Art (California) on 12/10/2022

In this new study (November 2022), the researchers discuss the multiple beneficial effects of Melatonin as a potential treatment to help deal with various LC symptoms. Something that is not mentioned in this study is that type 2 diabetes mellitus (T2DM) is being seen in post covid patients now and melatonin has previously shown benefit for T2DM. In any case they cover many side effects and how melatonin is likely to offer benefit via its multiple methods of action, which include antiapoptotic effects, antioxidant & radical scavenging effects, anti inflammatory effects and immunomodulatory effects Here is a link to the new study :

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9687267/

Here are some very relevant quotes from the study :

' This methoxyindole is found in all forms of life that express aerobic respiration; melatonin’s primary function is cytoprotection, displaying anti-inflammatory, antioxidant, and immunostimulant effects [29, 30] which together endow it with highly potent neuroprotective properties [31]. The anti-inflammatory action of melatonin involves a variety of mechanisms [32]. One of them is Sirtuin-1 induction, which decreases the polarization of macrophages toward a proinflammatory profile [33]. Suppression of nuclear factor (NF)-κB activation [34, 35] and stimulation of nuclear erythroid 2-related factor 2 are also detected after exposure to melatonin [36]. Melatonin reduces proinflammatory cytokines (tumor necrosis (TN)F-α, interleukin (IL)-1β, IL-6, and IL-8) and increases anti-inflammatory cytokines such as IL-10 [33, 37]. '

' The antioxidant and scavenging effects of melatonin on free radicals in both the cytoplasm and the cell nucleus are mainly independent of receptors [38]. To fulfill this, melatonin not only acts as a free radical scavenger but also gives rise to a cascade of molecules with high antioxidant activity. It also acts as an indirect antioxidant, enhancing the production of antioxidant enzymes while inhibiting that of prooxidant enzymes [39]. In addition, some antiapoptotic and cytoprotective effects are seen under ischemia, presumably due to melatonin’s stabilizing activity of the mitochondrial membrane [40]. '

' Thus, melatonin can reduce the damage resulting from sepsis mediated by COVID-19 through different mechanisms, I.e., by reversing the Warburg-type metabolism and transforming proinflammatory M1 macrophages into anti-inflammatory M2 macrophages [43], by mitigating the production of HIF-1α [44], by suppressing NF-κB [45], and by inhibiting NLRP3 inflammasome [46]. Circulating secreted phospholipase-A2 (Group IIA) correlated with the severity of COVID-19 disease [47]; hence, cyclooxygenase inhibition by melatonin [48, 49] is another potential mechanism by which the methoxyindole may inhibit viral infection. '

' It may well be true that higher doses of melatonin would be more beneficial in the COVID pandemic condition. For example, in a retrospective cross-sectional study of a closed population of 110 old adult patients treated with a mean melatonin daily dose of 46 mg for at least 12 months prior to the availability of COVID-19 vaccination, there was no death in the face of a lethality rate of 10.5% in the local population of elders suffering acute COVID-19 disease [64]. Indeed, animal studies support the use of high doses of melatonin to prevent infection in murine COVID-19 models [65]. From several animal studies, the human equivalent dose HED) of melatonin was calculated by allometry for a 75 kg adult [46]. Allometry is commonly employed for determining initial doses used in Phase I human clinical drug trials [66]. '

' As stated above, the deficits in attention, memory, verbal processing, and problem-solving seen in patients complaining of brain fog resemble MCI, the initial phase of Alzheimer’s disease (AD) [22]. The underlying neuroinflammation in this condition (Figure 1) could be effectively controlled by melatonin, as shown by studies in cell lines linked to AD, in which melatonin reverses abnormalities in the Wnt/β-catenin, insulin, and Notch signaling pathways, proteostasis disruption and abnormal autophagic integrity (reviewed in Refs. [67, 68, 69, 70, 71]). '

' The beneficial effects of melatonin on fibromyalgia (associated commonly with ME/CFS) were first described in one of our laboratories [90]. Since then, several studies have confirmed the initial findings (for a summary, see ref. [91]). A common pathogenic mechanism is suggested by the similarities among ME/CFS, fibromyalgia, and post-COVID syndrome. The multiplicity of pathophysiological abnormalities in ME/CFS patients opens the possibility of numerous potential therapeutic targets [24]. The several abnormalities described comprise increased oxidative stress, mitochondrial dysfunction, dysregulated bioenergetics, a proinflammatory state, the disruption of gut mucosal barriers, and autonomic nervous system disturbances related to autoimmunity [92] (Figure 2). The possible therapeutic options targeting these pathways include melatonin, coenzyme Q10, curcumin, molecular hydrogen, and N-acetylcysteine [24]. Among them, melatonin is the only compound that addresses all mentioned potential targets [24].'

' Considering the quantity of scientific/medical studies that have suggested melatonin use in the COVID-19 pandemic, the inability of melatonin to garner attention from public health authorities or the pharmaceutical industry is disheartening. More than 190 papers on pubmed.gov (accessed on 9 October 2022) have examined the use of melatonin as a safe and potentially effective therapy for the COVID-19 pandemic since its inception [93]. This might be due to several factors, including the fact that no influential organization has promoted its therapeutic use for this condition. Melatonin is non-patentable and cheap; therefore, the pharmaceutical business has little motive to encourage its usage. Meanwhile, several potentially harmful and costly medications have been repackaged as therapies for this disease [94]. '

' In critical situations, such as an Ebola outbreak or the COVID-19 pandemic, it is ethical to use all accessible and safe medicines, even if their usefulness has not been fully demonstrated, especially if the therapy has no major adverse side effects. From an analysis of 27 publications that were surveyed on the ability of drugs to successfully treat COVID-19, it was concluded that melatonin is at least twice as effective as remdesivir or tocilizumab in reducing the inflammatory markers of a coronavirus 2019 infection [94]. Given the substantial number of deaths caused by SARS-CoV-2 infections throughout the world, it seems to us that it is immoral to not take advantage of any such safe therapy, especially if the vaccinations become less effective as the virus continues to evolve. At the very least, well-controlled and powered clinical trials are essential to further establish the current evidence that melatonin is safe and efficacious in treating COVID-19 and its sequelae. '

As you can see from the above study quotes, melatonin covers a lot of known symptoms seen in LC and should clearly be a main candidate for not only treating Covid-19, but very importantly, LC also!

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