Two preprint studies cast doubt on vitamin D’s impact on COVID-19

11 Mar 2021 --- Two new studies awaiting publication suggest that vitamin D has no significant impact on COVID-19 outcomes.

The findings challenge circulating studies that suggest vitamin D plays a role in mitigating the coronavirus’s effects.

“Previous studies have not able to account for the fact that patients with lower vitamin D are intrinsically sicker than others, which makes vitamin D seem protective when it may not be,” says Guillaume Butler-Laporte, genetic epidemiologist at McGill University in Canada, and lead author on one study, tells NutritionInsight.

“Large scale vitamin D supplementation is unlikely to provide benefits for COVID-19. But we hope our results can help make governments and other funding agencies better allocate resources for COVID-19 trials.”

The problem with previous studies
Both studies, conducted independently from each other, highlight that past research did not sufficiently account for confounding factors. 

One used a Mendelian randomization method to compare effects of the vitamin, while the other examined vitamin D deficiency. 

Having led the study using Mendelian randomization, Butler-Laporte explains that assessing genetic markers can bypass the biases found in usual epidemiological studies.

This is important since lower vitamin D levels are associated with older age, institutionalization, complex medical diseases, such as cancer, all of which are known risk factors for COVID-19.

A study examining genetic markers of vitamin D metabolism in 440,000 participants found no relationship between COVID-19 and the vitamin.Randomized with genetics
Mendelian randomization is a type of genetic study where researchers are able to use the naturally occurring genetic variations among individuals to infer the effect of a cause (vitamin D levels) on a specific outcome (COVID-19). 

Mendelian randomization studies done for vitamin D in other conditions have usually predicted the results of randomized controlled trials, explains Butler-Laporte.

“Therefore, we know they have a good track record to study the effect of vitamin D on different diseases.”

In this case, the team used large-scale genetic studies to find genetic markers associated with vitamin D to see if it was associated with COVID-19 outcomes. 

Then they combined these associations to obtain the effect of vitamin D on COVID-19. 

“This mimics a randomized controlled trial, where the randomization is done by ‘Mother Nature,’” Butler-Laporte explains. 

Pinpointing deficiency over status
The other preprint study examined vitamin D deficiency and COVID-19 across 24 European countries in adults only. 

Corresponding author on the deficiency study, Michael Chourdakis, who is also an associate professor at the Aristotle University of Thessaloniki in Greece, explains that previous studies may be skewed by looking at mean vitamin D status. 

“Mean status can be distorted, since certain parts of a population can have very high or very low concentrations,” Chourdakis tells NutritionInsight. 

To overcome the challenge, the team used data on vitamin D deficiencies rather than status and did not use any data that was population-specific, such as data from institutionalized individuals. 

The paper examining deficiency is currently under peer review. 

Previously the relationship between vitamin D and COVID-19 has been examined using observational studies, which may not have accounted for confounding factors.Vitamin D for general immunity?
When asked if vitamins D might be beneficial against COVID-19 by supporting general immunity, the responses were inconclusive.  

“Yes and no. Our work shows that we do not have solid data to claim any benefit from vitamin D supplementation,” says Chourdakis.

Butler-Laporte is also skeptical on vitamin D’s effects on immunity in general, stating lacking randomized controlled trials are lacking to support this notion. 

“There are certainly reasons to supplement vitamin D in certain conditions, such as rickets in children, but there has not been – to my knowledge – any convincing randomized evidence to suggest immunologic benefits to taking vitamin D.”

Genetic markers for vitamin D
In order for Mendelian randomization to work in the study, Butler-Laporte describes that genetic variants known to be associated with vitamin D metabolism need to be used.

“The choice is important. In our work, we used results on genome-wide association studies of more than 440,000 participants to find these variants. We’re very confident that these genetic markers at least partly explain vitamin D levels.”

The Mendelian randomization study has been accepted for publication in the general medical journal PLoS Medicine. 

Vitamin D in NPD
Vitamin D continues to enjoy popularity in NPD and regulation that positions it to support immunity.

The “sunshine vitamin” is one of select vitamins and minerals with an approved immunity claim from the European Food and Safety Authority (EFSA). 

The organization has approved the claim that vitamin D contributes to the normal function of the immune system. 

In the US, the Centers for Disease Control and Prevention and the Food and Drug Administration were recently called on to issue new guidance that encourages vitamin D intake during the COVID-19 pandemic. 

By Missy Green