Zinc and copper supplementation in acute diarrhea in children: a double-blind randomized controlled trial

Double-blind randomized controlled trial in hospitalized children 6 months to 59 months old with acute watery or bloody diarrhea in Nagpur, India. Active intervention arms included zinc alone and zinc plus copper, compared with placebo, with treatment given during hospitalization and continued after discharge to complete 14 days.

Participants received oral zinc sulfate syrup at an elemental zinc dose of 2 mg/kg/day for 14 days. The combination arm received the same zinc regimen plus copper sulfate in an oral syrup (20 mg/5 ml elemental zinc and 2 mg/5 ml elemental copper) at 0.5 ml/kg/day for 14 days; doses were repeated if vomiting occurred. A placebo arm was included for comparison.

Zinc, with or without copper, did not show a consistent clinical benefit over placebo for acute diarrhea in this population. Duration of diarrhea from enrollment was similar across groups, with 64.4 hours in both the zinc and zinc plus copper arms versus 62.2 hours in placebo, and the log-rank p value was 0.6399. Stool weight during hospitalization and other adjusted clinical outcomes also did not differ significantly across groups. Complications were uncommon and not clearly reduced in the active arms, although serum zinc and copper levels increased with supplementation. The syrups were well tolerated, with no serious adverse events attributed to treatment.

Interpretation is limited by a single-center design in hospitalized children from Nagpur, India, and by the heterogeneous acute diarrhea population. The intervention period was short at 14 days, and the trial did not show a consistent effect across the main clinical outcomes, which reduces confidence in broad generalization. Some outcome reporting was complex, with multiple endpoints and no clear universal benefit.