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Cleveland Clinic Identifies Melatonin May Be an Important Adjunct To COVID-19 Treatment

Melatonin is a hormone synthesized in your pineal gland and many other organs.1 While it is most well-known as a natural sleep regulator, it also has many other important functions.2 For example, melatonin:

Is a potent antioxidant3 with the rare ability to enter your mitochondria,4 where it helps “prevent mitochondrial impairment, energy failure and apoptosis of mitochondria damaged by oxidation.”5 It also helps recharge glutathione,6 and glutathione deficiency has been linked to COVID-19 severity

Plays an important role in cancer prevention7

Is important for brain, cardiovascular and gastrointestinal health8

Boosts immune function in a variety of ways 

May improve the treatment of certain bacterial diseases, including tuberculosis9

Helps quell inflammation

May prevent or improve autoimmune diseases, including Type 1 diabetes10

Is an important energy hormone that can influence your energy level11

Helps regulate gene expression via a series of enzymes12

Has anticonvulsant and antiexcitotoxic properties13

Melatonin Also Has Important Role in COVID-19 Treatment

Melatonin has also been shown to play a role in viral infections14 and according to a June 2020 research paper15,16,17 in Life Sciences journal, it may be an important adjunct to COVID-19 treatment. According to the authors, melatonin attenuates several pathological features of COVID-19, including:18

  • Excessive oxidative stress and inflammation 
  • Exaggerated immune response resulting in a cytokine storm 
  • Acute lung injury
  • Acute respiratory distress syndrome 


They point out that melatonin is also “effective in critical care patients by reducing vessel permeability, anxiety, sedation use, and improving sleeping quality, which might also be beneficial for better clinical outcomes.”19

The scientific review paper,20 “Melatonin Potentials Against Viral Infections Including COVID-19: Current Evidence and New Findings,” published October 2020 in Virus Research journal, also summarizes the many potential mechanisms by which melatonin can protect against and ameliorate viral infections.

The authors review research looking at melatonin’s beneficial effects against a variety of viruses, including respiratory syncytial virus, Venezuelan equine encephalitis virus, viral hepatitis, viral myocarditis, Ebola, West Nile virus and dengue virus. Based on these collective findings, they believe melatonin may offer similar protection against SARS-CoV-2. 

Melatonin Reduces Risk of Positive COVID-19 Test

Data21,22 from Cleveland Clinic also supports the use of melatonin. Here, the researchers analyzed patient data from the Cleveland Clinic’s COVID-19 registry using an artificial intelligence platform designed to identify drugs that may be repurposed.23,24

By identifying clinical manifestations and pathologies shared by COVID-19 and 64 other diseases, they were able to conclude that certain proteins associated with chronic diseases are highly connected with SARS-CoV-2 proteins. Put another way, a number of proteins appear to play a key role in the pathologies seen both in COVID-19 and other chronic diseases. For example:25

“Analyses of single-cell RNA sequencing data show that co-expression of ACE2 and TMPRSS2 is elevated in absorptive enterocytes from the inflamed ileal tissues of Crohn disease patients compared to uninflamed tissues, revealing shared pathobiology between COVID-19 and inflammatory bowel disease. 

Integrative analyses of metabolomics and transcriptomics (bulk and single-cell) data from asthma patients indicate that COVID-19 shares an intermediate inflammatory molecular profile with asthma (including IRAK3 and ADRB2).”

The diagram below illustrates (among other things) the basic pathogenesis of SARS-CoV-2 (figure A) and the network of disease manifestations associated with the infection (figure C).

These connections suggest that drugs already in use for a chronic disease may be repurposed and used in the treatment of COVID-19, as it acts on one or more shared biological targets. Melatonin stood out in this regard. Patients who used melatonin as a supplement had, on average, a 28% lower risk of testing positive for SARS-CoV-2. Blacks who used melatonin were 52% less likely to test positive for the virus. 

Confounding variables adjusted for in the calculations included age, sex, race, smoking history and several known comorbidities. The authors point out that while the findings look promising, large observational studies and randomized controlled trials are still needed to validate the clinical benefits of melatonin. 

Two key data points missing from the analysis are the dosage used and the length of supplementation. These data were not included in the patient registry, so we don’t know how much melatonin is required to lower your risk of SARS-CoV-2 infection to the degree found in this study.