TUDCA and phenylbutyric acid accelerate thyroid hormone activation and energy expenditure

[Drareg]

Interesting study, combining both substances should have a positive effect.

21237159
Exposure of cell lines endogenously expressing the thyroid hormone activating enzyme type 2 deiodinase (D2) to the chemical chaperones tauroursodeoxycholic acid (TUDCA) or 4-phenylbutiric acid (4-PBA) increases D2 expression, activity and T3 production. In brown adipocytes, TUDCA or 4-PBA induced T3-dependent genes and oxygen consumption (∼2-fold), an effect partially lost in D2 knockout cells. In wild type, but not in D2 knockout mice, administration of TUDCA lowered the respiratory quotient, doubled brown adipose tissue D2 activity and normalized the glucose intolerance associated with high fat feeding. Thus, D2 plays a critical role in the metabolic effects of chemical chaperones.

 

[haidut]

Interesting study, combining both substances should have a positive effect.

21237159
Exposure of cell lines endogenously expressing the thyroid hormone activating enzyme type 2 deiodinase (D2) to the chemical chaperones tauroursodeoxycholic acid (TUDCA) or 4-phenylbutiric acid (4-PBA) increases D2 expression, activity and T3 production. In brown adipocytes, TUDCA or 4-PBA induced T3-dependent genes and oxygen consumption (∼2-fold), an effect partially lost in D2 knockout cells. In wild type, but not in D2 knockout mice, administration of TUDCA lowered the respiratory quotient, doubled brown adipose tissue D2 activity and normalized the glucose intolerance associated with high fat feeding. Thus, D2 plays a critical role in the metabolic effects of chemical chaperones.

Those chemicals activate the bile acid receptor, which is known to increase T4 to T3 conversion and promote thyroid function and synthesis or even more thyroid hormones by the gland. Taurine works the same way, and so do many of the pro-metabolic steroids. This is also the main mechanism behind their thermogenic effects - i.e. activating the bile receptor and increasing T3 levels. Considering their relative thermogenic effects, I'd say progesterone is probably the most effective as a metabolic/thyroid booster, but on par with strong androgens like DHT (those have been shown to increase peripheral T4 to T3 conversion even without bile acid receptor involvement).

How Pregnenolone And Progesterone Raise Metabolism

I know pregnenolone/progesterone work via multiple mechanisms such as inhibiting serotonin, opposing estrogen, lowering FFA, etc. However, this method caught my eye and I thought I'd share it since many people here have trouble converting T4 into T3. As you all know both pregnenolone and...

raypeatforum.com

 

[Mauritio]

Interesting study, combining both substances should have a positive effect.

21237159
Exposure of cell lines endogenously expressing the thyroid hormone activating enzyme type 2 deiodinase (D2) to the chemical chaperones tauroursodeoxycholic acid (TUDCA) or 4-phenylbutiric acid (4-PBA) increases D2 expression, activity and T3 production. In brown adipocytes, TUDCA or 4-PBA induced T3-dependent genes and oxygen consumption (∼2-fold), an effect partially lost in D2 knockout cells. In wild type, but not in D2 knockout mice, administration of TUDCA lowered the respiratory quotient, doubled brown adipose tissue D2 activity and normalized the glucose intolerance associated with high fat feeding. Thus, D2 plays a critical role in the metabolic effects of chemical chaperones.

Anybody tried phenylbutyrate ?
There's some interesting studies on it.

 

[Elie]

Those chemicals activate the bile receptor, which is known to increase T4 to T3 conversion and promote thyroid function and synthesis or even more thyroid hormones by the gland. Taurine works the same way, and so do many of the pro-metabolic steroids. This is also the main mechanism behind their thermogenic effects - i.e. activating the bile receptor and increasing T3 levels. Considering their relative thermogenic effects, I'd say progesterone is probably the most effective as a metabolic/thyroid booster, but on par with strong androgens like DHT (those have been shown to increase peripheral T4 to T3 conversion even without bile acid receptor involvement).

How Pregnenolone And Progesterone Raise Metabolism

I know pregnenolone/progesterone work via multiple mechanisms such as inhibiting serotonin, opposing estrogen, lowering FFA, etc. However, this method caught my eye and I thought I'd share it since many people here have trouble converting T4 into T3. As you all know both pregnenolone and...

raypeatforum.com

brilliant

 

[liam183]

I actually ordered TUDCA yesterday to help with my digestion issues, which seem to stem from a gallbladder/liver problem. This makes me more excited for it to come in now.

 

[Drareg]

Anybody tried phenylbutyrate ?
There's some interesting studies on it.

No, its prescription only, I think phenibut works the similarly via T3, Phenylbutyrate does sound better though.

 

[Raytoo]

Would Tudca help someone without a gallbladder?

 

[Lokzo]

This is one of the many reasons why I love TUDCA.

I got another video on TUDCA coming soon.

Here's my old one for those interested:


View: https://www.youtube.com/watch?v=uzU1Ok-SDcM

 

[liam183]

Would Tudca help someone without a gallbladder?

Yes, and I'd also suggest taking ox bile

 

[Raytoo]

Yes, and I'd also suggest taking ox bile

Thanks

 

[shine]

What should TUDCA smell like?

There's a lot of fake TUDCA being sold by bodybuilding supplement stores. What are some reliable brands?

 

[Drareg]

What should TUDCA smell like?

There's a lot of fake TUDCA being sold by bodybuilding supplement stores. What are some reliable brands?

I don't get any smell from it, the taste is very bitter.

 

[Drareg]

Those chemicals activate the bile acid receptor, which is known to increase T4 to T3 conversion and promote thyroid function and synthesis or even more thyroid hormones by the gland. Taurine works the same way, and so do many of the pro-metabolic steroids. This is also the main mechanism behind their thermogenic effects - i.e. activating the bile receptor and increasing T3 levels. Considering their relative thermogenic effects, I'd say progesterone is probably the most effective as a metabolic/thyroid booster, but on par with strong androgens like DHT (those have been shown to increase peripheral T4 to T3 conversion even without bile acid receptor involvement).

How Pregnenolone And Progesterone Raise Metabolism

I know pregnenolone/progesterone work via multiple mechanisms such as inhibiting serotonin, opposing estrogen, lowering FFA, etc. However, this method caught my eye and I thought I'd share it since many people here have trouble converting T4 into T3. As you all know both pregnenolone and...

raypeatforum.com

Do you think there is a tissue specific mechanism involved, progesterone does seem to be more systemic in effect, the TUDCA may just activate t4 to t3 already present in tissue areas whereas progesterone stimulates the gland to produce more as well as conversion in different tissues, I understand it looks like TUDCA is causing the gland to release more, Im just curious if the studies highlighting this are that good, is it a residual effect like DHT in the prostate or hair shafts.

With the above in mind TUDCA may have a topical effect with many issues, I found this study but im struggling to open it in scihub to see the full study-

908491
To define the relationship of bile acid retention to the pruritus of cholestasis, we quantified individual bile acids in serum, acetone swabs of skin, and skin tissue in 13 patients with cholestasis undergoing laparotomy and in 8 controls. There was no consistent relationship between pruritus and concentrations of either total or individual bile acids in serum. Skin tissue concentrations of bile acids were elevated in patients with cholestasis, were linearly related to serum levels, and did not differentiate between those patients with and those without pruritus. Concentrations of bile acids on the skin surface, which were lower than those reported by others, did not correlate with pruritus, and were decreased by simple soap and water washing. These data indicate that the pruritus of cholestasis is not directly related to the skin tissue concentration of any of the major bile acids, although a relationship to a particular molecular form of bile acids could not be excluded.

9747660
Tauroursodeoxycholic acid (TUDC) is one of the most hydrophilic taurin conjugated bile acids. TUDC has a suppressive effect on DNA synthesis in primary cultured rat hepatocytes. In this study, we investigated the growth inhibitory effect of TUDC on cultured human keratinocytes. TUDC suppressed the proliferation of keratinocytes in a dose dependent fashion, as measured by both cell counts and 5-bromo-2'-deoxyuridine (BrdU) uptake. Keratinocytes reproliferated and reached almost the same cell number as control after removal of TUDC from the medium. TUDC (1 mM) had no effect on the cell viability, as measured by the dye exclusion test. Epidermal sheets stratified in the presence of TUDC appeared thinner than those stratified without TUDC. These results suggest that TUDC has a reversible growth suppressive effect on human keratinocytes through the mechanism other than cytotoxicity and would be applicable for the treatment of hyperproliferative skin disorders such as psoriasis.

29965978
Stearoyl-CoA desaturase 1 (SCD1) catalyzes the rate limiting step in monounsaturated fatty acid synthesis by inserting a double bond at the delta-9 position of long-chain fatty acids. SCD1 converts stearate (18:0) to oleate (18:1n9) and palmitate (16:0) to palmitoleate (16:1n7), respectively. Mice with global and skin-specific deletion (SKO) of SCD1 exhibit increased whole body energy expenditure and protection against diet-induced adiposity, hepatic steatosis, insulin sensitivity and glucose intolerance. The mechanisms that link cutaneous lipid homeostasis with whole body energy balance are presently unknown. In this study, we reveal that SKO mice demonstrate increased skin surface free cholesterol, decreased circulating total cholesterol and increased taurine-conjugated and hydrophilic bile acids. Tauro-β-muricholic acid, which is a marker of extrahepatic bile acid synthesis, is significantly elevated in SKO plasma. Bile acid signaling through the bile acid-specific receptor TGR5 is known to be protective against obesity and metabolic disease; a phenotype that is similar to SKO mice. We therefore examined TGR5 expression and its downstream mediator, DIO2, in various tissues and found that both TGR5 and DIO2 expression were significantly increased in brown adipose tissue. In sum, we suggest that skin-derived bile acids are involved in the lean and metabolically healthy phenotype of SKO mice.

 

[Drareg]

This is one of the many reasons why I love TUDCA.

I got another video on TUDCA coming soon.

Here's my old one for those interested:


View: https://www.youtube.com/watch?v=uzU1Ok-SDcM

have you experimented topically with it?

 

[Drareg]

35049570
Clindamycin hydrochloride is a widely used antibiotic for topical use, but its main disadvantage is poor skin penetration. Therefore, new approaches in the development of clindamycin topical formulations are of great importance. We aimed to investigate the effects of the type of gelling agent (carbomer and sodium carmellose), and the type and concentration of bile acids as penetration enhancers (0.1% and 0.5% of cholic and deoxycholic acid), on clindamycin release rate and permeation in a cellulose membrane in vitro model. Eight clindamycin hydrogel formulations were prepared using a 23 full factorial design, and they were evaluated for physical appearance, pH, drug content, drug release, and permeability parameters. Although formulations with carbomer as the gelling agent exerted optimal sensory properties, carmellose sodium hydrogels had significantly higher release rates and permeation of clindamycin hydrochloride. The bile acid enhancement factors were higher in carbomer gels, and cholic acid exerted more pronounced permeation-enhancing effects. Since the differences in the permeation parameters of hydrogels containing cholic acid in different concentrations were insignificant, its addition in a lower concentration is more favorable. The hydrogel containing carmellose sodium as a gelling agent and 0.1% cholic acid as a penetration enhancer can be considered as the formulation of choice.