Melatonin in COVID-19: Treatment Hunting

Learning about the benefits of melatonin while creating my metabolic resuscitation lectures has been quite intriguing. The first time I was exposed to these beneficial antioxidant and anti-inflammatory effects was during a live lecture by Dr. Paul Marik. As of late, there have been three articles regarding utilizing melatonin in patients with COVID-19. Check here to learn more about utilizing melatonin in sepsis.

If you’re looking for robust randomized control trial data, you need to look elsewhere. It doesn’t exist nor do I think it ever will. I am aware we may be reaching here, but nothing we are currently using is impressively effective. Heck, even dexamethasone has a NNT of 8.3. We need all the help we can get. If combining melatonin to dexamethasone can shrink that NNT to 6, we would be very happy.

The very science-y stuff.. made easier.

Simplifying the concepts, melatonin has antioxidant and anti-inflammatory properties. This could potentially help during the cytokine storm phase of COVID. It could neutralize the generated free radicals.

We have learned that interleukin (IL)−10, 6 and tumor necrosis factor (TNF) -α increase in these patients. Those are the targets for some of the -mab medications. The levels tend to increase with severity.

There is a theory that COVID may cause damage to the melatonin synthetic pathway. If melatonin isn’t being made, then it will not be around to help us fight this infection off. The cited papers state that while melatonin does not directly fight off the infection, it could help reduce the severity of the infection.

A potential factor as to why the elderly are hit by COVID with greater intensity is that they do not produce as much endogenous melatonin.

The articles, especially the Zhang paper, go far deeper into the mechanisms that I have alluded to here.

Dosing Melatonin for COVID patients

First of all, big disclaimer: we do not know the exact dosing or if this works. There is no robust data on this. The following dosing strategy was taken from the Reiter paper cited below.

The general population and elderly who are out in the community are should take 3-10mg, 30-60 minutes before bedtime.

Healthcare professionals should take 40mg per day, 1 hour before bedtime.

For hospitalized patients not in the ICU they recommend 50mg twice daily for 7 days.

For hospitalized patients who are in the ICU they recommend 200mg twice daily for 7 days.

The authors threw in hydroxychloroquine stating that melatonin could reduce its toxicity and improve its efficacy. I’m not holding my breath.

Downsides of administering Melatonin to COVID-19 patients

There aren’t many. Melatonin is sold as an over-the-counter supplement. It is inexpensive and non-toxic over a wide dose range. I have heard commentary that it may make the patients too sleepy. I have not seen this in my practice nor when I take melatonin to sleep when I am working nights.

Other adverse effects include headache, fatigue and drowsiness. We don’t know the case in patients with COVID.

Why I don’t think we will be getting an RCT anytime soon regarding Melatonin in COVID

The following is my personal opinion. We are too busy trying out everything else in our patients COVID: dexamethasone, CD24FC medications, the newest -mab, remdesivir, other antivirals. Even collecting the data on those patients is quite messy. Many of them are due to big pharmaceutical companies. There isn’t a big financial gain from this for anyone outside of the NIH because it could save the governments big money in the long run. The other issue is that you need an academic institution to put aside their current bodies of work to start randomizing these patients. Many studies cannot be intertwined with other studies. Lots of caveats and nuance.

Also, when you mention melatonin in sepsis, something that has theoretical physiologic benefits, clinicians do a very good job of showing you how far their eyes roll back. Can you imagine how many patients you’d have to enroll into a study with melatonin to adequately power it?

Wrapping it up…

At this time I am not providing melatonin to my patients with COVID-19 in the ICU. At the time of my writing I am working a string of nights. When I am the day shift guy, I will strongly consider it. I cannot recommend you do it for your patients. I can solely say that there’s a potential benefit out there that we should explore.

Link to Podcast and YouTube video on using Melatonin in COVID


Zhang R, Wang X, Ni L, et al. COVID-19: Melatonin as a potential adjuvant treatment. Life Sci. 2020;250:117583. doi:10.1016/j.lfs.2020.117583
Link to Abstract
Link to FULL FREE Article

Reiter RJ, Sharma R, Ma Q, Dominquez-Rodriguez A, Marik PE, Abreu-Gonzalez P. Melatonin Inhibits COVID-19-induced Cytokine Storm by Reversing Aerobic Glycolysis in Immune Cells: A Mechanistic Analysis [published online ahead of print, 2020 May 11]. Med Drug Discov. 2020;6:100044. doi:10.1016/j.medidd.2020.100044
Link to Abstract
Link to FULL FREE Article

Reiter RJ, Abreu-Gonzalez P, Marik PE, Dominguez-Rodriguez A. Therapeutic Algorithm for Use of Melatonin in Patients With COVID-19. Front Med (Lausanne). 2020;7:226. Published 2020 May 15. doi:10.3389/fmed.2020.00226
Link to Abstract
Link to FULL FREE Article

Although great care has been taken to ensure that the information in this post is accurate, eddyjoe, LLC shall not be held responsible or in any way liable for the continued accuracy of the information, or for any errors, omissions or inaccuracies, or for any consequences arising therefrom.

Hat tip to @jaefur, @sumocrucial1, @acala91 for having sent me some of these papers.

There are now 4 studies looking at melatonin on CLICK HERE.

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