One of my colleagues prescribed it for me off-label after I had a retinal detachment, since there’s a study showing it can improve outcomes from that, but otherwise it might be a challenge to find a good reason for a health care provider to prescribe it since it only has specific indications that don’t include disease prevention.
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Ah OK that’s pretty bad. I think in Europe you can prescribe something without an indication. Or at least most pharmacies don’t check the indication. In some countries (e.g. Turkey or UAE) pharmacies don’t even ask for a prescription so you can get whatever you want (at least for “normal” drugs, o assume they check when someone asks for morphine…).
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Treatment of acyl-CoA oxidase 2 deficiency with ursodeoxycholic acid is discussed.
In ACOX2 deficiency there is evidence that liver disease may be improved by treatment with UDCA. UDCA does not inhibit the rate-limiting steps in bile acid synthesis but has unique choleretic properties that may improve bile flow when the production of conjugates of CDCA and CA is reduced.
Relevant @John_Hemming?
- AMX0035: sodium phenylbutyrate [PB] and taurursodiol [TURSO, also known as ursodoxicoltaurine]
- PSP: a Parkinsonian disorder that is different from Parkinson’s disease
It may link to ACBP, but I don’t know. I presume it is longer chain acyl groups.
More good news for UDCA?
Metabolomics reveals that influenza virus infection significantly reduced the concentrations of secondary bile acid (BA) in feces at 7 post-infection (dpi). Oral administration of B. dorei increased bile salt hydrolase (BSH) activity and restored the BA metabolism, thereby protecting wild-type but not TGR5-deficient mice from influenza virus infection. B.dorei-mediated TGR5 activation inhibited influenza virus-induced lung inflammation via cAMP-PKA pathway. Supplementing exogenous Ursodeoxycholic acid (UDCA) and Hyodeoxycholic acid (HDCA), two metabolites changed dramatically after B. dorei treatment, reproduced the protective effect of B. dorei.
UDCA and HDCA alleviate the severity of influenza infection
To explore whether UDCA or HDCA alone was sufficient to protect against influenza infection, the mice were also administered orally with UDCA or HDCA, as described previously. The results showed that UDCA slightly reduced weight loss, but significantly decreased lung index, protected the intestine, and inhibited viral replication at 7 dpi. HDCA dramatically reduced weight loss and lung index. No statistically significant differences were observed in colon shortening or M1 gene expression with HDCA treatment (Fig. 6A-D). Both UDCA and HDCA reduced inflammatory cell infiltration in lung tissue and the number of nucleated cells in BALF, which increased significantly after lung injury (Fig. 6E-F). As expected, UDCA and HDCA reduced the secretion of inflammatory factors in the lung caused by influenza virus, especially IL-1β (Fig. 6G). Western blot results also confirmed the activation of TGR5-cAMP-PKA pathway and inhibition of NLRP3 inflammasome activation (Fig. 6H). The above results suggest that UDCA and HDCA may provide protection against influenza infection and relieve lung inflammation, and UDCA has better effect than HDCA.
UDCA and HDCA inhibit NLRP3 inflammasome activation via cAMP-PKA pathway
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University of Helsinki
Hallmarks of sensorineural hearing loss are elevated hearing thresholds and defects in temporal auditory processing, the former being often caused by outer hair cell (OHC) damage, and the latter by the loss of synapses between inner hair cells (IHCs) and spiral ganglion neurons. In the well-studied CBA/CaJ mouse strain, these impairments are disconnected, IHC synaptopathy preceding OHC loss. We have investigated the relationship between IHC synaptopathy and OHC loss in the C57BL/6J (B6) and ICR mouse strains that model accelerated age-related hearing loss. Regression analysis revealed a strong correlation between these variables across the high-to-low frequency axis of the cochlea. Using the fluorescent dye FM1–43 as a proxy for mechanotransduction (MET) in the hair-cell stereocilia bundle, we found that MET malfunction coexisted with synaptopathy in IHCs. Thus, our results suggest that a MET defect drives IHC synaptopathy in the B6 and ICR strains known to carry a missense mutation of Cadherin 23, encoding a stereocilia bundle protein. Previous data have suggested that OHC stereocilia abnormalities could trigger OHC death. Therefore, stereocilia defect could be a trigger of intracellular stress that drives both IHC synaptopathy and OHC loss. To determine whether tauroursodeoxycholic acid (TUDCA), known to target several stress signalling pathways, could influence cochlear pathology, we conducted long-term TUDCA delivery to ICR mice. TUDCA provided partial protection against IHC synaptopathy but did not prevent OHC loss. These results in two mouse models of accelerated cochlear pathology provide novel insights into the mechanisms behind age-related hearing loss.
Considering that TUDCA administration is well-tolerated in long-term use, shown in human studies as well (Parry et al., 2010, Zucchi et al., 2023), TUDCA might have potential as a pharmacotherapeutic agent against auditory synaptopathy. TUDCA might slow down ribbon synapse loss with age, like it has been shown to attenuate neurodegeneration in an animal model of spinocerebellar ataxia type 3 (Duarte-Silva et al., 2024). It could be speculated that TUDCA’s efficiency in the cochlea is better when IHC synapse loss has a slower path, like in ageing B6 mice and in humans (Wu et al., 2019). To progress to validate TUDCA’s therapeutic potential in the pathological cochlea, understanding of its mode of action is needed, including its impact on the poorly understood molecular pathways promoting ribbon synapse maintenance.
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Imperial College London + John Hopkings University: Protective effect of ursodeoxycholic acid upon the post-myocardial infarction heart 2025
Our hypothesis was that UDCA protects the post-MI failing heart against dangerous arrhythmia through its dual effect as an anti-fibrotic and anti-arrhythmic agent.
We investigated the effect of UDCA upon a 16-week post-MI rat model.
We found that chronic dietary supplementation of UDCA prevents adverse remodelling of the myocardium, maintaining function so that it was comparable to sham. UDCA attenuated the structural and functional remodelling of the LV in the MI rat heart, when monitored by echocardiogram. At 16 weeks post-surgery the LVEDd, LVESd, area at diastole and area at systole of the MI group were significantly higher than the sham group (Figure 1Ai, ii, iv and v), this corresponded with a reduction of LV ejection fraction and fractional area shortening (Figure 1Aiii and vi). UDCA-treated animals showed a significant improvement over the MI group in LVEDd, LVESd and area at systole, but not area at diastole. The UDCA-treated animals were comparable to the sham group in all parameters at 8 and 16 weeks post-MI.
Transferring our experimental data to an in silico 3D human LV model, we found that a combination of reduced arrhythmic substrate area and improved CV (two identified benefits of UDCA-treated post-MI rats) acted together to reduce arrhythmogenicity.
This study identifies that UDCA is anti-fibrotic and anti-arrhythmic in post-MI rat. We found that simulation of UDCA treatment on a human model reduced the occurrence of VT. This indicates that UDCA is a candidate treatment for the prevention of post-MI HF (& arrhythmia) through anti-fibrotic and anti-arrhythmic effects.
Oral Ursodeoxycholic Acid Is Associated With Decreased Rate of AMD 2025
A total of 5,863 patients taking UDCA and 17,164 matched controls were analyzed. In both cohorts after IPTW, roughly 56% of patients had cholelithiasis, 16% had cholecystitis, and 28% had cholecystectomy. Age and sex were balanced at baseline between cohorts (UDCA: 70.5 ± 9.54 years old and 58.6% female; controls: 70.3 ± 9.59 years old and 57.4% female). In the UDCA cohort, 384/5,705 (6.74%) were diagnosed with AMD. In the control cohort, 1,559/17,322 (9.00%) were diagnosed with AMD. This corresponded to a significantly decreased hazard of AMD (adjusted hazard ratio = 0.65, 95% CI: 0.58–0.74, P < 0.0001).
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Chinese preprint: PET-Microplastics Trigger Endothelial Glycocalyx Loss via ER Stress and ROS Unleashing IL-1β-Driven SMC Switching and Early Aortic Structural Impairment 2025
Polyethylene terephthalate microplastics (PET-MPs), a major microplastics component identified in human vasculature, pose emerging environmental health risks. This study systemically profiled MPs in human aortic tissues and investigated the mechanisms underlying PET-MPs-induced aortic injury in vivo and in vitro. Chronic oral exposure of Sprague-Dawley rats to PET-MPs (1.0-100 mg/L) resulted in endothelial glycocalyx loss and structural impairment of aortic elastic fibers, with MPs accumulating within aortic endothelial cells. Transcriptomic and biochemical analyses revealed that PET-MPs triggered endoplasmic reticulum stress (ERS) and reactive oxygen species (ROS) generation in human aortic endothelial cells (HAECs), driving glycocalyx degradation and NF-κB-mediated inflammation. Proteomic profiling identified endothelial-derived IL-1β as a key mediator, which subsequently induced phenotypic switching in human aortic smooth muscle cells (HASMCs) in vitro. Pharmacological inhibition of ERS (TUDCA), ROS (NAC), or IL-1β (Canakinumab) attenuated this pathogenic cascade. Crucially, restoration of the glycocalyx using Sulodexide mitigated endothelial dysfunction and downstream HASMC phenotypic switching. These findings establish endothelial glycocalyx degradation via ERS-ROS as a novel mechanism for PET-MPs-induced vascular injury and highlight glycocalyx protection as a potential strategy against environmental microplastic hazards.
ROS not only poses a direct threat to glycocalyx but also enhances its proteolysis by activating matrix metalloproteinases (MMPs) and inactivating endogenous protease inhibitors.(29, 30) Furthermore, existing literature reports that ER stress accompanies vascular calcification in mice and rats.(54, 55) NAC is a broad-spectrum antioxidant that directly scavenges ROS and enhances glutathione synthesis, while TUDCA inhibits the source of ER stress by blocking PERK/IRE1 pathway activation, thereby indirectly alleviating ER oxidative stress. Following treatment with TUDCA or NAC, PET-MPs-induced endothelial glycocalyx damage was significantly mitigated. This indicates that, distinct from factors like inflammation or mechanical stress dysregulation, PET-MPs elevate ROS by inducing ER oxidative stress, subsequently damaging the endothelial glycocalyx via oxidative stress. Notably, the inhibitory effect of TUDCA surpassed that of NAC, suggesting that ER oxidative stress may be the primary trigger for endothelial glycocalyx disruption.
@AlexKChen: TUDCA to protect from microplastics’ harm?
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Another weird paper on plasticizer and UDCA: Ursodeoxycholic Acid Attenuates B Cell Susceptibility to SARS-CoV-2 Spike Protein by Interfering Its Binding to ACE2
B cells are essential for the defense against various infectious agents including severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) causing coronavirus disease 2019 (COVID-19). COVID-19 is caused by interaction of the spike protein (SP) with the receptor-binding domain (RBD) and its receptor, angiotensin converting enzyme 2 (ACE2). Bisphenol A (BPA), a plasticizer and endocrine-disrupting chemical, can enter the human body through several exposure routes. Previously, we reported human B cell death by BPA treatment via autophagy induction. Here, we investigated whether the exposure to BPA affects B cell susceptibility to SP of COVID-19 and how to interfere the interaction of SP and ACE2. We observed an increase in ACE2 gene expression in human B cells by BPA treatment and more SP binding in BPA-treated B cells. Our data also showed more B cell death accompanying increased autophagic puncta count and lysosomal intracellular activity by co-treatment with BPA and SP compared to those in BPA treatment alone. Ursodeoxycholic acid (UDCA) reduced SP binding in B cells in BPA-exposed B cells. UDCA treatment also inhibited B cell death and lysosomal enzyme activity which were enhanced by co-treatment of BPA and SP. Taken together, results demonstrate that BPA-exposed B cells are more susceptible to COVID-19. It also suggests that UDCA could be protective to SP-responding B cells exposed to BPA.
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UDCA/TUDCA continue to amaze me with their potential health benefits. I’ve recently stopped my SGLT2i because it was elevating my hematocrit too much when combined with TRT, but the anti-fibrotic/anti-arrhythmic potential of TUDCA gives me hope that I’m still getting some similar benefits (albeit via different mechanisms) without the hematocrit elevation. 
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Another benefit of UDCA @Davin8r:
I read this paper back then but didn’t pay attention to UDCA: Statins aggravate insulin resistance through reduced blood glucagon-like peptide-1 levels in a microbiota-dependent manner 2025
Highlights
- Statin alters gut microbiota and dysregulates bile acid metabolism and glucose homeostasis
- Statin causes dysregulated gut microbiota and decrease of the genus Clostridium
- Decreased Clostridium-rich microbiota after statin inhibits HSDH and lowers UDCA
- Transplanting Clostridium sp. or supplying UDCA ameliorates statin-induced hyperglycemia
Summary
Statins are currently the most common cholesterol-lowering drug, but the underlying mechanism of statin-induced hyperglycemia is unclear. To investigate whether the gut microbiome and its metabolites contribute to statin-associated glucose intolerance, we recruited 30 patients with atorvastatin and 10 controls, followed up for 16 weeks, and found a decreased abundance of the genus Clostridium in feces and altered serum and fecal bile acid profiles among patients with atorvastatin therapy. Animal experiments validated that statin could induce glucose intolerance, and transplantation of Clostridium sp. and supplementation of ursodeoxycholic acid (UDCA) could ameliorate statin-induced glucose intolerance. Furthermore, oral UDCA administration in humans alleviated the glucose intolerance without impairing the lipid-lowering effect. Our study demonstrated that the statin-induced hyperglycemic effect was attributed to the Clostridium sp.-bile acids axis and provided important insights into adjuvant therapy of UDCA to lower the adverse risk of statin therapy.
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Interesting! I wish they’d also tested TUDCA…
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Use of Ursodeoxycholic Acid and Cancer Risk for Patients With Primary Biliary Cholangitis 2025
In this study, UDCA treatment was associated with significantly lower risks of gastrointestinal cancer, liver cancer, and breast cancer but not colorectal cancer in patients with PBC.
Our findings suggest a potential chemopreventive effect of UDCA beyond its hepatic benefits, consistent with some prior reports. The underlying protective mechanism of UDCA remains to be elucidated but is presumably related to its anti-inflammatory, antiproliferative, and cytoprotective properties. Confirmation of our findings using prospective studies or randomized clinical trials is warranted, particularly for liver and breast cancer.
More good news @Davin8r.
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I didn’t know anything about UDCA/TUDCA, so I just found this easy to digest article with a great explanation. Those of you who are already knowledgeable about it don’t need to waste your time reading this.
It seems it might be something to learn more about if you don’t have a gallbladder (me). Also, as someone with good labs but poor post prandial glucose control, I looked and AI said they’ve done tests with TUDCA and it did not help with glucose spikes.
Sorry if this has already been shared:
The only part I didn’t understand is it says increasing insulin sensitivity could be a negative vs a positive. (I’ll assume this is something specifically an issue in PD?)
“There is one potential concern regarding TUDCA: it increases glucose-induced insulin release (via the cAMP/PKA pathway), which in turn could increase insulin sensitivity (Click here to read more about this). This could affect people with diabetes or glucose intolerance – a common feature of Parkinson’s “
EDIT:
I also see if you’ve had gallbladder removal, your TUDCA levels might increase so it seems to be a complex issue.
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Thank you for such a deep dive! One thing that ringed a bell is that if TUDCA helped with ALS it should also help protect the neural activation of muscle during aging, ergo reducing sarcopenia and losing respiratory function.
I am curious what the experts here say about reducing the apaptosis of cells or increasing the mithocondria turnover, both effects I understand are not desired for all your life, right?
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TUDCA doesn’t help with ALS: the phase 3 trial failed.
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The difficulties with anything caused by mitochondrial failure is that fixing it requires fixing the mitochondria.
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It seems that indeed, in worms at least, UDCA is beneficial at moderate dose while TUDCA is highly detrimental: Ora Biomedical Million Molecule Challenge Results - #452 by adssx
fwiw @Davin8r…
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Thanks for linking to that! I’m looking into prices to potentially switch. It might actually be cheaper than the Nootropics Depot brand TUDCA im taking.