Impact of vitamin D supplementation on short- and long-term mortality in sepsis: A systematic review and meta-analysis.

OBJECTIVE

This systematic review and meta-analysis evaluated the impact of vitamin D supplementation on sepsis outcomes, focusing on short- and long-term mortality.

METHODS

A comprehensive search of PubMed, EMBASE, Cochrane Library, and Web of Science was conducted for studies published up to February 10, 2025. Eligible studies enrolled patients with sepsis who received vitamin D supplementation and reported mortality outcomes, including 28-day, 90-day, or in-hospital mortality. Case reports, reviews, and studies with incomplete data were excluded. Data extraction and quality assessment were performed independently by two reviewers using the Cochrane Risk of Bias Tool and the Newcastle-Ottawa Scale. Meta-analysis was performed with Review Manager 5.3 and Stata 15, employing random-effects models. Publication bias was assessed with funnel plots and Egger's test, while the quality of evidence was graded using the GRADE system.

RESULTS

Five studies encompassing 42,915 patients met the inclusion criteria, including one randomized controlled trial and four large cohort studies. Pooled results demonstrated that vitamin D supplementation was may associated with reduction in 28-day mortality (OR: 0.59, 95 % CI: 0.51-0.69, P < 0.0001), 90-day mortality (OR: 0.56, 95 % CI: 0.46-0.68, P < 0.00001), and in-hospital mortality (OR: 0.61, 95 % CI: 0.50-0.73, P < 0.00001). Substantial heterogeneity was observed (I2 = 64 %-78 %). No significant publication bias was detected. However, the overall quality of evidence was rated low due to inconsistency and imprecision.

CONCLUSION

Vitamin D supplementation appears to reduce mortality in critically ill patients with sepsis. Nevertheless, the low certainty of evidence highlights the need for well-designed, large-scale randomized controlled trials to confirm these findings and guide clinical practice.