Daily zinc supplementation for children under five may reduce anemia infections, study finds

A recent randomized clinical trial in Uganda consisting of 100 children under five with sickle cell anemia has found that daily zinc supplementation at 20 mg reduced all-cause infections over six months compared to a placebo. 

According to the study authors, no adverse events requiring discontinuation of the study intervention were observed. However, they note that multisite trials are needed to validate the findings.

To discover the study’s implications for nutrition guidance, Nutrition Insight speaks to study co-author Chandy John, MD, from the Ryan White Center for Pediatric Infectious Diseases and Global Health, Indiana University School of Medicine, US.

“Zinc is critical for most immune functions, both innate and adaptive, so children with zinc deficiency are prone to infection,” he tells us. “Children with sickle cell anemia release more zinc into the blood when they have bone pain crises or breakdown of red cells, and this can be excreted in the urine, leading to zinc deficiency.”

“So zinc deficiency may be an important part of why children with sickle cell anemia have more infections, and removing that deficiency with zinc supplementation may lead in this way to fewer infections in these children.”

Addressing a major morbidity driver

The researchers flag that despite existing prevention strategies, infections remain a major cause of morbidity and mortality in children across multiple countries in Africa with sickle cell anemia.

In the study, child participants were supplemented daily with zinc sulfate at 20 mg or a placebo for six months.

“All of the children in the study were on hydroxyurea treatment and received penicillin prophylaxis against pneumococcal infections. They had also received immunization against the pneumococcus, the most common cause of pneumonia,” highlights John.

“So zinc’s benefits were observed when it was taken alongside interventions that we already knew decreased specific infections. We believe this shows zinc could be a highly effective and inexpensive way to further reduce infection in children with sickle cell anemia.”

John says that the daily dose of 20 mg was very well tolerated by children, while adding that some studies suggest that a dose of 30 mg daily or higher is not as well tolerated.

“Given the effectiveness of the 20 mg dose, I think it is likely the best dose for children under five years of age with sickle cell anemia,” he says. The ideal duration of zinc supplementation is still unclear.

Zinc outcomes

Looking at other outcomes, the researchers found that zinc reduces most infections, including respiratory infections and diarrhea, two of the most common infections.

However, zinc supplementation didn’t reduce malaria, which is another common public health threat on the continent. “Zinc has positive effects for the cells that line the lung, and inhibits one pathway that contributes to diarrhea, so this may be why it’s particularly effective against those two conditions,” John notes.

“It’s unclear why it doesn’t reduce malaria episodes, but presumably the key immune pathways for protection against malaria are not as affected by zinc deficiency as pathways involved in other infections.”

John adds that while the study prescribed supplementation for six months, the same protocol for a year or longer could be even more beneficial. “Future studies will need to assess the question of duration.”

He adds that the study was at a single site and was not aimed at detecting reductions in severe infectious diseases — those requiring hospitalization — or pneumonia. 

“We also need studies of zinc in children five years and older with sickle cell anemia to see what dose of zinc might be needed for that age group and how effective it is in older children.”

“So there are important remaining questions that need to be studied, but the current results suggest that zinc holds great promise for prevention of infection in children with sickle cell anemia,” he concludes.