Metformins is associated with Reduced SARS-2 Severity

Right once more.

Good night. A sort of short one, as once again I (and many other) have been slowly, but surely being proved right.

Since 2021 I and many others have been touting Metformin as a powerful prophylactic treatment against SARS-CoV-2 and in many cases, you could use it to “rescue” hospitalized people alongside other drugs. Metformin either diminishes or outright avoids the worst pathways that lead to bad outcomes from the viral infection.

Metformin is Associated with Reduced COVID-19 Severity in Patients with Prediabetes

Source

Cumulatively, the scientists found a significant correlation between less severe COVID-19 and metformin use among the prediabetes group relative to levothyroxine use adopting a binary categorization. The study results demonstrated that metformin use was connected to a reduced rate of SARS-CoV-2 infections among the prediabetes cohort that were mild ED, mild or worse, and moderate or worse in severity. Hence, the study data confirmed the relationship between metformin use and less severe SARS-CoV-2 infection.

On the other hand, the authors did not discover any correlation between metformin use and COVID-19 severity among PCOS patients. However, the number of patients was relatively limited. This inference might indicate that either the metformin-mediated reduction in COVID-19 severity was not occurring in individuals with PCOS or that the power of the study was insufficient to identify the metformin-mediated improvement. 

Furthermore, point estimations of the odds ratio of metformin compared to levothyroxine were directionally constant in PCOS and prediabetic populations. However, these associations were not statistically significant.

RAAS/SARS-CoV-2 axis in exaggerated immune response and acute pancreatic injury.

Viral pathogenesis and Metformin’s host- and virus-directed interventions in the attenuation of the disease process.

Source for the images above. The second image is a very good illustration of how many ways Metformin will inhibit or disrupt viral activity, and while there are many pathways there, these are but a few. Following below are other representations of what Metformin can do in this regard, easier to understand, but packet with information.

Multiple Benefits of Metformin Treatment against SARS-CoV-2 Infection. Metformin treatment-associated activation of AMPK-mediated signaling mechanisms is well studied and documented [79]. The AMPK-dependent increase in (A): ACE2 receptor phosphorylation (Ser680) causes a conformational change that inhibits ACE2 – viral spike protein binding and reduction of viral entry into the cell [15,16]. AMPK-mediated increase in (B): ACE2 phosphorylation (ACE2 phosphorylation prevents polyubiquitination and subsequent 26-proteasome-mediated degradation of ACE2). (C) ACE2 expression increases its half-life/stability and offers cardiopulmonary protection via RAAS regulation [14., 15., 16.]. The ability of metformin to reduce blood glucose levels and improve insulin stability (D) reduces the risk of SARS-CoV-2 infections [15]. Metformin treatment-associated increase in ACE2 levels and stability, in turn, regulates the ACE2/AngII/AT1R axis and suppresses (E) inflammatory response and release of proinflammatory cytokines by inhibiting macrophage activation and NF-κB signaling [16]. Metformin targets complex I of the mitochondrial electron transport chain (ETC), inhibits the generation of reactive oxygen species (ROS), and (F) suppresses the oxidative stress-mediated release of proinflammatory cytokines and attenuates inflammatory immune response [15,80]. Inhibition of ETC and mTORC1 signaling (via AMPK or PI3K/Akt) by metformin (G1 and G2) contributes to the suppression of host–viral protein interactions, such as NDUF (human)–Nsp7 (viral) and LARP/FKBP7 (human)–N/ORF8 (viral) interactions [81]. The suppression of the host–virus protein interactions inhibits host-dependent viral replication, synthesis of viral proteins, virion maturation, and release. Metformin, a strong base, targets the vacuolar ATPase (V-ATPase) and endosomal Na+/H+ exchangers (eNHEs) (H), increasing the cellular and endosomal pH and suppressing the endocytotic cycle and virion assembly and maturation [15,82]. The antihyperglycemic, antioxidant, immunomodulatory, and anti-inflammatory effects of metformin attenuate endothelial dysfunction and confer vascular protection, thus (I) reducing microvascular complications and thrombotic events during SARS-CoV-2 infection. Abbreviations: ACE2, angiotensin-converting enzyme 2; AGE, advanced glycation end-product; AMPK, AMP-activated protein kinase; AngII, angiotensin II; AT1R, AT1R, angiotensin II type I receptor; mTORC1, mammalian target of rapamycin complex 1; RAAS, renin–angiotensin–aldosterone system; RAGE, receptor of AGE; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2. Source.

Last year while researching the PAID hypothesis, I created a small little game, every time me or the friend I was researching with found a new pathway, or new biomarkers I would instinctively search for that thing + Metformin, and said friend would do it for Berberine (they are almost one and the same, with Berberine doing a few things Metformin doesn’t). You could do pretty much the same with most things I cover here or papers you find around, you will often be surprised.

In fact, as a practical example, I won’t cover the papers, just the titles and if you get interested, you read the papers.

Metformin and amyloid

Metformin and prion

Metformin and Th17 (highly inflammatory immune state, autoimmunity and etc)

Metformin improves cognition, heals leaky gut

Metformin benefits on gut microbiome of obese and Type 2 Diabetics

Metformin and Endothelial Dysfunction

Metformin DOWNREGULATES the Kynurenine Pathway

Post-publishing addendum. Doorless Carp has a comprehensive review of the scientific literature on Berberine. Check it out for the scientific curious.

Therapeutic properties of Berberine

These are a few, at the end of 2021, I had close to 200 papers on the benefits of Metformin in regards to many of the topics we researched, them I stopped focusing so much on this aspect and to find new pathways, new mechanisms, but in the end, my “stack” to heal or prevent damage stayed the same, the more evidence is published, the more it stays the same.

If Metformin is prescription only where you live, and you want to give it a try for these or any other myriad of beneficial reasons, you can easily substitute for Berberine, in fact, Berberine is often a better choice too, especially if you are “healthy”. People with autoimmune issues will often see glaring improvement after a few weeks of using any of these substances.

As a closing remark on this short one, don’t use these substances as an excuse to not exercise, or have a shitty diet. They are tools, not crutches. Have a nice day, whenever you are reading this. More to come later on other regards of the virus.

Massive appreciation to all supporters here and on Kofi !!!