Zinc Supplements Reduce Diarrhea in Children

Laurie Barclay, MD

May 15, 2014

The benefits on growth, health, and survival from preventive zinc supplementation in children outweigh the harms in areas with relatively high risk for zinc deficiency, according to findings of a review published online May 15 in the Cochrane Database of Systematic Reviews.

"We should remember that supplements are not a substitute for a well-balanced diet," senior author Zulfiqar Bhutta, PhD, from the Center of Excellence in Women and Child Health, Aga Khan University, Karachi, Pakistan, and the Sick Kids Center for Global Child Health, Toronto, Ontario, Canada, said in a journal news release. "However, in countries where zinc deficiency is common, supplements may help to reduce child deaths and related diseases in the short-term."

Zinc is essential for proper growth and function of the immune, nervous, and reproductive systems. It is not synthesized by the human body and must come from dietary sources. Zinc deficiency is prevalent in Southeast Asia, sub-Saharan Africa, and parts of Latin America; affects more than 1 in 6 people worldwide; and contributes to an estimated 1 in 58 deaths in children younger than 5 years.

"Eating foods with balanced energy and protein and multiple micronutrients would probably have a larger effect for many malnourished children," said lead author Evan Mayo-Wilson, PhD in the release.

Because zinc deficiency is common in low- and middle-income countries and may impair growth or aggravate diarrhea, pneumonia, and malaria among young children, Dr. Mayo-Wilson and colleagues reviewed randomized controlled trials to estimate the effects of zinc supplementation in children aged 6 months to 12 years.

The investigators searched numerous medical databases between December 2012 and January 2013 for relevant studies. Two authors screened the retrieved studies, extracted information, determined risk for bias, and contacted trial authors for missing data.

They included 80 trials, enrolling a total of 205,923 children . All of the trials compared preventive zinc supplementation with no intervention, placebo, or a waiting list control. They excluded trials of children who were hospitalized or who had chronic diseases or conditions and trials of food fortification or intake, sprinkles, and therapeutic interventions.

Zinc Supplements Linked to Lower Morbidity

The researchers found trends in favor of reduced mortality risk with zinc supplementation, but neither all-cause nor cause-specific differences reached statistical significance. The risk ratio (RR) for all-cause mortality was 0.95 (95% confidence interval [CI], 0.86 - 1.05) with data from 14 studies, judged to be high-quality evidence.

The risk ratios for cause-specific mortality were similar, including mortality resulting from diarrhea (RR, 0.95; 95% CI, 0.69 - 1.31; 4 studies, moderate-quality evidence), lower respiratory tract infection (RR, 0.86; 95% CI, 0.64 - 1.15, 3 studies, moderate-quality evidence), or malaria (RR, 0.90; 95% CI, 0.77 - 1.06; 2 studies, moderate-quality evidence).

Zinc supplementation was associated with a statistically significant reduction in morbidity from diarrhea and with lower incidence of all-cause diarrhea (RR, 0.87; 95% CI, 0.85 - 0.89; 26 studies, moderate-quality evidence). The results for lower respiratory tract infection and malaria were inconclusive and based on moderate-quality evidence.

Zinc supplementation was also linked to a medium to large positive effect on zinc status and to a very small improvement in height (standardized mean difference, −0.09; 95% CI, −0.13 to −0.06; 50 studies, moderate-quality evidence). However, the authors suggest the small size of this effect might not be clinically important.

In terms of harms, zinc supplementation was associated with a negative effect on copper status and an increase in the number of participants who had 1 or more episodes of vomiting (RR, 1.29; 95% CI, 1.14 - 1.46; 5 studies, high-quality evidence). Hemoglobin or iron status was not clearly affected by zinc supplementation.

"In our opinion, the benefits of preventive zinc supplementation outweigh the harms in areas where the risk of zinc deficiency is relatively high," the authors write. "Further research should determine optimal intervention characteristics such as supplement dose."

"Policymakers in low and middle income countries need evidence that directly addresses the needs of their own health services," David Tovey, MD, editor-in-chief of the Cochrane Library, said in the news release. "This comprehensive review makes a very valuable contribution to the evidence base around interventions [that] may make an important contribution to improving Global Health."

The authors have disclosed no relevant financial relationships.

Cochrane Database Syst Rev. 2014;4:CD009384. Abstract

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