Studies on the Bioavailability of Zinc in Humans: Mechanism of the Intestinal Interaction of Nonheme Iron and Zinc

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Abstract
The mechanisms of the previously described competitive zinc:iron interaction were explored in healthy human volunteers, using the increment in plasma zinc concentration after an oral dose of 25 mg of zinc as zinc sulfate as the index of zinc absorption. Ferric iron in a 2:1 Fe/Zn ratio reduced the plasma uptake of zinc, but to a significantly lesser degree than ferrous iron; addition of 1 g of ascorbic acid increased the magnitude of the inhibitory effect of ferric iron to that seen with ferrous iron. An inverse relationship between some indices of iron status in adult women, or of parenteral iron administration in a child, and the magnitude of zinc:iron interaction was observed. Saturation of the intestinal mucosa with consecutive-day doses of therapeutic iron did not influence the uptake of zinc administered alone or in the context of a 2:1 ferrous iron:zinc ratio in solution. The results are most consistent with a combination of an intraluminal competition of the two minerals and an intracellular competition at a site “distal” to the regulatory step by which iron nutriture modulates the entry of iron into the body, but “proximal” to the site at which the daily administration of therapeutic doses of iron blocked the passage of dietary iron.