Copper deficiency reduces iron absorption and biological half-life in male rats

Dietary copper deficiency (CuD) in rats leads to iron (Fe) deficiency anemia. Is this because CuD reduces Fe absorption? Fe absorption in CuD rats was determined by feeding diets labeled with (59)Fe and using whole-body counting (WBC) to assess the amount retained over time. Two groups, each with 45 male weanling rats, were fed an AIN-93G diet low in Cu (<0.3 mg/kg; CuD) or one containing adequate Cu (5.0 mg/kg; CuA). At intervals over the next 42 d, 5 rats per group were killed and blood was drawn to determine hematocrit, hemoglobin, and other indicators of Fe status. At d 7 and 25, 5 rats per group were fed 1.0 g of their respective diets that had been labeled with (59)Fe. Retained (59)Fe was monitored for 10 d by WBC; then rats were killed and (59)Fe was measured in various organs. Signs of Fe deficiency, such as low hemoglobin, hematocrit, and RBC count, were evident in CuD rats by d 14. At d 7, CuD rats absorbed 90% as much Fe as CuA rats (P > 0.20), but at d 25, CuD rats absorbed only 50% as much as CuA rats (P < 0.001). In the study beginning at d 7, the biological half-life (BHL) of (59)Fe in CuD rats was less (P < 0.02) than that in CuA rats [geometric mean (-SEM, +SEM); 75(62,91) d vs. 175(156,195) d]. In the study beginning at d 25, the BHL was again less (P < 0.02) in the CuD rats than in the CuA rats [33(23,49) d for CuD and 157(148,166) d for CuA]. Apparently, the route of Fe loss in the CuD rats was through the gut. At d 16 and 34, CuD rats lost 4 to 5 times more (P < 0.01) (59)Fe in the feces in a 24-h period than the CuA rats. Also, (59)Fe in the duodenal mucosa of CuD rats was approximately 100% higher (P < 0.01) than in CuA rats. These findings suggest that Fe deficiency anemia in CuD male rats is caused at least in part by reductions in Fe absorption and retention.