Combined iron and zinc supplementation in infants improved iron and zinc status, but interactions reduced efficacy in a multicountry trial in Southeast Asia

Deficiencies of iron and zinc are prevalent worldwide. Interactions between these micronutrients therefore have important consequences, also for supplementation. To investigate effects on hemoglobin and zinc concentrations and interactions of iron and zinc supplementation in infants, data from 4 parallel, randomized, placebo-controlled, double-blind trials in Indonesia, Thailand, and Vietnam were pooled. Infants (n = 2468), aged 4-6 mo, were supplemented daily with iron (10 mg) and/or zinc (10 mg) for 6 mo. At 3 sites, infants were given vitamin A capsules (VAC) at recruitment. Combined supplementation reduced prevalences of anemia by 21% (P < 0.01) and zinc deficiency by 10% (P < 0.05) but was less effective (P < 0.05) than supplementation with either iron (28% reduction in anemia) or zinc alone (18% reduction in zinc deficiency). Iron reduced the effect of zinc supplementation (interaction P < 0.01), but had no separate effect on zinc status, whereas zinc supplementation had a negative effect on hemoglobin concentrations (-22.5 g/L, P < 0.001), independent of iron supplementation (P_interaction = 0.25). The effect of iron supplementation on hemoglobin concentrations was almost twice as large in boys than in girls (effect size 12.0 vs. 6.8 g/L, respectively). In infants not receiving iron, VAC administration tended to be associated with lower (3.2%, P = 0.07) hemoglobin concentrations. Combined supplementation of iron and zinc was safe and effective in reducing the high prevalences of anemia and iron and zinc deficiencies. Zinc supplementation may negatively affect iron status but iron supplementation does not seem to affect zinc status. Furthermore, VAC administration in the absence of iron supplementation may increase the incidence of anemia.