Talis Shelbourne, Heavy.com, May 10, 2020
The study looked at the relationship between vitamin D deficiency and coronavirus deaths, and it also analyzed the overall vitamin D levels for the citizens of countries hit hardest with coronavirus deaths. However, other findings from the study have also suggested that vitamin D might be able to reduce the complications of coronavirus.
How? Researchers say the answer might lie in how coronavirus kills those infected with it.
New Scientist confirmed that the body’s overreactive immune response is largely responsible for causing the phenomenon which makes diseases such as COVID-19 and influenza fatal: cytokine storms.
Cytokines are small proteins involved in cell communication and inflammation. In an interview with Heavy, Washington State University Regents Professor James Krueger explained how coronavirus kills.
Krueger said there are more than 100 cytokines in the human body, most of which are anti-inflammatory, but contracting an infection is what typically triggers pro-inflammatory cytokines. New Scientist notes that this cytokine response is associated with MERS, multiple sclerosis, pancreatitis and SARS coronaviruses, such as COVID-19.
One of the reasons this can become problematic, Krueger said, is because of how many ways cytokines can be produced. For example, macrophages and immunocytes, which consume bacteria and viruses, are primed to produce more cytokines as products of their activity. Krueger also said the viral replication process can also kick-off cytokine production.
“The immune response causes a high production of cytokines,” Krueger said. “As the disease progresses, the cytokines go up.”
Krueger studied mice to find out how cytokine production affected the hypothalamus, a part of the brain which regulates body temperature, appetite, sleep, heart rate and other important functions. In his research, he found that the presence of cytokine clusters in the hypothalamus produced many of the same symptoms humans associate with being ill: the sweats and the chills, having a decreased appetite and feeling fatigued.
But the production of too many cytokines can cause a cytokine storm - a large collection of pro-inflammatory cytokines that cause blockages. Depending on where those are blockages are, they can affect things like breathing. For example, they can damage the alveoli of the lungs, which are responsible for helping exchange gas and air and they can also damage the bronchial tubes where air comes into the lungs.
Krueger said that in most patients, a high production of cytokines in the lungs, nasal passages, respiratory system and hypothalamus produces a lot of the symptoms associated with sickness: feeling tightness in your chest, fatigue and anosmia (loss of smell).
“Almost everyone will get increases in the production of cytokines,” he said. “They won’t be lethal - they will make the individual fatigued, make them sleepy.”
However, in patients where cytokine production is even higher, he said the results can be fatal:
The virus kicks off the production of a lot of different cytokines. When people die of COVID, often what happens is, they have intense cytokine storms. If they are in the wrong place, you get huge amounts of inflammation. If they’re in the lungs, it will reduce the space in the bronchioles of the alveoli and create a build-up of fluid. You essentially drown in your own fluid. It’s a terrible thing, that’s why people are worried about it.
The only way to reverse the cytokine reaction, he said, is with the production of anti-inflammatory cytokines or the inhibition of pro-inflammatory cytokines.
Vitamin D, which comes in the form of pills and naturally from foods and sunlight and help humans support bone health. The hormone calcifediol (also referred to as 25(OH)D in studies), is produced when after vitamin D goes through the liver and this metabolite is often what is used to measure someone’s vitamin D levels.
Vitamin D deficiency can cause several bone issues, including making them thin, brittle or curved. However, more importantly, studies have linked higher levels of vitamin D, which inhibits the activity of pro-inflammatory cytokines, to lower levels of inflammation.
Researchers at National Jewish Health published a study in 2012 which linked vitamin D deficiencies to inflammatory diseases. More importantly, the study found that vitamin D inhibits macrophages from producing pro-inflammatory cytokines.
“In their experiments, they showed that low levels of vitamin D, comparable to levels found in millions of people, failed to inhibit the inflammatory cascade, while levels considered adequate did inhibit inflammatory signaling,” a summary of the study found.
A 2014 study looked at whether low levels of vitamin D are a consequence or cause of chronic inflammation. The study ultimately concluded that chronic inflammation reduces the body’s ability to metabolize vitamin D.
However, a 2016 study examined the same question and concluded that both were true; vitamin D might decrease inflammation and some components of inflammation might inhibit the metabolism of vitamin D.
And a 2018 study examining whether vitamin D could affect cytokines involved in cancer metastasis, found that “Experimental data have also confirmed that vitamin D can inhibit the occurrence and metastasis of tumors through many different processes.”
Biomedical engineering professor Vadim Backman from Northwestern’s McCormick School of Engineering was the lead researcher for the team working on the study in question.
The team studied vitamin D deficiencies to severe cases of COVID-19 based on patient records from around the country: Germany, South Korea, China, Spain, Iran, Italy, the United Kingdom, the U.S. and France among others. Ultimately, they found a link between vitamin D levels and cytokine storm and a correlation between vitamin D deficiency and mortality.
One of the conclusions in the study stated that:
… Vit D may reduce COVID-19 fatality by suppressing cytokine storm [10,14,21]. Specifically, the risk of severe COVID19 cases among patients with severe Vit D deficiency is 17.3% while the equivalent figure for patients with normal Vit D level is 14.6% (a reduction of 15.6%). This potential effect may be attributed to Vit D’s ability to suppress the adaptive immune system, regulating cytokine level and thereby reducing the risk of developing severe COVID-19.
Backman told Science Daily, “Our analysis shows that it might be as high as cutting the mortality rate in half. It will not prevent a patient from contracting the virus, but it may reduce complications and prevent death in those who are infected.”
He also added that he does not believe people should begin taking excessive doses of vitamin D because it could cause negative side effects, but he thinks more research should be conducted on vitamin D’s ability to prevent complications from COVID-19.
It’s important to note that the study is an “unrefereed pre-print” which means that it has not gone through the peer review process necessary to check for flaws in data collection, analysis and other errors. Science Alert pointed out there are issues with cross-sectional reports because countries measure and collect vitamin D levels data differently.
Different studies have supported and/or narrowed the applicability of the study.
A May 6 study published in the Aging Clinical and Experimental Research journal looked at 20 European countries and also found a correlation of low vitamin D levels and high COVID-19 mortality.
The Center for Evidence-Based Medicine published a rapid review on whether vitamin D can treat or prevent COVID-19 and concluded the following:
We found no clinical evidence on vitamin D in COVID-19. There was no evidence related to vitamin D deficiency predisposing to COVID-19, nor were there studies of supplementation for preventing or treating COVID-19.
That same study, however, also found that “There is some evidence that daily vitamin D3 supplementation over weeks to months may prevent other acute respiratory infections, particularly in people with low or very low vitamin D status.”
An April 29 study actually examined how “vitamin D status impacts mortality from SARS-CoV-2 infection” and found that high-dose vitamin D didn’t help patients with COVID-19, but a standard dosage might have benefits.
The National Heart, Lung, and Blood Institute (NHBLI) performed a randomized controlled trial evaluating the role of high dose vitamin D (single dose of 540,000 IU of vitamin D3) in critically ill patients who were vitamin D deficient (25-hydroxyvitamin D level < 50 nmol/l) [17], the study failed to demonstrate any benefit from high dose vitamin D … we advise a vitamin D dosage at what would be considered a standard nutritional supplement that may be sufficient in providing clinical benefits.
All of the studies have suggested more research in this area could provide more conclusive evidence of vitamin D’s role in helping reduce COVID-19 complications.
“It is hard to say which dose is most beneficial for COVID-19,” Backman told Science Daily. “However, it is clear that vitamin D deficiency is harmful, and it can be easily addressed with appropriate supplementation. This might be another key to helping protect vulnerable populations, such as African-American and elderly patients, who have a prevalence of vitamin D deficiency.”
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