Effect of Preventive Supplementation with Zinc and Other Micronutrients on Non-Malarial Morbidity in Tanzanian Pre-School Children: A Randomized Trial

Abstract

BackgroundThe 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 FindingsRural 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.ConclusionsWe 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.Trial RegistrationClinicalTrials.gov NCT00623857

Vitamin-D status is not a confounder of the relationship between zinc and diarrhoea: a study in 6–24-month-old underweight and normal-weight children of urban Bangladesh

“…A recent randomised controlled trial among 6-60-month-old children receiving zinc alone also reported similar findings compared with children receiving other multinutrients with or without zinc. 39 We also did not find any role of zinc in incidence or severity of diarrhoea among undernourished/underweight children. The lack of catalysing enzymes and compromised immunity in undernourished children resulted in non-activation of immune response that initiated by serum zinc could be the explanation for such findings.…”

Daily Zinc but Not Multivitamin Supplementation Reduces Diarrhea and Upper Respiratory Infections in Tanzanian Infants: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial,

“…A different study of daily zinc and/or multiple micronutrient supplementation involving rural Tanzanian children 6-60 mo of age showed that zinc supplementation significantly decreased the rate of diarrhea and protected against fever without localizing signs; however, multiple micronutrient supplementation actually increased the rate of diarrhea by approximately one-quarter (9). Similarly, in a trial of micronutrient powders with or without zinc among Pakistani children 6-18 mo of age, Soofi et al (8) observed an increase in the proportion of days with diarrhea as well as higher rates of bloody diarrhea and chest indrawing among children in the 2 micronutrient groups compared with a nonsupplemented control group.…”

“…Two recent trials in Tanzania and Pakistan examined whether the provision of multiple micronutrients in addition to zinc confers additional benefits against diarrhea and other morbidities (8,9). Both trials, however, were restricted to children $6 mo of age, both included iron as part of the micronutrient supplement, and both reported that multiple micronutrients either increased diarrhea morbidity or conferred no additional benefit in comparison with zinc alone.…”

The effects of iron fortification and supplementation on the gut microbiome and diarrhea in infants and children: a review

“…A systematic review of randomized controlled trials of daily oral iron supplementation in children 4-23 mo of age concluded that iron significantly increased fever (RR: 1.16; 95% CI: 1.02, 1.31) and vomiting (RR: 1.38; 95% CI: 1.10, 1.73), but in the 6 trials that assessed diarrhea, iron did not increase the prevalence or incidence of diarrhea [RR: 1.03 (95% CI: 0.86, 1.23); rate ratio: 0.98 (95% CI: 0.88, 1.09), respectively] (13). In Tanzanian infants and young children, a 45-wk intervention study of multiple micronutrient supplementation containing 18 mg Fe as ferrous fumarate reported an increase in diarrhea (HR: 1.19; 95% CI: 0.94, 1.50) (54).…”