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

Double-blind, randomized, placebo-controlled trial; 808 children aged 6 months to 59 months with acute diarrhea; conducted at Indira Gandhi Government Medical College and Hospital, Nagpur, India; randomized to placebo, zinc-only, or zinc+copper; inclusion: >3 unformed stools in 24 h, diarrhea up to 72 h, able to take oral fluids.

0.5 ml/kg/day oral syrup for 14 days; zinc dose 2 mg/kg/day (as zinc sulfate); copper dose 0.2 mg/kg/day (as copper sulfate) in Zn+Cu arm; placebo syrup identical in appearance and taste; dosing repeated if vomiting; continued after discharge with standard treatment for acute diarrhea.

No significant differences across groups in duration of diarrhea, total stool weight, use of ORS/IV fluids, or dehydration-related outcomes. Median post-enrolment diarrhea duration and rates of prolonged diarrhea were similar. Serum zinc rose with zinc-containing regimens; serum copper rose with copper-containing regimen. Conclusion: therapeutic zinc or zinc+copper may not have a universal beneficial impact on the duration of acute diarrhea in children; results suggest heterogeneity and a need for further research to identify subgroups or contexts where benefit may occur.

Baseline imbalance across groups in dehydration status, prior ORS use, and serum zinc; serum zinc concentrations are not a reliable marker of body zinc status; adherence varied among groups; single-site, hospital-based trial; possible suboptimal zinc dose (2 mg/kg/day) relative to higher-dose regimens in other studies; heterogeneity in population and etiologies may affect generalizability.