Two questions, one post. Why some people get diarrhoea in the first week, and what happens to people who take it for eighteen months.
Tolerability splits into two questions that get answered by completely different evidence. The first is short-term: why do some people get cramping and urgent stools in the first week? The second is long-term: what happens to someone who takes this for a year or more?
Both are below. They have very different quality of evidence behind them.
Part one: the first week
On forums you will find people reporting cramping and urgent, watery stools shortly after starting TUDCA or any bile salt. You will also find people telling them this is a healing crisis, a flush, the body purging years of stagnant sludge, and that they should carry on.
That advice is wrong, and it is worth explaining why in detail, because the real explanation is more useful and points to a different response.
The enterohepatic loop has a capacity
Bile salts secreted into the small intestine are reabsorbed in the terminal ileum and returned to the liver for reuse. That recycling is efficient, and it has a ceiling.
Exceed the ceiling and the surplus passes into the colon. There, bile acids act as secretagogues: they stimulate the colonic mucosa to secrete water and electrolytes into the lumen and they increase motility. The result is watery, urgent stool with cramping.
Two things push you over that ceiling. Taking a dose on an empty stomach, so there is no fat in the intestine and transit is quick. And starting at a high dose before finding out what your own threshold is.
This is bile acid diarrhoea. It is the same mechanism whether the excess comes from a supplement or from disease, and it is the reason bile acid diarrhoea is treated by binding bile salts rather than by adding them. There is nothing being purged. The bowel is responding to a surfactant load it could not reabsorb.
Gastrointestinal effects, principally loose stools, are the most consistently reported adverse effect of TUDCA across its clinical trial record, and they are dose-related. In a trial of TUDCA at 1.75 to 2 grams daily in ulcerative colitis, diarrhoea was explicitly noted as a side effect at those doses.
A dose-response study in primary biliary cirrhosis compared 500, 1,000 and 1,500 mg daily and found no significant difference between the three doses on the primary endpoint. There is no published basis for assuming that a higher dose works better.
Crosignani A, Battezzati PM, Setchell KDR, et al. Tauroursodeoxycholic acid for treatment of primary biliary cirrhosis: a dose-response study. 1996. PMID: 8674405.
A specific warning worth taking seriously
Bile acids stimulate bile flow and gallbladder contraction. In someone with undiagnosed gallstones, stimulating contraction carries a real risk of mobilising a stone into the bile duct, which produces sudden severe pain in the upper right abdomen and is a medical emergency.
If you have not had your gallbladder imaged and you have a history of biliary pain, that is a conversation to have with a doctor before starting any bile acid, not after.
Sensible practice
Take it with food that contains fat
Mid-meal, with a meal that actually has fat in it. Never on an empty stomach.
Start low
Begin at the lower end and stay there for a week or more before considering any increase. Your threshold is individual and the only way to find it is slowly.
If you get loose stools, reduce or stop
That is the signal you have exceeded what your ileum will reabsorb. Do not push through it. Drop back down or discontinue, and speak to a healthcare professional if it persists.
Part two: what about taking it for a year?
Everything above concerns the first few weeks. The separate question is what continuous use does over a much longer period, and here the evidence comes from an unexpected place.
Most TUDCA research is small, old and short: a few dozen patients for a few weeks or months. The one genuinely large, long, well-controlled human trial of this compound was not run for digestion at all. It was run in amyotrophic lateral sclerosis, because that is where the research funding went. That trial failed to show any benefit for ALS. But because it ran for eighteen months against placebo with hundreds of participants and close monitoring, it produced by far the best safety and tolerability record TUDCA has.
In other words, the most useful thing that trial tells a person considering TUDCA for digestive reasons has nothing to do with what it was testing.
The TUDCA-ALS trial is by a wide margin the most rigorous long-term human data on this compound: randomised, double-blind, placebo-controlled, running 18 months across 25 centres in seven European countries with 334 participants, testing TUDCA added to riluzole.
Topline results announced in March 2024 reported that the trial did not meet its primary endpoint. There was no significant difference from placebo in slowing decline on the ALS Functional Rating Scale, and no significant difference on secondary endpoints including survival and neurofilament light chain.
On tolerability, adverse events were predominantly mild and gastrointestinal, occurring in both the treatment and placebo arms.
TUDCA-ALS phase 3 trial, ClinicalTrials.gov NCT03800524. Topline results announced March 2024; full publication pending at the time of writing.
Two conclusions from that, and both belong in the same paragraph. TUDCA did not work for ALS. And the trial that showed it did not work is also the best evidence available that the compound is tolerated over 18 months of continuous use. A brand that reports only the second half of that is not giving you the full picture.
References
- TUDCA-ALS phase 3 trial. ClinicalTrials.gov identifier NCT03800524. Topline results announced March 2024.
- Crosignani A, Battezzati PM, Setchell KDR, et al. Tauroursodeoxycholic acid for treatment of primary biliary cirrhosis: a dose-response study. 1996. PMID: 8674405.
- Conjugated bile acid replacement therapy in short bowel syndrome patients with a residual colon. Zeitschrift für Gastroenterologie 2004;42(7):583–589. DOI: 10.1055/s-2004-813059.
Educational and scientific information only. Tauroursodeoxycholic acid (TUDCA) is sold as a food supplement and has not been assessed by the Food Standards Agency, the MHRA, the European Food Safety Authority or the US Food and Drug Administration for preventing, treating or curing any disease. Ursodeoxycholic acid (UDCA) is a prescription-only medicine in the UK. Nothing here is a substitute for prescribed treatment. If you are under medical care or taking prescribed medication, speak to your doctor or pharmacist before starting any supplement.