- Vitamin D is known to provide some protection against respiratory tract infections.
- Some observational studies hint that vitamin D supplements could also help prevent COVID-19 infection and severe disease.
- However, newly published research that used gene variants to simulate a randomized clinical trial suggests higher levels of vitamin D do not prevent COVID-19.
- The study was unable to rule out the possibility that people who are deficient in vitamin D may benefit from taking a supplement.
The idea that a cheap, safe, and readily available supplement can help shield people against infection with SARS-CoV-2 and severe disease is appealing.
However, to date, the evidence that vitamin D really does protect against COVID-19 has been mixed.
The vitamin is essential for maintaining healthy bones and muscles, but there is also
So, in theory, it could protect against COVID-19, principally a respiratory infection.
An unpublished study found a link between mean levels of vitamin D in the populations of 20 European countries and the number of COVID-19 cases and mortality rates in the countries.
Several studies have found an association between vitamin D status and subsequent COVID-19 infection.
However, the scientists behind this research emphasized that only randomized clinical trials could provide definitive evidence that vitamin D supplementation can prevent COVID-19 and therefore save lives.
This is because observational studies like theirs are vulnerable to two statistical problems, known as “confounding” and “reverse causation.”
Confounding occurs when another variable that the researchers have not fully accounted for influences the outcome. For example, older age and chronic disease affect not only a person’s levels of vitamin D but also their risk of COVID-19.
Reverse causation occurs when the outcome itself affects the variable under investigation. For example, severe COVID-19 could reduce an individual’s vitamin D levels.
In a clinical trial, researchers avoid these problems by randomly assigning participants to receive either the treatment or a placebo, then following them to see what happens.
But clinical trials are costly and take a long time to yield any results.
Random genetic variation
Researchers at McGill University in Montreal, Canada, and collaborators from the University of Siena, Italy, used a technique called Mendelian randomization, which uses genetic variation between people to simulate a randomized controlled trial, to investigate the effects of vitamin D.
They first identified genetic variants known to influence a person’s vitamin D level.
In effect, these variants are randomly assigned to people at their conception by a combination of their parents’ gametes. This avoids any biases to the outcome from confounding variables — as the variants may break the associations with other confounders or from reverse causation — because the variants are determined before infection.
The researchers then used the presence of these variants as a proxy for vitamin D levels in 14,134 individuals from up to 11 countries testing positive for COVID-19 and over 1.2 million individuals without the disease.
They found no significant associations between the predicted vitamin D levels — by each individual’s genetic makeup — and COVID-19 infection, hospitalization, or severity of illness.
The study appears in PLOS Medicine.
Definitive clinical trials
“I guess this paper adds further caution to those who think vitamin D supplements will be a magic bullet against COVID-19, and there are many who still think this,” said Professor Naveed Sattar, Ph.D. from the Institute of Cardiovascular and Medical Sciences at the University of Glasgow in the United Kingdom.
Prof. Sattar was not involved in this research, but he and his colleagues recently published an observational study that found no association between vitamin D levels and risk of COVID-19 infection and mortality.
However, he told Medical News Today that the only way to settle the question is to run clinical trials of vitamin D supplementation. A few are already underway.
“One must always be open-minded about the success of any such trial, but, given these new genetic data added to our prior work and that of others, I remain pessimistic we will see any meaningful gain with vitamin D supplements in the prevention or treatment of COVID-19,” he said.
“I may be proven wrong but will be glad, if so,” he added.
The authors of the new paper caution that their study cannot rule out the possibility that people deficient in vitamin D — rather than having insufficient levels — might benefit from supplementation.
“The reason why we can’t specifically say anything about truly vitamin D-deficient individuals is that [Mendelian randomization] really looks at average effects,” said first author Guillaume Butler-Laporte, M.D.
The researchers designed the study to investigate the effects of average vitamin D levels across a population.
“Anytime we look at averages in statistics, there’s a [chance] that outliers may not be well represented,” he told MNT.
However, he pointed out that Mendelian randomization studies have proved very good at predicting the outcomes of clinical trials of vitamin D in other diseases, including cancer and asthma.
In their paper, Dr. Butler-Laporte and his colleagues suggest that the limited funding available for future randomized controlled trials should therefore focus on other potential treatments for COVID-19.
They note that one limitation of their study was that it only looked at individuals of European ancestry. The possibility remains that vitamin D levels may have different effects on COVID-19 outcomes in other populations.
However, they write, clinical trials of vitamin D supplementation for other diseases have yielded similar results in populations of various ancestries.
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