Growth effects of vanadium in the rat.

Vanadium is necessary for growing rats raised inside trace elementcontrolled, all plastic isolators on a highly purified amino acid diet. Addifion of vanadium to the diet enhances growth by over 40 percent. A nearly optimum effect is obtained with 10 micrograms of vanadium per 100 grams of diet in (0.1 part per million), supplied in the form of sodium orthovanadate, as seen from series of tests with levels ranging from 1 to 5 micrograms per 100 grams of diet. Different vanadium compounds show different potencies: sodium orthovanadate was effective, metavanadate less active, and pyrovanadate without activity. Tetravalent vanadium, supplied as vanadyl sulfate or acetate, was utilized but produced smaller responses. The amounts of vanadium required are those normally found in tissues and nutrients.

Copper intake and assessment of copper status.

The diagnosis of marginal copper deficiency has not been perfected despite an increased understanding of the physiologic roles of copper. The use of nonstandardized procedures and the effects of factors other than copper nutriture have impeded identification of an ideal indicator of copper nutritional status in humans. A review of studies of experimental copper deprivation conducted in adult humans over the past 12 y indicated that between 1.0 and 1.25 mg Cu/d is needed by adults for copper maintenance for periods of up to 6 mo and that < or = 2.6 mg Cu/d for periods of up to 42 d is not sufficient for recovery from copper deprivation. Copper-containing enzymes in blood cells, such as erythrocyte superoxide dismutase and platelet cytochrome-c oxidase, may be better indicators of metabolically active copper and copper stores than plasma concentrations of copper or ceruloplasmin because the enzyme activities are sensitive to changes in copper stores and are not as sensitive to factors not related to copper nutriture.

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.

Effects of age and sex on copper absorption, biological half-life, and status in humans.

Healthy, free-living men and women aged 20-83 y (n = 127) were studied to determine the effects of age and sex on copper absorption, biological half-life (BH), and status. Copper absorption was greater in women (71%) than in men (64%) aged 20-59 y (P = 0.02), but did not differ in men and women aged 60-83 y. BH of 67Cu ranged from 13 to 33 d and differed between men and women aged 20-59 y (P = 0.006), but not between men and women aged 60-83 y. Plasma copper, enzymatic ceruloplasmin (Cp), and immunoreactive (RID) Cp were significantly higher in women than in men (P < 0.005), but superoxide dismutase (SOD) and in vitro 67Cu uptake by red blood cells did not differ. Plasma copper, RID Cp, and cytochrome oxidase in platelets and mononuclear cells were significantly affected by age (P < 0.005). Oral contraceptives elevated plasma copper, enzymatic Cp, and SOD activity but not copper absorption and BH in women aged 20-39 y. Copper intake from self-selected diets was 0.9-1.2 mg/d for women and 1.2-1.3 mg/d for men, but net copper absorption (micrograms Cu.kg body wt-1.d-1) did not differ. Thus, dietary copper intake requirements may differ between men and 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.

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.

Folate status of adult males living in a metabolic unit: possible relationships with iron nutriture.

Folate and iron status was monitored at monthly intervals in 40 adult males who were living in a metabolic unit for 2 to 8 months and consuming diets containing 150 to 250 micrograms of folate per day. There were significant (p less than 0.02) declines in hematocrit, serum folate, and serum ferritin. Men who participated in studies for 6 months or more or those with initial serum folate levels more than 10.5 ng/ml and erythrocyte folate levels more than 481 ng/ml also exhibited a highly significant (p less than 0.001) decline in red blood cell folate. Men with erythrocyte folate below 480 ng/ml or serum folate below 10 ng/ml and who participated in the studies for less than 5 months showed little or no change in folate status. The findings may reflect adjustments in body folate to reflect dietary intakes. Also a folate intake of 200 +/- 68 micrograms/day appeared to be adequate for maintenance of folate stores in adult males. A correlation between iron stores and folate status was also observed. However, this relationship may be coincidental.

Maximal oxygen consumption as related to magnesium, copper, and zinc nutriture.

Forty-four healthy male university athletes and 20 untrained men underwent maximal treadmill exercise testing to determine the relationship between maximal oxygen consumption and various measurements of elemental nutriture. Hb and mean plasma and erythrocyte concentrations of magnesium, copper, and zinc were within established norms for both groups after a 12-h fast. Mean plasma copper concentration was significantly (p less than 0.01) higher in the athletes (90 +/- 14.3 versus 81 +/- 8.0 micrograms/dl). Average maximal oxygen consumption also was significantly (p less than 0.001) higher in the athletes [4.5 +/- 0.5 versus 3.3 +/- 0.6 L/min and 55.5 +/- 7.1 versus 47.0 +/- 6.0 ml/(kg x min)]. Plasma magnesium was significantly correlated (r = 0.46; p less than 0.002) with maximal oxygen consumption, ml/(kg x min), among the athletes. This relationship persisted when the effect of Hb concentration was removed by covariance analysis (p less than 0.005). Only a weak association (r = -0.32; p = 0.17) was found between oxygen consumption and plasma magnesium in the untrained men. We hypothesize that ionic magnesium may facilitate oxygen delivery to working muscle tissue in trained subjects.

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.

Iron status and brain function: serum ferritin levels associated with asymmetries of cortical electrophysiology and cognitive performance.

Levels of serum ferritin and iron were examined in relation to cognitive performance and quantitative EEG measures in 69 normal university students. Higher levels of serum ferritin were associated with greater activation of the left hemisphere relative to the right, indicated by less power in the EEG spectra from left hemisphere electrodes. Iron status was significantly related to cognitive performance on two of the cognitive tasks, and these relationships were consistent with the EEG asymmetries: higher ferritin predicted greater verbal fluency but poorer nonverbal auditory task performance. These results suggest that body iron stores are relevant to specific neurophysiological processes supporting attention.

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.

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.

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 dietary zinc on whole body surface loss of zinc: impact on estimation of zinc retention by balance method.

Whole-body sweat losses of zinc were studied in men during three separate studies on the effects of marginal intake of zinc. Zinc lost via the sweat appeared to be directly related to dietary zinc intake. Whole body zinc losses of an average of 0.49 mg/day were observed in the men during the control period when zinc intakes averaged 8.3 mg/day. On the other hand, when zinc intakes were 3.6 mg/day, whole body surface zinc losses were substantially lower, averaging 0.24 mg/day in two of the studies and slightly lower than control values in the third study. A loss of 0.62 mg of zinc/day was observed when 33.7 mg of zinc was fed. These losses reduced apparent balances by 12 to 84% and need to be considered when evaluating zinc retention. When men were eating the diets with marginal levels of zinc (3.6 mg/day), zinc losses in sweat gradually declined with time. This suggested a homeostatic mechanism to conserve zinc during periods of depletion.

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.

Homeostatic control of zinc metabolism in men: zinc excretion and balance in men fed diets low in zinc.

Zinc metabolism was studied in 11 men. The study began with 28-d equilibration when dietary zinc was 159 mumol/d (X), followed by 35-d periods when the diet contained 21.9 (I), 37.5 (II), 51.6 (III), or 67.8 (IV) mumol Zn/d in random order, and ended with 35 d with X. The diet was conventional foods and egg white protein. Zinc balance, including surface and semen losses, was zero only during I. Semen zinc was unaffected by diet. Plasma zinc dropped to 0.44 and 0.49 mumol/L in two subjects during I and was significantly decreased during I compared with X (P < 0.0002). Urinary zinc declined with decreasing zinc intake. A combination of urinary and plasma zinc criteria from Baer and King (Am J Clin Nutr 1984; 39:556-70) could be used to distinguish stages of zinc deficiency. By these criteria, no subjects were deficient during IV, one was marginally deficient during III, three were marginally deficient during II, and seven were deficient during I.

Whole body surface loss of trace metals in normal males.

Whole body surface losses of zinc, copper, and iron were measured in 13 male volunteers who lived in a controlled environment for 4 to 9 months. For 88 daily samples, the mean losses for zinc, copper, and iron were 0.50, 0.34, and 0.33 mg/day (3.9, 26, and 2.1% of the mean dietary intakes, respectively). There was a large variance in metal losses with no significant differences in variance within-versus-between subjects or on the same-versus-different diets. The surface losses of zinc and iron increased the apparent dietary requirements determined by balance measurements only 5 and 3%, respectively, while the increase in copper requirement due to surface loss was 25 to 30%.

The effect of temporary venous occlusion on trace mineral concentrations in plasma.

The effects of short-term venous occlusion on plasma concentration of trace minerals--zinc, iron, and copper--were studied in normal volunteers. In one experiment, antecubital vein blood samples were drawn simultaneously from both arms of 14 subjects while their left arms remained free and their right arms had been occluded from 60 s at 40 mm Hg pressure. Statistical comparison of paired samples showed a significant increase in zinc (p less than 0.05) and iron (p less than 0.001), but not copper concentrations in plasma from the occluded extremity. The mean increase in concentration in the right (ligated) arms with respect to the left (unligated) arms was 3.7 and 24.6%, for zinc and iron, respectively. In a second experiment, simultaneous blood samples were drawn from five subjects with neither arm occluded. No significant difference between right and left was observed. Thus, application of tourniquets during the sampling of venous blood for trace mineral analysis introduces a nonrandom factor. Standardization of sampling techniques is essential to overall reliability of trace mineral determinations.

Influence of type and amount of dietary lipid on plasma lipid concentrations in endurance athletes.

Changes in plasma total cholesterol, triglyceride, and lipoprotein concentrations were assessed in three male endurance cyclists who consumed isoenergetic diets for 28-day periods in which carbohydrate, polyunsaturated fat, or saturated fat contributed about 50% of the daily energy intake. Dietary cholesterol was similar among the diets. Maximal aerobic capacity was maintained at 62 ml O2/(kg X min). Body weights were held within 3% of admission levels. The polyunsaturated fat diet significantly (p less than 0.05) reduced mean fasting plasma total cholesterol in comparison to the saturated fat and carbohydrate diets (160 versus 254 and 243 mg/dl, respectively). Similarly, the polyunsaturated fat diet depressed (p less than 0.05) mean plasma triglycerides relative to the saturated fat and carbohydrate diets (37 versus 62 and 79 mg/dl, respectively). No significant dietary effects were seen on high-density lipoprotein cholesterol. The observed changes in plasma total cholesterol were not significantly different than the values predicted by the Keys' equation, delta CHL = 1.35(2 delta S-delta P) + 1.5 delta Z. We conclude that under controlled conditions in which physical activity is constant l) dietary lipid differences influence fasting serum lipid and lipoprotein concentrations among men with high energy expenditures, and 2) the Keys' equation gives useful predictions of changes in plasma total cholesterol among vigorous men consuming different types and amounts of dietary lipid.

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.