COVID Strategy: MetforminAugust 16, 2020
COVID-19 Strategy: Metformin
How would you like to reduce your risk of dying with COVID by 75%? Whatever risk group you are in. I’m in. Just explain why and how.
Here is an observational study from China just published a few weeks ago. 283 patients admitted to a hospital in Wuhan were selected. All were diabetic. Of that group, 104 were on metformin and 179 were not. All were reasonably well controlled in their diabetes. They were matched to be just about identical in every aspect including age, gender, and other risk factors. They stayed in the hospital for the same 20 some days. But survival wasn’t the same. Diabetes is one of the clearly identified risks of COVID-19 mortality. Of those on metformin, 3 died. Of those not on metformin, 22 of 179 died. That is 2.9 % compared to 12.3 %. A 75% reduction in mortality. Wow!
Why? Well, we aren’t certain we know exactly why but this sure brings up a lot of excitement. The authors reference some prior research that may give us a clue. Metformin appears to slow down Complex 1in the Electron Transport Chain in mitochondria. That is the first step of taking fuel (known as glucose or fat) and turning it into water and carbon dioxide and ATP, your energy molecule), and burning it. Slowing it down has the same effect as fasting or intense exercise. You make your cell feel like it’s not getting as much fuel as it needs, so it has to hunker down and go into survival mode.It turns on AMPK, the critical switch to turn on your “hunker down and wait it out” mechanism. That is of high interest for those working on lifespan and longevity. But here it appears to cross-reference to enhanced immune function. When you turn on AMPK, you then inhibit mTOR and its downstream immune effects: instead of turning monocytes into macrophages (Pitbulls) you slow all that down as your cell goes into “hunker down and wait it out mode”. You don’t get the cytokine storm you have been hearing so much about.
And that’s not all. Metformin also inhibits the whole NF-kappa B complex that is the basic pathway to starting inflammation. It’s the activation of that that curcumin inhibits. Putting a clamp on that activation is at the exact pivot point of systemic inflammation. NF-kappa-b is the nexus of the cytokine storm. It is where all the hundreds of cytokines that COVID-19 appears to initiate meet and fuel the fire of inflammation. Without it, inflammation goes nowhere.
Finally, metformin appears to augment autophagy, which is the programmed recycling of dead and dying cells. That is the organized garbage removal your body is meant to do when it has junk to dispose of. Disorganized, chaotic cell death happens when viruses kill the cell and they spew out by the millions. All the cell contents just blow up. That is unorganized and leads to a much greater inflammatory response. By boosting autophagy, you dampen uncontrolled, runaway inflammation. Metformin is being used in tuberculosis treatment to help conquer antibiotic-resistant TB by just this mechanism.
But there is something about ketones that metformin also induces. We know COVID, and all viruses, hijack your mitochondrial energy glucose pathway to make fats instead of energy. But there are hints that taking ketones bypasses that and feeds your starving cell just when it is being overwhelmed by the virus duplicating itself. (See last week’s newsletter). If you take purified ketone products like KE4 (10 ccs three times a day) you restore energy to cells and prevent cell death. When you prevent cell death, the virus is trapped inside and now spread. That allows your immune system time to race to the rescue and kill that cell (and its viruses).
Metformin induces mild ketosis. Is that how it works? It shifts you from glucose metabolism to ketone metabolism? We see it working in the lab, and now in 278 diabetic Chinese. 75% reduction in mortality!
WWW: What will work for me? I’m taking it for longevity reasons. I’ve been on 850 mg a day now for about 6 months, starting, paradoxically, just before COVID showed up. I’ve had no side effects. I’ve lost maybe one pound. My ketones have been getting up to 4.4 and 4.7 when I’m on my 5-day fast mimicking diet when I take metformin concurrently, which is the highest I’ve been able to ever get, so I’m tickling the idea that metformin really does induce ketones. Ketone, or beta-hydroxybutyrate, are just tiny fragments of fat. That’s otherwise known as weight loss. If I haven’t convinced you to take metformin for longevity, for goodness sake, take it for COVID protection.
1. Metformin is a drug used for what? Answer: The number one drug in the world to treat adult-onset diabetes. Available over the counter in most countries. Costs about $ 0.02 a pill in other countries.
2. Metformin is a pharmaceutical, foreign substance, not safe to take? T or F. Answer: this is actually a fascinating saga. It is an extract of the French Lilac plant discovered because folk medicine had used it for sweet urine for centuries. In Mid 1800s two Frenchmen isolated it and eventually, metformin was produced. It’s pretty safe. You could call it an herbal extract.
3. Its use in diabetes has been found to help COVID-19 patients reduce their mortality by how much? Answer: 75%
4. This type of study Is considered sufficient to proves its value. T or F. Answer: False. A retrospective, observational study could be in error and randomized, placebo-controlled trials are warranted. The fact that so much basic science supports the mechanism is tempting to call it a day. During science on the fly during pandemics is tricky.
5. Would you take it if you could get it? Answer. ?
References: Am Jr Tropical Medicine, Current Drug Therapies, Diabetes, Metab and Sig Transduction, Cell, PLoS One,