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Institute of Medicine Department of Clinical Nutrition Sahlgrenska University Hospital Annedalsklinikerna S-41345 Göteborg Sweden
Dear Sir:
In the June 2000 issue of the Journal, Bovell-Benjamin et al (1) compared the absorption of iron from ferrous sulfate, ferrous bisglycinate, and ferric trisglycinate added to a whole-maize meal. They concluded that iron absorption was better from ferrous bisglycinate than from ferrous sulfate or ferric trisglycinate and that ferrous bisglycinate was an effective and safe source of iron that was particularly useful as an iron fortificant in diets rich in phytate. Their other main conclusion was that iron from ferrous bisglycinate does not exchange in the intestinal nonheme-iron pool with the iron from maize or ferrous sulfate.
In comparisons of iron absorption from meals, the percentage absorption, based on tracer methodology, needs to be multiplied by the amounts of iron present in the corresponding labeled pools. Bovell-Benjamin et al concluded that iron from ferrous bisglycinate does not exchange with the iron from maize or ferrous sulfate. This conclusion was based on observations that, when the same amounts of iron as ferrous sulfate and ferrous bisglycinate were given separately together with the maize meal, iron absorption was 1.7% and 6.0%, respectively; when the same amounts of iron were added to the same maize meal, absorption of the tracers was 1.0% and 6.8%, respectively. The authors combined the mean percentage absorption in their studies 1A and 1B, which were then 1.3% and 6.4%, respectively, indicating a 4.7 times greater absorption of iron from ferrous bisglycinate (P < 0.05). It is not clear how the conclusion of "no exchange" was drawn between the labels in the intestinal pool in study 1B. However, because the absorption studies were done in the same subjects, the data can be analyzed in a way that is more sensitive and specific by comparing the absorption in the same subjects and not in 2 groups of subjects. The mean absorption of iron from the tracer for ferrous sulfate given alone with maize was 1.7% (study 1A); when ferrous sulfate was given together with maize and ferrous bisglycinate (study 1B) the absorption was lower (1.0%). These mean values suggest that the absorption was different in the 2 studies. When we compared more correctly the individual ratios in absorption of the ferrous sulfate tracer in studies 1A and 1B, this mean ratio was 1.653 (t = 2.436, P = 0.0375). A corresponding comparison of ferrous bisglycinate in studies 1A and 1B showed that the absorption was the same when ferrous sulfate was given alone in study 1A and when given together with the same amount of ferrous sulfate in the same meals in study 1B (mean ratio: 0.956, t = -0.299, P = 0.77). This implies 1) that the absorption of iron from the nonheme-iron pool dropped by 40% (1/1.65) when ferrous sulfate was given together with ferrous bisglycinate and 2) that the percentage absorption of iron from a hypothetical chelate pool of ferrous bisglycinate was not influenced. The most obvious explanation is that some iron moved from "the ferrous bisglycinate pool" to the "maize pool," which we know from several previous studies is uniformly labeled by the added ferrous sulfate.
All this implies that the iron absorption from ferrous sulfate given with maize in study 1A was measured correctly. However, the absorption of iron from ferrous bisglycinate in study 1A cannot be calculated because we do not know 1) how much iron moved from ferrous bisglycinate to the nonheme-iron pool in maize, and thus 2) how much iron remained in chelate form. We know from study 2A that iron in ferrous bisglycinate is less well absorbed than is ferrous sulfate when given alone. It may be assumed that ferrous bisglycinate is partly dissociated and that an unknown, but possibly considerable, amount of iron is released into the nonheme-iron pool (maize-meal pool). An absolute condition in these kinds of tracer studies is to know the specific activity of the iron.
This would imply that it is impossible to estimate the total amounts of iron absorbed. Actually, the only way to correctly analyze the isotopic exchange between an iron compound and iron in a food is by comparing iron absorption from a biosynthetically radioiron-labeled food (eg, maize) and the iron compound to be tested. An incomplete isotopic exchange between iron in another iron chelate, FeNaEDTA, and biosynthetically radioiron-labeled maize was observed by several investigators (3–5). In unpublished studies in our laboratory we found an absorption ratio of 0.58 ± 0.044 between biosynthetically radioiron-labeled maize and the iron in FeNaEDTA (n = 10). All these results suggest that a fraction of iron chelates may form a separate pool, that some iron is dissociated and exchanges with the nonheme-iron pool, and that some unknown fraction is absorbed from a kind of possible mucosal-iron pool.
An interesting part of the discussion in the present study (1) addressed the process of absorption of iron from the intestines when strong iron chelates are also present. Our assumption is that there is a pool at the intestinal mucosal surface from which iron is taken up by special nonheme-iron receptors. This mucosal pool is directly connected with the nonheme, intraluminal nonheme-iron pool. In that pool, ferric iron is probably reduced to ferrous iron to be absorbable. Iron chelates such as ferrous bisglycinate and FeNaEDTA are present initially in an iron chelate pool that is connected both with the common nonheme intraluminal pool (where an isotopic exchange may take place) and directly with the mucosal nonheme-iron pool, where its iron may be released and absorbed. In this way, iron status influences the absorption from both the iron in the chelate pool (as reported here) and the iron in the usual intraluminal nonheme-iron pool. Such a hypothesis might explain many of the seemingly contradictory results.
On the basis of our analysis of the data presented, we cannot accept the main conclusions drawn by Bovell-Benjamin et al. There is no evidence to support the conclusion that ferrous bisglycinate is useful as an iron fortificant.
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