Does vitamin D protect against COVID-19?

In the absence of a COVID-19 cure or vaccine, scientists are investigating whether vitamin D can reduce the risk of COVID-19 infection or the severity of the disease. Indeed, the idea of taking a vitamin to ward off COVID-19 infection certainly is appealing.

But although some recent studies have suggested a link between low vitamin D levels and a higher risk of catching the disease, experts say it's not enough to prove that vitamin D itself protects against the disease, or if other factors are playing a role. 

One study, published Sept. 3 in JAMA Network Open, found that the risk of COVID-19 infection in people with vitamin D deficiency was nearly two  times higher than in people with sufficient levels of the vitamin. Another study, published Oct. 27 in The Journal of Clinical Endocrinology & Metabolism, found that hospitalized COVID-19 patients had higher rates of vitamin D deficiency than a control group of patients who didn't have COVID-19 but whose vitamin D status was measured pre-pandemic.

These associations don't prove that vitamin D deficiency causes increased COVID-19 risk, said Adrian Martineau, who studies respiratory infections and immunity at Queen Mary University of London, and , who was not involved with either study. "But it's suggestive and it's enough to justify doing further research to find out whether or not there is a true cause-effect relationship," Martineau told Live Science. 

Related: 9 Good Sources of Disease-Fighter Vitamin D 

A protective effect? 

There are several reasons to hypothesize that vitamin D might reduce COVID-19 risk, Martineau said. Vitamin D has been shown to boost the immune system's response to viruses and dampen its inflammatory response; an excessive inflammatory response characterizes severe COVID-19 cases, he said. 

According to a meta-analysis by Martineau, first published in 2017 in the journal BMJ and updated to include more recent studies this July on the preprint server medRxiv, vitamin D supplementation reduced the risk of acute respiratory tract infections in general compared with a placebo. (However, the meta-analysis did not include studies about COVID-19.) 

Additionally, there's an overlap between the groups of people with higher risk of vitamin D deficiency, such as older people and people with darker skin, and those at higher risk for COVID-19, Martineau said. "People put two and two together and thought, 'Well, this is quite a striking coincidence, if it is indeed a coincidence.".

An earlier study published May 6 in the journal Aging Clinical and Experimental Research found that in 20 European countries, the lower the average vitamin D levels, the higher the rate of coronavirus cases  and deaths were for a given country. 

Still, not all studies have suggested a protective effect. A study published May 7 in the journal Diabetes & Metabolic Syndrome found no statistically significant association between vitamin D levels and COVID-19 risk once the researchers took into account other factors that could affect COVID-19 risk. 

The chicken or the egg

In the JAMA Network Open study, the researchers examined the relationship between likely vitamin D levels and COVID-19 risk in 489 people who took a COVID-19 test at the University of Chicago Medicine between March 3 and April 10 and whose vitamin D levels had been measured within the previous year. The study researchers found that the risk of testing positive for COVID-19 in people whose vitamin D levels were likely deficient — patients with low vitamin D at their last test and who hadn't changed their treatment — was 1.77 times greater than that of patients whose vitamin D levels were likely sufficient. That's according to the researchers' analysis which accounted for other differences between the two groups that could affect COVID risk. 

The Journal of Clinical Endocrinology & Metabolism study compared the vitamin D levels of 216 patients hospitalized with COVID-19 at University Hospital Marqués de Valdecilla in Santander, Spain, from March 10 to March 31 with a control group of 197 patients who had their vitamin D levels tested the previous year as part of a different study. Of the COVID-19 patients, 82% had vitamin D deficiency compared with 47% of control patients, a statistically meaningful difference. 

A strength of the University of Chicago study is that vitamin D levels were measured before patients' COVID-19 tests, Martineau said. For the Spanish study, on the other hand, patients had vitamin D levels measured after they had tested positive for COVID-19. "You can't tell the chicken from the egg. In other words, the COVID might have caused the low vitamin D or it might be a consequence of it," Martineau said. Because the University of Chicago study was observational — participants were not randomly assigned to take vitamin D or not — it still doesn't prove that vitamin D deficiency increases COVID risk, Martineau said.

Dr. David Meltzer, a University of Chicago researcher who led the study there, agrees. "None of that proves that vitamin D deficiency is causing COVID," Meltzer said, referring to his study and to other associations between vitamin D and COVID risk. "It may be that people who are sicker in general are more likely to have low vitamin D levels," he added.  

To try to answer the chick-and-egg question, Martineau is leading a study in which participants are randomized to take differing doses of vitamin D, then followed to see whether taking more vitamin D reduces COVID-19 risk or severity. The database ClinicalTrials.gov lists about 30 such studies of vitamin D and COVID, according to The Scientist.

While studies are underway, should people start popping supplements? Martineau's advice would be yes, but only if they aren't already meeting current guidelines for vitamin D intake from food. In the U.S., the daily recommended vitamin D intake is 600 international units (IUs) for adults up to age 70 and 800 IUs for adults 71 and up, according to the National Institutes of Health Office of Dietary of Dietary Supplements. "My recommendation would be to follow that advice because it's well established that this will have benefits for bone and muscle, and there's a chance, a good chance, perhaps, that it may also have some benefit against COVID, although that remains unproven," Martineau said. Martineau does not, however, recommend that people start taking higher doses of the vitamin in the absence of more data about how dosage and COVID-19 risk are related. 

Originally published on Live Science.