Niclosamide reduces serotonin and glutamate
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@Mauritio its mostly inhibiting just the variant there (not normal androgen receptors) splice variants lack parts that de-activate them so continually active https://www.nature.com/articles/nrurol.2015.13
ironically depleting androgens in prostate cancer can induce more of them (and more significant amounts in the extracted cells part but idk how much they contribute)
https://aacrjournals.org/clincancerres/article/20/6/1590/211454/Rapid-Induction-of-Androgen-Receptor-SpliceAR-FL (normal receptors) arent getting inhibited much but AR- variants gone
|1 found mild estrogenic activity in vitro in cancered cell lines which doesnt match with the in vivo anti tumor activity,
but mainly on ERRy and ERRa estrogen related receptor, 30% max transcriptional activity of estradiol on estrogen receptors, (maybe displacing estrogens for milder effect lower transcription? but potent on ERRs in these cells)
,https://www.sciencedirect.com/science/article/abs/pii/S0300483X21001281
They found some hormone reducing effects in fish but idk how relevant to mammals
In adrenocortical cancer cells it reduced hormones production at nM concentration,
https://academic.oup.com/jcem/article/103/10/3706/5056322
- It has a mutagenic effect at higher end dose
humans show lymphocyte abnormalities from treatment at higher end dose. apparently its lethal in 100% of some strains of mice injected at low dose 7.5mg/kg. needs to be transformed in the gastrointestinal tract first & go through the liver https://pubmed.ncbi.nlm.nih.gov/3278217/
orally 60mg/kg ~300mg-400mg human dose starts to give a rise in abnormal sperm
its a mild effect there but thats only with 5 consecutive daysin humans the mutagenic effects on lymphocytes with 1g-2g for a day then 6 days of 500mg increased. (i'd guess red blood cells might be more vulnerable) doi: 10.1016/0165-7992(86)90015-1)
so to be on the safer side i wouldn't take >100mg of this regularly, 25mg has effects. and maybe good to have a few days off a week just incase.
@Mauritio said in Niclosamide reduces serotonin and glutamate:
Didn't you write something about cancer and pH? Niclosamide seems to affect that :
https://pubmed.ncbi.nlm.nih.gov/22474287/cool thanks , yeah lowering pH to a certain level helps make the apoptosis process more effective
"Self-organizing systems decay only if they have assimilated inertia, and — with a little support of the right kind— the centers of degeneration can become centers of regeneration."
"world," as a source of new perceptions
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@cs3000 ok thanks !
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@bio3nergetic if you look at the traffic it's all but dead anyway, let the pain go young warrior.
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@cs3000 said in Niclosamide reduces serotonin and glutamate:
and showing the anti fibrosis effect (reversed fibrosis / ED in penis of diabetic rats) https://academic.oup.com/jsm/article-abstract/21/12/1111/7822244?redirectedFrom=fulltext
"Both functional and molecular alterations in DMED were effectively reversed by Nic-treated diabetic rats without a glycemic alteration. Nic could be a promising candidate for the treatment of DMED due to its antifibrotic effects."The antifibrotic effect can be expected with ANY drug or substance antagonizing serotonin receptors. This has been well-established, even acknowledged by conventional medicine, though perhaps not as widely as we might hope. It has been known for at least 50 years that children suffering from cystic fibrosis, fibrosis, or liver disorders have significantly higher serotonin levels in their blood and central nervous system, coupled with a deficiency in monoamine oxidase A. The promotion of fibrosis is characteristic of 5-HT2A and 5-HT2B, and their hyperactivation leads to the expression of fibrosis-related genes.
In this study (https://www.sciencedirect.com/science/article/abs/pii/S2405457721000292), the effect of cyproheptadine on appetite in children with cystic fibrosis was evaluated, which unsurprisingly resulted in an increase in BMI. However, the researchers also noted a "mild improvement" in lung function, which they attributed to improved nutrition rather than to cyproheptadine's serotoninolytic action—something I believe is a misinterpretation.
I would recommend that anyone dealing with fibrosis-related issues adopt a diet that supports proper central serotonin regulation. I don’t believe that medication is always necessary in every case, although it can be a valuable tool. Serotonin is merely a signaling molecule, and regardless of how one views it, its canonical harmfulness is directly linked to its excessive signaling.
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Took 50mg niclosamide today . Resulted in strong fatigue and low energy. Hypoglycemia and hunger increases as well.
Probably better to take in the evening.Edit: i ate an insane amount of food yesterday and still woke up weighing exactly the same as the day before .
I also slept very well and feel refreshed. Maybe taking it in the last part of the day is more sustainable. The malaise I felt yesterday might also be some sort of microbial die off.Dare to think.
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@Mauritio said in Niclosamide reduces serotonin and glutamate:
Took 50mg niclosamide today . Resulted on strong fatigue and low energy. Hypoglycemia and hunger increase as well.
Probably better in the evening.Do you take thiamine? I recommend taking it, as niclosamide can uniquely activate AMPK and disrupt the proton gradient. Higher glucose intake will likely have a compensatory effect, but it does not guarantee that the redox balance will return to normal levels.
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@war4512 said in Niclosamide reduces serotonin and glutamate:
@Mauritio said in Niclosamide reduces serotonin and glutamate:
Took 50mg niclosamide today . Resulted on strong fatigue and low energy. Hypoglycemia and hunger increase as well.
Probably better in the evening.Do you take thiamine? I recommend taking it, as niclosamide can uniquely activate AMPK and disrupt the proton gradient. Higher glucose intake will likely have a compensatory effect, but it does not guarantee that the redox balance will return to normal levels.
I only take whatever is in a few drops ofEnergin.
l noticed thatmy Buteyko Pause increased significantly,meaning I could hold my breath longer. It seems to increaseCO2 not sure if via uncoupling or another mechanism. I suspect it might be a carbonic anhydrase inhibitor similarly to acetozolamide and Aspirin.next time ill probably try a snaller dose to avoid hypoglycemia.
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I might have to change my opinion on Niclosamide. Today I woke up weighing 850g less! So not only did it not lead to weight gain when binging the same day, butit lead to drastic weight loss the next day.
The effects seemed to last quite long. As I felt warmer the day after and as I said sleep was great as well.
It seems to good for liver fuction. So maybe I'll do small (~ 25mg), infrequent doses for liver health regularly.Dare to think.
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They're catching up! They're using A combo of niclosamide and acetazolamide to treat cancer.
https://pmc.ncbi.nlm.nih.gov/articles/PMC10214212/ -
https://www.mdpi.com/2073-4425/14/12/2196
The weight loss is likely due to glycogen depletion and the water associated with it. What's worse, the use of niclosamide has been observed to lower CO2 levels and increase LDH levels. This makes the use of carbonic anhydrase inhibitors even more justified when taking niclosamide.
..Meanwhile, exposure to NIC resulted in a decrease in the liver glucose (Glu) level, gut cholesterol (CHO), and glycogen (Gln) and triglyceride (TG) content in all examined tissues. Conversely, it led to an increase in tissue lactic acid (LA) and acetyl-CoA levels, as well as LDH activity."
,,It is hypothesized that NIC has the ability to disrupt the process of mitochondrial oxidative phosphorylation via uncoupling. In the case of tapeworms (Cotugnia digonopora), exposure to NIC led to the accumulation of lactate, decreased production of CO2, and reduced glycogen levels, indicating a potential impairment in aerobic ATP synthesis"
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@war4512 I’ll read more about niclosamide today because it seems to me that a single study is not necessarily conclusive on this matter. Especially since it was a study conducted on carp.
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@war4512 said in Niclosamide reduces serotonin and glutamate:
@war4512 I’ll read more about niclosamide today because it seems to me that a single study is not necessarily conclusive on this matter. Especially since it was a study conducted on carp.
Agreed.
Of course there is glycogen depletion at first when you increase your metabolism. But if that was the cause the weight loss would have shown the next day and not the day after that . Plus glycogen is quickly refilled when having meals.The opposite of what you said concerning glycogen might even be what's happening.
Subjectively I notice that I can go alittle longer between meals and my muscles look fulller.The paragraph you quoted merely describes how niclosamide kills parasites.
Yes that happens through uncoupling, and yes if we uncoupled our metabolism too much we would die too (ever heard of DNP?) .
That does not make physhological ucoupling unhealthy . the lowering of ATP is made up for by increases in temperature and metabolism and reduction in oxidative stress.I suggest you read about the basics and benefits of uncoupling and their effects on humans. Georgi has a lot of good content on that.
Dare to think.
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@Mauritio said in Niclosamide reduces serotonin and glutamate:
Of course there is glycogen depletion at first when you increase your metabolism. But if that was the cause the weight loss would have shown the next day and not the day after that . Plus glycogen is quickly refilled when having meals.
Well, if you've noticed that your muscles are fuller, it’s probably because you are compensatorily consuming large amounts of glucose. T3 also has some ability to reduce glycogen, but this depends on the dose and metabolism. When I take thyroid hormones, I also notice that I’m fuller, but that’s because I consume around 600/700g of carbohydrates a day, which has a compensatory effect.
@Mauritio said in Niclosamide reduces serotonin and glutamate:
I suggest you read about the basics and benefits of uncoupling and their effects on humans. Georgi has a lot of good content on that.
I’m familiar with the process of uncoupling. It’s an extraordinary mechanism, but as I mentioned, it depends on the substance or another physiological factor that induces it. PUFA, for example, also promote uncoupling, but through PPAR-gamma, impairing biogenesis, which T3 does not do. However, if there is a noticeable increase in lactate, it is probably related to limiting OxPHOS, resulting in increased glycolysis.
@Mauritio said in Niclosamide reduces serotonin and glutamate:
The paragraph you quoted merely describes how niclosamide kills parasites.
Yes that happens through uncoupling, and yes if we uncoupled our metabolism too much we would die too (ever heard of DNP?) .I fully agree, however, the pharmacological action of niclosamide on parasites should also have systemic effects. I didn’t say that mitochondrial uncoupling is bad – it depends on the substance that causes it. For example, T3 also uncouples mitochondria, but it has a beneficial effect. There are also uncoupling substances that cause negative symptoms.
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@war4512 said in Niclosamide reduces serotonin and glutamate:
Well, if you've noticed that your muscles are fuller, it’s probably because you are compensatorily consuming large amounts of glucose.
As i said susected its probably from higher glycogen synthesis, which was almost twice as high.
"Moreover, the NEN-treated mice exhibited higher glycogen synthesis rates (Table 1), which were further confirmed by a direct measurement of glycogen synthesis showing higher rates in both liver and muscle (data not shown)."
https://pmc.ncbi.nlm.nih.gov/articles/PMC4299950/ -
Here are a few resources for further reading on uncoupling
"When mitochondria are “uncoupled,” they produce more carbon dioxide than normal, and the mitochondria produce fewer free radicals. Animals with uncoupled mitochondria live longer than animals with the ordinary, more efficient mitochondria, that produce more reactive oxidative fragments. One effect of the high rate of oxidation of the uncoupled mitochondria is that they can eliminate polyunsatured fatty acids that might otherwise be integrated into tissue structures, or function as inappropriate regulatory signals."
Ray Peathttps://lowtoxinforum.com/threads/vos-uncoupling-thread.5037/
https://lowtoxinforum.com/threads/uncoupling-increases-t3.40540/
