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Prostate Enlargement (BPH) May Be Due To Endotoxin

haidut

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BPH is a very common problem, apparently affecting more than 70%of men over 50. Ray has said in some email exchanges that prostatitis and BPH are linked with endotoxin. I was not able to find much published research on the topic but this new study finally makes that claim. What is more important, blocking the endotoxin "receptor" TLR4 may treat BPH and even prevent it from happening. Niacinamide and emodin are two of the most well-known TLR4 antagonists.
Of note is that the study also found strong associations between TLR4 expression and BMI, and PSA. So, endotoxin makes you fat and balloons your prostate.

LPS/TLR4 Signaling Enhances TGF-β Response Through Downregulating BAMBI During Prostatic Hyperplasia : Scientific Reports
Inhibition of TLR4 Signaling May Decrease BPH Chronic Inflammation, According to Study - BPH News

"...Novel therapeutic targeting of TLR4 signaling pathway may halt chronic inflammation leading to benign prostate hyperplasia (BPH), according to a study, “LPS/TLR4 Signaling Enhances TGF-β Response Through Downregulating BAMBI During Prostatic Hyperplasia,” published in the journal Scientific Reports."

"...The transforming growth factor-β1 (TGF-β1) cytokine is a strong extracellular inducer of EMT and it was shown to induce EMT phenotypes in prostatic epithelial cells. In follow-up studies, researchers found that TGF-β1 expression was increased with LPS treatment. LPS, short for lipopolysaccharide, is the major component of the outer membrane of Gram-negative bacteria. Researchers also observed that injection of LPS into rat prostates leads to an EMT phenotype."

"...Researchers analyzed TLR4 expression in BPH tissues with inflammation, and found it to be significantly higher, when compared to BPH tissues without inflammation. Correlation studies also suggested TLR4 expression (at the level of messenger RNA) associated with age, BMI, serum PSA levels, urgency and nocturia in the inflammatory group. In conclusion, these results suggest a link between prostatic hyperplasia and inflammation mediated by modulation of TGF-β induced EMT by LPS/TLR4 axis. Therefore, therapeutic targeting of TLR4 signaling may benefit BPH patients."
 

Nighteyes

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Would good old cyproheptadine help in this regards as well? Not sure if it acts on TLR4 directly though.
 

haidut

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Would good old cyproheptadine help in this regards as well? Not sure if it acts on TLR4 directly though.

I think it would work. The Wiki page lists mianserin as a known antagonist but other drugs with similar structure like cyproheptadine should work as well.
 
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a drop of progest-e on the scrotum works wonders.

I think high estrogen plays a part. Of course, estrogen may be brought on by endotoxins.

Also, high CO2 levels in the body shrink the prostate.

I think the whole idea of BPH is wrong. Prostates aren't static. They can swell up and shrink down pretty quickly, I think.
 

jyb

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BPH is a very common problem, apparently affecting more than 70%of men over 50. Ray has said in some email exchanges that prostatitis and BPH are linked with endotoxin. I was not able to find much published research on the topic but this new study finally makes that claim. What is more important, blocking the endotoxin "receptor" TLR4 may treat BPH and even prevent it from happening. Niacinamide and emodin are two of the most well-known TLR4 antagonists.
Of note is that the study also found strong associations between TLR4 expression and BMI, and PSA. So, endotoxin makes you fat and balloons your prostate.

That's to reduce the inflammation due to endotoxin, but what about the root of the problem - why is there endotoxin in the first place? Lower gut integrity? I'd like to know. Chicken and egg problem, I guess.
 

haidut

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That's to reduce the inflammation due to endotoxin, but what about the root of the problem - why is there endotoxin in the first place? Lower gut integrity? I'd like to know. Chicken and egg problem, I guess.

Endotoxin is there because of the bacteria in the gut, and that bacteria being fed on resistant starch and other undigested food. So, no starch or resistant starch in the diet should greatly limit the endotoxin produced. Also, avoiding things that activate the TLR4 like alcohol and even acetic acid would also help. And for the more adventurous, keeping the gut clean with antibiotics could provide even more drastic reductions in endotoxin levels. But given all the other chemicals that activate TLR4 I think it is more important to be aware of those activators and keep endotoxin low with diet vs. trying to kill the bacteria completely as it won't solve the problem completely.
Finally, keeping metabolic rate high ensures good levels of gastric acid which reduces the amount of undigested food reaching the colon.
 

jyb

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Endotoxin is there because of the bacteria in the gut, and that bacteria being fed on resistant starch and other undigested food. So, no starch or resistant starch in the diet should greatly limit the endotoxin produced. Also, avoiding things that activate the TLR4 like alcohol and even acetic acid would also help. And for the more adventurous, keeping the gut clean with antibiotics could provide even more drastic reductions in endotoxin levels. But given all the other chemicals that activate TLR4 I think it is more important to be aware of those activators and keep endotoxin low with diet vs. trying to kill the bacteria completely as it won't solve the problem completely.
Finally, keeping metabolic rate high ensures good levels of gastric acid which reduces the amount of undigested food reaching the colon.

Ok, but why is it causing a problem then and not before? The gut integrity seems to be lowered, enabling toxins to finally pass through.

Otherwise agree with the gastric acid problem. That's why I avoid things like drinking milk before bedtime, or just snack many times randomly during the day. I imagine the stomach is made to work well two, maybe three times a day during sunlight. Proteins need pH to be lower than a threshold, otherwise it's incomplete.
 
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haidut

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Ok, but why is it causing a problem then and not before? The gut integrity seems to be lowered, enabling toxins to finally pass through.

Otherwise agree with the gastric acid problem. That's why I avoid things like drinking milk randomly before bedtime, or just snack many times randomly during the day. I imagine the stomach is made to work well two, maybe three times a day during sunlight. Proteins need pH to be lower than a threshold, otherwise it's incomplete.

Gut integrity is not everything. Endotoxin generated by the bacteria goes into the portal vein and back to the liver. So, over time it overburdens the liver and it becomes chronically elevated due to the liver's inability to excrete all of it. A colonic breach is obviously going to make things much much worse and possibly trigger sepsis. But the endotoxin poisoning is chronic, low-grade, and it takes its sweet time to develop as it goes through the liver first.
 

tyw

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Finally, keeping metabolic rate high ensures good levels of gastric acid which reduces the amount of undigested food reaching the colon.

Regarding this point, a practitioner friend of mine has good experience with using Betaine HCL for gut issues when already sick and unable to produce enough stomach acid in the first place.

I speculate that it is the chloride ions that is actually preventing bacterial overgrowth, but am not 100% sold on this mechanic (and I'm definitely not sold on the definite efficacy of the many gut-specific chloride ion remedies out there -- Betaine HCL is far safer for this particular issue).

Sometimes we're talking pretty high amounts of Betaine HCL which are required o_O -- like 20-40g a day.

....
 

haidut

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Regarding this point, a practitioner friend of mine has good experience with using Betaine HCL for gut issues when already sick and unable to produce enough stomach acid in the first place.

I speculate that it is the chloride ions that is actually preventing bacterial overgrowth, but am not 100% sold on this mechanic (and I'm definitely not sold on the definite efficacy of the many gut-specific chloride ion remedies out there -- Betaine HCL is far safer for this particular issue).

Sometimes we're talking pretty high amounts of Betaine HCL which are required o_O -- like 20-40g a day.

....

Oh, wow, those are VERY high amounts! What about glycine and/or caffeine with their known ability to increase gastric acid output and of course glycine's ability to activate the chloride "channels"?
 

tyw

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Oh, wow, those are VERY high amounts! What about glycine and/or caffeine with their known ability to increase gastric acid output and of course glycine's ability to activate the chloride "channels"?

Firstly, this guy is a practitioner usually dealing with sick and crazy people ..... blunt weapons are needed in that scenario, and HCL directly added to force the system along; It's still easier to ask a sick person to swallow 40 Betaine HCL pills ......

Regarding caffeine, all I know is that signals an increase in gastric acid production. Whether or not you actually get extra gastric acid production IMO, is dependent on the health and responsiveness of parietal cells.

I have no clue how to measure "parietal cell health", and thus can't speak for this direct effect. Caffeine would likely improve metabolism acutely though, and if so, that may provide the CO2 needed for Gastric acid production.

And for those wonder, yes, gastric acid production requires CO2, see -- Parietal cell - Wikipedia, the free encyclopedia . This is probably why: "good metabolism => sufficient CO2 => good stomach acid production"​

I'm not clear on my research regarding glycine ;) Need to read up on this first.

....
 

NathanK

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I think high estrogen plays a part. Of course, estrogen may be brought on by endotoxins.

Also, high CO2 levels in the body shrink the prostate.

I think the whole idea of BPH is wrong. Prostates aren't static. They can swell up and shrink down pretty quickly, I think.
I agree. In my experience, I tried clomid for a couple months once and my estradiol elevated well out of range and had my PSA go through the roof. I stopped the clomid and never had a PSA or estradiol lab result anywhere near those ranges since. Though I didnt have gut issues, im sure estrogen can play a part in endotoxin or vice versa as well.
 

Makrosky

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Endotoxin is there because of the bacteria in the gut, and that bacteria being fed on resistant starch and other undigested food. So, no starch or resistant starch in the diet should greatly limit the endotoxin produced. Also, avoiding things that activate the TLR4 like alcohol and even acetic acid would also help. And for the more adventurous, keeping the gut clean with antibiotics could provide even more drastic reductions in endotoxin levels. But given all the other chemicals that activate TLR4 I think it is more important to be aware of those activators and keep endotoxin low with diet vs. trying to kill the bacteria completely as it won't solve the problem completely.
Finally, keeping metabolic rate high ensures good levels of gastric acid which reduces the amount of undigested food reaching the colon.
haidut, it would be great if you could summarize a list of things that activate TLR4 and things that block it.

Apparently sat fat can activate TLR4 ?
http://www.jneurosci.org/content/29/2/359.full
Dietary oil composition differentially modulates intestinal endotoxin transport and postprandial endotoxemia
Saturated Fatty Acids and Inflammation: Who Pays the Toll?
Saturated fatty acids activate TLR-mediated proinflammatory signaling pathways. - PubMed - NCBI
 

haidut

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The Wiki page has a decent list.
TLR4 - Wikipedia, the free encyclopedia

From that list you can make an educated guess on other substances based on chemical similarity or you just search PubMed for thinks like "SUBSTANCE TLR4" where the substance is whatever you are looking for. For instance "ethanol TLR4".
It is worth noting that of the agonists listed on the Wiki page, the majority are opioids. So, this explains immediately why Peat has said opioids release histamine and why they should not be given for pain. They probably accelerate dramatically the decline of critically ill people just based on their TLR4 activity, and they have other bad mechanisms as well.
 

Makrosky

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The Wiki page has a decent list.
TLR4 - Wikipedia, the free encyclopedia

From that list you can make an educated guess on other substances based on chemical similarity or you just search PubMed for thinks like "SUBSTANCE TLR4" where the substance is whatever you are looking for. For instance "ethanol TLR4".
It is worth noting that of the agonists listed on the Wiki page, the majority are opioids. So, this explains immediately why Peat has said opioids release histamine and why they should not be given for pain. They probably accelerate dramatically the decline of critically ill people just based on their TLR4 activity, and they have other bad mechanisms as well.
Oh, thanks haidut, that was a case of RTFW (read the ******* wikipedia)! I don't know why I didn't think about it. Thanks!!!!
 

Makrosky

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The Wiki page has a decent list.
TLR4 - Wikipedia, the free encyclopedia

From that list you can make an educated guess on other substances based on chemical similarity or you just search PubMed for thinks like "SUBSTANCE TLR4" where the substance is whatever you are looking for. For instance "ethanol TLR4".
It is worth noting that of the agonists listed on the Wiki page, the majority are opioids. So, this explains immediately why Peat has said opioids release histamine and why they should not be given for pain. They probably accelerate dramatically the decline of critically ill people just based on their TLR4 activity, and they have other bad mechanisms as well.
Yes I see the opioids... And I can see a couple of the antagonists are famous antidepressants. Nice coincidence knowing for self experience that endotoxin cause depression symptoms.
 

Parsifal

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The Wiki page has a decent list.
TLR4 - Wikipedia, the free encyclopedia

From that list you can make an educated guess on other substances based on chemical similarity or you just search PubMed for thinks like "SUBSTANCE TLR4" where the substance is whatever you are looking for. For instance "ethanol TLR4".
It is worth noting that of the agonists listed on the Wiki page, the majority are opioids. So, this explains immediately why Peat has said opioids release histamine and why they should not be given for pain. They probably accelerate dramatically the decline of critically ill people just based on their TLR4 activity, and they have other bad mechanisms as well.
Interesting! What should be given for pain?
 

haidut

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Interesting! What should be given for pain?

The safest drugs are the *caines - i.e. procaine, lidocaine, benzocaine, etc. They actually have pro-metabolic and anti-aging effect, which is probably why Peat has spoken so fondly of them. Apparently oral procain is the well-kept anti aging secret in Hollywood.
BUSM Researcher Warns Banned Fountain of Youth Drug May be Making a Comeback » Boston University Medical Campus | Blog Archive | Boston University
Gerovital - Wikipedia, the free encyclopedia
 

Parsifal

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The safest drugs are the *caines - i.e. procaine, lidocaine, benzocaine, etc. They actually have pro-metabolic and anti-aging effect, which is probably why Peat has spoken so fondly of them. Apparently oral procain is the well-kept anti aging secret in Hollywood.
BUSM Researcher Warns Banned Fountain of Youth Drug May be Making a Comeback » Boston University Medical Campus | Blog Archive | Boston University
Gerovital - Wikipedia, the free encyclopedia
Didn't you say that cocaine is a SSRI, SNRI and SDRI inhibitor? What about the other caines?
 

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