title: Vitamin A supplementation in children with poor vitamin A and iron status increases erythropoietin and hemoglobin concentrations without changing total body iron.
abstract: BACKGROUND
  Vitamin A deficiency impairs iron metabolism; vitamin A supplementation of vitamin A-deficient populations may reduce anemia. The mechanism of these effects is unclear. In vitro and in animal models, vitamin A treatment increases the production of erythropoietin (EPO), a stimulant of erythropoiesis.
  
  
  OBJECTIVE
  We measured the effect of vitamin A supplementation on hemoglobin, iron status, and circulating EPO concentrations in children with poor iron and vitamin A status.
  
  
  METHODS
  In a double-blind, randomized trial, Moroccan schoolchildren (n = 81) were given either vitamin A (200,000 IU) or placebo at baseline and at 5 mo. At baseline, 5 mo, and 10 mo, hemoglobin, indicators of iron and vitamin A status, and EPO were measured.
  
  
  RESULTS
  At baseline, 54% of children were anemic; 77% had low vitamin A status. In the vitamin A group at 10 mo, serum retinol improved significantly compared with the control group (P < 0.02). Vitamin A treatment increased mean hemoglobin by 7 g/L (P < 0.02) and reduced the prevalence of anemia from 54% to 38% (P < 0.01). Vitamin A treatment increased mean corpuscular volume (P < 0.001) and decreased serum transferrin receptor (P < 0.001), indicating improved iron-deficient erythropoiesis. Vitamin A decreased serum ferritin (P < 0.02), suggesting mobilization of hepatic iron stores. Calculated from the ratio of transferrin receptor to serum ferritin, overall body iron stores remained unchanged. In the vitamin A group at 10 mo, we observed an increase in EPO (P < 0.05) and a decrease in the slope of the regression line of log10(EPO) on hemoglobin (P < 0.01).
  
  
  CONCLUSIONS
  In children deficient in vitamin A and iron, vitamin A supplementation mobilizes iron from existing stores to support increased erythropoiesis, an effect likely mediated by increases in circulating EPO.
authors.affiliation: Human Nutrition Laboratory, Swiss Federal Institute of Technology, Zürich, Switzerland, and The Ministry of Health, Rabat, Morocco. michael.zimmerman@ilw.agrl.ethz.ch
authors.forename: Michael B
authors.initials: MB
authors.lastname: Zimmermann
authors.forename: Ralf
authors.initials: R
authors.lastname: Biebinger
authors.forename: Fabian
authors.initials: F
authors.lastname: Rohner
authors.forename: Abdeljawad
authors.initials: A
authors.lastname: Dib
authors.forename: Christophe
authors.initials: C
authors.lastname: Zeder
authors.forename: Richard F
authors.initials: RF
authors.lastname: Hurrell
authors.forename: Nourredine
authors.initials: N
authors.lastname: Chaouki
mesh_terms: D000293:Adolescent; D018798:Anemia, Iron-Deficiency / Q000097:blood / Q000453:epidemiology* / Q000209:etiology / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D019587:Dietary Supplements; D004311:Double-Blind Method; D004909:Erythrocyte Indices; D004920:Erythropoiesis; D004921:Erythropoietin / Q000096:biosynthesis* / Q000493:pharmacokinetics; D005260:Female; D005293:Ferritins / Q000097:blood; D006454:Hemoglobins / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D007501:Iron / Q000378:metabolism*; D033862:Iron-Binding Proteins / Q000097:blood; D008297:Male; D009018:Morocco; D011956:Receptors, Cell Surface / Q000097:blood; D016896:Treatment Outcome; D014801:Vitamin A / Q000008:administration & dosage / Q000494:pharmacology*; D014802:Vitamin A Deficiency / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D014815:Vitamins / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D006454:Hemoglobins; D033862:Iron-Binding Proteins; D011956:Receptors, Cell Surface; D014815:Vitamins; C027293:ferritin receptor; D004921:Erythropoietin; D014801:Vitamin A; D005293:Ferritins; D007501:Iron