Over the past few months, several investigations have highlighted the apparent influence of vitamin D in COVID-19 incidence, severity and mortality. Interestingly, recent genetic analysis has produced a novel hypothesis1 that helps explain the unusual disease progression of COVID-19.
The hypothesis,2 published in the journal eLife in July 2020, specifically identifies bradykinin, a blood pressure regulating chemical controlled by your renin-angiotensin system (RAS), as a primary culprit.
As reviewed in greater depth in "Bradykinin Hypothesis Explains COVID-19 Complexities," the lethality of COVID-19 may be due to the virus' ability to induce a bradykinin storm. The effects of the virus on your RAS also adds further support to the recommendation to optimize your vitamin D.
In fact, the researchers who came up with the novel bradykinin hypothesis stress the usefulness of vitamin D, as it plays an important role in the RAS system3,4,5,6 and suppresses the biosynthesis of a compound called renin (REN), thereby preventing a deadly bradykinin storm.
Conversely, if you are vitamin D deficient, your renin expression is stimulated, and based on the latest data, that may render you more prone to bradykinin storm. Other studies have also emerged in recent weeks, showing that raising patients' vitamin D levels has a dramatic and beneficial effect on COVID-19 outcomes.
Vitamin D Massively Reduces ICU Admissions
Among them is a pilot randomized clinical study7,8,9 published online August 29, 2020, which found hospitalized COVID-19 patients in Spain who were given supplemental calcifediol (a vitamin D3 analog also known as 25-hydroxycholecalciferol or 25-hydroxyvitamin D) in addition to standard of care — which included the use of hydroxychloroquine and azithromycin — had significantly lower intensive care unit admissions.
Patients in the vitamin D arm received 532 micrograms of calcifediol on the day of admission (equivalent to 106,400 IUs of vitamin D10) followed by 266 mcg on Days 3 and 7 (equivalent to 53,200 IUs11). After that, they received 266 mcg once a week until discharge, ICU admission or death.
Of those receiving calcifediol, only 2% required ICU admission, compared to 50% of those who did not get calcifediol. None of those given vitamin D supplementation died, and all were discharged without complications.
CDC Warns of Second Wave of COVID-19
In the video above, NBC News interviews Michael Osterholm, virologist and director of the Center for Infectious Disease Research and Policy at the University of Minnesota in Minneapolis, about the prospect of a second wave of COVID-19.
According to Osterholm, we likely have another 12 to 14 months of "a really hard road ahead of us." While Swedish statistics suggest the virus can and is dying off naturally, Osterholm believes cases will again rise as we move into fall and winter. Even if a vaccine does become available, it will take months to vaccinate the population, he notes.
Chief epidemiologist in charge of Sweden's coronavirus response, Anders Tegnell, has stated12 he does not believe Sweden will see a second wave with widespread contagion as the country is seeing a rapid decline in positive tests, indicating herd immunity is being achieved.13
That said, there are still open questions as to how long natural immunity might last.14 Some evidence points to months,15 while other data point to several years.16 Then there are the data suggesting herd immunity for COVID-19 occurs at much lower rates than normal.
As reported17 by Dr. James Hamblin in The Atlantic, infectious disease modeling by Gabriela Gomes, who specializes in nonlinear chaos dynamics, "selective depletion" of individuals susceptible to infection can rapidly reduce viral spread, and in the case of SARS-CoV-2, models suggest the threshold for herd immunity may occur below 20% of the population.
Yet other data18,19,20,21 suggest certain antibodies against other coronaviruses, such as the common cold, appear to provide some protection against SARS-CoV-2 as well, such that a majority of people may already have some level of immunity. So, there's a variety of "moving parts" that still need to be nailed down before we can come to any firm conclusions about future risks.
Vitamin D Versus Vaccine
While Osterholm22 and other health officials are still focused on getting people onboard with vaccination, both against influenza and COVID-19, no one at the federal level has as of yet addressed the elephant in the room, which is vitamin D deficiency and its impact on these infections.
Importantly, influenza vaccination has been shown23,24 — by the Department of Defense, no less — to increase the risk of subsequent coronavirus infections by 36%. If we are to follow the science, as Osterholm says, then we should not be so quick to overlook such findings.
Then, of course, there's the issue of whether a safe and effective COVID-19 vaccine is achievable. I've discussed the reasons for why I believe COVID-19 vaccines will fail in several previous articles. Vitamin D optimization, in contrast, is already known to be both safe and effective against not only influenza but also COVID-1925,26,27 and other respiratory infections.28
According to a 2017 systematic review29,30,31 published in The BMJ, vitamin D supplementation protected against acute respiratory tract infection. The number needed to treat (NNT) was 33, meaning 33 people had to take the supplement in order to prevent a single case of infection. Among those with severe vitamin D deficiency at baseline, the NNT was 4.
Meanwhile, a systematic review32 by the Cochrane Database of Systematic Reviews found that to prevent one case of influenza-like illness (defined33 by the World Health Organization as an acute respiratory infection), the NNT for inactivated vaccines was 40. To prevent a single case of confirmed influenza, the number needed to vaccinate (NNV) was 71.
Vitamin D Is an Important Modifier of COVID-19 Risk
In a November 1, 2020, commentary34 in the journal Metabolism Clinical and Experimental, JoAnn Manson and Shari Bassuk call for the elimination of vitamin D deficiency to effectively squelch the COVID-19 pandemic, noting that 23.3% of the total U.S. population have insufficient or deficient vitamin D levels, with people of color having disproportionately lower levels than non-Hispanic whites.
They list several types of studies showing vitamin D deficiency is "an important modifiable risk factor for COVID-19," including:35
• Laboratory studies that demonstrate how vitamin D helps regulate immune function and the RAS, and modulate inflammatory responses to infection.
• Ecologic studies showing populations with lower vitamin D levels or lower UVB radiation exposure have higher COVID-19 mortality,36,37,38 and the fact that people identified as being at greatest risk for COVID-19 hospitalization and death (people of color, the elderly, nursing home residents and those with comorbidities such as obesity, vascular conditions and chronic kidney disease) also have a higher risk of vitamin D deficiency.
• Observational studies showing low vitamin D levels are associated with a greater risk of testing positive for SARS-CoV-2 and contracting acute respiratory infections.
According to a September 3, 2020, JAMA study,39,40 people who tested positive for SARS-CoV-2 were 1.77 times more likely to be deficient in vitamin D than those who tested negative for the virus — a statistically significant difference.
CTV News, which reported the JAMA results, also pointed out that:41 "The connection between vitamin D and other respiratory illnesses is well known.
According to the World Health Organization,42 vitamin D deficiency has been linked to pneumonia, tuberculosis and bronchiolitis," and that "research43 out of New Orleans found 100% of its sickest COVID-19 patients were deficient in vitamin D."
• Randomized clinical trials showing vitamin D inhibits respiratory tract infections, especially in those with lower vitamin D levels at baseline.
Vitamin D Protects Your Lungs
A 2020 GrassrootsHealth study published in the journal Nutrients44 describes how vitamin D can reduce the risk of both influenza and SARS-CoV-2 infection by lowering the viral replication rate and reducing the pro-inflammatory cytokines that damage the lungs, leading to pneumonia.
Vitamin D also helps increase concentrations of anti-inflammatory cytokines that may help protect your lungs. The researchers recommended those at risk for COVID-19 take:
"10,000 IU/d of vitamin D3 for a few weeks to rapidly raise 25(OH)D concentrations, followed by 5000 IU/d. The goal should be to raise 25(OH)D concentrations above 40-60 ng/mL (100-150 nmol/L)."
Vitamin D and COVID-19 Comorbidities
Vitamin D may also help protect against COVID-19 by beneficially impacting many of the comorbidities associated with poor COVID-19 prognosis. In an August 2020 paper45 published in the NSF Journal, the authors review the "fatal relationship" between vitamin D deficiency in combination with comorbidities in COVID-19 patients, noting that:
" … low vitamin D status is common in Europe with the exception of the Scandinavian countries. The calculated COVID-19 mortality rate from 12 European countries shows a significant inverse correlation with the mean 25(OH)D plasma concentration.
This raises the question whether insufficient vitamin D supply has an influence on the course of COVID-19 disease? An analysis of the distribution of COVID-19 infections showed a correlation between geographical location (30–50° N+), mean temperature between 5–11 °C and low humidity.
In a retrospective cohort study (1,382 hospitalized patients) 326 died … The mortality of COVID-19 (cases/ million population) shows a clear dependence on latitude. Below latitude 35, mortality decreases markedly. Indeed, there are exceptions … however, the management of the pandemic may increase infection risk …
Older age and comorbidities are linked to an insufficient vitamin D supply. Over 60 years of age, a reduction in the synthesis of vitamin D in the skin becomes apparent, which further increases getting older …
Based on a meta-analysis including 30 studies with 53,000 COVID-19 patients, co-morbidities are risk factors for disease severity … Comorbidities and old age show a relationship with Renin-Angiotensin-Aldosteron-System (RAS), vitamin D status and COVID-19 infection."
How Vitamin D Helps Modulate SARS-CoV-2 Infection
This brings us back to where I started. While this NSF Journal study does not make reference to bradykinin storm being part of the disease progression and lethality of COVID-19, it does review how vitamin D impacts your RAS (which regulates bradykinin), and how your RAS in turn plays a role in the progression of SARS-CoV-2 infection:46
"Infection with SARS-CoV-2 causes the virus spike protein to come into contact with ACE2 on the cell surface and thus to be transported into the cell. This endocytosis causes upregulation of a metallopeptidase (ADAM17), which releases ACE2 from the membrane, resulting in a loss of the counter regulatory activity to RAS.
As a result, proinflammatory cytokines are released extensively into the circulation. This leads to a series of vascular changes, especially in the case of preexisting lesions, which can promote further progression of cardiovascular pathologies.
SARS-CoV-2 not only reduces the ACE2 expression, but also leads to further limitation of the ACE2/Ang 1–7/Mas axis via ADAM17 activation, which in turn promotes the absorption of the virus. This results in an increase in Ang II, which further upregulates ADAM 17.
Thus a vicious circle is established turning into a constantly self-generating and progressive process. This process may contribute not only to lung damage (Acute respiratory distress syndrome - ARDS), but also to heart injury and vessels damage, observed in COVID-19 patients …
Several studies have shown increased plasma renin activity, higher Ang II concentrations and higher RAS activity as a consequence of low vitamin D status. The same applies to the decreasing Renin activity with increasing vitamin D levels. There is an inverse relationship between circulating 25(OH)D and renin, which is explained by the fact that vitamin D is a negative regulator of renin expression …"
The NSF Journal paper goes on to review the connections found between the RAS, vitamin D levels and a list of comorbidities shown to worsen COVID-19 outcomes, including high blood pressure, cardiovascular diseases, obesity, Type 2 diabetes and ARDS. It also reviews how vitamin D levels, RAS function and cytokine storms are interconnected. The authors state, in conclusion:47
"There is ample evidence that various non-communicable diseases (hypertension, diabetes, CVD, metabolic syndrome) are associated with low vitamin D plasma levels. These comorbidities, together with the often concomitant vitamin D deficiency, increase the risk of severe COVID-19 events.
Much more attention should be paid to the importance of vitamin D status for the development and course of the disease. Particularly in the methods used to control the pandemic (lockdown), the skin's natural vitamin D synthesis is reduced when people have few opportunities to be exposed to the sun.
The short half-lives of the vitamin therefore make an increasing vitamin D deficiency more likely. Specific dietary advice, moderate supplementation or fortified foods can help prevent this deficiency. In the event of hospitalization, the status should be urgently reviewed and, if possible, improved."
Summary
To summarize what the NSF and eLife journals tell us, when your vitamin D is low, your risk of COVID-19 complications and death increases because your renin expression is stimulated.
High renin increases both cytokines and bradykinin, placing you at risk for increased inflammation and oxidative stress resulting in both cytokine storm (as discussed in the NSF paper48) and bradykinin storm (as discussed in the eLife paper49).
Considering cytokine and/or bradykinin storms are key factors in COVID-19 mortality, it seems reasonable to conclude that anything that can help modulate and prevent these devastating storms would be of significant value. As of right now, the one thing we know can do that is vitamin D.
In addition to that, vitamin D lowers viral replication,50 boosts your overall immune function by modulating both innate and adaptive immune responses, reduces respiratory distress,51 improves overall lung function and helps produce surfactants in your lungs that aid in fluid clearance.52
Vitamin D also lowers your risk of comorbidities associated with poor COVID-19 prognosis, including obesity,53 Type 2 diabetes,54 high blood pressure55 and heart disease.56 In my view, there's every reason to believe vitamin D optimization will help lower your risk of COVID-19 complications and death, and no reason to dismiss this strategy.
Optimize Your Vitamin D Level Now
My #StopCOVIDCold campaign seeks to raise awareness about the importance of vitamin D optimization to prevent a resurgence of COVID-19 hospitalizations and deaths.
As temperatures and humidity levels drop — two factors that influence the viability of the virus in air and on surfaces — it's quite likely we'll see a reemergence. But a surge in positive tests, by itself, should not be cause for panic.
Remember, a vast majority of so-called "cases," meaning positive tests, remain asymptomatic. I believe raising vitamin D levels among the general public can go a long way toward increasing the number of people who have no symptoms or only mild illness.
Now is the time to check your vitamin D level and start taking action to raise it if you're below 40 ng/mL. An easy and cost-effective way of measuring your vitamin D level is to order GrassrootsHealth's vitamin D testing kit and learn more about vitamin D and its impact on your health.
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