Melatonin is a hormone synthesized in your pineal gland and many other organs. While it is most well-known as a natural sleep regulator, it also has many other important functions.
- Research has also found that melatonin is important in several other ways:
- It plays an important role in cancer prevention
- Is important for brain, cardiovascular, and gastrointestinal health
- Boosts immune function in a variety of ways
- May improve the treatment of certain bacterial diseases, including tuberculosis
- Helps quell inflammation
- May prevent or improve autoimmune diseases, including Type 1 diabetes
- Is an important energy hormone that can influence your energy level
- Helps regulate gene expression via a series of enzymes
- Has anticonvulsant and antiexcitotoxic properties
Melatonin’s Role in COVID-19 TreatmentMelatonin has also been shown to play a role in viral infections and according to a June 2020 research paper in Life Sciences journal, it may be an important adjunct to COVID-19 treatment. According to the authors, melatonin curbs several pathological features of COVID-19, including:
- Excessive oxidative stress and inflammation
- Exaggerated immune response resulting in a cytokine storm
- Acute lung injury
- Acute respiratory distress syndrome
”The scientific review paper, “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 reduce the severity of viral infections.
Melatonin Reduces Risk of Positive COVID-19 TestData 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.
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, a peer-reviewed research paper published in PLOS Biology noted :
“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."
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.
High-Dose Melatonin Successfully Treats COVID-19It’s possible that higher doses than those used for sleep may be needed, at least when treating an active infection. A recent case series26 published in the journal Melatonin Research details how high-dose intravenous melatonin can benefit patients with COVID-19 pneumonia.
Here, patients were given 36 mg to 72 mg per day in four divided doses as an adjunct therapy to standard of care. Most supplements contain between 0.5 mg and 5 mg, and when used for sleep, you’d typically start with the lowest dose and work your way up as needed.
Other Doctors Are Also Using Melatonin Against COVID-19Dr. Richard Neel and colleagues at Little Alsace and Uvalde Urgent Care clinics in Texas also report using high-dose melatonin in combination with vitamin C and vitamin D, and had as of the last week of July 2020 successfully treated more than 400 patients.
As reviewed in a section below, melatonin enhances vitamin D signaling and the two work synergistically to enhance your mitochondrial function. Melatonin and vitamin C are both also involved with ACE2, the receptor that SARS-CoV-2 uses to gain entry into the cell.
How Melatonin Combats COVID-19Research suggests melatonin may have the ability to combat COVID-19 via several different mechanisms. For example, it’s been shown to regulate immune responses and prevent cytokine storms.29 As explained by the authors of one such study published in Medicine in Drug Discovery when your immune cells are in a hyper-inflammatory state, their metabolism changes in a way similar to that of cancer cells:
“Melatonin is an effective anti-inflammatory agent … Its anti-inflammatory action has been attributed to inhibition of nitric oxide synthase with consequent reduction of peroxynitrite formation, to the stimulation of various antioxidant enzymes thus contributing to enhance the antioxidant defense, and to protective effects on mitochondrial function and in preventing apoptosis.”
“In a number of animal models of septic shock, as well as in patients with septic disease, melatonin reportedly exerts beneficial effects to arrest cellular damage and multiorgan failure …”
“Apart from action on the local sites of inflammation, melatonin also exerts its beneficial actions through a multifactorial pathway including its effects as an immunomodulatory, antioxidant and antiapoptotic agent."
More recently, a 2019 animal study in the journal Frontiers in Immunology discusses how melatonin can protect against polymicrobial sepsis—i.e., sepsis caused by more than one microbial organism—which has a twofold higher lethality than unimicrobial sepsis (sepsis caused by a single microbe).
- Suppressing oxidative stress
- Regulating blood pressure (a risk factor for severe COVID-19)
- Improving metabolic defects associated with diabetes and insulin resistance (risk factors for severe COVID-19) via inhibition of the renin-angiotensin system (RAS)
- Protecting mesenchymal stem cells (MSCs, which have been shown to ameliorate severe SARS-CoV-2 infection) against injuries and improving their biological activities
- Promoting both cell-mediated and humoral immunity
- Promoting synthesis of progenitor cells for macrophages and granulocytes, natural killer (NK) cells and T-helper cells, specifically CD4+ cells
- Inhibiting NLRP3 inflammasomes
General Guidance for SupplementationAs mentioned, it’s very difficult to make dosage recommendations based on the limited evidence currently at hand, but since Cleveland Clinic looked at the supplements patients reported using, it seems reasonable to assume they were using it as you typically would. Most melatonin supplements contain between 0.5 mg and 5 mg.
In the case report mentioned earlier, patients were given 36 mg to 72 mg of melatonin intravenously per day, which would likely be excessive for prophylactic use. That said, research37 has found no adverse effects for dosages ranging from 20 mg up to 100 mg.
Whatever dose you take, and I recommend starting low, at 1 mg or less, be sure to take melatonin at night, before bed. Rising melatonin levels is the reason you feel sleepy in the evening, so it’s ill-advised to take it in the morning or during the day, when your natural level is (and should be) low. If you happen to wake up in the middle of the night, especially if you’re exposed to a light source, you could also take some then, to help you go back to sleep.
Melatonin and Vitamin D Are a Winning ComboAnother supplement of crucial importance in the age of COVID-19 is vitamin D. Interestingly, melatonin enhances vitamin D signaling, and optimizing your vitamin D may be one of the most beneficial steps you can take to lower all of the risks associated with COVID-19, from reducing your risk of testing positive to lowering your risk of severe infection and death.
A deficiency in either vitamin D or melatonin has been associated with the pathogenesis of several chronic diseases, including high blood pressure, cardiovascular disease, metabolic syndrome, and diabetes, just to name a few.
Make More Melatonin and Vitamin DKeep in mind, however, that it makes little sense to take a supplement unless you’re also seeking to optimize your body’s natural production of these compounds. In the case of melatonin, this includes making sure you get good sleep on a regular basis.
You also need a good dose of natural sunlight around midday to synchronize your circadian clock so that your body produces melatonin at the appropriate time (i.e., in late evening). As the evening wears on and the sun sets, you’ll want to avoid bright and all blue lighting, as blue light inhibits melatonin synthesis. Blue lighting is predominant in LED and fluorescent bulbs that are “cool white.”