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United States Department of Agriculture

Agricultural Research Service

Title: Copper Deficiency Reduces Iron Absorption and Biological Half-Life in Male Rats

item Reeves, Phillip
item Demars, Lana

Submitted to: Journal of Nutrition
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: May 11, 2004
Publication Date: August 1, 2004
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Citation: Reeves, P.G., Demars, L.C. 2004. Copper deficiency reduces iron absorption and biological half-life in male rats. Journal of Nutrition. 134:1953-1957.

Interpretive Summary: It is important for us to know the concentration of a mineral nutrient in the diet so that we can keep track of how much we consume, and if it meets the recommended intake. However, we also need to know if a nutrient is available for absorption. Many factors affect absorption of minerals, and one of the most important ones is the interaction of one mineral with another that might reduce or enhance absorption and utilization. In this study, we determined whether low intakes of dietary copper influence the absorption and utilization of iron. The concentration of copper in the diet was less than 1 mg/kg diet in one group (deficient copper) and 5 mg/kg (adequate copper) in another; the amount of iron was 35 mg/kg (adequate) in both groups. The diets were fed to rats, and after 1 week and 4 weeks, radioactive iron was fed to the rats and the amount that was retained in the body was determined. This procedure allows us to estimate how much iron was absorbed. When dietary copper was low, rats absorbed only half as much iron as when copper was adequate. In addition, low dietary copper increased the speed at which iron left the body. Copper deficiency also reduced iron utilization in the rat, which resulted in anemia. This was expressed as low blood hemoglobin, low red cell count, and low hematocrit. This study shows the importance of having adequate intakes of all nutrients, because too little of one might reduce the utilization of another, even though it might normally be considered in adequate supply.

Technical Abstract: 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 59Fe 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 devoid of 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 homatocrit, hemoglobin, and other indicators of Fe status. At day-7 and day-25, 5 rats per group were fed 1.0 g of their respective diets that were labeled with 59Fe. Retained 59Fe was monitored for 10 days by WBC. Rats were killed and 59Fe was measured in various organs. Signs of Fe deficiency, i.e., low hemoglobin, hematocrit, and RBC count, were evident in CuD rats by day-14. At day-7, CuD rats absorbed 90% (p>0.05) as much Fe as CuD rats, but at day-25, CuD rats absorbed only 50% (p<0.001) as much as CuA rats. For the study beginning at day-7, the biological half-life (BHL) of 59Fe in CuD rats was less (p<0.02) than that in CuA rats [geometric means (-SEM, +SEM); 75(62, 91) days vs. 175 (156,195) days]. In the study beginning at day-25, the BHL was 33(23, 49) days for CuD and 157 (148, 166) days for CuA (p<0.02). Apparently, the site of this rapid loss of Fe in the CuD rats was through the gut. At days 16 and 34, CuD rats lost 2 to 3 times more (p<0.01) 59Fe in the feces in a 24-hr period than the CuA rats. Also, 59Fe in the duodenal mucosa of CuD rats was about 2 times higher (p<0.01) that in CuA rats. These findings suggest that Fe deficiency anemia in the CuD male rat model is at least partially caused by reductions in Fe absorption and retention.

Last Modified: 4/19/2014
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