Vitamin D status and COVID-19: reviewing the evidence

Our bodies require Vitamin D to absorb calcium for strong bones, teeth and to maintain muscle strength and normal function [1]. Research shows that Vitamin D may have a role beyond skeletal wellness as Vitamin D seems to correlate well with decreased incidence for many conditions. Vitamin D has been a subject of more scientific articles in the 21st century than any other vitamin, reflecting the rapid growth and interest in Vitamin D research. [2]

Study on Vitamin D and COVID-19 Infection

Vitamin D has been making headlines as the pandemic evolved for the past two years, as researchers linked it to competent immunity. While vaccination seems crucial in reducing the risk of acute life-threatening COVID-19, it does not guarantee complete immunity against the virus. As a precautionary measure, and even if fully vaccinated, the public has been encouraged to support the normal function of their immune system. [3]

In a time of social responsibility, one may ask, "what can I do to support the normal function of my immune system to reduce the severity of a more than possible COVID-19 infection?"

To that effect, a new and insightful systematic review from Borsche, Glauner and Mendel, 2021 [4] three independent novel authors that despite no previous publications, may have written a relevant paper that could help clarify this question and spark a productive conversation.

The novel German researchers set to demonstrate the hypothesis that Vitamin D3 deficiency is one of the main reasons for severe SARS-CoV-2 infections and that supplementation might be the easiest and simplest action one may take to improve the odds. In the researchers own words: "Could a virus that is spreading so easily and is much deadlier than H1N1 influenza be kept under control if the human immune system could work at its fullest capacity?"

After a thorough triage of the available clinical and epidemiological papers published in the past 18 months for COVID and Vitamin D, the researchers identified 8 out of 44 published studies for quality and statistical potency. The studies included several meta-analyses, hospital studies for 1,607 patients and one general population study that spanned 19 countries.

"Could a virus that is spreading so easily and is much deadlier than H1N1 influenza be kept under control if the human immune system could work at its fullest capacity?" Borsche et al. 2021

The resulting statistical analysis showed a strong correlation between serum Vitamin D levels as a marker of a patient's immune competence and resilience against respiratory tract infections, including SARS-CoV-2. The resulting correlations based on the available papers show that the higher the serum Vitamin D3, the more likely to experience a mild to asymptomatic COVID-19 infection. So much so, that theoretically and per extrapolation, COVID mortality would approach zero as blood serum Vitamin D3 reached 50 ng/mL [4].

The authors conclude that "... strong evidence that low D3 is a predictor rather than just a side effect of the infection." and that "[the authors] strongly recommend combining vaccination with routine strengthening of the immune system of the whole population by vitamin D3 supplementation to consistently guarantee blood levels above 50 ng/mL (125 nmol/L)".

Possible underlying mechanism of Vitamin D in COVID-19 infection

To understand how Vitamin D may work against the virus, it is essential to remember what COVID-19 does to the body. The most life-threatening event in the course of a COVID-19 infection is the Acute Respiratory Distress Syndrome (ARDS) mediated by multiple mechanisms, including an out of control, dangerous immune response to the infection called "cytokine storm". ARDS results in fluid accumulating in the lungs' air sacs, leading to a significant decrease in oxygen reaching the bloodstream and difficulty breathing. [5]

A cytokine storm occurs when immune cells rapidly and uncoordinatedly release a flood of cytokines into the bloodstream to fight the viral infection, causing more harm than good, including multiple organ dysfunctions. [6]

According to the authors, SARS-CoV-2 virus interferes with the normal regulation of the body's system to control blood pressure and volume. This system is called the renin-angiotensin system (RAS). The virus has been studied in relation to a key component of the system called Angiotensin II, potentially affecting its conversion to Angiotensin-(1,7) by inhibiting the enzyme responsible for this step. The virus hijacks this enzyme called ACE2 to enter cells, leaving Angiotensin II to accumulate. This accumulation then triggers vasoconstriction and results in inflammation, fibrosis, and oxidative stress that eventually leads to ARDS. [4,7] Vitamin D counteracts this virus hijack by stimulating the ACE2 enzyme to clear Angiotensin II to Angiotensin-(1,7) which tapers down the route to ARDS.

Prior research has also shown that Vitamin D3 may attenuate the inflammatory response due to viral infection by increasing regulatory T Cells (Treg) - immune cells that curb excessive immune response to maintain homeostasis. Tregs may play a role in preventing the unleash of cytokine storm whilst conserving the ability of the immune system to coordinate its response to the viral infection. [8]

Revisiting Vitamin D3 Supplementation in the light of new findings

Considering these new independent findings, it would seem logical to advise the public to increase its Vitamin D levels to better react to a COVID-19 infection, escape any future variants, or offset decreasing antibody activity.

However, current Vitamin D recommendations seem far too low to attain the desired pre-emptive protection level and improve the odds of future infection outcomes.

Historically, serum Vitamin D recommendations were initially established over a century ago at 20 ng/ml, which has been studied in relation to rickets, the softening and the weakening of children's bones. [9] Current WHO recommendations upped the level and set it at 30 ng/ml in the late 20th century.

One repeated primary concern preventing higher levels of Vitamin D recommendations relies upon the widespread belief that higher supplementation would increase the risk of calcium deposits in the arterial lining. However, it is now known that adequate levels of Vitamin K2 may play a role in preventing arterial calcification, with Vitamin K2 potentially directing available calcium to the bones rather than the vascular walls. [10]

"To maintain these blood levels [40-60 ng/ml] with minimal sunlight exposure, a person would require ingestion of 4000–6000 IUs of vitamin D daily" Charoenngam et al. 2021

More voices in the scientific and medical community are pushing the current WHO recommendation of serum Vitamin D3 levels from the low 30's to over 50 ng/ml.

Borsche et al. also conclude in their review that Vitamin D supplementation ranging from 4000-10000 IU/day to generate the desired new levels of 50 ng/ml is safe if levels of Vitamin K2 are at 200 µg/ml. [4]

Bottom-line

Multiple publications support the correlation of Vitamin D3 to benefits other than musculoskeletal maintenance, including proper immune function.

As the pandemic evolved during the past two years, accumulating epidemiological data seem to confirm that pre-infection Vitamin D3 status may be a factor correlated with COVID-19 infection outcomes.

Disclaimer:

This article is for educational purposes only and must not replace advice from your own health care provider. Always consult your own doctor before taking any medication or supplements.