Alternatives to current management strategies for managing dietary iron deficiency can help compensate for the relative expense of food supplementation, for noncompliance with specific therapies and for interactions between supplements and endogenous food components such as phytate. Dietary iron deficiency and anemia afflict an estimated 1.5 billion people world. In the United States estimates of iron deficiency in women of reproductive age are approximately 6.6 percent and for children and adolescents, approximately 11 percent. The link between slow cognitive development and iron deficiency makes the potential economic impact great. Certain disease states such as Sickle Cell Disease (SCD), hereditary hemochromatosis (HH), and beta-thalassemia (beta-thal) have altered gut iron uptake that is poorly characterized. In addition, the consequences of Fe overload are different for SCD, beta-thal and HH. Such observations illustrate disease-dependent variations in handling iron. With more information, recommendations for different dietary iron sources in each disease states might need to be developed. Ferritin is a major source of iron in the early development of humans, other animals and plants. Legume seeds consumed by humans are rich in iron and ferritin. Soybean seed iron (largely ferritin) and horse spleen ferritin are available iron sources for iron deficient rats. During the last grant period soybean iron has been shown to be readily available to humans and horse spleen ferritin iron was shown to be taken up by cultured cells. However, there is little information about the molecular mechanism of iron uptake from ferritin. The impact of ferritin iron on expression of iron uptake and export proteins in normal or the disease states SCD, HH and beta-thal is not known, and the nutritional impact of differences in the mineral structure of plants (high phosphate) and animals (low phosphate) has not been explored. Proposed are three sets of experiments: 1. Uptake, metabolism and transport of iron from ferritin in Caco-2 cells and the fate of ferritin during digestion. 2. Comparison of ferritin and iron salts for of red cell iron, in mouse models of human disease. 3. Ferritin with high (plant) and low (animal) phosphate mineral for dietary iron in humans-whole body analyses. The results will clarify mechanisms of ferritin iron uptake and characterize molecular genetic differences in iron uptake for improving dietary iron sources in health and disease.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL056169-06
Application #
6621749
Study Section
Nutrition Study Section (NTN)
Program Officer
Evans, Gregory
Project Start
1998-06-18
Project End
2005-11-30
Budget Start
2002-12-01
Budget End
2003-11-30
Support Year
6
Fiscal Year
2003
Total Cost
$342,017
Indirect Cost
Name
Children's Hospital & Res Ctr at Oakland
Department
Type
DUNS #
076536184
City
Oakland
State
CA
Country
United States
Zip Code
94609
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Miller 3rd, Russell R; MacIntyre, Neil R; Hite, R Duncan et al. (2012) Point: should positive end-expiratory pressure in patients with ARDS be set on oxygenation? Yes. Chest 141:1379-1382
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Kalgaonkar, Swati; Lonnerdal, Bo (2008) Effects of dietary factors on iron uptake from ferritin by Caco-2 cells. J Nutr Biochem 19:33-9
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Theil, Elizabeth C (2007) Coordinating responses to iron and oxygen stress with DNA and mRNA promoters: the ferritin story. Biometals 20:513-21
Liu, X; Hintze, K; Lonnerdal, B et al. (2006) Iron at the center of ferritin, metal/oxygen homeostasis and novel dietary strategies. Biol Res 39:167-71

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