Previous observational studies have suggested that increased Vitamin D levels may protect against the novel coronavirus (COVID-19).
However, these studies were inconclusive and possibly subject to confounding. A study published in PLOS Medicine by Guillaume Butler-Laporte and Tomoko Nakanishi at Canada’s McGill University and colleagues suggests that genetic evidence does not support Vitamin D as a protective measure against COVID-19.
The ability of Vitamin D to protect against severe COVID-19 illness is of great interest to public health experts, but has limited supporting evidence.
To assess the relationship between the two, researchers conducted a Mendelian randomisation study using genetic variants strongly associated with increased Vitamin D levels.
The authors analysed genetic variants of 4,134 individuals with COVID-19, and 1,284,876 without COVID-19, from 11 countries. This sought to determine whether genetic predisposition for higher Vitamin D levels were associated with less-severe disease outcomes in people with COVID-19.
The results showed no evidence for an association between genetically predicted Vitamin D levels and COVID-19 susceptibility, hospitalisation, or severe disease. This suggests that raising circulating Vitamin D levels through supplementation may not improve COVID-19 outcomes in the general population.
However, the study had several important limitations, including that the research did not include individuals with Vitamin D deficiency. As a result, it remains possible that truly deficient patients may benefit from supplementation for COVID-19-related protection and outcomes.
Additionally, the genetic variants were obtained only from individuals of European ancestry, so future studies will be needed to determine the relationship with COVID-19 outcomes in other populations.
According to the authors, “Vitamin D supplementation as a public health measure to improve outcomes is not supported by this study.”
They added, “Most importantly, our results suggest that investment in other therapeutic or preventative avenues should be prioritized for COVID-19 randomised clinical trials.”
Butler-Laporte noted, “Most Vitamin D studies are very difficult to interpret since they cannot adjust for the known risk factors for severe COVID-19, such as older age, institutionalisation, and having chronic diseases, which are also predictors of low Vitamin D.”
The best way to answer the question of the effect of Vitamin D would be through randomised trials, but these are complex and resource intensive, and take a long time during a pandemic.
According to Butler-Laporte, Mendelian randomisation can provide more clear insights into the role of risk factors like Vitamin D.
This is because they can decrease potential bias from associated risk factors such as institutionalisation and chronic disease. In the past, Mendelian randomisation 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.