The Nuance
Vitamin D for Covid-19: New Research Shows Promise
Studies highlight potential life-saving benefits. But some experts aren’t convinced.
The study’s findings were significant — “spectacular” even, in the words of at least one expert commenter.
A team of doctors at Reina Sofía University Hospital in Córdoba, Spain, split 76 newly admitted Covid-19 patients into two groups. One group got the standard treatment at the time, which included a cocktail of antibiotics and immunosuppressant drugs. The second group got the same standard treatment — plus a drug designed to raise vitamin D levels in the blood.
Among the 26 hospitalized people who received standard care alone, fully half went on to the intensive care unit (ICU) because their disease had worsened. Two of them died. But among the 50 people who received the vitamin D treatment on top of standard care, only one person ended up in the ICU. None died.
In their study write-up, published in October in the Journal of Steroid Biochemistry and Molecular Biology, the Spanish researchers explained that their experiment was a “pilot” study that requires follow-up work. But they also pointed out that theirs is not the first piece of evidence linking vitamin D to a reduced risk for severe respiratory infection. Far from it.
“Vitamin D supports a range of innate antiviral immune responses while simultaneously dampening down potentially harmful inflammatory responses,” says Adrian Martineau, PhD, a clinical professor of respiratory infection and immunity at Queen Mary University of London.
“The evidence that low vitamin D levels are a risk factor for severe [Covid-19] disease is not definitive, but many lines of research suggest that this is likely.”
Martineau was not involved with the Spanish study, but he has published several papers on vitamin D for the treatment and prevention of viral infections. In a 2017 research review, which appeared in the journal BMJ, he and his co-authors concluded that taking a daily or weekly vitamin D supplement is associated with a reduced risk for respiratory infection — especially among those who have low levels of the vitamin in their blood.
Martineau and others say it’s very possible — though not yet proven — that a vitamin D supplement could provide a measure of protection against SARS-CoV-2 and Covid-19.
How vitamin D may combat the coronavirus
Thanks in part to Martineau’s work on vitamin D and respiratory infections, the “sunshine vitamin” — so called because the human body requires UV light to make it — has been the focus of Covid-19 research almost since the start of the pandemic.
During the spring, several groups identified apparent associations between low levels of vitamin D and increased Covid-19 risks. Since that time, others have replicated their work. For a study published September 17 in PLOS One, researchers found that a person’s risk for a positive SARS-CoV-2 infection is “strongly and inversely” associated with blood levels of vitamin D. Taken together, these findings suggest that adequate vitamin D levels may help prevent a SARS-CoV-2 infection and also keep infections that do occur from growing worse.
The mechanisms that may explain vitamin D’s benefits are numerous. For example, macrophages are helpful white blood cells that play a number of virus-clearing roles. “Vitamin D deficiency impairs the ability of macrophages to mature,” says Petre Cristian Ilie, PhD, a Covid-19 investigator and research director at The Queen Elizabeth Hospital in the U.K. Moreover, Ilie says that vitamin D may increase levels of certain cell enzymes that help repel the coronavirus. There’s also evidence that the presence of vitamin D may dampen elements of the immune system that are involved in the so-called cytokine storm that is associated with severe Covid-19. These are just a sampling of the many ways in which vitamin D may protect against SARS-CoV-2.
“Even before the coronavirus pandemic, I think there was good evidence to support taking vitamin D supplements,” says Walter Willett, MD, a professor of epidemiology and nutrition at Harvard T.H. Chan School of Public Health. “This pandemic adds another reason.”
Since the early days of the pandemic, Willett has been investigating the relationship between vitamin D and Covid-19. “The evidence that low vitamin D levels are a risk factor for severe [Covid-19] disease is not definitive, but many lines of research suggest that this is likely,” he says.
“The healthier you are, the more your vitamin D levels will rise naturally.”
He points out that African Americans and other people of color, due to elevated levels of melanin in the skin, require more sun exposure than lighter-skinned individuals to produce like amounts of vitamin D. “We know from national surveys that Black people living in the U.S. have about 17 times higher rates of severe vitamin D deficiency than White people,” he says. Black Americans have also experienced disproportionately high rates of severe Covid-19. While many other factors contribute to these inequalities — including differences in income, work, and health care access — Willett says that it is “highly possible that low vitamin D levels can explain part of the huge disparities in severe Covid-19 infection.”
Research from Europe has found that countries hit hardest by Covid-19 — such as Spain and Italy — have a higher prevalence of vitamin-D deficiency than countries with populations that tend to be sufficient in D. It’s also worth noting that the burden of deadly Covid-19 appeared to dip during the sunnier summer months in the U.S., U.K., and elsewhere. There are many plausible explanations for this drop that have nothing to do with vitamin D or sun exposure — including improved clinical management of the disease. But some researchers have speculated that populationwide increases in sun exposure during the summer, and consequently improved vitamin D status, may have contributed to the disease’s apparent softening.
Not everyone is convinced
For all vitamin D’s promise, some experts say that the sunshine vitamin may turn out to be fool’s gold.
“I’m as excited as anyone about vitamin D, but I’m not ready to jump on the bandwagon,” says Mark Moyad, MD, the Jenkins/Pokempner director of preventive and alternative medicine at the University of Michigan Medical Center.
Moyad is among the world’s leading authorities on the risks and benefits of supplements. He reels off a number of potential confounders or complicating factors that could eventually squelch the current enthusiasm for vitamin D. “As you gain weight, vitamin D goes down because it’s sequestered in adipose tissue,” he explains. In fact, almost any disease that is associated with metabolic dysfunction or inflammation tends to drive down the blood’s quantity of vitamin D. And so it’s possible that low vitamin D is simply a marker of health issues — such as obesity and Type 2 diabetes — that are known to make Covid-19 worse, he says. (Similarly, some researchers have posited that vitamin D is an indicator of adequate sun exposure, which they say may provide a number of health benefits that are frequently misattributed to vitamin D.)
For those who want to raise their vitamin D levels safely, Moyad says that the best way to do so doesn’t involve a pill.
Furthermore, Moyad points out that some researchers have failed to find correlations between low levels of vitamin D and an increased risk for Covid-19 — including among people of color. Even if it turns out that vitamin D plays a role in moderating some aspect of SARS-CoV-2 infection or disease, it’s not a certainty that swallowing the vitamin as a supplement will do any good. “We’ve been trolled and teased before by these sorts of correlations, and we’ve paid the price,” he says.
To illustrate his point, he describes the decades of promising research that linked low vitamin D levels to bone weakness. But when, for a 2019 JAMA study, people took high daily doses of vitamin D for three years, their bones actually got weaker, not stronger. While the known risks of taking moderate amounts of vitamin D as a supplement are minimal, the JAMA study’s findings — as well as the findings of many other past vitamin studies — show that there can be unexpected and often unwanted consequences associated with supplement use.
For those who want to raise their vitamin D levels safely, Moyad says that the best way to do so doesn’t involve a pill. “Eat right, stop smoking, get some exercise, get outside in the sun, lose weight,” he says. “The healthier you are, the more your vitamin D levels will rise naturally.” For those dead set on taking a vitamin D supplement, he recommends taking no more than 600 to 800 IU per day, which is the National Institutes of Health (NIH) recommended daily amount for kids and adults.
Martineau — the London-based respiratory disease expert — offers similar advice. Based on some of his recent work, he says that daily doses of vitamin D in the 400 to 1,000 IU range appear to be safe and effective for the prevention of infections. Harvard’s Willett is a bit more bullish. He says that 2,000 IU per day is “a reasonable dose” for adults. But he also says more research is needed to identify optimal intakes.
“I love vitamin D, and I’m excited to see if it works,” Moyad adds. “But we may end up disappointed.”
