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There have been many common drugs used as off-label treatments for COVID-19, including Ivermectin and Hydroxychloroquine. But even those demand a prescription. On his blog, Dr. Joseph Mercola suggests a treatment that can be purchased in the vitamin section of any drug store today, melatonin. He writes:
Melatonin is a hormone synthesized in your pineal gland and several other organs,1 indeed in most cells, including human lung monocytes and macrophages, as it is actually synthesized in your mitochondria.2
While most well-known as a natural sleep regulator, melatonin also has many other important functions.3 Notably, it plays an important role in cancer prevention4 and may prevent or improve certain autoimmune diseases, such as Type 1 diabetes.5
It also has anticonvulsant and antiexcitotoxic properties,6 and is a potent antioxidant7 with the rare ability to enter your mitochondria,8 where it helps prevent mitochondrial impairment, energy failure and the death of mitochondria damaged by oxidation.9 It also:
- Boosts immune function
- Helps recharge glutathione10 (and glutathione deficiency has been linked to COVID-19 severity)
- May improve the treatment of certain bacterial diseases, including tuberculosis11
- Helps regulate gene expression via a series of enzymes12
As noted in the Journal of Critical Care:13
“Melatonin is a versatile molecule … Melatonin plays an important physiologic role in sleep and circadian rhythm regulation, immunoregulation, antioxidant and mitochondrial-protective functions, reproductive control, and regulation of mood. Melatonin has also been reported as effective in combating various bacterial and viral infections.”
Melatonin Also Has Important Role in COVID-19 Treatment
Over the past two years, melatonin has emerged as a surprise weapon against COVID-19. It’s been shown to play a role in viral, bacterial and fungal infections14 and as early as June 2020, researchers suggested it might be an important adjunct to COVID-19 treatment.15,16,17 According to the authors of that paper, melatonin attenuates several pathological features of COVID-19, including:18
- Excessive oxidative stress and inflammation
- Exaggerated immune response resulting in a cytokine storm
- Acute lung injury
- Acute respiratory distress syndrome
In October 2020, a scientific review,19 “Melatonin Potentials Against Viral Infections Including COVID-19: Current Evidence and New Findings,” summarized the mechanisms by which melatonin can protect against and ameliorate viral infections such as respiratory syncytial virus, viral hepatitis, viral myocarditis, Ebola, West Nile virus and dengue virus.
Based on these collective findings, they hypothesized melatonin may offer similar protection against SARS-CoV-2. One mechanistic basis for this relates to melatonin’s effects on p21-activated kinases (PAKs), a family of serine and threonine kinases. The authors explain:20
“In the last decade, PAKs have acquired great attention in medicine due to their contribution to a diversity of cellular functions. Among them, PAK1 is considered as a pathogenic enzyme and its unusual activation could be responsible for a broad range of pathologic conditions such as aging, inflammation, malaria, cancers immunopathology, viral infections, etc …
Interestingly, melatonin exerts a spectrum of important anti-PAK1 properties … It has been proposed that coronaviruses could trigger CK2/RAS-PAK1-RAF-AP1 signaling pathway via binding to ACE2 receptor.
Although it is not scientifically confirmed as yet, PAK1-inhibitors could theoretically exert as potential agents for the management of a recent outbreak of COVID-19 infection. Indeed, Russel Reiter, a leading pioneer in melatonin research, has recently emphasized that melatonin may be incorporated into the treatment of COVID-19 as an alternative or adjuvant.”
Melatonin Lowers COVID-19 Mortality
Then, on the last day of 2021, Melatonin Research published a research commentary21 discussing an October 2021 study22 by Hasan et. al., which found melatonin significantly lowered mortality when given to severely infected COVID patients. According to the authors:
“In a single-center, open-label, randomized clinical trial, it was observed that melatonin treatment lowered the mortality rate by 93% in severely-infected COVID-19 patients compared with the control group.
This is seemingly the first report to show such a huge mortality reduction in severe COVID-19 infected individuals with a simple treatment. If this observation is confirmed by more rigorous clinical trials, melatonin could become an important weapon to combat this pandemic.”
The commentators point out that, at less than $5 per course of treatment, melatonin is a cost-effective addition to any treatment plan. For comparison, Regeneron monoclonal antibodies cost about $2,100 per dose and remdesivir is $3,100 per treatment. Melatonin also has no serious side effects, so it can be universally used.
The Hasan trial23 included 158 hospitalized COVID patients between the ages of 18 and 80. All had confirmed severe SARS-CoV-2 infection.
Eighty-two of the patients were enrolled in the melatonin arm and received 10 milligrams (mg) of melatonin half an hour before bedtime for 14 days, in addition to standard therapeutic care, which included oxygen intubation, remdesivir, levofloxacin (an antibiotic for protection against secondary bacterial infections), dexamethasone (an anti-inflammatory) and enoxaparin (an anticoagulant).
In the standard care only group, 13 of the 76 patients died (17.1%), compared to just one of the 82 patients (1.2%) who received melatonin in addition to everything else. That’s a reduction in mortality of 93%, which is quite remarkable. Three mechanisms of action responsible for this success appears to be a combination of its antioxidant, anti-inflammatory and immunoregulatory activities.24
During the second week of infection, a time when severely infected patients can take a drastic turn for the worse, the melatonin group fared much better than the standard care only group, with only two patients developing sepsis, compared to eight in the standard care only group.25
The Hasan trial also supports findings from a clinical case series26 published in 2020, where patients diagnosed with COVID-19 pneumonia received 36 mg to 72 mg of melatonin intravenously per day, in four divided doses, as an adjunct therapy to standard of care.
All of the patients given melatonin improved within four to five days, and all survived. On average, those given melatonin were discharged from the hospital after 7.3 days, compared to 13 days for those who did not get melatonin.
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