Serum 25-hydroxyvitamin D response to oral vitamin D intake in children

The results of our study (1) show that an important fraction of iron from iron bis-glycine chelate (Fe-bis-gly) is delivered to the stomach or duodenum and forms part of the nonheme-iron pool. We do not think that the results of our study contradict those of previously published studies (2–4). Pineda supports the existence of special nonheme-iron receptors, which take up iron from an iron chelate pool at the intestinal mucosal surface (4, 5). Data from our study do not support this hypothesis. Furthermore, there is neither direct scientific evidence that shows the presence of the intact Fe-bis-gly within the enterocyte nor evidence of the existence of a specific receptor. Differences in the absorption of nonheme-iron sources do not necessarily indicate the existence of different absorption pathways. Differences could be explained on the basis of physical and chemical characteristics that determine different iron bioavailabilities. There is growing evidence that supports the hypothesis, first proposed by Olivares et al (2), that a significant but not quantified fraction of iron from Fe-bis-gly is dissociated in the gastrointestinal tract, where it can interact with other dietary constituents and enter the common nonheme-iron pool (4, 6, 7). This hypothesis is supported by studies that showed that 1) iron from Fe-bis-gly is affected by inhibitors and enhancers in the diet, as occurs with nonheme iron but not with heme iron, which is absorbed intact (2, 3, 8), and 2) iron from Fe-bis-gly competes for the nonheme-iron absorption pathway but not for the heme-iron absorption pathway (1). The results of our study, discussed by Pineda in his letter, provide strong evidence supporting our hypothesis. Our study was designed to show the competition of a small trace (0.5 mg) of a labeled ionic iron (ferrous sulfate) and heme iron (hemoglobin) with increasing doses of Fe-bis-gly. We labeled ferrous sulfate and hemoglobin, an approach widely used to assess competition for intestinal uptake, because both compounds have well-known absorption pathways. Whenever 2 compounds compete for the same absorption pathway, their dose-response curves are alike. Pineda argued that the results of the study performed by BovellBenjamin et al (4) support the lack of competition between Fe-bisgly and nonheme iron. However, we believe that the design of this study did not allow for the characterization of competition because only one low dose of iron (1 mg) with a ratio of Fe-bis-gly to ferrous sulfate of 1:1 was administered. Competition between the 2 compounds cannot be observed under this condition because, despite the greater bioavailability of iron from Fe-bis-gly, the quantity of available iron at this dose and ratio would not be sufficient to saturate the receptors and transporters of iron in the enterocyte. In contrast, this ratio ranged from 1:10 to 1:200 in our study. Our results showed that Fe-bis-gly did not compete with hemoglobin for the heme-iron absorption pathway. The mild decrease in the dose-response curve for competition between Fe-bis-gly and hemoglobin may have been due to the competition between a small fraction of nonheme iron dissociated from labeled hemoglobin and nonheme iron from Fe-bis-gly. Differences in the magnitude observed between the doseresponse curves of coated ferrous sulfate and Fe-bis-gly can be explained—as Pineda does in his letter—by differences in the bioavailability of both compounds under the environmental conditions of the duodenum. Both curves have a similar trend, with differences only in the magnitude of the changes in absorption of the tracer. If Fe-bis-gly did not compete with the tracer of ferrous sulfate, the trend of the curve would be different.