Can Melatonin be used as a COVID-19 Treatment?


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Melatonin is a Hormone that is synthesized in the pineal gland and many other organs. While it is known primarily as a natural sleep regulator, it also has many other important functions.

Advantages of Melatonin

For example, Melatonin:

  • Is a potent antioxidant with the rare ability to enter mitochondria, where it helps “prevent mitochondrial impairment, energy failure, and apoptosis of mitochondria damaged by oxidation. “5 It also helps recharge glutathione, and a deficiency of glutathione has been linked to the severity of COVID-19
  • Plays an important role in cancer prevention
  • Is important for brain, cardiovascular and gastrointestinal health
  • Strengthens immune function in a variety of ways
  • May improve the treatment of certain bacterial diseases, including tuberculosis
  • Helps suppress inflammation
  • May prevent or improve autoimmune diseases, including type 1 diabetes
  • Is an important energy hormone that can affect your energy levels
  • Helps regulate gene expression through a number of enzymes
  • Has anticonvulsant and antiexcitotoxic properties

Melatonin also plays important role in COVID-19 Treatment

Melatonin has also been shown to play a role in viral infections and could be an important adjunct to COVID-19 treatment, according to research published in June 2020 in the journal Life Sciences.

According to the authors, melatonin attenuates several pathological features of COVID-19, including:

  • Excessive oxidative stress and inflammation.
  • Exaggerated immune response leading to a cytokine storm
  • Acute lung injury
  • Acute respiratory distress syndrome

They note that melatonin is also “effective in intensive care patients by reducing blood vessel permeability, anxiety, and the use of sedatives, and improving sleep quality, which could also have a positive impact on clinical outcomes.

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

The authors review research looking at melatonin’s beneficial effects on 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 results, they believe melatonin may provide similar protection against SARS-CoV-2.

Melatonin reduces Risk of Positive COVID-19 Test

Data from the Cleveland Clinic also support the use of melatonin. Here, researchers analyzed patient data from the Cleveland Clinic’s COVID-19 registry using an artificial intelligence platform designed to identify drugs that can be repurposed.

Patients taking melatonin as a dietary supplement had, on average, a 28% lower risk of testing positive for SARS-CoV-2. Black people taking melatonin were 52% less likely to test positive for the virus.

By identifying clinical manifestations and pathologies common to COVID-19 and 64 other diseases, they found that certain proteins associated with chronic diseases were strongly linked to SARS-CoV-2 proteins. In other words, a number of proteins appear to play key roles in the pathologies that occur in both COVID-19 and other chronic diseases. For example:

Analyses of single-cell RNA sequencing data show that co-expression of ACE2 and TMPRSS is increased in absorptive enterocytes from inflamed ileum tissue of Crohn’s disease patients compared with non-inflamed tissue, suggesting a shared pathobiology of COVID-19 and inflammatory bowel disease.

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

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

basic pathogenesis

 

These compounds suggest that drugs already used for chronic disease can be repurposed for the treatment of COVID-19 by acting on one or more common biological targets. Melatonin stood out in this regard. Patients taking melatonin as a dietary supplement had, on average, a 28% lower risk of testing positive for SARS-CoV-2. Black people taking melatonin were 52% less likely to test positive for the virus.

Variables considered in the calculations included age, sex, race, smoking, and several known comorbidities. The authors note that while the results are promising, large observational studies and randomized controlled trials are still needed to confirm the clinical benefits of melatonin.

Two important data are missing from the analysis: the dosage used and the duration of use. These data were not included in the patient registry, so we do not know how much melatonin is needed to reduce the risk of SARS-CoV-2 infection as much as was found in this study.

High-dose Melatonin Works Successfully on COVID-19

It is possible that higher doses than those used for sleep may be needed, at least when treating an active infection. A recent case series published in Melatonin Research describes how high-dose intravenous melatonin can help patients with COVID-19 pneumonia.

Here, patients received 36 mg to 72 mg per day in four divided doses as add-on therapy to standard treatment. Most supplements contain between 0.5 mg and 5 mg, and when used for sleep, people usually start with the lowest dose and increase as needed.

All patients who received melatonin improved within four to five days, and all survived. On average, patients treated with melatonin were discharged from the hospital in 7.3 days, compared with 13 days for patients who did not receive melatonin. That’s far better than the expensive treatment remdesivir, which costs more than $3,000 and doesn’t produce nearly that improvement.

Other Doctors Also Use Melatonin Against COVID-19

Dr. Richard Neel and his colleagues at Little Alsace and Uvalde Urgent Care clinics in Texas report that they also use high-dose melatonin in combination with vitamin C and vitamin D and have successfully treated more than 400 patients as of the last week of July 2020.

As described in a section below, melatonin enhances vitamin D signaling and both act synergistically to improve mitochondrial function. Melatonin and vitamin C are also both involved in ACE2, the receptor that SARS-CoV-2 uses to enter the cell.

Together, melatonin and vitamin C help reduce the virulence of SARS-CoV-2 by inhibiting NLRP3 inflammasomes, which in turn inhibits cytokine storms. The Front Line COVID-19 Critical Care Working Group (FLCCC) also lists melatonin as an optional add-on to its MATH+ protocol for COVID-19.

How Melatonin Combats COVID-19

Research suggests that melatonin has the ability to target COVID-19 through several mechanisms. For example, melatonin has been shown to regulate immune responses and prevent cytokine storms. As the authors of one such study explain, when immune cells are in a hyperinflammatory state, their metabolism changes in a manner similar to that of cancer cells:

Similar to cancer cells … immune cells such as macrophages/monocytes forgo mitochondrial oxidative phosphorylation for ATP production under inflammatory conditions in favor of cytosolic aerobic glycolysis (also known as the Warburg effect)…

The switch to aerobic glycolysis allows immune cells to become highly phagocytic, accelerate ATP production, intensify their oxidative burst, and provide the abundant metabolic precursors required for enhanced cell proliferation and increased cytokine synthesis and release…

Because of melatonin’s potent antioxidant and anti-inflammatory effects, it would normally reduce the highly proinflammatory cytokine storm and neutralize the free radicals generated, thereby maintaining cellular integrity and preventing lung damage.

The cytokine storm is one of the reasons why sepsis (blood poisoning) is so deadly, and studies have confirmed that melatonin has a beneficial effect on sepsis. (Sepsis is also a feature of severe COVID-19.) As reported in a 2010 study in the Journal of Critical Care:

Melatonin is a potent anti-inflammatory agent … Its anti-inflammatory effects have been attributed to inhibition of nitric oxide synthase and the resulting reduction in peroxynitrite formation, stimulation of various antioxidant enzymes that contribute to the enhancement of antioxidant defenses, and protective effects on mitochondrial function and prevention of apoptosis.

In a number of animal models of septic shock, as well as in patients with septic disease, melatonin reportedly exerts beneficial effects in arresting cell damage and multiorgan failure…

Apart from acting on local inflammatory foci, melatonin also exerts its beneficial effects through a multifactorial pathway that includes its action as an immunomodulatory, antioxidant, and antiapoptotic agent.

A 2019 animal study published in Frontiers in Immunology discusses how melatonin may protect against polymicrobial sepsis – sepsis caused by more than one microbial organism – which has twice the mortality of unimicrobial sepsis (sepsis caused by a single microbe).

In this case, melatonin appears to provide protection by having an antibacterial effect on white blood cells called neutrophils. A high neutrophil count is an indicator of infection.

Melatonin may also combat SARS-CoV-2 infection by:

  • Suppression of oxidative stress
  • Regulation of blood pressure (a risk factor for severe COVID-19)
  • Improving metabolic disorders associated with diabetes and
    Insulin resistance (risk factors for severe COVID-19) by inhibiting the renin-angiotensin system (RAS)
  • Protecting mesenchymal stem cells (MSCs, which have been shown to alleviate severe SARS-CoV-2 infections) from injury and enhancing their biological activities
  • Promotion of both cell-mediated and humoral immunity
  • Promote the synthesis of macrophage and granulocyte progenitor cells, natural killer (NK) cells, and T-helper cells, especially CD4+ cells
  • Inhibition of NLRP3 inflammasomes

General notes on Nutritional Supplementation

As mentioned earlier, it is very difficult to make dosage recommendations based on the limited data currently available. However, since the Cleveland Clinic examined the supplements reported by patients, it is reasonable to assume that they were taking them as you normally would. Most melatonin supplements contain between 0.5 mg and 5 mg.

In the case report mentioned earlier, patients received 36 mg to 72 mg of melatonin intravenously per day, which would likely be too much for prophylactic use. However, in studies37 no adverse effects were noted at doses of 20 mg up to 100 mg.

Regardless of the dose you take, and I recommend starting with a low dose of 1 mg or less, be sure to take melatonin at night before bed. The increase in melatonin levels is what makes you feel sleepy in the evening, so it is not advisable to take it in the morning or during the day when your natural levels are (and should be) low. If you wake up in the middle of the night, especially if you are exposed to a light source, you can also take some then to help you get back to sleep.

Melatonin is also best taken sublingually, either in the form of a spray or a sublingual tablet. When taken sublingually, melatonin enters the bloodstream directly and does not have to pass through the digestive tract. As a result, its effects are felt more quickly.

Melatonin and Vitamin D are a successful Combination

Another supplement that is of critical importance in the age of COVID-19 is vitamin D. Interestingly, melatonin boosts vitamin D signaling, and optimizing your vitamin D levels may be one of the most beneficial steps you can take to lower all the risks associated with COVID-19, from reducing your risk of testing positive to lowering your risk of serious infection and death.

To learn more, download my free vitamin D report from StopCovidCold.com. Melatonin and vitamin D work synergistically to optimize your mitochondrial function. In fact, your mitochondria are the ultimate common target for both.

A deficiency of vitamin D or melatonin has been linked to the development of several chronic diseases, including hypertension, cardiovascular disease, metabolic syndrome, and diabetes, to name a few.

These diseases have also been shown to be comorbidities that significantly increase the risk of dying from COVID-19. Synthesis of vitamin D and melatonin also decreases dramatically with age, and age is a major risk factor for death from COVID-19, so taking vitamin D3 and melatonin can be beneficial for most people, but is especially important for the elderly.

Support the Body’s Own Production of Melatonin and Vitamin D

Keep in mind, however, that taking supplements only makes sense if you also want to optimize your body’s own production. In the case of melatonin, this means making sure you get enough sleep on a regular basis.

You also need a good dose of natural sunlight around midday to synchronize your internal clock so that your body produces melatonin at the right time (i.e., late evening). When evening comes and the sun sets, you should avoid bright and blue light, as blue light inhibits melatonin synthesis. Blue light is found primarily in LED and fluorescent lights, which are “cool white.”

Sun exposure, of course, is also the ideal way to optimize your vitamin D levels. I recommend that you get regular sun exposure, ideally daily, for large portions of your body.

If for some reason you can’t get enough sun exposure, consider taking a vitamin D3 supplement (along with a little extra vitamin K2 to maintain a healthy balance between these two nutrients).

Sources

1. Journal of Critical Care 2010 Dec;25(4):656.e1-6

2. Pharmacological Research April 2012; 65(4): 437-444

3. Journal of Pineal Research December 17, 2002; 34(1)

4. The Journal of Steroid Biochemistry and Molecular Biology May 2020; 199: 105595, Page 13

5. Front Biosci. 2007 Jan 1;12:947-63

6. Neuro Endocrinol Lett. 2006 Jun;27(3):365-8

7. International Journal of Molecular Sciences, 2013 Jan 24;14(2):2410-30

8. Current Neuropharmacology, 2017 Apr;15(3):434-443

9. Antimicrobial Agents and Chemotherapy, 1999 Apr;43(4):975-7

10. International Journal of Molecular Sciences, 2013 Apr; 14(4):8638-8683

11. Stanford University, Melatonin and Energy Levels, Sierra Kersten, May 24, 2018

12. Life Sciences June 1, 2020; 250:117583

13. Psychology Today May 8, 2020

14. Chronobiology Melatonin May Help Fight Coronavirus

15. Life Sciences June 1, 2020; 250:117583, Abstract

16. Virus Research October 2, 2020; 287: 198108

17. PLOS Biology November 6, 2020 DOI: 10.1371/journal.pbio.3000970

18. Cleveland Clinic November 9, 2020

19. Melatonin Research 2020; 3(3)

20. Devinenews.com July 22, 2020

21. Front Line COVID-19 Critical Care Working Group (FLCCC)

22. Medical Drug Discoveries June 2020; 6:100044

23. Frontiers in Immunology 2019 Jun 19;10:1371

24. Critical Care 2010; 14(Suppl 1): P62

25. Current Neuropharmacology 2010 Sep; 8(3): 228–242

26. Evolutamente.it March 14, 2020

27. Journal of Pineal Research 2014 May;56(4):427-38, Abstract

28. The Journal of Steroid Biochemistry and Molecular Biology May 2020; 199: 105595