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Faridzadeh A, Tabashiri A, Miri HH, Mahmoudi M. The role of melatonin as an adjuvant in the treatment of COVID-19: A systematic review. Heliyon. 2022;8(10):e10906. doi:10.1016/j.heliyon.2022.e10906

This systematic review, carried out under the PRISMA guidelines, summarizes the findings of 10 studies on the use of melatonin in COVID-19 patients. Melatonin has been explored in clinical studies due to its anti-inflammatory, antioxidant, and immunoregulatory properties. In addition to being a potent ROS scavenger, melatonin is also a potent myeloperoxidase (MPO) inhibitor.  Myeloperoxidase is produced with the over-activation of neutrophils, known as a “cytokine storm”. 


Our comments/takeaway from the article:

This review of studies, including humans, is relevant as the literature is still emerging on the use of melatonin in COVID-19 patients, with a number of studies or trials focused on a molecular base or animal models. As it is well established that melatonin is a powerful antioxidant, free radical scavenger, and anti-inflammatory agent, it is plausible that the use of melatonin may help in the recovery of COVID-19 patients. As the clinical use and dose of melatonin have not yet been established for COVID-19, it is best to work with a healthcare provider to determine if this is a viable option in the management of COVID-19.


PICO framework included:

  • Population- Adults over 18 years of age with COVID-19 (mild to severe symptoms), diagnosed by CT or PCR testing (n=665)

  • Intervention- Melatonin

  • Comparison- Comorbidities, gender, severity, melatonin dosage, and duration

  • Outcomes – changes in inflammatory markers, clinical signs, and symptoms (from baseline to last available follow-up)


Studies included:

  • Observational retrospective cohorts (2)

  • Randomized controlled trials (5)

  • Clinical trials* (3)

*High risk of bias was noted for the clinical trials.


Melatonin dosing:

  • 2-10 mg/day



Melatonin decreased inflammatory markers, including:

  • c-reactive protein (CRP)

  • erythrocyte sedimentation rate (ESR)

  • lactate dehydrogenase (LDH)


Melatonin decreased inflammatory cytokines, including:

  • interleukin (IL)-4

  • interferon- g (IFN-g)

  • IL-6

  • IL-1B

  • Tumor necrosis factor-a (TNF-a)

A decrease was noted after 14 days of consumption.


Melatonin decreased gene expression, including:

  • Signal transducer and activator of transcription (STAT) 4

  • STAT-6

  • T-box expressed in T cell (T-bet)

  • GATA binding protein 3 (GATA3)

  • Apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC)

  • Caspase 1 (CASP1)

These immune cell regulatory genes are upregulated in COVID-19, leading to an excessive immune response and cytokine storm.

Melatonin improved clinical signs and symptoms, including:

  • Sleep

  • Cough

  • Fatigue

  • Dyspnea

  • Decreased intubation period

  • Quicker return to baseline health


Authors (of article) conclusion:

The authors conclude that there is a probable role of melatonin as a potential adjuvant in the treatment of COVID-19, when taken for 2 weeks, to reduce recovery time, though further studies are warranted, including larger RCTs.

Article reviewed by Kim Ross, DCN

Content reviewed by Deanna Minich, PhD

October 28, 2022

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