|Prentice, Andrew -|
|Doherty, Conor -|
|Abrams, Steven -|
|Cox, Sharon -|
|Atkinson, Sarah -|
|Verhoef, Hans -|
|Armitage, Andrew -|
|Drakesmith, Hal -|
Submitted to: Blood
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: December 22, 2011
Publication Date: February 23, 2012
Citation: Prentice, A.M., Doherty, C.P., Abrams, S.A., Cox, S.E., Atkinson, S.H., Verhoef, H., Armitage, A.E., Drakesmith, H. 2012. Hepcidin is the major predictor of erythrocyte iron incorporation in anemic African children. Blood. 119(8):1922-1928. Interpretive Summary: Iron supplementation strategies in the developing world remain controversial owing to fears of worsening prevalent infectious diseases. Understanding the conditions in which iron will be absorbed and incorporated into blood is therefore important. We studied children in the nation of The Gambia who were anemic with or without also having malaria, who were given oral iron supplements daily for 30 days.We found that the most consistent predictor of iron absorption as measured at the CNRC using mass spectrometry after stable isotope dosing, was a biochemical maker called hepcidin. We conclude that hepcidin powerfully controls the use of dietary iron. We suggest that low-cost hepcidin assays that could be done in developing countries would aid iron supplementation programs.
Technical Abstract: Iron supplementation strategies in the developing world remain controversial owing to fears of exacerbating prevalent infectious diseases. Understanding the conditions in which iron will be absorbed and incorporated into erythrocytes is therefore important. We studied Gambian children with either post-malarial or non-malarial anemia, who were given oral iron supplements daily for 30 days. Supplements administered on days 1 and 15 contained the stable iron isotopes (57)Fe and (58)Fe respectively, and erythrocyte incorporation was measured in blood samples drawn 14 days later. We investigated how the iron regulatory hormone hepcidin and other inflammatory/iron-related indices, all measured on the day of isotope administration, correlated with erythrocyte iron incorporation. In univariate analyses, hepcidin, ferritin, C-reactive protein (CRP) and soluble transferrin receptor (sTfR) strongly predicted incorporation of (57)Fe given on day 1, while hepcidin, ferritin and sTfR / log Ferritin correlated with (58)Fe incorporation. In a final multivariate model, the most consistent predictor of erythrocyte isotope incorporation was hepcidin. We conclude that under conditions of competing signals (anemia, iron deficiency and infection) hepcidin powerfully controls utilisation of dietary iron. We suggest that low-cost point-of-care hepcidin assays would aid iron supplementation programs in the developing world.