Effect Of Copper Supplementation Research Articles

Effects of Copper Supplementation on Lipid Oxidation and Meat Quality of Merino X Texel Lambs

Two levels of copper sulphate and copper-methionine were evaluated on lipid oxidative stability in liver and Longissimus thoracis (LT) muscle, measured by thiobarbituric acid reactive substances (TBARS) and activities of superoxide dismutase (SOD) and glutathione peroxidase (GPx) in liver. 40 Merino x Texel lambs were randomly distributed into 5 treatments with 8 animals each. Treatments were: control, without copper addition; 10 or 30 mg of Cu/Kg DM complete diet in the form of Cu-sulphate or Cu-methionine. After 120 days period, animals were slaughtered and samples collected, for analyses on activities of SOD, GPx and TBARS in livers. LT muscle was collected for TBARS analysis at carcass dressing, 3 and 6 days after chilling at 4°C and 12 months after vacuum freezing. SOD and GPx activities were higher in animals receiving copper. TBARS values in muscle were higher in the control group at the time of boning but did not differ after 12 months of vacuum freezing. TBARS values in muscle during shelf life, with a linear increase over the days, did not vary. It was found that copper supplementation, even at considered toxic levels of 30mg/kg DM, plus 9mg/kg basal diet, resulted in increased hepatic concentration of liver antioxidant enzymes and showed no detrimental effects on muscle oxidative stability.

The effect of copper supplementation on in vitro maturation of porcine cumulus-oocyte complexes and subsequent developmental competence after parthenogenetic activation

Copper (Cu) ions have redox activity and act as cofactors of enzymes related to respiration, radical detoxification, and iron metabolism. In this study, we aimed to examine the effects of copper (II) chloride dihydrate (CuCl2·2H2O) on porcine oocytes during in vitro maturation (IVM) and subsequent embryonic development following parthenogenetic activation (PA). Nuclear maturation, intracellular glutathione (GSH) and reactive oxygen species (ROS) levels, cumulus expansion, the mRNA expression levels of various genes, and developmental competence were analyzed. During IVM, the maturation medium was supplemented with various concentrations of Cu (0, 0.7, 1.4, and 2.8 μg/mL). After 42 h of IVM, Cu supplementation significantly increased the number of oocytes in the metaphase II stage. Further, the 1.4 μg/mL Cu group showed significantly higher intracellular GSH levels than the control group. However, Cu supplementation increased intracellular ROS levels regardless of their concentration. Additionally, the mRNA levels of Has-2, the cumulus cell expansion-related gene, were higher in all the Cu-treated groups than in the control group. The cumulus cell expansion index was higher in the 0.7 and 1.4 μg/mL Cu groups than in the other groups. In the 0.7 μg/mL Cu group, the mRNA expression levels of PCNA, Zar1, and NPM2, which are related to developmental competence, were significantly higher than those in the control group. Moreover, increased levels of Sod1 transcript, correlated with the antioxidative response, were observed in the 0.7 and 1.4 μg/mL Cu groups. The apoptosis rate in Cu-treated cumulus cells and oocytes was decreased compared to that in the corresponding control groups. Upon evaluation of subsequent embryonic development after PA, the 0.7 μg/mL Cu group showed significantly improved cleavage and blastocyst formation rate compared to the control group. In conclusion, our results suggest that Cu supplementation at appropriate concentrations in IVM medium improves porcine oocyte maturation and the subsequent embryonic potential of PA embryos by reducing oxidative stress and apoptosis.

COPPER AND IRON SUPPLEMENTATION IN THE DIETS OF LAYING HENS IN THE TROPICAL ENVIRONMENT — EFFECTS ON PRODUCTION TRAITS

One hundred and thirty-five fifty-two-week-old hybrid layers (Hubbard Strain), were allocated to 9 dietary treatments of 15 birds each. The birds were fed, on one of 9 diets, consisting of three levels of supplemental copper: 0,200 and 400 ppm and three levels of supplemental iron: 0,100 and 200 ppm for 12 weeks. Per cent day egg production, egg grade, feed intake, efficiency of teed conversion, mortality and body weight change were measured. No significant effects of copper or iron or their interaction, were observed for any of the traits measured in the study. However, diets supplemented with 100ppm Fe/400ppm Fe/0 ppm Cu, showed slight improvements in egg production and efficiency of feed conversion over the control. The diet supplemented with 100ppm Fe/200ppm Cu also showed the most marked body weight gain. The results of this study seem to indicate that the effects of copper supplements, equivalent to those found to stimulate growth in pigs and chicks, are of little or no significance in old layers in a tropical environment. The results also showed that concurrent supplementation of copper containing diet with iron is not necessary for old layers.

Effects of Copper Supplementation on Blood Lipid Level: a Systematic Review and a Meta-Analysis on Randomized Clinical Trials.

Studies have evaluated the effect of copper (Cu) supplementation on blood lipid level. We therefore investigated whether the supplement of Cu on blood lipid level will have an impact in a meta-analysis on randomized controlled trials (RCTs). Literature search was conducted in Scopus, PubMed, Web of Science, and Cochrane Library (from database to January 2020). Randomized controlled trials of Cu supplementation on blood lipid level were retrieved according to the requirements of systematic review, and the quality of the included research was evaluated. Then the meta-analysis was performed. Data from 5 trials representing 176 participants were examined. Pooled mean net change in total cholesterol (TC) (standard mean difference(SMD) [95% CI] = - 0.05 [- 0.52, 0.43]), low density lipoprotein cholesterol (LDL-C) (SMD [95% CI] = 0.22 [- 0.46, 0.89]), and high density lipoprotein cholesterol (HDL-C) (SMD [95% CI] = 0.18 [- 0.14, 0.49]) for those treated with Cu supplementation had no significant difference when compared with control. Cu supplementation has not affected blood lipids in the result of meta-analysis. More research is needed to determine if this pattern will apply broadly.

Co-digestion of food waste and domestic wastewater – effect of copper supplementation on biogas production

This work aims to study the effect of copper supplementation (as CuCl2), at different concentrations (10, 30, and 50 mg/L Cu2+) to enhance the conversion of organics present in a mixture of food waste and domestic wastewater (0.183, v/v) to biogas. The UASB reactor was operated under mesophilic conditions (35±0.1°C) at hydraulic retention time of 10 days in the intermittent feed mode (48 h feed/48 h feedless). Regardless of the Cu2+ concentration supplemented, a higher cumulative biogas yield (260-329 mL CH4/g CODremoved) was obtained compared to the control without supplementation (175 mL CH4/g CODremoved). The microelement supplementation reduced the amount of short chain fatty acids accumulated in the reactor by 35%, stimulating the methane production.

Evaluating the effects of copper supplement during pregnancy on premature rupture of membranes and pregnancy outcome

Objective: To evaluate the effects of copper (Cu) supplementation during pregnancy on the rupture of membranes and pregnancy outcomes.Methods: Study was conducted as a triple-blind randomized clinical trial. In one group, Cu in a dose of 1000 mg per day, and in the other group, placebo was prescribed orally from 16th week of pregnancy.Results: The women of the two groups did not have significant difference according to age, gestational age at recruitment, BMI, and socioeconomic conditions. There was no statistically significant difference between case and control group regarding the incidence of PPROM, PROM, preterm labor, vaginal bleeding during pregnancy, preeclampsia, and the incidence of placenta abruption. There was a 75% and 90% decrease in depressive symptoms in 2nd trimester and 3rd trimester in supplemented group, respectively. Also, there was a 45% and 80% decrease in anxiety symptoms in 2nd trimester and 3rd trimester in the supplemented group, respectively The rate of infection during pregnancy was significantly higher in control group (p = 0.046). There was no difference between the two groups according to neonatal outcomes.Conclusions: Cu supplementation during pregnancy could not influence positively on ROM; however, it could improve some mood status of the women.

Effect of Copper Supplementation on Performance, Eggshell Quality and Heterophil: Lymphocyte Ratio in Aged Laying Hens Housed at Different Stocking Densities

This study was conducted to determine the effects of additional dietary copper on performance, eggshell quality and heterophil: lymphocyte ratio in aged laying hens housed at different stocking densities. For this purpose, 216 Nick Chick laying hens of 106 weeks of age, were housed at three different stocking densities i.e. 500, 417 and 357 cm2/hen, respectively and copper (0, 150 and 300 mg/kg) was added in the basal diet for a period of 10 weeks using a 3x3 factorial arrangement. The effect of the treatments on body weight gain, feed intake, damaged eggs, specific gravity and eggshell breaking strength were not significant (P>0.05). However, eggshell thickness was improved (P<0.05) with increasing stocking density in the aged laying hens. Additionally, added copper had a significant effect on egg production (P<0.05), egg weight (P<0.01), egg mass (P<0.01), feed conversion ratio (P<0.01) and eggshell weight (P<0.01). While added copper had a significant adverse effect on eggshell weight, the addition of copper had a significant positive effect on performance parameters. Highest stocking density resulted in increased (P<0.05) heterophil: lymphocyte ratio. Addition of 150 and 300 mg/kg copper in the diet of the birds kept at 500 cm2/hen stocking density reduced heterophil: lymphocyte ratio as compared to other groups. It may be concluded that supplementation copper in the diet of aged laying hens decreased stress under normal stocking density, while stress was increased to the birds under high stocking density.

Effect of dietary copper addition on lipid metabolism in rabbits

ABSTRACTThe present study was conducted to investigate the effect of copper supplementation on lipid metabolism in rabbits. Our study showed dietary copper addition (5-45 mg/kg) increased body mass gain, but decreased fat and liver weights compared with those in the control group (P < 0.05). Copper (45 mg/kg) addition significantly increased the skeletal muscle weight, but inhibited cytoplasmic lipid accumulation in liver, skeletal muscle and adipose tissue (P < 0.05). Compared with the control group, dietary copper addition (45 mg/kg) significantly increased plasma triglyceride levels but decreased very low density lipoprotein levels (P < 0.05). Copper treatment significantly increased gene expression of carnitine palmitoyltransferase (CPT) 1, CPT2 and peroxisome proliferator-activated receptor (PPAR) a in liver (P < 0.05). In skeletal muscle, CPT1, CPT2, fatty acid transport protein, fatty acid-binding protein, and PPARa mRNA as well as phosphorylated AMP-activated protein kinase (AMPK) levels were significantly up-regulated by copper treatment (P < 0.05). Rabbits receiving copper supplementation had higher CPT1, CPT2, PPARa and hormone-sensitive lipase mRNA levels in adipose tissue (P < 0.05). In conclusion, copper promoted skeletal muscle growth and reduced fat accretion. PPARa signaling in liver, skeletal muscle and adipose tissues and AMPK signaling in skeletal muscle tissue were involved in the regulation of lipid metabolism by copper.

Dose-dependent effects of copper supplementation of nursery diets on growth performance and fecal consistency in weaned pigs1

Pharmacological levels of dietary copper (150–250 mg/kg) improve growth performance in pigs, but the majority of Cu is excreted in the manure and may contribute to accumulation in the soil. This experiment with 4 levels of dietary Cu supplementation (15, 80, 120, and 160 mg/kg) from weaning to d 56 after weaning was conducted to determine the dose-dependent effects of dietary Cu on growth performance and fecal consistency in pigs. From d 56 to slaughter, all pigs received the same grower and finisher diets supplemented with 15 mg/kg Cu. Each treatment comprised 10 pens with 8 pigs each, mixed males and females, as experimental units. The pigs were housed in a nursery unit until d 40 after weaning and in a grow–finish unit thereafter. Growth performance and fecal consistency were determined in 2-wk intervals until d 56; thereafter, growth performance was monitored between d 56 and slaughter. The Cu supplementation linearly increased ADFI and ADG (P Pharmacological levels of dietary copper (150–250 mg/kg) improve growth performance in pigs, but the majority of Cu is excreted in the manure and may contribute to accumulation in the soil. This experiment with 4 levels of dietary Cu supplementation (15, 80, 120, and 160 mg/kg) from weaning to d 56 after weaning was conducted to determine the dose-dependent effects of dietary Cu on growth performance and fecal consistency in pigs. From d 56 to slaughter, all pigs received the same grower and finisher diets supplemented with 15 mg/kg Cu. Each treatment comprised 10 pens with 8 pigs each, mixed males and females, as experimental units. The pigs were housed in a nursery unit until d 40 after weaning and in a grow–finish unit thereafter. Growth performance and fecal consistency were determined in 2-wk intervals until d 56; thereafter, growth performance was monitored between d 56 and slaughter. The Cu supplementation linearly increased ADFI and ADG (P

Effect of Copper Supplementation with Different Energy Levels on Broilers: (A) - Productive Performance

Effect of Copper Supplementation with Different Energy Levels on Broilers: (A) - Productive Performance

Is Copper Supplementation Required in Formulated Feeds forOctopus vulgaris(Cuvier, 1797)?

The aim of this study was to test the effect of copper supplementation in a formulated feed on the growth, feed efficiency, and nutritional composition of subadults Octopus vulgaris, with particular reference to the differences in the content of copper in the tissues (muscle, digestive gland, and hemolymph). Two formulated feeds were supplied to subadults octopuses kept individually for 56 days: Basal diet [11.6 mgCu/kg dry weight (dw)], and another feed with a similar composition but including a copper supplementation (copper diet: 115.2 mgCu/kg dw). No significant differences (P > 0.05) were detected in the respective growth rates (0.88% body weight/day), FE (79.5%–82.1%), proximate composition, hemolymph hemocyanin (1.6–1.8 mmol/L), hemolymph copper (0.19–0.20 mgCu/mL), or muscle copper levels (22.7–23.2 mgCu/kg dw). No significant changes were detected on proximate composition, hemocyanin and hemolymph, and muscle copper levels between animals fed formulated feeds and an initial group fed natural diet based on crab and fish (P > 0.05). The only parameter which showed a significant difference (P < 0.05) was the copper level in the digestive gland: 1,797, 390, and 1,148 mgCu/kg dw for initial (natural diet), basal and copper diet, respectively (P < 0.05). Considering the experimental conditions of this study, copper supplementation is not effective in improving the performance of a formulated feed for octopus.

Effects of copper supplementation on feedlot performance, carcass characteristics, and rumen sulfur metabolism of growing cattle fed diets containing 60% dried distillers grains1

The effects of 3 supplemental Cu concentrations on feedlot performance, mineral absorption, carcass characteristics, and ruminal S metabolism of cattle fed diets containing 60% dried distillers grains with solubles (DDGS) were evaluated in 2 experiments. Experiment 1 was conducted with 84 Angus-cross yearling steers and heifers (initial BW = 238 ± 36 kg), which were blocked by gender and allocated to 12 pens. Supplemental dietary Cu (tribasic copper chloride) treatments were: 1) 0 mg Cu/kg diet DM, 2) 100 mg Cu/kg diet DM, 3) 200 mg Cu/kg diet DM. The remainder of the diet was DDGS (60%), grass hay (10%), pelleted soy hulls (15%), and a vitamin-mineral supplement (15%). Diets were offered ad libitum throughout the finishing phase (168 d). Three cattle from each pen (n = 36) were harvested on d 168 and carcass data and liver samples were collected. Copper supplementation did not affect ADG (P = 0.22). However, the nonsignificant trend for increased ADG and decreased DMI led to a linear increase (P = 0.02) feed efficiency (G:F = 0.167, 0.177, and 0.177 for 0, 100, and 200 mg Cu/kg diet DM, respectively). The apparent absorption of Cu decreased quadratically (P = 0.07) and the apparent absorption of Mn and Zn were decreased linearly (P = 0.03 and P = 0.05, respectively) with increased Cu supplementation. Cattle supplemented with 100 or 200 mg Cu/kg diet DM had greater liver Cu concentrations (P < 0.01) than cattle that were not supplemented with Cu. There were no treatment effects (P > 0.10) on HCW, LM area, USDA yield grade, backfat, or marbling score. Experiment 2 was conducted with 6 ruminally fistulated steers that were fed the same diets as in Exp 1 in a replicated 3 × 3 Latin Square design. Copper supplementation did not affect (P > 0.10) ruminal pH or liquid S(2-) concentrations in steers consuming 60% DDGS diets (total dietary S = 0.55%). From 3 to 9 h after feeding, H(2)S gas concentration was decreased in those cattle supplemented with 100 mg Cu/kg diet. Concentration of H(2)S gas did not differ among cattle supplemented with 0 or 200 mg Cu/kg diet DM on 60% DDGS diets. Supplemental Cu improved feed efficiency in cattle consuming diets containing 60% DDGS; however, effects of Cu on rumen S metabolism were minimal even when supplemented at twice the maximum tolerable limit for beef cattle (NRC, 2000).

ATP7A Gene Addition to the Choroid Plexus Results in Long-term Rescue of the Lethal Copper Transport Defect in a Menkes Disease Mouse Model

Menkes disease is a lethal infantile neurodegenerative disorder of copper metabolism caused by mutations in a P-type ATPase, ATP7A. Currently available treatment (daily subcutaneous copper injections) is not entirely effective in the majority of affected individuals. The mottled-brindled (mo-br) mouse recapitulates the Menkes phenotype, including abnormal copper transport to the brain owing to mutation in the murine homolog, Atp7a, and dies by 14 days of age. We documented that mo-br mice on C57BL/6 background were not rescued by peripheral copper administration, and used this model to evaluate brain-directed therapies. Neonatal mo-br mice received lateral ventricle injections of either adeno-associated virus serotype 5 (AAV5) harboring a reduced-size human ATP7A (rsATP7A) complementary DNA (cDNA), copper chloride, or both. AAV5-rsATP7A showed selective transduction of choroid plexus epithelia and AAV5-rsATP7A plus copper combination treatment rescued mo-br mice; 86% survived to weaning (21 days), median survival increased to 43 days, 37% lived beyond 100 days, and 22% survived to the study end point (300 days). This synergistic treatment effect correlated with increased brain copper levels, enhanced activity of dopamine-β-hydroxylase, a copper-dependent enzyme, and correction of brain pathology. Our findings provide the first definitive evidence that gene therapy may have clinical utility in the treatment of Menkes disease.

The Effects of Copper Supplementation on the Performance and Hematological Parameters of Broiler Chickens

To determine the efficiency of copper (Cu) supplementation, a feeding experiment was carried out with 240 day old broiler chicks (vencobb-100). Birds were divided into four dietary treatments: i) C - no additives, ii) T1-75 mg inclusion of Cu/kg diet, iii) T2-150 mg inclusion of Cu/kg diet, iv) T3-250 mg inclusion of Cu/kg diet. The present study was carried out in the Department of Animal Physiology, West Bengal University of Animal and Fishery Sciences, Kolkata, India for a period of 42 days (6 weeks). Growth performance was measured in terms of live weight gain, cumulative feed intake and feed conversion ratio at the end of 21 st and 42 nd day of the experiment and the result was found to be encouraging for commercial enterprises when the chickens were fed at 150 mg Cu/kg (T2) of their diet. Excess dietary copper more than 150 mg/kg reduced the haemoglobin (Hb) concentration in blood and resulted in the accumulation of copper in the liver with decreased blood Hb concentration and packed cell volumes (PCV). Copper supplementation increased the total erythrocyte count (TEC) as copper is involved in erythropoiesis. But, from the result it is indicated that the dietary copper concentration could not alter the total leukocyte count (TLC). In case of different leucocytes count (DLC), there were no significant differences observed among the different treated groups. Statistical analysis showed significant (p<0.01) difference in plasma concentration of copper, zinc, ferrous and cholesterol among the different copper treated groups. The result indicates that supplementation of copper is an effective way of improving the production performance and haematological parameters in broiler

Effect of Copper on the Expression of TGF-β in Incubated Chondrocytes of Newborn Pigs

This experiment was conducted to measure the effect of copper supplementation on TGF-β gene expression in chondrocytes of newborn pigs. Chondrocytes were cultured in media containing 15% fetal calf serum supplemented with 0, 15.6, 31.2, and 62.5μmol/L copper in 90-mm culture plate. Total RNA was isolated from chondrocytes, and TGF-β cDNA was synthesized, amplified, and sequenced. The expression level of TGF-β was examined by reverse transcription polymerase chain reaction. The results showed that the sequence of the cloned TGF-β gene was 99.4% identical to that in GenBank. The expression of TGF-β increased in culture media added with final concentration of 15.6, 31.2, and 62.5μmol/L copper. In this study, the optimal copper concentration and optimal culture time for the highest level of TGF-β expression were 31.2μmol/L and 48h, respectively.

Effects of Copper Supplementation on the Structure and Content of Elements in Kidneys of Mosaic Mutant Mice

Menkes disease is an effect of ATP7A gene mutation in humans, coding the Cu-ATP-ase which is essential in intestinal copper absorption and its subsequent transfer to circulation. This mutation results in a deficiency of copper in all tissues except the epithelia of intestine and kidney tubules. Subcutaneous injection of copper ions is the main therapy for Menkes patients. Mosaic (Atp7a(mo-ms)) mice closely simulate the situation in Menkes disease. The aim of this study was to evaluate the changes in structure and element content in kidneys of mosaic mice after copper supplementation. Hematoxylin-eosin staining was used to analyze tissue morphology and atomic absorption spectrometry to estimate Cu and Zn content. X-ray microanalysis was performed to measure Na, Mg, P, Cl, and K content in the cells of the proximal and distal tubules. Copper administration lengthened the lifespan of the mutants but led to its high accumulation and results in severe kidney damage. Karyomegalia, necrosis of tubular and Bowman's capsule epithelium, lesions, and atrophy of glomeruli were observed in the treated mutants. Copper treatment afterwards led to sclerosis of glomeruli and tubules enhanced proliferation of epithelial cells and formation of both polycystic and papillary carcinoma patterns in kidney. We suggest that copper excess may impair the activity of Na(+)/K(+) ATP-ase in renal tubules of ms/- males. The content of Mg, P, and Cl in kidneys in mutants was also changed after copper administration.

Copper deficiency and effects of copper supplementation in a herd of red deer (Cervus elaphus)

Copper (Cu) deficiency was diagnosed in a Norwegian red deer (Cervus elaphus) herd subsequent to deaths due to emaciation in late autumn 1999. The animals had free access to salt licks containing 3000 mg Cu/kg. An evaluation of the herd revealed poor calf growth rate, low weights of adult hinds, dull and light-coloured hair coats and cases of diarrhoea. The herd was subsequently monitored throughout a three-year period of Cu-supplementation. The monitoring regimen included clinical observation, copper serum examination, weighing, faecal parasitological examination, and reproduction control by ultrasound. During the period January 2000 to May 2001, the animals were treated with Cu oxid capsules (1 g CuO/10 kg liveweight) at 2–4 months intervals, with the exception of March to September 2000. The animals were fed continuously with Cu-enriched concentrates containing 300 mg Cu/kg, at a rate of 1/2 kg per head and day, from May 2001 to January 2003. Following both copper supplementation regimens adequate serum Cu concentrations were measured, and markedly improved body weights, coat quality and reproductive results were observed, except for the period from March to September 2000 when no treatment was given. The results showed that in a deer herd, with a diet low in Cu, supplementation with CuO capsules had to be given at intervals of a few months to maintain adequate serum Cu levels. Free access to Cu-containing salt licks did not meet the animals' Cu demand. Good and stable results were achieved by the daily feeding of Cu-enriched concentrates.

高齢銅欠乏患者に対する銅補充による血清脂質への影響

The purpose of this study was to examine the effects of copper supplementation on lipid profiles in elderly patients with copper deficiency. Nine long-term bed-ridden, patients (5 men and 4 women, mean age 83.3+/-8.7 years old) with severe copper deficiency, who had a serum copper of 15 microg/dL or less (normal range 70-140 microg/dL), had their diets supplemented with copper sulfate (3 mg/day) over 12 weeks in addition to their diet of only one kind of enteral food with a low concentration of copper. Copper, ceruloplasmin, total cholesterol (TC), triacylglycerides (TG), HDL-cholesterol (HDL-C), c-reactive protein (CRP), creatinine (Cr), zinc (Zn) and albumin (Alb) in the serum were measured before, 4 weeks and 12 weeks after copper supplementation. Serum copper and ceruloplasmin were significantly increased at 4 weeks after copper supplementation. TG was significantly increased at 4 weeks after copper supplementation, but at 12 weeks the increase of TG was not significant. TC, HDL-C, CRP, Cr, Zn and Alb were not changed by copper supplementation. TG was transiently increased by copper supplementation in elderly patients with copper deficiency. TC and HDL-C were not changed by copper supplementation.

In Long-Term Bedridden Elderly Patients with Dietary Copper Deficiency, Biochemical Markers of Bone Resorption Are Increased with Copper Supplementation during 12 Weeks

Background: Although the effect of copper on bone has been tested in animals and healthy subjects, no studies concerning the effect of copper supplementation on bone metabolism in patients with copper deficiency have been reported because of the rarity of these patients. This study was conducted to investigate the effect of copper supplementation on bone metabolism in copper-deficient patients. Method: This study included 10 patients (83.7 ± 8.3 years) with dietary copper deficiency under long-term bed rest for more than 12 months. They had their diets supplemented with copper sulfate (3 mg/day) over 12 weeks in addition to their diet of only one kind of enteral food with a low concentration of copper. Serum copper and ceruloplasmin, urinary deoxypyridinoline (DPD) and collagen-type 1 N-telopeptide (NTX) (biomarkers of bone resorption), serum osteocalcin (OC) and bone-specific alkaline phosphatase (Bone ALP) (biomarkers of bone formation) were analyzed at baseline, 4 and 12 weeks after copper supplementation. Results: DPD and NTX excretion were significantly increased 4 weeks after copper supplementation (p = 0.009 and p = 0.013, respectively). Serum bone ALP and OC were not significantly changed 12 weeks after copper supplementation (p = 0.051 and p = 0.594). Conclusions: In patients with nutritional copper deficiency, bone resorption markers are increased with copper supplementation.

Effect of copper and zinc supplementation on peripheral leukocytes in neutropenia due to copper deficiency

Background: Recent quantitative and qualitative studies in animals suggest that copper deficiency causes immunological impairment and a decrease in leukocytes. We investigated the effect of copper supplementation in remedying these effects of its deficiency and whether zinc, a trace element that is significant to the immune status modifies such effects.Methods: In the present investigation, the effects of copper supplementation on circulating lymphocyte levels of 18 patients (aged 61–98 years, mean 85 years) with severe copper deficiency, elicited by a long‐term low copper diet, were examined in comparison with six age and sex‐matched healthy elderly subjects. Every day for 28 days, 2 mg of copper sulfate was added to the diets of 12 of the copper‐deficient subjects. The remaining copper‐deficient subjects received 2 mg of copper sulfate daily in their diets and were also given 17.3 mg of zinc sulfate every day by intravenous infusion, both supplements were also given for 28 days. Two‐color flow‐cytometry was conducted and the blastogenesis of circulating lymphocytes was examined.Results: Copper supplementation increased the number of circulating CD2+, CD4+, CD20+ cells without affecting numbers of NK‐type CD8+ T cells (CD11b+ and CD57+ lymphocytes). The percentage of monocytes to total leukocytes decreased after copper supplementation. Zinc supplementation, however, did not augment these effects and did not increase the total number of CD57+ cells. The ratio of pokeweed mitogen reactivity to concanavalin‐A reactivity was diminished by copper supplementation but not additional zinc. There was no change in the immunological colloid reaction in the zinc sulfate turbidity test.Conclusion: Our results suggest that copper depletion has a deleterious effect on the immune system, with a decrease in circulating lymphocytes numbers. Monocytes seemed to be more resistant to copper deficiency than neutrophils, and to play a significant role in lymphocyte activation. Despite this, however, it seems unlikely that there is any synergy between copper supplementation and zinc supplementation.