Serotonin (due To Bacteria) Is The Master Regulator Of Metabolism, Insulin Sensitivity, And Weig

haidut

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Over the last year I posted a number of studies demonstrating strong link between serotonin and chronic conditions such as obesity, insulin resistance, and even diabetes.

Augmented capacity for peripheral serotonin release in human obesity
https://medicalxpress.com/news/2018-03-obesity-trigger-human-gut.html

However, when those studies came out the medical authorities immediately countered with the argument that it is not serotonin that is the culprit but changes in the microbiome that make the bacteria in our guts less "beneficial". This statement is strange in light of the numerous other studies demonstrating that there is no such thing as "beneficial" gut bacteria. Rather, there are only variations of harmfulness and any bacterial overgrowth has strong links to very serious conditions such as cancer, Alzheimer, Parkinson, CVD, etc.

https://www.mdlinx.com/allergy-immunology/top-medical-news/article/2019/04/16/7564232
The enemy within: Gut bacteria drive autoimmune disease
https://www.eurekalert.org/pub_releases/2019-03/fda-dut031919.php

Yet, behind our backs, Big Pharma has quietly been running clinical trials with drugs that inhibit gut serotonin synthesis as a way of treating obesity, diabetes, osteoporosis, etc.

Serotonin as a New Therapeutic Target for Diabetes Mellitus and Obesity
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6015967/
https://www.gastrojournal.org/article/S0016-5085(15)00714-3/fulltext
https://www.cell.com/trends/pharmacological-sciences/comments/S0165-6147(18)30056-7
https://www.nature.com/articles/nm.3797

So, once again, I see enough evidence to suggest malice instead of stupidity. It just works so well for the medical/food complex to sell us both the poison (toxic food and drugs) and the remedy (serotonin inhibitors). Well, the study below claims to finally put the questions on the role of serotonin in obesity/diabetes to rest. It demonstrates that sterilizing the guts of mice has the exact same protective effects on their metabolism/weight/health as inhibiting gut serotonin synthesis (with a TPH-1 inhibitor). Administering both the antibiotics and the serotonin synthesis inhibitors did NOT have additive effects, thus exposing serotonin as the direct pathological agent. As such, there is little doubt that the "happy hormone" is anything but. There is already a mountain of evidence sanctioned by Big Pharma implicating gut bacteria in virtually every psychiatric condition. Now, we can replace the convenient euphemisms such as "microbiome imbalance", "dysbiosis", "bacterial overgrowth", "SIBO", etc with a single word - SEROTONIN. Aside from estrogen, there is probably no other endogenous mediator of such importance for systemic health, and the sooner the profitable myths about these two chemicals collapse the better for the (literal) survival of humanity. Btw, mainstream media is complicit in these crimes against humanity. As readers can see from the the popular press articles, the wording is such that it creates a narrative as if there are somehow two forms of serotonin - "happy" (beneficial) and "unhappy" (harmful). This toxic and manipulative word game persists despite the fact that there is only one form of serotonin and the actual study clearly stating that (elevated) serotonin is pathological beyond any doubt.

https://www.pnas.org/content/early/2019/09/10/1909311116

"...An intraperitoneal (i.p.) glucose tolerance test (IPGTT) was used to examine the links between peripheral 5-HT and the gut microbiome on host glucose homoeostasis. Comparisons within the same animal over time were used to remove potentially confounding interanimal variance. Glucose tolerance was unchanged after 28 d in vehicle-treated control mice (Fig. 1A) but improved significantly in mice treated with LP533401 (Fig. 1B), Abx (Fig. 1C), or combined LP533401 and Abx treatment (Fig. 1D). Importantly, these positive effects of inhibiting 5-HT synthesis and antibiotic-associated microbiota perturbation on glucose tolerance were not additive, as seen using paired comparisons within each mouse over time (Fig. 1E), demonstrating their interdependence. Importantly, all treatments had similar effects in reducing both serum (Fig. 1F) and colonic mucosal (Fig. 1G) 5-HT levels. The effects of 5-HT inhibition and antibiotic-associated microbiota perturbation on glucose homeostasis are not due to differences in energy expenditure (Fig. 1H), substrate use (Fig. 1I), activity (Fig. 1J), or body weight (Fig. 1K)."

"...The outcomes of our study address a question which has long been unanswered. We used genetic and pharmacological models to provide evidence that gut-derived serotonin is the link through which the gut microbiome affects host glucose metabolism. The key evidence supporting this conclusion is that the combination of depleted EC cell 5-HT and gut antibiotic-associated microbiota perturbation did not show any additive effect compared to the individual treatments alone, demonstrating that the gut microbiome and EC cell 5-HT act via the same pathway to influence host glucose metabolism. If the microbiome were regulating host glucose homeostasis via another route, we would have seen improved glucose tolerance in the LP533401 + Abx group compared to Abx alone or in the Tph1−/− day 0 vs. day 28 comparisons. These impacts of antibiotic-associated microbiota perturbation in the presence or absence of gut-derived 5-HT on glucose handling are not driven by potentially confounding factors such as altered basal energy expenditure, physical activity, substrate use, or body weight."

https://medicalxpress.com/news/2019-09-gut-bacteria-negatively-blood-sugar.html

"...Serotonin, a neurotransmitter in the brain, is nicknamed the 'happy hormone' and is normally linked with regulating sleep, well-being and metabolism. But the gut actually produces 95 percent of it, and not in the happy form like we know about in the brain. In a study published in the leading international journal Proceedings of the National Academicy of Sciences (PNAS) today, researchers from Flinders, SAHMRI, and McMaster University in Canada show exactly how bacteria living in the guts of mice, the microbiome, communicate with cells producing serotonin to influence blood sugar levels in the host body. Professor Damien Keating, Head of Molecular and Cellular Physiology at Flinders University and Deputy Director of the Flinders Health and Mecical Research Institute, says this study sheds light on the unanswered question about exactly how bacteria in the microbiome communicate to control glucose levels in the metabolism. "We found that the microbiome worsens our metabolism by signalling to cells in the gut that produce serotonin. They drive up serotonin levels, which we previously showed to be increased in obese humans, and this rise in blood serotonin causes significant metabolic problems."
 

ScurveDream

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Kind of confusing how some of this info is conflated with supposed brain serotonin that influences criminal activity as is found in other studies.

This seems to suggest that serotonin and bacteria work in a symbiotic sort of way that creates likelihood of illness -- but the whole understanding of serotonin expressed here comes across more as psychological and physical than just the physical (like degenerative diseases and obesity).

I guess the whole serotonin role in the body and regarding not just diseases in particular but supposed behavior as well is just really complex (at least to me).

I wonder because it seems hard to deduce from examples of high serotonin and behaviors with just serotonin and, say, obesity but no particular impact on behavior that would possibly affect one's likelihood of crime/erratic behavior/etc. as other studies correlate it with.
 

Hildy

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Oct 2, 2019
Messages
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Over the last year I posted a number of studies demonstrating strong link between serotonin and chronic conditions such as obesity, insulin resistance, and even diabetes.

Augmented capacity for peripheral serotonin release in human obesity
https://medicalxpress.com/news/2018-03-obesity-trigger-human-gut.html

However, when those studies came out the medical authorities immediately countered with the argument that it is not serotonin that is the culprit but changes in the microbiome that make the bacteria in our guts less "beneficial". This statement is strange in light of the numerous other studies demonstrating that there is no such thing as "beneficial" gut bacteria. Rather, there are only variations of harmfulness and any bacterial overgrowth has strong links to very serious conditions such as cancer, Alzheimer, Parkinson, CVD, etc.

https://www.mdlinx.com/allergy-immunology/top-medical-news/article/2019/04/16/7564232
The enemy within: Gut bacteria drive autoimmune disease
https://www.eurekalert.org/pub_releases/2019-03/fda-dut031919.php

Yet, behind our backs, Big Pharma has quietly been running clinical trials with drugs that inhibit gut serotonin synthesis as a way of treating obesity, diabetes, osteoporosis, etc.

Serotonin as a New Therapeutic Target for Diabetes Mellitus and Obesity
Inhibition of Serotonin Synthesis Induces Negative Hepatic Lipid Balance
https://www.gastrojournal.org/article/S0016-5085(15)00714-3/fulltext
https://www.cell.com/trends/pharmacological-sciences/comments/S0165-6147(18)30056-7
Reducing peripheral serotonin turns up the heat in brown fat

So, once again, I see enough evidence to suggest malice instead of stupidity. It just works so well for the medical/food complex to sell us both the poison (toxic food and drugs) and the remedy (serotonin inhibitors). Well, the study below claims to finally put the questions on the role of serotonin in obesity/diabetes to rest. It demonstrates that sterilizing the guts of mice has the exact same protective effects on their metabolism/weight/health as inhibiting gut serotonin synthesis (with a TPH-1 inhibitor). Administering both the antibiotics and the serotonin synthesis inhibitors did NOT have additive effects, thus exposing serotonin as the direct pathological agent. As such, there is little doubt that the "happy hormone" is anything but. There is already a mountain of evidence sanctioned by Big Pharma implicating gut bacteria in virtually every psychiatric condition. Now, we can replace the convenient euphemisms such as "microbiome imbalance", "dysbiosis", "bacterial overgrowth", "SIBO", etc with a single word - SEROTONIN. Aside from estrogen, there is probably no other endogenous mediator of such importance for systemic health, and the sooner the profitable myths about these two chemicals collapse the better for the (literal) survival of humanity. Btw, mainstream media is complicit in these crimes against humanity. As readers can see from the the popular press articles, the wording is such that it creates a narrative as if there are somehow two forms of serotonin - "happy" (beneficial) and "unhappy" (harmful). This toxic and manipulative word game persists despite the fact that there is only one form of serotonin and the actual study clearly stating that (elevated) serotonin is pathological beyond any doubt.

The gut microbiome regulates host glucose homeostasis via peripheral serotonin

"...An intraperitoneal (i.p.) glucose tolerance test (IPGTT) was used to examine the links between peripheral 5-HT and the gut microbiome on host glucose homoeostasis. Comparisons within the same animal over time were used to remove potentially confounding interanimal variance. Glucose tolerance was unchanged after 28 d in vehicle-treated control mice (Fig. 1A) but improved significantly in mice treated with LP533401 (Fig. 1B), Abx (Fig. 1C), or combined LP533401 and Abx treatment (Fig. 1D). Importantly, these positive effects of inhibiting 5-HT synthesis and antibiotic-associated microbiota perturbation on glucose tolerance were not additive, as seen using paired comparisons within each mouse over time (Fig. 1E), demonstrating their interdependence. Importantly, all treatments had similar effects in reducing both serum (Fig. 1F) and colonic mucosal (Fig. 1G) 5-HT levels. The effects of 5-HT inhibition and antibiotic-associated microbiota perturbation on glucose homeostasis are not due to differences in energy expenditure (Fig. 1H), substrate use (Fig. 1I), activity (Fig. 1J), or body weight (Fig. 1K)."

"...The outcomes of our study address a question which has long been unanswered. We used genetic and pharmacological models to provide evidence that gut-derived serotonin is the link through which the gut microbiome affects host glucose metabolism. The key evidence supporting this conclusion is that the combination of depleted EC cell 5-HT and gut antibiotic-associated microbiota perturbation did not show any additive effect compared to the individual treatments alone, demonstrating that the gut microbiome and EC cell 5-HT act via the same pathway to influence host glucose metabolism. If the microbiome were regulating host glucose homeostasis via another route, we would have seen improved glucose tolerance in the LP533401 + Abx group compared to Abx alone or in the Tph1−/− day 0 vs. day 28 comparisons. These impacts of antibiotic-associated microbiota perturbation in the presence or absence of gut-derived 5-HT on glucose handling are not driven by potentially confounding factors such as altered basal energy expenditure, physical activity, substrate use, or body weight."

https://medicalxpress.com/news/2019-09-gut-bacteria-negatively-blood-sugar.html

"...Serotonin, a neurotransmitter in the brain, is nicknamed the 'happy hormone' and is normally linked with regulating sleep, well-being and metabolism. But the gut actually produces 95 percent of it, and not in the happy form like we know about in the brain. In a study published in the leading international journal Proceedings of the National Academicy of Sciences (PNAS) today, researchers from Flinders, SAHMRI, and McMaster University in Canada show exactly how bacteria living in the guts of mice, the microbiome, communicate with cells producing serotonin to influence blood sugar levels in the host body. Professor Damien Keating, Head of Molecular and Cellular Physiology at Flinders University and Deputy Director of the Flinders Health and Mecical Research Institute, says this study sheds light on the unanswered question about exactly how bacteria in the microbiome communicate to control glucose levels in the metabolism. "We found that the microbiome worsens our metabolism by signalling to cells in the gut that produce serotonin. They drive up serotonin levels, which we previously showed to be increased in obese humans, and this rise in blood serotonin causes significant metabolic problems."
As I haven't been on the forum that long, please pardon my ignorance.

Based on what you have written here, what then is the conclusion? Don't eat serotonin producing foods and take antibiotics in order to have a sterile gut so that you don't gain weight?

Help me out here.
Also, what is the role that probiotics play in this? Are they good or bad for the gut? I would think that specific strains of probiotics would be good as promoting a balance to the gut perhaps keeping the gut more "sterile"? Sterile in the sense that the good bacteria dominates over the bad bacteria.
 
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Broken man

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There is also study that mice without microbiota have thinner mucus inside intestines while mice with microbiota have thicker. I dont want to speculate here but I know about study that microbiota will adapt in hours to things that will pass into intestines. Also microbiota could help us with digestion of milk and gluten.
 

Sativa

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Based on what you have written here, what then is the conclusion? Don't eat serotonin producing foods and take antibiotics in order to have a sterile gut so that you don't gain weight?
...
Also, what is the role that probiotics play in this? Are they good or bad for the gut? I would think that specific strains of probiotics would be good as promoting a balance to the gut perhaps keeping the gut more "sterile"? Sterile in the sense that the good bacteria dominates over the bad bacteria.
There doesn't seem to be any 'good' / 'bad' bacteria - all seem to contribute to undesirable endotoxin, & as mentioned - serotonin production. Neither are desirable.
The implication is that anything that promotes bacterial growth - including pre/probotics would be undesirable.
Fermentable material would also contribute to bacterial growth.

There are, i'm sure, natural antibiotics which would help to reduce gut bacteria population.

The main 'nausea'-related serotonin receptor is called 5-HT3 and is present in large numbers in the gut. Excess serotonin will activate these 5-HT3 receptors, leading to undesirable effects.
5-HT3 receptors are involved in information transfer in the gastrointestinal tract, and in the enteric nervous system they regulate gut motility and peristalsis
Aside - many essential oils contain terpenes which block 5-HT3 (aka antagonists eg limonene; 1,8 cineole; pinene...)

BTW - I'm not specifically trying to solve a gut issue for myself, I just minimize my exposure to pro-bacterial growth foods, as a matter of 'sustainability', and continued vitality.
 

Hildy

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Messages
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As I haven't been on the forum that long, please pardon my ignorance.

Based on what you have written here, what then is the conclusion? Don't eat serotonin producing foods and take antibiotics in order to have a sterile gut so that you don't gain weight?

Help me out here.
There doesn't seem to be any 'good' / 'bad' bacteria - all seem to contribute to undesirable endotoxin, & as mentioned - serotonin production. Neither are desirable.
The implication is that anything that promotes bacterial growth - including pre/probotics would be undesirable.
Fermentable material would also contribute to bacterial growth.

There are, i'm sure, natural antibiotics which would help to reduce gut bacteria population.

The main 'nausea'-related serotonin receptor is called 5-HT3 and is present in large numbers in the gut. Excess serotonin will activate these 5-HT3 receptors, leading to undesirable effects.

Aside - many essential oils contain terpenes which block 5-HT3 (aka antagonists eg limonene; 1,8 cineole; pinene...)

BTW - I'm not specifically trying to solve a gut issue for myself, I just minimize my exposure to pro-bacterial growth foods, as a matter of 'sustainability', and continued vitality.
Well I know that oregano oil helped heal IBS. But I also took specific strains of probiotics afterwards and that helped as well.
You think all bacteria , good and bad, contribute to endotoxins? That would contradict what all the so called experts say about needing good probiotics bacteria via resistant starch.......I think.
 

Kartoffel

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@haidut When will we get LP533401 as SerotoNon?
 

Sativa

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You think all bacteria , good and bad, contribute to endotoxins? That would contradict what all the so called experts say about needing good probiotics bacteria via resistant starch.......I think

All bacteria produce endotoxin, yes. Haidut mentioned this somewhere else on the forum (i've mostly combed all his posts for relevant insights).
And yes, many perceived 'experts' are absolutely simply following the status quo/conventional perspective & interpretation. Many experts still claim that fish/omega oils are necessary, essential for biological vitality; yet as Ray impeccably details - this is not the case; in-fact it seems to be the opposite...
Personally, I have become my own authority, and learn the underlying mechanisms & dynamics so I can make up my own mind; i do not rely on the 2nd/3rd hand interpretations of so called 'experts'.
 

Sativa

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That's not true. Only gram-negative bacteria contain and release endotoxin.
Indeed, so no endotoxin from gram-positive bacteria, but they can trigger other seemingly undesirable processes.

Gram Positive Bacterial Compounds Are Capable Of Potentiating The Effects Of LPS
Gram Positive Bacterial Compounds Are Capable Of Potentiating The Effects Of LPS

Also:
Gram Positive Sepsis
Gram-positive Sepsis
"This article [reviews] the mechanisms by which gram-positive bacteria lead to septic shock, with regard to bacterial structure and toxicology and the host responses elicited both in animal models and in the clinical setting. Gram-positive organisms are better suited to invade host tissues and elicit, in general, a brisker phagocytic response than gram-negative organisms. The lack of endotoxin in the outer cell wall is compensated for by the presence of exposed peptidoglycan and a range of other toxic secreted products. It appears that cell wall components of gram-positive bacteria may signal via the same receptor as gram-negative endotoxin, although the type of signal and coreceptor may differ. Both animal and clinical data suggest that, unlike endotoxin-mediated shock, gram-positive infection produces a modest TNF response only and does not respond well to anti-TNF therapies. This leads one to conclude that the mechanisms leading to shock in gram-positive infection may be multifactorial and perhaps more difficult to treat."
@Hildy
"...I already posted a study showing that probiotics are dangerous and some doctors call for them to be regulated like drugs."
As Peat has written many times, there is truly no such thing as “beneficial” gut bacteria as long as they are capable of producing endotoxin (LPS). And since most bacterial species known to colonize the gut can produce LPS when exposed to undigested food or mechanical stimulation (stretching or even bouncing the intestine through say running), the conclusion that one could make is that all gut bacteria can be pathogenic. I already posted a study showing that probiotics are dangerous and some doctors call for them to be regulated like drugs.

The study below corroborates once again that gut bacteria is pathogenic, at least as far as liver cancer is concerned, and shows that administration of antibiotics (tetracyclines anyone?) is curative in the majority of the cases. Since vitamin K2 (MK-4) is expected to be approved soon for treating liver cancer (HCC) it suggests that it may have some antibiotic effects of its own.
 
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yerrag

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"We found that the microbiome worsens our metabolism by signalling to cells in the gut that produce serotonin. They drive up serotonin levels, which we previously showed to be increased in obese humans, and this rise in blood serotonin causes significant metabolic problems."

Ever since I started to use proteolytic enzymes to lyse away arterial and capillary plaque in an attempt to lower my blood pressure, over 6 months my weight has crept up on me from 150 to 165 lbs. It wasn't until I made the connection with endotoxins to serotonin that I realized what was causing me to gain weight. Endotoxins (as well as bacteria) were being released as plaque was being lysed. The rate of release is much more significant than when the endotoxin was being released by a recurring periodontal infection I had (which was latent and undetected over a period of close to twenty years, which is imho the cause of my hypertensive condition). I can say this only because during the time when I had periodontal infection, I didn't have a belly this large and my weight was normal without much effort on my part.

This would also explain why, in this period, I would experience hunger occasionally when I wouldn't all the years prior to using proteolytic enzymes. My sugar regulation mechanism, which was working well prior, has been put out of whack by serotonin.
 

yerrag

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Ever since I started to use proteolytic enzymes to lyse away arterial and capillary plaque in an attempt to lower my blood pressure, over 6 months my weight has crept up on me from 150 to 165 lbs. It wasn't until I made the connection with endotoxins to serotonin that I realized what was causing me to gain weight. Endotoxins (as well as bacteria) were being released as plaque was being lysed. The rate of release is much more significant than when the endotoxin was being released by a recurring periodontal infection I had (which was latent and undetected over a period of close to twenty years, which is imho the cause of my hypertensive condition). I can say this only because during the time when I had periodontal infection, I didn't have a belly this large and my weight was normal without much effort on my part.

This would also explain why, in this period, I would experience hunger occasionally when I wouldn't all the years prior to using proteolytic enzymes. My sugar regulation mechanism, which was working well prior, has been put out of whack by serotonin, as effected through endotoxins.
 

Kartoffel

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Indeed, so no endotoxin from gram-positive bacteria, but they can trigger other seemingly undesirable processes.

Gram Positive Bacterial Compounds Are Capable Of Potentiating The Effects Of LPS
Gram Positive Bacterial Compounds Are Capable Of Potentiating The Effects Of LPS

Also:
Gram Positive Sepsis
Gram-positive Sepsis

@Hildy
"...I already posted a study showing that probiotics are dangerous and some doctors call for them to be regulated like drugs."

I just wanted to clarify that they don't contain LPS. I also think the statement that all bacteria are bad is a bit of an over-generalization. Several gram-positive bacteria can be quite beneficial, not just because they are less bad than their gram-negative counterparts, but also because they actively fight many very harmful strains of other bacteria. For example, B.Subtilis (which Peat recommensd occasionally and has used himself) forms spores and produces substances that can kill off even pathogenic bacteria such as E.coli. I think it is good to have those around in your gut to prevent much more dangerous strains from taking over. I have used B.subtilis and B.Licheniformis, and I am quite happy with the results. Those can't be that bad, if people even go so far as to eat fresh camel dung in order to get them into their intestine.
 
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Sativa

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I think it is good to have those around in your gut to prevent much more dangerous strains from taking over.
For sure, I don't wish to come across like I am making any absolutist statements - there's are always indeed 2 sides to everything.
I am simply acting as a funnel for the comments/perspectives of others. (I don't have any vested interests in the outcome of the judgement on gram-+'ve bacteria)
 
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Sativa

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in a broader sense when shamans based 'toxins arising internally' in mind
Shamans you say?
Ok, so it's a parasite, but it for sure would lead to someone consuming plenty of mainstream pro-endotoxin foods!

Wetiko is an Algonquin word for a cannibalistic spirit that is driven by greed, excess, and selfish consumption.
It deludes its host into believing that cannibalizing the life-force of others (others in the broad sense, including animals and other forms of Gaian life) is a logical and morally upright way to live.
Wetiko short-circuits the individual’s ability to see itself as an enmeshed and interdependent part of a balanced environment and raises the self-serving ego to supremacy. It is this false separation of self from nature that makes this cannibalism, rather than simple murder.
Seeing Wetiko: On Capitalism, Mind Viruses, and Antidotes for a World in Transition – Kosmos Journal
 

Tarmander

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Cool study

However any attempt to alter gut flora to lose weight or increase metabolism still a crap shoot/individual basis.
 
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