Circulating non-transferrin-bound iron after oral administration of supplemental and fortification doses of iron to healthy women: a randomized study

Background: After the oral administration of iron, the production of circulating non-transferrin-bound iron may contribute to an increased risk of illness in malaria-endemic areas that lack effective medical services. Objective: In healthy women with a range of body iron stores, we aimed to determine effects on the production of circulating non-transferrin-bound iron resulting from the oral administration of 1) a supplemental dose of iron (60 mg) with water; 2) a supplemental dose of iron (60 mg) with a standard test meal, and 3) a fortification dose of iron (6 mg) with a standard test meal. Design: With the use of serum ferritin as the indicator, healthy women with replete iron stores (ferritin concentration >25 mu g/L; n = 16) and reduced iron stores (ferritin concentration <= 25 mu g/L; n = 16) were enrolled in a prospective, randomized, crossover study. After the oral administration of aqueous solutions of ferrous sulfate isotopically labeled with Fe-54, Fe-57, or Fe-58, blood samples were collected for 8 h, and iron absorption was estimated by erythrocyte incorporation at 14 d. Results: At 4 h, serum non-transferrin-bound iron reached peaks with geometric mean (95% CI) concentrations of 0.81 mu mol/L (0.56, 1.1 mu mol/L) for 60 mg Fe with water and 0.26 mu mol/L (0.15, 0.38 mu mol/L) for 60 mg Fe with food but was at assay limits of detection (0.1 mu mol Fe/L) for 6 mg Fe with food. For the 60 mg Fe without food, the area under the curve over 8 h for serum non-transferrin-bound iron was positively correlated with the amount of iron absorbed (R = 0.49, P < 0.01) and negatively correlated with serum ferritin (R = -0.39, P < 0.05). Conclusions: In healthy women, the production of circulating non-transferrin-bound iron is determined by the rate and amount of iron absorbed. The highest concentrations of non-transferrin-bound iron resulted from the administration of supplemental doses of iron without food. Little or no circulating non-transferrin-bound iron resulted from the consumption of a meal with a fortification dose of iron.