Response of putative indices of copper status to copper supplementation in human subjects

Abstract

No sensitive functional index is currently available to assess Cu status in healthy human populations. This study evaluated the effect of Cu supplementation on putative indices of Cu status in twelve women and twelve men, aged between 22 and 45 years, who participated in a double-blind placebo controlled crossover study. The study consisted of three 6-week supplementation regimens of 3 mg CuSO4, 3 mg Cu-glycine chelate and 6 mg Cu-glycine chelate, each separated by placebo periods of equal length. Women had significantly higher caeruloplasmin oxidase activity (P < 0·001), caeruloplasmin protein concentration (P < 0·05), and serum diamine oxidase activity (P < 0·01) at baseline than men. Erythrocyte and leucocyte superoxide dismutase activity, leucocyte cytochrome c oxidase activity, and erythrocyte glutathione peroxidase activity did not respond to Cu supplementation. Platelet cytochrome c oxidase activity was significantly higher (P < 0·01), after supplementation with 6 mg Cu-glycine chelate in the total group and in women but did not change in men. Caeruloplasmin oxidase activity was significantly higher (P < 0·05), in men after supplementation with 3 mg Cu-glycine chelate, while caeruloplasmin protein concentration was significantly lower in men after supplementation with 6 mg Cu-glycine chelate (P < 0·05). Serum diamine oxidase activity was significantly higher after all supplementation regimens in the total group and in both men and women (P < 0·01). These results indicate that serum diamine oxidase activity is sensitive to changes in dietary Cu intakes and may also have the potential to evaluate changes in Cu status in healthy adult human subjects.

Effect of different level and source of copper supplementation on immune response and copper dependent enzyme activity in lambs

“…In contrast, Dorton et al (2003) reported no difference in RBC SOD activity for control and steers supplemented with 10 or 20 mg Cu/kg DM from organic or inorganic source. This enzyme also has been shown to be unresponsive to Cu supplementation compared to diamine oxidase activity in Cu status assessment study on human subjects (Kehoe et al 2000).…”

Influence of Estrogens on Copper Indicators: In Vivo and In Vitro Studies

“…One might expect that the earliest effects of copper exposure are of lesser intensity; therefore, it is most relevant that the traditional indicators measured in blood to assess copper status, liver function, and oxidative stress vary as described here in relation to the estradiol/progesterone blood concentrations. Identifying blood predictors of biologically relevant changes in copper status has proved to be difficult [2,4,5,7]; the influence of uncontrolled factors such as the hormones evaluated here may be part of the explanation. Cellular studies show that estradiols increase both copper transporters (mRNA and protein) and hence cell copper uptake; since copper favors cell proliferation and differentiation [32], the increase of copper derived from the presence of estrogen would help in improving cell copper bioavailability for metabolic needs, including those related to cell growth, proliferation, and reproduction [33,40].…”

“…In recent years, several investigations explored the magnitude and duration of excess copper intake necessary to induce detectable effects in apparently healthy individuals. In these studies, blood indicators have repeatedly failed to detect significant changes in adult women and men exposed to a range of copper dosing [1][2][3][4][5]; yet, principal component analysis and linear discriminant analysis showed that the variable most closely associated with the results observed was the participant's sex [6]. Women developed significantly more adverse effects after acute exposure to copper [7,8], but no differences have been demonstrated when copper exposure is for longer periods [5,6].…”

Searching for Specific Responses to Copper Exposure: An In Vitro Copper Challenge in Peripheral Mononuclear Cells

“…This is mainly due to lack of sensitive markers able to detect them. Efforts to identify sensitive and specific responses at whole body, blood biochemistry, or cellular levels have yielded unsatisfactory results [1,2]. Only rather intense alterations of copper metabolism like in Menkes syndrome, Wilson disease, and hepatitis can be diagnosed by measuring plasma copper concentration and ceruloplasmin [3,4]; otherwise, blood biochemical indicators are not sensitive indicators.…”