Simultaneous zinc and vitamin A supplementation in Bangladeshi children: randomised double blind controlled trial

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Abstract
Objective: To evaluate the effect of simultaneous zinc and vitamin A supplementation on diarrhoea and acute lower respiratory infections in children. Study design: Randomised double blind placebo controlled trial. Setting: Urban slums of Dhaka, Bangladesh. Participants and methods: 800 children aged 12-35 months were randomly assigned to one of four intervention groups: 20 mg zinc once daily for 14 days; 200 000 IU vitamin A, single dose on day 14; both zinc and vitamin A; placebo. The children were followed up once a week for six months, and morbidity information was collected. Results: The incidence and prevalence of diarrhoea were lower in the zinc and vitamin A groups than in the placebo group. Zinc and vitamin A interaction had a rate ratio (95% confidence interval) of 0.79 (0.66 to 0.94) for the prevalence of persistent diarrhoea and 0.80 (0.67 to 0.95) for dysentery. Incidence (1.62; 1.16 to 2.25) and prevalence (2.07; 1.76 to 2.44) of acute lower respiratory infection were significantly higher in the zinc group than in the placebo group. The interaction term had rate ratios of 0.75 (0.46 to 1.20) for incidence and 0.58 (0.46 to 0.73) for prevalence of acute lower respiratory infection. Conclusions: Combined zinc and vitamin A synergistically reduced the prevalence of persistent diarrhoea and dysentery. Zinc was associated with a significant increase in acute lower respiratory infection, but this adverse effect was reduced by the interaction between zinc and vitamin A. What is already known on this topic Trials of vitamin A supplementation have failed to show a beneficial effect on morbidity in children Experimental studies have shown that, in the presence of zinc deficiency, vitamin A supplementation fails to reverse vitamin A deficiency Coexistence of deficiencies of zinc and vitamin A could be a reason for the failure of vitamin A supplementation, but data in humans are limited What this paper adds Combined zinc and vitamin A supplementation is more effective in reducing persistent diarrhoea and dysentery than either vitamin A or zinc alone Zinc alone increased respiratory illnesses, but interaction between zinc and vitamin A reduced this adverse effect