Practitioners explore use of melatonin as adjuvant therapy for COVID-19

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By Andrea Kagey, Integrative Practitioner Correspondent

While dietary supplements are not formulated to prevent or treat illnesses on their own, many supplements and natural remedies have been the focus of research as possible supportive options amid the novel coronavirus (COVID-19) pandemic. Melatonin, a hormone produced in the body to regulate circadian rhythms and help with internal sleep-wake cycles, has garnered attention from the medical research community.

Most notably considered a sleep aid, two recent studies conducted during the wake of the COVID-19 pandemic have recognized melatonin’s anti-inflammatory and antioxidative properties as two reasons why the supplement may be a viable option to support immune recovery.

In November 2020, The Cleveland Clinic Lerner Research Institute published a study that identified a direct correlation between melatonin supplement usage and a reduced likelihood in testing positive for SARS-CoV-2, the virus that causes COVID-19. Upon analyzing a large-scale COVID-19 patient registry database, and adjusting for age, sex, race, smoking history, and various disease comorbidities, the study identified that melatonin usage was significantly associated with a 28 percent reduced likelihood of a positive laboratory test result for SARS-CoV-2.

The study also showed that melatonin usage in Blacks increased that reduced likelihood of a positive laboratory test result for SARS-CoV-2 to 52 percent, indicating that low dose over-the-counter (OTC) melatonin may have some effect in the prevention of COVID-19.

The research team, led by lead author, Feixiong Cheng, PhD, genomic medicine researcher at the Cleveland Clinic Lerner’s Research Institute, also identified multiple proteins within SARS-CoV-2 that shared similarities with proteins associated with respiratory distress syndrome and sepsis. Two main causes of death in patients with severe cases of COVID-19.

In an interview with a local television station, Cheng told reporters he hypothesized that melatonin might have the potential to treat earlier stages of COVID-19, but that treatment would be most effective administered in higher dosage. This would have to be determined by clinical trials, he said.  

While COVID-19 has non-discriminately targeted people of all ages and health, some demographics have been considered more at-risk for death due to SARS-CoV-2 complications. Amongst those high-risk individuals, people living with obesity and diabetes can be more likely to get severely ill from COVID-19, according to the U.S. Centers for Disease Control and Prevention (CDC).

A June 2020 study published in the European Journal of Pharmacology examined melatonin as a potential adjuvant to improve clinical trials in obese and diabetic individuals. They found that obese and diabetic COVID-19 patients had low levels of blood melatonin, consequently making these high-risk individuals more susceptible to respiratory distress. The study cited certain melatonin characteristics that would benefit these patients, such as potent antioxidant effects, improving the endogenous antioxidant system, immunomodulatory properties, and a strong anti-inflammatory capability.

While controlled trials are necessary to determine the true efficacy of melatonin as an adjuvant treatment for COVID-19, melatonin supplements already have a place within integrative medicine. Melatonin is most often used to induce sleep in those suffering from insomnia, jet lag, and other sleep-wake disorders. Further, a 2018 article in the Journal of Behavior Therapy and Experimental Psychiatry, explored the mental health benefits of extended sleep duration, a good night’s sleep is also paramount to rebuilding and maintaining a healthy immune system. According to Robert Silverman, DC, MS, CNS, CCN, CSCS, CKTP, CES, CIISN, DACBN, DCBCN, HKC, FAKTR, founder of Westchester Integrative Health in White Plains, New York, a lack of good sleep can leave the immune system vulnerable and compromised.

“Sleep is the time to allow for immuno-rejuvenation of your cells,” Silverman said. “What I’ve found in my patients, if I’m able to get them a good night sleep and allow them to have the possibilities of immuno-rejuvenation, that leads them down a path of hopefully having a more immuno-resilient system.”

Silverman said he sees melatonin for more than just its sleep aid capabilities.

“The key to melatonin is that it [doesn’t] just help you sleep,” he said, “but there are all of these health promoting factors.”

Immune function, Silverman said, can benefit from the adjuvant use of melatonin within integrated healthcare.

In addition to melatonin’s discussed anti-inflammatory properties and antioxidized effects, studies have pointed towards melatonin as a possible adjuvant treatment in lowering cholesterol. A 2017 study that analyzed eight randomized controlled studies concluded that melatonin supplementation was found to improve blood lipid status. Ultimately it found that melatonin had a significant effect on triglycerides and total cholesterol levels when administered at doses over 8 milligrams.

According to Danielle Greenman, MD, functional medicine physician at Blum Center for Health in Rye Brook, New York, melatonin is part of the fine balance and community between the two roles of the immune system.

“We know it’s an immune buffer, it can act under normal circumstances to stimulate or suppress. It has anti-inflammatory and antioxidant components which we really see in acute inflammation,” Greenman said, discussing why, specifically, melatonin works well in addressing acute bacterial, viral, and parasitic infections. “The neuroendocrine system, which is estrogen, cortisol, acetylcholine, epinephrine, so your fight or flight, your rest and digest, your sex hormones and your melatonin, those all directly impact and influence each other and the immune system.”

Greenman cautions, however, that melatonin isn’t an appropriate adjuvant treatment option for every patient, “because melatonin has this balance between stimulant and suppression, it could have deleterious effects.”   

Patients with certain specific TH2 dominant auto-immune diseases, like rheumatoid arthritis, type 1 diabetes, and lupus, Greenman said, could experience a negative effect to their treatment due to an inclusion of melatonin. The decision to include melatonin in a treatment plan, she said, should be tailored individually and with the consultation of a healthcare professional.

References

Cheng, F. (2020) A network medicine approach to investigation and population-based validation of disease manifestations and drug repurposing for COVID-19. PLOS BIOLOGY. Retrieved from: https://journals.plos.org/plosbiology/article/authors?id=10.1371/journal.pbio.3000970

El-Missiry, M., Othman, A., and El-Missiry, Z. (2020) Melatonin is a potential adjuvant to improve clinical outcomes in individuals with obesity and diabetes with coexistence of Covid-19. Elsevier Public Health Emergency Collection. Retrieved from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7324339/

Hopp, D. and Shurtleff, D. (2021) Melatonin: What You Need To Know. National Center for Complementary and Integrative Health. Retrieved from: https://www.nccih.nih.gov/health/melatonin-what-you-need-to-know?nav=govd

Kaczor, T. (2010) An Overview of Melatonin and Breast Cancer: Exploring melatonin’s unique effects on breast cancer cells. Natural Medicine Journal. Retrieved from: https://www.naturalmedicinejournal.com/journal/2010-02/overview-melatonin-and-breast-cancer

Mohammadi-Sartang, M., Ghorbani M., and Mazloom, Z. (2017) Effects of melatonin supplementation on blood lipid concentrations: A systematic review and meta-analysis of randomized controlled trials. Clinical Nutrition Journal. Retrieved from: https://www.clinicalnutritionjournal.com/article/S0261-5614(17)31401-2/abstract

Nota J., and Coles M. (2018) Shorter sleep duration and longer sleep onset latency are related to difficulty disengaging attention from negative emotional images in individuals with elevated transdiagnostic repetitive negative thinking. Journal of Behavior Therapy and Experimental Psychiatry. Retrieved from: https://www.sciencedirect.com/science/article/abs/pii/S0005791617300629?via%3Dihub

U.S. Centers for Disease Control and Prevention (2021) People with Certain Medical Conditions. Retrieved from: https://www.cdc.gov/coronavirus/2019-ncov/need-extra-precautions/people-with-medical-conditions.html