Study suggests possible benefit of melatonin in COVID-19

The coronavirus disease 2019 (COVID-19) pandemic continues to persist due to emerging variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that are associated with immune evasion and increased infectivity. This has led to an increasing number of breakthrough infections; however, vaccines continue to protect against serious and critical illnesses.

A new Journal of the American Board of Family Medicine The study discusses the usefulness of vitamin C and melatonin as potentially therapeutic and able to prevent acute lung injury in COVID-19.

Study: A pilot of a randomized controlled trial of melatonin and vitamin C for mild to moderate COVID-19. Image Credit: STOP_WAR /


Successive waves of COVID-19 cases have led to millions of hospitalizations and deaths around the world, which has subsequently placed considerable pressure on health systems. This has prompted intensive efforts to find or repurpose drugs that could protect against the overactive systemic inflammation characteristic of severe and deadly COVID-19.

COVID-19 appears to create oxidative stress which subsequently causes an inflammatory cascade leading to cell damage and damage to multiple organs.

Many patients who test positive for COVID-19 can take nutritional supplements; however, evidence of their usefulness in the treatment of this infection remains limited. The current study explores the effects of the antioxidant molecules of ascorbic acid (vitamin C) and N-acetyl-5-methoxytryptamine (melatonin) to limit the release of cytokines and, therefore, stop the progression of COVID-19 .

Previous animal research has shown weakened immunity in vitamin C deficiency and increased lung damage in H1N1 flu infection. Additionally, vitamin C levels drop in acute illness.

A cocktail of antioxidants, including ascorbic acid, given in COVID-19 revealed an association with reduced inflammatory markers in 80% of cases.

Likewise, the production of melatonin in the body decreases with age and has been postulated to underlie the increased severity of COVID-19 with age, given the immunomodulatory effects of this molecule.

The nuclear factor kB (NFkB) pathway and NLRP3 inflammasomes, both activated during viral replication, are inhibited by melatonin. Melatonin also protects against lung damage by oxidizing molecules and reducing inflammatory cell infiltration during viral infection.

Previous studies have shown shorter hospital stays, better oxygenation and improved sleep after melatonin treatment.

Study results

Researchers used an authorized modified version of the Wisconsin Upper Respiratory Symptom Survey (WURSS) to assess upper respiratory tract symptoms and effects on daily activities. The study was conducted between October 2020 and June 21, 2021 in Pennsylvania.

Patients took vitamin C, melatonin or a placebo for two weeks. All three groups had comparable symptoms and quality of life at baseline. However, the group receiving melatonin showed improvement in symptoms between days three and nine, which was not seen in those receiving vitamin C.

Similarly, quality of life improved faster over the same period in the melatonin group. There was no significant difference in sleep duration.

The changes described in the present study were minimal, as the observation period was short and the survey time points were daily.

By day 14, all participants reported stabilization of symptoms and quality of life. Further investigation at day 30 demonstrated that some continued to experience symptoms and a lower quality of life.


The current study used a daily survey protocol to track small changes in symptoms and quality of life with the use of ascorbic acid and melatonin. The results indicate that 1,000 mg of vitamin C daily produced no change in the rate of symptom relief or improved quality of life in COVID-19 patients, despite its antioxidant characteristics.

Previous studies with vitamin C have shown conflicting results.

However, melatonin at a dose of 10 mg per day was associated with a favorable symptom score from the third to the ninth day of the study. This is the first time that melatonin has been tested for its usefulness in treating outpatients with COVID-19. The apparent benefits of this drug may be due to its effects on oxidative stress and immune signaling.

However, not all patients started their supplements at the same time. Although most began on day three of study enrollment, the time from symptom onset was not equal for all patients. Delayed treatment has been shown to reduce the beneficial effects of these agents.

The small study size makes further research necessary to validate the effects of melatonin supplementation in COVID-19 in both the acute and long Covid stages.

It is important to note that differences between the time of diagnosis and the day of illness on which drug therapy was initiated may more accurately reflect real-life situations, where presentation, testing, and when test results become available vary from patient to patient.

Over-the-counter medications are readily available to most patients and their usefulness should be carefully considered.

Patients infected with COVID-19 whose recovery process could be accelerated by safe and accessible supplements could resume their professional and personal activities more quickly and, therefore, meaningful interventions could impact society as a whole..”

This requires large-scale studies to validate the modified WURSS scale used in the current study, as well as any improvements associated with the use of melatonin.

Journal reference:

  • Fogleman, C., Cohen, D., Mercier, A., et al. (2022). A pilot of a randomized controlled trial of melatonin and vitamin C for mild to moderate COVID-19. Journal of the American Board of Family Medicine. doi:10.3122/jabfm.2022.04.210529.

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