Iron bis-glycine chelate competes for the nonheme-iron absorption pathway

Latin American Center for Nutrition and Metabolic Studies—CELANEM, 5a Avenue Sur No. 23, Antigua 03001, Guatemala, E-mail: celanem{at}terra.com.gt

Dear Sir:

Pizarro et al (1) reported that iron bis-glycine chelate (Fe-bis-gly) ionizes in stomach acid to free iron cations, which are absorbed from the intestinal lumen via the nonheme-iron pathway. They stated that these findings contradict those of previously published articles (2–4). If Fe-bis-gly were to hydrolyze before the absorption of its iron component, the released iron cations would compete with iron absorbed from FeSO₄, and the rates of absorption would depend on the relative amounts of free iron dissociated from each source by acid digestion. Several research studies have shown that iron from Fe-bis-gly is preferentially absorbed over iron from FeSO₄ (5–8). The results of studies that used radiolabeled iron indicate that Fe-bis-gly is absorbed intact (4).

Data from the study by Pizarro et al support the intact absorption of Fe-bis-gly by a pathway other than nonheme absorption, on the basis of the following observations: 1) Fe-bis-gly was not directly measured—its effects were surmised on the basis of the absorption of radiolabeled iron from either FeSO₄ or lyophilized hemoglobin both in and out of the presence of unlabeled Fe-bis-gly; 2) ingested Fe-bis-gly does not need to participate in the absorption pathway of FeSO₄ when the 2 compounds are administered together—it is absorbed independently via the mucosal cell receptors that consistently work best for it; 3) there was no significant difference in the absorption of radiolabeled iron from FeSO₄ that had no enteric protection, whether Fe-bis-gly was present or not, which indicated that there was no competition for the nonheme FeSO₄ pathway; 4) absorption of radiolabeled iron from hemoglobin was significantly enhanced (P < 0.01) in the presence of Fe-bis-gly, which indicated an augmenting effect of Fe-bis-gly on the heme uptake pathway; and 5) when FeSO₄ and Fe-bis-gly were administered together with enteric protection, iron absorption from FeSO₄ was significantly suppressed (P < 0.001). This finding indicates that the iron requirements of the mucosal cells in a high-pH environment were being met by the absorption of iron as Fe-bis-gly, given that there was no other alimentary iron present (because the test subjects had fasted overnight and were prevented from eating for 4 h after dosing).

Bovell-Benjamin et al (4) used different radioisotopes to label the iron in each of FeSO₄ and Fe-bis-gly. They compared the absorption of the 2 sources in whole-maize meal porridge consumed by 10 noniron-deficient, nonanemic, fasted men. After initial whole-blood samples were taken, all of the men received porridge containing ⁵⁹FeSO₄ on day 1 and porridge with ⁵⁵Fe-bis-gly on day 2. On day 14, three 10-mL fasting blood samples were drawn from each test subject, and the contents of both radiolabeled iron compounds were measured in the same samples. On day 16, the same men were given porridge containing both labeled iron sources; blood samples were recovered on day 31 for the measurement of ⁵⁹FeSO₄ and ⁵⁵Fe-bis-gly. Results from the combined tests showed that the absorption of iron from ⁵⁵Fe-bis-gly was 4.7 times that of iron from ⁵⁹FeSO₄, even though both ⁵⁹FeSO₄ and ⁵⁵Fe-bis-gly were obviously down-regulated (r = 0.99, P < 0.001) by iron stores in the individual men. The percentage of iron absorbed from each iron source was unaffected by the presence of the other iron source. This finding indicates that there was no cross-exchange of iron between the 2 sources and that Fe-bis-gly was absorbed intact, because FeSO₄ must release iron before its uptake. This study showed that the characteristics of iron absorption from FeSO₄ and from Fe-bis-gly are different, with Fe-bis-gly being favored when doses of phytate are high.

On the basis of the findings of Pizarro et al, Fe-bis-gly has a relation with the heme-absorbing pathway. Heme is also a chelate, the chelating ligand being cyclic porphyrin. Heme iron is far more bioavailable than are inorganic sources of iron. In a diet containing only 6% of the total iron as heme, 30% of the iron absorbed was acquired from heme, to the exclusion of other dietary sources (9). Pizarro et al found that heme absorption increased significantly (P < 0.01) in the presence of Fe-bis-gly. This indicates that the 2 sources were mutually compatible. Clearly, the uptake of one of the iron compounds was influenced by the presence of the other, which was the criterion that Bovell-Benjamin et al (4) used to assess iron absorption from iron sources. On the basis of this criterion and according to the data of Pizarro et al, heme and Fe-bis-gly share similar absorption properties.

REFERENCES

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