A daily zinc pill cut infections by nearly 40% in young children with sickle cell anemia

A randomized trial published 19 August in JAMA found that a daily 20-milligram zinc sulfate supplement reduced all-cause infections by 38% in young children with sickle cell anemia in Uganda, on top of the hydroxyurea therapy most were already receiving [s1]. The finding, from a single hospital site, is small — but sickle cell anemia's infection burden in African children is not: it remains a leading cause of illness and death in the population the trial enrolled [s1].

What the trial did

Researchers at Jinja Regional Referral Hospital in Uganda ran a randomized, double-blind, placebo-controlled trial in children aged 1 to just under 5 with confirmed sickle cell anemia. Of 118 children screened, 100 were enrolled between February and April 2025 and randomly assigned to receive either 20 mg of zinc sulfate daily or a placebo for six months, with follow-up continuing through November 2025 [s1]. The two groups were similar at enrollment — mean age about 36 months, 45% girls — and 45% of participants were already taking hydroxyurea, the standard disease-modifying therapy for sickle cell anemia, when the trial began; all participants started or continued hydroxyurea over the course of the study [s1]. There was complete follow-up on all 100 children, with no one lost to the study [s1].

What it found

The primary outcome was the rate of all-cause infections per 100 person-years, using standardized clinical criteria. Children on zinc had 80 infections over the six-month period, compared with 124 in the placebo group — a rate of 305.7 infections per 100 person-years versus 480.7 [s1]. After adjusting for baseline age, sex and hydroxyurea use, that translates to an incidence rate ratio of 0.62 (95% CI, 0.45–0.86), meaning zinc-supplemented children experienced roughly 38% fewer infections than those on placebo [s1]. No adverse events serious enough to require stopping the supplement occurred in either group [s1].

Why zinc, and why this population

Zinc deficiency is common in sickle cell anemia because the disease increases the body's zinc turnover, and deficiency itself impairs immune function — the biological rationale the trial was built to test directly [s1]. Sub-Saharan Africa carries the largest global burden of sickle cell disease, and infection remains one of the leading causes of death in affected children there, which is part of why a low-cost, widely available supplement carries outsized practical interest if the effect holds up: unlike many disease-modifying therapies for sickle cell disease, zinc sulfate is inexpensive and does not require specialized administration or monitoring infrastructure.

That combination — a cheap, shelf-stable oral supplement layered on top of a therapy patients are already taking — is what separates this kind of trial from the more heavily covered advances in sickle cell care, such as gene therapies that require specialized infusion centers and cost hundreds of thousands of dollars. Nothing in this study suggests zinc could substitute for hydroxyurea or for gene-based treatments where they're accessible; the trial was explicitly designed and analyzed as an add-on, not a replacement, and 45% of the enrolled children were already on hydroxyurea when the study began [s1]. What it tests is a much narrower and more exportable question: whether a supplement that costs a fraction of those interventions, and requires no infusion infrastructure, can meaningfully cut the day-to-day infection burden in the setting where sickle cell anemia's mortality toll is highest.

The limits, in the authors' own words

The study's own conclusion is careful rather than sweeping: the authors state that zinc supplementation "reduced all-cause infection in children with sickle cell anemia younger than 5 years in Uganda" and explicitly call for "multisite clinical trials" to validate the finding and to test whether the effect extends to older children, who were not studied here [s1]. That caveat matters for three reasons a reader should weigh alongside the topline number. First, this was a single hospital site — real, but not yet representative of the range of settings and children the finding would need to hold up in before it influences guidelines. Second, the age range studied stops just under five years old; whether older children with sickle cell anemia would see a similar benefit is untested. Third, nearly half the cohort was already on hydroxyurea, and the results reflect zinc's effect as an add-on to that therapy rather than as a standalone intervention — a distinction that matters in settings where hydroxyurea access varies widely.

What to watch next

The trial is registered as NCT06561061 [s1], and its authors have effectively proposed their own next step: a larger, multisite trial to confirm the effect and extend it to older children. Until that happens, this remains a single, well-conducted but modestly sized study — genuine evidence that a cheap supplement might meaningfully reduce infections in a high-burden population, not yet a basis for changing how sickle cell anemia is managed.

Sources

• Daily Zinc Supplementation for Infection Prevention in Children With Sickle Cell Anemia, JAMA, 19 August 2026