Reply to L Hallberg and L Hulthén

Department of Nutrition University of California Davis, CA 95616 E-mail: lhallen{at}ucdavis.edu
Department of Nutritional Sciences University of California Berkeley, CA 94720

Dear Sir:

Hallberg and Hulthén question the interpretation of our data that showed that ferrous bisglycinate is absorbed better from whole maize than is ferrous sulfate. Specifically, they question our conclusion that there was no exchange in the intestinal pool between iron from ferrous bisglycinate and iron from ferrous sulfate.

The basis of our conclusion is that absorption of iron from ferrous sulfate and ferrous bisglycinate was the same whether the labeled forms of these compounds were given separately or mixed together in the same meal. Our data were analyzed correctly because it is appropriate to control for the repeated-measures nature of the design. Also, because a log transformation was used, in effect the absorption ratios were compared, not the absolute values. As stated in our article, the average absorption of iron from ferrous sulfate was about one-fifth that of its absorption from ferrous bisglycinate (P < 0.0001).

What we did not do was use the repeated-measures procedure to examine the interaction between study and iron source. We have since used that procedure and found the interaction to be significant (P = 0.01). It is therefore appropriate to make a comparison of iron sources between studies. This comparison showed that iron absorption from the bisglycinate was the same in each trial (P = 0.77, Tukey's test) but, as noted by Hallberg and Hulthén, the absorption from ferrous sulfate differed between studies 1A and 1B (P = 0.04). However, the results do not support their interpretation that there is an exchange between iron from ferrous bisglycinate and the nonheme-iron pool.

If the iron from these sources had exchanged in the intestinal pool there would have been a similar trend in iron absorption from both iron sources in studies 1A and 1B. In fact, the opposite occurred. As the geometric mean absorption ratio of iron from ferrous sulfate between studies 1A and 1B dropped to 0.59, a significant difference, it increased to 1.13 for ferrous bisglycinate, which was not significant. If, as Hallberg and Hulthén suggest, the explanation is that some iron moved from the ferrous bisglycinate into the "maize pool," which is equilibrated with the ferrous sulfate iron, less label from bisglycinate would have been absorbed in study 1B, and there would have been less of a difference between the geometric absorption means. However, the means became more separated: the ratio of absorption of iron from ferrous bisglycinate to absorption of iron from ferrous sulfate in study 1A was 3.5 and increased to 6.8 in study 1B. In addition, even if the cause of the 41% lower absorption of iron from ferrous sulfate in study 1B was dilution with iron from ferrous bisglycinate, it still could not explain this amount of divergence. Importantly, care was taken to provide the same amount of iron as sulfate or bisglycinate, or both, so that the size of the intestinal iron pool was similar in the 2 studies.