Vitamin A supplementation in children with poor vitamin A and iron status increases erythropoietin and hemoglobin concentrations without changing total body iron

Am J Clin Nutr. 2006 Sep;84(3):580-6. doi: 10.1093/ajcn/84.3.580.


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.

Design: 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).

Conclusion: 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.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Anemia, Iron-Deficiency / blood
  • Anemia, Iron-Deficiency / epidemiology*
  • Anemia, Iron-Deficiency / etiology
  • Anemia, Iron-Deficiency / metabolism
  • Child
  • Child, Preschool
  • Dietary Supplements
  • Double-Blind Method
  • Erythrocyte Indices
  • Erythropoiesis
  • Erythropoietin / biosynthesis*
  • Erythropoietin / pharmacokinetics
  • Female
  • Ferritins / blood
  • Hemoglobins / drug effects
  • Hemoglobins / metabolism*
  • Humans
  • Iron / metabolism*
  • Iron-Binding Proteins / blood
  • Male
  • Morocco
  • Receptors, Cell Surface / blood
  • Treatment Outcome
  • Vitamin A / administration & dosage
  • Vitamin A / pharmacology*
  • Vitamin A Deficiency / blood
  • Vitamin A Deficiency / complications
  • Vitamin A Deficiency / drug therapy*
  • Vitamins / administration & dosage
  • Vitamins / pharmacology*


  • Hemoglobins
  • Iron-Binding Proteins
  • Receptors, Cell Surface
  • Vitamins
  • ferritin receptor
  • Erythropoietin
  • Vitamin A
  • Ferritins
  • Iron