New Cornell-led research finds “little to no evidence” of a link between a person’s normal blood levels of vitamin D and risk of getting COVID-19, or the severity of an infection, in the most comprehensive study of its kind to date.

Multiple studies had suggested an association between vitamin D and COVID-19 risk, raising hopes that vitamin D supplements might help to prevent or minimize infections – speculation that has received widespread media attention and boosted consumer interest.

The new study, however, which analyzed a publicly available genomic data bank and 38 different COVID-19 studies worldwide – a total sample including nearly 1.4 million people – does not support those claims.

“The evidence says that your long-term, usual nutritional status of vitamin D has no effect on whether or not you get COVID-19 and how severe the case is,” said Bonnie Patchen, a doctoral student in the field of nutrition and member of the Cassano Research Group. “That suggests vitamin D supplementation is unlikely to be an effective public health strategy to slow the spread of COVID-19.”

Patchen is the lead author of “Genetically Predicted Serum Vitamin D and COVID-19: A Mendelian Randomization Study,” published May 4 in the journal BMJ Nutrition, Prevention and Health. Co-authors are Patricia A. Cassano, the Alan D. Mathios Professor in the College of Human Ecology (CHE) and director of the Division of Nutritional Sciences; Andrew G. Clark, professor in the Department Molecular Biology and Genetics and chair of the Department of Computational Biology; and Nathan Gaddis and Dana Hancock of the GenOmics, Bioinformatics and Translational Research Center at RTI International.

The researchers performed an analysis called Mendelian randomization, using genetically predicted variation in vitamin D to estimate its effect on COVID-19 risk.

They hypothesized that vitamin D could be helpful in preventing or treating COVID-19, as multiple observational studies had suggested. There were underlying biological reasons to support the idea, Patchen said, since vitamin D has known effects on the immune system and has been shown to reduce the viral load of the SARS-CoV-2 virus in infected cells in culture.

But further investigation was needed because observational studies couldn’t establish a causal link between blood vitamin D levels and COVID-19. The challenge in establishing a causal link arises because blood vitamin D levels are influenced by multiple factors including genetics, exposure to sunlight, diet and supplements, and are associated with other risk factors for COVID-19, the researchers said.

“We were trying to get at the part of the variation in vitamin D that’s genetic and leave aside the rest to see whether or not there’s an association with the risk of getting COVID-19,” Cassano said. “And when we do it that way, we find no association, and that’s telling.”

That means, the authors concluded, that the associations highlighted by prior studies likely were the result of other factors known to be related to low vitamin D, such as weight, high blood pressure, chronic disease and age – which are also risk factors for COVID-19.

The Cornell and RTI team’s findings are consistent with the largest and arguably strongest observational study to date, Patchen and Cassano said, by the U.K. Biobank, whose biomedical database contains genetic and health information from a half-million participants in the United Kingdom and was part of this study's analysis.

In addition to its large sample size, the researchers described their study as comprehensive in its examination of multiple definitions of genetic variation in vitamin D and multiple outcomes related to COVID-19 infection and severity, from positive tests to hospitalization.

One weakness, they said, is the sample’s high proportion of people of European ancestry. They recommended further study of more diverse and higher-risk populations, for whom vitamin D’s effects might differ.

The study does not directly address whether an acute treatment with vitamin D could be helpful for infected individuals, Patchen said, nor does it imply that one shouldn’t take vitamin D supplements, which could be beneficial for things other than COVID-19.

But it appears to dash the hope that a relatively simple nutritional intervention might help reduce the risk of COVID-19 or the severity of the infection.

The research was supported by funding from the National Institutes of Health.

The Division of Nutritional Sciences is housed jointly between CHE and the College of Agriculture and Life Sciences (CALS), the Department of Molecular Biology and Genetics between CALS and the College of Arts and Sciences (A&S), and the Department of Computational Biology between CALS, A&S and the Cornell Ann S. Bowers College of Computing and Information Science.