A new study published in PLOS Medicine suggests that genetic evidence does not support vitamin D as a protective measure against COVID-19.
Vitamin D and COVID-19. Image Credit: Alrandir/Shutterstock.com
No evidence for high Vitamin D benefits against COVID-19
The ability of vitamin D to protect against COVID-19 is of valuable interest for public health but has limited supporting evidence. Previous studies using observational data have suggested that increased vitamin D levels may protect against COVID-19. However, these findings proved inconclusive and possibly subject to confounding, with limited consideration of genetic factors.
However, results from researchers based at McGill University in Quebec, Canada, including Guillaume Butler-Laporte and Tomoko Nakanishi and colleagues now indicate that the association between Vitamin D production and COVID-19 protection is uncertain.
The team conducted a Mendelian randomization study using genetic variants strongly associated with increased vitamin D production to assess the relationship between vitamin D levels and COVID-19 susceptibility and severity. Genetic data was collected from 4,134 individuals with COVID-19, and 1,284,876 without COVID-19 from 11 countries.
The analysis aimed to determine whether genetic predisposition for higher vitamin D levels was associated with less severe disease outcomes in people with COVID-19. Such a relationship would prove a link between Vitamin D levels and disease resilience.
Results of the analysis revealed no association between genetically determined Vitamin D levels and the outcome of COVID-19 infection. Indeed, individuals showed no differences in susceptibility, hospitalization, or severe disease.
Such findings suggest that genetic predisposition to higher Vitamin D production or further supplementation of Vitamin D through dietary supplements may not improve COVID-19 outcomes in the general population.
Vitamin D supplementation as a public health measure to improve outcomes is not supported by this study. Most importantly, our results suggest that investment in other therapeutic or preventative avenues should be prioritized for COVID-19 randomized clinical trials".
Factors of uncertainty and future research
Due to the nature of data collection and analysis, the present study does contain certain limitations.
For instance, the research did not include individuals with a deficiency in Vitamin D production, which may represent a portion of individuals that could benefit from supplementation. This could be an additional factor to include in future research. Further factors may also include countries with comparatively lower dietary Vitamin D levels, which in a similar way to deficient individuals, could benefit from further supplementation.
Such characteristics demonstrate the complexity of studying vitamin-related effects. Dr. Butler-Laporte notes, "Most vitamin D studies are very difficult to interpret since they cannot adjust for the known risk factors for severe Covid-19 (e.g. older age, institutionalization, having chronic diseases) which are also predictors of low vitamin D. Therefore, the best way to answer the question of the effect of vitamin D would be through randomized trials, but these are complex and resource-intensive, and take a long time during a pandemic”.
Moreover, the genetic variants were obtained only from individuals of European ancestry, so future research will be needed to determine the relationship with COVID-19 outcomes in populations of other descent. Using other methods of randomization and procedural techniques may also be helpful.
Mendelian randomization can provide more clear insights into the role of risk factors like vitamin D because they can decrease potential bias from associated risk factors like institutionalization and chronic disease.
In the past Mendelian randomization has consistently predicted results of large, expensive, and timely vitamin D trials. Here, this method does not show clear evidence that vitamin D supplementation would have a large effect on COVID-19 outcomes."
Including factors of complexity such as additional countries, diet composition, and descent, may further elucidate the potential association between Vitamin D levels and COVID-19 severity. Studies will benefit from integrating greater complexity, which in turn will limit the transmission and effects of the COVID-19 pandemic, yet other potential solutions should be prioritized.
- Butler-Laporte G, Nakanishi T, Mooser V, Morrison DR, Abdullah T, Adeleye O, et al. (2021) Vitamin D and COVID-19 susceptibility and severity in the COVID-19 Host Genetics Initiative: A Mendelian randomization study. PLoS Med 18(6): e1003605. https://doi.org/10.1371/journal.pmed.1003605