Vitamin D3 Supplementation and Childhood Diarrhea: A Randomized Controlled Trial

Abstract

WHAT'S KNOWN ON THIS SUBJECT: Hypovitaminosis D is common among children. Although there is prolific biochemical literature linking vitamin D to enteric immunologic function, there is a paucity of prospective data exploring the role of supplementation in prevention of diarrheal illnesses. WHAT THIS STUDY ADDS:In a high-risk population, quarterly supplementation with 100 000 IU of vitamin D 3 did not reduce the risk for first or recurrent diarrheal illnesses in a population of children aged 1 to 29 months in a low-income inner city setting. abstract OBJECTIVE: To investigate the effect of vitamin D 3 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 3046 high-risk 1-to 11-month-old infants to receive 6 quarterly doses of oral vitamin D 3 (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 KaplanMeier 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 D 3 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 D 3 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 D 3 supplementation for prevention of diarrheal diseases.

Vitamin-D Deficiency Predicts Infections in Young North Indian Children: A Secondary Data Analysis

“…Another randomized controlled trial with 3-monthly bolus supplementation with 100,000 IU of vitamin D3 among children aged 1 to 29 months, showed no effect on the risk of diarrheal illnesses [41]. The finding of this study underscores the need for further research to explore vitamin D serologic levels in relation to immune function and physiologic responses to gut infections.…”

Vitamin-D deficiency predicts infections in young north Indian children: A secondary data analysis

“…A randomized controlled trial with 3-monthly bolus supplementation with 100,000 IU of vitamin D3 among children aged 1 to 29 months, showed no effect on diarrheal illnesses [47]. Our study was done in urban slum where constant exposure to pathogenic organisms and subsequent enteric infection is common in children [48].…”

Vitamin-D status is not a confounder of the relationship between zinc and diarrhoea: a study in 6–24-month-old underweight and normal-weight children of urban Bangladesh

“…However, a recently conducted randomised controlled trial with quarterly bolus dose of vitamin-D at high-risk population aged 1-29 months did not find any effect on first or recurrent incidence of diarrhoea. 13 In a longitudinal study, among school-going children (mean age 8.9 years) in Colombia, it was found that vitamin-D-deficient children were at greater risk of gastrointestinal illness. 12 Our study consisted of children 6-24 months of age living in urban slums, where the burden of disease is highest because of poor sanitation and socioeconomic status.…”

“…Probably for this reason, our study findings were concordant with the finding of randomised controlled trial with vitamin-D supplementation conducted in a similar setting like in Afghanistan. 13 Population-based studies conducted to determine the effect of serum retinol or zinc in incidence and severity of childhood diarrhoea did not consider the nutritional status of children nor targeted the population most at risk, especially undernourished children. 4,5 To that extent, our finding that normal-weight children with insufficient serum zinc had an increased incidence and severity of diarrhoea compared with children with sufficient serum zinc status is a novel finding.…”

“…13 The heterogeneous findings and lack of studies among younger children warranted a comprehensive evaluation of association of vitamin-D status with incidence and severity of diarrhoea.…”