Increased vitamin D levels have been associated with a protective effect against COVID-19 in observational studies. However, these studies were inconclusive and may have been influenced by confounding variables.
Guillaume Butler-Laporte and Tomoko Nakanishi of McGill University in Quebec, Canada, and colleagues report in PLOS Medicine that genetic evidence does not support vitamin D as a COVID-19 protective measure.
Vitamin D’s ability to protect against severe COVID-19 illness is of great interest to public health experts, but there is limited evidence to support this claim. Vitamin D levels were correlated with COVID-19 susceptibility and severity in a Mendelian randomization study using genetic variants strongly associated with increased vitamin D levels.
The authors analysed genetic variants in 4,134 individuals with COVID-19 and 1,284,876 individuals without COVID-19 from 11 countries to determine whether a genetic predisposition for increased vitamin D levels was associated with less severe disease outcomes in individuals with COVID-19.
The findings indicated that there was no correlation between genetically predicted vitamin D levels and COVID-19 susceptibility, hospitalisation, or severe disease, implying that supplementing with vitamin D may not improve COVID-19 outcomes in the general population.
However, the study had several significant limitations, including the absence of vitamin D deficiency, and it remains possible that truly deficient patients would benefit from supplementation for COVID-19-related protection and outcomes.
Additionally, because the genetic variants were obtained exclusively from individuals of European ancestry, additional research will be required to determine the relationship between the genetic variants and COVID-19 outcomes in other populations.
The authors assert that “This study does not support vitamin D supplementation as a public health measure to improve outcomes. Most importantly, our findings suggest that funding for COVID-19 randomised clinical trials should be prioritised over other therapeutic or preventative avenues.”
Dr Butler-Laporte stated that the majority of vitamin D studies are difficult to interpret because they do not account for known risk factors for severe Covid-19 (e.g., older age, institutionalisation, and having chronic diseases), all of which are also predictors of vitamin D deficiency.
Thus, the most effective way to answer the question of vitamin D’s effect would be through randomised trials, but these are complex and resource-intensive, and would take an inordinate amount of time during a pandemic. Mendelian randomization can shed more light on the role of risk factors such as vitamin D by removing potential confounding variables such as institutionalisation and chronic disease.
Historically, Mendelian randomization accurately predicted the outcomes of large, costly, and timely vitamin D trials. This method does not demonstrate conclusively that vitamin D supplementation has a significant effect on Covid-19 outcomes in this case.
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