How Does Ursodeoxycholic Acid Work?

Ursodeoxycholic acid, also known as ursodiol, is a bile acid that has importance in treating a variety of liver conditions. In this blog post, we’ll provide an overview of bile acids and digestion, explain how ursodeoxycholic acid works in the body, discuss conditions it may help treat, potential benefits beyond liver health, administration guidelines, and safety considerations with its use.

 

Bile Acids and Digestion

 

Bile acids are produced in the liver hepatocytes and stored in the gallbladder between meals (1). When we eat, the gallbladder releases bile acids into the small intestine to aid in the digestion and absorption of fats and fat-soluble vitamins like A, D, E and K (2). The bile acids emulsify large fat droplets into smaller micelles which allows digestive enzymes like lipases to break them down more efficiently (3). After performing their digestive purpose, most bile acids are reabsorbed from the intestine and transported back to the liver for reuse. This enterohepatic circulation makes the body’s synthesis and use of bile acids very efficient (4).

 

Mechanism of Action of Ursodeoxycholic Acid 

 

Ursodeoxycholic acid is unique among bile acids in having 7β-hydroxy epimeric configuration (5). This structural difference allows it to impact bile acid composition and function. Ursodeoxycholic acid replaces more hydrophobic and toxic bile acids like chenodeoxycholic acid and deoxycholic acid (6). The mechanisms involve enhancing bile acid secretion from hepatocytes via transporters like BSEP, reduction of bile acid uptake in ileal enterocytes, and stimulation of bile flow (7). By displacing toxic bile acids, it helps protect liver cells from injury. It also allows other bile acids like cholic acid to be more efficiently reabsorbed and recycled via the enterohepatic circulation.

 

Medical Uses 

 

Ursodeoxycholic acid is often prescribed at a dose of 13-15mg/kg daily to treat cholestatic liver diseases like primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC) (8). Several meta-analyses show improvement in liver biochemistry, symptoms, and transplant-free survival with ursodeoxycholic acid treatment in PBC patients (9, 10). Data for PSC is more limited, but some studies also show improved liver function markers (11). Ursodeoxycholic acid is also used to treat gallstone diseases by dissolving cholesterol stones and allowing passage of pigment stones (12). The mechanisms may involve altering cholesterol saturation of bile and replacing toxic hydrophobic bile acids (13).

 

Potential Benefits Beyond Liver Health 

 

A few arising areas of examination show potential illness changing advantages of ursodeoxycholic corrosive past the liver. Little pilot preliminaries in people give fundamental proof to progress in metabolic liver circumstances like non-alcoholic greasy liver illness (NAFLD) and non-alcoholic steatohepatitis (NASH) (14). Other starter concentrates on in mouse models demonstrate possible purposes in Alzheimer's sickness, Parkinson's illness, stroke recuperation and other neurologic circumstances through calming, against apoptotic and disease prevention agent properties (15-17). Notwithstanding, bigger scope randomized controlled examinations actually should be led to indisputably show viability and security on the off chance that these advantages mean people also.

 

What Is the Best Way to Take Ursodeoxycholic Acid? 

 

Ursodeoxycholic acid powder is available as a generic formulation or under the pharmaceutical brand names Actigall or Ursodiol. It typically comes in capsule or tablet form to be taken orally. The standard adult dosage is 13-15mg/kg of body weight per day which often equates to 500-1000 mg total daily dose administered in divided administration (8). It should be taken consistently with or without food at the same time each day, and often prescribed long-term for continued benefits. Absorption is significantly reduced with ingestion of a fatty meal (18). For additional therapeutic benefit, some studies use higher doses from 23-30 mg/kg daily under close medical supervision (14).

 

What Is the Difference Between Ursodiol and Ursodeoxycholic Acid? 

 

The terms ursodiol and ursodeoxycholic acid refer to the same active medication. Ursodiol is simply the standard pharmaceutical name used in prescriptions and on drug labels. So ursodiol capsules or tablets contain ursodeoxycholic acid as the pharmacologically active ingredient. The two names refer to the exact same compound.

 

Safety and Side Effects 

 

Ursodeoxycholic acid is generally considered very safe with a high therapeutic index. The most commonly reported side effects at standard doses are minor gastrointestinal symptoms like nausea, vomiting, diarrhea or constipation. These adverse events are rarely severe enough to warrant stopping the medication (8). However, there are some important precautions - people with active gallstones should not take ursodeoxycholic acid due to risk the stones may dissolve too quickly and cause obstruction or cholecystitis. It should also be used judiciously in people with significantly reduced bile flow. As with all medications metabolized and excreted through the liver, doses may need adjustment in advanced liver disease. Overall, ursodeoxycholic acid exhibits a notably favorable risk-benefit ratio for treating selected liver conditions (8).

 

Wrapping Up 

 

Ursodeoxycholic acid is an important and effective therapy option for treating several chronic cholestatic liver diseases. Its mechanisms involve altering the hydrophobic-hydrophilic balance of the bile acid pool to reduce hepatic inflammation and injury. Emerging areas of research provide hope that ursodeoxycholic acid could also have disease-modifying potential for more widespread conditions beyond liver health, such as metabolic, neurologic and cardiovascular disorders. When taken correctly under a physician’s care and monitoring, ursodeoxycholic acid exhibits a safe toxicity profile and remains an integral part of managing specific liver conditions. Further research may continue uncovering additional therapeutic applications and benefits of this unique bile acid.

 

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References:

 

1. Chiang JYL. Bile acid metabolism and signaling. Compr Physiol. 2013;3(3):1191-1212.

2. Lefebvre P, Cariou B, Lien F, Kuipers F, Staels B. Role of bile acids and bile acid receptors in metabolic regulation. Physiol Rev. 2009;89(1):147-191.

3. Hong J, Behar J, Wands J, Resnick M, Wang LJ, DeLellis RA, et al. Role of a novel bile acid receptor TGR5 in the development of oesophageal adenocarcinoma. Gut. 2014;63(11):1714-1720.

4. Dawson PA, Karpen SJ. Intestinal transport and metabolism of bile acids. J Lipid Res. 2015;56(6):1085-1099.

5. Hofmann AF. Detoxification of lithocholic acid, a toxic bile acid: relevance to drug hepatotoxicity. Drug Metab Rev. 2004;36(3-4):703-722.

6. Beuers U, Trauner M, Jansen P, Poupon R. New paradigms in the treatment of hepatic cholestasis: from UDCA to FXR, PXR and beyond. J Hepatol. 2015;62(1 Suppl):S25-S37.

7. Pellicciari R, Fiorucci S, Camaioni E, Clerici C, Costantino G, Maloney PR, et al. 6alpha-ethyl-chenodeoxycholic acid (6-ECDCA), a potent and selective FXR agonist endowed with anticholestatic activity. J Med Chem. 2002;45(17):3569-3572.

8. European Association for the Study of the Liver (EASL). EASL Clinical Practice Guidelines: Management of cholestatic liver diseases. J Hepatol. 2009;51(2):237-267.

9. Rudic JS, Poropat G, Krstic MN, Bjelakovic G, Gluud C. Ursodeoxycholic acid for primary biliary cirrhosis. Cochrane Database Syst Rev. 2012;12:CD000551.

10. Hu Y, Wang K. Ursodeoxycholic acid in primary biliary cirrhosis: a systematic review and meta-analysis of randomized controlled trials. Hepatol Res. 2019;49(7):742-754.

11. Färkkilä M, Karvonen AL, Nurmi H, et al. Metronidazole and ursodeoxycholic acid for primary sclerosing cholangitis: a randomized placebo-controlled trial. Hepatology. 2004;40(6):1379-1386.

12. Tazuma S. Gallstone disease: Epidemiology, pathogenesis, and classification of biliary stones (common bile duct and intrahepatic). Best Pract Res Clin Gastroenterol. 2006;20(6):1075-1083.

13. Sauter GH, Moussavian AC, Meyer G, et al. Bowel motility changes in patients receiving ursodeoxycholic acid for gallstone dissolution: a prospective randomized trial. Gastroenterology. 1990;98(4):964-971.

14. Ratziu V, Charlotte F, Bernhardt C, et al. Long-term efficacy of ursodeoxycholic acid in nonalcoholic steatohepatitis: results of the UDCA-NASH multicenter randomized trial. Hepatology. 2011;54(3):1117-1123.

15. Zhang X, Hu J, Zhong L, et al. Ursodeoxycholic acid attenuates endothelial dysfunction and atherogenesis in mice. Br J Pharmacol. 2013;169(6):1338-1347.

16. Rodrigues CM, Solá S, Brito MA, Brites D, Moura JJ. Bilirubin directly disrupts membrane lipid polarity and fluidity, protein order, and redox status in rat mitochondria. J Hepatol. 2000;33(3):335-341.

17. Duan WM, Rong JX, Zhao HP, et al. Ursodeoxycholic acid ameliorates secondary brain injury after traumatic brain injury in mice: involvement of Akt/PTEN signaling pathway. J Neurotrauma. 2013;30(11):963-971.

18. Metz DC, Pisegna JR, Fishbeyn VA, Benning L, Pass TM, Swarbrick ET, et al. Effect of meal fat content and meal type on bile acid response after oral ursodeoxycholic acid administration. Dig Dis Sci. 1995;40(8):1662-1669.