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Hepcidin is the major predictor of erythrocyte iron incorporation in anemic African children.

Prentice AM, Doherty CP, Abrams SA, Cox SE, Atkinson SH, Verhoef H, Armitage AE, Drakesmith H - Blood (2012)

Bottom Line: Iron supplementation strategies in the developing world remain controversial because of fears of exacerbating prevalent infectious diseases.In univariate analyses, hepcidin, ferritin, C-reactive protein, 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.We suggest that low-cost point-of-care hepcidin assays would aid iron supplementation programs in the developing world.

View Article: PubMed Central - PubMed

Affiliation: Medical Research Council International Nutrition Group, London School of Hygiene & Tropical Medicine, London, United Kingdom. andrew.prentice@lshtm.ac.uk

ABSTRACT
Iron supplementation strategies in the developing world remain controversial because of 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 postmalarial or nonmalarial 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, 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 use of dietary iron. We suggest that low-cost point-of-care hepcidin assays would aid iron supplementation programs in the developing world.

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Scatterplots of oral iron incorporation versus hepcidin. (A) Serum hepcidin measured on day 1 is plotted against incorporation of 57Fe (which was administered on day 1). (B) Serum hepcidin measured on day 15 is plotted against incorporation of 58Fe (which was administered on day 15). ● indicates children admitted into the study with postmalarial anemia; and ○, children admitted into the study with nonmalarial anemia. Line depicts best-fit regression.
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Figure 2: Scatterplots of oral iron incorporation versus hepcidin. (A) Serum hepcidin measured on day 1 is plotted against incorporation of 57Fe (which was administered on day 1). (B) Serum hepcidin measured on day 15 is plotted against incorporation of 58Fe (which was administered on day 15). ● indicates children admitted into the study with postmalarial anemia; and ○, children admitted into the study with nonmalarial anemia. Line depicts best-fit regression.

Mentions: The strongest predictor of 57Fe erythrocyte incorporation was hepcidin, which was significantly negatively associated (adjusted R2 = 67%, P < .0001; Figure 2A); CRP and ferritin were also highly significant negative predictors of 57Fe incorporation. A strong positive association of 57Fe erythrocyte incorporation with sTfR, and a weaker, but significant, positive correlation with sTfR-F index were also found. These data suggest that at the start of the course of iron supplementation, there was an influence of both inflammatory stimuli and iron status on oral iron use.


Hepcidin is the major predictor of erythrocyte iron incorporation in anemic African children.

Prentice AM, Doherty CP, Abrams SA, Cox SE, Atkinson SH, Verhoef H, Armitage AE, Drakesmith H - Blood (2012)

Scatterplots of oral iron incorporation versus hepcidin. (A) Serum hepcidin measured on day 1 is plotted against incorporation of 57Fe (which was administered on day 1). (B) Serum hepcidin measured on day 15 is plotted against incorporation of 58Fe (which was administered on day 15). ● indicates children admitted into the study with postmalarial anemia; and ○, children admitted into the study with nonmalarial anemia. Line depicts best-fit regression.
© Copyright Policy - creativecommons
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3351093&req=5

Figure 2: Scatterplots of oral iron incorporation versus hepcidin. (A) Serum hepcidin measured on day 1 is plotted against incorporation of 57Fe (which was administered on day 1). (B) Serum hepcidin measured on day 15 is plotted against incorporation of 58Fe (which was administered on day 15). ● indicates children admitted into the study with postmalarial anemia; and ○, children admitted into the study with nonmalarial anemia. Line depicts best-fit regression.
Mentions: The strongest predictor of 57Fe erythrocyte incorporation was hepcidin, which was significantly negatively associated (adjusted R2 = 67%, P < .0001; Figure 2A); CRP and ferritin were also highly significant negative predictors of 57Fe incorporation. A strong positive association of 57Fe erythrocyte incorporation with sTfR, and a weaker, but significant, positive correlation with sTfR-F index were also found. These data suggest that at the start of the course of iron supplementation, there was an influence of both inflammatory stimuli and iron status on oral iron use.

Bottom Line: Iron supplementation strategies in the developing world remain controversial because of fears of exacerbating prevalent infectious diseases.In univariate analyses, hepcidin, ferritin, C-reactive protein, 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.We suggest that low-cost point-of-care hepcidin assays would aid iron supplementation programs in the developing world.

View Article: PubMed Central - PubMed

Affiliation: Medical Research Council International Nutrition Group, London School of Hygiene & Tropical Medicine, London, United Kingdom. andrew.prentice@lshtm.ac.uk

ABSTRACT
Iron supplementation strategies in the developing world remain controversial because of 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 postmalarial or nonmalarial 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, 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 use of dietary iron. We suggest that low-cost point-of-care hepcidin assays would aid iron supplementation programs in the developing world.

Show MeSH
Related in: MedlinePlus