The hair cells of the inner ear do not regenerate in mammals. Once they die, the hearing they carried is gone, which is why so much hearing research is about preventing the death rather than repairing the damage. That framing makes an anti-apoptotic chaperone an obvious thing to test, and five published studies have done so. The same chaperone-and-cell-survival logic has been applied at length to retinal tissue, including diabetic retinopathy.
All five are in rodents or in cultured cells. There is no human trial of TUDCA for hearing of any kind, the doses used are far above anything a person takes by mouth, and one of the studies delivered the compound directly through the eardrum. This page describes a small, consistent and entirely preclinical literature. Nothing here is medical advice.
Key Takeaways
- In mice carrying a mutation that models human autosomal recessive deafness DFNB12, systemic TUDCA significantly reduced hearing loss and hair cell death, and suppressed apoptotic genes and caspase-3 activation in the cochlea[1].
- In rats given cisplatin, TUDCA reduced auditory brainstem response threshold shifts by both subcutaneous injection at 500 mg/kg per day and direct trans-tympanic delivery[2].
- A separate rat study using 100 mg/kg TUDCA found lower threshold shifts, less cleaved caspase-3, and more surviving spiral ganglion cells and outer hair cells[3].
- Against the antibiotic gentamicin, TUDCA reduced hair cell death in culture, lowered the Bax to Bcl2 ratio, and suppressed the ER stress markers BiP and CHOP[4].
- The proposed mechanism is protein quality control. In a cell-free system, TUDCA inhibited aggregation of denatured albumin, and knocking down three ER quality control proteins reduced its protective effect[2].
- Every dose here is a research dose in an animal. No human has been given TUDCA for hearing protection in a published trial.
Why the Cochlea Turns Up in ER Stress Research
Cochlear hair cells are metabolically demanding, densely packed with structural proteins, and impossible to replace. Several groups have asked whether the unfolded protein response is part of how they die.
A 2017 rat study answered that directly for cisplatin, the chemotherapy drug whose hearing toxicity is its best-known dose-limiting side effect[5]. Cisplatin upregulated active caspase-12 in cochlear cells, which indicates activation of ER-specific apoptosis, and increased CHOP and cleaved caspase-9, pointing at a link between severe ER stress and mitochondria-dependent cell death. The same study reported that TUDCA had a protective effect on cisplatin-induced hearing loss[5].
That established the target. The rest of the literature tests the compound against it. The same ER stress mechanism described elsewhere on this site is what is being invoked here, applied to a tissue most supplement writing never mentions.
Cisplatin: Two Rat Studies, Two Doses, Two Routes
The larger of the two is a 2021 study in Sprague-Dawley rats[2]. TUDCA was given either subcutaneously at 500 mg/kg per day for three days alongside cisplatin at 4.6 mg/kg per day, or trans-tympanically at 0.5 mg/mL with cisplatin delivered by pump. Both routes alleviated the cisplatin-induced rise in auditory brainstem response thresholds[2].
The mechanistic work went further than most. In cochlear explants and OC1 auditory hair cell-like cells, TUDCA reduced apoptosis and ER stress. Cisplatin raised expression of calreticulin, UGGT1 and OS9, three components of the ER protein quality control system, while total ubiquitinated protein fell. TUDCA attenuated the cisplatin effect on UGGT1 and OS9 and restored ubiquitination levels[2].
Two further experiments make this more than a marker story. When calreticulin, UGGT1 or OS9 were individually knocked down, TUDCA’s protective effect decreased[2]. And in a cell-free system containing only 0.2 percent bovine serum albumin, TUDCA at 10 millimolar inhibited aggregation of the denatured protein[2]. That last result is chemistry rather than biology: it shows the molecule physically interferes with protein aggregation, with no cell involved at all.
A 2020 study in eight-week-old female Sprague-Dawley rats used a fifth of the dose, 100 mg/kg intraperitoneally on days one to three, against cisplatin at 5 mg/kg on the same days[3]. Mean threshold shifts were lower in the TUDCA group. Cisplatin elevated heme oxygenase 1 and superoxide dismutase 2 messenger RNA, and TUDCA reversed both. Caspase 3, cleaved caspase 3 and aryl hydrocarbon receptor all rose with cisplatin, and TUDCA attenuated the cleaved caspase-3 increase but did not reverse the aryl hydrocarbon receptor activation[3]. Histologically, the TUDCA group retained more spiral ganglion cells and outer hair cells[3].
The honest detail there is the one that did not work. Reporting that aryl hydrocarbon receptor activation persisted is what makes the rest of the paper credible: the protection was partial and the authors said so.
Aminoglycoside Antibiotics
Gentamicin and its relatives kill hair cells through intrinsic apoptosis, which is a separate insult from cisplatin. A 2018 study used HEI-OC1 cells and explanted cochlear tissue and found TUDCA significantly attenuated gentamicin-induced damage in both[4].
The pattern matched: reduced apoptosis with a lower Bax to Bcl2 ratio, decreased nitric oxide production and protein nitration, and suppression of gentamicin-induced ER stress reflected in BiP, CHOP and caspase 3 expression[4]. Two different ototoxic drugs, two different primary mechanisms, and the same chaperone intervention blunting both. That convergence is the most interesting feature of this small literature.
The Genetic Model
The 2016 study is different in kind, because the hearing loss was not caused by a drug. The Cdh23(erl/erl) mutation in mice is a model of human autosomal recessive nonsyndromic deafness DFNB12, and hair cell apoptosis was implicated as the cellular mechanism[1].
Systemic TUDCA significantly alleviated hearing loss and suppressed hair cell death in these mice, and inhibited apoptotic genes and caspase-3 activation in the cochlea[1]. The authors suggested TUDCA as a potential therapeutic agent for human DFNB12[1].
That is a genuinely interesting result, because a genetic deafness has no drug to stop and no exposure to avoid. It is also a mouse with a specific mutation, and the distance between that and a person with inherited hearing loss is not small.
What Would Have To Be True for This to Matter Clinically
Three things, none of which has been shown.
First, oral dosing would need to reach the inner ear. The cochlea sits behind a blood-labyrinth barrier, and the studies that worked best used injection or direct delivery through the eardrum[2]. The absorption evidence for oral TUDCA does not address inner ear concentrations at all.
Second, the dose would need to translate. Five hundred milligrams per kilogram in a rat is not a number that maps onto a human capsule by any straightforward conversion.
Third, and most awkwardly, the most obvious clinical use runs into a problem covered elsewhere on this site. The population most exposed to cisplatin is people receiving chemotherapy for cancer, and the evidence on TUDCA and chemotherapy response includes a study finding TUDCA associated with reduced response to gemcitabine-based treatment in advanced pancreatic cancer. Protecting hearing during chemotherapy is a real clinical goal, and it is not one to pursue with an unsupervised supplement.
Frequently Asked Questions
Does TUDCA protect hearing in humans?
Unknown. Every published study is in rodents or cultured cells, and there is no human trial. The animal results are consistent across cisplatin[2][3], gentamicin[4] and a genetic deafness model[1], which is a reason to study it further rather than a reason to take it.
Could TUDCA help with age-related hearing loss?
No study has tested that. The published models are drug-induced ototoxicity and a specific inherited mutation. Age-related hearing loss involves additional processes, including noise exposure history and vascular changes, that these models do not reproduce.
What dose was used in the animal studies?
Five hundred milligrams per kilogram per day subcutaneously in one rat study[2] and 100 mg/kg intraperitoneally in another[3]. One study also delivered TUDCA at 0.5 mg/mL directly through the eardrum[2]. None used oral dosing, and none of these are supplement doses.
Should someone on cisplatin take TUDCA to protect their hearing?
That is a question for the oncology team. Cisplatin-related hearing loss is a recognised problem that oncologists monitor for, and any supplement taken during chemotherapy belongs in that conversation. There is a specific published reason for caution about TUDCA during chemotherapy, covered on the cancer and apoptosis page.
References
- Tauroursodeoxycholic acid prevents hearing loss and hair cell death in Cdh23(erl/erl) mice. Neuroscience (2016).
- Tauroursodeoxycholic acid attenuates cisplatin-induced ototoxicity by inhibiting the accumulation and aggregation of unfolded or misfolded proteins in the endoplasmic reticulum. Toxicology (2021).
- Tauroursodeoxycholic acid attenuates cisplatin-induced hearing loss in rats. Neuroscience Letters (2020).
- Tauroursodeoxycholic acid attenuates gentamicin-induced cochlear hair cell death in vitro. Toxicology Letters (2018).
- Endoplasmic Reticulum Stress Is Involved in Cochlear Cell Apoptosis in a Cisplatin-Induced Ototoxicity Rat Model. Audiology and Neurotology (2017).
These statements have not been evaluated by the Food and Drug Administration. This information is not intended to diagnose, treat, cure, or prevent any disease. Content is for informational purposes only and is not medical advice; consult a qualified healthcare provider before starting any supplement. As an Amazon Associate we earn from qualifying purchases.
