TUDCA: Effects on the Liver and Kidneys

TUDCA is often called a “liver protector”, and in the sports community also a “kidney protector”. The editorial team examined which mechanisms of TUDCA’s action on these organs are actually described in the scientific literature, where the clinical data end and animal experiments begin, and what should not be expected from the supplement.

How TUDCA Reaches the Liver

TUDCA is a conjugate of ursodeoxycholic acid with the amino acid taurine. After oral intake it is absorbed in the small intestine, mainly in the ileum, and reaches the liver through the portal vein system. Hepatocytes actively take up bile acids from the blood and secrete them back into bile.

This is how the enterohepatic circulation is formed: bile acids travel the “liver — bile — intestine — liver” route many times a day. With regular intake of TUDCA or UDCA, the share of hydrophilic bile acids in the total pool gradually increases, while the share of the more toxic hydrophobic ones decreases.

It is precisely this change in the composition of the pool that is considered one of the main mechanisms of action. Hydrophobic bile acids, accumulating during bile stasis, damage cell membranes and mitochondria. Hydrophilic conjugates are much milder and partly “dilute” this toxicity.

Part of the TUDCA in the intestine is deconjugated by bacteria into UDCA, so the effects of the two substances largely overlap in vivo. This is one of the reasons why clinical reviews often consider them together.

Mechanisms of Action on the Liver

The literature describes several interrelated mechanisms through which UDCA and TUDCA affect the liver. Most of them are examined in detail in the reviews by Paumgartner and Beuers devoted to the treatment of cholestasis.

• Choleretic effect— stimulation of bile secretion by hepatocytes and cholangiocytes, including through enhanced bicarbonate secretion.
• Cytoprotection— protection of cell membranes from hydrophobic bile acids.
• Antiapoptotic action— stabilization of mitochondria and reduced triggering of programmed cell death.
• Reduction of ER stress— the “chemical chaperone” function, described in obesity models (Özcan, 2006).

It is important that these mechanisms work best precisely in cholestasis — bile stasis. Where the main problem lies not in bile acids but, for example, in viral injury or alcohol, the benefit is much less obvious.

For non-alcoholic fatty liver disease (MAFLD), the results of UDCA studies were mostly disappointing, and current guidelines do not recommend it as a standard treatment for steatohepatitis. For TUDCA, there are only limited data here on hepatic insulin sensitivity (Kars, 2010).

Another important nuance: in the study by Lindor et al., very high doses of UDCA in primary sclerosing cholangitis were associated with worse outcomes than placebo. This is a reminder that “more” does not mean “better”, even for relatively safe bile acids.

Drug-Induced Liver Injury and TUDCA

The most common reason for interest in TUDCA among athletes is the desire to “cover” the liver while taking hepatotoxic substances, primarily 17α-alkylated oral steroids. Such substances can cause cholestatic liver injury, up to severe jaundice.

The American College of Gastroenterology’s clinical guideline on drug-induced liver injury (Chalasani, 2021) emphasizes that the main step when toxic injury is suspected is to stop taking the causative substance. Bile acids may be used to relieve the symptoms of cholestasis, but there is no high-quality randomized evidence of their effectiveness specifically for prevention.

In other words, there are no data that TUDCA allows hepatotoxic compounds to be taken “safely”. The supplement does not neutralize the toxic substance and does not cancel the risks of peliosis, liver adenomas, or severe cholestasis described for oral anabolics.

A dangerous side effect of this approach is a false sense of protection. A person may ignore alarming symptoms or postpone tests, relying on a “hepatoprotector”.

Kidneys: What the Experiments Show

There are practically no direct clinical studies of TUDCA as a “nephroprotector” in humans. Claims of kidney protection are based on experiments in rodents and cell cultures.

In such models, TUDCA reduced signs of ER stress and apoptosis in tubular cells during acute kidney injury, ischemia-reperfusion, diabetic nephropathy, and the action of some nephrotoxic drugs. The mechanism is generally the same as in the liver: stabilization of the cell’s protein “conveyor”.

However, transferring these results to humans requires caution. The doses in the experiments, the route of administration, and the duration often do not correspond to real-world use, and the disease models only partly reproduce human pathology.

For the kidneys in athletes, other factors are far more important: blood pressure control, adequate hydration, avoiding NSAID abuse, adequate protein intake, and abstaining from nephrotoxic substances. No supplement compensates for these basic things.

Safety and Tolerability

In clinical studies, TUDCA and UDCA were generally well tolerated. The most common adverse effect was diarrhea or loose stools, which is explained by the effect of bile acids on secretion in the large intestine.

Less often, abdominal discomfort, nausea, and itching are described. In patients with advanced cirrhosis, taking bile acids requires special caution and medical supervision.

A separate risk is associated with the quality of supplements. Unlike registered medicines, the composition and content of the active substance in dietary supplements are controlled less strictly, so the actual dose may differ from the stated one.

It is also worth remembering possible interactions: bile acids can affect the absorption of some drugs, and binding agents (cholestyramine, aluminum-containing antacids) can reduce the absorption of TUDCA itself.

Editorial Conclusions

The best evidence of an effect on the liver concerns cholestatic diseases and was obtained mainly for UDCA. TUDCA acts through similar mechanisms, but its own clinical base is more modest.

Data on kidney protection are so far limited to experiments in animals and cells. Calling TUDCA a proven nephroprotector is incorrect.

TUDCA does not make taking hepatotoxic substances safe. The only reliable way to protect the liver from toxic injury is not to subject it to that injury and to monitor tests in a timely manner.

We also recommend reading the articles “Tests While Taking TUDCA”, “Who Should Not Take TUDCA”, and “N-Acetylcysteine: Effects on the Liver and Kidneys”.

References

1. Paumgartner G, Beuers U. Ursodeoxycholic acid in cholestatic liver disease: mechanisms of action and therapeutic use revisited. Hepatology. 2002;36(3):525–531.
2. Hofmann AF, Hagey LR. Bile acids: chemistry, pathochemistry, biology, pathobiology, and therapeutics. Cell Mol Life Sci. 2008;65(16):2461–2483.
3. 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.
4. 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.
5. Lindor KD, Kowdley KV, Luketic VA, et al. High-dose ursodeoxycholic acid for the treatment of primary sclerosing cholangitis. Hepatology. 2009;50(3):808–814.
6. Chalasani NP, Maddur H, Russo MW, et al. ACG Clinical Guideline: diagnosis and management of idiosyncratic drug-induced liver injury. Am J Gastroenterol. 2021;116(5):878–898.
7. European Association for the Study of the Liver. EASL Clinical Practice Guidelines: management of cholestatic liver diseases. J Hepatol. 2009;51(2):237–267.