Progress 08/01/02 to 07/31/06
Outputs
Objective 1 was to determine the efficacy of fortifying food with elemental iron powders, relative to equivalent amounts of ferrous sulfate, or of supplementing with a limited amount of iron in the heme form, on serum ferritin in women with low iron stores. In a randomized, blinded trial, 51 premenopausal women with moderate to low iron stores received daily for 12 wk: a) placebo; b) 5 mg iron as heme iron; or 50 mg iron as c) electrolytic iron; d) reduced iron; or e) FeSO4. Treatments were provided in 2 capsules (heme carrier) and 3 wheat rolls (other iron sources). Iron treatments did not affect food iron absorption. The 50 mg/d iron treatments increased fecal iron and free-radical generating capacity in vitro, but did not affect fecal water cytotoxicity. FeSO4 slightly increased fecal water content. Iron treatments did not affect most tests of mood, depression or attention, but the sensitivity of these comparisons was likely diminished by the broad range of iron
status of the subjects, from marginal to moderate. Electrolytic iron was ~86% as efficacious as FeSO4 for improving body iron, but the power of this study was insufficient to detect any efficacy of the reduced or heme iron within 12 weeks. Objective 2 was to determine the absorption of irradiated electrolytic iron powder, relative to ferrous sulfate, as affected by dose and by interactions with ascorbic acid and phytic acid (3 experiments). Iron absorption by 56 volunteers was measured from a farina cereal breakfast radiolabeled with 59FeSO4 or an electrolytic 55Fe powder irradiated by neutron activation. Absorption of iron from the irradiated electrolytic powder was 5-15% that of FeSO4. Ascorbic acid (~160 mg) enhanced iron absorption from FeSO4 by 5 times vs. 2 times from electrolytic iron (p< 0.01 for interaction). Phytic acid from wheat bran inhibited iron absorption from FeSO4 and electrolytic iron by 73 and 50%, respectively (NS for interaction). Compared to 3 mg, a 20 mg dose
reduced fractional absorption from FeSO4, but not electrolytic iron (p< 0.0001 for interaction). Despite a much higher bioavailability (50% relative to FeSO4) of this same electrolytic iron when previously tested in a pig model, the bioavailability of the irradiated electrolytic iron was poor when fed to humans. Additional work tested the relationship between serum prohepcidin and iron absorption in healthy premenopausal women. Hepcidin is proposed as a regulator of iron absorption, but it has only been possible to immunologically measure the larger pro-peptide in serum. Serum pro-hepcidin concentrations were relatively stable within subjects, and correlated with serum ferritin. However, unlike serum ferritin, neither serum nor urinary pro-hepcidin concentrations were related to iron absorption in healthy women. Further work evaluated the relationship of dietary iron and other dietary factors on human zinc absorption. A resulting bioavailability algorithm for zinc absorption from
human diets explained ~83% of the variation in zinc absorption based on dietary content of zinc, phytic acid, calcium and iron.
Impacts
This demonstration of the usefulness of electrolytic iron powder as a food fortificant to improve iron status of women will be useful to developing nations as they develop food fortification policies that specify methods of iron fortification. The diminished influence of ascorbic acid on the absorption of less soluble iron sources such as elemental iron powders may be an important consideration when choosing iron fortificants such as elemental iron powders. Elucidation of the role of the antibacterial peptide hepcidin in regulating human iron absorption will help in understanding the interaction between iron absorption and infection, and may influence guidelines for iron fortification of populations with a high incidence of infection. Readily available estimates of iron or zinc absorption from diets are useful to evaluate and improve the diets of populations at risk of zinc deficiency, and to evaluate the potential impact of changes in US diets.
Publications
- Hadley KB, Johnson LK, and Hunt JR. Iron absorption by healthy women is not associated with either serum or urinary pro-hepcidin. Am J Clin Nutr 84:150-155, 2006.
- Swain JH, Johnson LK, and Hunt JR. Combating iron deficiency: Bioavailability of iron from two elemental iron powders and a heme iron supplement in humans. FASEB J 18: A155, 2004 (abstract).
- Beiseigel JM and Hunt JR. Algorithms for estimating zinc absorption from whole diets. FASEB J 19:A456, 2005 (abstract).
- Hunt JR and Swain JH. Bioavailability to humans of an electrolytic elemental iron fortificant, assessed after radiolabeling by neutron activation. FASEB J 19:A1468, 2005 (abstract).
- Hadley KB, Johnson LK and Hunt JR. Serum prohepcidin does not predict iron absorption in healthy women. FASEB J 19:A1481, 2005 (abstract).
- Swain JH, Johnson LK, and Hunt JR. An irradiated electrolytic iron fortificant, poorly absorbed by human subjects, is also less responsive to the enhancing effect of ascorbic acid. J Nutr 136:2167-2174, 2006.
- Hunt JR, Hadley KB, and Johnson LK. Serum prohepcidin was not associated with iron absorption by healthy women in a dose-response assessment of elemental iron powders. First Congress of the International BioIron Society, May 22-26, Prague, Czech Republic: Abstracts, p. 57, 2005 (abstract).
- Swain JH, Penland JG, Johnson LK, Hunt JR. Energy, mood and attention did not consistently improve with iron status in non-anemic women with moderate to low iron stores. FASEB J 20:A191-2, 2006 (abstract).
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Progress 10/01/03 to 09/30/04
Outputs
This report serves to document research conducted under ARS CRIS project 5450-51000-035-00D (formerly 5450-51000-032-00D), concerning the USDA CSREES NRI competitive grant 2002-01885 (and tracked by CREES as CRIS 0192629) entitled Combating Iron Deficiency: Absorption and Efficacy in Humans of Elemental Iron Powders and Heme Iron. This project has two objectives: 1) to determine the efficacy of fortifying food with elemental iron powders, relative to equivalent amounts of ferrous sulfate, or of supplementing with a limited amount of iron in the heme form, on serum ferritin in women with low iron stores, and 2) to determine the absorption of irradiated electrolytic iron powder, relative to ferrous sulfate, as affected by dose and by interactions with ascorbic acid and phytic acid. This year we report the results of the first objective. In a randomized, blinded, controlled efficacy trial, 52 premenopausal women with moderate to low iron stores received: a) placebo; b) 5
mg iron as heme iron (VitaHeme, USA); or 50 mg iron as c) electrolytic iron (A-131, USA); d) reduced iron (ATOMET 95SP, Canada); or e) bakery-grade FeSO4 (FeSO4.H2O, USA). The heme iron was given in 2 capsules/d and the other sources in 3 wheat rolls/d, provided for 12 wk. The change in body iron was assessed from the serum transferrin receptor/serum ferritin ratio. Body iron (mg/kg body wt) increased with all four iron sources (LSM+/-SEM): FeSO4 (2.0+/-0.5, p<0.004), electrolytic (1.7+/-0.5, p<0.008), reduced (1.0+/-0.4, p<0.03), and heme (1.0+/-0.4, p<0.04), but not with placebo (0.1+/-0.3, NS). Fecal iron fractions and free radical-generating capacity were also evaluated. Each of the four iron treatments, but not the placebo, increased fecal iron content, and all of the 50 mg/d iron treatments increased the soluble and chelatable fecal iron fractions and the in vitro free radical-generating capacity of the feces. The cytotoxicity of fecal water to HT29 cells increased with fecal
water concentration, but was unaffected by iron treatment. In assessments of mood and attention, iron treatments had no effect on depression or attention. Iron treatment significantly affected the energetic-tired scale of the Profile of Mood States; however, the results were not fully consistent with the changes observed in iron status, as improved energy was observed with heme and ferrous sulfate treatments, but not with the elemental iron powders. Changes in body iron with iron treatment did not significantly predict changes in mood, depression, or attention. The results indicate that the reduced and electrolytic iron sources were approximately 50 and 85% as effective as FeSO4 and that 5 mg iron in the heme form was half as effective as 50 mg of iron from FeSO4 for improving body iron in humans. A manuscript has been prepared for submission to a peer-reviewed journal.
Impacts
This research will help establish the efficacy of elemental iron powders used in food fortification for addressing human iron deficiency. Because, in comparison with FeSO4, the reduced and electrolytic iron sources are more stable and can extend the shelf-life with fewer adverse organoleptic changes in fortified foods, these results can be useful in selecting forms and amounts of iron to use for food fortification.
Publications
- Swain JH, Johnson LK, Hunt JR. 2004 Combating iron deficiency: Bioavailability of iron from two elemental iron powders and a heme iron supplement in humans. [abstract] FASEB J 18: A155
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Progress 10/01/02 to 09/30/03
Outputs
(Please note that this project is CRIS 0192629 for CREES and CRIS 0405631 for ARS). Under approved human studies protocols, sample collection was completed for 52 women for objective 1, to determine the efficacy of fortifying food with elemental iron powders, relative to equivalent amounts of ferrous sulfate, or of supplementing with a limited amount of iron in the heme form, on serum ferritin in women with low iron stores. Sample collection was also completed for an additional 56 subjects for objective 2, to determine the absorption of irradiated electrolytic iron powder, relative to ferrous sulfate, as affected by dose and by interactions with ascorbic acid and phytic acid. Chemical analyses of the data are in the final stages of completion, and statistical analysis of the data has begun. The results are not yet ready for reporting, but completion of data analysis and reporting for the first objective is expected within the next year.
Impacts
This research will help establish the efficacy of elemental iron powders used in food fortification for addressing human iron deficiency, a global nutrition problem. It will also evaluate the benefit of supplementation with the efficiently absorbed heme form of iron.
Publications
- No publications reported this period
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