Vitamin D₃ supplementation and childhood diarrhea: A randomized controlled trial

Objective: To investigate the effect of vitamin D₃ supplementation on the incidence and risk for first and recurrent diarrheal illnesses among children in Kabul, Afghanistan. Methods: This double-blind placebo-controlled trial randomized 3046high-risk 1- to 11-month-old infants to receive 6 quarterly doses of oral vitamin D₃ (cholecalciferol 100 000 IU) or placebo in inner city Kabul. Data on diarrheal episodes (≤3 loose/liquid stools in 24 hours) was gathered through active and passive surveillance over 18 months of follow-up. Time to first diarrheal illness was analyzed by using Kaplan-Meier plots. Incidence rates and hazard ratios (HRs) were calculated by using recurrent event Poisson regression models. Results: No significant difference existed in survival time to first diarrheal illness (log rank P = .55). The incidences of diarrheal episodes were 3.43 (95% confidence interval [CI], 3.28-3.59) and 3.59 per childyear (95% CI, 3.44-3.76) in the placebo and intervention arms, respectively. Vitamin D₃ supplementation was found to have no effect on the risk for recurrent diarrheal disease in either intention-to-treat (HR, 1.05; 95% CI, 0.98-1.17; P = .15) or per protocol (HR, 1.05; 95% CI, 0.98-1.12; P = .14) analyses. The lack of preventive benefit remained when the randomized population was stratified by age groups, nutritional status, and seasons. Conclusions: Quarterly supplementation with vitamin D₃ conferred no reduction on time to first illness or on the risk for recurrent diarrheal disease in this study. Similar supplementation to comparable populations is not recommended. Additional research in alternative settings may be helpful in elucidating the role of vitamin D₃ supplementation for prevention of diarrheal diseases.