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Two 6-wk double-blind studies evaluated the effects of supplements of 2 or 3 mg Cu/d on serum copper, ceruloplasmin, red-blood-cell super oxide dismutase (RBC-SOD), total serum cholesterol, and serum lipoprotein-cholesterol fractions in adult males. Study I had 6 supplemented and 8 placebo subjects, whereas study II had 7 and 6, respectively. Copper supplementation did not appear to affect serum copper levels, RBC-SOD, hematocrit, and ceruloplasmin levels when assayed by radial immunoassay diffusion. Supplementation with 2 mg Cu/d produced an increase in LDL cholesterol and the percentage of cholesterol as LDL at wk 4 compared to the placebo group, and a concomitant decline in VLDL-cholesterol levels and the percentage of cholesterol as VLDL. At wk 6, the percentage of cholesterol as LDL increased and that of cholesterol as VLDL decreased compared to baseline values in the supplemented group. Supplements of 3 mg Cu/d increased hemoglobin levels, ceruloplasmin activity, and serum total-cholesterol levels at wk 6 compared to placebos. Differences in cholesterol may be partly explained by variability in the placebo groups in both studies. Copper supplementation effects on cholesterol deserves further investigation.

Histological aspects of Cu-deficient hypertrophied rat hearts were evaluated to determine causal factors. Twenty-four male weanling rats were fed either Cu-adequate (8.0 mg/kg diet) or Cu-deficient (0.4 mg/kg diet) diets until 9 or 11 wk of age. Copper-deficient rats had increased mitochondrial:myofibrillar ratios compared with Cu-adequate rats. Mitochondria were vacuolated. Cristae seemed fragmented and matrix seemed translucent and they tended to distort the myofibrils. Glycogen granules and lipid droplets were more frequently observed in Cu-deficient rats. When the Cu-deficient rats were examined separately, the larger hearts in the older rats had smaller mitochondrial:myofibrillar ratios, but had larger myofibrillar volume densities. Valves from Cu-deficient rats had less connective tissue and seemed fragmented in areas. In 9-wk-old Cu-deficient rats, there was a negative correlation between heart: body weight ratios and bicuspid valve scores, whereas 11-wk-old rats demonstrated the same relationship for tricuspid valves with myofibril volume density. These results suggest that there are two components contributing to cardiac hypertrophy in copper deficient rats: 1) an enlarged mitochondrial area and 2) myofibrillar enlargement. Hematocrit values did not seem to be related to cardiac hypertrophy.

A variety of behaviors was assessed in Long-Evans male rats placed on either a low copper diet, a marginal copper diet, or an adequate copper diet at weaning. Rats in the low copper group had slightly, but significantly, enlarged hearts and gained less weight than rats fed diets containing higher copper levels. Treatment effects were not detected in measurements of muricide, open-field activity, water intake, shock sensitivity, and shock avoidance and memory.

The relationship of copper and zinc status with blood pressure in young adults was studied (N=59). Copper and zinc status was assessed through analysis of serum, urine, hair, and diet records. Males (N=27) had greater systolic and pulse pressures than females (N=32). Multiple regression analysis suggested that males and higher caloric and dietary copper intakes were the predominant factors associated with higher systolic and diastolic pressures, whereas higher dietary zinc intakes were associated with lower pressures. Higher urine zinc excretion rates and serum zinc concentrations were associated with higher diastolic pressures. The sex variable was the strongest factor affecting pulse pressures, with males having higher pulse pressures. Serum zinc concentrations had an inverse relationship to pulse pressures. The data suggest that the weight/height index and age had a low association with blood pressure in this normotensive sample.

The effect of copper deficiency on liver, cardiac and adipose fatty acids was studied in the Long-Evans rat. Rats were fed diets adequate in copper (8.5 mg Cu/kg diet, group AC, n = 10) or with no added copper (0.4 mg Cu/kg diet, group NC, n = 9) or were pair-fed an adequate copper diet in amounts eaten by group NC rats (group PF, n = 10), from weaning until 8 wk thereafter. Group NC rats exhibited typical copper deficiency signs such as decreased body weight, hematocrit and liver copper levels but increased heart/body weight ratios. Adipose and cardiac triglycerides of group NC rats had greater 18:0 to 18:1n-9 ratios. All tissues in group NC rats had higher levels of longer-chain polyunsaturated fatty acids in triglycerides than those in AC or PF rats. Specifically, the following triglyceride fatty acids were in greater concentration in NC rats than in AC or PF rats: for liver, 18:2n-6, 22:5n-6, 22:5n-3 and 22:6n-3; for cardiac, 20:3n-6, 20:4n-6 and 22:5n-6. Liver phospholipids had lower levels of 20:4n-6 in NC rats than in AC or PF rats. These results suggest that copper deficiency results in the accumulation of both n-3 and n-6 longer-chain polyunsaturated fatty acids in triglycerides of various tissues.

A 12-wk double-blind study was conducted to determine the effect of oral zinc supplementation upon serum total cholesterol, lipoprotein-cholesterol fractions, and serum triglycerides in white males. The subjects were randomly assigned to one of three treatment groups and consumed either a placebo tablet (n = 9), 50 mg Zn/d (n = 13), or 75 mg Zn/d (n = 9) as Zn gluconate. Serum total cholesterol, low-density-lipoprotein (LDL) cholesterol, very-low-density-lipoprotein (VLDL) cholesterol, and triglycerides were not affected by Zn supplements. However, serum high-density-lipoprotein (HDL)-cholesterol levels in subjects assigned to the 75 mg Zn/d group were significantly lower at weeks 6 and 12 than those for the placebo group and lower at weeks 6, 8, and 12 than at baseline; subjects assigned to the 50 mg Zn/d group had lower serum HDL-cholesterol levels at week 12 than did the placebo group and lower at week 12 than at base line.

The effect of copper and sodium intake upon liver cholesterol concentrations, fatty acid profile, and mineral concentrations were studied in the Long-Evans rat. Forty-eight male weaning rats were divided into three groups of 16 each and fed a semipurified diet containing either 0, 3, or 8 mg of added copper/kg of diet. At 100 d of age, half of the animals in each group were given 1% NaCl as drinking water and the other half was given deionized-distilled water for 12 wk. Copper deficiency in rats produced elevations in liver palmitate and oleate concentrations, but decreases in linoleate concentrations. The ratio of oleate:stearate was higher in copper deficient rats. Liver copper levels were decreased, but liver iron concentrations were elevated in copper deficient rats. Sodium intake did not have an effect on any of the parameters studied. These results suggested that dietary copper deficiency alters both liver mineral and fatty acid composition.

Seven western states (Arizona, California, Idaho, Nevada, New Mexico, Oregon, and Wyoming) were surveyed in 1986 to determine the extent of vitamin/mineral supplementation and dosage levels of single supplements. Questionnaires were mailed to 3,500 individuals. A 57.8% response rate was obtained from the deliverable surveys, with a sample size of 1,730. The sample consisted of 54% women and 46% men and was predominantly white (88.9%). Fifty-four percent of the sample consumed some type of supplement; multiple vitamin/minerals were consumed with the greatest frequency. For single supplements, vitamin C was reported with the greatest frequency (23.1%), followed by some type of calcium supplement (22.5%) and vitamin E (11.1%). More than 80% of the vitamin C users indicated a dosage of 250 mg/day. Most respondents consumed calcium dosages of less than 1,000 mg/day. For vitamin E, 75% of the users consumed more than 200 IU/day. The data suggest that the potential for toxicity due to excess supplementation levels exists in the western states studied.

Myofibrillar and nonmyofibrillar proteins from hearts of copper-adequate (n = 9) and copper-deficient (n = 10) rats were compared. Male weanling Long-Evans rats were fed copper-deficient or copper-adequate diets for 9 wk. Twelve additional rats were fed similar diets and cardiac tissue was evaluated by transmission electron microscopy. Ventricular myocytes were glycerinated and homogenized in 0.1 M KCl and 1.5% Triton X-100, and suspensions were centrifuged at 1100 x g. The supernatant was removed and designated Triton X-100-soluble non-myofibrillar protein, and the pellet was resuspended and recentrifuged several times to obtain myofibrillar protein. Sodium dodecyl sulfate--polyacrylamide gel electrophoresis (SDS-PAGE) analysis was conducted on both protein fractions. Densitometer scans of SDS-PAGE pherograms of myofibrillar protein revealed no significant difference between copper-adequate and copper-deficient groups. Similar analysis of nonmyofibrillar protein revealed a consistent decrease or diminished level of a 23-kDa polypeptide among copper-deficient rat hearts. These results may be consistent with the findings that demonstrated fragementation of mitochondrial cristae and an increased area occupied by mitochondria in copper-deficient rat hearts.

This study investigated the relationships between mineral elements and Prader-Willi syndrome (PWS) and determined which minerals, if any, separated a group of PWS individuals (N = 19) from a non-PWS mentally retarded control group (N = 60). The PWS group had significantly raised hair magnesium levels and significantly lower hair silicon levels than controls. The PWS group was also elevated in hair calcium, magnesium, and copper in relation to laboratory standards, while their hair silicon, chromium, and lithium levels were deficient in relation to laboratory norms. Discriminant function analysis revealed that by using 16 hair minerals subjects could be correctly classified as PWS or non-PWS with 89.5% and 95.0% accuracy, respectively. It is concluded that continuing research is needed to study the relationship between mineral element patterns and PWS.

A variety of behaviors was measured in adult Long-Evans male rats fed ground rat chow containing either no added aluminum, low aluminum (1500 mg/kg), moderate aluminum (2500 mg/kg), or high aluminum (3500 mg/kg). There were no effects of aluminum on either body weight or mouse killing. There was an inverse relationship between brain aluminum and open-field activity. Elevated brain aluminum was correlated with relatively poor performance on a single-trial passive-avoidance task and on a visual discrimination with reversal task.