TUDCA

What is TUDCA?

Tauroursodeoxylic acid - better known as TUDCA - is a bile acid that is found in minimal amounts in the human body. Bile acids are compounds produced by the gallbladder that aid in the digestion of fats.

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

How is TUDCA produced?

Bear bile, which contains large amounts of TUDCA, has been used in traditional Chinese medicine. 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 the animal and environmentally friendly production of these substances, such as through the fermentation of certain bacterial strains.

What mechanisms does TUDCA use?

Scientists assume that TUDCA works via the following mechanisms:

• Increasing glucose-induced insulin secretion via the cAMP/PKA pathway, which increases insulin sensitivity (1).
• Alleviation of stress in the endoplasmic reticulum (ER). The ER ensures that proteins are folded correctly (14).
• Reduction of 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 triggers enzymes (capsases) to initiate apoptosis.
• Inactivation of the Bcl-2-associated death promoter (BAD) - a molecule involved in apoptosis (16).
• Removal of toxic bile acids from the liver, preventing them from damaging liver cells (2).

What are the potential health benefits of TUDCA?

Can TUDCA relieve cholestasis?

Cholestasis is a condition in which 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 often associated with other liver diseases including primary bile acid-induced cirrhosis. In scientific studies, TUDCA was able to reduce cholestasis caused by liver damage due to insufficient blood flow (3).

What effects does TUDCA have on 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 bile acid-related cirrhosis (an autoimmune disease that destroys the bile ducts) or hepatitis.

In a study of 12 women suffering from primary bile acid-related cirrhosis, treatment with TUDCA over a period of 2 months reduced liver enzyme levels by 51% (4).

In another study of 23 subjects suffering from the same disease, TUDCA significantly improved levels of the liver enzymes ALT, AST, GGT and alkaline phosphatase (5).

Some scientists hypothesize that TUDCA at low doses may lower liver enzyme levels, although clinical data are still lacking. A study of 5 patients suffering from liver disease found that as little as 10 to 13 mg of TUDCA daily over a 3-month period was able to lower levels of the liver enzyme ALT (6).

Can TUDCA help with liver cirrhosis?

Cirrhosis is a disease of the liver in which scar tissue replaces healthy liver cells. Cirrhosis is a common cause of death and a cause of many diseases, and is one of the 14 leading causes of death worldwide. A study of 18 subjects found TUDCA to be a safe and effective treatment for this condition (7).

Can TUDCA help with hepatitis?

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

In another study, TUDCA reduced liver damage, oxidative stress and liver tissue scarring in mice with fatty liver disease (9). However, the effects of TUDCA on fatty liver disease in humans 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 used to measure disability in ALS patients, with higher scores indicating less disability. A study of 34 ALS patients showed that patients taking 1 gram of TUDCA daily had higher ALSFRS-R scores after one year (17). TUDCA was found to be well tolerated and there was no difference in side effects between the TUDCA and placebo groups.

Can TUDCA help with diabetes complications?

Copper levels are often elevated in diabetes patients. One study found that TUDCA was able to reduce high copper levels to normal levels 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 exposed to high blood glucose levels.

However, there is no research to date that supports the use of TUDCA for diabetes complications in humans.

Can TUDCA help with Alzheimer's disease

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

Scientists are interested in learning whether TUDCA can reduce neuron cell death (apoptosis) in the test tube, as this process is involved in Alzheimer's and other brain diseases.

Can TUDCA help with Parkinson's disease?

TUDCA was able to protect nerve cells in mice with Parkinson's disease. It also reduced the rate of cell death in a rat model of Parkinson's disease (11). However, no clinical studies have yet been conducted with Parkinson's patients.

A randomized, placebo-controlled, double-blind clinical trial to investigate the effects of TUDCA on the progression of Parkinson's disease is currently recruiting subjects.

Scientists believe that UDCA may maintain mitochondrial function and prevent c-Jun N-terminal kinase (JNK) activation. The JNK pathway leads to neuronal death in Parkinson's disease.

Can TUDCA help with Huntington's disease

A study found that TUDCA protected neurons in a mouse model of Huntington's disease. It also reduced the death of brain cells in rats with symptoms of Huntington's disease. However, human studies on the subject 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 bile acid levels in the brain. Scientists believe that this may help with recovery from a stroke, although human studies on the subject are still lacking.

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

Can TUDCA have positive effects on heart health?

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

Can TUDCA have positive effects on retinal health?

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

TUDCA slowed retinal degeneration in mice and slowed retinal degeneration and vision loss in rats.

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

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

Can TUDCA support weight loss?

Based on the existing study results, TUDCA is likely ineffective in supporting weight loss. In a study of 20 obese volunteers, 1,750 mg of TUDCA per day for 4 weeks increased insulin sensitivity in muscle and liver tissue by 30% (13). However, no change in insulin sensitivity of adipose tissue was observed in the same study. Furthermore, no effects on blood glucose and insulin levels were 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 doses in the range of 1,000 to 1,500 mg TUDCA, diarrhea has been observed as a side effect. The following side effects have been observed with UDCA, which is very similar to TUDCA:

• Worsening of existing psoriasis
• Other skin problems (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
• Coughs and colds

Dosage

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

1500 mg was the most effective dosage for reducing 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 reduce liver enzyme levels. Scientists use 15 - 20 mg/kg body weight to improve bile salt composition.

In otherwise healthy obese individuals, doses of 1,750 mg TUDCA per day for 4 weeks were well tolerated. In liver transplant patients, 500 mg of TUDCA daily for a period of one year was not associated with adverse 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.. Rodrigues, 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.