Vitamin D Levels and Covid 19 infection - new meta-analysis

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 strengthen their immune system. [3]

In a time of social responsibility, one may ask, “what can I do to enhance 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 hit 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 prevents a key component of the system called Angiotensin II to convert 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 can potentially 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 would prevent the unleash of cytokine storm, while 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 to prevent 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 prevent arterial calcification as Vitamin K2 directs 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. Last year, a review on "Immunologic Effects of Vitamin D on Human Health and Disease" suggested serum Vitamin D3 levels between 40 to 60 ng/ml. [11] According to the study: "To maintain these blood levels with minimal sunlight exposure, a person would require ingestion of 4000–6000 IUs of vitamin D daily." Charoenngam et al. 2020.

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] It is also important to note that Vitamin K2 may interfere with some anticoagulant medications, so if it is advisable to consult with a health professional for individualised advice.

Bottom-line

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

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

Although further research is needed to enlighten further the mechanisms by which Vitamin D3 protects during a COVID-19 infection, more voices in the scientific community have started to propose the regular supplementation of this common Vitamin as a preventive agent for current and future immune challenges, including those of the respiratory tract.

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. 

[1] Sunyecz JA. The use of calcium and vitamin D in the management of osteoporosis. Ther Clin Risk Manag. 2008;4(4):827-836.

[2] Glade MJ. Vitamin D: health panacea or false prophet? Nutrition. 2013 Jan;29(1):37-41. doi: 10.1016/j.nut.2012.05.010. Epub 2012 Oct 22. PMID: 23085014.

[3] Adams JS, Hewison M. Unexpected actions of vitamin D: new perspectives on the regulation of innate and adaptive immunity. Nat Clin Pract Endocrinol Metab. 2008 Feb;4(2):80-90. PMID: 18212810; PMCID: PMC2678245.

[4] Borsche L, Glauner B, von Mendel J. COVID-19 Mortality Risk Correlates Inversely with Vitamin D3 Status, and a Mortality Rate Close to Zero Could Theoretically Be Achieved at 50 ng/mL 25(OH)D3: Results of a Systematic Review and Meta-Analysis. Nutrients. 2021; 13(10):3596.

[5] -The High Cost of Surviving Acute Respiratory Distress Syndrome- Hopkinsmedicine.org as accessed Dec 16th 2021

[6] Que Y, Hu C, Wan K, et al. Cytokine release syndrome in COVID-19: a major mechanism of morbidity and mortality [published online ahead of print, 2021 Feb 22]. Int Rev Immunol. 2021;1-14.

[7] Jose Manuel Quesada-Gomez, Marta Entrenas-Castillo, Roger Bouillon, Vitamin D receptor stimulation to reduce acute respiratory distress syndrome (ARDS) in patients with coronavirus SARS-CoV-2 infections: Revised Ms SBMB 2020_166, The Journal of Steroid Biochemistry and Molecular Biology,Volume 202,2020,105719,ISSN 0960-0760

[8] Lemire JM, Archer DC, Beck L, Spiegelberg HL. Immunosuppressive actions of 1,25-dihydroxyvitamin D3: preferential inhibition of Th1 functions. J Nutr. 1995 Jun;125(6 Suppl):1704S-1708S. PMID: 7782931.

[9] Michigami T. [Rickets/Osteomalacia. Consensus on Vitamin D Deficiency and Insufficiency in Children.] Clinical Calcium. 2018;28(10):1307-1311. DOI: clica181013071311. PMID: 30269111.

[10] Adriana J. van Ballegooijen, Stefan Pilz, Andreas Tomaschitz, Martin R. Grübler, Nicolas Verheyen, "The Synergistic Interplay between Vitamins D and K for Bone and Cardiovascular Health: A Narrative Review", International Journal of Endocrinology, vol. 2017, Article ID 7454376, 12 pages, 2017.

[11] Charoenngam N, Holick MF. Immunologic Effects of Vitamin D on Human Health and Disease. Nutrients. 2020; 12(7):2097.

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