-selected diets. Low fiber white bread served as a control. In study A, 10 subjects consumed 26 g fiber source daily; in study B, eight subjects consumed 52 g fiber source. Biochemical tests, including a 2-h postprandial glucose test using a low fiber formula meal, were scheduled after 2 and 4 wk of each dietary treatment. Soy hull consumption slightly improved some measures of glucose tolerance, with results varying between the studies. Consumption of 52 g corn bran decreased very low-density lipoprotein cholesterol, triglycerides, and glycosylated Hb, but subject tolerance was poor with the particle size used. Consumption of 52 g apple powder increased low-density lipoprotein and total cholesterol levels.

Severe zinc deficiency: effects on the distribution of nine elements (potassium, phosphorus, sodium, magnesium, calcium, iron, zinc, copper and manganese) in regions of the rat brain.

The effect of severe zinc deficiency on the distribution of nine elements (potassium, phosphorus, sodium, magnesium, calcium, iron, zinc, copper and manganese) in brain regions (olfactory lobes, right and left hippocampi, cerebellum and the rest of the brain) has been studied. After male rats (30 days old) were fed a zinc-deficient diet for 28 days, the zinc concentration of most brain parts was similar to zinc-adequate control values. Olfactory lobe zinc, on the other hand, was slightly depressed. However, the levels of other metals were dependent on zinc nutriture. Zinc deficiency caused an elevation in copper concentrations in most brain parts. Restriction of food intake caused a similar increase in brain copper but generally the effect was less than with zinc deficiency. Levels of calcium, manganese, sodium and potassium, in certain brain regions, also appeared to be altered by the zinc status of an animal. Of the minerals examined, only zinc and copper displayed asymmetrical distribution between the right and left hippocampus, and severe zinc deficiency did not affect lateral distribution of these trace metals in the hippocampus. The data suggest the hypothesis that changes in brain metal content, associated with zinc deficiency, contribute to the behavioral abnormalities that occur.

Effect of a moderate increase in dietary protein on the retention and excretion of Ca, Cu, Fe, Mg, P, and Zn by adult males.

Mineral utilization was studied by metabolic balance techniques in 10 healthy male volunteers fed diets containing 65 and 94 g protein. Both diets contained approximately 650 mg calcium, 1 mg copper, 16 mg iron, 250 mg magnesium 1000 mg phosphorus, and 7 mg zinc. The diet consisted of conventional foods; the additional 29 g protein was egg white protein mixed into a beverage and fed twice per day. Plasma mineral levels were not affected by the increase in dietary protein. When the diet provided 94 g of protein, urinary calcium and zinc were slightly, but significantly, increased by an average of 35 mg (p less than 0.05) and 0.15 mg (p less than 0.001), respectively. Apparent mineral absorption and balance were unchanged by this modest increase in dietary protein.

Effect of ascorbic acid on copper and cholesterol in adult cynomolgus monkeys fed a diet marginal in copper.

The effects of prolonged consumption of high levels of dietary ascorbic acid on copper metabolism and cholesterol in adult monkeys fed a diet low or marginal in copper were investigated. Small reductions in serum copper and in serum ceruloplasmin levels were observed when high levels of ascorbic acid were fed. During the period of copper depletion there was a gradual but significant (p less than 0.001) increase in serum cholesterol. The level of ascorbic acid supplementation had no effect during this phase. When copper was added back to the diet, serum cholesterol levels leveled off or declined in the monkeys receiving the low (1 mg/day/kg body weight) dose of ascorbic acid. Cholesterol levels continued to increase in the group receiving the higher ascorbic acid supplement (25 mg/day/kg body weight). These data suggest that high levels of ascorbic acid supplementation may make dietary copper relatively unavailable for regulating cholesterol metabolism.

Effect of vitamin C on copper and iron metabolism in the guinea pig.

Although interaction of vitamin C, copper and iron have been studied in several species, little is known about these interactions in species which require the vitamin in the diet. Young male Hartley guinea pigs were fed a basal diet, or a basal diet and supplemented daily with vitamin C, p.o. Pharmacologic doses (25 mg per 100 g BW per day) of vitamin C resulted in two-to-three-fold decreases in liver copper, when compared with those receiving normal (0.5 mg per 100 g BW per day) intakes. Under conditions of vitamin C deficiency, serum copper and ceruloplasmin were elevated along with liver copper. Serum and hepatic iron levels, hepatic microsomal cytochrome P-450 and cytochrome b5, and blood heme parameters all appeared to be directly related to vitamin C intake, i.e. the iron and heme parameters increased as the vitamin dose increased. These data are consistent with the hypothesis that interaction between vitamin C, copper and iron influence normal heme formation through the oxidation/reduction of iron and/or by regulating iron absorption and availability at the gut level.