- A genetic analysis suggests that vitamin D supplements may not reduce people’s risk for coronavirus infection or COVID-19.
- The study focused on genetic variants that are linked to increased vitamin D levels.
- In the blood, vitamin D can be found in two forms: bound to a protein or free floating. The latter is the one that matters most when talking about innate immunity.
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Like other nutrients that play a role in immune function, vitamin D supplements have been offered as way to prevent or treat COVID-19.
This stems in part from several observational studies showing that populations that are
But a new genetic study suggests that giving people extra vitamin D may not protect against coronavirus infection or COVID-19.
In the study, which was published on June 1 in the journal PLOS Medicine, researchers at McGill University in Quebec, Canada, focused on genetic variants that are linked to increased vitamin D levels.
People whose DNA contains one of these variants are more likely to naturally have higher levels of vitamin D, although diet and other environmental factors can still affect those levels.
The researchers analyzed genetic variant data from around 14,000 people who had COVID-19 and compared it to genetic data from over 1.2 million people who didn’t have COVID-19.
This type of analysis, called a Mendelian randomization study, is like a genetic simulation of a randomized controlled trial, the “gold standard” for clinical research.
Researchers found that people who have one of these variants — who are more likely to have higher vitamin D levels — didn’t have a lower risk for coronavirus infection, hospitalization, or severe illness due to COVID-19.
This suggests that giving people vitamin D supplements won’t lower their risk for COVID-19, although some experts think we still need real-world clinical trials to know for certain.
Dr. Martin Kohlmeier, a professor of nutrition in the Gillings School of Global Public Health at the University of North Carolina, said that this study and similar ones are well-designed and “technically excellent.”
But they’re limited by the genetic variants being examined.
“The challenge is to find an instrument — which is what we call a group of genetic variants — that simulate what we think vitamin D supplementation would do,” Kohlmeier said.
Vitamin D plays a role in the body’s innate immunity, which deals with invaders like a virus before the immune system can generate antibodies. The innate immune response happens immediately or within hours of an invader entering the body.
In the blood, vitamin D can be found in two forms: bound to a protein or free floating. The latter is the one that matters most when talking about innate immunity.
“If you feed somebody a vitamin D supplement, it doesn’t matter how much you change the bound amount,” said Kohlmeier, “it’s how much you change the free amount that matters for innate immunity.”
The problem, he explained, is that the genetic variants used in Mendelian randomization studies of vitamin D are mainly related to the gene-binding protein for vitamin D.
While people with these variants are more likely to have higher levels of vitamin D, the presence of the variant doesn’t indicate how much free vitamin D they have available to assist the innate immune response.
Bonnie Patchen, a PhD student at Cornell University, is the lead author on another Mendelian randomization study looking at the link between vitamin D and COVID-19.
She said that the findings of the new study are similar to what she and her colleagues found with their research, which was published May 4 in the journal
But she pointed out that this type of genetic analysis does have its limitations.
One is that the new paper relied on genetic data from people of European ancestry, so the results may not apply to other populations, particularly people with darker skin who are more likely to have lower vitamin D levels.
Patchen said that in their research, she and her colleagues looked at how well the genetic variants predicted vitamin D levels across different populations.
Their results were consistent for people of European ancestry, she said, even when taking into account other factors that can affect vitamin D levels such as body mass index (BMI) and older age.
“But the associations were less consistent in African ancestry individuals,” Patchen said, “suggesting that further work might need to be done to optimize [these genetic instruments] for use with non-European ancestry populations.”
Another limitation of this type of genetic analysis is that it only looks at the variation in vitamin D levels driven by genetics — it can’t take into account a person’s diet or other factors that might affect their levels.
Patchen said this level of variation is “similar to a change that might be seen with taking a low-level supplement,” around 400 to 600 International Units (IU) of vitamin D.
“But it doesn’t necessarily address the kind of acute changes in vitamin D levels that you might get with a high-dose treatment,” Patchen explained.
While this type of genetic analysis can’t rule out the potential benefits of higher doses of vitamin D, Patchen said “at least two randomized trials have come out showing no effect of high-dose vitamin D in patients hospitalized with COVID-19.”
One of these studies, published February 17 in the journal
Doctors gave patients hospitalized with COVID-19 either a single oral dose of 200,000 IU of vitamin D — which is a very high dose, one that should only be taken under medical supervision — or an inactive placebo.
Researchers found that the large dose of vitamin D had no effect on patients’ length of stay in the hospital.
Dr. David Meltzer, a professor of medicine at The University of Chicago Medicine, and his colleagues did their own analysis of the data from this study.
They found that for people with low vitamin D levels, there was no effect of vitamin D levels on COVID-19 outcome. But it was a different story for people who entered the hospital with higher levels.
“The people with high vitamin D who were given additional vitamin D actually did better,” said Meltzer. “They were less likely to have mechanical ventilation, and they were less likely to have an ICU stay.”
While this difference wasn’t statistically significant, Meltzer said that this trend suggests that something important is happening there.
In this study, patients were given vitamin D after they had arrived at the hospital, when they were further along in their illness — which may explain the lack of a benefit.
“Doctors started vitamin D supplementation when people were already sick, many days into the infection,” said Kohlmeier. “This doesn’t address the phase of innate immunity at all. So there may or may not be a benefit of vitamin D at this later stage of illness.”
Because of vitamin D’s role in the early immune response to a virus, Kohlmeier explained that people need to be enrolled in randomized controlled trials before they get ill.
Meltzer is recruiting people for two vitamin D clinical trials along these lines.
Both involve giving people daily vitamin D supplements before they contract the coronavirus and monitoring them to see if their risk for COVID-19 changes.
Like Kohlmeier, Meltzer thinks it’s important to test the effect of vitamin D supplementation on COVID-19 risk, rather than just look at the levels in the blood.
“The vitamin D intake that you have on a daily basis — or the amount you produce through sun exposure — probably matters to some degree,” he said, “independently of your blood levels.”
The results from these studies, which may not be available until later this year, may provide a better idea of whether vitamin D can prevent respiratory infections such as COVID-19.