Tauroursodeoxycholic acid (TUDCA), also known as ursodoxicoltaurine, is a naturally occurring bile-acid derivative synthesized in the body from ursodeoxycholic acid (UDCA) and taurine.^[10][11] TUDCA is also available as a supplement. Because it can modulate cellular stress responses, TUDCA might have several therapeutic effects.^{[10][11][12][13][14]}

TUDCA’s main benefit is maintaining cellular health by reducing cellular stress and inhibiting inflammatory pathways.^{[12][13][14][10]} For this reason, TUDCA has been proposed to have therapeutic effects on several conditions, including retinal disorders, metabolic conditions, liver-related conditions, neurodegenerative conditions (Alzheimer's disease, Parkinson's disease, and Huntington's disease), and amyotrophic lateral sclerosis (ALS).^[15][16][10]

Although some clinical studies have shown promise in the treatment of ALS,^[1][2] primary biliary cholangitis,^[5][6][7] insulin resistance,^[8] and endothelial function,^[9] TUDCA’s widespread therapeutic claims are largely derived from in vitro experiments^{[10][11][13][14]} and preclinical studies in rats^[17][18][19] and mice.^{[20][21][22][23][24][25][26][27][28][14]} Consequently, the benefits of TUDCA to humans are unclear because there is a lack of robust evidence to support its clinical efficacy.

Despite promising results from in vitro experiments and rodent studies, the main drawback is the lack of large, high-quality randomized controlled trials to validate the therapeutic efficacy of TUDCA on the various conditions it is claimed to treat. While there is one large multicenter trial on primary biliary cholangitis^[5] and a couple of large trials on ALS,^[29] most of the clinical studies that have examined the effects of TUDCA only include a small number of participants (<30) and the effects are variable and small at best.^{[2][6][7][8][9]}

TUDCA appears to be well tolerated in humans: side effects — primarily gastrointestinal issues like diarrhea, nausea, flatulence, and mild abdominal discomfort — are rare and mild,^[5][30][1] and no major safety concerns have been identified in clinical trials. However, many clinical studies of TUDCA fail to report whether any side effects occurred. Furthermore, the exact pathways through which TUDCA exerts its effects are not fully understood (see faq:how-does-TUDCA-work). Consequently, a full understanding of TUDCA’s safety profile in humans is lacking, and the tolerable upper intake level is currently unknown. That said, the ongoing TUDCA-ALS trial includes long-term safety and tolerability as a secondary outcome, which suggests that comprehensive safety data will become available when that data is published.^[31]

TUDCA has potential drug interactions. For example, some evidence has shown that TUDCA might bind to the insulin receptor, which means it could interact with drugs like insulin analogs or insulin sensitizers.^[32] Furthermore, bile acid sequestrant drugs (e.g., cholestyramine, colestipol, or colesevelam) interfere with the absorption of bile acids,^[33][34] which means that bile acid sequestrants could reduce the absorption of TUDCA when it is taken as a supplement. TUDCA might also interact with doxycycline, but the clinical relevance of this interaction is currently unclear.^[35][36] Always consult your doctor or pharmacist before considering using TUDCA to check for drug interactions.

In vitro and animal studies have demonstrated that TUDCA can maintain cellular health by reducing stress to the endoplasmic reticulum (ER).^[12][13][10] The ER is an organelle inside cells that folds proteins so they can function properly. ER stress occurs under certain physiological conditions and results in poor protein folding, a lack of proper protein function, and the triggering of the unfolded protein response which leads to inflammation, fibrosis, or apoptosis (cell death).^[12] Because ER stress is a key component of several chronic conditions, molecules like TUDCA that can reduce ER stress have potential therapeutic value.^[12] Additionally, TUDCA can inhibit inflammatory pathways by reducing NF-kB activity;^[13][14][10] therefore, the potential therapeutic effects of TUDCA may be caused by its effects on ER stress and/or inflammation. That said, it is not completely understood how TUDCA causes these effects.^[12] However, in liver cells, TUDCA has been shown to bind to integrins — receptors on the cellular surface that enable cell-to-cell communication^[37] — and subsequently activate several downstream pathways that prevent apoptosis and enhance bile acid uptake and secretion to prevent cholestasis.^[11] So, there are several mechanisms by which TUDCA might work. However, they are all “potential” mechanisms of action, because further clinical trials are needed to test whether TUDCA conveys therapeutic benefits in humans (see What are TUDCA’s main benefits?).