TUDCA: Uses, Benefits, and Properties Explained
Tauroursodeoxycholic Acid (TUDCA) is a water soluble secondary bile acid that is found in large amounts in bear bile. In humans, trace amounts of TUDCA are formed when primary bile acids undergo bacterial metabolism to UDCA, and are then conjugated with Taurine to give TUDCA. TUDCA is a very promising molecule known for its ability to counteract regular bile acid toxicity in the liver, but also has many other beneficial effects. Another unique ability of TUDCA is its ability to prevent protein unfolding in the Endoplasmic Reticulum, reducing cell death. This ability is responsible for many of the benefits of TUDCA, such as reducing insulin resistance and having neuroprotective benefits including potential treatment for Alzheimer’s, Parkinson’s, and other neurological disorders.
Bile Acids
To understand TUDCA and its properties, it is first important to understand the larger class of compounds it belongs to: The Bile Acids. Bile Acids are synthesized from Cholesterol in the liver via cytochrome P450, a system of enzymes responsible for drug metabolism. From Cholesterol two Bile acids are made: Cholic Acid and Chenodeoxycholic Acid1. These are known as the primary bile acids.
Figure 1: The Two Primary Bile Acids
From the primary bile acids, bacterial metabolism which results in the reduction of the alpha hydroxyl group at carbon position 7 is how the secondary bile acids: Deoxycholic and Lithocholic acid are made.
Ursodeoxycholic Acid (UDCA) is synthesized when deoxycholic acid undergoes reduction of its hydroxyl group on carbon position 12 and the addition of a 7-beta hydroxyl group. Compared to its parent primary acid cholic acid, UDCA has its hydroxyl groups on opposite sides of the three-dimensional molecular structure.
This could be a reason for some of its unique effects. From here, UDCA can be conjugated with either glycine or taurine to give either Glycoursodeoxycholic acid or Tauroursodeoxycholic Acid (TUDCA).
It is important to note that all bile acids, primary or secondary, can be conjugated with an amino acid: Taurine or glycine to form a bile salt. The addition of the amino acid makes the bile salt more water soluble. Bile salts are amphipathic, meaning they are both water and fat soluble. This property allows them to emulsify lipids and digest fats. Bile salts are responsible for digesting fats as well as fat soluble vitamins, while bile acids are unable to digest fats1.
Bile Acid production from Cholesterol is the bodies’ primary pathway for maintaining healthy cholesterol levels. About half of the total cholesterol in the body is used to make bile acids2. Bile salts inhibit cholesterol 7alpha-hydroxylase, the enzyme responsible for producing bile acids from cholesterol. This enzyme inhibition decreases production of bile acid. Due to being potentially toxic to cells, the concentrations of bile acids are tightly regulated3.
While amphipathic bile acids like TUDCA have beneficial properties in the liver, buildup of the bile acids chenodeoxycholic acid or deoxycholic acid or their glycine or taurine conjugates have toxic effects on the liver.
TUDCA and the Liver
A buildup of too many lipophilic bile acids in the liver such as Chenodeoxycholic acid or deoxycholic acid can cause toxic effects like cell death, leading to cholestasis. Since TUDCA is amphipathic, it is able to antagonistically compete with these harmful bile acids in the liver, displacing them from the liver, lowering their concentration and harmful effects.
TUDCA is incredibly potent at reducing liver enzymes, where one study showed a reduction of liver enzymes by 51% over a two month period at 750mg/day4.
In addition to reducing liver enzyme levels, TUDCA has been shown to stimulate hepatocyte proliferation (Growth of new liver cells) in humans at doses as low as 10-13mg/day for 3 months5.
TUDCA has also been shown to be effective at treating chronic hepatitis (Liver inflammation that has occurred for 6+ months) in doses of 500-750mg/day6.
TUDCA is a candidate drug in the treatment of Non Alcoholic Fatty Liver Disease (NAFLD) and has been shown to reduce progression of NAFLD by reducing gut inflammation, improving intestinal barrier function, decrease intestinal fat transport, and controlling gut flora in the intestine7.
TUDCA vs UDCA
Although UDCA is also an amphipathic bile acid used to treat cholestasis, TUDCA has superior bioavailability and absorption due to the attached taurine molecule. In one study comparing the effects of TUDCA vs UDCA for treatment of biliary cirrhosis (An autoimmune disease which destroys the bile ducts) patients were given either TUDCA or UDCA at 750mg/day for 2 months. Enrichment by Ursodeoxycholic acid was significantly higher in the group given TUDCA than the group given UDCA itself. The group given UDCA also had higher lithocholic acid levels (A toxic bile acid) than the TUDCA group. Bile excretion was measured at 8% for the TUDCA group vs 23% for the UDCA group, meaning more TUDCA was absorbed and retained vs UDCA. This study shows concrete evidence that TUDCA is more effective than UDCA in real human studies4.
TUDCA and the Kidneys
TUDCA has been shown as an effective treatment for damaged and inflamed kidneys caused by high salt intake by decreasing renal cell death and inflammation8.
In addition, TUDCA treats acute kidney injury caused by reduced blood flow to the kidney by inhibiting endoplasmic reticulum stress. This is caused by TUDCA increasing the protein folding ability in the Endoplasmic Reticulum, which results in reduction of the death of cells by protein unfolding9.
TUDCA and Neuroprotective Properties
Due to the ability for Bile acids to cross the blood brain barrier (BBB), TUDCA has a direct neuroprotective effect and possibly an indirect neuroprotective effect by inhibiting glia and endothelium activation, reducing neuro-inflammation10.
TUDCA and the Heart
TUDCA has been shown to reduce apoptosis (cell death) in the heart following myocardial infarction (heart attack), showing its potential for treatment of acute myocardial infarction11.
TUDCA and Insulin Sensitivity
Studies have demonstrated that Endoplasmic Reticulum (ER) stress contributes to insulin resistance. In one study, 20 subjects were given 1750mg TUDCA/day for 4 weeks. By the end of the study, liver and muscle insulin sensitivity had increased by 30%. Muscle insulin signaling was also increased in the group given TUDCA compared to the control group13.
TUDCA and Eye Health
Bear bile such as TUDCA has been used in Chinese medicine for thousands of years, mostly for liver diseases and eye health. TUDCA has been shown to slow retinal degeneration, and preserve the function of rods and cones12.
TUDCA and Endoplasmic Reticulum Folding
As can be seen from most of the benefits of TUDCA that have been listed here, these benefits are due largely in part by the ability of TUDCA to reduce Endoplasmic Reticulum (ER) Stress and reduce the levels of misfolded proteins. Misfolded proteins can lead to many neurodegenerative diseases, and ER stress is involved in aging, inflammation, diabetes, neurodegenerative diseases, and cardiovascular diseases14. TUDCA is a known ‘chemical chaperone’ – a class of molecules which function to enhance the folding or stability of proteins. TUDCA’s ability as a chemical chaperone has also shown promise in alleviating different forms of colitis, suggesting potential treatment for inflammatory bowel diseases15. Compared to another chemical chaperone, TUDCA showed better cell viability and decreased cell apoptosis (cell death), showing a superior ability to protect cells16.
TUDCA Metabolism and Bioavailability
Compared to many supplements, TUDCA is highly bioavailable and does not have issues with being properly absorbed. Indeed, TUDCA is better absorbed than its prescription drug counterpart UDCA, where bile excretion in patients given 750mg TUDCA/day was only 8% compared to those given the same amount of UDCA was 23%4.
Hydrophilic Bile acids such as TUDCA induce CYP3A, a major drug metabolizing enzyme, while toxic bile acids such as chenodeoxycholic acid and deoxycholic acid show inhibition of CYP3A17. The enzyme metabolizing properties of CYP3A are important to understand, as some drugs and supplements are CYP3A inducers, while others are CYP3A inhibitors. It Is a common practice in supplements to combine products with the ingredient Piperine, which is a CYP3A inhibitor that is known to increase the bioavailability of other CYP3A inhibiting supplements such as Curcumin18, Quercetin19, and Resveratrol20. Due to the fact that TUDCA is a CYP3A inducer while more toxic bile acids are CYP3A inhibitors, combining piperine with TUDCA may decrease the bioavailability of TUDCA due to competing drug metabolism interactions17.
TUDCA: Effective Dosing and Recap
To conclude, TUDCA is the taurine conjugated bile salt of the bile acid UDCA, with unique properties, mainly in reducing ER stress by protein unfolding due to its 7-beta hydroxyl group and increased hydrophilic properties. TUDCA is able to compete with water insoluble toxic bile acids in the liver to eliminate them from the liver, resulting in a decrease of liver enzymes and alleviation of problematic issues. Doses as low as 10-13mg/day of TUDCA have been linked with a decrease in liver enzymes5, while doses up to 1500mg/day for 6 months have been given with no side effects21. With doses of 500mg, 1000mg, and 1500mg/day given in patients with biliary cirrhosis, the group given 1500mg/day saw the most beneficial results, while all doses were considered effective22.
At Leviathan Nutrition, our TUDCA is routinely check for quality (Lab results here: https://leviathan-nutrition.com/pages/testing-results) to ensure a high quality product. Readers of this blog can use the discount: 'TUDCA' to receive 10% off of our TUDCA: https://leviathan-nutrition.com/products/leviathan-nutrition-tudca
References:
- https://www.ncbi.nlm.nih.gov/books/NBK470209/
- https://aasldpubs.onlinelibrary.wiley.com/doi/full/10.1002/hep.24107
- https://www.ncbi.nlm.nih.gov/pubmed/17720959
- https://www.ncbi.nlm.nih.gov/pubmed/9918905
- https://www.ncbi.nlm.nih.gov/pubmed/8541578
- https://www.ncbi.nlm.nih.gov/pubmed/9840118
- https://www.ncbi.nlm.nih.gov/pubmed/29139555
- https://www.ncbi.nlm.nih.gov/pubmed/30501003
- https://www.ncbi.nlm.nih.gov/pubmed/22212133
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5319238/
- https://www.ncbi.nlm.nih.gov/pubmed/17436368
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2798994/
- https://www.ncbi.nlm.nih.gov/pubmed/20522594
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5126306/
- https://www.ncbi.nlm.nih.gov/pubmed/23336977
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5476595/
- https://aasldpubs.onlinelibrary.wiley.com/doi/pdf/10.1053/jhep.2002.34939
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2574793
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5822518
- https://www.ncbi.nlm.nih.gov/pubmed/11294598
- https://www.ncbi.nlm.nih.gov/pubmed/8674405
- https://www.ncbi.nlm.nih.gov/pubmed/8675100
DISCLAIMER: These statements have not been evaluated by the Food and Drug Administration, these products are not intended to diagnose, treat, cure, or prevent any disease.