Best TUDCA dosing for liver enzymes? (Benefits, Side Effects)

What is the recommended TUDCA dosing?

  • Liver regenesis: 10-13 mg daily for 3 months.
  • Improving bile salt composition: 15-20 mg per kg of bodyweight.
  • Muscle and liver insulin sensitivity: 1750 mg daily for up to 4 weeks.
  • Primary biliary cirrhosis: 750 mg daily for 2 months.
  • Liver transplant: 500 mg daily for 1 year.
  • Chronic hepatitis: 500 mg daily, for 6 months.
  • ALS: 1 g twice daily for 1 year.
  • Liver and eye health: two 250 mg capsules daily.
  • Primary biliary cholangitis: 250 mg
  • Bodybuilders: 500 – 1500 mg daily.

A wash out period of 3 months is recommended after each 6 month period of ingestion.


The bile acid known as Tauroursodeoxycholic acid (TUDCA) may be be effective for the treatment of chronic liver diseases, especially for Hepatitis C Virus related chronic hepatitis, in which bile duct damage and some degree of cholestasis occur.

On the video below, Dr. Jerry Brainum explains how TUDCA can act as a liver protection supplement.


What are TUDCA’s side effects?

Diarrhea was the only TUDCA side effect with doses over 1000 mg daily.


TUDCA benefits

TUDCA benefits include the treatment of the following health conditions:

  • Primary biliary cirrhosis
  • Chronic hepatitis caused by HCV
  • ALS
TUDCA_liver_enzymes
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Chronic Hepatitis

Study 1

  • Title: Does tauroursodeoxycholic acid (TUDCA) treatment increase hepatocyte proliferation in patients with chronic liver disease?.
  • Duration: 3 months.

Subject Information

  • Health Status: chronic liver disease.
  • Number of subjects: 5.

Despite numerous studies on the effects of bile salts therapy in chronic liver disease, there are no reports on the influence such therapy has on hepatocyte proliferation.

Method used

The aim of this preliminary study was to evaluate the effect of TUDCA on hepatocyte proliferation in 5 patients with HCV-correlated chronic liver disease. All patients were treated with TUDCA (10-13 mg/day) for three months and the determination of PCNA (Proliferating Cell Nuclear Antigen) expression was used to assess the proliferative activity of hepatocytes at the beginning and at the end of treatment.

Results

TUDCA reduced both ALT and Knodell’s score in the 5 patients in whom a significant increase of PCNA-LI was observed after treatment.

Conclusion

TUDCA administration seems to stimulate hepatocyte proliferation in man.

Study 2

  • Title: Tauroursodeoxycholic acid for the treatment of HCV-related chronic hepatitis: a multicenter placebo-controlled study.
  • Duration: 6 months.

Subject Information

  • Health Status: chronic hepatitis.
  • Number of subjects: 150.

Method used

One hundred and fifty patients with chronic hepatitis were randomly assigned to receive tauroursodeoxycholic acid at daily doses of 500 mg or 750 mg, or a placebo for 6 months.

Results

A consistent decrease in aminotransferase serum levels was observed in patients treated with tauroursodeoxycholic acid compared with placebo (p<0.001) and a progressive improvement with time was also found (p<0.05; linear time effect).

Conclusions

Tauroursodeoxycholic acid improves the biochemical expression of chronic hepatitis. Long-term studies with clinically relevant end-points are warranted.


Primary biliary cirrhosis

Study 1

  • Title: Tauroursodeoxycholic acid for treatment of primary biliary cirrhosis. A dose-response study.
  • Duration: 6 months.

Subject Information

  • Health Status: primary biliary cirrhosis.
  • Number of subjects: 24.

Method used

We performed a dose-response study on 24 patients with primary biliary cirrhosis who were randomly assigned to receive 500, 1000, or 1500 mg daily of tauroursodeoxycholic acid for six months.

Results

  • Biliary enrichment with ursodeoxycholic acid ranged from 15% to 48% and was not related with the dose.
  • Liver enzyme levels decreased significantly after the first month of treatment with all three doses.
  • No significant difference among the three doses was found, although further reduction over time occurred with 1000 and 1500mg daily.
  • Plasma total and HDL cholesterol significantly decreased in patients administered the two higher doses.
  • Diarrhea was the only side effect.

Conclusion

A dose of about 10mg/kg body wt/day of tauroursodeoxycholic acid should be used for long-term studies in patients with primary biliary cirrhosis.

Study 2

  • Title: Differences in the metabolism and disposition of ursodeoxycholic acid and of its taurine-conjugated species in patients with primary biliary cirrhosis.
  • Duration: 2 months.

Subject Information

  • Health Status: primary biliary cirrhosis.
  • Number of subjects: 12.
  • Gender: female.

The clinical effectiveness of ursodeoxycholate in the treatment of liver disease may be limited by its poor absorption and extensive biotransformation. Because in vitro and in vivo studies suggest that the more hydrophilic bile acid tauroursodeoxycholate has greater beneficial effects than ursodeoxycholate, we have compared for the first time the absorption, metabolism, and clinical responses to these bile acids in patients with primary biliary cirrhosis (PBC).

Method used

Twelve female patients with PBC were administered tauroursodeoxycholate and ursodeoxycholate (750 mg/d for 2 months) in a study. Bile acids were measured in serum, duodenal bile, urine, and feces.

Results

  • Biliary ursodeoxycholate enrichment was higher during tauroursodeoxycholate administration (32.6% vs. 29.2% during ursodeoxycholate).
  • Lithocholic acid concentration was consistently higher in all biological fluids during ursodeoxycholate administration.
  • Fecal bile acid excretion was the major route of elimination of both bile acids; ursodeoxycholate accounted for 8% and 23% of the total fecal bile acids during tauroursodeoxycholate and ursodeoxycholate administration, respectively.
  • Tauroursodeoxycholate was better absorbed than ursodeoxycholate, and, although it was partially deconjugated and reconjugated with glycine, it underwent reduced biotransformation to more hydrophobic metabolites.

Conclusion

This comparative study suggests that tauroursodeoxycholate has significant advantages over ursodeoxycholate that may be of benefit for long-term therapy in PBC.

Study 3

  • Title: Ursodeoxycholic and tauro-ursodeoxycholic acids for the treatment of primary biliary cirrhosis: a pilot crossover study.
  • Duration: 15 months.

Subject Information

  • Health Status: primary biliary cirrhosis.
  • Number of subjects: 23.

Method used

The effects of ursodeoxycholic and tauro-ursodeoxycholic acids were compared in 23 patients with primary biliary cirrhosis according to a crossover design. Both drugs were administered at the daily dose of 500 mg. in a randomly assigned sequence for two 6-month periods separated by a 3-month wash-out period.

Results

Serum liver enzymes related to cholestasis and cytolysis consistently improved, as compared to baseline values, during the administration of both ursodeoxycholic and tauro-ursodeoxycholic acids, but no significant difference between these two bile acids was found. Both treatments were well tolerated and no patient complained of side effects.

Conclusion

In the short-term, tauro-ursodeoxycholic acid appears to be safe and at least as effective as ursodeoxycholic acid for the treatment of primary biliary cirrhosis.

Study 4

  • Title: Efficacy and safety of tauroursodeoxycholic acid in the treatment of liver cirrhosis: a double-blind randomized controlled trial .
  • Duration: 6 months.

Subject Information

  • Health Status: patients with liver cirrhosis.
  • Number of subjects: 23 patients were randomly divided into TUDCA group (12) and UDCA group (11).

Method used

The patients were given TUDCA and UDCA respectively at the daily dose of 750 mg, in a randomly assigned sequence for a 6-month period.

Results

  • Albumin levels were significantly increased in both TUDCA and UDCA groups.
  • Markers for liver fibrosis were slightly decreased with the difference being not significant in either group.
  • Only one patient in TUDCA group had significant relief.
  • Both treatments were well tolerated and no patient complained of side effects.

Conclusion

  • It is suggested that TUDCA therapy is safe and appears to be more effective than UDCA in the treatment of liver cirrhosis.
  • However, both drugs exert no effect on the serum markers for liver fibrosis during 6-month treatment.

TUDCA dose for ALS

  • TUDCA 1 g twice daily (2g daily) for 54 weeks.
  • Riluzole 50 mg twice daily (100 mg daily).

Study Info

  • Title: Tauroursodeoxycholic acid in the treatment of patients with amyotrophic lateral sclerosis.
  • Duration: 54 weeks.

Subject Information

  • Health Status: ALS.
  • Number of subjects: 34.

Method used

Patients under treatment were randomized to placebo or TUDCA and were evaluated after a lead‐in period of 3 months.

Results

  • Tauroursodeoxycholic acid was well tolerated; there were no between‐group differences for adverse events.
  • The proportion of responders was higher under TUDCA (87%) than under placebo (43%).

Conclusion

This pilot study provides preliminary clinical data indicating that TUDCA is safe and may be effective in ALS.


Insulin resistance

Study Info

  • Title: Tauroursodeoxycholic Acid may improve liver and muscle but not adipose tissue insulin sensitivity in obese men and women.
  • Duration: 4 weeks.

Subject Information

  • Health Status: obese.
  • Number of subjects: 20.

Method used

Patients were randomized to 4 weeks of treatment with TUDCA (1,750 mg/day) or placebo.

Results

  • Liver and muscle insulin sensitivity increased by approximately 30% after treatment with TUDCA but did not change after placebo therapy.
  • In addition, therapy with TUDCA, but not placebo, increased muscle insulin signaling.
  • Markers of stress in muscle or adipose tissue did not change after treatment with either TUDCA or placebo.

Conclusion

This data demonstrates that TUDCA might be an effective pharmacological approach for treating insulin resistance. Additional studies are needed to evaluate the target cells and mechanisms responsible for this effect.


Liver Transplant

Study Info

  • Title: One-year pilot study on tauroursodeoxycholic acid as an adjuvant treatment after liver transplantation.
  • Duration: 12 months.

Subject Information

  • Health Status: undergoing liver transplantation.
  • Number of subjects: 33.

Method used

  • Sixteen patients were randomized to receive tauroursodeoxycholic acid (250 b.i.d. for 12 months) and 17 served as controls.
  • Tauroursodeoxycholic acid was given from day 5 after transplantation for one year.

Results

  • Tauroursodeoxycholic acid treatment was safe and well tolerated.
  • No drop outs occurred.
  • The one-year actuarial survival was 78.6% in patients treated with tauroursodeoxycholic acid and 86.7% in controls.
  • No differences were observed with respect to early or late graft function and survival, nor to acute cellular rejection.
  • Tauroursodeoxycholic acid therapy was associated with lower cholesterol levels during the early postoperative months; with milder cholestasis; with a drop in biliary cholates but no changes in bile salts.

Conclusion

Long-term treatment with low dose tauroursodeoxycholic acid after liver transplantation is safe but does not affect graft function and survival.


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Sources

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  2. Invernizzi P, Setchell KD, Crosignani A, Battezzati PM, Larghi A, O’Connell NC, Podda M. Differences in the metabolism and disposition of ursodeoxycholic acid and of its taurine-conjugated species in patients with primary biliary cirrhosis. Hepatology. 1999 Feb;29(2):320-7. doi: 10.1002/hep.510290220. PMID: 9918905.
  3. Crosignani A, Budillon G, Cimino L, Del Vecchio Blanco C, Loguercio C, Ideo G, Raimondo G, Stabilini R, Podda M. Tauroursodeoxycholic acid for the treatment of HCV-related chronic hepatitis: a multicenter placebo-controlled study. Hepatogastroenterology. 1998 Sep-Oct;45(23):1624-9. PMID: 9840118.
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  5. Panella C, Ierardi E, De Marco MF, Barone M, Guglielmi FW, Polimeno L, Francavilla A. Does tauroursodeoxycholic acid (TUDCA) treatment increase hepatocyte proliferation in patients with chronic liver disease? Ital J Gastroenterol. 1995 Jun;27(5):256-8. PMID: 8541578.
  6. Elia, A E et al. “Tauroursodeoxycholic acid in the treatment of patients with amyotrophic lateral sclerosis.” European journal of neurology vol. 23,1 (2016): 45-52. doi:10.1111/ene.12664