Impact of vitamin D supplementation on COVID-19 mortality: A systematic review and meta-analysis

Abstract

Background and aims This study aimed to synthesize available evidence on the impact of vitamin D supplementation on COVID-19-related mortality through a systematic review and meta-analysis. Methods We systematically searched major databases for randomized controlled trials (RCTs), quasi-RCTs, and cluster-randomized trials published between October 1, 2019, and December 14, 2024, evaluating vitamin D supplementation in adult patients with laboratory-confirmed COVID-19. Studies were included if they reported mortality outcomes and compared vitamin D with placebo, standard care, or no intervention. Risk of bias was assessed using the Cochrane tool. Pooled odds ratios (ORs) were calculated using a random-effects model. Subgroup analyses were performed by age and sex composition. Publication bias was assessed via funnel plot symmetry and Egger's test. Results A total of 24 studies encompassing diverse populations across hospital, ICU, and community settings were included. Sample sizes ranged from 32 to 6200 participants, and intervention durations from 5 to 180 days. A pooled analysis revealed that vitamin D supplementation was associated with a significant 33% reduction in COVID-19 mortality (OR = 0.67; 95% CI: 0.46–0.98; P = 0.04), with moderate heterogeneity (I2 = 48.2%). Subgroup analysis revealed a greater benefit among patients aged 65 years or older (minimal heterogeneity; I2 = 4.3%) and among studies with more than 50% female participants (OR = 0.47; P = 0.01). No significant publication bias was detected. Conclusions Vitamin D may confer a protective effect against COVID-19 mortality, particularly among older adults and women. It represents a promising adjunctive strategy in COVID-19 management.