title: Overweight impairs efficacy of iron supplementation in iron-deficient South African children: a randomized controlled intervention.
abstract: BACKGROUND
  Many countries in the nutrition transition have high rates of iron deficiency (ID) and overweight (OW). ID is more common in OW children; this may be due to adiposity-related inflammation reducing iron absorption.
  
  
  OBJECTIVE
  We investigated whether weight status predicts response to oral iron supplementation in ID South African children.
  
  
  METHODS
  A placebo-controlled trial of oral iron supplementation (50 mg, 4 × weeks for 8.5 months) was done in ID 6- to 11-year-old children (n=321); 28% were OW or obese. BMI-for-age z-scores (BAZ), hepcidin (in a sub-sample), hemoglobin, serum ferritin (SF), transferrin receptor (TfR), zinc protoporphyrin (ZnPP) and C-reactive protein (CRP) were measured; body iron was calculated from the SF to TfR ratio.
  
  
  RESULTS
  At baseline, BAZ correlated with CRP (r=0.201, P<0.001) and CRP correlated with hepcidin (r=0.384, P<0.001). Normal weight children supplemented with iron had significantly lower TfR concentrations at endpoint than the OW children supplemented with iron and the children receiving placebo. Higher BAZ predicted higher TfR (β=0.232, P<0.001) and lower body iron (β=-0.090, P=0.016) at endpoint, and increased the odds ratio (OR) for remaining ID at endpoint in both the iron and placebo groups (iron: OR 2.31, 95% CI: 1.13, 4.73; placebo: OR 1.78, 95% CI: 1.09, 2.91). In the children supplemented with iron, baseline hepcidin and BAZ were significant predictors of endpoint TfR, with a trend towards a hepcidin × BAZ interaction (P=0.058).
  
  
  CONCLUSIONS
  South African children with high BAZ have a two-fold higher risk of remaining ID after iron supplementation. This may be due to their higher hepcidin concentrations reducing iron absorption. Thus, the current surge in OW in rapidly developing countries may undercut efforts to control anemia in vulnerable groups. The trial is registered at clinicaltrials.gov as NCT01092377.
authors.affiliation: Centre of Exellence for Nutrition (CEN), North-West University, Potchefstroom, South Africa. jeannine.baumgartner@gmail.com
authors.forename: J
authors.initials: J
authors.lastname: Baumgartner
authors.forename: C M
authors.initials: CM
authors.lastname: Smuts
authors.forename: I
authors.initials: I
authors.lastname: Aeberli
authors.forename: L
authors.initials: L
authors.lastname: Malan
authors.forename: H
authors.initials: H
authors.lastname: Tjalsma
authors.forename: M B
authors.initials: MB
authors.lastname: Zimmermann
mesh_terms: D018798:Anemia, Iron-Deficiency / Q000097:blood* / Q000178:diet therapy / Q000453:epidemiology; D023181:Antimicrobial Cationic Peptides / Q000378:metabolism; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000378:metabolism; D002648:Child; D019587:Dietary Supplements; D005260:Female; D006454:Hemoglobins / Q000378:metabolism; D064451:Hepcidins; D006801:Humans; D007249:Inflammation / Q000097:blood; D007501:Iron / Q000097:blood*; D000090463:Iron Deficiencies; D008297:Male; D050177:Overweight / Q000097:blood* / Q000178:diet therapy / Q000453:epidemiology; D011446:Prospective Studies; D011524:Protoporphyrins / Q000097:blood; D011990:Receptors, Transferrin / Q000097:blood; D012307:Risk Factors; D013019:South Africa / Q000453:epidemiology; D014168:Transferrin / Q000378:metabolism
chemical_list: D023181:Antimicrobial Cationic Peptides; D015415:Biomarkers; C578702:HAMP protein, human; D006454:Hemoglobins; D064451:Hepcidins; D011524:Protoporphyrins; D011990:Receptors, Transferrin; D014168:Transferrin; C017803:zinc protoporphyrin; D002097:C-Reactive Protein; D007501:Iron