In the past decade, researchers have uncovered intriguing links between low levels of vitamin D and a host of immune system problems, including respiratory infections and “cytokine storms,” the runaway inflammation that also kills many COVID-19 patients.
At the same time, scientists have found people with darker skin generally have low vitamin D levels in their blood, especially those living in colder climates.
Bruce Hollis has been studying vitamin D for decades at the Medical University of South Carolina. He had this research in mind earlier this year when the novel coronavirus began circulating across the world.
“The first thing I did was ask for some racial breakdown data, even though I knew what I was going to find,” said Hollis, professor emeritus of pediatrics, biochemistry and molecular biology.
Early reports in Michigan showed that 40 percent of the state’s coronavirus deaths involved black residents, while the state’s African American population was 12 percent. In Sweden, 40 percent of the COVID-19 deaths in Stockholm were Somali immigrants, who make up less than 1 percent of the population.
Hollis was well aware of arguments that people of color have higher rates of obesity, cancer and diabetes — the kinds of underlying conditions that can make a viral assault more deadly.
But he and other longtime investigators think low levels of vitamin D could be part of the coronavirus prevention equation. They’re calling for more research to examine its potential while urging people to make sure they’re getting enough vitamin D even if it has no effect on the coronavirus.
“It can’t hurt, and it might help,” Hollis said.
Can a common, off-the-shelf supplement make a dent in the pandemic? The coronavirus has triggered a global push to find a vaccine and effective treatments — as well as a growing roster of fake cures and claims. The virus is so new that scientists are still wrestling with basic questions about why some infected people show few or no symptoms while others, including seemingly healthy people, suffer catastrophic attacks.
No one is suggesting that vitamin D is anything close to a cure. Yet, in the absence of a vaccine or effective treatment, even incremental improvements in our ability to ward off the disease would have widespread benefits, Hollis said. A look at the evolution of vitamin D research is revealing, both for its potential and reasons for caution.
The vitamin connection
For more than three decades, Hollis has been on the leading edge of this field. On a recent morning, he sat in a park outside MUSC, soaking up some sun. Wearing an Ohio State shirt, he talked about how he grew up on a vegetable farm in northern Ohio, where, he joked, “no one even knew what a Ph.D. was.”
At Ohio State, he wavered between human and veterinary medicine. As a graduate student, he grew fascinated by “milk fever,” a calcium deficiency often seen in older cows. That’s when he first started thinking hard about vitamin D.
Vitamin D is a critical substance for cows — and humans. It’s a hormone that we naturally create when our skin is exposed to the sun. It helps build stronger bones. Nerves need it to carry messages between the brain and other parts of the body. It helps the immune system ward off bacteria and viruses. But as people moved from farms to cities — and spent more time indoors — vitamin D deficiency became a widespread health problem.
This deficiency was most evident in children who developed rickets, a deformation that makes bones soft and muscles weak. In the mid-1800s, scientists noticed that city children were more likely to have rickets than children in rural areas. But it wasn’t until the 1920s that scientists proved that ultraviolet light from the sun helped the body create a substance that affects bone growth. Scientists named that substance vitamin D.
Hollis eventually obtained a Ph.D. in nutrition with a focus on vitamin D. He established his place in the field in 1993 with the creation of a new test to diagnose vitamin D deficiency in the blood. He's written or collaborated on more than 300 scientific papers.
Early in his career, many researchers focused on vitamin D’s connection to bones. Federal health agencies eventually established a daily recommended allowance of 400 to 600 units per day to prevent bone problems. But, over time, it became clearer that vitamin D affected many health conditions beyond bones. Hollis thought those federal guidelines were too low for these problems — especially for people with darker skin.
Biology and evolution explain this, he said. People in sun-rich climates adapted to the sun’s power by accumulating more melanin in their skin to protect against burns. But this protection also slows the production of vitamin D. As a result, people with darker skin pigmentation may need 10 times as much sun exposure to create the same amounts of vitamin D as people with lighter skin.
Hollis said supplements are the best way to fix this, and that most people need 4,000 to 6,000 units a day. Good diets typically provide most of the vitamins we need, with the exception of the sun-dependent vitamin D. A few foods, including egg yolks and seafood provide some vitamin D, but not in the amounts the body produces when exposed to the sun.
“The bottom line is that you have to take enough for it to matter.”
Positive and negative results
About 20 years ago, Hollis and Carol Wagner, a doctor and professor of pediatrics at MUSC, had offices next to each other. She began to talk to Hollis about his research.
“I was very naïve about vitamin D,” Wagner said. “The only thing I remembered was what I’d learned in medical school — that it was important for bones.”
She dug into the history of vitamin D, and something caught her eye: Children with rickets often had respiratory infections.
“I said to Bruce, ‘Wow, that’s odd, do you think vitamin D has anything to do with immunity?’ ”
At the time, the consensus was that children with rickets had such weak ribs that they couldn’t breathe properly. But there was no definitive proof of that.
“He said, ‘We don’t even know how much vitamin D pregnant women need.' That was the beginning of our collaboration.”
They focused much of their research on pregnant women. Among their findings: Women who got sufficient amounts of vitamin D during pregnancy lowered their risks of infections and premature deliveries; breastfeeding mothers and their newborns also benefited from higher supplementation — 6,400 units a day.
Time and again, Wagner said, she found that African American participants in the studies had lower vitamin D levels and benefited the most from supplements.
“In South Carolina, we have a profound deficiency in our African American and often our Hispanic population.”
Hollis also looked at its effects on cancer. In a small trial, an MUSC team found that men with prostate cancer showed improvements when they took 4,000 units a day. That study came amid others that showed the vitamin having an important impact on the immune system.
In 2016, a global team of scientists analyzed 25 clinical trials and concluded that vitamin D supplements helped protect people against severe respiratory infections, including those from colds and flus. People with low vitamin D levels in their blood benefited the most, cutting their risks in half.
But other large studies concluded that vitamin D supplements had little or no benefit. One of the largest, a Harvard-led project called VITAL, involved more than 25,000 patients who took 2,000 units per day. Scientists followed them for more than five years. Researchers concluded that vitamin D didn’t lower risks of heart disease and strokes and cancer, with a notable exception. African Americans saw a 23 percent reduction in their cancer risk.
Because studies had mixed results, interest in vitamin D research had waned in recent years, said Martin Hewison, a professor of endocrinology in the United Kingdom who has researched vitamin D’s impact on the immune system.
Then the coronavirus hit.
Hewison said COVID-19 suddenly injected new energy into the field. As in the United States, the disease in the United Kingdom disproportionately affected black and Asian groups — groups that typically had low levels of vitamin D. In the past week alone, he said, he’s been asked to participate in three COVID-19 research projects.
One reason for this interest is the disease’s effect on cytokines. Cytokines are soldiers in the immune system that help our bodies deal with diseases and infections. But certain triggers, including COVID-19, can turn them into marauding armies that wreak havoc on the body’s organs. These “cytokine storms” can be more harmful than the infection itself.
One recent study looked at blood levels of 212 COVID-19 patients in three South Asian hospitals. Researchers found that most patients with high levels of vitamin D had mild symptoms. But 40 percent of the patients with vitamin D deficiency had severe problems. Another study last week by Louisiana State University involved 20 COVID-19 patients in Louisiana intensive care units. The authors found that 85 percent had deficient levels of vitamin D.
These studies have yet to go through the normal scientific vetting process, but the coronavirus’s rapid march across the globe has added a sense of urgency to find anything to slow its spread.
Last month, John Umhau, a recently retired investigator at the National Institutes of Health, pointed to research showing how the lack of sun-induced vitamin D in winter and early spring leads to an epidemic of respiratory infections. He urged people to get a decent amount of sun, even though doing so carries its own risks of skin cancer.
“Any risk of exposing the body to sunshine while sheltering in place is clearly outweighed by the risk of COVID-19.”
Back outside MUSC, Hollis squinted in the sun as two Air Force jets roared above in a noontime salute to the health care workers below.
“If I’m sitting out here in the sunlight today, midday, and I have most of my body exposed to the sun, I’m going to make between 10,000 to 20,000 international units naturally,” he said. That’s equivalent to five to 10 typical vitamin D pills.
You don’t have to be in the sun for long periods because, at a certain point, the body begins to regulate its vitamin D production. He cited an analysis of athletes training in the Wyoming sun; they didn't produce more than 100,000 units a day, despite spending long periods exposed to the sun.
Such findings tell him and other researchers that taking a few vitamin D pills a day won’t create any toxicity issues. The government’s recommended dose of 600 units a day “isn’t nearly enough,” he said.
“It’s based on bones, and this gets back to COVID-19, we’re seeing African Americans suffer disproportionately from this, and given what I know about this group’s history of vitamin D deficiency, I thought that was totally predictable. Can we help them with vitamin D supplementation at levels that actually have an effect? I think so. Though I know a lot of people are very skeptical out there.”