The History of TUDCA: From Bear Bile to Modern Research
Few supplements have a back story as strange as TUDCA. Tauroursodeoxycholic acid began as an ingredient in dried bear bile, prized for centuries in East Asian medicine, and ended up in laboratory studies on diabetes, eye disease, and ALS. Our editorial team traces how this bile acid traveled from folk pharmacy to the modern supplement shelf.
A bile acid with an unusual origin
Bile acids are made in the liver from cholesterol and help the body digest fats. Most mammals produce a similar mix of them, but bears are an exception: their bile contains unusually large amounts of ursodeoxycholic acid (UDCA), much of it bound to the amino acid taurine. That taurine-bound form is TUDCA.
A comparative study by Hagey and colleagues in 1993 analyzed the bile of bears, pandas, and related carnivores and confirmed how distinctive the bear profile is. The very name "urso" comes from the Latin ursus, meaning bear, a reminder of where the molecule was first found.
Biologically, UDCA and TUDCA are more water-soluble and less toxic to cells than many other bile acids. This "gentle" profile is the foundation of nearly everything that later made them interesting to medicine.
In humans, UDCA occurs only in small quantities, and the liver can attach either taurine or glycine to it. That is why TUDCA and its glycine counterpart both appear in human bile after a person takes UDCA as a medication.
Traditional medicine and the bear bile trade
Dried bear bile, known as xiong dan in Chinese, appears in traditional texts going back well over a thousand years. Practitioners used it for liver complaints, eye conditions, fever, and convulsions. Without any chemistry to guide them, they had stumbled on a substance that later research would connect to liver protection.
The demand created a grim industry. In parts of Asia, bears have been kept on farms where bile is extracted from living animals, a practice condemned by animal welfare organizations worldwide. International trade in bear parts is regulated under CITES, and in the United States the sale of bear gallbladders is restricted by many state laws.
Modern synthesis made animal sources unnecessary. UDCA can be produced chemically from cholic acid obtained from cattle bile, and TUDCA is then made by conjugating UDCA with taurine. Supplements sold today use this semi-synthetic route rather than bear bile.
For readers, this history is a useful reminder that "traditional" does not automatically mean ethical or safe. The modern molecule offers the same compound without the cruelty and contamination risks of the old trade.
From chemistry lab to liver clinic
In the early twentieth century, chemists began isolating bile acids. Swedish chemist Olof Hammarsten reported a new bile acid from polar bear bile around 1902, and in the 1920s Japanese researcher Masato Shoda crystallized and named ursodeoxycholic acid from bear bile. Structural work followed over the next decades.
The clinical breakthrough came with UDCA rather than TUDCA. In the 1970s, researchers found that UDCA could dissolve cholesterol gallstones in some patients. Later it became a standard treatment for primary biliary cholangitis (PBC), a chronic autoimmune liver disease.
In the U.S., UDCA (ursodiol) is a prescription medication sold under names such as Actigall and Urso. TUDCA itself, by contrast, has been used as a prescription drug in some countries, including Italy, but in the U.S. it is marketed as a dietary supplement rather than an FDA-approved drug.
Italian groups in the 1990s studied TUDCA directly in PBC patients and found it improved liver enzyme levels in a dose-dependent manner, adding to a picture of the conjugated form as at least as useful as UDCA in cholestatic conditions.
The "chemical chaperone" era
The modern wave of interest started in 2006, when Özcan and colleagues published a landmark paper in Science. Working with obese, diabetic mice, they showed that TUDCA and another compound reduced endoplasmic reticulum (ER) stress and restored insulin sensitivity. They described these molecules as "chemical chaperones."
ER stress occurs when cells struggle to fold proteins correctly. It is implicated in diabetes, fatty liver, neurodegeneration, and retinal disease. If a supplement-grade molecule could ease ER stress, the implications seemed enormous, and research groups around the world began testing TUDCA in animal models.
Human data came more slowly. In 2010, Kars and colleagues gave obese adults 1,750 mg of TUDCA per day for four weeks and reported improved insulin sensitivity in liver and muscle, but not in fat tissue. It was a small study, yet it showed that the mouse findings had at least partial relevance to people.
Key areas investigated since then include:
- liver disease and cholestasis;
- insulin resistance and type 2 diabetes;
- neurodegenerative disorders, including ALS and Parkinson's disease;
- retinal degeneration and other eye conditions.
ALS, approval, and the modern supplement market
The most dramatic chapter involved amyotrophic lateral sclerosis. In 2020, Paganoni and colleagues published the CENTAUR trial in the New England Journal of Medicine, testing a combination of sodium phenylbutyrate and taurursodiol (TUDCA). The combination slowed functional decline compared with placebo over 24 weeks.
Based in part on those results, the FDA approved the combination, marketed as Relyvrio, in 2022. However, the larger confirmatory PHOENIX trial did not show a benefit, and in 2024 the manufacturer withdrew the drug from the U.S. market. The episode illustrates how promising early data can fail to hold up.
Meanwhile, TUDCA found a separate audience in the fitness world, where it is marketed for liver support. That popularity has grown faster than the evidence, especially among users of oral anabolic steroids, who sometimes assume TUDCA cancels out liver toxicity. No clinical trial has shown that, and our editorial team cautions strongly against this assumption.
| Period | Main use | Status in the U.S. |
|---|---|---|
| Traditional medicine | Bear bile for liver and eye complaints | Bear parts restricted |
| 1970s onward | UDCA for gallstones and PBC | Prescription drug |
| 2006 onward | TUDCA in ER stress research | Research compound / supplement |
| 2022–2024 | TUDCA + phenylbutyrate for ALS | Approved, then withdrawn |
Editorial Team Conclusions
TUDCA's story spans folk medicine, organic chemistry, hepatology, and cutting-edge neurology. Its parent compound UDCA is a proven liver drug, while TUDCA itself remains a molecule with intriguing laboratory data and modest human evidence.
The history also teaches restraint: a successful mouse study or an early-phase trial does not guarantee a real-world benefit, as the ALS saga showed. Supplement users should keep that in mind before treating TUDCA as a universal liver shield.
To continue reading, we suggest our articles on lab tests to monitor while taking TUDCA, on the difference between UDCA and TUDCA, and on how liver enzymes respond to intense training.
References
- Hagey LR, Crombie DL, Espinosa E, et al. Ursodeoxycholic acid in the Ursidae: biliary bile acids of bears, pandas, and related carnivores. J Lipid Res. 1993;34(11):1911–1917.
- Paumgartner G, Beuers U. Ursodeoxycholic acid in cholestatic liver disease: mechanisms of action and therapeutic use revisited. Hepatology. 2002;36(3):525–531.
- Özcan U, Yilmaz E, Özcan L, et al. Chemical chaperones reduce ER stress and restore glucose homeostasis in a mouse model of type 2 diabetes. Science. 2006;313(5790):1137–1140.
- Kars M, Yang L, Gregor MF, et al. Tauroursodeoxycholic acid may improve liver and muscle but not adipose tissue insulin sensitivity in obese men and women. Diabetes. 2010;59(8):1899–1905.
- Paganoni S, Macklin EA, Hendrix S, et al. Trial of sodium phenylbutyrate–taurursodiol for amyotrophic lateral sclerosis. N Engl J Med. 2020;383(10):919–930.
- Hofmann AF. The continuing importance of bile acids in liver and intestinal disease. Arch Intern Med. 1999;159(22):2647–2658.
