Art (California) on 06/14/2022
https://link.springer.com/article/10.1007/s00018-022-04390-3
Here is a relevant quote from the study:
>>> ' In conclusion, we disclosed ACE2 as a new binding target of melatonin, which leads to allosteric negative modulation of the spike/ACE2 interaction. This effect on the SARS-CoV-2 entry receptor function of ACE2, combined with the inhibition of NFKB expression and endogenous ACE2 expression in endothelial cells, is most likely the predominant mechanism for impaired SARS-CoV-2 brain invasion by melatonin and its derivatives. ' <<<
An important point of this study is that melatonin binds to ACE2 receptors interfering with the ability of the SARS CoV-2 virus to dock on ACE2 receptors and melatonin does this without serious side effects.
Art
Replied By Marshagail (Georgia) on 02/21/2023
Replied By Art (California) on 02/22/2023
Marshagail,Thank you very much for your kind and thoughtful words!
Art
Replied By Paola (Roma) on 10/06/2023
I would be interested in knowing your opinion on a potential side effect of this drug. There is the suspicion that taken every day as we do Melatonin may damage the retina over time. "High retinal melatonin levels combined with exposure to bright light might cause retinal damage."
I tried to google this but the info online is not much at the moment....
thank you so much and please keep up the good work!! Grazie mille from Italy!!!
Paola
Replied By Art (California) on 10/07/2023
Paola,If the reason you are taking melatonin is to fight Covid, it only need be taken while you have Covid and up to 2 months after as a long Covid preventative.
The topic of retinal damage and melatonin was based on an old study in animals, where they gave high dose melatonin and then exposed them to very bright light which caused damage. First the melatonin was taken during the day when melatonin levels are lower. Most studies I have seen recommend and use melatonin at night and this is what I do also. Melatonin levels are normally higher at night and lower during the daylight hours. What was done to the animals in that study I would consider a form of torture.
So this was an abnormal use of melatonin and very bright light which humans don't regularly do. I only mention daytime use of melatonin for severe diseases such as Covid or cancer. In any case I have not seen similar results in human studies, but I have seen newer studies that suggest that melatonin use has beneficial effects for the retinas as discussed in this newer (May 2023) review of studies :
https://www.sciencedirect.com/science/article/pii/S0753332223002640
Here are two relevant quotes :
' MT synthesis-related genes in retinal tissue may be affected by age. Our study shows that MT can effectively restore NaIO3-induced retinopathy and maintain retinal structural integrity. Importantly, MT may assist the conversion of M1 to M2 macrophages to promote tissue repair, which may be caused by the increased infiltration of Tregs. Moreover, MT treatment may upregulate TET2, and further NT5E demethylation is associated with Treg recruitment in the retinal microenvironment. '
' Our findings suggest that MT can effectively ameliorate retinal degeneration and regulate immune homeostasis via Tregs. Modulation of the immune response may provide a key therapeutic strategy. '
The science of melatonin is continually evolving as new studies discover more positive effects that melatonin has on human, animal and plant health.
I have taken higher dose melatonin for over a decade based on studies I have read. I currently take my 132 mg of melatonin in the evening.
Art
Replied By BellaPaolina (Roma) on 10/09/2023
1- The only side effect I've noticed till now is that whenever I bump into something I get a big hematoma afterwards. Have you noticed this on yourself too?
2- So I assume blue light glasses are not necessary while we use our laptops in the evening?
thank you again for your very informative reasearch, God bless you!
Paola
Replied By Art (California) on 10/09/2023
BellaPaolina,Regarding your first question, that is not an issue I have seen reported in the literature, but melatonin does have blood thinning and anticlotting properties, so in order to find out if it is the cause for the hematoma, try stopping it for a month and see if that resolves the issue. If it does help, and since you are in good health, perhaps you can use a lower dose. Melatonin at 50 mg/day has shown the ability to return elevated oxidative stress levels, in people with disease, back to healthy control levels and this would be very useful for maintaining health long term. Lastly, you can get melatonin naturally by exposing yourself to earlier morning and later afternoon sunlight and get a little vitamin d at the same time. I always recommend this to people who do not tolerate oral melatonin because naturally derived melatonin seems to come with no side effects. I wrote a little about that here :
https://www.earthclinic.com/supplements/how-to-increase-melatonin-naturally.html
Regarding blue light glasses and whether they are useful for preventing eye fatigue and blue light exposure, so far they have not shown a good ability to do that and the following article discusses that topic :
https://www.publish.csiro.au/hc/Fulltext/HC23101
Continued good health to both you and your husband!
Art
Replied By BellaPaolina (Roma) on 10/10/2023
My question about the blue light glasses was referred to systemic melatonin and the influence of light exposure. High melatonin ingestion coupled with the bright light from laptops at night might damage the retina?Excuse me for my terrible english, I realize now my question was not formulated clearly. Thank you again from the other side of the ocean!!!
Replied By Art (California) on 10/10/2023
BellaPaolina,Yes, things definitely get lost in the translation sometimes!
I will have to look for the old study I mentioned, but they were using very bright light in that study which was far brighter than a computer monitor and that light could have been retina damaging on its own. I have been taking higher dose melatonin for over a decade and spend a lot of time on my computer and have not had a problem with my eyes, but I also take my melatonin at night except when I had Covid. In current studies, as I linked to previously, melatonin is retina protective, not degenerative or damaging.
Older studies hold some weight until they are proven incorrect by newer more comprehensive studies. If you have a newer study showing retinal damage, please link to it. I read melatonin studies everyday and have not seen this.
Art
Replied By BellaPaolina (Roma) on 10/12/2023
I have not found any newer studies, so I assume that the studies you have linked are correct. Thank you so much for taking the time to answer to my questions. The research you do for Earthclinic is very helpful to many!!!Paola
Replied By Paola (Italy - IT) on 08/15/2024
Hi again Art and hope all is well in your place in the world! I was hoping to find some of your well researched info on melatonin effect on avian flu and monkey pox, but it seems you still haven't posted any.Also, my husband and I have taken ivermectin when down with Covid in november 2022 ( coupled with melatonin as per FLCCC protocol) -and this combination has healed us in just 3 days.I would like to know your opinion on ivermectin and if it could be useful to take if there ever is another terror pandemic scenario with avian flu/monkey pox. Thank you so much and arrivederci from Italy
Replied By Art (California) on 08/15/2024
Hi Paola,To date, studies still do not show a high efficacy rate for Ivermectin in use against SarsCoV-2 virus in humans. Dosing as high as 1200 mcg/day per kilogram have been used in a human study and while it did have an effect on modestly lowering viral load, that dose showed no benefit in terms of symptom reduction. Here is one RCT that shows viral load lowering effects, but minimal to no symptom improvement :
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8734085/
Here is a relevant quote from the RCT :
' This was the study with the highest dose of ivermectin ever used in a clinical trial for the treatment of COVID-19 or, indeed, for any other condition. The higher dosage (1200 μg/kg for 5 days) showed no safety concerns as no SADRs were observed. The co-primary efficacy outcome was the reduction in viral load on Day 7. The reduction (expressed in log10) was 2.9 for the higher dose (arm C), 2.5 for the lower dose (arm B) and 2.0 for placebo, but the differences were not statistically significant. No significant differences were observed in the clinical outcome either, although the study was not powered sufficiently to detect differences in the secondary outcomes. Concerning AEs, three of the four SAEs (hospitalisation for worsening of the disease) reported were in arm C and 1 in arm B. '
That dose for me would be almost 100 mg/day. In the study above they also tested a lower dose closer to the FLCCC protocol dose and it performed even poorer in terms of viral load reduction. I realize this goes against some anecdotal reports, but while I do consider anecdotal evidence to have value, I lean toward the scientific evidence that can be reproduced in subsequent studies and so far I have only seen modest benefit with Ivermectin alone at various doses in terms of significant efficacy.
For a more recent perspective, this is a July, 2024 study that used a dose similar to the lower dose of the FLCCC protocol at .4 mg per kg/day :
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11264372/
Here is a relevant study quote :
'Although viral load showed a significant reduction, there was no significant difference in the clinical progression of the disease according to the WHO clinical progression scale during the 28-day follow-up in the two arms (Table (Table3).3). Similarly, no difference was observed in the progression of clinical symptoms experienced by the patients during the follow-up period in the two groups (Fig. (Fig.2).2). These included specific symptoms such as loss of smell and taste as well as constitutional and respiratory symptoms, most of which were resolved by day 28. Nausea and vomiting were observed more in the ivermectin arm (Fig. (Fig.2)2) any serious adverse events were not noted with ivermectin. One patient died due to the development of severe Covid-19 pneumonia who was in the ivermectin arm, but it was not considered related to ivermectin. '
IMO, all of the above results suggest to me that Ivermectin, like many of the treatments for Covid-19 are better suited for use alongside other drugs or supplements than as a stand alone treatment.
Regarding melatonin, very early on in the pandemic (April 18, 2020), I wrote a significant amount about its potential use for Covid-19 here :
https://www.earthclinic.com/melatonin-protocol-for-coronavirus.html
Studies since then have consistently shown that melatonin has multiple benefits in the treatment of SARS Cov-2 / Covid-19 and because of its multiple methods of action is likely to be beneficial for long covid also which I have written about here:
https://www.earthclinic.com/cures/supplements-for-long-covid.html
There are numerous studies showing the effectiveness of melatonin to reduce or prevent the use of a ventilator, to prevent covid pneumonia, to reduce hospital days required, significantly reduce symptoms and significantly reduce death from Covid-19 as well other health benefits.
Here is a more recent study (June 19, 2023) discussing melatonin and Covid-19 :
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10614475/
Here is a relevant quote from the link :
' The hormone melatonin works as an anti-inflammatory, antioxidant, immunomodulator, and strategically slows down the cytokine release which is observed in the COVID-19 disease, thereby improving the overall health of afflicted patients. The medical community is expected shortly to use remedial attributes like anti-inflammatory, antioxidant, antivirals, etc., of melatonin in the successful prevention and cure of COVID-19 morbidity. Thus, the administration of melatonin seems auspicious in the cure and prevention of this COVID-19 fatality. Moreover, melatonin does not seem to reduce the efficiency of approved vaccines against the SARS-CoV-2 virus. Melatonin increases the production of inflammatory cytokines and Th1 and enhances both humoral and cell-mediated responses. Through the enhanced humoral immunity, melatonin exhibits antiviral activities by suppressing multiple inflammatory products such as IL-6, IL1β, and tumor necrosis factor α, which are immediately released during lung injury of severe COVID-19. Hence, the novel use of melatonin along with other antivirals as an early treatment option against COVID-19 infection is suggested. Here, we have chalked out the invasion mechanisms and appropriate implications of the latest findings concerned with melatonin against the virus SARS-CoV-2. '
Imo, melatonin has the anecdotal reports and the backing science to establish itself as an important supplement for the treatment of Covid-19 as well as long covid. In my limited experience I have seen melatonin reverse mild to moderate Covid-19 in 3 days, similarly to what you reported.
Regarding avian bird flu (H5N1) Ivermectin may be worth considering, but data is scarce. Same with melatonin. Melatonin is thought to be beneficial via its known methods of action and has proven itself to prevent a cytokine storm which can be deadly.
Art
Replied By Paola (Usa) on 08/16/2024
Thank you for the quick answer. And regarding Monkey flu? Is there any preventive supplement that my husband and I can add to the 40 mg melatonin we take every night? Your suggestions will be much welcomed!! GraziePaola
Replied By Art (California) on 08/16/2024
Hi again, Paola,In my opinion, silver nanoparticles (AgNPs) are likely going to be helpful for both H5N1 and monkeypox, but I would not use it as an oral preventative because I don't think it is good to take it everyday in the long run, due to the potential for bacterial resistance. Oral AgNPs are likely best used during active infection and the earlier it is started the better. I can also inhale the AgNPs using a nebulizer or cold process vaporizer for specifically targeting the lungs. Obviously I would use melatonin simultaneously for its multiple methods of protective action to try and offset the negative health effects of viral diseases.
If I want to use AgNPs as a preventative for monkeypox virus or H5N1, I use it as a spray that you carry with you and use as I mentioned that I do for Covid-19, by spraying it up my nose, in my mouth and on my skin, if needed, whenever I am in crowded places where monkeypox or H5N1 can transfer from person to person. I carry a two ounce spray bottle in my pocket and it works well for me for these purposes.
The following article discusses the antiviral activity of AgNPs against various viruses :
https://www.sciencedirect.com/science/article/pii/S205566402300016X
Here is a relevant quote from the article :
' Recently, the antiviral activity of AgNPs against viruses such as HIV-1, 11, 12 hepatitis B, 13 herpes simplex, 14 respiratory syncytial, 15 and monkeypox16 has also been studied. Their primary antiviral mechanism is the physical inhibition of binding between the virus and the host cell. The dependence of antiviral activity on the size of AgNPs was observed for all the above viruses. For example, AgNPs less than 10 nm specifically inhibit HIV-1 infection.11 They exhibit anti-inflammatory, antiplatelet, and antiangiogenic activity17, 18, 19 and generally have a broad biological activity spectrum. Thus, AgNPs could potentially be used as antiviral drug with a wide range of action, minimum toxicity, and be capable of altering their mode of action during their interaction with various viruses. '
Note in the article above, they discuss a little bit about the particle size of AgNPs influencing their activity against specific viruses such as HIV. From everything I have read, particle size in the the 10 to 20 nm size is the range that will have the higher effectiveness against pathogens while being less toxic to normal cells. Particles smaller than 10 nm can be more effective against pathogens, but that size range is also more toxic toward normal cells. When the particle size goes above 25 nm, the toxicity of the AgNPs to pathogens decline the larger the particle size gets. So the particle size range in the 10 to 20 nm range is a more optimal size range for toxicity to pathogens and less toxicity to normal cells.
AgNPs have also shown significant activity against various influenza viruses.
I don't know if EC still sells AgNPs or not, but based on the color of their product in the yellow range as well as it being 20 PPM, it is likely to mainly be in the 10 to 20 nm particle size range.
Art
Replied By Paola (Usa) on 08/17/2024
Thank you again for your research. If I may suggest, you should start a new thread in EC with this info....here in Europe the first monkey pox case in a human has been recently detected, and everybody is searching for a valid natural supplement against this disease and also against the avian flu.arrivederci!!!
EC: We put Art's post in the Monkeypox page article yesterday. Thank you, Art!
Replied By Art (California) on 08/17/2024
Hi again, Paola.Thank you to EC for adding that to the monkey pox virus (MPV) list.
Regarding monkey pox virus MPV, it seems like it may come and go for awhile, so being prepared as is practical seems warranted.
One of the problems with MPV is that it also can make it possible for bacterial infections to get started while you are infected as discussed here :
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9685019/
Here is a relevant quote from the link :
' Secondary bacterial infection: most common, may include furuncle, carbuncle, cellulitis, abscess, necrotizing soft tissue infection, suppurative lymphadenitis, and posterior pharyngeal abscess. Sepsis (bloodstream infection) and septic shock can also occur.'
Given that the virus can replicate on the skin, the topical use of a potent antimicrobial such as colloidal silver (CS) may be useful, however the cost for colloidal silver in this situation may be a bit costly for those who don't make their own CS as frequent application may be needed to large areas of the body. In such a case, having another inexpensive antimicrobial option in place of topical CS would be highly desirable. Such an antimicrobial could be Boric Acid solution which is very inexpensive and easy to make. This could allow a person to conserve their CS for oral and nebulizer use, helping to keep costs minimal.
To make boric acid solution, I use one teaspoon of boric acid powder for every four ounces of distilled water. Simple and inexpensive. You can also put the solution in a spray bottle for easier topical application. You can also wet a towel with the solution to apply to a specific area and let the towel sit on the affected area to try and concentrate the antimicrobial activity. It is clear and colorless and does not stain clothing or bedding.
Here is a link to a typical powder product :
You can also use a weaker boric acid solution in the eyes, but I always use a store bought eye solution to help insure that it is sterile such as this :
Art
Replied By Paola (Italy - IT) on 08/22/2024
Thank you again for the useful info. If I may, a last question: What else besides melatonin would you recommend for avian flu?
Replied By Art (California) on 08/22/2024
Hi Paola,Another helpful supplement would be berberine as discussed here regarding the influenza A virus of which avian bird flu is a subtype :
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7150991/
Another supplement I would consider is a homeopathic remedy that I have had very good experience with for flu in general :
Art