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United States Department of Agriculture

Agricultural Research Service


item Hunt, Janet

Submitted to: American Journal of Clinical Nutrition
Publication Type: Other
Publication Acceptance Date: 1/13/2005
Publication Date: 5/1/2005
Citation: Hunt, J.R. 2005. Letter to the editor: absorption of iron from ferritin. American Journal of Clinical Nutrition. 81(5):1178-79.

Interpretive Summary:

Technical Abstract: Your Manuscript Number (MS #) is: 21351, Version 1 Letter to the Editor: Absorption of Iron from Ferritin Dear Sir: I would like comment on the paper, 'Iron in ferritin or in salts (ferrous sulfate) is equally bioavailable in nonanemic women' by P. Davila-Hicks, E. C. Theil, and B. Lonnerdal (1). The conclusion indicated in the title is based on measurements of iron absorption from horse spleen ferritin that was radiolabeled in vitro, and appears to contrast with the results of others whose studies using ferritin radiolabeled in vivo were not cited (2-4). For example, Skikne and colleagues (4) also found that iron from ferritin radiolabeled in vitro was absorbed similarly to iron from ferrous sulfate. However, the same group further reported that radioiron incorporated into bovine spleen ferritin in vivo was significantly less absorbed than iron from ferrous sulfate: (respectively) 3.2 vs. 8.2% from a 3 mg dose with food, 3.8 vs. 24.1% from the 3 mg without food, 0.6 vs. 2.6 from 50 mg with food, and 0.7 vs. 7.9 from 50 mg without food (4). Those who have studied ferritin radiolabeled in vivo have concluded that ferritin iron is poorly absorbed, and that it is not part of the nonheme pool of dietary iron that is readily exchangeable in and similarly absorbed from the intestinal lumen (2-4). For instance, in vivo-labeled ferritin 59Fe was only 36% as well absorbed as 55Fe from intrinsically labeled soybeans consumed in the same meal (2). Its possible that lower absorption of ferritin-iron may explain the slightly increased (10%) absorption of nonheme iron from extrinsic over intrinsically labeled foods (5), which would suggest that the ferritin-iron content of the foods is only a minor portion of total food iron. It is worth noting that the ferritin iron content of foods has not been widely determined because of the lack of species-specific antibodies as well as the insolubility and possible time-dependent molecular changes that may make ferritin iron less exchangeable (6). Each labeling method has potential problems. On the one hand, the in vivo labeling of animal ferritin has in some (2, 4), but not all (3) reports involved procedures to limit the radiolabel incorporation into blood by reducing erythrocyte synthesis or increasing erythrocyte breakdown, and it is not known whether these techniques may alter ferritin isomerization. It is clear that the in vivo procedure does not uniformly label all of the iron in ferritin, but this would not necessarily explain the reduced iron bioavailability, as the portion that is unlabeled may be less, not more exchangeable/absorbable. On the other hand, the in vitro labeling results in higher bioavailability whether the ferritin has first been depleted of iron (1) or not (4), and in vitro iron exchange can induce ferritin degradation through Fenton chemistry (6). Skikne et al. (4) observed a minor small molecular peak in the Sepharose 6B elution pattern of in vitro, but not in vivo labeled ferritin, that they proposed to be denatured ferritin. Those investigators (4) determined that in vitro procedures labeled a full range of isoferritins, but with slightly higher isotope incorporation into the more acidic forms (4). It is unlikely that horse spleen ferritin labeled with extra phosphorus in vitro (1) is comparable to plant ferritin. Using Mössbauer spectroscopy, Ambe et al. (7) found that the form of ferric iron, representing about 95% of the iron in soybeans, was clearly distinguishable from, but more similar to horse spleen ferritin than to ferric phytate. Although physicochemical methods detected only minor alterations in ferritin labeled in vitro (1, 4), the human absorption results provide a distinguishing bioassay for ferritin labeled in vitro vs. in vivo. Davila-Hicks et al. (1) proposed that a high absorption of iron from the Tokyo soybean cultivar is partially explained by a

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