TUDCA Side Effects and Contraindications
TUDCA is often described online as virtually free of side effects. Bile acids are indeed generally well tolerated, but "well tolerated" is not the same as "suitable for everyone". Our editorial team gathered what clinical trials and prescribing information for related bile acids tell us about adverse effects, contraindications and interactions.
Why safety data on TUDCA are limited
Most of what we know about the safety of TUDCA comes from two sources: trials in specific patient groups, such as people with cholestatic liver disease, obesity or ALS, and decades of experience with its close relative ursodeoxycholic acid (UDCA), a licensed medicine in the UK. Because TUDCA and UDCA convert into each other in the gut, UDCA data are a reasonable guide, though not a perfect one.
As a food supplement, TUDCA has not gone through the regulatory safety assessment required of medicines. There is no official summary of product characteristics for TUDCA in the UK, no mandatory adverse event reporting by sellers, and product quality varies.
Clinical trials have typically lasted weeks to a couple of years. Data on long-term use over many years in healthy people simply do not exist. This uncertainty matters most for those who take TUDCA continuously "just in case".
It is also worth remembering that adverse events in trials are recorded under medical supervision, with blood tests and follow-up. Someone self-supplementing at home will not have that safety net.
Reported side effects
Across studies, the most frequently reported adverse effects of TUDCA and UDCA involve the digestive system. In the CENTAUR trial of a sodium phenylbutyrate and taurursodiol combination, gastrointestinal events were more common in the active group, although part of this may relate to the phenylbutyrate component.
| Side effect | Frequency in studies | Comment |
|---|---|---|
| Loose stools, diarrhoea | Most common | Often dose-related; bile acids draw water into the bowel |
| Abdominal discomfort, nausea | Occasional | Usually mild and settles |
| Itching | Uncommon | Reported in some liver disease patients |
| Rash | Rare | Possible hypersensitivity reaction |
| Gallstone calcification | Rare (UDCA data) | Relevant for people with existing stones |
Diarrhoea arises because unabsorbed bile acids reaching the colon stimulate fluid secretion. Reducing the amount or splitting it through the day often helps, but persistent diarrhoea warrants stopping the product and seeking advice.
In the small trial of obese adults by Kars and colleagues, 1,750 mg daily for four weeks was well tolerated, with no serious adverse events. Similarly, the ALS trial by Elia and colleagues reported good tolerability over a year. These reassuring findings come from carefully monitored settings.
Contraindications: who should avoid TUDCA
Based on prescribing information for UDCA and general pharmacological principles, TUDCA is not appropriate, or should only be used under specialist supervision, in the following situations:
- Acute inflammation of the gallbladder or bile ducts.
- Blockage of the bile ducts, for example by a stone or tumour.
- Frequent episodes of biliary colic.
- Calcified or radio-opaque gallstones, or a non-functioning gallbladder.
- Advanced liver cirrhosis, unless directed by a hepatologist.
- Active inflammatory bowel disease, where diarrhoea may worsen.
- Pregnancy and breastfeeding, owing to insufficient data.
- Children, except under specialist care.
In all these situations, symptoms such as pain in the upper right abdomen, fever or yellowing of the skin and eyes need prompt medical assessment rather than a supplement.
People who have had their gallbladder removed generally tolerate bile acids, but some already experience bile acid diarrhoea after surgery and may find symptoms worsen.
Interactions with medicines
Because TUDCA behaves like other bile acids, interactions described for UDCA are relevant. They are not always dramatic, but they can change the effect of important medicines.
Bile acid sequestrants such as colestyramine, and antacids containing aluminium, bind bile acids in the gut and reduce their absorption; doses should be separated by several hours. UDCA can increase the absorption of ciclosporin, so people taking this immunosuppressant need monitoring if they start or stop a bile acid.
Oestrogen-containing medicines and some cholesterol-lowering drugs increase cholesterol secretion into bile and may counteract the effect of bile acids on gallstones. Because TUDCA may improve insulin sensitivity, people taking diabetes medication should monitor their glucose and inform their doctor.
Long-term and high-dose concerns
The most important safety signal for bile acids comes from high-dose UDCA in primary sclerosing cholangitis. A trial by Lindor and colleagues, published in Hepatology in 2009, found that 28–30 mg per kilogram per day was associated with more serious adverse events, including progression to transplant, than placebo. A follow-up analysis by Eaton and colleagues linked high-dose UDCA with an increased risk of colorectal neoplasia in patients with ulcerative colitis and sclerosing cholangitis.
These findings concern a specific disease and doses well above those typically used in supplements, so they cannot be directly applied to healthy people. Nonetheless, they show that more is not necessarily better and that bile acids are pharmacologically active substances.
Another frequent misconception is that TUDCA can neutralise the liver toxicity of other substances, such as excessive alcohol or hepatotoxic drugs. No controlled human study supports this. Relying on TUDCA as a safety net may encourage riskier behaviour and delay medical attention.
Anyone with abnormal liver function tests, unexplained fatigue, dark urine or jaundice should be assessed by a doctor. A supplement is not a substitute for diagnosis.
Conclusions of the editorial team
TUDCA is generally well tolerated in clinical studies, with digestive upset, particularly loose stools, the most common complaint. Serious side effects are rare in the doses and durations studied.
However, there are clear contraindications, including bile duct obstruction and acute gallbladder disease, and relevant interactions with medicines such as ciclosporin and bile acid binders. High-dose data from UDCA in sclerosing cholangitis are a reminder that bile acids are active drugs, and long-term safety in healthy people remains unknown.
For further reading, consider our articles on what clinical studies show about TUDCA, on understanding liver function tests, and on gallstones and diet.
References
- Lindor KD, Kowdley KV, Luketic VA, et al. High-dose ursodeoxycholic acid for the long-term treatment of primary sclerosing cholangitis. Hepatology. 2009;50(3):808–814.
- Eaton JE, Silveira MG, Pardi DS, et al. High-dose ursodeoxycholic acid is associated with the development of colorectal neoplasia in patients with ulcerative colitis and primary sclerosing cholangitis. Am J Gastroenterol. 2011;106(9):1638–1645.
- 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.
- Elia AE, Lalli S, Monsurrò MR, et al. Tauroursodeoxycholic acid in the treatment of patients with amyotrophic lateral sclerosis. Eur J Neurol. 2016;23(1):45–52.
- European Association for the Study of the Liver. EASL Clinical Practice Guidelines: the diagnosis and management of patients with primary biliary cholangitis. J Hepatol. 2017;67(1):145–172.
