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Long Covid - Article Update

Art (California) on 12/10/2022
5 out of 5 stars

As promised, I will update this thread on long Covid(LC) as studies become available regarding LC.

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!

Art

REPLY   12      

Replied by Krysia from Glenview, IL on 12/18/2022

Thanks, I'll give the Melatonin a try. Just read it is also good for non-alcoholic fatty liver.
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Replied by Sharon from Missouri on 01/27/2023

Would you please cite the article you read about melatonin and nafld? I would like to learn more. I have also read the lecithin is good for it, but I’m still stumbling around the edges of seeing what will be good.
REPLY         

Replied by Art from California on 01/28/2023

Sharon,

I wrote the following in December of 2022 which you may find useful for NAFLD or non alcoholic fatty liver disease :

https://www.earthclinic.com/cures/nonalcoholic-fatty-liver-disease.html

Art

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Replied by Marsh from Colorado on 02/13/2023

Thanks for this, Art. Ironically my sister, a friend, and I started about 3 weeks ago with the same sensation of needing to draw phlegm out from our sinuses (and we don't live near each other). Nothing has helped, it's just ongoing. Friend is an RN and said it's a post-covid symptom. Any suggestions?
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Replied by Art from California on 02/13/2023

Marsh,

Four things I have used that have helped with excess phlegm issues are melatonin, NAC, quercetin and stinging nettle extract. If there is still an infection issue, colloidal silver (CS) and or grapefruit seed extract (GSE) are helpful. You can get the GSE from using XLEAR Nasal Spray (XNS) at the maximum label dose. XNS and CS are both potent antimicrobials and XNS also contains xylitol with the GSE which both help breakdown biofilms in the sinuses and it is easy to apply the maximum label dose of XNS.

Art

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Replied by Art from California on 04/22/2024

To further update on the usage of effective supplements to treat long covid (LC), the following study in humans suggests that the supplement Palmitoylethanolamide commonly referred to as PEA is another effective supplement to treat LC as discussed here :

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9326613/

Here are some relevant quotes from the study :

' As far as we know, this is the first study showing the potential efficacy of PEA in improving symptomatology of patients with long COVID. Indeed, most of our patients obtained a significant improvement in PCFS score (p = 0.0000) after treatment with PEA and without any side effects. Therefore, a causal beneficial effect of this 3-month therapy seems to be a reasonable assumption in our population. '

' The neuroprotective and anti-inflammatory effect of PEA has been recently studied in patients with smell dysfunction. In a recent clinical trial on the efficacy of PEA on olfactory dysfunction, it has shown that a combination of PEA and luteolin (PEA-LUT) with olfactory training was more efficient in recovering smell than olfactory training alone [71]. '

' Moreover, in the case of asymptomatic persistence of the virus, PEA has been shown to have antiviral mechanisms [73]. Indeed, PEA disassembles lipid droplets, avoiding the fonts of energy and defense by SARS-CoV-2 against innate cellular defenses, thanks to the activation of PPAR-α. Then, as the persistence of low-level virus particles/mRNA can be detected for long time after clinical recovery, this further mechanism of action can help in treating long COVID. '

So this study suggests that PEA may be an effective treatment for LC. I would also like to add that there are two other forms of PEA that are considered to be more effective than regular PEA. These two forms are called ultra micronized PEA or micronized PEA (umPEA) and may also be worth considering for LC as well as other health issues. The other form of PEA combines PEA + Luteolin.

Art

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Replied by Art from California on 04/23/2024

Previously I have discussed the use of melatonin as highly likely to be useful for long covid (LC). A new review a new (April, 2024) adds further confirmation to that idea as discussed here :

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11031980/

Here is a relevant quote from the review :

' According to various studies, melatonin has proven efficacy in attenuating the severity of certain COVID-19 manifestations, validating its reputation as an anti-viral compound. Melatonin has well-documented anti-aging properties and combating neurodegenerative-related pathologies. Melatonin can block the leading events of ferroptosis since it is an efficient anti-inflammatory, iron chelator, antioxidant, angiotensin II antagonist, and clock gene regulator. Therefore, we propose ferroptosis as the culprit behind the post-COVID-19 trajectory of aging and neurodegeneration and melatonin, a well-fitting ferroptosis inhibitor, as a potential treatment. '

I was not previously aware that LC /Covid-19 could promote accelerated aging and neurodegeneration, but knowing that now, imo, makes melatonin even more useful for LC because of its known health promoting multiple methods of action.

Art

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Replied by Phyllis from Florida on 11/09/2024

Hello Art:

Ever since I had Covid about 3 years ago or more, I have had a constant clearing my throat with phlegm especially at night time. Is there anything that would help or cure this. Have you heard of anyone else having this?It even affects how I can talk and my voice sounds horse.

Thanks for all your help on different health problems.

REPLY   1      

Replied by Art from California on 11/09/2024

Hi Phyllis,

Long term mucus in the throat with a cough is a common long covid symptom, but you made no mention of a cough. I'm a little surprised that you have put up with this for 3 years. In 3 years I would have thought that you would already tried all of the common remedies and eventually talked to your doctor about it.

One consideration is that you may have post nasal drip (PND), post covid which can also be a long covid symptom. PND is often seen after respiratory tract infections as discussed in this thread on the subject :

https://connect.mayoclinic.org/discussion/phlegm-in-my-throat-and-post-nasal-drip-after-covid/

Here is a link describing typical PND symptoms that you can compare to your own symptoms :

https://my.clevelandclinic.org/health/diseases/23082-postnasal-drip

Here is a quote from the article describing typical PND symptoms :

  • A feeling of mucus draining into your throat.
  • Frequent swallowing.
  • Gurgling or hoarseness.
  • Urge to clear your throat.
  • Bad breath (halitosis).
  • Cough that bothers you more at night.
  • Nausea and vomiting from excess mucus draining to your stomach.

Postnasal drip can also cause painful ear infections if mucus clogs up your Eustachian tubes. Your Eustachian tubes are what connect your nose and throat to your middle ears.

The above article links list some potential remedies.

Five supplements that I feel could be beneficial for your symptoms are these :

1. NAC

2. Quercetin

3. Bromelain

Quercetin + Bromelain is available in a combination supplement which will be easier to take than taking both separately. Here is a link to a typical product on Amazon :

https://www.amazon.com/NOW-Quercetin-Bromelain-120-Capsules/dp/B0013OSQ5I/ref=sr_1_5?crid=29OK97B7ADFVT&dib=eyJ2IjoiMSJ9.Lj5-25dNmlGW7Cd1iX5nDPKjyoG6dOxGXkdyXiSA6j1gPQzwJO6GW32lAH4Jav3_fsA-aDeI4KbckylhNlomarKPA3CA7wSHIiRUoMs061WCCWSv82ShfF_RfUD6MqaY7KgLy8NdHDt8h6wR4DjYaKv8xwmPfavyjXh7QS9y8zbhztGg5RU13MvUbJQy6tDsuQKtEEyC_lQQUhQSR23uYTTcwF3OUh8Ife6sXSjpiB8WujPPiCqE9ikD7GovBVPG7Lvfwwqvormy9Kt7tiVF6GZV0NtLsHC49k4DsIGyHZM.bipuUTvZ1WDCwH2jvnkxduHmf2JPZTWUeMmKUdqfy40&dib_tag=se&keywords=quercetin+bromelain&qid=1731210612&sprefix=quercetin+bromelain,aps,184&sr=8-5

4. Potent Synbiotics - Synbiotics are probiotics that also contain prebiotics or the prebiotics are used separately at higher dosing than normally available in a synbiotic. Covid-19 is known to alter the gut microbiome toward more pathogenic bacteria. Probiotics plus prebiotics (Synbiotic) can help to improve the gut microbiome toward more health promoting bacteria.

5. R-Alpha Lipoic Acid

If your mucus is very thick, NAC can help thin it to help it flow out more easily. If the five supplements do not thin your mucus enough, you can consider an over the counter medication called Mucinex which also helps thin thick mucus.

You don't have to take all five, just decide which ones you feel comfortable with taking and start with those. The quercetin + bromelain may be an important one to consider.

Given the length of time that you have had this condition, I highly recommend that you see your doctor first, to rule out other potentially more serious conditions, to be safest for yourself.

Please keep us updated on how you make out.

Art

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Replied by Phyllis from Florida on 11/10/2024

Hello again Art.

I did mention it to my gp but he subscribed a liquid medication and after reading the side effects I decided not to take it.

Thanks for your suggestions. I also found out that to gargle pink salt several times daily will help a lot. I will try that. thanks

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Replied by Art from CA on 12/20/2025

To update the original post on Long Covid, this newer study (October, 2025) adds further confirmation that melatonin is useful for this purpose as discussed here :

https://pmc.ncbi.nlm.nih.gov/articles/PMC12688923/

Here is a relevant quote from the link :

' Post-COVID syndrome (long COVID) is increasingly recognized as a state of chronic inflammation, immune imbalance, and multiorgan dysfunction. Emerging evidence highlights circadian rhythm disruption and melatonin dysregulation as overlooked drivers of persistent symptoms such as fatigue, cognitive impairment, and immune dysregulation. Reduced melatonin impairs cytokine suppression, antioxidant defense, and mitochondrial protection, fueling inflammation and oxidative stress. These disruptions, coupled with autoimmune responses targeting adrenergic and muscarinic receptors, exacerbate systemic pathology. Preliminary data suggest that melatonin supplementation and chronotherapy may restore circadian alignment, rebalance immunity, and mitigate disease progression, although robust large-scale trials remain limited. Integrating circadian science into therapeutic protocols may provide a novel avenue for improving long-term outcomes in post-COVID patients. '

Melatonin has shown this ability to realign circadian rhythms and now that the latest information is showing the importance of realigning the circadian rhythms in Long Covid/Post Covid Syndrome, this mechanism of melatonin is showing its value for this purpose and adding further confirmation as to the multiple beneficial health effects of melatonin for post covid syndrome.

Art

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