Why Melatonin Should Be a Part of COVID-19 Treatment

by Dr. Daniel
Published on April 14, 2020

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In an article published on March 23, 2020 in Life Sciences, scientists suggest that melatonin could play a role in combating COVID-19. [1]

It's already established that the inflammation, oxidation and exaggerated immune response of a COVID-19 infection is what causes serious harm for individuals.

This immune reaction is known as a cytokine storm that progresses into acute lung injury (ALI) and acute respiratory distress syndrome (ARDS).

In this new study, the anti-inflammatory, anti-oxidant and immuno modulating effects of melatonin were shown to be protective against viral induced ALI and ARDS.

What is a Cytokine Storm?

An immune reaction gone wild is a short and accurate description for cytokine storms.

Normally, when the human body encounters a germ, the immune system attacks the invader and then stands down.

But sometimes, the army of cells attacking can get out of control, turning from obedient soldiers into an unruly, pitchforked-bearing mob of attackers.

There are various types of hyperactive immune reactions that can be triggered by different infections, faulty genes or autoimmune disorders.

Even people who suffer from seasonal allergies could be experiencing cytokine storms.

Doctors are just now coming to understand cytokine storms and how to treat them.

There’s no fail-safe diagnostic test to measure cytokine storms, but there are signs that they could be underway.

For example, blood levels of the protein ferritin may rise, as may blood concentrations of the inflammation indicator C-reactive protein, which is made by the liver.

The first hints that severe Covid-19 cases included a cytokine storm came out of Chinese hospitals near the outbreak’s epicenter.

Physicians in Wuhan, in a study of 29 patients, reported that higher levels of the cytokines IL-2R and IL-6 were found in more severe Covid-19 infections. [2]

Another team, analyzing 150 cases in Wuhan, found that an array of molecular indicators for a cytokine storm — including IL-6, CRP and ferritin — were higher in those who died than in those who survived. [3]

Melatonin has Indirect Anti-Viral Actions

Melatonin has indirect anti-viral actions due to its anti-inflammatory, anti-oxidant, and immune-enhancing features.

Melatonin has also been shown to reduce the ability for viruses to enter the bloodstream, eventual paralysis, and death in mice infected with viral encephalitis; and has led to down regulation of acute lung oxidative injury, pro-inflammatory cytokine release, and inflammatory cell recruitment in respiratory syncytial virus models.

These findings support a rationale for melatonin use in viral diseases.

Additionally, the anti-inflammatory, anti-oxidant, and immunomodulating actions of melatonin support its potential attenuation of COVID-19 infection. [1, 4, 5]

Melatonin has Anti-Inflammatory Actions

Melatonin exerts anti-inflammation effects through various pathways.

Melatonin suppresses NF-kB, a protein complex that controls cytokine production in ARDS.

Conversely, melatonin stimulates NF-E2 related factor 2 (Nrf2), crucial in protecting against lung, liver, and cardiovascular injury.

Inflammation generally involves an increase in the production of the cytokines and chemokines TNF-α, IL-1β, IL-6, and IL-8, whereas melatonin has been shown to reduce them. [1, 6, 7, 8]

Melatonin Reduces Cytokine Levels in Humans

There is no research related to the use of melatonin in patients with COVID-19, but the use of melatonin has shown to be effective in other diseases with an increased level of inflammation.

At doses of 6 mg/d and 25mg/d, respectively, melatonin has been shown to decrease serum levels of IL-6, TNF-α, and hs-C-reactive protein (hs-CRP) in patients with diabetes mellitus and periodontitis, and promotes a significant reduction in serum concentrations of TNF-α, IL-6, IL-1β and lipoperoxides in patients with MS.

Additional studies of melatonin at intakes of 5-10mg/d have been shown to decrease many of the same inflammatory cytokines found in COVID-19. [1, 9, 10, 11]

Melatonin Should Be Considered as Supportive Therapy for Covid-19

In closing, the short-term use of melatonin has been deemed safe, even at higher than physiologic doses (physiologic doses being in the 0.5 – 1mg range).

While the safety of melatonin has been verified in many human studies, its effect when given to COVID-19 patients remains unknown and should be monitored closely.

Its use in experimental animal models and human studies has continuously documented its efficacy and safety.

Patients prone to viral infections or dealing with inflammation-based chronic conditions may benefit from melatonin usage.

Melatonin testing can reveal the baseline status of this important anti-inflammatory, immune-modulating hormone, providing a framework for supplementation.