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Malaria death 3X less likely in mice given vitamin D (looks good for humans too) – meta-analysis June 2023

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

Malaria Journal volume 22, Article number: 173 (2023) https://doi.org/10.1186/s12936-023-04612-4
Narges Kalantari, Mahdi Sepidarkish, Salman Ghaffari & Sahar Rostami-Mansoor

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%).

Note: 50 µg/kg would be a single dose of 160,000 IU for a 80 kg (176 lb) human

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.

Clipped from PDF

Vitamin D has two distinct mechanisms of action to diminish parasites: genomic and non-genomic.

  • The genomic mechanism involves vitamin D indirectly protecting patients by regulating the immune system through binding to intracellular receptors that modulate gene expression.
  • The non-genomic mechanism of vitamin D, on the other hand, is characterized by its ability to directly kill parasites.

Previous studies on humans have shown that administering vitamin D can improve anaemia by increasing the proliferation of erythroid progenitor cells and reducing pro-inflammatory cytokines [17]. The findings obtained from present study demonstrated that cholecalciferol had a more positive effect on the survival rate of infected mice. This could be explained by the efficient conversion of cholecalciferol stored in adipose tissue and muscle into the active form of vitamin D (1,25 (OH)2 D3) [18]. Moreover, this study showed a greater RR for the effect of vitamin D on the survival rates of mice infected with P berghei. It is well documented that P. berghei is a lethal form of Plasmodium that induces CM in C57BL/6 mice, while P chabaudi elicits partial mortality in C57BL/6 and C57BL/10 mice [19]. Therefore, the differences between the case and control were less significant in mice infected with P chabaudi.

 Download the PDF from VitaminDWiki

See VitaminDWiki: Vitamin D and malaria – many studies

Note: Malaria peaks each year when vitamin D levels are low (after 3 month rainy season)


26,000 hits from Google Scholar query: malaria "vitamin d”

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  • Oral administration of vitamin D and importance in prevention of cerebral malaria - Nov 2018 https://doi.org/10.1016/j.intimp.2018.08.041 FREE PDF
    • "In summary, the use of Vit.D as a nutritional supplement in malaria-endemic regions may help reduce the severity and mortality of CM."

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