Vitamin D3 Supplementation May Not Be Beneficial for Pediatric Infectious Diarrhea

Adjunctive vitamin D3 supplementation failed to reduce the risk for recurrent infectious diarrhea among children, and no associations were found between vitamin D levels and diarrhea occurrence.

Vitamin D3 supplementation may not be effective as adjunctive therapy for infectious diarrhea among children, with no correlation observed between serum vitamin D levels and diarrhea occurrence. These findings were published in BMC Infectious Diseases

Researchers conducted a systematic review to evaluate the efficacy of adjunctive vitamin D3 in the management of infectious diarrhea among pediatric patients. A total of 9 studies were reviewed, including 2 cohort, 3 cross-sectional, 1 case-control, and 2 longitudinal studies, as well as 1 randomized controlled trial (RCT). The included studies assessed the relationship between diarrhea and vitamin D status, either as serum 25-hydroxyvitamin D or vitamin D-binding protein levels as surrogate markers. No meta-analysis was conducted because of differences in endpoints and study design among the studies included in the review.

A total of 5545 patients were evaluated across the 9 studies, of whom the majority were younger than 5 years. 

Among patients included in the RCT who were randomly assigned to receive either quarterly oral vitamin D3 supplementation (100,000 IU; n=1523) or placebo (n=1524), the incident risk for diarrhea per child-year was 3.59 (95% CI, 3.44-3.76) and 3.43 (95% CI, 3.28-3.59), respectively. Further analysis showed no association between quarterly vitamin D3 supplementation and the risk for recurrent diarrheal disease.

For the first longitudinal study (N=475), patients who were vs were not deficient in vitamin D3 had higher rates of diarrhea with vomiting (adjusted incidence rate ratio [aIRR], 2.05; 95% CI, 1.19-3.53) and earache/discharge with fever (aIRR, 2.36; 95% CI, 1.26-4.44). Results of the second longitudinal study (N=540) indicated an inverse association between vitamin D binding protein levels and episodes of diarrhea with vomiting and earache/discharge with fever. Of note, associations between vitamin D binding protein and morbidity were not mediated via 25-hydroxyvitamin D.

For future research direction, we recommended more adequately-powered RCTs on oral vitamin D’s role in reducing diarrhea risk.

In regard to the 2 cohort studies, results of the first indicated that patients with (n=30) vs without (47) risk factors for severe diarrhea were more likely to have insufficient serum vitamin D3 levels (median, 53.63 nmol/L vs 66.09 nmol/L, respectively). Results of the second cohort study showed no association between vitamin D status and the risk for diarrhea caused by either Escherichia coli, enteropathogenic E coli, or enteroaggregative E coli pathogens among children who were underweight. Similar findings were observed on analysis of the cross-sectional studies.

The case-control study assessed the relationship vitamin D status and diarrhea occurrence among children with diarrhea (n=47), unhealthy control patients (n=94), and healthy control patients (n=94). Results showed that children who were vs were not deficient in vitamin D were at decreased risk for diarrhea. In addition, vitamin D deficiency was significantly more likely among patients with diarrhea and unhealthy control patients when compared with healthy control patients.

The researchers noted that associations between serum vitamin D3 levels and diarrhea risk differed on the basis of age in subgroup analyses, potentially explaining the lack of correlation found between vitamin D deficiency and diarrheal disease.

Limitations of this review include significant heterogeneity across the 9 studies, the predominance of noninterventional studies, and the high prevalence of vitamin D deficiency among patients included in the case-control study.

“For future research direction, we recommended more adequately-powered RCTs on oral vitamin D’s role in reducing diarrhea risk,” the researchers concluded.


Uwaezuoke SN, Odimegwu CL, Mbanefo NR, et al. Vitamin D3 supplementation as an adjunct in the management of childhood infectious diarrhea: a systematic review. BMC Infect Dis. 2023;23(1):159. doi:10.1186/s12879-023-08077-3.