Source: AGRICULTURAL RESEARCH SERVICE submitted to
COMBATING IRON DEFICIENCY: ABSORPTION & EFFICACY IN HUMANS OF ELEMENTAL IRON POWDERS & HEME IRON
Sponsoring Institution
Agricultural Research Service/USDA
Project Status
TERMINATED
Funding Source
Reporting Frequency
Annual
Accession No.
0405631
Grant No.
(N/A)
Project No.
5450-51000-035-13T
Proposal No.
(N/A)
Multistate No.
(N/A)
Program Code
(N/A)
Project Start Date
Jul 1, 2002
Project End Date
Sep 30, 2006
Grant Year
(N/A)
Project Director
HUNT J R
Recipient Organization
AGRICULTURAL RESEARCH SERVICE
(N/A)
GRAND FORKS,ND 58201
Performing Department
(N/A)
Non Technical Summary
(N/A)
Animal Health Component
(N/A)
Research Effort Categories
Basic
25%
Applied
75%
Developmental
0%
Classification

Knowledge Area (KA)Subject of Investigation (SOI)Field of Science (FOS)Percent
5022499101010%
5023999101010%
7026010101060%
7026099101020%
Goals / Objectives
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. As supporting objectives, we will assess the effect of these iron sources on: absorption of nonheme iron from other dietary sources, oxidative stress in the lower intestine, plasma zinc, attention, and affect (mood). 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.
Project Methods
The efficacy of two elemental iron powders (objective 1) will be assessed in a human study of premenopausal women with low iron stores. In a 17 week study, healthy premenopausal women, admitted with moderate to low iron stores (serum ferritin <30 ug /L), will have their iron stores reduced to low using individualized phlebotomy schedules for 5 weeks. Then for 12 weeks, one of the following 5 iron sources or placebo will be added to their diets: ferrous sulfate monohydrate (a positive control), electrolytic iron powder, reduced iron powder (each providing 50 mg iron daily), heme iron (providing 5 mg iron daily), or placebo. Serum ferritin, an indicator of body iron stores, will be the primary outcome variable. Other blood measurements will include additional iron status variables and plasma zinc. Stool indices of oxidative stress, psychological tests of affect and attention, and nonheme iron absorption from foods will be measured at the beginning and end of the 12-week period of iron treatment. The absorption of irradiated electrolytic iron powder, relative to ferrous sulfate (Objective 2), will be determined using radiolabeled meals consumed by healthy adults. Absorption of a commercially available electrolytic iron powder labeled with Fe-55 isotope by previous neutron activation will be compared with absorption of ferrous sulfate radiolabeled with Fe-59. A series of three radiolabeled meal studies will be used to assess the effects of the iron source and of one of the dietary modifiers (ascorbic acid, phytic acid, or dose), in a 2X2 factorial design. Each experiment will last for 29 days, with 4 different radiolabeled meals served on days 1, 2, 15, and 16. Erythrocyte isotope incorporation will be measured 2 weeks after each set of 2 meals. Experiment 1 will compare the absorption of electrolytic iron and ferrous sulfate, and assess the effects of ascorbic acid. A farina test meal will be fortified with 3 mg of iron as either ferrous sulfate (labeled with Fe-59) or electrolytic iron (labeled with Fe-55), and these two sources will be tested with and without orange juice to provide approximately 100 mg ascorbic acid to increase nonheme iron absorption by two-fold, or 100%. Experiment 2 will compare the absorption of the same two forms of iron with and without wheat bran, a source of phytic acid. Approximately 300 mg phytic acid will reduce nonheme iron absorption from a meal by 75%. This amount of phytic acid is contained in 10 g of wheat bran, which will be added to the farina meal. Experiment 3 will compare the absorption of the two forms of iron as affected by the iron dose, tested at doses of 1 and 20 mg. The latter amount is comparable to the amount of iron in some highly fortified breakfast cereals on the US market. This increase in the iron dose is predicted to reduce percent iron absorption from ferrous sulfate by one-half (the absolute amount of iron absorbed will be increased at the higher dose).

Progress 07/01/02 to 09/30/06

Outputs
Progress Report 4d Progress report. This is the final report to document research conducted under a trust fund cooperative agreement between ARS and the USDA CSREES Nutritional Research Initiative 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 had two objectives. 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 ~85% 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. 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. 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. 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. 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. 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. 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. 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.

Impacts
(N/A)

Publications

  • Swain, J.H., Johnson, L.K., Hunt, J.R. 2004. Combating iron deficiency: bioavailability of iron from two elemental iron powders and a heme iron supplement in humans [abstract]. Federation of American Societies for Experimental Biology Journal. 18:A155.


Progress 10/01/04 to 09/30/05

Outputs
4d Progress report. This report serves to document research conducted under trust agreement 03-5450-3-0237, concerning the USDA CSREES Nutritional Research Initiative 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. Additional information can be found in the parent CRIS project 5450-51000-035-00D. 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 second objective. In 3 experiments, iron absorption was measured in 56 volunteers, using Fe-59 labeled ferrous sulfate, and an electrolytic iron powder that had been labeled with Fe-55 by neutron activation several years earlier. The iron absorbed from the irradiated electrolytic powder was much lower than expected, 5-10% that of ferrous sulfate, in contrast with earlier results (J Nutr 1999;129:181-7) using this same iron powder, which showed retention of 50% relative to ferrous sulfate in pigs. This observed low absorption was also in contrast to the efficacy results (with non- irradiated powder) in objective 1, as reported last year. This raises the possibility that the heat of the irradiation process had reduced the bioavailability, and that pigs may not be a good model of human iron absorption. Ascorbic acid enhanced iron absorption from ferrous sulfate more than from electrolytic powder, and a higher administered iron dose reduced iron absorption from ferrous sulfate more than from electrolytic. Phytic acid inhibition did not significantly interact with the iron source, but this was likely because the inhibition was extensive, with a meal that was already poorly bioavailable. The results support the conclusion that the reduced bioavailability of some elemental iron powders (previously shown to correlate with the solubility of the powder) renders them less interactive with other enhancers and inhibitors of iron absorption. Additional data analysis and manuscript preparation is in progress.

Impacts
(N/A)

Publications

  • Swain, J.H., Johnson, L.K., Hunt, J.R. 2004. Combating iron deficiency: bioavailability of iron from two elemental iron powders and a heme iron supplement in humans [abstract]. Federation of American Societies for Experimental Biology Journal. 18:A155.


Progress 10/01/03 to 09/30/04

Outputs
4. What were the most significant accomplishments this past year? A. None B. None C. None D. This report serves to document research conducted under 3-5450-3-0237 Trust Agreement. Additional details can be found in the report for the parent CRIS 5450-51000-035-00D (formerly 5450-51000-032-00D), concerning the USDA CSREES Nutritional Research Initiative 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 (FeSO4DTH2O, 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 (JD Cook. Blood 101:3359, 2003), which detected the treatment differences more sensitively than several other indexes of iron status. 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). 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. Because the reduced and electrolytic iron sources are more stable and can extend the shelf-life with fewer adverse organoleptic changes in fortified foods, in comparison with FeSO4, these results can be useful in selecting forms and amounts of iron to use for food fortification. Additional data analysis and manuscript preparation is in progress.

Impacts
(N/A)

Publications

  • Swain, J.H., Johnson, L.K., Hunt, J.R. 2004. Combating iron deficiency: bioavailability of iron from two elemental iron powders and a heme iron supplement in humans [abstract]. Federation of American Societies for Experimental Biology Journal. 18:A155.


Progress 10/01/02 to 09/30/03

Outputs
4. What were the most significant accomplishments this past year? A. None. B. None. C. None. D. This is a report of research conducted under the USDA ARS CRIS project 5450-51000-032-00D, concerning the USDA CSREES Nutritional Research Initiative competitive grant 2002-01885 (CREES CRIS 0192629) entitled "Combating Iron Deficiency: Absorption and Efficacy in Humans of Elemental Iron Powders and Heme Iron". This project has the following 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. Supporting objectives include assessment of the effect of these iron sources on: absorption of nonheme iron from other dietary sources, oxidative stress in the lower intestine, plasma zinc, attention, and affect (mood). 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 funding was received. Approved human studies protocols were completed for 52 subjects for objective 1 and an additional 56 subjects for objective 2. 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. Completion of data analysis and reporting for the first objective is expected within the next year. This research will help establish the efficacy of elemental iron powders used in food fortification for improving human iron deficiency, a global nutrition problem. This year funding was received, subjects were successfully recruited for studies addressing both objectives and biological samples were collected for further chemical and statistical analysis. Results are not yet available. Completion of data analysis and reporting for the first objective is expected within the next year. This research will help establish the efficacy of elemental iron powders used in food fortification for improving human iron deficiency, a global nutrition problem.

Impacts
(N/A)

Publications

  • None.


Progress 10/01/01 to 09/30/02

Outputs
4. What was your most significant accomplishment this past year? D. This report serves to document research conducted under USDA CSREES Nutritional Research Initiative competitive grant 2002-01885 (CREES CRIS 0192629) entitled "Combating Iron Deficiency: Absorption and Efficacy in Humans of Elemental Iron Powders and Heme Iron." This year funding was awarded to meet the following 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. As supporting objectives, we will assess the effect of these iron sources on: absorption of nonheme iron from other dietary sources, oxidative stress in the lower intestine, plasma zinc, attention, and affect (mood). 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. Work on these objectives has been initiated.

Impacts
(N/A)

Publications

  • None.