TUDCA's most-cited mechanism has nothing to do with digestion. Here is what the primary study found, including the part that does not flatter it.
Search TUDCA and you will quickly meet the phrase chemical chaperone. It is used in longevity and metabolic health circles as though it settles something. It refers to a real and well-characterised mechanism, and it is worth understanding at the level of what was actually measured.
Protein folding and the stress response
The endoplasmic reticulum is where cells fold newly made proteins into their working shapes. Under stress from toxins, inflammation or metabolic strain, that machinery falters and misfolded proteins accumulate.
The cell responds with the unfolded protein response, a signalling programme that first tries to restore folding capacity. GRP78, also called BiP, is the chaperone protein whose upregulation marks that the response has been triggered. If the stress persists, the programme shifts towards apoptosis, driven in part by CHOP, a pro-apoptotic transcription factor.
A chemical chaperone is a small molecule that stabilises protein conformation and prevents aggregation, taking pressure off that system from the outside.
The structure-function study
Researchers tested TUDCA in Mode-K small intestinal epithelial cells stressed with tunicamycin, a compound used to induce severe ER stress.
Pre-incubation with TUDCA almost completely suppressed the induction of GRP78 and CHOP at both mRNA and protein level.
In a cell-free assay using thermally denatured protein, the team then separated the molecule into its parts. Taurine alone did nothing. UDCA and TUDCA both prevented aggregation, so the chaperone activity belongs to the bile acid structure rather than the taurine.
The finding that complicates the marketing: in that cell-free assay, unconjugated UDCA was around ten times more effective than TUDCA, attributed to its lower water solubility allowing easier passive diffusion across membranes.
Berger E, Haller D. Structure-function analysis of the tertiary bile acid TUDCA for the resolution of endoplasmic reticulum stress in intestinal epithelial cells. Biochemical and Biophysical Research Communications 2011;409(4):610–615.
That last point deserves to be stated rather than buried. On this specific mechanism, in this specific assay, the unconjugated form outperformed the conjugated one. Anyone claiming TUDCA is superior to UDCA as a chaperone is not reporting the source accurately.
The gap between cells and people
There is a human trial that bears on this directly, and it cuts both ways.
Twenty obese subjects were randomised to TUDCA at 1,750 mg per day or placebo for four weeks, assessed with a hyperinsulinaemic-euglycaemic clamp and muscle and adipose biopsies.
Hepatic and muscle insulin sensitivity rose by about 30% on TUDCA and did not change on placebo. Adipose insulin sensitivity did not change.
ER stress markers in muscle and adipose tissue did not change in either arm. The metabolic effect appeared without a measurable change in the mechanism supposed to explain it.
Kars M, Yang L, Gregor MF, et al. Tauroursodeoxycholic acid may improve liver and muscle but not adipose tissue insulin sensitivity in obese men and women. Diabetes 2010;59(8):1899–1905. PMID: 20522594.
So: the chaperone mechanism is real in cells, the human metabolic signal is real but small and short, and the link between the two has not been demonstrated in human tissue. That is a more accurate summary than either the enthusiasm or the dismissal.
References
- Berger E, Haller D. Structure-function analysis of the tertiary bile acid TUDCA for the resolution of endoplasmic reticulum stress in intestinal epithelial cells. Biochemical and Biophysical Research Communications 2011;409(4):610–615. DOI: 10.1016/j.bbrc.2011.05.043.
- Kars M, Yang L, Gregor MF, et al. Tauroursodeoxycholic acid may improve liver and muscle but not adipose tissue insulin sensitivity in obese men and women. Diabetes 2010;59(8):1899–1905. PMID: 20522594.
Educational and scientific information only. Tauroursodeoxycholic acid (TUDCA) is sold as a food supplement and has not been assessed by the Food Standards Agency, the MHRA, the European Food Safety Authority or the US Food and Drug Administration for preventing, treating or curing any disease. Ursodeoxycholic acid (UDCA) is a prescription-only medicine in the UK. Nothing here is a substitute for prescribed treatment. If you are under medical care or taking prescribed medication, speak to your doctor or pharmacist before starting any supplement.