TUDCA

[Mauritio]

"The TUDCA-treated mice (Stz + TUDCA) displayed lower food intake, higher energy expenditure (EE) and respiratory quotient."

Energy homeostasis deregulation is attenuated by TUDCA treatment in streptozotocin-induced Alzheimer's disease mice model - PubMed

Alzheimer's disease (AD) is a progressive neurodegenerative disorder and the most common cause of dementia. While cognitive deficits remain the major manifestation of AD, metabolic and non-cognitive abnormalities, such as alterations in food intake, body weight and energy balance are also...

pubmed.ncbi.nlm.nih.gov

 

[Bart1]

Tudca and alcohol. I see a lot that it shouldn’t be combined. I have to take some tinctures everyday, anyway to circumvent this problem? Taking it before bedtime?

 

[A.R]

I've tried this for months and didn't notice much. I have cholestasis and gallstones.

Over the years what has helped you the most in managing/recovering from gallbladder problems?

 

[Pointless]

Over the years what has helped you the most in managing/recovering from gallbladder problems?

I havent seen a resolution of this. Digestive issues and surgery are holding me back

 

[A.R]

I havent seen a resolution of this. Digestive issues and surgery are holding me back

So have you got surgery done on your gallbladder or looking to get surgery done?

Have you looked in to Nigella sativa seed? There are some studies showing it’s beneficial effect for liver I think(also for depression if I remember correctly) Regular use of this amazing seed has done wonders for my liver and gallbladder health, you could maybe try this natural route.

 

[RealNeat]

I havent seen a resolution of this. Digestive issues and surgery are holding me back

Any updates?

 

[ddjd]

as Haidut mentioned, Bile Acid -> FXR activation for the win - can overcome type 2 generated by HFD by increasing our cholesterol use for the good stuff (steroidogenesis)

The study mentions both saturated and PUFA as bad tho (Oleic and Palmitic) but largely follows Rays line on the havoc FFA can cause

Steroidogenic acute regulatory protein (StAR) overexpression attenuates HFD-induced hepatic steatosis and insulin resistance - ScienceDirect

Steroidogenic acute regulatory protein (StAR), one of the mitochondrial cholesterol delivery proteins, transfers cholesterol from the outer mitochondrial membrane to the inner mitochondrial membrane, which plays an important role in the maintenance of intracellular lipid homeostasis [28]. Our previous in vivo investigations showed that StAR played an important role in regulating cholesterol and triglyceride levels in the process of atherosclerosis [29]. Thus, targeting StAR- bile acid synthesis pathway may significantly contribute to a decrease in cholesterol accumulation in the liver and potentially reduce liver damage.
Other than disorders in lipid content, increased FFA levels also led to glucose disorders, resulting in more gluconeogenesis and less glycogen synthesis and glucose consumption [30], [31], the main symptoms and manifestations of insulin resistance. In the present study, we provided insight into the effect of StAR on hepatic lipid/glucose metabolism and insulin resistance, using both in vitro and in vivo models for NAFLD.
According to the most widespread and prevalent “two-hit” model for NAFLD, while the “first hit” refers to lipid accumulation (including FFA, cholesterol and triglyceride) in the hepatocytes [32], the second is subsequent hepatic injury, inflammation and fibrosis. Consistent with this theory, our models of NAFLD induced by OA/PA overloading or HFD feeding resulted in marked up-regulation of lipid accumulation, de novo lipogenesis, and inflammatory response. At the same time, the expression of StAR were significantly decreased whether in FFA-overloaded hepatocytes or in livers of NAFLD mice and patients, indicating that StAR played an important role in preventing the development of NAFLD. Furthermore, we introduced the adenovirus encoding StAR gene to rival this inhibitory effect. Our data demonstrated that StAR overexpression decreased the levels of hepatic lipids and maintained the hepatic glucose homeostasis in FFA-overloaded hepatocytes and livers of NAFLD mice induced by HFD. Expressions of genes involved in hepatic lipid metabolism (HMGCR, SREBP1c, FASN, ACC1), inflammatory response (TNF-α, MCP-1, IL-β) as well as gluconeogenesis genes (Pcx, G6PC) were decreased, while genes involved in glycogen synthesis (GSK-3β, Gys2) were increased significantly in hepatocytes by StAR overexpression.
Insulin resistance is suggested to be the key pathogenic factor in the development of hepatic steatosis [33]. It is well established that the insulin signaling pathway plays a central role in regulating glucose, lipid, and energy metabolism [34]. Phosphorylation of insulin receptor subsrate-1 (IRS-1) and Akt is a marker of insulin signaling pathway [25]. Diacylglycerol (DAG), a second messenger signaling lipid, and its target phosphorylated PKCε are among the main negative regulators for insulin signaling that may induce serine phosphorylation of IRS-1[26], [35], [36]. The data from this study showed that the content of intracellular DAG and phosphorylated PKCε were significantly decreased after StAR overexpression, indicating that the inhibited insulin signaling in NAFLD was reversed by StAR. As a result, the tyrosine phosphorylation of IRS-1 and Akt were markedly increased by StAR overexpression.
LIPIN1 is a mammalian phosphatidic acid phosphatase for diacylglycerol (DAG) synthesis. Knockdown of LIPIN1 ameliorates hyperglycemia and insulin resistance by reducing DAG and PKCɛ activity in db/db mice [19], which is consistent with our study. Our present data showed that StAR overexpression decreased expression of LIPIN1 in livers of NFALD mice. These data suggested that StAR could improve insulin signaling and inhibit the progression of NAFLD by reducing activity of DAG and PKCɛ.
In addition, StAR plays a critical role in bile acid synthesis by enhancing the delivery of substrate cholesterol into mitochondria via the “acidic” pathway [8]. It was demonstrated that bile acids lowered TG synthesis via activating FXR-SHP-SREBP-1c regulatory cascade. Bile acids activate FXR to induce SHP synthesis, and SHP suppresses the transcriptional function of SREBP-1c, leading to the suppression of lipogenic gene expression [12]. Moreover, Ishimoto et al. demonstrated that SREBP-1c mediated the transcription of LIPIN1 gene [37]. In our study, hepatic overexpression of StAR significantly increased both serum and hepatic bile acid levels in mice, which was consistent with previous studies [38], [39]. Furthermore, the expression of FXR downstream genes such as SHP, SREBP-1c and LIPIN1 was regulated by StAR overexpression, indicating that FXR was activated by bile acid, although the expression of FXR gene was not affected. FXR activation might control lipogenesis through both SREBP-1c-dependent and -independent mechanisms. Several other mechanisms have been implicated in the TG-lowering effect of FXR activation. FXR ligands induce the expression of PPARα, which is a key player in hepatic lipid metabolism, and its target gene pyruvate dehydrogenase kinase-4 (PDK4) [40]. Our study indicated FXR activation by StAR overexpression resulted in PPARα up-regulation in NAFLD mice.

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Our findings indicate that supraphysiological bile acid levels as observed in cholestasis stimulate steroidogenesis via an S1PR2‐ERK‐SF‐1 signalling pathway.

This one says FXR represses CYP17A1 steroidogenesis in the liver in a fed state but not in ketogenesis when DHEA is formed in the liver and hits PPARa

Steroidogenic control of liver metabolism through a nuclear receptor-network - ScienceDirect

By contrast, the FXR is activated postprandially by bile acids returning to the liver from the intestine [6]. As such, FXR and PPARα can directly drive expression of genes involved in anabolic and catabolic processes, respectively, in the liver. However, FXR can also act as a trans-repressor of gene expression. In the bile-acid synthesis pathway, for example, FXR induces the expression of the small heterodimer partner (SHP), which represses expression of Cyp7a1 by preventing binding of the liver receptor homologue 1 (LRH1) to its promoter [10]. Intriguingly, FXR is also expressed in steroidogenic cells of the gonads [11], many of its target-genes are P450-enzymes, and bile acids themselves are steroid-like molecules that provide feedback on its activity [12]. As such, FXR may potentially represent a previously unexplored integrator of metabolic and steroidogenic processes.

Here, we have discovered that the steroidogenic enzyme Cyp17a1 is repressed by FXR-action in the liver in the fed-state. However, during starvation, Cyp17a1 is de-repressed and produces a hormone-ligand (DHEA) for PPARα.

How does tudca affect StAR then?

 

[RealNeat]

I made a big mistake. I mixed pure TUDCA powder with water and drank it. My body feels fine but my tastebuds are fried. This is the most bitter stuff i have ever tasted in my life. Im not a sensitive sally but its worth putting the powder in capsules or youll never take it. Why not just buy the capsules you say? I couldn't find one without additives. Im using nutricost currently. It would be a pretty sick joke to give someone a glass of TUDCA water, it looks and smells like water but one sip and youre on your a$$.

 

[Peater]

I made a big mistake. I mixed pure TUDCA powder with water and drank it. My body feels fine but my tastebuds are fried. This is the most bitter stuff i have ever tasted in my life. Im not a sensitive sally but its worth putting the powder in capsules or youll never take it. Why not just buy the capsules you say? I couldn't find one without additives. Im using nutricost currently. It would be a pretty sick joke to give someone a glass of TUDCA water, it looks and smells like water but one sip and youre on your a$$.

Well, it's synthetic bile!!

I have to say I am in love with this stuff.

 

[moa]

I made a big mistake. I mixed pure TUDCA powder with water and drank it. My body feels fine but my tastebuds are fried. This is the most bitter stuff i have ever tasted in my life. Im not a sensitive sally but its worth putting the powder in capsules or youll never take it. Why not just buy the capsules you say? I couldn't find one without additives. Im using nutricost currently. It would be a pretty sick joke to give someone a glass of TUDCA water, it looks and smells like water but one sip and youre on your a$$.

i have bought tudca power 2 years ago, i never took more than twice.

the taste is bad, but mostly I'm worried it could cause tooth decay.

 

[Mossy]

i have bought tudca power 2 years ago, i never took more than twice.

the taste is bad, but mostly I'm worried it could cause tooth decay.

Based on your comment, I did a search online and didn't find anything about TUDCA and tooth decay. Can you elaborate on that?

 

[moa]

Based on your comment, I did a search online and didn't find anything about TUDCA and tooth decay. Can you elaborate on that?

I mean direct contact with tooth (not from pills). Since it's called a "bile acid" i thought it would act like an acid, just because it has acid in the name.

but it seems they have both an acid and base, maybe they are not causing tooth decay, at normal pH ?

I'm not sure about the chemistry, i was just cautious because of the qualifier "acid" in their name, not that I've read anything it could cause tooth decay.

 

[Mossy]

I mean direct contact with tooth (not from pills). Since it's called a "bile acid" i thought it would act like an acid, just because it has acid in the name.

but it seems they have both an acid and base, maybe they are not causing tooth decay, at normal pH ?

I'm not sure about the chemistry, i was just cautious because of the qualifier "acid" in their name, not that I've read anything it could cause tooth decay.

Ah, ok. I now understand where your concern was coming from. Thank you.

 

[Mossy]

Does anyone have any thoughts on why I can't take TUDCA without it making me feel very bad? I would seem to be the perfect candidate for it—slow digestion, varying degrees of fatty liver type symptoms, hypothyroid, to name a few. Is the bile being released but backing up in the liver or some other area?

 

[moa]

Does anyone have any thoughts on why I can't take TUDCA without it making me feel very bad? I would seem to be the perfect candidate for it—slow digestion, varying degrees of fatty liver type symptoms, hypothyroid, to name a few. Is the bile being released but backing up in the liver or some other area?

Do you have similar symptoms with you take 300 or 400mg oral magnesium for a few days ? or with lots of coffee? or with 3g taurine supplements for a few days ? they increase bile flow.

do you have gallbladder sensitivity prior to feeling bad (or during) ?

do you also get yellow stools from fast transit time, or very dark constipated stools, or very sticky stools the day after gallbladder sensitivity symptoms ? or any colon cramps, IBS-c like symptoms ? this could mean there's lots of (toxic) bile released, i think.

i realized for me, the is something i could call "toxic bile" release that causes gut distress and the corresponding feeling bad.

Beans are supposed to bind toxic bile well. carrots, or fiber in general i think, not to mention activated charcoal for short term use.

i think, the bile released in the intestine, if not bound and excreted immediately, can trigger serotonin symptoms, and gets reabsorbed with toxins into general blood circulation causing very bad general symptoms.

 

[Bluebell]

Does anyone have any thoughts on why I can't take TUDCA without it making me feel very bad? I would seem to be the perfect candidate for it—slow digestion, varying degrees of fatty liver type symptoms, hypothyroid, to name a few. Is the bile being released but backing up in the liver or some other area?

I've heard of people needing bile absorbers in the diet, in order to take TUDCA. Also I've heard of people with clogged/sludgy livers having to take it in small amounts and slowly build up.

 

[Mossy]

Do you have similar symptoms with you take 300 or 400mg oral magnesium for a few days ? or with lots of coffee? or with 3g taurine supplements for a few days ? they increase bile flow.

Magnesium makes me feel off and I'd say taurine make me feel very off, like a bad malaise, but TUDCA I would say is worse than both. Lot's of coffee would make me very hyped up and jittery; and then the next day I would feel off.

do you have gallbladder sensitivity prior to feeling bad (or during) ?

If gallbladder sensitivity would be determined by pain in the gallbladder, I would say no, If it is referring to constipation or digestive distress, I would say most likely, because that is so common with me it seems like a regular occurrence.

do you also get yellow stools from fast transit time, or very dark constipated stools, or very sticky stools the day after gallbladder sensitivity symptoms ? or any colon cramps, IBS-c like symptoms ? this could mean there's lots of (toxic) bile released, i think.

I rarely get yellow stools. When I first got sick, over 10 years ago, I did have a few occasions of yellow/tan stools. I must not be attentive enough to my symptoms, or maybe they are so regular they don't stand out, because varying stools and digestive distress is the norm for me.

i realized for me, the is something i could call "toxic bile" release that causes gut distress and the corresponding feeling bad.

Ok, so maybe that is what is happening. I wonder if I continue with it if the toxic bile will eventually pass through and out?

Beans are supposed to bind toxic bile well. carrots, or fiber in general i think, not to mention activated charcoal for short term use.

I do attempt to have the carrot salad at least 5 days a week. Though, I've stopped adding the vinegar the last month or so, due to something Haidut posted. I'll probably add that back in soon.

i think, the bile released in the intestine, if not bound and excreted immediately, can trigger serotonin symptoms, and gets reabsorbed with toxins into general blood circulation causing very bad general symptoms.

Ok, that kind of fits with my thought of bile backing up.

 

[Mossy]

I've heard of people needing bile absorbers in the diet, in order to take TUDCA. Also I've heard of people with clogged/sludgy livers having to take it in small amounts and slowly build up.

That fits with my initial thoughts, and with some of what @moa was saying. I think activated charcoal along with TUDCA could be a possible approach. Thank you.

 

[moa]

@Mossy i myself would like to know how to manage this.

Also i forgot, maybe vitamin K also trigger this some times, also it increase liver activity.

i think is only the first time, after a pause, if i am regular i think it should fade away. right now i started taking K2 regularly, and coffee. if all goes ok for a week or so, maybe I'll add taurine too, and if all goes well, maybe add magnesium (this is what's very problematic, also causing possible GERD).

hope it will work, magnesium being the most challenging for me (because of GERD but also because of colitis, toxic bile). hope will work this time.

 

[Mossy]

@Mossy i myself would like to know how to manage this.

Also i forgot, maybe vitamin K also trigger this some times, also it increase liver activity.

i think is only the first time, after a pause, if i am regular i think it should fade away. right now i started taking K2 regularly, and coffee. if all goes ok for a week or so, maybe I'll add taurine too, and if all goes well, maybe add magnesium (this is what's very problematic, also causing possible GERD).

hope it will work, magnesium being the most challenging for me (because of GERD but also because of colitis, toxic bile). hope will work this time.

Good luck. Let us know how it goes. I'll do the same if I attempt it.