Abstract:
Background: The efficacy of preventive zinc supplementation against diarrhea and respiratory illness may depend on
simultaneous supplementation with other micronutrients. We aimed to assess the effect of supplementation with zinc and
multiple micronutrients on diarrhea and other causes of non-malarial morbidity.
Methods and Findings: Rural Tanzanian children (n = 612) aged 6–60 months and with height-for-age z-score , –1.5 SD
were randomized to daily supplementation with zinc (10 mg) alone, multi-nutrients without zinc, multi-nutrients with zinc,
or placebo. Children were followed for an average of 45 weeks. During follow-up, we recorded morbidity episodes. We
found no evidence that concurrent supplementation with multi-nutrients influenced the magnitude of the effect of zinc on
rates of diarrhea, respiratory illness, fever without localizing signs, or other illness (guardian-reported illness with symptoms
involving skin, ears, eyes and abscesses, but excluding trauma or burns). Zinc supplementation reduced the hazard rate of
diarrhea by 24% (4%–40%). By contrast, multi-nutrients seemed to increase this rate (HR; 95% CI: 1.19; 0.94–1.50),
particularly in children with asymptomatic Giardia infection at baseline (2.03; 1.24–3.32). Zinc also protected against
episodes of fever without localizing signs (0.75; 0.57–0.96), but we found no evidence that it reduced the overall number of
clinic visits.
Conclusions: We found no evidence that the efficacy of zinc supplements in reducing diarrhea rates is enhanced by
concurrent supplementation with other micronutrients. By reducing rates of fever without localizing signs, supplementation
with zinc may reduce inappropriate drug use with anti-malarial medications and antibiotics.
