Friday Hope: Magnesium: Inhibiting Spike Protein Cleavage by Inducing Methylation Changes of TMPRSS2

Magnesium also optimizes Vitamin D, Reduces Severity and Symptoms of COVID and improves Endothelial function.

Possible mechanism of the role of magnesium in COVID-19. 

As those who have read this Substack from the beginning know, and I believe to now be common knowledge, preventing the Spike Protein from attaching to receptors/entering cells is paramount in defending oneself against the protein. One of the key mechanisms required for the Spike to enter cells is the Transmembrane Serine Protease TMPRSS2. This protease cleaves the Spike, releasing the formidably dangerous S1 and S2 units. Fortunately, we have a safe, effective natural therapeutic which prevents TMPRSS2 from providing this assistance to the Spike. It does this by downregulating the gene’s expression. This therapeutic is Magnesium. 

Magnesium is an essential mineral for the human body. It may be surprising to some readers how important it is for an abundant number of functions. 

Magnesium is a cofactor in more than 300 enzyme systems that regulate diverse biochemical reactions in the body, including protein synthesis, muscle and nerve function, blood glucose control, and blood pressure regulation [1-3]. Magnesium is required for energy production, oxidative phosphorylation, and glycolysis. It contributes to the structural development of bone and is required for the synthesis of DNA, RNA, and the antioxidant glutathione. Magnesium also plays a role in the active transport of calcium and potassium ions across cell membranes, a process that is important to nerve impulse conduction, muscle contraction, and normal heart rhythm. 

Magnesium 
https://ods.od.nih.gov/factsheets/Magnesium-HealthProfessional/ 

What is additionally fascinating about Magnesium is that it has the ability to methylate the TMPRSS2 gene, thereby downregulating (basically shuts the door on the cell’s gene transcription machinery) its transcription. 

In this personalized precision-based randomized trial, we found that 12 wk of Mg treatment significantly increased 5-mC DNA methylation at the cg16371860 CpG site and decreased 5-hmC cytosine modification at the cg26337277 CpG site in TMPRSS2 compared to placebo among participants ages < 65 y. To the best of our knowledge, no study has evaluated how to modify TMPRSS2 cytosine modification, nor examined the effect of Mg treatment on cytosine modification in TMPRSS2. 

Our observations that Mg treatment induced increases in 5-mC methylation at cg16371860 and decreases in 5-hmC methylation at cg26337277 CpG in the promoter indicate a hindered process of transcription initiation and, subsequently, lower levels of TMPRSS2 expression. 

Magnesium treatment on methylation changes of transmembrane serine protease 2 (TMPRSS2) 
https://pmc.ncbi.nlm.nih.gov/articles/PMC8102075/ 

So, if the Spike is not cleaved, the Spike cannot function properly. We have yet another natural way to block the Spike. 

It is true that the above-mentioned benefit of lowered TMPRSS2 levels was not observed in those over 65. However, there are many reasons to still advocate for Magnesium when treating Spike Protein disease and injury.  

First, Magnesium optimizes the body’s use of Vitamin D. 

First, vitamin D has been proposed to generate beneficial effects in acute respiratory distress syndrome through activation of the vitamin D receptor signaling pathway by reducing the cytokine storm, regulating the renin-angiotensin system, maintaining the integrity of the pulmonary epithelial barrier, and tapering down the increased coagulability [16]. Our and other studies have found that Mg optimized body vitamin D status and substantially reduced the dose requirement for vitamin D. 

Magnesium treatment on methylation changes of transmembrane serine protease 2 (TMPRSS2) 
https://pmc.ncbi.nlm.nih.gov/articles/PMC8102075/ 

Magnesium improves Endothelial function. 

Hypomagnesemia is believed to play a significant role in the development of cardiovascular disease, hypertension, and thrombosis in the general population.20,21 Magnesium is well known to modulate vascular tone and response, and act as a cofactor for Ach-induced endothelium-dependent relaxation.1 Magnesium deficiency promotes oxidative stress in various cell types, including endothelial cells.22,23 In addition, oral magnesium therapy is associated with significant improvement in endothelial function in patients with coronary artery disease. 

The Relationship between Magnesium and Endothelial Function in End-Stage Renal Disease Patients on Hemodialysis 
https://pmc.ncbi.nlm.nih.gov/articles/PMC5011277/ 

And, should you find yourself with a case of COVID, Magnesium reduces the severity and symptoms of the disease. 

Magnesium is an anti-inflammatory mineral that plays a role in reducing inflammation and oxidative stress during cytokine storms and in relaxing airway smooth muscle. As a result of its role in systemic and respiratory problems in COVID-19, magnesium intake has gained more interest in this regard. While the association between serum magnesium levels and COVID-19 has been studied previously, little attention has been paid to the relationship between dietary magnesium intake as measured by the FFQ and COVID-19 severity and associated symptoms. We found that higher dietary magnesium intake was inversely associated with COVID-19 severity and symptoms in hospitalized patients. More precisely, higher magnesium intake was associated with a shorter duration of hospitalization and convalescence, as well as a lower chance of having COVID-19 symptoms, including dyspnea, cough, fever, chills, weakness, myalgia, nausea, vomiting, and sore throat. Additionally, a higher dietary magnesium intake was associated with lower inflammatory biomarker concentrations (CRP and ESR). 

Higher Intake of Dietary Magnesium Is Inversely Associated With COVID-19 Severity and Symptoms in Hospitalized Patients: A Cross-Sectional Study 
https://pmc.ncbi.nlm.nih.gov/articles/PMC9132593/ 

Clearly, Magnesium is a heavy hitter in our roster of natural players. Fortunately, many of the foods I love are rich sources of Magnesium, such as Spinach, Dark Chocolate and Almonds. I definitely plan on enjoying all three this weekend! After an extremely warm Halloween, we are getting back to seasonal temps today. But, at least to me, every Autumn day in Vermont is beautiful.  

Of course, the above is a work of medical research and not medical advice. Please consult with your Primary Care Provider before using any medication or supplement. 

I wish everyone a joyous, blessed and peaceful first weekend of November. I think we can all agree we certainly need it.