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Vitamin A supplementation in children with poor vitamin A and iron status increases erythropoietin and hemoglobin concentrations without changing total body iron ^1,2,3

¹ From the Human Nutrition Laboratory, Swiss Federal Institute of Technology, Zürich, Switzerland (MBZ, RB, FR, CZ, and RFH), and The Ministry of Health, Rabat, Morocco (AD and NC).

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.

Key Words: Vitamin A • iron • deficiency • supplementation • hemoglobin • anemia • erythropoietin • children • Morocco

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