Interactions of pH and Ascorbate in Intestinal Iron Absorption

Iron absorption is frequently studied experimentally in animals by placing iron directly into tied-off intestinal segments in vivo, usually in acid solutions. We have monitored the changes in pH that occur in the intestinal lumen when acid iron solutions are administered and have related this to the time course of iron absorption in iron-deficient rats. Within 5 minutes of giving of 5.6 g Fe (FeCl2), in 0.50 ml 0.01 M HCl, 0.9% NaCl, the pH of the lumen had climbed above pH 4, where Fe3+ is insoluble; it reached 6.8 by 10-15 minutes. In parallel with rising pH, mucosal Fe uptake ceased by 5 minutes after its administration. Addition of 2 mM ascorbate to the same solution prevented the cessation of iron uptake despite the usual pH rise. Intestinal fluid of fasted rats had a limited buffering capacity from pH 7 to 3. When added to this fluid, 59FeCl3 largely precipitated, but microgram quantities bound to components with apparent molecular weights >25,000. This iron was available to desferrioxamine B. The results demonstrate the dramatic effects of pH on iron bioavailability, in the absence of chelators such as ascorbate, and the importance of considering iron solubility in measurements of iron absorption.