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Thu Jul 23, 2020, 05:44 PM

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-α IL-1β, 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-1α (hypoxia inducible factor-1α 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 ).




https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7211589/?fbclid=IwAR3EKCn7MtmGk3GxhLboOhUCDIEtDbxEnJe8sBJWXHjc7velVxJAAlYOB2Q

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Reply Melatonin Inhibits COVID-19-induced Cytokine Storm by Reversing Aerobic Glycolysis in Immune Cells (Original post)
at140 Jul 23 OP
Roland99 Jul 23 #1
Thekaspervote Jul 23 #4
niyad Jul 23 #11
at140 Jul 23 #15
Faux pas Jul 23 #2
Moostache Jul 23 #13
Faux pas Jul 23 #41
Cha Jul 27 #52
Faux pas Jul 27 #53
Cha Jul 27 #59
Faux pas Jul 29 #60
Cha Jul 29 #61
Faux pas Jul 23 #42
Eliot Rosewater Jul 23 #3
Thekaspervote Jul 23 #6
qazplm135 Jul 23 #10
awesomerwb1 Jul 23 #23
Nevilledog Jul 23 #43
Cha Jul 27 #51
Miguelito Loveless Jul 23 #8
Miguelito Loveless Jul 23 #22
Ilsa Jul 23 #29
Miguelito Loveless Jul 23 #34
Miguelito Loveless Jul 23 #36
Ilsa Jul 23 #37
Eliot Rosewater Jul 23 #33
Miguelito Loveless Jul 23 #35
Kahuna Jul 23 #24
ChazII Jul 27 #55
Kahuna Jul 27 #57
ChazII Jul 27 #58
Thekaspervote Jul 23 #5
Stallion Jul 23 #7
Goodheart Jul 23 #12
Stallion Jul 23 #14
a kennedy Jul 23 #17
Goodheart Jul 23 #21
EllieBC Jul 23 #9
at140 Jul 23 #18
triron Jul 23 #40
LeftInTX Jul 23 #16
leftyladyfrommo Jul 23 #19
Voltaire2 Jul 23 #20
niyad Jul 23 #25
MissB Jul 23 #26
niyad Jul 23 #28
MissB Jul 23 #31
niyad Jul 23 #32
jmbar2 Jul 27 #48
gristy Jul 23 #27
oswaldactedalone Jul 23 #30
triron Jul 23 #39
triron Jul 23 #38
myccrider Jul 24 #44
triron Jul 24 #45
myccrider Jul 24 #47
mvd Jul 24 #46
Raine Jul 27 #50
helpisontheway Jul 27 #49
triron Jul 27 #54
helpisontheway Jul 27 #56
LAS14 Jul 29 #62

Response to at140 (Original post)

Thu Jul 23, 2020, 05:46 PM

1. Here's the best part

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-1α 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.

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Response to Roland99 (Reply #1)

Thu Jul 23, 2020, 05:50 PM

4. Thx for the detailed explanation!!

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Response to Roland99 (Reply #1)

Thu Jul 23, 2020, 05:55 PM

11. Melatonin?? The stuff I get from the vitamin wall? Or the health food store? No scrip, no vaccine?

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

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Response to niyad (Reply #11)

Thu Jul 23, 2020, 06:04 PM

15. Exactly my first thought as well

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

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Response to at140 (Original post)

Thu Jul 23, 2020, 05:46 PM

2. Translation?

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Response to Faux pas (Reply #2)

Thu Jul 23, 2020, 05:55 PM

13. If you use Melatonin as a sleep aid, better go buy up all you can NOW...

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.


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Response to Moostache (Reply #13)

Thu Jul 23, 2020, 09:38 PM

41. Thank you

I used to take it, then I switched to ashwagandha. Guess I'll switch back.

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Response to Faux pas (Reply #41)

Mon Jul 27, 2020, 03:21 AM

52. You just introduced me to ashwagandha..

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

I just ordered it

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Response to Cha (Reply #52)

Mon Jul 27, 2020, 08:51 AM

53. Your welcome

for sure Cha. It's great stuff!

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Response to Faux pas (Reply #53)

Mon Jul 27, 2020, 04:57 PM

59. Good information exchange on DU!

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Response to Cha (Reply #59)

Wed Jul 29, 2020, 12:19 PM

60. Glad

I could be of some assistance. It's done wonders for me.

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Response to Faux pas (Reply #60)

Wed Jul 29, 2020, 06:36 PM

61. I'm happy it's helped you.. I'm anxiously awaiting my bottle..

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Response to Moostache (Reply #13)

Thu Jul 23, 2020, 09:47 PM

42. PS

Just read ashwagandha may help too.

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Response to Eliot Rosewater (Reply #3)

Thu Jul 23, 2020, 05:52 PM

6. The best way to take melatonin is sublingual, faster better absorption

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Response to Thekaspervote (Reply #6)

Thu Jul 23, 2020, 05:54 PM

10. for the vast majority of folks who have no idea what that means

it means under the tongue.

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Response to qazplm135 (Reply #10)

Thu Jul 23, 2020, 06:16 PM

23. Oh so no submarine needed? nt

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Response to Thekaspervote (Reply #6)

Thu Jul 23, 2020, 09:48 PM

43. That's what I take. Get it at Costco.

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Response to Thekaspervote (Reply #6)

Mon Jul 27, 2020, 03:08 AM

51. That's how I take it.. spray melatonin every other

night for awhile now.

Thanks, Kasper.

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Response to Eliot Rosewater (Reply #3)

Thu Jul 23, 2020, 05:52 PM

8. Costco is probably safe

Others, not so sure.

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Response to Miguelito Loveless (Reply #22)

Thu Jul 23, 2020, 06:39 PM

29. Of course, one must pay for results. nt

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Response to Ilsa (Reply #29)

Thu Jul 23, 2020, 06:58 PM

34. My apologies

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

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Response to Ilsa (Reply #29)

Thu Jul 23, 2020, 07:09 PM

36. I posted the top picks

in this thread.

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Response to Miguelito Loveless (Reply #36)

Thu Jul 23, 2020, 07:15 PM

37. Thank you. You're a mensch! nt

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Response to Miguelito Loveless (Reply #22)

Thu Jul 23, 2020, 06:58 PM

33. Did you pay to get the results? What are the results?

please

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Response to Eliot Rosewater (Reply #33)

Thu Jul 23, 2020, 07:08 PM

35. Sorry, they placed them behind the paywall

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

Low dose: Swanson Melatonin 1mg
Moderate dose: Trader Joeís chewable 3mg
Timed Release: CVS 5mg

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

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Response to Eliot Rosewater (Reply #3)

Thu Jul 23, 2020, 06:16 PM

24. That's what I use, the Natrol but 10mg....

I have 2 new unopened bottles and just ordered 4 more.

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Response to Kahuna (Reply #24)

Mon Jul 27, 2020, 09:45 AM

55. This is what I use as well. n/t

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Response to ChazII (Reply #55)

Mon Jul 27, 2020, 11:49 AM

57. That's the good stuff. I tried other brands and dosages before I settled.

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Response to Kahuna (Reply #57)

Mon Jul 27, 2020, 11:50 AM

58. My neurologist is the

one who recommended it to me.

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Response to at140 (Original post)

Thu Jul 23, 2020, 05:51 PM

5. Really good news!

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Response to at140 (Original post)

Thu Jul 23, 2020, 05:52 PM

7. I Use Melatonin to Help me Sleep

hope I'm safe

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Response to Stallion (Reply #7)

Thu Jul 23, 2020, 05:55 PM

12. So do I. Love it.

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Response to Goodheart (Reply #12)

Thu Jul 23, 2020, 05:58 PM

14. Leaves You a Little Foggy in the Morning-but after 30 Minutes I'm good

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

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Response to Goodheart (Reply #12)

Thu Jul 23, 2020, 06:06 PM

17. Only problem I've had with it is, my eyes are a tad dry when I wake up.....

other then that I love it. Whatís your dose? Iím doing 2.5 milligrams. I cut a 10 milligram in half and then in half again.....so itís 2.5 when I use it UNDER MY TONGUE.

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Response to a kennedy (Reply #17)

Thu Jul 23, 2020, 06:16 PM

21. I do much less than that. 3/10 of a milligram

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.

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Response to at140 (Original post)

Thu Jul 23, 2020, 05:53 PM

9. Bookmarking. Should we be taking melatonin supplements

now? Or no is it just as a treatment?

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Response to EllieBC (Reply #9)

Thu Jul 23, 2020, 06:07 PM

18. More as a treatment but taking it could make you less susceptible

to inflammation if you do come down with infection.

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Response to EllieBC (Reply #9)

Thu Jul 23, 2020, 07:36 PM

40. Melatonin is good for you in many ways. Just research it.

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Response to at140 (Original post)

Thu Jul 23, 2020, 06:06 PM

16. Sounds more scientific than kimchi!

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Response to at140 (Original post)

Thu Jul 23, 2020, 06:11 PM

19. I take it every night to help me sleep.

If I take too much I have really weird bad dreams.

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Response to at140 (Original post)

Thu Jul 23, 2020, 06:13 PM

20. Well at least FLOTUS is good for something.

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Response to Voltaire2 (Reply #20)

Thu Jul 23, 2020, 06:31 PM

25. ??????

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Response to niyad (Reply #25)

Thu Jul 23, 2020, 06:35 PM

26. Some folks call her melatonin

Instead of her name.

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Response to MissB (Reply #26)

Thu Jul 23, 2020, 06:37 PM

28. Ahh. Much more polite than what I call her.

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Response to niyad (Reply #28)

Thu Jul 23, 2020, 06:50 PM

31. Same.

Iíve used melanoma before though.

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Response to MissB (Reply #31)

Thu Jul 23, 2020, 06:56 PM

32. melanoma and malaria are the polite terms.

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Response to niyad (Reply #32)

Mon Jul 27, 2020, 01:37 AM

48. I thought she was Melanomia

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Response to at140 (Original post)

Thu Jul 23, 2020, 06:37 PM

27. hmmm. I googled "melatonin covid treatment" (without the quotes)

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.

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Response to at140 (Original post)

Thu Jul 23, 2020, 06:50 PM

30. I've had to increase to 10 mg

about 2 hours before I hope to be asleep and I donít use the sublingual tablets. I found that the effects of the quick dissolving tablets wear off too fast and I wouldnít get more than 2 hours of sleep.

Last night, I wanted some extra sleep so took 5 addíl mgs just before going to bed. Had the unusual experience of getting 9 uninterrupted hours of sleep. However, I wouldnít recommend more than 3-5 mgs at first, and I wonít take more than 10 often at all.

Did I miss the mention of a recommended dosage?

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Response to oswaldactedalone (Reply #30)

Thu Jul 23, 2020, 07:35 PM

39. Many doctors say 10 mg is fine. I usually take anywhere from 5 or 6 mg up to about 10.

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Response to at140 (Original post)

Thu Jul 23, 2020, 07:33 PM

38. This is great news. I and my gf take melatonin every night. I take more than she.

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Response to at140 (Original post)

Fri Jul 24, 2020, 11:05 AM

44. I also use it for sleep some nights

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. Itís 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.
https://clinicaltrials.gov/ct2/show/NCT04353128

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Response to myccrider (Reply #44)

Fri Jul 24, 2020, 11:13 AM

45. This is from the description of the study:

"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."

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Response to triron (Reply #45)

Fri Jul 24, 2020, 07:46 PM

47. Thanks for the info

Seems itís 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.

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Response to at140 (Original post)

Fri Jul 24, 2020, 11:41 AM

46. Cool. I used to take it for insomnia

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

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Response to mvd (Reply #46)

Mon Jul 27, 2020, 02:48 AM

50. Same thing with me, it quit working but

I'll give it another try.

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Response to at140 (Original post)

Mon Jul 27, 2020, 02:45 AM

49. Already taking Vitamin D,Vitamin C immunity boost and Zinc everyday

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

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Response to helpisontheway (Reply #49)

Mon Jul 27, 2020, 09:17 AM

54. Me too. Sometimes add astragulus. Also take an immune senescence formula (by Life Extension)

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Response to triron (Reply #54)

Mon Jul 27, 2020, 10:03 AM

56. This is the immune booster I take

https://www.amazon.com/gp/aw/d/B086MWXW3B?psc=1&ref=ppx_pop_mob_b_asin_image

It has a few other things plus vitamin C.

Now gonna research the things that you are taking..

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Response to at140 (Original post)

Wed Jul 29, 2020, 06:43 PM

62. Never did I ever expect to see a post like this on DU! But thanks! I think.... nt

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