Oral administration of ferrous sulfate, but not of iron polymaltose or sodium iron ethylenediaminetetraacetic acid (NaFeEDTA), results in a substantial increase of non-transferrin-bound iron in healthy iron-adequate men.

Oral iron supplementation with ferrous sulfate (FeSO₄) at dosage levels suggested by the international guidelines poses a safety hazard to young children with malaria. Exposure to loosely bound iron in the circulation has been advanced as a potential factor. To evaluate the kinetics of circulating concentrations of plasma iron and non-transferrin-bound iron (NTBI) in response to oral iron administration in healthy adults. Plasma samples were collected at 90-minute intervals over a period of 270 minutes from 10 healthy Guatemalan men after oral administration of water or 100 mg of iron from each of three iron compounds: FeSO₄, sodium iron ethylenediaminetetraacetic acid (NaFeEDTA), and iron polymaltose. The four tests were administered in an individually randomized sequence. Serum iron concentration was measured spectrophotometrically by the ferrozine method, and NTBI concentration was measured by a fluorometric competitive binding assay. The kinetic response and the maximal and cumulative changes in circulating concentrations of the biomarkers of interest were compared. Serum iron and NTBI responses to oral administration of FeSO₄ were significantly greater than responses to plain water or the other two iron compounds. NTBI concentrations after NaFeEDTA or iron polymaltose ingestion were not different from those determined after water intake. Administration of two iron compounds of proven bioavailability, but with complex absorption characteristics, is associated with a negligible NTBI response, potentially mitigating the safety concerns associated with iron supplementation in malarial areas.