Looking for what dose others have taken they come in 250 mg capsules i have seen doses as high as 1000mgs a day, is it necessary to go that high when going with tbol?
I would go with 500mg-700mg.
I was using 450mg tudca(+nac,liv52) on 100mg anadrol and my alt/ast came back at high end but still in range, was pleased because otherwise i'm always out of range without it.
I read recently not to take it on cycle and to actually wait and take it after. Thoughts?
That doesn't make sense to me. What would the difference be if you took it on cycle or after? It's to help protect the liver so I would think it's more important to take it during cycle.
I need to do more reading on this before forming an opinion, but there certainly are reasons to think that (T)UDCA use while on oral steroids could be counterproductive. Especially at high dosages.I read recently not to take it on cycle and to actually wait and take it after. Thoughts?
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3430272/Ursodeoxycholic acid (UDCA) is a steroid bile acid approved for primary biliary cirrhosis (PBC). UDCA is reported to have “hepato-protective properties”. Yet, UDCA has “unanticipated” toxicity, pronounced by more than double number of deaths, and eligibility for liver transplantation compared to the control group in 28 mg/kg/day in primary sclerosing cholangitis, necessitating trial halt in North America. UDCA is associated with increase in hepatocellular carcinoma in PBC especially when it fails to achieve biochemical response (10 and 15 years incidence of 9% and 20% respectively). “Unanticipated” UDCA toxicity includes hepatitis, pruritus, cholangitis, ascites, vanishing bile duct syndrome, liver cell failure, death, severe watery diarrhea, pneumonia, dysuria, immune-suppression, mutagenic effects and withdrawal syndrome upon sudden halt. UDCA inhibits DNA repair, co-enzyme A, cyclic AMP, p53, phagocytosis, and inhibits induction of nitric oxide synthatase. It is genotoxic, exerts aneugenic activity, and arrests apoptosis even after cellular phosphatidylserine externalization. UDCA toxicity is related to its interference with drug detoxification, being hydrophilic and anti-apoptotic, has a long half-life, has transcriptional mutational abilities, down-regulates cellular functions, has a very narrow difference between the recommended (13 mg/kg/day) and toxic dose (28 mg/kg/day), and it typically transforms into lithocholic acid that induces DNA strand breakage, it is uniquely co-mutagenic, and promotes cell transformation. UDCA beyond PBC is unjustified.
Well, the subject matter is very complicated and the article is badly written. The author also seems to be on a crusade against UDCA use and has this 'everyone else is wrong' anti-mainstream medicine attitude that biases his conclusions. Still, there's some interesting points made in the paper:I read some of Jeff post but it’s to much for me to understand. Last I heard from a doc was on only one study on alcoholic with fatty liver that udac n I think tudca was used during the study to. The concussion was that the compounds actually made the toxicity worse. I believe that either they also used a controlled without alcohol or figured out that it was the mechanism that were making thing more toxic.
There is a lot of lab result out there claiming used after would have a pretty good impact on acute liver enzymes. I used it as a medicinal everyday supp for a month or so because my AST runes 25 points high and ALT runs about 10-15 points high from training. While taking tudca took 2 blood test and both test enzymes were below range by around 10 points. No orals n just trt though.
UDCA does not affect long-term survival, or transplant free survival and does not slow progression of the PBC, but achieves a 25% drop in serum bilirubin, a 35% drop in serum alanine aminotransferase, a 33% drop in aspartate aminotrasferase, 40% drop in alkaline phosphatase and a 50% drop in gamma glutamyl transpeptidase, that is not associated with control of pruritus, fatigue or weakness. Evidence is lacking to support effectiveness of UDCA in PBC, beyond the control of serum bilirubin, and hepatic transaminases
https://www.ncbi.nlm.nih.gov/pubmed/19585548/During therapy, aspartate aminotransferase and alkaline phosphatase levels decreased more in the UDCA group than the placebo group (P < 0.01), but improvements in liver tests were not associated with decreased endpoints. By the end of the study, 30 patients in the UDCA group (39%) versus 19 patients in the placebo group (26%) had reached one of the pre-established clinical endpoints. After adjustment for baseline stratification characteristics, the risk of a primary endpoint was 2.3 times greater for patients on UDCA than for those on placebo (P < 0.01) and 2.1 times greater for death, transplantation, or minimal listing criteria (P = 0.038). Serious adverse events were more common in the UDCA group than the placebo group (63% versus 37% [P < 0.01]).
Long-term, high-dose UDCA therapy is associated with improvement in serum liver tests in PSC but does not improve survival and was associated with higher rates of serious adverse events.
UDCA increases bile flow. However, the mere increase of bile flow in obstructive cholestasis without resolution of the cause may worsen the disease course due to increase of biliary pressure and leading to rupture of cholangioles and to development of bile infarcts. Obstructive cholestasis refers to obliterative and non-obliterative obstructions .
Non-obliterative small bile duct obstructions include late stages of PBC, primary sclerosing cholangitis, paucity of intrahepatic biliary radicals and vanishing bile duct syndrome [115,125].
Stimulation of bile flow even with the hydrophilic bile acid UDCA in a mouse model of sclerosing cholangitis and in bile duct ligated mice increased liver injury, aggravated bile infarcts and induced hepatocyte necrosis .
https://www.ncbi.nlm.nih.gov/pubmed/20564380/High-dose (28-30 mg/kg/day) ursodeoxycholic acid (UDCA) treatment improves serum liver tests in patients with primary sclerosing cholangitis (PSC) but does not improve survival and is associated with increased rates of serious adverse events. The mechanism for the latter undesired effect remains unclear. High-dose UDCA could result in the production of hepatotoxic bile acids, such as lithocholic acid (LCA), because of limited small bowel absorption of UDCA and conversion of UDCA by bacteria in the colon. We determined the serum bile acid composition in 56 patients with PSC previously enrolled in a randomized, double-blind controlled trial of high-dose UDCA versus placebo. Samples for analysis were obtained at the baseline and at the end of treatment. The mean changes in the UDCA level (16.86 versus 0.05 micromol/L) and total bile acid level (17.21 versus -0.55 micromol/L) were significantly higher in the UDCA group (n = 29) versus the placebo group (n = 27) when pretreatment levels were compared (P < 0.0001). LCA was also markedly increased (0.22 versus 0.01 micromol/L) in the UDCA group compared to the placebo group (P = 0.001). No significant changes were detected for cholic acid, deoxycholic acid, or chenodeoxycholic acid. Patients (n = 9) in the UDCA group who reached clinical endpoints of disease progression (the development of cirrhosis, varices, liver transplantation, or death) tended to have greater increases in their posttreatment total bile acid levels (34.99 versus 9.21 micromol/L, P < 0.08) in comparison with those who did not.
High-dose UDCA treatment in PSC patients results in marked UDCA enrichment and significant expansion of the total serum bile acid pool, including LCA.
UDCA Interferes with Drug Metabolism and Detoxification
UDCA is a potent inducer of the cytochrome NADPH-CYP-c-reductase, Aminopyrine N-demethylase CYP3A1/2, p-Nitrophenol hydroxylase CYP2E1, Ethoxycoumarin O-deethylase, Pentoxyresorufin O-dealkylase CYP2B1/2, Methoxyresorufin O-demethylase CYP1A2, Ethoxyresorufin O-deethylase CYP1A1, and Lauric acid hydroxylase CYP4A and inhibits their inactivation , raises glutathione plasma levels albeit still subnormal or within normal levels , and induces multidrug resistance protein 3, but not multidrug resistance protein 4, and 5. UDCA ability to counteract bile acid toxicity is compromised .
Lipid soluble xenobiotics (drugs and compounds foreign to a human biochemistry) in need of detoxification freely diffuse across cellular membrane of hepatocytes. They undergo detoxification in a common pathway through phases I (detoxification), II (conjugation) and III (excretion). In phase I, hepato-cellular enzymes introduce reactive and polar groups to compound. This phase might result in activation of the xenobiotic being detoxified. Phase I involves a major contribution of the cytochrome P-450 super family oxidation. The introduced hydroxyl groups, or N-, O- and S-dealkylation of substrates result in electrophiles (acceptor of eclectrons, mostly positively charged) and nucleophiles (donors of electrons, i.e., act as a base). Phase II scavenges the resultant of phase I, by active conjugation to glucouronic acid, sulfate, glutathione, and glycine [116–120]. Phase III is handled by the efficient membrane transporters family of the multi drug resistance protein. This family is involved with ATP-dependant transport of a huge variety of hydrophobic anions, to the extracellular matrix for further excretion or metabolism [121,122].
Xenobiotic timely coordinated detoxification is vital in infectious and malignant diseases development, management and prognosis .
UDCA accentuates phase I more than phase II, and does not influence all the multiple drug resistance proteins. Moreover, UDCA consumes glycine and conjugation of liver for its own detoxification and compete with other toxic xenobiotics, for phase II detoxification [25,26].
Well, the subject matter is very complicated and the article is badly written. The author also seems to be on a crusade against UDCA use and has this 'everyone else is wrong' anti-mainstream medicine attitude that biases his conclusions. Still, there's some interesting points made in the paper:
UDCA use in PBC leads to improvements in blood markers, but does not actually improve disease progression and survival. So in a sense, it may merely hide these disease symptoms. Much like statins lower LDL but do not reduce cardiovascular mortality. Similarly, the lowered AST and ALT when oral steroid users take (T)UDCA may not actually reflect improved liver health.
Here the study referenced:
This certainly lends some credence to the hypothesis that UDCA itself has some hepatotoxic effects at high dosages.
Oral steroids lead to a condition called drug-induced cholestasis. Bile ducts are obstructed in this condition, and while 17aa AAS use is continued they remain obstructed. If you concurrently increase bile flow with (T)UDCA, this could lead to ruptures and thereby reduce bile duct function even more in the medium term.
Consistent with this idea, the following study found that the greater the increase in bile acid levels from UDCA, the higher the chance of disease progression:
This part is particularly poorly written and it's not entirely clear that the text leads to the conclusion that 'UDCA Interferes with Drug Metabolism and Detoxification'. Maybe because it only increases phase 1 detox, while inhibiting phase 2? So I can't tell if this is indeed an issue. But if it is, then UDCA would actually interfere with the metabolization of 17aa AAS, thereby increasing their toxicity.
TLDR: There are real concerns that (T)UDCA use while taking oral steroids could be counterproductive, with the decreases in ALT and AST merely masking the damage. The higher the (T)UDCA dosage, the more likely are adverse effects. So either take (T)UDCA after your oral steroid use, or at least limit the dosage of TUDCA to no more than, say, 500mg.