Calcium and zinc decrease intracellular iron by decreasing transport during iron repletion in an in vitro model.

PURPOSE: Iron is an essential micronutrient that participates in a number of vital reactions and its absorption may be altered by various nutritional factors such as other micronutrients. Our hypothesis is that iron absorption is decreased because of the interactions with zinc and calcium. We evaluated the interaction between calcium and zinc on iron uptake and transport, intracellular Fe and Zn levels and mRNA expression of DMT1, ferroportin, Zip4 and ZnT1 in an in vitro model.

METHODS: Caco-2 cells were cultivated with 1 mM Ca; 10 or 30 µM Zn and/or 10, 20 or 30 µM Fe for 24 h.

RESULTS: Intracellular Fe decreased in cells incubated with 30 µM Zn or with the mix Ca/10 µM Zn/Fe. Zn mostly increased under Ca, Zn and Fe treatment. DMT1 mRNA expression decreased when intracellular Fe increased. Ferroportin expression displayed no change in cells cultured with different Fe concentrations. The mix of Ca, Zn and Fe increased DMT1 and ferroportin expression mainly under high Zn concentration. Zip4 expression was mostly augmented by Ca and Fe; however, ZnT1 showed no change in all conditions studied. Fe uptake was higher in all the conditions studied compared to control cells; however, Fe transport increased only in cells incubated with Fe alone. In all the other conditions, Fe transport was lower than that in control cells.

CONCLUSIONS: The present findings suggest that Ca and Zn interfere with iron metabolism. This interference is through an increase in ferroportin activity, which results in a diminished net iron absorption.