Melatonin’s Multiple Actions Against COVID-19

Melatonin is part of the FLCCC’s I-MASK+ FLCCC protocol for preventing and early treatment of COVID-19.

The prevention Protocol recommends 6 mg before bedtime to fortify the immune system, and the Early Treatment Protocol (for Delta Variant) recommends 10 mg of Melatonin before bedtime.

Are there studies to support the Melatonin for COVID-19?

c19melatonin.com is a website that compiles studies and meta-analyses about Melatonin’s use in COVID-19.

Here is how to understand the tables below. The names listed on the left are the principal authors of the studies. The green numbers next to the authors show the Relative Risk (RR). Green means positive results.

The size of the squares reflects the number of study subjects. The green diamonds reflect the size of the meta-analyses. A meta-analysis puts together studies with the same objective to make a more meaningful conclusion.

You can see below that Melatonin improves early treatment (73%), late treatment (71%), and prevention (40%) in COVID-19 patients.

Three studies about Melatonin’s effect on COVID-19 mortality

Melatonin is commonly known as a sleep aid but the pineal gland produces it while we sleep. Recent research shows other organs have Melatonin in the body. However, as we get older, melatonin secretion decreases.

COVID-19 has two phases. The first is viral replication with mild symptoms, and the second is when the body develops a hyperimmune response. The immune system attacks the body during the hyperimmune response, leading to a cytokine storm.

Acute Respiratory Distress Syndrome (ARDS) is a cytokine storm and is the number one killer of COVID-19 patients.

This article presents studies showing Melatonin’s anti-viral, antioxidative and anti-inflammatory effects against two phases of COVID-19. Melatonins’ actions optimize the body’s immune system to prevent and fight infection. At the same time, it enhances the immune system and regulates it to avoid a hyperimmune response.

You can see the different phases of COVID-19 in this image from FLCCC. Melatonin is at the bottom, showing that it is helpful for all stages.

Safety of Melatonin

Melatonin is safe. According to the FLCCC protocol for prevention and treatment, the melatonin dose is 6 and 10 mg, respectively. Melatonin should be taken at bedtime since it can cause drowsiness.

One study used Melatonin at 36-72mg/day by mouth in 4 divided doses to 10 COVID-19 patients as an added therapy. Three of them had moderately severe Acute Respiratory Distress Syndrome (ARDS), and 1 with mild ARDS. All survived. None required mechanical ventilation, and all of them were subsequently discharged earlier than other patients who were not on Melatonin.[6]

The discussion below is quite technical but included to provide more details.

Anti-viral effects of Melatonin

Melatonin decreases the number of ACE2 on cell surfaces. SARS-CoV-2 has to attach to the ACE2 receptors before entering the cells and replicating. Lower numbers of ACE2 decrease viral entry.
Melatonin inhibits chymotrypsin-like proteases to restrain viral replication.
Melatonin improves the proliferation and maturation of natural killing cells, T and B lymphocytes, granulocytes, and monocytes and enhances anti-viral activity.

Antioxidative effects of Melatonin

Reactive oxygen species (ROS) or free radicals are negatively-charged molecules needed for fighting infection and body repair processes. However, excess ROS leads to oxidative damage, cellular destruction, and a hyperimmune response.

Almost all cells in the human body have mitochondria. The mitochondria supply power to the cells so that the cell for cellular functions like moving towards the infection (chemotaxis), “eating” the viruses (phagocytosis), and programmed cell death (apoptosis).

Excessive ROS damages the mitochondria, the source of cellular energy, and its absence prevents the immune cells from killing the viruses.

With that background, Melatonin exerts its antioxidative effects through the following:

Melatonin increases antioxidants like superoxide dismutase, glutathione synthase, and catalase. All of them reduce free radicals to allow a robust immune response.
Melatonin is proven to be superior to Vitamin C as an antioxidant. Antioxidants eliminate and protect against free radical damage. [7]
Melatonin potentiates the effects of Vitamin C, thus adding more antioxidant capability. [7]

Anti-inflammatory effects of Melatonin

Inflammation is part of the immune response. But, excess inflammation in COVID-19 leads to cytokine storms. Acute Respiratory Distress Syndrome (ARDS) and multi-system organ failure are manifestations of a cytokine storm.

Melatonin exerts its anti-inflammatory actions thru several mechanisms.

Melatonin affects several molecules like nuclear factor kappa B (NF-kB), inducible nitric oxide synthase, and others to decrease inflammatory cytokines like Tumor-necrosis factor α and several interleukins (IL) like IL-1b, IL-8, IL-6, and IL-18. [7]
Melatonin decreases Angiotensin II, which prevents constriction of the blood vessels. Normal diameter blood vessels help the white blood cells reach the infection.
Melatonin increases angiotensin 1-7 activity, promoting vasodilation, anti-inflammation, antioxidant, and anti-fibrotic effects. Lung fibrosis is a consequence of severe COVID-19 pneumonia. Normal lungs expand quickly, and Fibrotic lungs are stiff, making it harder to breathe.
Melatonin promotes silent information regulator (SIRT1) activity. Higher SIRT1 enhances the anti-viral activity of Type I Type interferons and downregulates macrophage function to prevent cell damage.
Melatonin suppresses the activity of the pro-inflammatory factor nuclear factor kappa B (NF-kB) transcription factor and increases nuclear factor erythroid 2-related factor 2 (Nrf2). Low Nf-kB and Nrf2 lead to the production of more antioxidant proteins.
Melatonin inhibits the COVID-19 cytokine storm by reversing aerobic glycolysis. Aerobic glycolysis is needed to fight an infection, but if Melatonin is lacking, aerobic glycolysis goes full bore, and the inflammatory state in COVID-19 becomes uncontrolled. [2]

Take away message

Melatonin has anti-viral, antioxidative, anti-inflammatory effects. It is proven effective as an adjunctive treatment for COVID-19, and it is safe, inexpensive, and easy to get.

Knowledge about Covid-19 is rapidly evolving. Information may update as new studies are made. Stay current by subscribing. Feel free to share and like.

Don’t Get Sick!

Related:

References:

Camp OG, Bai D, Gonullu DC, Nayak N, Abu-Soud HM. Melatonin interferes with COVID-19 at several distinct ROS-related steps. J Inorg Biochem. 2021 Oct;223:111546. doi: 10.1016/j.jinorgbio.2021.111546. Epub 2021 Jul 17. PMID: 34304092; PMCID: PMC8285369.
Reiter RJ, Sharma R, Ma Q, Dominquez-Rodriguez A, Marik PE, Abreu-Gonzalez P. Melatonin Inhibits COVID-19-induced Cytokine Storm by Reversing Aerobic Glycolysis in Immune Cells: A Mechanistic Analysis. Med Drug Discov. 2020;6:100044. doi:10.1016/j.medidd.2020.100044
Lee RU, Glickman GL. Sleep, Circadian Health, and Melatonin for Mitigating COVID-19 and Optimizing Vaccine Efficacy. Front Neurosci. 2021;15:711605. Published 2021 Aug 18. doi:10.3389/fnins.2021.711605
Anderson G, Reiter RJ. Melatonin: Roles in influenza, Covid-19, and other viral infections. Rev Med Virol. 2020;30(3):e2109. doi:10.1002/rmv.2109
DiNicolantonio JJ, McCarty M, Barroso-Aranda J. Melatonin may decrease risk for and aid treatment of COVID-19 and other RNA viral infections. Open Heart. 2021 Mar;8(1):e001568. doi: 10.1136/openhrt-2020-001568. PMID: 33741691; PMCID: PMC7985934.
Castillo, R.R., Quizon, G.R.A., Juco, M.J.M., Roman, A.D.E., de Leon, D.G., Punzalan, F.E.R., Guingon, R.B.L., Morales, D.D., Tan, D.-X. and Reiter, R.J. 2020. Melatonin as adjuvant treatment for coronavirus disease 2019 pneumonia patients requiring hospitalization (MAC-19 PRO): a case series. Melatonin Research. 3, 3 (Jun. 2020), 297-310. DOI:https://doi.org/https://doi.org/10.32794/mr11250063.
High doses of Melatonin as a potential therapeutic tool for the neurologic sequels of covid-19 infection. DP Cardinali – Melatonin Research, 2020 – melatonin-research.net
Cardinali DP (2019) Are melatonin doses employed clinically adequate for melatonin-induced cytoprotection? Melatonin Res. 2: 106-132. doi: 10.32794/mr11250025.

Knowledge about Covid-19 is rapidly evolving. Information may update as new studies are made. Stay current by subscribing. Feel free to share and like.

Don’t Get Sick!