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Over Activation of Farnesoid X Receptor In the Ilium Driving Liver and Gut Disharmony

Bdeep86

Senior Member
Messages
278
@Bdeep86

What do think about Hulda Clark style liver flushes?

I don't have much experience with those, so its hard for me to say. I do believe people when they say they derive some benefit. I think once the issue is corrected they won't be necessary.

Have you tried them before?
 

Bdeep86

Senior Member
Messages
278
Does anyone following this entry experience symptomatic relief after ingesting acute alcohol? If so can you please let me know I have a few questions. I am preparing to release another entry that I think will be fairly significant.
 

MonkeyMan

Senior Member
Messages
405
Does anyone following this entry experience symptomatic relief after ingesting acute alcohol? If so can you please let me know I have a few questions. I am preparing to release another entry that I think will be fairly significant.

Hi Bdeep86. Your theory is very interesting to me (as a PWC for 32 years, with a definite gut component and detoxification issues in my illness), and although I haven't had a drop of alcohol to drink for many years, I did notice something recently that you may find interesting (although it is almost impossible for me to believe it's true, but it is!). When I rub alcohol-containing hand sanitizer on my hands a few times a day, my bowel movements improve significantly. I tried this with pure ethanol and the same thing happened ... normal bowel movements, for a change. It feels like a magic trick but it really works. Would love to get your thoughts on this. Thanks.

(P.S. One glass of pure cranberry juice has the exact opposite effect ... it wreaks havoc on my bowel movements)
 
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aquariusgirl

Senior Member
Messages
1,732
So I am taking taurine & glycine which apparently = bile ....& I wake up feeling kind of naseous .....I think this is the bile pushing out or mobilizing fat soluble toxins right?
 

Bdeep86

Senior Member
Messages
278
Bile is only one mechanism involved. There are about 8 steps after this that allow this system of dysfunction to be sustained. I don't think in many cases addressing bile acid is going to heal the condition, at least not by addressing it on its own. People with CFS are going to have a mess when it comes to phase 1 or phase 2 detox. Or by my estimation a problem with both. Taking something that stimulates one of them on its own is going to offset this balance and it is possible that toxins that aren't getting through this dysfunctional system are being actually mobilized into the fat areas.

Have you been gaining weight since taking these?
 

aquariusgirl

Senior Member
Messages
1,732
http://onlinelibrary.wiley.com/doi/10.1111/bpa.12388/full

The hypothesis of a metaflammasome is based on the concept that failure of endoplasmic reticulum function (due to accumulation of newly synthesized unfolded proteins) results in the activation of an unfolded protein response and upregulated inflammation [30]. Our data in part appear to support this concept as in AD the accumulation of Aβ and Tau might lead to an unfolded protein response and inflammation, hence precipitating neurodegeneration.
 

Hilary

Senior Member
Messages
190
Location
UK
Hi @Bdeep86 - just wondering if you've posted the whole of your theory anywhere yet? Interested to know more especially as I've been advised by functional medicine practitioner to try Tudca but reluctant to start in view of what you've mentioned previously?

I've recently added quite high doses of Betaine HCl which seem to have eased gall bladder issues. OAT test suggested I'm not absorbing nutrients - or not very well, especially protein.
 

jump44

Senior Member
Messages
122
Also wouldnt mind hearing this theory. I have tried androsterone as put forth by @Tunguska a few times at very small doses along with low dose dhea and Ive found this to reliably be a great combo for me at least. I will have to keep experimenting more with it to see if it is able to be good in the long term. Idk if this is due to the FXR receptor or simply the neuro-anti inflammatory effects of these androgens, but they definitely help--in a low dose
 

Bdeep86

Senior Member
Messages
278
Hey @Hilary I have not written everything out to this point. I am trying to think of the best possible way to deliver what is going to be quite a bit of information. It will happen within the next month most likely on my blog as there are a couple people with access to this account on Phoenix. It sounds like you are starting to knock on the right doors. TUDCA in my opinion should only be started after a couple other systems are supported.

I feel it will be best to put out the full story rather than a piece of it in the future and I have not found the time up until now. My goal is to have it out by the end of September. I think for many people involved in research who come from the western world they are looking for something very specific. A missing enzyme or a dysfunction in specific organ / gland. However, CFS is a dysfunction of multiple systems and processes which need to be explained completely. After I released this initial entry many people ran and got on all sorts of bile acids and other supplements for the FXR. It worried me so I have held off on adding to this and I will most likely take that entry down and start over so that people can follow the pattern.

Not everyone is going to be the same. I do feel that a bulk of the people that suffer from this condition do suffer from a specific process that has become dysfunctional, which CAN BE FIXED!
 

Bdeep86

Senior Member
Messages
278
Also wouldnt mind hearing this theory. I have tried androsterone as put forth by @Tunguska a few times at very small doses along with low dose dhea and Ive found this to reliably be a great combo for me at least. I will have to keep experimenting more with it to see if it is able to be good in the long term. Idk if this is due to the FXR receptor or simply the neuro-anti inflammatory effects of these androgens, but they definitely help--in a low dose

I am not familiar with this theory. I am more than happy to look into this. What sort of symptom relief do you experience when taking this?
 

jump44

Senior Member
Messages
122
I am not familiar with this theory. I am more than happy to look into this. What sort of symptom relief do you experience when taking this?

If you look earlier in the thread its proposed that androsterone has effects on the FXR recepto, so thats what initially peeked my interest in it..Keep in mind its only been a couple weeks.. But I started using the combo during a pretty nasty "crash", where I couldnt sleep even though my body was exhausted my brain just wouldnt shut off, brain freaking out, couldnt tolerate noises or light. It didnt totally fix this but it makes the sleep I do get much more repairing. I guess thats the best way to describe it- it feels like it shifts the body from total survival freak out mode into a more calm, repairing mode.

The first day after I took the andro I had more and healthier bowel movements. Appetite increase, sense of being more in touch with reality, my brain feels very much calmed down, less overall pain, and m complexion seems to have changed( I look somewhat healthy lol) I am taking it very slow, I only dose once every 2-3 days and in much smaller doses than people normally take of this stuff, but so far its been extremely effective with little to no downsides.
 

Bdeep86

Senior Member
Messages
278
If you look earlier in the thread its proposed that androsterone has effects on the FXR recepto, so thats what initially peeked my interest in it..Keep in mind its only been a couple weeks.. But I started using the combo during a pretty nasty "crash", where I couldnt sleep even though my body was exhausted my brain just wouldnt shut off, brain freaking out, couldnt tolerate noises or light. It didnt totally fix this but it makes the sleep I do get much more repairing. I guess thats the best way to describe it- it feels like it shifts the body from total survival freak out mode into a more calm, repairing mode.

The first day after I took the andro I had more and healthier bowel movements. Appetite increase, sense of being more in touch with reality, my brain feels very much calmed down, less overall pain, and m complexion seems to have changed( I look somewhat healthy lol) I am taking it very slow, I only dose once every 2-3 days and in much smaller doses than people normally take of this stuff, but so far its been extremely effective with little to no downsides.

What form are you taking the andro? Sounds as though it caused a shift in nervous system activity. It maybe boosting the function of one of your digestive organs. I'm not sure that long term this will continue to be honest. I have not seen great things happen with pro-hormones.
 

jump44

Senior Member
Messages
122
What form are you taking the andro? Sounds as though it caused a shift in nervous system activity. It maybe boosting the function of one of your digestive organs. I'm not sure that long term this will continue to be honest. I have not seen great things happen with pro-hormones.

Its a transdermal type of delivery. Im using oral dhea with it in doses of 2-3 mg..You could be correct, but for now I will take the symptom relief. Im hoping by only usig a couple times a week and tiny dose that there wont be much acclimation. It certainly -feels- like it does something very good for the digestive system, which has been a huge source of problems for me throughout this whole thing. Ive been on testosterone before early on in the illness and that both helped and hurt me I think, but this combination feels much different than that.
 

Bdeep86

Senior Member
Messages
278
Its a transdermal type of delivery. Im using oral dhea with it in doses of 2-3 mg..You could be correct, but for now I will take the symptom relief. Im hoping by only usig a couple times a week and tiny dose that there wont be much acclimation. It certainly -feels- like it does something very good for the digestive system, which has been a huge source of problems for me throughout this whole thing. Ive been on testosterone before early on in the illness and that both helped and hurt me I think, but this combination feels much different than that.

Oh yeah i'm not telling you to stop using it. I'm going to look into it. I just worry with any long term use of Pro-hormones, I had to mention that. Anything that can assist in digestive function is going to be a positive, this is in essence the core of CFS in many ways. If I were to guess off the top of my head I would say that the hormone is most likely causing a shift in vagus signaling.

I did find this in Pubmed

"A number of compounds unrelated to BAs were also found to act as FXR ligands with varying degrees of affinity, including androsterone38 and the exogenous natural products such as forskolin39, epigallocatechin-3-gallate40 and cafestol41"

I have not read the full piece but I will today.
 

Bdeep86

Senior Member
Messages
278
Its a transdermal type of delivery. Im using oral dhea with it in doses of 2-3 mg..You could be correct, but for now I will take the symptom relief. Im hoping by only usig a couple times a week and tiny dose that there wont be much acclimation. It certainly -feels- like it does something very good for the digestive system, which has been a huge source of problems for me throughout this whole thing. Ive been on testosterone before early on in the illness and that both helped and hurt me I think, but this combination feels much different than that.

"It now turns out that androsterone does activate a nuclear receptor: FXR. These data are in line with those from another study reporting that androsterone up-regulates FXR-mediated transactivation in an in vitro cis/trans assay (14). In the present issue, the authors determined also whether the expression of the small heterodimer partner (SHP), another nuclear receptor and well-characterized FXR target gene, is regulated by androsterone. They show that the treatment of castrated male mice or mouse AML-12 hepatocytes with androsterone indeed induces SHP mRNA expression, suggesting that androsterone increases the activity of mouse FXR. Using nuclear magnetic resonance spectroscopy technology, the authors show that androsterone directly binds to the ligand binding domain of human FXR. This binding leads to the simultaneous recruitment of the coactivator peptide steroid receptor coactivator-1."


https://academic.oup.com/endo/article/147/9/4022/2528306/FXR-More-than-a-Bile-Acid-Receptor


Its hard to say definitively that this is whats giving you symptom relief but it does seem that andro has a clear impact on FXR activity. This study was done on mice.
 

jump44

Senior Member
Messages
122
"It now turns out that androsterone does activate a nuclear receptor: FXR. These data are in line with those from another study reporting that androsterone up-regulates FXR-mediated transactivation in an in vitro cis/trans assay (14). In the present issue, the authors determined also whether the expression of the small heterodimer partner (SHP), another nuclear receptor and well-characterized FXR target gene, is regulated by androsterone. They show that the treatment of castrated male mice or mouse AML-12 hepatocytes with androsterone indeed induces SHP mRNA expression, suggesting that androsterone increases the activity of mouse FXR. Using nuclear magnetic resonance spectroscopy technology, the authors show that androsterone directly binds to the ligand binding domain of human FXR. This binding leads to the simultaneous recruitment of the coactivator peptide steroid receptor coactivator-1."


https://academic.oup.com/endo/article/147/9/4022/2528306/FXR-More-than-a-Bile-Acid-Receptor


Its hard to say definitively that this is whats giving you symptom relief but it does seem that andro has a clear impact on FXR activity. This study was done on mice.

interesting. Im obviously in no way qualified to analyze any of this lol but I can tell you its potent stuff and has a clear impact within a short period of time. Im always waiting on the other shoe to drop on anything I take that ends up just not working or turns on me, but so far this stuff gets a thumbs up. Just as an aside- other things that help me are

Nicotinamide Riboside
B12
TUDCA(was much more helpful at first)
align probiotic
Xifaxin
LDN

these are the things that I can point to that over the years have had impacts I could feel on my body in a positive manner, that have actually been maintained for the most part, with the caveat that when im in a relapse state not much seems to work-thats why it was so nice to have the andro/dhea sort of bring me out of it.
 

Bdeep86

Senior Member
Messages
278
Can you send me a link to the cream you are taking so I can see what else is in it? It seems that it does increase FXR signaling, when people describe the sensation of being more present I almost always look at CNS and Liver in particular.
 

Hilary

Senior Member
Messages
190
Location
UK
Hi @Bdeep86 - I completely understand your caution around this - we are all desperate for relief so I think there is an evident tendency to latch onto anything that might help..

I'm fairly cautious as have tried things in the past that have made me feel worse - hence the TUDCA has been sitting in my kitchen untouched for a couple of weeks and it will stay there until I feel confident I've done the groundwork. I did try Biotics Research Beta-TCP ("Support for normal cholesterol to bile acid conversion and healthy bile flow. Contains digestive and antioxidant enzymes, vitamin C, taurine and organic beet concentrate.") to support gall bladder but felt really rough pretty quickly - so not wanting to be hasty with the TUDCA....

And it's the groundwork I'm interested in at the moment. Should all sugar, including fruit be excluded? and presumably this is because of the dysbiosis inherent in the whole picture? I haven't been rigorous about sugar but I'm not getting any better....