The study of Cu metabolism is hampered by a lack of sensitive and specific biomarkers of status and suitable isotopic labels, but limited information suggests that Cu homeostasis is maintained through changes in absorption and endogenous loss. The aim of the present study was to employ stable-isotope techniques to measure Cu absorption and endogenous losses in adult men adapted to low, moderate and high Cu-supplemented diets. Twelve healthy men, aged 20–59 years, were given diets containing 0·7, 1·6 and 6·0 mg Cu/d for 8 weeks, with at least 4 weeks intervening washout periods. After 6 weeks adaptation, apparent and true absorption of Cu were determined by measuring luminal loss and endogenous excretion of Cu following oral administration of 3 mg highly enriched65Cu stable-isotope label. Apparent and true absorption (41 and 48% respectively) on the low-Cu diet were not significantly different from the high-Cu diet (45 and 48% respectively). Endogenous losses were significantly reduced on the low- (0·45mg/d;P<0·001) and medium- (0·81 mg/d;P=0·001) compared with the high-Cu diet (2·46mg/d). No biochemical changes resulting from the dietary intervention were observed. Cu homeostasis was maintained over a wide range of intake and more rapidly at the lower intake, mainly through changes in endogenous excretion.
Application of the Stable Isotope Label Approach in Clinical Development—Supporting Dissolution Specifications for a Commercial Tablet Product with Tafenoquine, a Long Half-life Compound
