Observational studies have suggested that increased vitamin D levels may protect against 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 McGill University in Quebec, Canada, 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 vitamin D levels and COVID-19 susceptibility and severity, 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 to determine whether genetic predisposition for higher vitamin D levels was associated with less severe disease outcomes 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, suggesting 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, and 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. Most importantly, our results suggest that investment in other therapeutic or preventative avenues should be prioritised for COVID-19 randomised clinical trials.
Dr. 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 (e.g. older age, institutionalisation, 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 randomised trials, but these are complex and resource-intensive, and take a long time during a pandemic.’
‘Mendelian randomisation 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 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 significantly affect COVID-19 outcomes.’