How serotonin is the primary driver of digestive problems (and how to address it)

Joined
Mar 28, 2021
Messages
53
I had absolutely debilitating digestive problems for years. I went to all of the “top GI docs'' and they had NO answers. They said we don’t know what’s wrong with you. One even told me it was all in my head. Take pill, drink water, eat fiber, take probiotics, etc.

I was furious. I even tried some of these “expert recommendations” and they made my gut even worse. I was absolutely miserable. Imagine the worst stomach ache or vomiting episode you’ve ever had. Now imagine that nonstop for around 2.5 years. That was me.

I later learned that I was not alone. This one study is remarkable, showing that people with GI problems and brain fog (often go hand in hand) would often take probiotics. But getting them off of the probiotics and giving them antibiotics cured them:

Not just nausea though. ZERO appetite even if I fasted for days. Didn’t defecate for weeks at a time. Acid reflux. Inconceivable bloating. I remember after Thanksgiving seeing my pregnant looking belly in the mirror and starting to cry.
Fortunately, I stumbled upon the right information (Danny's youtube)

I had read about people with similar issues who took a drug called cyproheptadine, an anti-serotonin, antihistamine drug. I wasn’t too keen on pharmaceuticals but at this point I was desperate. So I tried it. The results were absolutely stunning. I had a near complete reversal of ALL symptoms.

I became pretty obsessed with this topic and wanted to learn all there was to know.
I wanted my gut to feel like that all the time, without constantly using cyproheptadine.
I found out that serotonin is elevated in the gut of every GI disease.
Is this overlooked? Or intentionally dismissed by the media?

Well NO, it’s not overlooked. In fact, big pharma tried running clinical trials for a drug that inhibits serotonin synthesis for IBS behind your back. In the meantime, your GI doc has been giving you an SSRI. We already know why this is the case:
View: https://twitter.com/Outdoctrination/status/1677349779163029516


Cyproheptadine has a near curative effect on GI problems in the literature. Ondansetron is a highly efficacious anti-nausea drug, which also blocks serotonin. Meanwhile, to induce IBS in an animal, give them the genetic equivalent of an SSRI.

Serotonin's role in the gut is to trigger the necessary response to irritation or pathogens. This involves stimulating motility to rid the pathogen, pain/sensitization of the area and a lack of appetite to discourage further eating.

Excess bacteria, whether labeled good or bad (even those WITHOUT endotoxin), can stimulate serotonin production in the gut. Antigens on bacteria trigger inflammatory cascades, resulting in increased serotonin. Constipation, leading to bacterial buildup, is a huge issue here.

One way that has been extremely useful for me in diagnosing these issues is looking at the tongue. The tongue should be a vibrant pink, almost red, in good health. Saliva production should be strong. When bacterial issues arise, the tongue gets a white coating, especially in the back.

What most may not understand is that the mouth to the anus is really one long track, and thus bacterial issues in the intestines can cause not just white tongue, but other dental problems like bad breath and even cavities. I still use my tongue to guide what I should do on a day to day basis.

Serotonin can bind to mast (immune) cells, which can in turn release histamine. It’s been hypothesized that histamine intolerance actually starts in the gut. This goes both ways, antihistamines also tend to lower serotonin, and diamine oxidase supplementation shows some promise.

Any type of fiber can promote serotonin production. Soluble fiber feeds bacteria, and insoluble fiber acts as an irritating agent. Other irritants like gums and dyes can cause gut serotonin levels to rise. The short chain fatty acids produced by the microbial fermentation of soluble fibers also drive serotonin production in the gut.

Low or no fiber can CURE many of these problems. IBS patients consistently improve massively from no fiber diets. Again, I think this is because these problems often result from excess bacteria/serotonin, which fiber directly contributes to.

Many people do benefit specifically from insoluble fiber (raw carrot). I think this is mainly due to the pro-motility effect, and the fact that they actually lower the bacterial load over time. However, insoluble fiber by definition works as an irritant. In fact, you can replace insoluble fiber with plastic and get similar results
View: https://twitter.com/Outdoctrination/status/1607786778060279813?s=20


In severe cases (like mine), pharmaceutical antibiotics may be necessary. Docs often like to give very high doses of toxic antibiotics. However, at low doses, using older types of antibiotics and listening to your body, can have some incredible effects. It’s something worth considering [NOT MEDICAL ADVICE].

Natural laxatives like coffee or Cascara are helpful for alleviating constipation by stimulating motility, as well as ensuring adequate magnesium intake.
Gentler antibacterial agents like raw honey, white button mushrooms, coconut oil, vinegar and mastic can be beneficial. Cop some mastic gum here: Mastic Droplets

Not only does this gum have antibacterial effects (always cleans up my tongue), it is also pro-motility and thus increases bowel movements, and increases saliva output, our endogenous antimicrobial. Motility is slowed in all types of gut problems, even diarrhea.

Poor stool quality/infrequent movements lead to incomplete bacterial elimination and thus excess serotonin. This can become a vicious cycle, as bacteria use serotonin as a signaling molecule, enhancing their virulence through biofilm formation. Focusing on this in the long term has been CRUCIAL for me
View: https://twitter.com/Outdoctrination/status/1553386855126671365?s=20


One thing that has helped me tremendously in inducing more frequent and healthier bowel movements has been focusing on relaxation, breathing and movement. I cover that here:
View: https://twitter.com/Outdoctrination/status/1657019737908592640?s=20


Vitamins A, D, and zinc inhibit TPH, the key enzyme responsible for serotonin synthesis. All of the fat soluble vitamins also have direct antimicrobial properties. K2 has been vital for me personally. Health Natura has the highest quality fat soluble vitamins I know of, individually or as a mix: Products - Liquid Vitamins - healthnatura.com

Bacterial issues can especially arise when gut metabolism is suboptimal, and thus oxygen is not used for energy, and instead leaks into the gut. Higher oxygen environments foster the growth of more / more pathogenic gut bacteria, and this is seen in every GI disease.

A lack of allopregnanolone (a primary metabolite of pregnenolone) and/or DHT, is known to induce gut problems via serotonin increase. Allopregnanolone reverses this effect. You can cop some pregnenolone here, again the one I use: Pregnenolone 20 grams

Dopamine inhibits serotonin synthesis and promotes colonic motility. We’ve touched more on that here:
View: https://twitter.com/Outdoctrination/status/1659949243598245888?s=20


Of course, there are also antiserotonin drugs. Cyproheptadine played an absolutely huge role in my recovery from debilitating gut problems. Some other antiserotonin agents are L-Lysine, methysergide, metergoline, LSD, ketanserin, and ondansetron. [NOT MEDICAL ADVICE]

The serotonin transporter relies on sodium to pull serotonin into cells and deactivate it, and consequently low salt diets increase serotonin. Lower salt diets also impair insulin sensitivity and can raise cortisol. Insulin helps dampen serotonin signaling, while cortisol promotes serotonergic function. Salt Loading Affects Cortisol Metabolism in Normotensive Subjects: Relationships with Salt Sensitivity

Fasting actually increases serotonin levels in the gut and systemically. One of the ways it might do this is by increasing cortisol and its precursor, CRH. Again, pregnenolone has been massive for me in this regard as it is our endogenous anti-CRH steroid. https://twitter.com/Outdoctrination/status/1671525436172513286

This hit home for me big time because my issues STARTED after a lot of fasting and carnivore dieting. I get that it may help in certain situations, but I wouldn’t personally advocate for such an approach.

Some foods contain serotonin, but I wouldn’t worry too much about this, at least to start. Same goes for tryptophan, the serotonin precursor amino acid. It may help in really bad circumstances, but to me, there’s much bigger fish to fry.
 

Jam

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Excellent post.
 

Greg says

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I had absolutely debilitating digestive problems for years. I went to all of the “top GI docs'' and they had NO answers. They said we don’t know what’s wrong with you. One even told me it was all in my head. Take pill, drink water, eat fiber, take probiotics, etc.

I was furious. I even tried some of these “expert recommendations” and they made my gut even worse. I was absolutely miserable. Imagine the worst stomach ache or vomiting episode you’ve ever had. Now imagine that nonstop for around 2.5 years. That was me.

I later learned that I was not alone. This one study is remarkable, showing that people with GI problems and brain fog (often go hand in hand) would often take probiotics. But getting them off of the probiotics and giving them antibiotics cured them:

Not just nausea though. ZERO appetite even if I fasted for days. Didn’t defecate for weeks at a time. Acid reflux. Inconceivable bloating. I remember after Thanksgiving seeing my pregnant looking belly in the mirror and starting to cry.
Fortunately, I stumbled upon the right information (Danny's youtube)

I had read about people with similar issues who took a drug called cyproheptadine, an anti-serotonin, antihistamine drug. I wasn’t too keen on pharmaceuticals but at this point I was desperate. So I tried it. The results were absolutely stunning. I had a near complete reversal of ALL symptoms.

I became pretty obsessed with this topic and wanted to learn all there was to know.
I wanted my gut to feel like that all the time, without constantly using cyproheptadine.
I found out that serotonin is elevated in the gut of every GI disease.
Is this overlooked? Or intentionally dismissed by the media?

Well NO, it’s not overlooked. In fact, big pharma tried running clinical trials for a drug that inhibits serotonin synthesis for IBS behind your back. In the meantime, your GI doc has been giving you an SSRI. We already know why this is the case:
View: https://twitter.com/Outdoctrination/status/1677349779163029516


Cyproheptadine has a near curative effect on GI problems in the literature. Ondansetron is a highly efficacious anti-nausea drug, which also blocks serotonin. Meanwhile, to induce IBS in an animal, give them the genetic equivalent of an SSRI.

Serotonin's role in the gut is to trigger the necessary response to irritation or pathogens. This involves stimulating motility to rid the pathogen, pain/sensitization of the area and a lack of appetite to discourage further eating.

Excess bacteria, whether labeled good or bad (even those WITHOUT endotoxin), can stimulate serotonin production in the gut. Antigens on bacteria trigger inflammatory cascades, resulting in increased serotonin. Constipation, leading to bacterial buildup, is a huge issue here.

One way that has been extremely useful for me in diagnosing these issues is looking at the tongue. The tongue should be a vibrant pink, almost red, in good health. Saliva production should be strong. When bacterial issues arise, the tongue gets a white coating, especially in the back.

What most may not understand is that the mouth to the anus is really one long track, and thus bacterial issues in the intestines can cause not just white tongue, but other dental problems like bad breath and even cavities. I still use my tongue to guide what I should do on a day to day basis.

Serotonin can bind to mast (immune) cells, which can in turn release histamine. It’s been hypothesized that histamine intolerance actually starts in the gut. This goes both ways, antihistamines also tend to lower serotonin, and diamine oxidase supplementation shows some promise.

Any type of fiber can promote serotonin production. Soluble fiber feeds bacteria, and insoluble fiber acts as an irritating agent. Other irritants like gums and dyes can cause gut serotonin levels to rise. The short chain fatty acids produced by the microbial fermentation of soluble fibers also drive serotonin production in the gut.

Low or no fiber can CURE many of these problems. IBS patients consistently improve massively from no fiber diets. Again, I think this is because these problems often result from excess bacteria/serotonin, which fiber directly contributes to.

Many people do benefit specifically from insoluble fiber (raw carrot). I think this is mainly due to the pro-motility effect, and the fact that they actually lower the bacterial load over time. However, insoluble fiber by definition works as an irritant. In fact, you can replace insoluble fiber with plastic and get similar results
View: https://twitter.com/Outdoctrination/status/1607786778060279813?s=20


In severe cases (like mine), pharmaceutical antibiotics may be necessary. Docs often like to give very high doses of toxic antibiotics. However, at low doses, using older types of antibiotics and listening to your body, can have some incredible effects. It’s something worth considering [NOT MEDICAL ADVICE].

Natural laxatives like coffee or Cascara are helpful for alleviating constipation by stimulating motility, as well as ensuring adequate magnesium intake.
Gentler antibacterial agents like raw honey, white button mushrooms, coconut oil, vinegar and mastic can be beneficial. Cop some mastic gum here: Mastic Droplets

Not only does this gum have antibacterial effects (always cleans up my tongue), it is also pro-motility and thus increases bowel movements, and increases saliva output, our endogenous antimicrobial. Motility is slowed in all types of gut problems, even diarrhea.

Poor stool quality/infrequent movements lead to incomplete bacterial elimination and thus excess serotonin. This can become a vicious cycle, as bacteria use serotonin as a signaling molecule, enhancing their virulence through biofilm formation. Focusing on this in the long term has been CRUCIAL for me
View: https://twitter.com/Outdoctrination/status/1553386855126671365?s=20


One thing that has helped me tremendously in inducing more frequent and healthier bowel movements has been focusing on relaxation, breathing and movement. I cover that here:
View: https://twitter.com/Outdoctrination/status/1657019737908592640?s=20


Vitamins A, D, and zinc inhibit TPH, the key enzyme responsible for serotonin synthesis. All of the fat soluble vitamins also have direct antimicrobial properties. K2 has been vital for me personally. Health Natura has the highest quality fat soluble vitamins I know of, individually or as a mix: Products - Liquid Vitamins - healthnatura.com

Bacterial issues can especially arise when gut metabolism is suboptimal, and thus oxygen is not used for energy, and instead leaks into the gut. Higher oxygen environments foster the growth of more / more pathogenic gut bacteria, and this is seen in every GI disease.

A lack of allopregnanolone (a primary metabolite of pregnenolone) and/or DHT, is known to induce gut problems via serotonin increase. Allopregnanolone reverses this effect. You can cop some pregnenolone here, again the one I use: Pregnenolone 20 grams

Dopamine inhibits serotonin synthesis and promotes colonic motility. We’ve touched more on that here:
View: https://twitter.com/Outdoctrination/status/1659949243598245888?s=20


Of course, there are also antiserotonin drugs. Cyproheptadine played an absolutely huge role in my recovery from debilitating gut problems. Some other antiserotonin agents are L-Lysine, methysergide, metergoline, LSD, ketanserin, and ondansetron. [NOT MEDICAL ADVICE]

The serotonin transporter relies on sodium to pull serotonin into cells and deactivate it, and consequently low salt diets increase serotonin. Lower salt diets also impair insulin sensitivity and can raise cortisol. Insulin helps dampen serotonin signaling, while cortisol promotes serotonergic function. Salt Loading Affects Cortisol Metabolism in Normotensive Subjects: Relationships with Salt Sensitivity

Fasting actually increases serotonin levels in the gut and systemically. One of the ways it might do this is by increasing cortisol and its precursor, CRH. Again, pregnenolone has been massive for me in this regard as it is our endogenous anti-CRH steroid. https://twitter.com/Outdoctrination/status/1671525436172513286

This hit home for me big time because my issues STARTED after a lot of fasting and carnivore dieting. I get that it may help in certain situations, but I wouldn’t personally advocate for such an approach.

Some foods contain serotonin, but I wouldn’t worry too much about this, at least to start. Same goes for tryptophan, the serotonin precursor amino acid. It may help in really bad circumstances, but to me, there’s much bigger fish to fry.

Thiamine deficiency maybe the underlying cause.
 

Daniel North

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My key takeaways is this:
"serotonin is the primary driver of digestive problems"


"Serotonin's role in the gut is to trigger the necessary response to irritation or pathogens."

"Vitamins A, D, and zinc inhibit TPH, the key enzyme responsible for serotonin synthesis."

"A lack of allopregnanolone (a primary metabolite of pregnenolone) and/or DHT, is known to induce gut problems via serotonin increase."

"Dopamine inhibits serotonin synthesis and promotes colonic motility. "
Wow:
"The serotonin transporter relies on sodium to pull serotonin into cells and deactivate it, and consequently low salt diets increase serotonin. "

"Fasting actually increases serotonin levels in the gut and systemically. One of the ways it might do this is by increasing cortisol and its precursor, CRH. "

"Some foods contain serotonin, but I wouldn’t worry too much about this, at least to start. Same goes for tryptophan, the serotonin precursor amino acid. It may help in really bad circumstances, but to me, there’s much bigger fish to fry."
 

hierundjetzt

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@Outdoctrination: how much cyproheptadine did you take and for how long? I've tried small (0.5mg) as well as medium (8mg) doses at night and the next day I'm always a zombie...
 

Roni123@

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very low fat, high carb and no fiber ? and high choline? the Tim berzis recomend very high carb, medium protein and very very low fat (-50g) and high choline to improve glycogen in liver.... and says the fat is the number one endotoxin promoter, what your opinion?

no gluten and alchool...

(my english is bad)

only starch for carbs*
 

Sampa

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Such great info.
Can you please elaborate more on antibiotic selection ?
 

mostlylurking

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youngsinatra

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I think serotonin is a big part of the mechanism, how digestive issues affect the entire body - especially the so called gut-brain axis.

I always notice better mood and improved mental capabilities when I eat non-irritating foods.

I usually eat primarily meat and white rice, but for dessert I usually have fruit. I recently started eating cooked (or microwaved) instead of raw fruit like cooked apples, pears, bananas, berries, cherries and found out that I tolerate those much better and have better overall well-being.

But there was a time where I had terrible digestion even with a almost no-fiber diet at all. I used to take penicillin to clear my chronic SIBO, but it did not resolve and always came back. I think that’s because I did not address other issues with my overall digestion system like impaired bile flow, low HCL, low digestive enzyme production and so on.

I needed to improve those before real significant improvements could be made with digestion. I think good amounts of HCL and bile are our endogenously made disinfectants for the bowels, but if those get low, bacterial overgrowth and dysbiosis is always the consequence and it does not resolve by just taking antibiotics.

I personally don’t recommend antibiotics, except when really needed, because they have been consistently associated with a significantly increased risk for developing psychiatric diseases like anxiety and depression. (5 or more rounds of penicillin in a life time is associated with an almost 50% increased risk of developing depression and anxiety)

 

Don

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I think serotonin is a big part of the mechanism, how digestive issues affect the entire body - especially the so called gut-brain axis.

I always notice better mood and improved mental capabilities when I eat non-irritating foods.

I usually eat primarily meat and white rice, but for dessert I usually have fruit. I recently started eating cooked (or microwaved) instead of raw fruit like cooked apples, pears, bananas, berries, cherries and found out that I tolerate those much better and have better overall well-being.

But there was a time where I had terrible digestion even with a almost no-fiber diet at all. I used to take penicillin to clear my chronic SIBO, but it did not resolve and always came back. I think that’s because I did not address other issues with my overall digestion system like impaired bile flow, low HCL, low digestive enzyme production and so on.

I needed to improve those before real significant improvements could be made with digestion. I think good amounts of HCL and bile are our endogenously made disinfectants for the bowels, but if those get low, bacterial overgrowth and dysbiosis is always the consequence and it does not resolve by just taking antibiotics.

I personally don’t recommend antibiotics, except when really needed, because they have been consistently associated with a significantly increased risk for developing psychiatric diseases like anxiety and depression. (5 or more rounds of penicillin in a life time is associated with an almost 50% increased risk of developing depression and anxiety)

Thanks that last bit is interesting !
 

Peatress

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A large carbohydrate meal increases the ratio of tryptophan to the competing amino acids, and it has been proposed that this can shift the body’s balance toward increased serotonin. In an animal study, bromocriptine, which shifts the balance away from serotonin, reduced obesity and insulin and free fatty acids, and improved glucose tolerance. Ray Peat
 

ChadGPT

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But there was a time where I had terrible digestion even with a almost no-fiber diet at all. I used to take penicillin to clear my chronic SIBO, but it did not resolve and always came back. I think that’s because I did not address other issues with my overall digestion system like impaired bile flow, low HCL, low digestive enzyme production and so on.
How did you fix these things?
 
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