Tauroursodeoxycholic acid (TUDCA)

[Hoopoe]

TUDCA is a hydrophilic bile acid that is produced in the liver. It is used for the treatment of chronic cholestatic liver diseases and for gallstone. TUDCA is orally bioavailable and blood–brain barrier permeable. Bile salts, including TUDCA, play a role in intestinal homeostasis by controlling the size and the composition of the intestinal microbiota. Clinical studies performed on patients with different medical conditions over the last years unanimously report that the chronic administration of hydrophilic bile acids is safe and well-tolerated. It has been shown that TUDCA has neuroprotective effects in a variety of models of different neurodegenerative diseases.

Summarized from: Tauroursodeoxycholic acid in patients with amyotrophic lateral sclerosis: The TUDCA-ALS trial protocol

TUDCA was used in a study of chronic fatigue and ME/CFS: WASF3 disrupts mitochondrial respiration and may mediate exercise intolerance in myalgic encephalomyelitis/chronic fatigue syndrome

There was a small clinical trial of TUDCA for multiple sclerosis which found a limited benefit on some outcomes: Trial of Tauroursodeoxycholic Acid Supplementation in Patients with Progressive MS

There was a clinical trial of TUDCA + sodium phenylbutyrate for ALS which showed a beneficial effect. A subsequent analysis found TUDCA on its own was effective.

To me all this suggests it might be treatment with some effect on ME/CFS.

 

[Hutan]

Tauroursodeoxycholic acid: a potential therapeutic tool in neurodegenerative diseases, 2022 ( a review)

We report here the current knowledge on the potential therapeutic action of hydrophilic bile acids in neurodegenerative conditions, focusing in particular on TUDCA, the most hydrophilic among bile acids.

In another study on the same PD model, the authors reported that TUDCA prevents the MPTP-dependent decrease of dopaminergic fibers and ATP levels, mitochondrial dysfunction and neuroinflammation. Following TUDCA administration (50 mg/kg), the mice also displayed reduction in foot dragging and an overall improvement in gait [61]. These observations suggest TUDCA as a prophylactic treatment in animal models, shedding light on therapies in translational preventative medicine for risk groups.

Another study in the MPTP mouse model of PD also highlighted an anti-neuroinflammatory potential of TUDCA. This bile acid was shown to reduce the pro-inflammatory cytokine interleukin 1 beta and markers of astro- and microgliosis, while increasing the level of the anti-inflammatory protein Annexin-A1 [62]. These data suggest a possible link between suppression of neuroinflammation by TUDCA and neuroprotection, which deserves further characterization in future studies.

The anti-degenerative properties of TUDCA have also been investigated in acute conditions, particularly in rat models of transient focal cerebral ischemia. In a model of middle cerebral artery occlusion, experimental ischemia was found to induce mitochondrial swelling and caspase activation [26]. TUDCA administration 1 h after ischemia resulted in significantly increased bile acid levels in the brain, improved neurologic function, and ~ 50% reduction in infarct size, as assessed 2 and 7 days after reperfusion. In addition, TUDCA significantly reduced mitochondrial swelling, and partially inhibited caspase-3 processing and substrate cleavage [26]. These findings suggest that the mechanisms of in vivo neuroprotection by TUDCA are, at least in part, mediated by inhibition of mitochondrial dysfunction and consequent energetic deficit that triggers caspase activation, subsequently leading to cell death.

Looks as though there are a number of human trials of TUDCA in neurodegenerative diseases underway.

Safety of experimental compounds is of paramount importance for clinical testing in humans. A wide experience on the safety of hydrophilic bile acids has been obtained on hepatobiliary indications. UDCA and TUDCA have been used in the treatment and prevention of cholesterol gallstones and in a variety of conditions, such as primary biliary cirrhosis, liver cirrhosis, primary sclerosing cholangitis, chronic hepatitis C, polycystic liver disease, intrahepatic cholestasis of pregnancy and fatigue in chronic liver disease (Table (Table2).2). All these studies have generally confirmed a good safety profile, reporting mostly mild gastrointestinal adverse events, particularly diarrhoea, abdominal pain, nausea and vomiting, and less frequently rashes and pruritus.

 

[mariovitali]

As probably being one of the first patients that have used TUDCA for ME/CFS and having researched and identified about ER Stress being an important research target ( https://algogenomics.blogspot.com/2017/08/dili-viruses-and-er-stress.html ), some comments :

-I do not believe that ER Stress management alone will bring benefit to most patients (my hypothesis)
-We have to also improve oxidative stress -probably on a personalised level- and make sure that any underlying conditions are managed (my hypothesis)
-TUDCA is considered one of the most effective hepatoprotective substances
-If you consider taking TUCDA, make sure that you choose a good brand. Unfortunately, TUDCA is an expensive supplement.