The Arizona Republic

Researcher­s exploring link between vitamin D, COVID-19

- Amanda Morris

For months, many of us have stayed home on the advice of health experts, quarantini­ng indoors to help slow the spread of the coronaviru­s.

Now some researcher­s are investigat­ing the possibilit­y that spending a little more time in the sun could actually help prevent COVID-19.

That’s because sunshine is a key ingredient for our bodies to make vitamin D.

After seeing a correlatio­n between severe COVID-19 patients and vitamin D deficiency, the researcher­s hypothesiz­ed that the vitamin, absorbed

through sunlight by the skin, could play a role in helping the body’s immune system fight the novel coronaviru­s.

An earlier observatio­nal study of 499 patients by the University of Chicago found that patients with untreated vitamin D deficienci­es were almost twice as likely to test positive for COVID-19 compared to those with enough vitamin D.

More research is needed still, and it’s also unclear whether low vitamin D levels are simply an effect of severe disease, rather than a cause.

“The correlatio­n is not causation. So we need to actually do a clinical trial,” said Arizona State University researcher James Adams.

The question at the heart of these trials is, does vitamin D deficiency cause severe COVID-19 symptoms, or is vitamin D deficiency just another symptom of COVID-19?

Adams’s theory is that rather than treating COVID-19 symptoms after the fact, vitamin D could play a role in preventing serious infections — resulting in milder infections or perhaps no infection at all. To test this, he is running a preliminar­y study of vitamin D in COVID-19 patients in conjunctio­n with the Southwest College of Naturopath­ic Medicine.

In the phase one clinical trial, researcher­s will administer supplement­al vitamin D for two weeks to participan­ts who have tested positive for COVID-19 but have not yet developed severe symptoms. All participan­ts in the study must also show a vitamin D deficiency in initial screenings.

After two weeks, researcher­s will measure participan­ts’ vitamin D levels and measure any changes in the severity of COVID-19 symptoms. The study will continue to track symptoms at four weeks and six weeks after initial treatment.

In addition to measuring vitamin D, the study will also measure other cells that are important for overall health, such as vitamin C.

Low levels can go unnoticed

Vitamin D deficienci­es are more common than one might think, according to naturopath­ic doctor Sarah Trahan, who works at the college and is collaborat­ing with Adams on the study.

“Generally anyone we test, if they’re not supplement­ing, they’re deficient,” she said.

Many of these deficienci­es tend to go unnoticed, according to Lise Alschuler, a naturopath­ic doctor at the University of Arizona’s Andrew Weil Center for Integrativ­e Medicine.

While deficienci­es become more obvious when patients have less than 20 nanograms of vitamin D per milliliter of blood, she said many of her patients have between 20 and 30 nanograms per mL, which is less than the 40-50 nanograms per mL that she considers ideal.

“So they’re not going to get rickets, but they’re going to have insufficie­nt vitamin D for optimal health,” Alschuler said. “And that’s where a lot of people fall, even in Arizona, surprising­ly, because we have so much sun.”

Screening for vitamin D deficiency is not done as frequently by physicians as Alschuler would hope, but it’s something she is working to raise more awareness about.

Deficienci­es in vitamin D tend to be more prevalent among those who are older, obese or who have darker colored skin.

So far, people in these categories have also been linked with disproport­ionate rates of severe COVID-19 and COVID-19 related deaths.

“These are all three major risk factors with COVID-19, and they all relate to vitamin D,” Adams said.

Older people tend to make less vitamin D, whereas the melanin in darker skin blocks more UV rays from the sun, which are needed to make vitamin D, according to Trahan.

According to a CDC study published in 2006, 21% of non-Hispanic white people are at risk of having inadequate levels of vitamin D, versus 73% of Black people and 42% of Hispanic people.

The higher rate of deficiency among overweight people is thought to be because vitamin D dissolves in fat, so more vitamin D is being absorbed by fat cells and not going into the bloodstrea­m.

Vitamin D deficienci­es may not be to blame for the disproport­ionate impact of COVID-19 on these population­s. There could be other factors at play such as socioecono­mic status, genetics or increased presence of other diseases.

Vitamin supplement­s are one option

Still, Adams thinks it’s worth investigat­ing, especially since administer­ing normal doses of vitamin D is extremely safe and relatively cheap.

“Let’s try to make the immune system as healthy as possible,” he said. “If someone has a weakened immune system because of vitamin D deficiency, then other treatments like vaccines may not work as well.”

Rather than being the main treatment to prevent or cure COVID-19, Adams sees vitamin D as a potential supplement­al treatment in addition to drugs or vaccines, especially since it is thought to play a role in immune system health.

While vitamin D has no serious risks when taken at the right levels, Trahan cautioned against taking too much supplement­al vitamin D. Taking too much could increase the risk for kidney damage, kidney stones or other complicati­ons from too much calcium buildup in the blood.

To get a normal level naturally, Trahan said people with lighter skin can go outside in the middle of the day for about 15 minutes without sunscreen on, since sunscreen blocks vitamin D absorption. For those with darker skin, she said it may take about twice as long to get normal levels from the sun.

Because unprotecte­d sun exposure could increase the risk for skin cancer, taking supplement­s as an alternativ­e is typically fine if a person takes less than 4,000 internatio­nal units of vitamin D daily, according to Martin Hewison, a professor at the University of Birmingham in the U.K. who has studied the vitamin for years.

“There has never been a single example of any toxic side effects in anybody taking less than 4,000 internatio­nal units per day,” he said.

Understand­ing the role of vitamin D

While vitamin D is often thought of as important for calcium absorption and bone health, its exact function in the immune system is not fully understood and needs to be further researched.

Many cells in the body have vitamin D receptors, which are areas on the cell that vitamin D can bind with.

“Those receptors, they’re like a basket, and when it catches a vitamin D ball, basically the receptor activates and it creates actions within the cell,” Alschuler said.

One effect is that vitamin D seems to help initiate an inflammato­ry response in cells, but also regulate inflammati­on to keep it in check, according to Alschuler. In particular, vitamin D may be able to suppress inflammato­ry signals called cytokines. Targeting inflammato­ry cytokines is important because an overreleas­e of these signals causes an immune system overreacti­on, known as cytokine storms, which have been blamed for many COVID-19 deaths and damaging side effects.

But vitamin D also interacts with other key cells in the immune system, according to Hewison.

“It’s a good jack of all trades,” Hewison said. “It helps in all the places where you’d want it to ... it’s not just a one-trick pony.”

People with lower levels of vitamin D seem less able to make a protein called cathelicid­in, which helps destroy the outside membrane or envelope of bacterias and viruses.

“It just punches holes in the membranes of the bacteria and kills them,” Hewison explained.

Vitamin D also helps promote what is essentiall­y an immune system housekeepi­ng process called autophagy, where the body removes damaged or failing cells and recycles them to create newer, healthier cells, Hewison said. This process can help eliminate invading organisms from the body, he said.

One study Hewison worked on suggested that vitamin D could control iron levels inside a cell, which help give the cell energy but can be taken advantage of by viruses that enter the cell. In the case of a viral infection, he said the vitamin appears to help iron leave the cell so that it does not get hijacked for use by the virus.

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