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TUDCA

Also known as: Tauroursodeoxycholic acid, Tauroursodeoxycholate, Ursodoxicoltaurine, Taurursodiol

Overview

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

Benefits

In vitro and animal studies have demonstrated that TUDCA can maintain cellular health by reducing stress to the endoplasmic reticulum (ER). 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). Because ER stress is a key component of several chronic conditions, molecules like TUDCA that can reduce ER stress have potential therapeutic value. Additionally, TUDCA can inhibit inflammatory pathways by reducing NF-kB activity; 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. However, in liver cells, TUDCA has been shown to bind to integrins — receptors on the cellular surface that enable cell-to-cell communication — and subsequently activate several downstream pathways that prevent apoptosis and enhance bile acid uptake and secretion to prevent cholestasis. 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.

How it works

TUDCA’s main benefit is maintaining cellular health by reducing cellular stress and inhibiting inflammatory pathways. 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). Although some clinical studies have shown promise in the treatment of ALS, primary biliary cholangitis, insulin resistance, and endothelial function, TUDCA’s widespread therapeutic claims are largely derived from in vitro experiments and preclinical studies in rats and mice. Consequently, the benefits of TUDCA to humans are unclear because there is a lack of robust evidence to support its clinical efficacy.

Side effects

Formulation: Tablets/Loose powder. Range of dosages studied: 250 to 2,000 milligrams per day (mg/day). Effective Dosages: Amyotrophic lateral sclerosis (ALS) Adults: The effective dosage for improving ALS is unclear. Some benefits have been found with 1,000 mg taken by mouth twice a day for up to 18 months; however, not all clinical studies confirm this efficacy. Primary biliary cholangitis Adults: The effective dosage for improving primary biliary cholangitis might be 500 to 1,500 mg/day by mouth for up to 6 months; however, more clinical research is needed to confirm this effect. Insulin resistance Adults: The effective dosage for improving insulin resistance might be 1,750 mg/day by mouth for 4 weeks; however, only a single clinical study has examined the effect of TUDCA on insulin resistance.

Dosage

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, 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. 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. 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. Furthermore, bile acid sequestrant drugs (e.g., cholestyramine, colestipol, or colesevelam) interfere with the absorption of bile acids, 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. Always consult your doctor or pharmacist before considering using TUDCA to check for drug interactions.

FAQs

What is TUDCA?

What are bile acids?

Bile acids are molecules synthesized from cholesterol in the liver that play a critical role in the digestion and absorption of dietary fat and fat-soluble vitamins (e.g., vitamin A). Bile acids also act as signaling molecules that regulate the expression of genes involved in energy metabolism and immune responses, and they can be metabolized by gut bacteria, which influences microbial composition and intestinal barrier function.

What are TUDCA’s main benefits?

Does TUDCA treat neurodegenerative diseases?

While the preclinical evidence is promising, it is not currently possible to conclude whether TUDCA is of therapeutic benefit to people with neurodegenerative diseases because of the lack of clinical trials. A detailed explanation is provided below.

Does TUDCA treat ALS (amyotrophic lateral sclerosis)?

TUDCA has been investigated as a potential treatment for amyotrophic lateral sclerosis (ALS, also known as motor neuron disease or Lou Gehrig's disease). While TUDCA appears safe and showed potential in earlier studies, robust evidence from large randomized controlled trials does not support its efficacy in treating ALS. Further research is needed to clarify its role, if any, in managing the disease.

What are TUDCA’s main drawbacks?

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 and a couple of large trials on ALS, 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.