Submitted to: American Journal of Clinical Nutrition
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: May 13, 2004
Publication Date: October 1, 2004
Citation: Hunt, J.R., Zeng, H. 2004. Iron absorption by heterozygous carriers of the HFE C282Y mutation associated with hemochromatosis. American Journal of Clinical Nutrition. 80:924-31. Interpretive Summary: A possible diet and genetic interaction was investigated by testing iron absorption of people who carry the genetic mutation associated with hemochromatosis, a serious iron storage disorder. Carriers of the mutation, who have received the genetic trait from one, but not both parents, are approximately 10% of the white population in the US. If these people absorb iron excessively, their risk of disease could be increased by the fortification of foods with iron and vitamin C. We conducted genotyped volunteers from the community, and measured their absorption of iron (both the form commonly in foods and the heme form found in meat, poultry and fish) from a hamburger meal, with and without additional iron and vitamin C fortification. Carriers of the mutation associated with hemochromatosis did not absorb either form of iron differently than control subjects who did not carry the mutation. This was true whether or not the meal was highly fortified. We conclude that people who carry this genetic trait are not at an increased risk of excessive absorption of iron from fortified foods.
Technical Abstract: Background: Research conducted before genotyping was possible suggested that subjects heterozygous for the genetic mutation associated with hemochromatosis absorbed nonheme iron more efficiently than controls, when tested with a fortified meal. Heme iron absorption in these subjects has not been reported. Objective: To compare HFE C282Y heterozygotes and wildtype controls, for their absorption of heme and nonheme iron from minimally or highly fortified test meals. Design: After prospectively genotyping 256 healthy volunteers, 11 C282Y heterozygotes and 12 controls (matched for serum ferritin, age, and sex) were recruited and their iron absorption was compared using a hamburger meal with or without added iron and ascorbic acid. After retrospectively genotyping 103 participants in previous iron absorption studies, 5 C282Y heterozygotes were compared with 72 wildtype controls. Results: HFE C282Y heterozygotes did not differ significantly from wildtype controls in their absorption of either heme or nonheme iron from either minimally or highly fortified test meals. No differences were detected in blood indices of iron status, including serum ferritin, transferrin saturation, and non-transferrin-bound iron (NTBI), or in blood lipids or transaminases, but heterozygotes had significantly greater, although normal, fasting glucose than wildtype controls. Compound heterozygotes (with both HFE C282Y and H63D mutations) absorbed more nonheme (but not heme) iron from high (but not low) bioavailability meals. Conclusions: Heterozygous carriers of the HFE C282Y mutation did not absorb dietary iron more efficiently, even when foods were fortified with extra iron and ascorbic acid. Therefore, iron fortification of foods should not pose an additional health risk to these people.