TUDCA

What is TUDCA?

Tauroursodeoxycholic acid – better known as TUDCA – is a bile acid that occurs in minimal amounts in the human body. Bile acids are compounds that are produced by the gallbladder and help with the digestion of fats.

TUDCA is essentially the same molecule as ursodeoxycholic acid (UDCA), which is used in the medical field for the treatment of gallstones and liver diseases. TUDCA is UDCA with added (conjugated) taurine. Both are bile acids and both act via similar pathways. They differ only in their solubility and bioavailability in the body. There is some research that goes beyond the use of TUDCA for the treatment of liver diseases. TUDCA is sold as a supplement.

How is TUDCA produced?

In the field of traditional Chinese medicine, bear bile was used, which contains large amounts of TUDCA. However, TUDCA from bear bile is highly controversial for animal welfare reasons.

Today, TUDCA and UDCA are produced synthetically. Scientists are constantly developing new methods for an animal-friendly and environmentally friendly production of these substances, such as through fermentation of certain bacterial strains.

Through which mechanisms does TUDCA act?

Scientists assume that TUDCA acts via the following mechanisms:

• Increase of glucose-induced insulin secretion via the cAMP/PKA pathway, which increases insulin sensitivity (1).
• Alleviation of stress in the area of the endoplasmic reticulum (ER). The ER makes sure that proteins are folded correctly (14).
• Reduction of the programmed cell death known as apoptosis in healthy cells (15). TUDCA prevents the molecule BAX from reaching the mitochondria. BAX causes the mitochondria to release cytochrome C, which causes enzymes (caspases) to initiate apoptosis.
• Inactivation of the Bcl-2-associated death promoter (BAD) – a molecule that is involved in apoptosis (16).
• Removal of toxic bile acids from the liver, which prevents them from damaging liver cells (2).

What potential health benefits does TUDCA have?

Can TUDCA alleviate cholestasis?

Cholestasis is a condition in which the bile acid cannot flow properly from the liver into the gallbladder and then into the small intestine. This condition is characterized by a lack of bile acid in the small intestine and an accumulation of bile acid in the liver. Cholestasis is frequently associated with other liver diseases including primary biliary cirrhosis. In scientific studies, TUDCA was able to reduce cholestasis that was caused by liver damage due to insufficient blood flow (3).

What effects does TUDCA have on the liver enzymes in cholestasis?

Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) are two important liver enzymes. Elevated levels of these enzymes can indicate liver problems such as primary biliary cirrhosis (an autoimmune disease that destroys the bile ducts) or hepatitis.

In a study with 12 women who suffered from primary biliary cirrhosis, a treatment with TUDCA over a period of 2 months was able to lower the levels of the liver enzymes by 51% (4).

In a further study with 23 subjects who suffered from the same disease, TUDCA significantly improved the levels of the liver enzymes ALT, AST, GGT and alkaline phosphatase (5).

Some scientists hypothesize that TUDCA in low dosages can lower the levels of the liver enzymes, even though clinical data on this is still lacking. A study with 5 patients who suffered from liver diseases found that as little as 10 to 13 mg of TUDCA daily over a period of 3 months was able to lower the levels of the liver enzyme ALT (6).

Can TUDCA help with liver cirrhosis?

Cirrhosis is a disease of the liver in the course of which scar tissue replaces healthy liver cells. Liver cirrhosis is a widespread cause of death and a cause of numerous diseases, and it ranks among the 14 leading causes of death worldwide. A study with 18 subjects found that TUDCA represents a safe and effective treatment method for this condition (7).

Can TUDCA help with hepatitis?

A study with 150 patients with hepatitis C found that TUDCA was more effective than a placebo and progressively alleviated a chronic hepatitis over a period of 6 months (8).

In another study, TUDCA reduced liver damage, oxidative stress and a scarring of the liver tissue in mice with fatty liver disease (9). The effects of TUDCA in fatty liver disease in humans, however, remain unclear. Scientists are also investigating the effects of TUDCA on hepatitis B and D viruses in cells.

Can TUDCA help with ALS / Lou Gehring's disease?

ALSFRS-R is a functional rating scale for measuring disability in ALS patients, whereby higher values stand for less disability. A study with 34 ALS patients showed that patients who took 1 gram of TUDCA daily had higher ALSFRS-R values after one year (17). TUDCA proved to be well tolerated and there was no difference regarding side effects between the TUDCA and the placebo group.

Can TUDCA help with diabetes complications?

In diabetes patients, copper levels are frequently elevated. A study found that TUDCA was able to lower high copper levels to normal values in mice with type 1 diabetes. Human studies on this topic are still lacking.

Diabetic retinopathy is a complication of diabetes in which the blood cells of the light-sensitive tissue of the eye (the retina) are damaged. Scientists are investigating the effects of TUDCA on human retinal cells that are exposed to high blood sugar levels.

So far, however, there are no studies that support the use of TUDCA for diabetes complications in humans.

Can TUDCA help with Alzheimer's

Amyloid beta (Aβ) plaques are proteins that play a decisive role in the development of Alzheimer's. In mice with Alzheimer's symptoms, TUDCA was able to reduce amyloid beta plaques in the brain. It also prevented memory deficits in mice with Alzheimer's. The effects of TUDCA on Alzheimer's symptoms and the progression of the disease in humans, however, have not yet been investigated more closely (10).

Scientists are interested in finding out whether TUDCA can reduce neuronal cell death (apoptosis) in the test tube, since this process is involved in Alzheimer's and other diseases of the brain.

Can TUDCA help with Parkinson's?

TUDCA was able to protect nerve cells of mice with Parkinson's. It also reduced the rate of cell death in the rat model of Parkinson's disease (11). So far, however, no clinical studies with Parkinson's patients have been carried out.

Subjects are currently being recruited for a randomized, placebo-controlled double-blind clinical study that is intended to investigate the effects of TUDCA on the progression of Parkinson's disease.

Scientists believe that UDCA could maintain the function of the mitochondria and prevent a c-Jun N-terminal kinase (JNK) activation. In Parkinson's disease, the JNK pathway leads to the death of neurons.

Can TUDCA help with Huntington's disease

A study found that TUDCA protected nerve cells in the mouse model of Huntington's disease. It also reduced the death of brain cells in rats with symptoms of Huntington's disease. Human studies on the topic, however, are still lacking.

Can TUDCA reduce the effects of a stroke?

In one study, rats were given TUDCA one hour after a stroke. This study found that TUDCA increased the bile acid levels in the brain. Scientists believe that this can be helpful in the recovery from a stroke, although human studies on the topic are still lacking.

In another study, TUDCA reduced the volume of blood clots and the cell death due to a stroke in animals. TUDCA reduced both the lesion volume and the cell death in the striatum (a part of the brain) in rats after a stroke by 50%.

Can TUDCA have positive effects on heart health?

In rats, TUDCA reduced the death of heart cells after a heart attack (12). This study suggests that the effects of TUDCA on heart function should be investigated further within the scope of animal and human studies.

Can TUDCA have positive effects on the health of the retina?

Retinitis pigmentosa (RP) is a neurodegenerative disease of the brain that leads to blindness. A study carried out with mice was able to show that TUDCA could alleviate RP. The authors of the study noted that TUDCA protected the cone and rod function (cells of the eye that are responsible for vision) and prevented a cell death of these cells.

In mice, TUDCA slowed a degeneration of the retina, and in rats it slowed a retinal degeneration and a loss of vision.

Leber's congenital amaurosis (LCA) is an eye disease that damages the retina. In mice, TUDCA was able to alleviate LCA.

Choroidal neovascularization (CNV) is the formation of new blood vessels in the choroid of the eye – a thin layer directly behind the retina that absorbs stray light. CNV results in a significant and permanent loss of vision through the formation of scar tissue. In mice whose eyes were exposed to laser beams that caused a CNV, TUDCA protected against a CNV formation. This study suggests that TUDCA should be investigated further for its effects on retinal diseases associated with CNV.

Can TUDCA support weight loss?

Based on the existing study results, TUDCA is probably ineffective for supporting weight loss. In a study with 20 obese volunteers, 1.750 mg of TUDCA per day over a period of 4 weeks increased insulin sensitivity in muscle and liver tissue by 30% (13). In the same study, however, no change in the insulin sensitivity of the fat tissue could be observed. In addition, no effects on blood sugar and insulin levels could be observed and TUDCA had no significant effects on body fat or body weight.

Despite these negative research results, bodybuilders use TUDCA as a weight loss or muscle building supplement.

TUDCA side effects and precautions

At dosages in the range of 1.000 to 1.500 mg of TUDCA, diarrhea could be observed as a side effect. The following side effects have been observed with UDCA, which is very similar to TUDCA:

• Worsening of an existing psoriasis
• Other skin problems (skin rashes, dry skin)
• Sweating
• Thinning hair
• Biliary pain and cholecystitis
• Digestive problems (constipation, inflammation of the oral mucosa, flatulence)
• Headaches
• Exhaustion
• Mental disorders (anxiety, depression, sleep disorders)
• Joint pain, muscle pain and back pain
• Cough and runny nose

Dosage

A dose-dependent study investigated dosages of 500 mg, 1000 mg and 1500 mg of TUDCA per day over a period of 6 months. This study found only minor differences in the effects of the dosages on liver markers.

1500 mg was the most effective dosage for reducing the enzyme levels, while the cost-benefit ratio was best at 500 mg. One study found 60 mg/kg/day to be a tolerable dosage for humans.

TUDCA at a dosage of 10 – 13 mg per day for 3 months is able to lower the liver enzyme levels. Scientists use 15 – 20 mg/kg of body weight in order to improve the bile salt composition.

In otherwise healthy obese individuals, dosages of 1.750 mg of TUDCA per day over a period of 4 weeks were well tolerated. In liver transplant patients, 500 mg of TUDCA daily over a period of one year was not associated with undesirable side effects.

References:

1. Vettorazzi JF, Ribeiro RA, Borck PC, Branco RC, Soriano S, Merino B, Boschero AC, Nadal A, Quesada I, Carneiro EM. The bile acid TUDCA increases glucose-induced insulin secretion via the cAMP/PKA pathway in pancreatic beta cells. Metabolism. 2016 Mar;65(3):54-63. doi: 10.1016/j.metabol.2015.10.021. Epub 2015 Oct 17. PMID: 26892516.
2. Piazza F, Montagnani M, Russo C, Azzaroli F, Aldini R, Roda E, Roda A. Competition in liver transport between chenodeoxycholic acid and ursodeoxycholic acid as a mechanism for ursodeoxycholic acid and its amidates' protection of liver damage induced by chenodeoxycholic acid. Dig Liver Dis. 2000 May;32(4):318-28. doi: 10.1016/s1590-8658(00)80025-0. PMID: 11515630.
3. Baiocchi L, Tisone G, Russo MA, Longhi C, Palmieri G, Volpe A, Almerighi C, Telesca C, Carbone M, Toti L, De Leonardis F, Angelico M. TUDCA prevents cholestasis and canalicular damage induced by ischemia-reperfusion injury in the rat, modulating PKCalpha-ezrin pathway. Transpl Int. 2008 Aug;21(8):792-800. doi: 10.1111/j.1432-2277.2008.00682.x. Epub 2008 Apr 23. PMID: 18435680.
4. 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.
5. Larghi A, Crosignani A, Battezzati PM, De Valle G, Allocca M, Invernizzi P, Zuin M, Podda M. Ursodeoxycholic and tauro-ursodeoxycholic acids for the treatment of primary biliary cirrhosis: a pilot crossover study. Aliment Pharmacol Ther. 1997 Apr;11(2):409-14. doi: 10.1046/j.1365-2036.1997.124295000.x. PMID: 9146783.
6. 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.
7. Pan XL, Zhao L, Li L, Li AH, Ye J, Yang L, Xu KS, Hou XH. Efficacy and safety of tauroursodeoxycholic acid in the treatment of liver cirrhosis: a double-blind randomized controlled trial. J Huazhong Univ Sci Technolog Med Sci. 2013 Apr;33(2):189-194. doi: 10.1007/s11596-013-1095-x. Epub 2013 Apr 17. PMID: 23592128.
8. 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.
9. Cho EJ, Yoon JH, Kwak MS, Jang ES, Lee JH, Yu SJ, Kim YJ, Kim CY, Lee HS. Tauroursodeoxycholic acid attenuates progression of steatohepatitis in mice fed a methionine-choline-deficient diet. Dig Dis Sci. 2014 Jul;59(7):1461-74. doi: 10.1007/s10620-014-3217-0. Epub 2014 May 28. PMID: 24865256.
10. Nunes AF, Amaral JD, Lo AC, Fonseca MB, Viana RJ, Callaerts-Vegh Z, D'Hooge R, Rodrigues CM. TUDCA, a bile acid, attenuates amyloid precursor protein processing and amyloid-β deposition in APP/PS1 mice. Mol Neurobiol. 2012 Jun;45(3):440-54. doi: 10.1007/s12035-012-8256-y. Epub 2012 Mar 23. PMID: 22438081.
11. Duan WM, Rodrigues CM, Zhao LR, Steer CJ, Low WC. Tauroursodeoxycholic acid improves the survival and function of nigral transplants in a rat model of Parkinson's disease. Cell Transplant. 2002;11(3):195-205. Erratum in: Cell Transplant. 2002;11(6):619.. Rodrigures, Cecilia MP [corrected to Rodrigues, Cecilia MP]. PMID: 12075985.
12. Rivard AL, Steer CJ, Kren BT, Rodrigues CM, Castro RE, Bianco RW, Low WC. Administration of tauroursodeoxycholic acid (TUDCA) reduces apoptosis following myocardial infarction in rat. Am J Chin Med. 2007;35(2):279-95. doi: 10.1142/S0192415X07004813. PMID: 17436368.
13. Kars M, Yang L, Gregor MF, Mohammed BS, Pietka TA, Finck BN, Patterson BW, Horton JD, Mittendorfer B, Hotamisligil GS, Klein S. Tauroursodeoxycholic Acid may improve liver and muscle but not adipose tissue insulin sensitivity in obese men and women. Diabetes. 2010 Aug;59(8):1899-905. doi: 10.2337/db10-0308. Epub 2010 Jun 3. PMID: 20522594; PMCID: PMC2911053.
14. Xie Y, He Y, Cai Z, Cai J, Xi M, Zhang Y, Xi J. Tauroursodeoxycholic acid inhibits endoplasmic reticulum stress, blocks mitochondrial permeability transition pore opening, and suppresses reperfusion injury through GSK-3ß in cardiac H9c2 cells. Am J Transl Res. 2016 Nov 15;8(11):4586-4597. PMID: 27904664; PMCID: PMC5126306.
15. Vang S, Longley K, Steer CJ, Low WC. The Unexpected Uses of Urso- and Tauroursodeoxycholic Acid in the Treatment of Non-liver Diseases. Glob Adv Health Med. 2014 May;3(3):58-69. doi: 10.7453/gahmj.2014.017. PMID: 24891994; PMCID: PMC4030606.
16. Miller SD, Greene CM, McLean C, Lawless MW, Taggart CC, O'Neill SJ, McElvaney NG. Tauroursodeoxycholic acid inhibits apoptosis induced by Z alpha-1 antitrypsin via inhibition of Bad. Hepatology. 2007 Aug;46(2):496-503. doi: 10.1002/hep.21689. PMID: 17559149.
17. Elia AE, Lalli S, Monsurrò MR, Sagnelli A, Taiello AC, Reggiori B, La Bella V, Tedeschi G, Albanese A. Tauroursodeoxycholic acid in the treatment of patients with amyotrophic lateral sclerosis. Eur J Neurol. 2016 Jan;23(1):45-52. doi: 10.1111/ene.12664. Epub 2015 Feb 9. Erratum in: Eur J Neurol. 2017 Apr;24(4):659. PMID: 25664595; PMCID: PMC5024041.