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(6,104 posts)
Thu Jul 23, 2020, 04:44 PM Jul 2020

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) [1]. 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) [2]. 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 ).


Melatonin Inhibits COVID-19-induced Cytokine Storm by Reversing Aerobic Glycolysis in Immune Cells (Original Post) at140 Jul 2020 OP
Here's the best part Roland99 Jul 2020 #1
Thx for the detailed explanation!! Thekaspervote Jul 2020 #4
Melatonin?? The stuff I get from the vitamin wall? Or the health food store? No scrip, no vaccine? niyad Jul 2020 #11
Exactly my first thought as well at140 Jul 2020 #15
Translation? Faux pas Jul 2020 #2
If you use Melatonin as a sleep aid, better go buy up all you can NOW... Moostache Jul 2020 #13
Thank you Faux pas Jul 2020 #41
You just introduced me to ashwagandha.. Cha Jul 2020 #52
Your welcome Faux pas Jul 2020 #53
Good information exchange on DU! Cha Jul 2020 #59
Glad Faux pas Jul 2020 #60
I'm happy it's helped you.. I'm anxiously awaiting my bottle.. Cha Jul 2020 #61
PS Faux pas Jul 2020 #42
So any melatonin supplement from the drug store or Eliot Rosewater Jul 2020 #3
The best way to take melatonin is sublingual, faster better absorption Thekaspervote Jul 2020 #6
for the vast majority of folks who have no idea what that means qazplm135 Jul 2020 #10
Oh so no submarine needed? nt awesomerwb1 Jul 2020 #23
That's what I take. Get it at Costco. Nevilledog Jul 2020 #43
That's how I take it.. spray melatonin every other Cha Jul 2020 #51
Costco is probably safe Miguelito Loveless Jul 2020 #8
Had to look for this link Miguelito Loveless Jul 2020 #22
Of course, one must pay for results. nt Ilsa Jul 2020 #29
My apologies Miguelito Loveless Jul 2020 #34
I posted the top picks Miguelito Loveless Jul 2020 #36
Thank you. You're a mensch! nt Ilsa Jul 2020 #37
Did you pay to get the results? What are the results? Eliot Rosewater Jul 2020 #33
Sorry, they placed them behind the paywall Miguelito Loveless Jul 2020 #35
That's what I use, the Natrol but 10mg.... Kahuna Jul 2020 #24
This is what I use as well. n/t ChazII Jul 2020 #55
That's the good stuff. I tried other brands and dosages before I settled. Kahuna Jul 2020 #57
My neurologist is the ChazII Jul 2020 #58
Really good news! Thekaspervote Jul 2020 #5
I Use Melatonin to Help me Sleep Stallion Jul 2020 #7
So do I. Love it. Goodheart Jul 2020 #12
Leaves You a Little Foggy in the Morning-but after 30 Minutes I'm good Stallion Jul 2020 #14
Only problem I've had with it is, my eyes are a tad dry when I wake up..... a kennedy Jul 2020 #17
I do much less than that. 3/10 of a milligram Goodheart Jul 2020 #21
Bookmarking. Should we be taking melatonin supplements EllieBC Jul 2020 #9
More as a treatment but taking it could make you less susceptible at140 Jul 2020 #18
Melatonin is good for you in many ways. Just research it. triron Jul 2020 #40
Sounds more scientific than kimchi! LeftInTX Jul 2020 #16
I take it every night to help me sleep. leftyladyfrommo Jul 2020 #19
Well at least FLOTUS is good for something. Voltaire2 Jul 2020 #20
?????? niyad Jul 2020 #25
Some folks call her melatonin MissB Jul 2020 #26
Ahh. Much more polite than what I call her. niyad Jul 2020 #28
Same. MissB Jul 2020 #31
melanoma and malaria are the polite terms. niyad Jul 2020 #32
I thought she was Melanomia jmbar2 Jul 2020 #48
hmmm. I googled "melatonin covid treatment" (without the quotes) gristy Jul 2020 #27
I've had to increase to 10 mg oswaldactedalone Jul 2020 #30
Many doctors say 10 mg is fine. I usually take anywhere from 5 or 6 mg up to about 10. triron Jul 2020 #39
This is great news. I and my gf take melatonin every night. I take more than she. triron Jul 2020 #38
I also use it for sleep some nights myccrider Jul 2020 #44
This is from the description of the study: triron Jul 2020 #45
Thanks for the info myccrider Jul 2020 #47
Cool. I used to take it for insomnia mvd Jul 2020 #46
Same thing with me, it quit working but Raine Jul 2020 #50
Already taking Vitamin D,Vitamin C immunity boost and Zinc everyday helpisontheway Jul 2020 #49
Me too. Sometimes add astragulus. Also take an immune senescence formula (by Life Extension) triron Jul 2020 #54
This is the immune booster I take helpisontheway Jul 2020 #56
Never did I ever expect to see a post like this on DU! But thanks! I think.... nt LAS14 Jul 2020 #62


(53,341 posts)
1. Here's the best part
Thu Jul 23, 2020, 04:46 PM
Jul 2020

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 [13]. 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 [14]. 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 [[3], [4], [5], [6], [7]]. 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.


(108,020 posts)
11. Melatonin?? The stuff I get from the vitamin wall? Or the health food store? No scrip, no vaccine?
Thu Jul 23, 2020, 04:55 PM
Jul 2020

Ohhh desr, donnie bodybags and big pharma are not going to like that!!


(6,104 posts)
15. Exactly my first thought as well
Thu Jul 23, 2020, 05:04 PM
Jul 2020

Big profits Big Pharma would prefer meds costing thousands of dollars.


(9,885 posts)
13. If you use Melatonin as a sleep aid, better go buy up all you can NOW...
Thu Jul 23, 2020, 04:55 PM
Jul 2020

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.


(291,804 posts)
52. You just introduced me to ashwagandha..
Mon Jul 27, 2020, 02:21 AM
Jul 2020

Mahalo, Faux pas.. it sounds like just what I need!

I just ordered it

Miguelito Loveless

(4,404 posts)
34. My apologies
Thu Jul 23, 2020, 05:58 PM
Jul 2020

Their policies have changed since i was last on their site. As they do not accept ads, they are now behind a paywall.

Miguelito Loveless

(4,404 posts)
35. Sorry, they placed them behind the paywall
Thu Jul 23, 2020, 06:08 PM
Jul 2020

which was not the case the last time I was there.

Low dose: Swanson Melatonin 1mg
Moderate dose: Trader Joe’s chewable 3mg
Timed Release: CVS 5mg

Consumer Labs tests for the actual presence of ingredients and the absence of harmful impurities or adulterations.


(6,462 posts)
14. Leaves You a Little Foggy in the Morning-but after 30 Minutes I'm good
Thu Jul 23, 2020, 04:58 PM
Jul 2020

I know I take it too late but I'm out usually within :30 minutes and I'm a nightowl

a kennedy

(28,983 posts)
17. Only problem I've had with it is, my eyes are a tad dry when I wake up.....
Thu Jul 23, 2020, 05:06 PM
Jul 2020

other then that I love it. What’s your dose? I’m doing 2.5 milligrams. I cut a 10 milligram in half and then in half again.....so it’s 2.5 when I use it UNDER MY TONGUE.


(4,969 posts)
21. I do much less than that. 3/10 of a milligram
Thu Jul 23, 2020, 05:16 PM
Jul 2020

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.


(6,104 posts)
18. More as a treatment but taking it could make you less susceptible
Thu Jul 23, 2020, 05:07 PM
Jul 2020

to inflammation if you do come down with infection.


(10,666 posts)
27. hmmm. I googled "melatonin covid treatment" (without the quotes)
Thu Jul 23, 2020, 05:37 PM
Jul 2020

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.


(3,483 posts)
30. I've had to increase to 10 mg
Thu Jul 23, 2020, 05:50 PM
Jul 2020

about 2 hours before I hope to be asleep and I don’t use the sublingual tablets. I found that the effects of the quick dissolving tablets wear off too fast and I wouldn’t get more than 2 hours of sleep.

Last night, I wanted some extra sleep so took 5 add’l mgs just before going to bed. Had the unusual experience of getting 9 uninterrupted hours of sleep. However, I wouldn’t recommend more than 3-5 mgs at first, and I won’t take more than 10 often at all.

Did I miss the mention of a recommended dosage?


(484 posts)
44. I also use it for sleep some nights
Fri Jul 24, 2020, 10:05 AM
Jul 2020

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. It’s 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.


(21,591 posts)
45. This is from the description of the study:
Fri Jul 24, 2020, 10:13 AM
Jul 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."


(484 posts)
47. Thanks for the info
Fri Jul 24, 2020, 06:46 PM
Jul 2020

Seems it’s 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.


(65,032 posts)
46. Cool. I used to take it for insomnia
Fri Jul 24, 2020, 10:41 AM
Jul 2020

It stopped being as effective for sleep after a while, but maybe I will try it again.


(4,982 posts)
49. Already taking Vitamin D,Vitamin C immunity boost and Zinc everyday
Mon Jul 27, 2020, 01:45 AM
Jul 2020

Guess it will not hurt to add Melatonin. Anything to prevent or lessen the severity of this awful disease.

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