Daily zinc supplements reduced infections in young children with sickle cell anemia in a new randomized trial, adding to evidence that zinc may have a useful role in this high-risk group.
The study included 100 children ages 1 to 4 in Uganda. Half received 20 mg of zinc each day for six months, while the other half received a placebo. During that time, researchers recorded 80 infections in the zinc group and 124 in the placebo group, amounting to a 38% lower infection rate among children taking zinc.
The findings, published in JAMA, are notable because children with sickle cell anemia are especially vulnerable to infection, and zinc deficiency is also common in people with sickle cell disease.
This was not a trial in otherwise healthy children, and zinc was not used instead of standard medical care. All participants received treatment and prevention measures for sickle cell anemia, including hydroxyurea, penicillin, routine vaccinations and malaria prevention. The study tested whether adding zinc could provide extra protection.
The biggest differences were seen in upper respiratory infections and suspected severe bacterial infections. Zinc did not reduce malaria, and the study was too small to show clearly whether it lowered hospitalizations, pneumonia or diarrhea.
That narrower pattern matters because it suggests the result was not simply a drop in every type of illness.
Zinc is essential for normal immune function, and deficiency can make it harder for the body to respond to infection. In sickle cell disease, zinc deficiency may be more common because of changes in how the body handles and loses the mineral.
At the start of the trial, 46% of children in the zinc group and 38% in the placebo group were zinc deficient. By six months, zinc levels had improved in the supplement group, and the proportion with deficiency dropped to 26%.
Interestingly, the reduction in infections did not appear to depend on whether children were zinc deficient when the study began. That means the findings cannot be explained simply by correcting a known deficiency, although the researchers said larger studies are needed to better understand who benefits most.
The 20 mg dose was also chosen for a reason.
The same research group had previously tested 10 mg of zinc a day in children with sickle cell anemia and did not find a reduction in infections. Many children in that earlier trial remained zinc deficient, leading researchers to test the higher dose in the new study.
The 20 mg dose was well tolerated over six months. No child had to stop the supplement because of side effects, and serious adverse events were uncommon in both groups.
Still, the dose should not be interpreted as something parents should give young children on their own.
The study involved children with a serious medical condition who were closely monitored. Researchers also noted that higher doses of zinc have been linked to more side effects in young children, and this trial did not measure every possible effect of longer-term supplementation, including changes in copper levels.
The study also had important limits.
It was conducted at a single hospital in Uganda and included only 100 children younger than 5. Although every child completed follow-up, the small size made it difficult to answer questions about less common outcomes, including hospitalizations and specific infections.
There was also an imbalance in the number of boys and girls assigned to the two groups, though the researchers adjusted for sex in their analysis and said it did not change the results.
The findings may have relevance beyond Uganda, but that is not yet established. Previous studies in North America have also found high rates of zinc deficiency in children with sickle cell disease, suggesting the question may be worth studying in other settings.
For now, the trial provides encouraging evidence that zinc may reduce infections in young children with sickle cell anemia when used alongside standard care. Larger, multisite studies will be needed to confirm the finding and determine whether the same benefit extends to older children and those living in other countries.
The study was supported by the Wells Center for Pediatric Research at Indiana University School of Medicine, Cures Within Reach and an endowment from the Indiana University Dance Marathon administered by Riley Children’s Foundation. One author reported nonfinancial support from Jinja Regional Referral Hospital outside the study.