Plasma Copper Concentrations Research Articles

Changes in zinc and copper concentrations in breast milk and blood of Japanese women during lactation.

To evaluate the changes in zinc and copper concentrations in breast milk and maternal blood during lactation, milk and blood samples were obtained from 80 lactating women during the period between 2 and 201 days of lactation. Zinc and copper concentrations were measured by atomic absorption spectrophotometry. Breast milk zinc and copper concentrations markedly decreased during the first few weeks of lactation and gradually declined for the remaining period. Mean values of milk zinc and copper levels were 1.76 and 0.29 micrograms/ml, respectively, between 15 and 84 days after parturition and were 0.76 and 0.19 microgram/ml between 85 and 201 days of lactation. Calculated daily intakes of these minerals for infants from breast milk were markedly lower than those of US Recommended Dietary Allowances. Plasma zinc levels of lactating mothers increased as lactation progressed, whereas erythrocyte zinc and plasma copper concentrations decreased. Plasma zinc and copper and erythrocyte zinc values returned to normal approximately three months after parturition.

The influence of high dietary protein, energy and mineral intake on deficient young camel ( Camelus dromedarius)—II. Changes in mineral status

1. 1. Mangrove Avicennia marina is poor in some trace elements such as copper, zinc and manganese. In a trial we used 32 young camels divided into four groups. 2. 2. Groups 1 and 3 were supplemented with copper and zinc in drinking water after 1 month of mangrove feeding. 3. 3. Groups 2 and 3 received concentrate rich in protein and energy. The supplementation was stopped after 2 months. 4. 4. All the camels were deficient in trace elements at the beginning of mineral supplementation. 5. 5. The plasma concentration of copper increased significantly up to normal levels (<70 μg/100 ml) in energy protein supplemented groups, but the quantity supplied (100 mg of copper sulphate/day) was not sufficient to maintain this level after the end of supplementation. 6. 6. The original zinc deficiency was too severe to observe a significant effect of the mineral supplementation. 7. 7. Calcium, magnesium and phosphorus levels were improved during the supplementation period in protein-energy supplemented groups. 8. 8. A high interaction between mineral absorption and quality of the diet was observed. A well-balanced diet seems essential to avoid deficient mineral status.

Trace element status in vegetarians from Southern India

Trace element status in 83 vegetarians from southern India was studied by measuring the concentration of zinc, copper, magnesium and selenium in plasma and hair, and the content of mercury, lead and cadmium in hair, results being compared with those obtained in 47 Swedish controls on mixed diet. Of plasma values among the vegetarians, those for zinc were significantly lower than those among controls, and those for magnesium significantly higher; plasma copper values were significantly higher among female vegetarians and significantly lower among male vegetarians than among the respective control subgroups; the vegetarians' plasma concentrations of zinc, copper and magnesium peaked at 30–40 years of age, and then declined; their plasma zinc concentrations were negatively correlated to their plasma copper concentrations, and positively correlated to body weight and height. Of hair values among the vegetarians, those for zinc were similar to those of controls, but those for copper, magnesium, selenium, mercury, lead and cadmium were significantly higher. There were no correlations between hair and plasma values. It is concluded that the traditional vegetarian diet of Hindus in southern India suffices to maintain adequate trace element status except for zinc.

Plasma zinc, copper, selenium, ferritin and whole blood manganese concentrations in children with kwashiorkor in the acute stage and during refeeding.

Plasma zinc, copper, selenium, ferritin and whole blood manganese concentrations were measured in 22 children with kwashiorkor on admission to hospital and on days 5, 10 and 30 of refeeding. Twenty similarly aged, healthy, well nourished children served as controls. The mean (SEM) zinc, copper and selenium concentrations of 7.5 (0.93), 10.8 (0.64) and 0.29 (0.02) mumol/l, respectively, in the children with kwashiorkor on admission were all significantly lower than the values of 13.7 (0.66), 25.6 (1.72) and 0.72 (0.04) mumol/l in the controls. In contrast, the erythrocyte manganese level of 1.67 (0.09) micrograms/gHb and the median ferritin concentration of 293 micrograms/dl were significantly higher than in the controls. After 30 days there was full clinical recovery with significant weight gain and a return of the plasma albumin, caeruloplasmin, copper and ferritin to normal. However, manganese remained elevated and zinc and selenium concentrations remained significantly low. Our results suggest that nutritional rehabilitation of children with kwashiorkor is incomplete by 30 days and cannot be judged purely by a return of the plasma proteins to normal. Addition of selected trace elements to the diet may hasten full recovery.

Plasma zinc and copper concentrations in rheumatoid arthritis: influence of dietary factors and disease activity

Forty patients with rheumatoid arthritis performed a thorough 7-d diet recording. The food diaries were analyzed together with clinical and laboratory data by means of stepwise multiple linear regression to clarify the effects of both diet and the inflammatory disorder on the plasma concentrations of zinc and copper. The patients' daily dietary intakes of zinc and copper (24.3 +/- 7.54 and 3.48 +/- 1.55 mg/MJ) were comparable to the corresponding intakes in the ordinary Finnish diet (24.0 and 3.68 mg/MJ). In multivariate analyses the best predictors of plasma trace elements were the measures of disease activity and not the dietary factors. As an exception to this, there was a strong correlation between plasma copper-copper intake ratio and zinc intake both in univariate (r = -0.638, P less than 0.001) and multivariate analysis. This suggests that zinc depresses copper absorption with intakes in normal, physiological ranges.

Copper, Zinc, Manganese, and Magnesium Status and Complications of Diabetes Mellitus

To evaluate copper, zinc, manganese, magnesium, and other indices of peroxidative status in diabetic and nondiabetic human subjects. Convenience sample of 57 insulin-dependent or non-insulin-dependent diabetic subjects recruited from the diabetes clinic of the University of California, Davis, Medical Center and 28 nondiabetic subjects recruited from the staffs of the Departments of Internal Medicine and Nutrition. Individuals conducting laboratory analyses were blind to subject group. A fasting blood sample was collected from all subjects and appropriately processed for future analyses. A 24-h urine collection was obtained in a subset of subjects. Hyperzincuria and hypermagnesuria were evident in diabetic subjects compared with control subjects. There were no differences in plasma magnesium or whole-blood manganese between groups. Plasma copper was higher and plasma zinc was lower in diabetic than in control subjects. When data were viewed with respect to specific diabetes-associated complications, diabetic subjects with retinopathy, hypertension, or microvascular disease had higher plasma copper concentrations compared with both diabetic subjects without complications and with control subjects. There were no significant differences between control and diabetic subjects in erythrocyte copper-zinc superoxide dismutase activity or whole-blood glutathione peroxidase or glutathione reductase activities. Plasma peroxide concentrations were higher in diabetic than control subjects. Diabetes can alter copper, zinc, magnesium, and lipid peroxidation status. Perturbations in mineral metabolism are more pronounced in diabetic populations with specific complications. It is not known whether differences in trace element status are a consequence of diabetes, or alternatively, whether they contribute to the expression of the disease.

Copper Uptake and Retention in Liver Parenchymal Cells Isolated from Nutritionally Copper-Deficient Rats

Copper uptake and retention were studied in primary cultures of liver parenchymal cells isolated from copper-deficient rats. Male Sprague-Dawley rats were fed a copper-deficient diet (less than 1 mg Cu/kg) for 10 wk. Copper-deficient rats were characterized by low copper concentrations in plasma and liver, anemia, low plasma ceruloplasmin oxidase activity and increased 64Cu whole-body retention. Freshly isolated liver parenchymal cells from copper-deficient rats showed a higher 64Cu influx, which was associated with a higher apparent Vmax of 45 +/- 4 pmol Cu.mg protein-1.min-1 as compared with 30 +/- 3 pmol Cu.mg protein-1.min-1 for cells isolated from copper-sufficient rats. No significant difference in the apparent Km (approximately 30 mumol/L) was observed. Relative 64Cu efflux from cells from copper-deficient rats was significantly smaller than the efflux from cells from copper-sufficient rats after prelabeling as determined by 2-h efflux experiments. Analysis of the medium after efflux from cells from copper-deficient rats showed elevated protein-associated 64Cu, suggesting a higher incorporation of radioactive copper during metalloprotein synthesis. Effects of copper deficiency persist in primary cultures of parenchymal cells derived from copper-deficient rats, and short-term cultures of these cells offer a prospect for the study of cell biological aspects of the metabolic adaptation of the liver to copper deficiency.

The effect of dietary vitamin E deficiency on plasma zinc and copper concentrations

Vitamin E and zinc have a number of functions in common, including membrane stabilisation, antioxidant function and modulation of prostaglandin metabolism. Previous studies have shown vitamin E malabsorption during zinc depletion and it appears that there is an interaction between the two nutrients. In this study we have investigated whether vitamin E deficiency affects zinc and copper concentrations in experimental animals. Male Wistar rats were maintained on a vitamin E deficient diet for either 6 or 10 months. At the end of the experimental period all animals had undetectable plasma vitamin E levels and increased red cell fragility. Plasma zinc concentrations were significantly reduced in all vitamin E deficient animals compared to control rats (p<0·002) and copper levels were reciprocally elevated (p<0·002). It appears likely that decreased zinc levels may represent redistribution of circulating zinc to tissues and cells as a secondary antioxidant, or for membrane stabilisation or prostaglandin synthesis.

Influence of hypertension and dietary copper on indexes of copper status in rats.

The Dahl salt-sensitive rat was used to investigate the effect of hypertension on indexes of copper status and to determine the extent to which dietary manipulation of copper attenuated, or exacerbated, the rate of sodium chloride-induced hypertension. Weanling salt-sensitive rats were fed, in a 2 x 3 factorial design, one of six diets that contained one of three levels of copper (2.0 micrograms/g marginal, 12 micrograms/g adequate, or 50 micrograms/g supplemental) and either control (0.4%) or high (4%) levels of sodium. Diets were fed to the rats for 11 weeks. Rats fed the high sodium diets were characterized by high plasma copper concentrations and ceruloplasmin activities compared with their respective control sodium rats. The magnitude of the sodium-induced rise in plasma copper and ceruloplasmin was affected by dietary copper intake; however, dietary copper intake had no effect on the development of hypertension in the high sodium groups. These results suggest that altered copper metabolism is secondary, rather than primary, to the development of sodium chloride-induced hypertension in the salt-sensitive rat. Red blood cell superoxide dismutase activity was reduced in rats fed the low copper diets compared with the adequate and supplemented copper groups. At the lower levels of copper intake, sodium chloride-induced hypertension increased red blood cell superoxide dismutase activity in a manner consistent with the plasma copper and ceruloplasmin changes observed. However, at adequate or supplemental levels of dietary copper, red blood cell superoxide dismutase activity plateaued, suggesting possible saturation of copper at sites of hematopoeisis.

Reduced Erythrocyte Superoxide Dismutase Activity in Low Birth Weight Infants Given Iron Supplements

Erythrocyte superoxide dismutase (ESOD) activity reflects copper utilization and the risk of copper deficiency. To investigate the possible effects of inorganic iron on the metabolism of copper in low birth weight infants, we have measured ESOD activities in three groups of infants receiving different iron supplements. Fifty-five low birth weight infants were randomly assigned to receive daily from 28 d either 13.8 mg (HiFe), 7 mg (MidFe), or no elemental iron (NatFe) as iron edetate. At 27 d, 8, 12, and 20 wk postnatal age, infants were weighed and measured and hematologic indices, plasma ferritin, zinc, and copper concentrations, and ESOD activities were assayed. Anthropometrical and hematologic indices and plasma copper and zinc concentrations did not differ among treatment groups at any time, but at 20 wk, plasma ferritin concentrations [(micrograms/L) mean; SD] were lower in the NatFe group (17; 2.0) than in the HiFe group (32; 1.9: 95% confidence interval for mean difference 6.6 to 22.0, p less than 0.01). ESOD activities (U/g Hb) were similar in HiFe (1447; 263), MidFe (1552; 322), and NatFe (1538; 382) groups at 27 d, but by 20 wk activities in the HiFe group (1537; 211) were lower than in the MidFe (1789; 403: 95% confidence interval 38 to 466, p less than 0.05) and NatFe (1858; 304: 95% confidence interval 150 to 492, p less than 0.01) groups. The lower ESOD activities found in the HiFe group at 20 wk may reflect altered copper metabolism induced by the iron supplement, but the clinical importance of this observation is unknown.

Effect of intravenously administered tetrathiomolybdate on plasma copper concentrations of Copper-loaded sheep

Chronic copper toxicity was induced in 14 ewes in two groups by oral dosing with CuSO4. Copper dosing was stopped in sheep of groups 1 and 2 at the first rise of serum acid phosphatase activity and on the first day of haemolysis, respectively. Thiomolybdate was administered intravenously (i.v.) to sheep of group 2 at the rate of 100 mg on the first day of haemolysis and at 24-h intervals, with a maximum of 3 doses during haemolysis. Thiomolybdate was also given intravenously at a dose of 50 mg twice weekly for 11 weeks to four sheep of group 1 after the cessation of copper dosing (group 1B) and to five sheep of group 2 at the end of haemolysis. Plasma copper concentration was determined before and 24 h after each injection of 50 mg thiomolybdate and "elevations" of plasma copper concentration were seen after each injection of thiomolybdate. The differences between plasma copper concentrations observed before and after each thiomolybdate injection for doses 1 to 11 were significantly higher than those seen for doses 12 to 22. Following thiomolybdate administration, the copper content of the liver of sheep in groups 1B and 2 was reduced much more than in sheep of group 1A, in which copper dosing also ceased but which did not receive thiomolybdate. It was concluded that the high plasma copper response to thiomolybdate doses 1 to 11 was due to an influx of copper into the bloodstream from the heavily copper-loaded liver cells. The lower plasma copper response during the latter part of thiomolybdate administration was due to a gradual reduction in the amount of copper entering the bloodstream from the liver cells, as these cells became depleted of copper. Some of this copper may become part of the glomerular filtrate and be taken up by the cells of the proximal convoluted tubules of the kidney or may be excreted in the urine.

Oral copper supplementation: effect on copper and zinc balance during acute gastroenteritis in infants

To evaluate the effect of copper supplementation during recovery from acute diarrhea, we randomly assigned 14 hospitalized infants to receive either 80 micrograms copper sulfate.kg body wt-1.d-1 or a placebo. Metabolic balance and plasma copper and zinc concentrations were measured before randomization (period 1) and 6 d after admission (period 2). Fifteen control subjects were studied after respiratory illness. Fecal copper was not affected by supplementation; fecal zinc during period 2 rose significantly only in the copper-supplemented group. Copper retention was significantly higher in the supplemented infants; plasma concentrations increased for period 2 but were similar to those in the placebo group. Zinc concentrations improved over time in both groups but zinc retention was higher in the placebo group for period 2. A significant interference by copper supplementation on zinc absorption was noted. Copper supplementation during the early phase of recovery from diarrhea is not recommended.

Plasma and total blood cell copper in rheumatoid arthritis

The results summarized above confirm that copper increases in the plasma and in the cell fraction of blood of RA patients, as reported in a previously published work [3]. In RA patients, the plasma copper concentration values may barely discriminate patients in remission, whereas total blood cell copper concentration seems to be more strictly correlated with the severity of the disease. Similar data were obtained studying the copper concentration in plasma and total blood cells in complete-adjuvant tail-injected female rats during the symptomatic phase of the disease [1]. In fact plasma copper concentration was found unable to discriminate severe (high score) from moderate (low score) arthritic rats, whereas the concentration of the metal in the cell fraction of blood of high score rats was found significantly higher not only when compared with control animals but also when compared with the low score group. This statistically significant increase of total blood cell copper may be the expression of an increase of the intra-cellular enzyme superoxide dismutase (SOD) although some authors have actually found a decrease of erythrocyte SOD activity in this disease [5]. Alternatively it may indicate an increase of the non-SOD-bound fraction of red cell copper, which may, in turn, suggest an increase in the non-cerulo-plasmin-bound fraction of plasma copper, which is possibly in equilibrium with the former [6].

Zinc status in human immunodeficiency virus infection

Plasma zinc and copper concentrations, erythrocyte zinc concentration, copper-zinc superoxide dismutase activity and urinary zinc concentrations were determined for control subjects and individuals with AIDS, ARC, or asymptomatic HIV infection. Significant differences among the population groups were not noted for the above parameters with the exception of plasma copper which was higher in the AIDS group than in other patient groups. These results do not support the idea that zinc deficiency is a common contributory factor of HIV infectivity or clinical expression, nor that HIV infection induces a zinc deficiency.

Dietary supplementation with t-butylhydroquinone reduces cardiac hypertrophy and anemia associated with copper deficiency in rats

The effect of dietary supplementation with the antioxidant, t-butylhydroquinone (TBHQ), on some of the cardiovascular consequences of copper deficiency was investigated. Rats were fed copper-deficient (CuD) diet containing 0.3 μg Cu/g of diet that were either nonsupplemented or supplemented with TBHQ (supplied in the dietary safflower oil at a concentration of 0.02%). Control rats were fed copper adequate (CuA) diet containing >5.0 μg Cu/g (CuA) that also were either nonsupplemented or supplemented with TBHQ. After five weeks, rats consuming CuD diet supplemented with TBHQ exihibited plasma copper concentrations, ceruloplasmin activities, and liver and heart copper concentrations that were significantly (P<0.05) lower than those of rats consuming either nonsupplemented or TBHQ supplemented CuA diet, but no different from those of rats consiming nonsupplemented CuD diet. However, rats consuming CuD diet supplemented with TBHQ had significantly (P<0.05) higher growth, hemoglobin concentrations, hematocrits, and red blood cell qistribution widths but lower heart weights than rats consuming nonsupplemented CuD diet. TBHQ supplementation had no effect on these variables in rats fed CuA diet. Thus, while TBHQ did not improve copper status, it did ameliorate the growth reduction, anemia, and cardiac hypertrophy associated with copper deficiency. These findings indirectly support the contention that oxidative damage contributes to the pathophysiological consequences of copper deficiency.

Vitamin and trace element status of women with disordered eating

We studied biochemical measures of vitamin B-6, zinc, and copper in a group of 96 women and vitamin A and vitamin E concentrations in 89 women, all suffering from an eating disorder. Twenty-three control subjects were studied. Eating-disorder patients not taking vitamin or mineral supplements had significantly higher plasma concentrations of vitamins A and E than did control subjects (also not taking supplements). No difference was found in indices indicating vitamin B-6 status or in plasma zinc or copper concentrations. Self-induced vomiting was the only significant predictor of upper-quartile vitamin A concentrations. Upper-quartile vitamin B-6 activations (indicating lower vitamin B-6 activity) were significantly predicted only by low actual body weight. These results suggest that supplementation of micronutrient intake needs only to be considered for those eating-disorder patients at low weight and then only with water-soluble vitamins.

Copper supplementation: failure to increase plasma copper and ceruloplasmin concentrations in healthy infants

Plasma copper and ceruloplasmin concentrations at ages 0, 2, 4, 6, 9, and 12 mo were longitudinally evaluated in our Finnish nutritional survey of 200 infants. The infants, who were weaned by age 3.5 mo, were randomly assigned to receive either a liquid cow-milk-based formula containing 1.3 mumol Cu/L (n = 16) or the same formula supplemented with 7.8 mumol Cu/L as Cu sulfate (n = 16). They were compared with exclusively breast-fed infants. Plasma Cu and ceruloplasmin concentrations increased steadily and similarly in all three groups from 4.6 +/- 0.2 mumol/L (means +/- SEM) and 0.9 +/- 0.1 mumol/L, respectively, in umbilical samples to 19.7 +/- 0.3 mumol/L and 3.2 +/- 0.1 mumol/L, respectively, at age 12 mo. Our results indicate that concentrations of plasma Cu and ceruloplasmin in healthy full-term infants are resistant to dietary supplementation.

Dietary intakes and plasma concentrations of zinc, copper, iron, magnesium, and selenium of young, middle aged and older men

The relationship of age with dietary intake and plasma concentrations of zinc, copper, iron, magnesium, and selenium was investigated in 36 free-living healthy men, in age ranges 25–35, 45–55, and 65–75 years (n=12/group). Three day average daily dietary intakes of energy, protein, zinc, copper, magnesium, and iron were not significantly different among groups. Plasma concentrations of zinc, copper, iron, magnesium, and selenium were also not significantly different among groups. Dietary intakes of zinc, copper, iron, and magnesium were not correlated with the plasma concentration of the respective mineral. Age was signficantly correlated with dietary magnesium intake (r=−0.37, p<0.02) and plasma copper concentration (r=0.38, p<0.02). These data sugest that healthy, free-living elderly men and younger adult men had comparable dietary intakes and plasma concentrations of zinc, copper, iron, magnesium, and selenium in this study.

Zinc and copper concentration in plasma of pregnant women in Nigeria

The concentration of plasma zinc and copper were determined by atomic absorption spectrophotometry in 58 Nigerian women at various times in pregnancy and compared with those of 11 non-pregnant controls. The results showed 67.5% decrease in zinc and 100% increase in copper over non-pregnant levels at the end of pregnancy. The mean plasma zinc levels were appreciably lower and copper the same as published values for Caucasian women at similar periods in pregnancy. Furthermore, there was no correlation between plasma zinc and copper and neonatal birthweight. We conclude that (1) a significant proportion of pregnant women in Nigeria have biochemical hypozincemia; (2) this hypozincemia is not responsible for fetal growth retardation in this population and (3) there is at present no justification for giving routine zinc supplementation to pregnant women in Nigeria.

Acute phase response in horses: changes in plasma cation concentrations after localised tissue injury

An acute phase reaction was elicited in four horses to which Freund's adjuvant was administered intramuscularly. The localised inflammation was accompanied by changes in the plasma concentrations of copper, iron and zinc. The plasma copper concentration, the plasma ceruloplasmin copper concentration and the ceruloplasmin oxidase activity in the plasma steadily increased to a maximum 24 days after the administration of the adjuvant. At this time, the plasma copper concentration was 2.2 micrograms/ml, a 90 per cent increase over the baseline concentration. The ratio of the concentration of plasma ceruloplasmin copper to plasma copper remained constant, indicating that the non-ceruloplasmin bound copper component of the plasma is also an acute phase reactant in the horse. The plasma zinc and iron concentrations decreased to 59 per cent and 30 per cent of their respective baseline concentrations and the severity of the inflammation appeared to influence the plasma concentrations of each metal. Weak correlations between the plasma fibrinogen concentration and the plasma copper and zinc concentrations of 25 horses with plasma fibrinogen concentrations of 5 g/litre or greater indicated that a single measurement of plasma copper concentration is not useful in the diagnosis of non-specific inflammatory disorders of the horse. However, the results suggest that the plasma copper concentrations in serial samples may be used to monitor the resolution of inflammatory disorders in the horse.