June 21, 2021 ~ VitaminDWiki.com ~ Dr. Eduardo P. Beltran
600,000 IU of Vitamin D helped 26 out of 28 COVID-19 patients in ICU (Brazil and Bolivia) June 2021
UNDERSTANDING THE RELATIONSHIP BETWEEN COVID19, VITAMIN D LEVELS, CYTOCHROME P450 ENZYMES & PARATHYROID LEVELS
A Case for using High Loading Dose Vitamin D (600,000UI) in 26 patients
When it comes to understanding the relationship between Vitamin D3 (Cholecalciferol) and the Cytokine Storm induced by COVID19 (SARS- COV2), it becomes more clear when we have a more in-depth understanding of liver and kidney metabolism. Before I get into the biochemistry and pathophysiology of this subject I must emphasize the importance of early detection and quick treatment of patients with COVID19 symptoms.
I have lost track of how many studies across the globe have demonstrated that 80% of all COVID19 patients have vitamin D3 deficiency or insufficiency. Approximately 8 out of 10 patients in the ICU have vitamin D3 deficiency or insufficiency.
But today I would like to share a couple of words regarding the existing correlation between cytochrome P450 enzymes, specially CYP2R1, vitamin D, PTH levels and COVID19
Vitamin D Metabolism
As we know through basic biochemistry, vitamin D synthesis derives from the sun exposure (UVB rays), where 7-dehydroxicholesterol is converted into cholecalciferol.
Cholecalciferol through systemic circulation, reaches hepatic metabolism where a series of cytochrome P450 enzymes express CYP2R1 (25 hydroxylases).
This enzyme converts cholecalciferol into calcifediol. Once calcifediol enters systemic circulation it reaches the proximal convoluted tubules (PCT) found in the kidneys where 1 alfa 25 hydroxylase is expressed helping convert Calcifediol into vitamin D active form, calcitriol.
Many cofactors are all also necessary for an adequate Vitamin D metabolism such as magnesium, boron, vitamin E, vitamin B2, B3, B6, B9, B12, CoQ10 and vitamin K2 allow for adequate phase I hepatic metabolism of cytochrome P450 enzymes, but this is another topic for later discussion.
When it comes to the innate and acquired immune system, we know that macrophages, T cells, and B cells are equipped with their own converting enzymes, allowing them to convert calcifediol into calcitriol. This means they don’t require kidney conversion through 1 alfa hydroxylase.
Intracellular calcitriol upregulates protein transcription mediators which will allow the immune cells to make Cathelicidins and Beta-defensins helping fight off SARS-COV2.
Beta-defensins help penetrate the enveloped SARS- COV2 membrane creating pores that generate loss of viral genetic material and inhibiting viral replication.
It is very important recognizing that vitamin D reduces dramatically the levels of IFN alfa, gamma, IL-1, IL-6, IL-12, IL-33, TNF, CCL-2,3,5, CXCL-8.9, and 10. Basically, all of the inflammatory mediators found in the cytokine storm!.
When our immune system is confronted with the SARS-COV2, it is the innate immune system that gets the first hand of interaction. Eventually, the acquired immune system kicks in leading to the synthesis of specific neutralizing antibodies, IgM being the first and finally IgG granting immunity to the individual.
When vitamin D levels are low (<40ng/ml), the maturation of naive T cells convert into Th1 cells that end up expressing IL-1 and Interferon-gamma. This activates the proinflammatory pathway that promotes the cytokine storm.
Obviously, this is a very summarized version of what actually happens. But once the cytokine storm gains momentum, it starts causing damage to many other organs like the lungs, heart, kidneys and liver.
On the other hand when adequate levels of vitamin D (>40ng/ml) are circulating, naive T cells mature into Th2 cells which end up activating B Cells (acquired immune system) and promoting antibody synthesis (anti-inflammatory pathway) avoiding the cytokine storm.
High Loading Dose of Vitamin D
Commentary from Mark Bricca, ND
Link above is to a recent article that demonstrates clear correlation between vitamin D status and severity of Covid-19 illness. Of course, there could be other relevant factors to consider as well, and correlation does not prove causation. Those with higher vitamin D may also have better overall health status, they may have better nutrition, they may get more exercise, etc.
That being said, data on vitamin D and Covid-19 is abundant and consistent at this point, and I wish public health authorities would come out with population-wide guidelines for testing and supplementation. It’s so easy, and there is next to no downside to moderate supplementation (and it may benefit bone health and reduce risk of several other diseases, too).
This article is from Eduardo Beltran, MD, who is a Brazilian physician member of the MASTerMinds group. He has been treating Covid-19 ICU patients with high dose (600,000IUs) vitamin D, and remarkably he has seen *significant* benefit in 26 out of 28 treated patients. Impressive response from humble vitamin D, even in advanced illness!