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

doi:10.1136/bmj.323.7308.314

BMJ 2001;323:314-318 ( 11 August )

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

Mohammad M Rahman, associate scientist, ^a Sten H Vermund, professor, ^b Mohammad A Wahed, associate scientist, ^a George J Fuchs, director, clinical sciences division, ^a Abdullah H Baqui, scientist, ^a Jose O Alvarez, professor. ^b

^a International Centre for Diarrhoeal Disease Research, PO Box 128, Dhaka 1000, Bangladesh, ^b Department of Epidemiology and International Health, School of Public Health, University of Alabama at Birmingham, AL 35294, USA

Correspondence to: M M Rahman, Division of Infectious Diseases and Geographic Medicine, Stanford University School of Medicine, 300 Pasteur Drive, S-025 Stanford, CA 94305-5107, USA mujib_99{at}yahoo.com

Objective: To evaluate the effect of simultaneous zincand vitamin A supplementation on diarrhoea and acute lower respiratoryinfections inchildren.
Study design: Randomised double blind placebo controlledtrial.
Setting: Urban slums of Dhaka,Bangladesh.
Participants and methods: 800 children aged 12-35 months were randomlyassigned to one of four intervention groups: 20 mg zinc once dailyfor 14 days; 200 000 IU vitamin A, single dose on day 14; bothzinc and vitamin A; placebo. The children were followed up oncea week for six months, and morbidity information wascollected.
Results: The incidence and prevalence of diarrhoeawere lower in the zinc and vitamin A groups than in the placebogroup. Zinc and vitamin A interaction had a rate ratio (95% confidenceinterval) of 0.79 (0.66 to 0.94) for the prevalence of persistentdiarrhoea 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 lowerrespiratory infection were significantly higher in the zinc groupthan in the placebo group. The interaction term had rate ratiosof 0.75 (0.46 to 1.20) for incidence and 0.58 (0.46 to 0.73) forprevalence of acute lower respiratoryinfection.
Conclusions: Combined zinc and vitamin A synergisticallyreduced the prevalence of persistent diarrhoea and dysentery.Zinc was associated with a significant increase in acute lowerrespiratory infection, but this adverse effect was reduced bythe interaction between zinc and vitaminA.

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

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