Association between Vitamin D supplementation and mortality in critically ill patients: A systematic review and meta-analysis of randomized clinical trials

Background: Observational studies suggest that low 25-hydroxyvitamin D status is common and has been associated with higher mortality in critically ill patients. This study aim to investigate whether vitamin D supplementation is associated with lower mortality in critically ill patients. Method: We searched Medline, Embase, and Cochrane databases from inception to January 12, 2020, without language restrictions, for randomized controlled trials comparing the effect of vitamin D supplementation with placebo in critically ill patients. Two authors independently performed data extraction and assessed study quality. The primary outcome was all-cause mortality at the longest follow-up. Result: We identified nine trials with a total of 2066 patients. Vitamin D supplementation was not associated with reduced all-cause mortality at the longest follow-up (RR 0.90, 95% CI 0.74 to 1.09, I2 = 20%), at 30 days (RR 0.81, 95% CI 0.56 to 1.15), at 90 days (RR 1.15, 95% CI 0.92 to 1.44), and at 180 days (RR 0.82, 95% CI 0.65 to 1.03). Results were similar in the sensitivity analysis. The sample size met the optimum size in trial sequential analysis. Similarly, supplemental vitamin D was not associated with length of ICU stay, hospital stay, or mechanical ventilation. Conclusion: Vitamin D supplement was not associated with reduced all-cause mortality in critically ill patients. Systematic review registration: Open Science Framework https://osf.io/bgsjq