X-Message-Number: 27513 Date: Sun, 22 Jan 2006 19:09:00 -0800 (PST) From: Doug Skrecky <> Subject: the case for trace copper supplementation [As part of a well balanced trace mineral supplement, copper looks to useful for helping to minimize atherosclerosis.] Br J Nutr. 2005 Aug;94(2):231-6. Effect of copper supplementation on indices of copper status and certain CVD risk markers in young healthy women. Western diets containing suboptimal Cu concentrations could be widespread. A link between marginal Cu deficiency and CVD has been suggested. The objective of the present study was to investigate the effect of Cu supplementation on both Cu status and CVD risk factors in healthy young women. Sixteen women with a mean age of 24 (sd 2) years participated in a randomised crossover study of three 4-week periods with 3-week washouts between periods. During each intervention period, subjects received 0, 3 or 6 mg elemental Cu/d as CuSO4 in addition to their habitual diet. Blood samples were taken to assess the effect of supplementation on putative markers of Cu status. The content of plasma lipids, lipoprotein (a), apo and certain haemostatic factors, as putative indices of CVD, was also analysed. Daily supplementation with 3 mg Cu significantly increased (P < 0.05) serum Cu concentration and the activity of erythrocyte superoxide dismutase, although there was no further significant increase after an intake of 6 mg Cu/d. The concentration of the fibrinolytic factor plasminogen activator inhibitor type 1 was significantly reduced (P < 0.05) by about 30 % after supplementation with 6 mg Cu/d. No other marker of Cu status or CVD risk factor was affected by Cu supplementation. The results indicate that supplementation with 3 or 6 mg Cu/d may improve Cu status in these healthy young women. Increased Cu intake could reduce the risk of CVD and atherosclerosis in man by promoting improved fibrinolytic capacity. Ann Nutr Metab. 2005 Sep-Oct;49(5):283-8. Epub 2005 Aug 2. Beneficial effects of dietary copper supplementation on serum lipids and antioxidant defenses in rats. BACKGROUND: A nutrition experiment was utilized to investigate the effects of two levels of dietary copper (Cu) supplementation on lipid profile and antioxidant defenses in serum of rats. METHODS: Male Wistar rats (180-200 g; n = 10) were divided into three groups: control group (A), fed a basal diet with 6 microg Cu/g, and rats fed a basal diet with Cu (CuSO4) supplementation from aqueous solutions, for 4 weeks at the final concentrations of 2 mg Cu/rat (B) and 3 mg Cu/rat (C). RESULTS: No significant changes were observed in final body weight, body weight gain, food consumption, total serum protein and high-density lipoprotein. Cu supplementation reduced the triacylglycerol (TG), total cholesterol and low-density lipoprotein (LDL-C). The LDL-C/TG ratio and total antioxidant substances (TAS) were higher in (B) and (C) groups than in (A) group. There was a positive correlation between Cu supplementation and ceruloplasmin levels. The markers of oxidative stress, lipid hydroperoxide and lipoperoxide were decreased with Cu supplementation. No alterations were observed in superoxide dismutase, indicating saturation of Cu enzyme site. The glutathione peroxidase activities (GSH-Px) were increased in both Cu-supplemented groups. Considering that a copper-selenium interaction can affect mineral availability of both elements, the effects of Cu on TAS and GSH-Px activities were associated with increased selenium disposal. Conclusions: Dietary Cu supplementation had beneficial effects on lipid profile by improving endogenous antioxidant defenses and decreasing the oxidative stress in vivo. Int J Exp Pathol. 2005 Aug;86(4):247-55. Dietary copper supplements modulate aortic superoxide dismutase, nitric oxide and atherosclerosis. The objective was to test the hypothesis that dietary copper inhibits atherosclerosis by inducing superoxide dismutase (SOD) and potentiating nitric oxide (NO). New Zealand White rabbits were fed either a cholesterol diet (n = 8) or a cholesterol diet containing 0.02% copper acetate (n = 8) for 13 weeks. We found that the intimal area was significantly smaller in the animals supplemented with copper (P < 0.005), although integrated plasma cholesterol levels were not significantly different. This was associated with a significant increase in aortic copper content (P < 0.05), SOD activity (P < 0.05) and Cu/Zn SOD mRNA (P < 0.05) and a significant decrease in nitrotyrosine content (P < 0.05). Furthermore, there was a positive correlation between aortic copper content and SOD activity (P < 0.005, R(2) = 0.83) and a negative correlation between aortic superoxide dimutase activity and nitrotyrosine content (P < 0.005, R(2) = 0.93). In organ bath experiments, the relaxation of precontracted carotid artery rings to calcium ionophore was greater in animals supplemented with copper. No difference in response to sodium nitroprusside was observed. These data suggest that in the cholesterol-fed rabbit, copper supplements inhibit the progression of atherosclerosis by increasing SOD expression, thereby reducing the interaction of NO with superoxide, and hence potentiating NO-mediated pathways that may protect against atherosclerosis. Int J Exp Pathol. 2004 Oct;85(5):265-75. The effects of coadministration of dietary copper and zinc supplements on atherosclerosis, antioxidant enzymes and indices of lipid peroxidation in the cholesterol-fed rabbit. It has previously been shown that dietary copper can modulate the extent of atherosclerosis in the thoracic aorta of cholesterol-fed rabbits. The metabolism of copper and zinc are closely related, and it has been hypothesized that the balance of dietary copper to zinc may be important in determining coronary risk. Hence, we have investigated the interaction between dietary copper and zinc in atherogenesis in the New Zealand White rabbit. Juvenile male rabbits were randomly allocated to eight groups. Four groups were fed a normal chow diet with zinc (0.5%, w/w), copper (0.2%, w/w), copper plus zinc or neither in their drinking water for 12 weeks. Four other groups were fed a diet containing 0.25-1% (w/w) cholesterol plus zinc, copper, both or neither. Serum cholesterol of individual animals was maintained at approximately 20 mmol/l. Integrated plasma cholesterol levels were similar for all groups receiving cholesterol and significantly higher than those in the chow-fed groups (P < 0.001). Aortic copper concentrations were higher in the animals receiving cholesterol diets with copper compared to rabbits receiving normal chow and copper (P < 0.001). Aortic zinc content was significantly higher in cholesterol-fed rabbits supplemented with zinc alone or with copper than in those fed cholesterol alone (P < 0.001). Plasma ceruloplasmin concentrations were significantly higher in groups receiving cholesterol, irrespective of their trace element supplementation (P < 0.001). However, trace element supplementation increased the level significantly (P < 0.05). Trace element supplements did not appear to affect erythrocyte superoxide dismutase in the cholesterol-fed animals; however, zinc supplementation was associated with a significant increase in the enzyme in chow-fed animals (P < 0.05). The activity of the enzyme per mg of protein in aortic tissue was higher in animals receiving copper in the presence of cholesterol (P < 0.05) but not significantly so in its absence. Dietary trace element supplementation in cholesterol-fed animals was associated with a significant reduction in aortic lesion area. Plasma thiobarbituric acid-reactive substances and FOX concentrations were both significantly higher in the cholesterol-fed rabbits compared with the animals that fed on a chow diet (P < 0.001), and these were reduced significantly by dietary copper or zinc supplementation (P < 0.001). Hence, dietary supplements of copper or zinc at the doses used both inhibited aortic atherogenesis in the cholesterol-fed rabbits, although there was no significant additional effect when given in combination. Rate This Message: http://www.cryonet.org/cgi-bin/rate.cgi?msg=27513