Effect of oral zinc regimens on human hepatic copper content: a randomized intervention study

Zinc inhibits intestinal copper uptake, an effect utilized for treating Wilson's disease (WD). We used copper-64 (⁶⁴Cu) PET/CT to examine how much four weeks of treatment with different zinc regimens reduced the hepatic ⁶⁴Cu content after oral ⁶⁴Cu administration and test if alternative regimens were noninferior to the standard regimen of zinc acetate 50 mg × 3 daily. Forty healthy persons were randomized to four different zinc protocols. The WD standard treatment zinc acetate 50 mg × 3 reduced the hepatic ⁶⁴Cu content from 26.9 ± 7.5% to 13.3 ± 5.6% of the administered ⁶⁴Cu. Zinc gluconate 50 mg × 3 was noninferior (P = 0.02) (35.8 ± 9.0% to 17.4 ± 7.5%). Zinc acetate 150 mg × 1 (33.1 ± 9.9% to 17.4 ± 7.5%) and zinc gluconate 150 mg × 1 (28.1 ± 6.7% to 22.0 ± 6.7%) were less effective. These effects were intra- and inter-individually highly variable, and 14% had no effect of any zinc regimen, which may explain disparities in zinc treatment efficacy in WD patients.