What are the benefits of melatonin supplement to covid-19 patients?

What is melatonin?

This post describes the recent research on melatonin and covid-19. Melatonin is a hormone primarily released by the pineal gland at night. It regulates the sleep-wake cycle. It is present in food, such as milk, nuts, tart cherries, fatty fish, Goji berries, oats, mushrooms, corn and bananas. Melatonin supplement on the market is synthetic, and people use for insomnia, jet lag or shift work. Level of melatonin declines in old folks, and melatonin supplement may help them sleep better.

Melatonin and covid-19

The virus that causes covid-19 is SARS-cov-2. For more information, please read earlier post. Covid-19 is often lethal to patients of old age or with underlining health issues. However, the lethal condition is not due to the action of the virus, but due to the free radicals generated by the over-reacted immune system of the host (cytokine storm). Free radicals damage multiple vital organs of the host leading to organ failure and death. Therefore, agents that can mitigate these free radicals will improve the outcome of covid-19 infection.

Like resveratrol, melatonin can significantly reduce the mortality of severe covid-19 patients. It works via multiple pathways. It has anti-viral, anti-inflammatory, antioxidant, and immuno-regulatory activities. Melatonin is readily available from drug stores without prescription. It could relieve some of the symptoms of covid-19, and could protect vital organs from being damaged by cytokine storm. The results of studies using cell cultures and animal models look promising. However, results of clinical studies are limited. Because melatonin is not a patentable drug, drug companies are less likely to fund large scale clinical trials.

Anti-viral properties of melatonin

Melatonin binds to ACE2, and hence blocks SARS-cov-2 from entering into the cells. Furthermore, it upregulates antiviral genes that fight against virus. On the other hand, it inhibits viral protease (Mpro), an enzyme that is responsible for processing of viral replicase. Replicase is an enzyme required for viral replication and transcription. Therefore, melatonin will help reduce the viral load after one is infected.

Antioxidant and anti-inflammatory properties of melatonin

Melatonin and its metabolite are potent antioxidants that can scavenge free radicals. In addition, it also stimulates activity or production of several antioxidant enzymes. This indirectly enhances antioxidant capacity of the cells. Furthermore, it suppresses the activity or production of several pro-inflammatory enzymes. Together, these properties of melatonin will help protect cells from being damaged by overwhelming inflammatory reactions induced by cytokine storm during SARS-cov-2 infection.

Immuno-regulatory properties of melatonin

Melatonin down-regulates the over-reaction of innate immune response to SARS-cov-2 infection. This will help prevent the development of cytokine storm.

Clinical evidence

A number of small scale of clinical trials have been done using melatonin at 10 – 75 mg/day in addition to standard therapy on patients with severe covid-19. In all cases, the death rate of melatonin-treated group is significantly lower than that of the control group. In a recent randomized, double-blind study, a 2-week treatment of 3 mg melatonin for three times a day combined with standard care could relieve symptoms of patients with mild to moderate covid-19. This demonstrates that melatonin is indeed helpful to shorten the recovery time of covid-19 patients.

Conclusion

Studies show that melatonin is beneficial to covid-19 patients. Melatonin works by suppressing viral replication and by reducing the damage of vital organs by free radicals generated by over-reaction of the immune system. It is relatively nontoxic and readily available without prescription. It should improve the outcome of covid-19 infection. However, it should not be used as prophylaxis for covid-19 infection or as a substitute for vaccination.

References

1. Tan DX, Reiter RJ. Mechanisms and clinical evidence to support melatonin’s use in severe COVID-19 patients to lower mortality. Life Sci. 294:120368, 2022.
2. Farnoosh G, Akbariqomi M, Badri T, Bagheri M, Izadi M, Saeedi-Boroujeni A, Rezaie E, Ghaleh HEG, Aghamollaei H, Fasihi-Ramandi M, Hassanpour K, Alishiri G. Efficacy of a Low Dose of Melatonin as an Adjunctive Therapy in Hospitalized Patients with COVID-19: A Randomized, Double-blind Clinical Trial. Arch Med Res. 53:79-85, 2022.
3. Cardinali DP, Brown GM, Pandi-Perumal SR. Can Melatonin Be a Potential “Silver Bullet” in Treating COVID-19 Patients? Diseases. 8:44, 2020.