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

• Published in: The American journal of clinical nutrition 2006-09, Vol.84 (3), p.580-586
• Main Authors: Zimmermann, Michael B, Biebinger, Ralf, Rohner, Fabian, Dib, Abdeljawad, Zeder, Christophe, Hurrell, Richard F, Chaouki, Nourredine
• Format: Article
• Language: English
• Subjects: Adolescent; Anemia; Anemia, Iron-Deficiency - blood; Anemia, Iron-Deficiency - epidemiology; Anemia, Iron-Deficiency - etiology; Anemia, Iron-Deficiency - metabolism; Biological and medical sciences; Child; Child, Preschool; Children & youth; deficiency diseases; diet study techniques; diet therapy; diet-related diseases; Dietary Supplements; disease prevention; Double-Blind Method; Erythrocyte Indices; Erythropoiesis; erythropoietin; Erythropoietin - biosynthesis; Erythropoietin - pharmacokinetics; Feeding. Feeding behavior; Female; ferritin; Ferritins - blood; Fundamental and applied biological sciences. Psychology; Hemoglobin; Hemoglobins - drug effects; Hemoglobins - metabolism; human diseases; Humans; Iron; Iron - metabolism; iron deficiency anemia; Iron-Binding Proteins - blood; Male; Morocco; nutrient deficiencies; nutrient reserves; randomized clinical trials; Receptors, Cell Surface - blood; risk groups; school children; Treatment Outcome; Vertebrates: anatomy and physiology, studies on body, several organs or systems; Vitamin A; Vitamin A - administration & dosage; Vitamin A - pharmacology; Vitamin A Deficiency - blood; Vitamin A Deficiency - complications; Vitamin A Deficiency - drug therapy; vitamin supplements; Vitamins - administration & dosage; Vitamins - pharmacology
• ISSN: 0002-9165; 1938-3207
• 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.