- Zinc supplementation in children aged 6 months to 12 years makes little to no difference to all-cause mortality and probably makes no difference to deaths from diarrea. Zinc supplementation probably reduces mortality due to lower respiratory tract infections and malaria but a small possibility of increased risk of mortality cannot be ruled out.
- Zinc supplementation in children aged 6 months to 12 years might prevent illness due to diarrhea, but might lead to vomiting after supplementation. It might lead to a small increase in height gain.
Why is it important to study zinc supplementation?
Zinc is an essential micronutrient. It is important to help children grow normally and to promote a healthy immune system. Lack of zinc may lead to diarrhea, pneumonia, malaria and even death. Low dietary zinc intake is often linked to poverty. As many as half of all children in low- and middle-income countries may have zinc deficiency. Meat, fish, eggs and dairy products are good natural sources of zinc, but are expensive. Lack of clean water and poor sanitation increases exposure to diseases, which zinc might help to fight. The human body cannot produce or store zinc, so giving dietary supplements is important.
What did we want to find out?
We wanted to find out if giving children zinc supplements helps prevent child death and disease, and promotes growth.
What did we do?
We searched for studies that randomly assigned children aged 6 months to 12 years to receive zinc supplementation or no zinc.
We compared and summarized the results of the studies and rated our confidence in the evidence, based on factors such as study methods and sizes.
What did we find?
We included 96 studies in the review, with 219,584 children. Studies took place in 34, mainly low- to middle-income countries. Most of the children in the studies were under five years old. Zinc was most commonly given as a syrup (zinc sulfate), and the most common dose was between 10 mg and 15 mg daily.
We found that giving children zinc supplementation might lead to a small to no reduction in the risk of death for any reason and the risk of death due to diarrhea. The risk of death due to lower respiratory tract infections or malaria may be reduced. Children given zinc experienced less disease due to diarrhea than children not given zinc; however, zinc does not seem to reduce children's risk of respiratory infection. Zinc supplementation may have a small positive effect on growth. Children who take zinc supplementation may experience vomiting as an unwanted effect.
What are the limitations of the evidence?
We are confident about our results on the effects of zinc supplements on reducing the risk of death due to any cause, illness due to respiratory infection, and occurrence of vomiting after supplementation. Our confidence in the results for our other outcomes was moderate because relatively few studies reported these outcomes and because studies sometimes reported different results from other studies for the same outcomes.
How up to date is this evidence?
This review updates a previous version published in 2014. The evidence is current to February 2022.
Even though we included 16 new studies in this update, the overall conclusions of the review remain unchanged. Zinc supplementation might help prevent episodes of diarrhea and improve growth slightly, particularly in children aged 6 months to 12 years of age. The benefits of preventive zinc supplementation may outweigh the harms in regions where the risk of zinc deficiency is relatively high.
Zinc deficiency is prevalent in low- and middle-income countries, and is considered a significant risk factor for morbidity, mortality, and linear growth failure. The effectiveness of preventive zinc supplementation in reducing prevalence of zinc deficiency needs to be assessed.
To assess the effects of zinc supplementation for preventing mortality and morbidity, and for promoting growth, in children aged 6 months to 12 years.
A previous version of this review was published in 2014. In this update, we searched CENTRAL, MEDLINE, Embase, five other databases, and one trials register up to February 2022, together with reference checking and contact with study authors to identify additional studies.
Randomized controlled trials (RCTs) of preventive zinc supplementation in children aged 6 months to 12 years compared with no intervention, a placebo, or a waiting list control. We excluded hospitalized children and children with chronic diseases or conditions. We excluded food fortification or intake, sprinkles, and therapeutic interventions.
Two review authors screened studies, extracted data, and assessed the risk of bias. We contacted study authors for missing information and used GRADE to assess the certainty of evidence. The primary outcomes of this review were all-cause mortality; and cause-specific mortality, due to all-cause diarrhea, lower respiratory tract infection (LRTI, including pneumonia), and malaria. We also collected information on a number of secondary outcomes, such as those related to diarrhea and LRTI morbidity, growth outcomes and serum levels of micronutrients, and adverse events.
We included 16 new studies in this review, resulting in a total of 96 RCTs with 219,584 eligible participants. The included studies were conducted in 34 countries; 87 of them in low- or middle-income countries. Most of the children included in this review were under five years of age. The intervention was delivered most commonly in the form of syrup as zinc sulfate, and the most common dose was between 10 mg and 15 mg daily. The median duration of follow-up was 26 weeks. We did not consider that the evidence for the key analyses of morbidity and mortality outcomes was affected by risk of bias.
High-certainty evidence showed little to no difference in all-cause mortality with preventive zinc supplementation compared to no zinc (risk ratio (RR) 0.93, 95% confidence interval (CI) 0.84 to 1.03; 16 studies, 17 comparisons, 143,474 participants).
Moderate-certainty evidence showed that preventive zinc supplementation compared to no zinc likely results in little to no difference in mortality due to all-cause diarrhea (RR 0.95, 95% CI 0.69 to 1.31; 4 studies, 132,321 participants); but probably reduces mortality due to LRTI (RR 0.86, 95% CI 0.64 to 1.15; 3 studies, 132,063 participants) and mortality due to malaria (RR 0.90, 95% CI 0.77 to 1.06; 2 studies, 42,818 participants); however, the confidence intervals around the summary estimates for these outcomes were wide, and we could not rule out a possibility of increased risk of mortality.
Preventive zinc supplementation likely reduces the incidence of all-cause diarrhea (RR 0.91, 95% CI 0.90 to 0.93; 39 studies, 19,468 participants; moderate-certainty evidence) but results in little to no difference in morbidity due to LRTI (RR 1.01, 95% CI 0.95 to 1.08; 19 studies, 10,555 participants; high-certainty evidence) compared to no zinc.
There was moderate-certainty evidence that preventive zinc supplementation likely leads to a slight increase in height (standardized mean difference (SMD) 0.12, 95% CI 0.09 to 0.14; 74 studies, 20,720 participants).
Zinc supplementation was associated with an increase in the number of participants with at least one vomiting episode (RR 1.29, 95% CI 1.14 to 1.46; 5 studies, 35,192 participants; high-certainty evidence). We report a number of other outcomes, including the effect of zinc supplementation on weight and serum markers such as zinc, hemoglobin, iron, copper, etc. We also performed a number of subgroup analyses and there was a consistent finding for a number of outcomes that co-supplementation of zinc with iron decreased the beneficial effect of zinc.