Evaluating Iron Metabolism and Supplementation in Gambian Toddlers Using a Novel, High‐Precision Method Based on the Dilution of Labelled Body Iron
Authors: Moretti Diego , Wegmuller Rita , Speich Cornelia , Zeder Christophe , Cichucka Magdalena , Cercamondi Colin I. , Prentice Andrew M. , Brittenham Gary , Zimmermann Michael B. 
Published: November 2023

Global efforts to reduce iron deficiency anemia are hindered by the unreliability of current iron status biomarkers in the presence of infection and inflammation. We developed and evaluated a novel stable iron isotope method based on the dilution of labelled body iron to measure and quantify the efficacy of an iron intervention and to quantify iron balance in rural Gambian toddlers.To label total body iron, we orally administered 2 mg 57Fe as FeSO4 to anemic infants (mean(SD) age: 16.7(1.6) months; Hb < 11.0 g/dl) and waited 41(4.9) weeks for equilibration of the 57Fe in body iron. We then randomly allocated the toddlers to 12 weeks of directly supervised feeding with: A) a micronutrient powder (MNP) containing 12 mg Fe given every day; B) a MNP containing 12 mg Fe given for seven days when hepdicin < 5.5 ng/ml at weekly screening; C) a MNP containing 6 mg Fe given for seven days when hepdicin < 5.5 ng/ml at weekly screening. We quantified the rate of change of body iron (RCFe), iron absorption (FeAbs), as well as the change in Hb (ΔHb), soluble transferrin receptor (ΔsTfR) and plasma ferritin (ΔPF). These markers were assessed in all toddlers in blood samples on day 49 and 84 of the intervention, and after a 12‐week control period post‐intervention.Complete data from 41 subjects was available for analysis. Time elapsed from isotopic administration to intervention start was not correlated with RCFe, suggesting complete isotopic label equilibration. RCFe significantly differed between the intervention and control period (P < 0.01), as did ΔHb (P < 0.01) and ΔsTfR (P < 0.01) but not ΔPF (P = 0.17). Compared to conventional iron biomarkers, RCFe had the strongest association with total administered iron dose (R2 = 0.44, P < 0.01). RCFe was also associated with ΔHb, ΔsTfR and ΔPF (R2 = 0.37, P < 0.01; R2 = 0.49, P < 0.01 and R2 = 0.11, P < 0.05, respectively). Across the three groups, FeAbs during the intervention (0.36 ± 0.13 mg Fe/d) was significantly higher than during the control period (0.13 ± 0.07 mg Fe/d, P < 0.01). During the intervention, FeAbs was significantly higher in group A (0.47 ± 0.18 mg Fe/d) than in groups B or C (0.30 ± 0.10 mg Fe/d and 0.33 ± 0.12 mg Fe/d, P = 0.01). Daily iron losses were significantly higher during the intervention (0.25 ± 0.11 mg Fe/d) than during the control period (0.11 ± 0.12 mg Fe/d, P < 0.01); there were no significant differences in daily iron losses between the three groups.ConclusionsRCFe measured with this technique is superior to conventional iron biomarkers in prediction of the administered iron dose. It may allow to quantify iron absorption, losses and overall iron balance over the long term, and is a promising tool to evaluate iron interventions with high precision entirely free from confounding by inflammation.Support or Funding InformationThis study was funded by ETH Zurich and Bill & Melinda Gates Foundation.