Therapeutic effects of oral zinc in acute and persistent diarrhea in children in developing countries: Pooled analysis of randomized controlled trials

Z. A. Bhutta, S. M. Bird, R. E. Black, K. H. Brown, J. M. Gardner, A. Hidayat, F. Khatun, R. Martorell, N. X. Ninh, M. E. Penny, J. L. Rosado, S. K. Roy, M. Ruel, S. Sazawal, A. Shankar

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Background: Zinc deficiency is prevalent in children in developing countries. Supplemental zinc provides therapeutic benefits in diarrhea. Objective: We sought to measure the effect of supplemental zinc given with oral rehydration therapy during recovery from acute or persistent diarrhea. Design: We conducted pooled analyses including all available published and unpublished randomized controlled trials of the effects of supplementary oral zinc in children aged <5 y with acute or persistent diarrhea. We used Cox survival regression analysis to evaluate the overall effect of zinc on continuation of diarrhea and possible differential effects in subgroups divided by sex, age, weight-for-height, and initial plasma zinc concentration. Dichotomous outcomes were analyzed by logistic regression. To assess the effects of excluding studies without original data from the pooled analyses, effect-size was estimated for all studies by using random-effects models. Results: Zinc-supplemented children had a 15% lower probability of continuing diarrhea on a given day (95% CI: 5%, 24%) in the acute-diarrhea trials and a 24% lower probability of continuing diarrhea (95% CI: 9%, 37%) and a 42% lower rate of treatment failure or death (95% CI: 10%, 63%) in the persistentdiarrhea trials. In none of the subgroup analyses were the 2 subgroups of each pair significantly different from each other; however, in persistent diarrhea there tended to be a greater effect in subjects aged <12 mo, who were male, or who had wasting or lower baseline plasma zinc concentrations. Conclusion: Zinc supplementation reduces the duration and severity of acute and persistent diarrhea.

Original languageEnglish
Pages (from-to)1516-1522
Number of pages7
JournalAmerican Journal of Clinical Nutrition
Issue number6
Publication statusPublished - 2000
Externally publishedYes


  • Children
  • Developing countries
  • Diarrhea
  • Diarrheal disease
  • Infants
  • Malnutrition
  • Meta-analysis
  • Nutrition
  • Randomized controlled trial
  • Zinc
  • Zinc deficiency
  • Zinc supplementation


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