Why Every Athlete SHOULD Use TUDCA Part 2


Normally, athletes ingest TUDCA simply for those liver benefits it possesses, but little credit is ever given to its interactions with skeletal muscle, adipose tissue, and glucose metabolism. One of my more favorite TUDCA studies actually comes from Kars et al and looks directly at how it improves liver and muscle insulin sensitivity but does not improve adipose tissue insulin sensitivity (which is a good thing!) Insulin resistance is commonly associated with obesity. Studies conducted in obese mouse models found that endoplasmic reticulum (ER) stress contributes to insulin resistance, and treatment with tauroursodeoxycholic acid (TUDCA), a bile acid derivative that acts as a chemical chaperone to enhance protein folding and ameliorate ER stress, increases insulin sensitivity. The purpose of this study was to determine the effect of TUDCA therapy on multiorgan insulin action and metabolic factors associated with insulin resistance in obese men and women. In this study, twenty obese subjects ([means +/- SD] aged 48 +/- 11 years, BMI 37 +/- 4 kg/m2) were randomized to 4 weeks of treatment with TUDCA (1,750 mg/day) or placebo. A two-stage hyperinsulinemic-euglycemic clamp procedure in conjunction with stable isotopically labeled tracer infusions and muscle and adipose tissue biopsies were used to evaluate in vivo insulin sensitivity, cellular factors involved in insulin signaling, and cellular markers of ER stress. RESULTS Hepatic and muscle insulin sensitivity increased by approximately 30% (P < 0.05) after treatment with TUDCA but did not change after placebo therapy. In addition, therapy with TUDCA, but not placebo, increased muscle insulin signaling (phosphorylated insulin receptor substrate(Tyr) and Akt(Ser473) levels) (P < 0.05). Markers of ER stress in muscle or adipose tissue did not change after treatment with either TUDCA or placebo. This data demonstrate that TUDCA might be an effective pharmacological approach for treating insulin resistance. Additional studies are needed to evaluate the target cells and mechanisms responsible for this effect (4.)

Although that is the only credible study I can attribute positive results on those fronts, we can play “connect the dots” with some other pieces of literature such as the ones done on TUDCA supplementation in correlation to glucose metabolism. A study done in 2006 (5) linked endoplasmic reticulum stress to obesity, insulin resistance, and diabetes. They state” here, we provide evidence that this mechanistic link can be exploited for therapeutic purposes with orally active chemical chaperones. 4-Phenyl butyric acid and taurine-conjugated ursodeoxycholic acid alleviated ER stress in cells and whole animals. Treatment of obese and diabetic mice with these compounds resulted in normalization of hyperglycemia, restoration of systemic insulin sensitivity, resolution of fatty liver disease, and enhancement of insulin action in liver, muscle, and adipose tissues. Our results demonstrate that chemical chaperones enhance the adaptive capacity of the ER and act as potent antidiabetic modalities with potential application in the treatment of type 2 diabetes.” Another study along similar lines of endoplasmic reticulum stress and its correlation to insulin resistance looked at glucose-induced beta cell dysfunction in vivo in rats which showed a link between oxidative stress and endoplasmic reticulum stress. Healthy Wistar rats were infused i.v. with glucose for 48 h to achieve 20 mmol/l hyperglycaemia with or without the co-infusion of the superoxide dismutase mimetic tempol (TPO), or the chemical chaperones 4-phenylbutyrate (PBA) or tauroursodeoxycholic acid (TUDCA). This was followed by assessment of beta cell function and measurement of ER stress markers and superoxide in islets. Glucose infusion for 48 h increased mitochondrial superoxide and ER stress markers and impaired beta cell function. Co-infusion of TPO, which we previously found to reduce mitochondrial superoxide and prevent glucose-induced beta cell dysfunction, reduced ER stress markers. Similar to findings with TPO, co-infusion of PBA, which decreases mitochondrial superoxide, prevented glucose-induced beta cell dysfunction in isolated islets. TUDCA was also effective. Also similar to findings with TPO, PBA prevented beta cell dysfunction during hyperglycaemic clamps in vivo and after hyperglycaemia (15 mmol/l) for 96 h. Here, we causally implicate ER stress in hyperglycaemia-induced beta cell dysfunction in vivo. We show that: (1) there is a positive feedback cycle between oxidative stress and ER stress in glucose-induced beta cell dysfunction, which involves mitochondrial superoxide; and (2) this cycle can be interrupted by superoxide dismutase mimetics as well as chemical chaperones, which are of potential interest to preserve beta cell function in type 2 diabetes (6.)

I could continue on and on about the benefits of TUDCA! Heck, we didn’t even cover the fact that bile acids have the ability to induce energy expenditure by promoting intracellular thyroid hormone activation (7.) But, I do feel I’ve presented enough pertinent information to prove TUDCA has its place in everyone’s supplement regimen given the fact that it is a potent health and ergogenic aid that is more than affordable. In terms of practical application, there have been studies done showing improvements of liver regenesis rates at a dosage as low as 10mgs and other studies showing benefits for muscle tissue insulin sensitivity and for the treatment of liver disease as high as almost 2000mgs. In actual application I personally recommend my clients (that are competitive athletes) to supplement with 250mgs of TUDCA per day year round. Then, during periods of high stress such as a contest prep or anytime you’re truly pushing your “supplements”, upwards of 1000mgs per day. You will obviously need to get bloodwork done to see where your liver enzyme levels are and how they change at what specific dosage to know for sure (once again, thank you biological inter-individuality!) I have also included four more studies linked below in the reference section for your academic pleasure (8, 9, 10, 11.) Please read more and make the decision for yourself if TUDCA is something that could be beneficial in your everyday supplement stack.


  1. Metabolism of orally administered tauroursodeoxycholic acid in patients with primary biliary cirrhosis. K D Setchell, C M Rodrigues, M Podda, A Crosignani. Gut. 1996 (https://www.ncbi.nlm.nih.gov/pubmed/8675100)
  2. Ursodeoxycholic and tauro-ursodeoxycholic acids for the treatment of primary biliary cirrhosis: a pilot crossover study. A. Larghi, A. Crosignani, P. M. Battezzati, G. De Valle, M. Allocca, P. Invernizzi, M. Zuin, M. Podda. Aliment Pharmacol Ther. 1997 (https://www.ncbi.nlm.nih.gov/pubmed/9146783)
  3. Tauroursodeoxycholic acid for treatment of primary biliary cirrhosis. A dose-response study. A. Crosignani, P. M. Battezzati, K. D. Setchell, P. Invernizzi, G. Covini, M. Zuin, M. Podda. Dig Dis Sci. 1996 (https://www.ncbi.nlm.nih.gov/pubmed/8674405)
  4. Tauroursodeoxycholic Acid May Improve Liver and Muscle but Not Adipose Tissue Insulin Sensitivity in Obese Men and Women. Marleen Kars, Ling Yang, Margaret F. Gregor, B. Selma Mohammed, Terri A. Pietka, Brian N. Finck, Bruce W. Patterson, Jay D. Horton, Bettina Mittendorfer, Gökhan S. Hotamisligil, Samuel Klein. Diabetes. 2010 (https://www.ncbi.nlm.nih.gov/pubmed/20522594)
  5. Chemical Chaperones Reduce ER Stress and Restore Glucose Homeostasis in a Mouse Model of Type 2 Diabetes. Umut Özcan, Erkan Yilmaz, Lale Özcan, Masato Furuhashi, Eric Vaillancourt, Ross O. Smith, Cem Z. Görgün, Gökhan S. Hotamisligil. Science. Author manuscript; available in PMC 2016 Feb 4.. Published in final edited form as: Science. 2006 (https://www.ncbi.nlm.nih.gov/pubmed/16931765)
  6. Glucose-induced beta cell dysfunction in vivo in rats: link between oxidative stress and endoplasmic reticulum stress. C. Tang, K. Koulajian, I. Schuiki, L. Zhang, T. Desai, A. Ivovic, P. Wang, C. Robson-Doucette, M. B. Wheeler, B. Minassian, et al. Diabetologia. 2012 (https://www.ncbi.nlm.nih.gov/pubmed/22396011)
  7. Bile acids induce energy expenditure by promoting intracellular thyroid hormone activation. Mitsuhiro Watanabe, Sander M. Houten, Chikage Mataki, Marcelo A. Christoffolete, Brian W. Kim, Hiroyuki Sato, Nadia Messaddeq, John W. Harney, Osamu Ezaki, Tatsuhiko Kodama, et al. Nature. 2006 (https://www.ncbi.nlm.nih.gov/pubmed/16400329)
  8. Differences in the metabolism and disposition of ursodeoxycholic acid and of its taurine-conjugated species in patients with primary biliary cirrhosis. P. Invernizzi, K. D. Setchell, A. Crosignani, P. M. Battezzati, A. Larghi, N. C. O’Connell, M. Podda. Hepatology. 1999 (https://www.ncbi.nlm.nih.gov/pubmed/9918905)
  9. Does tauroursodeoxycholic acid (TUDCA) treatment increase hepatocyte proliferation in patients with chronic liver disease? C. Panella, E. Ierardi, M. F. De Marco, M. Barone, F. W. Guglielmi, L. Polimeno, A. Francavilla. Ital J Gastroenterol. 1995 (https://www.ncbi.nlm.nih.gov/pubmed/8541578)
  10. TUDCA and UDCA are incorporated into hepatocyte membranes: different sites, but similar effects. U. Leuschner, S. Guldutuna, S. Bhatti, A. Elze, M. Imhof, T. You, G. Zimmer. Ital J Gastroenterol. 1995 (https://www.ncbi.nlm.nih.gov/pubmed/8563010)
  11. Effects of prolonged glucose infusion on insulin secretion, clearance, and action in normal subjects. G. Boden, J. Ruiz, C. J. Kim, X. Chen. Am J Physiol. 1996 (https://www.ncbi.nlm.nih.gov/pubmed/8779946)

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