Does vitamin D reduce the mortality rate of Plasmodium infection?: a systematic review and meta-analysis

Vitamin D supplementation is recommended as an effective adjunct to counteract malaria pathogenesis, but the evidence on this point is limited and controversial. This systematic review and meta-analysis aimed to investigate the effect of vitamin D administration on the survival rate of Plasmodium-infected animals in experimentally-induced malaria on days 6 and 10 post-infection.

Five electronic databases were searched up to 20 December 2021. The pooled risks ratio (RR) and associated 95% confidence interval were estimated using the Restricted-maximum likelihood (REML) random-effects model. Heterogeneity was assessed by Cochran's Q test and I2 value. Sub-group analyses were used to identify the sources of heterogeneity for several variables, such as type of vitamin D, type of intervention, and dose of vitamin D.

Out of 248 articles found in the electronic database, six were eligible for inclusion in the meta-analysis. The current study found that the pooled random effect of risks ratio favored a statistically significant effect of vitamin D administration on survival rate in infected mice on day 6 post Plasmodium infection (RR = 1.08, 95%CI 1.03, 1.15, p < 0.99; I2 = 0%). It also found that vitamin D administration significantly affected the survival rate on day 10 post-infection (RR = 1.94, 95%CI 1.39, 2.71, p < 0.001; I2 = 69.02%). Subgroup analyses demonstrated a significant pooled RRs of the positive effect of vitamin D administration for cholecalciferol (RR = 3.11, 95%CI 2.41, 4.03, p < 0.001; I2 = 0%), doses higher than 50 µg/kg (RR = 3.37, 95%CI 2.55, 4.27, p < 0.001; I2 = 0%), and oral administration (RR = 3.01, 95%CI 2.37, 3.82, p < 0.001; I2 = 0%).

This systematic review and meta-analysis showed that vitamin D administration positively affects the survival rate in Plasmodium-infected mice. Since, the mouse model may not accurately reproduce the clinical and pathological features of human malaria, future research should investigate the impact of vitamin D in human malaria.