Melatonin Inhibits COVID-19-induced Cytokine Storm by Reversing Aerobic Glycolysis in Immune Cells
The pathogenesis of a COVID-19 respiratory infection, in a major way, is related to what is referred to as the cytokine storm [cytokine storm syndrome (CSS, hypercytokinemia, etc.], i.e., it is a hyper-inflammatory response. During this response, an explosive production of proinflammatory cytokines such as TNF-? IL-1?, and others occurs, greatly exaggerating the generation of molecule-damaging reactive oxygen species (free radicals) . In severe cases, the cytokine storm is responsible for the most obvious signs of a COVID-19 infection including fever, lung injury which causes cough and shortness of breath (and the long-term complication, lung fibrosis) and in death.
A causative factor related to the hyper-inflammatory state of immune cells is their ability to dramatically change their metabolism. Similar to cancer cells in many solid tumors, immune cells such as macrophages/monocytes under inflammatory conditions abandon mitochondrial oxidative phosphorylation for ATP production in favor of cytosolic aerobic glycolysis (also known as the Warburg effect) . This switch is driven by the transcription factor HIF-1? (hypoxia inducible factor-1? and the serine/threonine kinase, mTOR (mammalian target of rapamycin) and other proteins The change to aerobic glycolysis allows immune cells to become highly phagocytic, accelerate ATP production, intensify their oxidative burst and to provide the abundant metabolic precursors required for enhanced cellular proliferation and increased synthesis and release of cytokines (Fig. 1 ).
Given the above information, the use of supplemental melatonin as a treatment to overcome a COVID-19 infection is justified. Exogenously administered melatonin reverses aerobic glycolysis by repressing both HIF-1? and mTOR thereby disinhibiting PDC activity and allowing acetyl-coenzyme A synthesis which also ensures locally-produced melatonin production . The functionally re-instated mitochondria-generated melatonin in combination with the parenteral melatonin provides a formidable weapon to reduce the cytokine storm as well as its damaging consequences thereby relieving the signs of a COVID-19 infection.
The anti-inflammatory and antioxidant actions of melatonin in protecting the lungs from damage in many experimental models that involve inflammation or oxidative stress (or both) is well documented . Moreover, melatonin has anti-viral actions against viruses other than COVID-19 [15,16]. The collective data, in addition to its very high safety profile, indicate that melatonin would be effective as a treatment for COVID-19 and support the recommendation of the published reports that encourage its use for this purpose [, , , , ]. Melatonin is inexpensive, non-toxic over a very wide dose range, has a long shelf-life and can be self-administered which is a major advantage when large numbers of individuals are involved. Thus, the use of melatonin to mitigate the COVID-19 pandemic would be feasible and a socially-responsible measure to attempt.
Ohhh desr, donnie bodybags and big pharma are not going to like that!!
Very rough simplification:
The bug (COVID) causes your immune cells to utilize and generate energy (ATP) differently to fight infection. That change in energy source allows for benefits in fighting some disease, but comes with a cost - harder for the cells to regulate or act 'normal'.
Not 100% of the story - it also has to do with the way the cells trigger the immune response and gets more complicated from there, but that's the high-level gist of it.
Mahalo, Faux pas.. it sounds like just what I need!
I just ordered it
Brands you can trust
Their policies have changed since i was last on their site. As they do not accept ads, they are now behind a paywall.
which was not the case the last time I was there.
Low dose: Swanson Melatonin 1mg
Moderate dose: Trader Joes chewable 3mg
Timed Release: CVS 5mg
Consumer Labs tests for the actual presence of ingredients and the absence of harmful impurities or adulterations.
I have 2 new unopened bottles and just ordered 4 more.
I know I take it too late but I'm out usually within :30 minutes and I'm a nightowl
other then that I love it. Whats your dose? Im doing 2.5 milligrams. I cut a 10 milligram in half and then in half again.....so its 2.5 when I use it UNDER MY TONGUE.
A single 300 mcg tablet helps me sleep like a baby.... EXCEPT:
I have noticed that it's a potent diuretic. When I take it I get up about four times per night to pee... and I'm not talking little drips, either. Doesn't really bother me, though, because it makes me feel skinnier and I fall right back asleep.
to inflammation if you do come down with infection.
And I found articles at least as far back as April. So I worry that efficacy may not be all that is hoped, or we would have been hearing a lot more of this by now.
about 2 hours before I hope to be asleep and I dont use the sublingual tablets. I found that the effects of the quick dissolving tablets wear off too fast and I wouldnt get more than 2 hours of sleep.
Last night, I wanted some extra sleep so took 5 addl mgs just before going to bed. Had the unusual experience of getting 9 uninterrupted hours of sleep. However, I wouldnt recommend more than 3-5 mgs at first, and I wont take more than 10 often at all.
Did I miss the mention of a recommended dosage?
but have odd side effects if I take more than 4 or 5 mg or use it every night...severe headaches, hours-long grogginess the next morning. I now take a combo of approx. 3mg melatonin, 20 mg CBD and 5mg THC (which is legal here in California, thankfully) 3 or 4 nights a week. That lets me sleep well 4-6 hours with minimal side effects.
I use prescription meds other nights usually with some CBD. If I use anything every night it becomes less effective over time and/or I start having more severe side effects.
I have had a weird relationship with sleep for a long time.
It would be wonderful if melatonin turns out to be a therapeutic treatment for Covid. Its cheap and readily available OTC. Are there any trials going on with it, I wonder?
Looks like there is one in Spain. Started April 2020, results by Dec 2020.
"SARS-CoV 2 seems to relatively spare younger children and those who are infected develop the severe forms of the disease very rarely. Peak melatonin serum levels are higher in younger children and decrease with age. These levels are also higher in women, specially during pregnancy, who also seem to be less affected by the virus when compared to men.
The investigators hypothesize that elevating peak melatonin levels to a range similar to that of children by administering 2 mg of melatonin daily might prevent the infection with SARS-CoV 2 among exposed healthcare workers. The investigators also hypothesize that among those who develop the disease melatonin might prevent the more severe forms."
Seems its being tested as a prophylactic, not necessarily as a treatment. Hope the results will be positive. We need all the tools we can get to fight this thing.
It stopped being as effective for sleep after a while, but maybe I will try it again.
Guess it will not hurt to add Melatonin. Anything to prevent or lessen the severity of this awful disease.
It has a few other things plus vitamin C.
Now gonna research the things that you are taking..