Supplementing copper at the upper level of the adult dietary recommended intake induces detectable but transient changes in healthy adults

The health consequences of mild copper excess in humans are unknown. In a previous study, 2 mo of supplementation with up to 6 mg Cu/L in drinking water did not induce detectable changes. Here we assessed a copper supplement at the upper level of dietary recommendations for "healthy" adults. The study was a prospective controlled trial; participants (women and men, 18-50 y old), represented the upper and lower 5% of the ceruloplasmin distribution curve obtained from a community-based sample of 800 healthy adults (n = 41/ group, each similar to 50% men). Individuals received a single daily dose of 10 mg Cu for 60 d. Before and after supplementation, blood [copper, ceruloplasmin protein, homocysteine, liver aminotranferases, Cu-Zn -superoxide dismutase activity in erythrocytes (eSOD), and glutathione in peripheral mononuclear cells] and urine [copper excretion after a 5-h administration of a chelator 2,3-dimercapto-1-propano-sodium sulfonate (DMPS)] analyses were performed. After 2 mo, liver enzyme activities remained below the clinical cutoff value used to diagnose liver dysfunction, but had increased significantly in both groups and genders. These increases were no longer present 12 mo after the copper loading period was completed. Glutathione in mononuclear cells (mmol/g of protein) also increased after the 2-mo copper loading in both groups and in both genders (P = 0.01). eSOD activity, serum homocysteine concentration, and urinary copper excretion 5 h after DMPS administration were not affected. We conclude that copper administered as described induced a transient, mild, but significant elevation of aminotransferases.