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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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Schedule of malarial treatment and iron supplementation, including administration of stable iron isotopes. A course of iron supplementation was initiated in anemic Gambian children. Supplementation was initiated on day 1. Children who had presented with P falciparum parasitemia 3 days previously had their parasitemias cleared by a 3-day course of chloroquine/fansidar. The stable iron isotopes 57Fe and 58Fe were administered as sulfate on days 1 and 15, respectively. Iron, 2 mg/kg/d, was given as liquid iron glycine sulfate on all other days of the supplementation course starting from day 2.
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Figure 1: Schedule of malarial treatment and iron supplementation, including administration of stable iron isotopes. A course of iron supplementation was initiated in anemic Gambian children. Supplementation was initiated on day 1. Children who had presented with P falciparum parasitemia 3 days previously had their parasitemias cleared by a 3-day course of chloroquine/fansidar. The stable iron isotopes 57Fe and 58Fe were administered as sulfate on days 1 and 15, respectively. Iron, 2 mg/kg/d, was given as liquid iron glycine sulfate on all other days of the supplementation course starting from day 2.

Mentions: A study was previously carried out in anemic children (hemoglobin [Hb] < 110 g/L) aged 18-36 months recruited from the Medical Research Council (MRC) Keneba clinic in the West Kiang region of The Gambia during the malaria season of 2003. Children were considered as having postmalarial anemia if they presented with fever and with peripheral parasitemia (para00). Incorporation of stable iron isotopes into erythrocytes was compared between iron supplemented postmalarial anemic children (n = 37) after treatment of Plasmodium falciparum malaria (3 days of chloroquine/Fansidar, after which iron supplementation was initiated, on the day defined as “day 1, ” the fourth day after presentation with malaria) or matched anemic but nonmalarial children (n = 36), as previously described.19 Children were given a 30-day course of iron supplementation. Stable tracer isotopes consisting of non-heme 57Fe (ferrous sulfate, 3.9 mg) at day 1 and 58Fe (ferrous sulfate, 1.3 mg) at day 15 of the supplementation schedule were used, with all children receiving 2 mg/kg/d iron as liquid iron glycine sulfate on all other days of the supplementation course from day 2, as described previously.19 This schedule is depicted in Figure 1. Children were fasted for at least 2 hours before tracer dosing, which was followed by administration of 50 mg of vitamin C. These precautions minimize the influence of local inhibitory factors such as dietary phytates and facilitate iron absorption. Here, in subjects for whom sufficient residual plasma was available, we compared the relationships between hepcidin levels, other indices, and erythrocyte iron incorporation.


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)

Schedule of malarial treatment and iron supplementation, including administration of stable iron isotopes. A course of iron supplementation was initiated in anemic Gambian children. Supplementation was initiated on day 1. Children who had presented with P falciparum parasitemia 3 days previously had their parasitemias cleared by a 3-day course of chloroquine/fansidar. The stable iron isotopes 57Fe and 58Fe were administered as sulfate on days 1 and 15, respectively. Iron, 2 mg/kg/d, was given as liquid iron glycine sulfate on all other days of the supplementation course starting from day 2.
© Copyright Policy - creativecommons
Related In: Results  -  Collection

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

Figure 1: Schedule of malarial treatment and iron supplementation, including administration of stable iron isotopes. A course of iron supplementation was initiated in anemic Gambian children. Supplementation was initiated on day 1. Children who had presented with P falciparum parasitemia 3 days previously had their parasitemias cleared by a 3-day course of chloroquine/fansidar. The stable iron isotopes 57Fe and 58Fe were administered as sulfate on days 1 and 15, respectively. Iron, 2 mg/kg/d, was given as liquid iron glycine sulfate on all other days of the supplementation course starting from day 2.
Mentions: A study was previously carried out in anemic children (hemoglobin [Hb] < 110 g/L) aged 18-36 months recruited from the Medical Research Council (MRC) Keneba clinic in the West Kiang region of The Gambia during the malaria season of 2003. Children were considered as having postmalarial anemia if they presented with fever and with peripheral parasitemia (para00). Incorporation of stable iron isotopes into erythrocytes was compared between iron supplemented postmalarial anemic children (n = 37) after treatment of Plasmodium falciparum malaria (3 days of chloroquine/Fansidar, after which iron supplementation was initiated, on the day defined as “day 1, ” the fourth day after presentation with malaria) or matched anemic but nonmalarial children (n = 36), as previously described.19 Children were given a 30-day course of iron supplementation. Stable tracer isotopes consisting of non-heme 57Fe (ferrous sulfate, 3.9 mg) at day 1 and 58Fe (ferrous sulfate, 1.3 mg) at day 15 of the supplementation schedule were used, with all children receiving 2 mg/kg/d iron as liquid iron glycine sulfate on all other days of the supplementation course from day 2, as described previously.19 This schedule is depicted in Figure 1. Children were fasted for at least 2 hours before tracer dosing, which was followed by administration of 50 mg of vitamin C. These precautions minimize the influence of local inhibitory factors such as dietary phytates and facilitate iron absorption. Here, in subjects for whom sufficient residual plasma was available, we compared the relationships between hepcidin levels, other indices, and erythrocyte iron incorporation.

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