Bile acids, once considered mere dietary surfactants, now emerge as critical modulators of macronutrient metabolism as well as immune and metabolic mediators. Bile acid metabolism and signaling pathways may strongly influence health due to the nearly ubiquitous nature of their receptor sites.[1]
The scientific understanding of bile and its components began to emerge in the mid-19th century. With advancements in research, we now possess detailed knowledge about the composition of the bile acid pool and how altered bile acid metabolism may affect health. Endogenous bile acids are those made by the body, whereas exogenous bile acids are those consumed for a beneficial effect. Both endogenous and exogenous bile acids are broken down into secondary bile salts in the body. Bile acids play a significant role in gastrointestinal health and have been shown to influence metabolic function and liver/gallbladder health.*[2],[3],[4] Emerging research also suggests potential benefits for skin.*[5]
The therapeutic use of bile has a long history, with origins traced back to ancient practices. Historical records from Traditional Chinese Medicine (TCM) dating as far back as the Zhou dynasty (1046-256 BCE) document the use of bile from various animals for therapeutic purposes.[6] In TCM, bile acids were utilized for various health concerns including gallbladder health, skin health, vision and eye health, respiratory health, and neurological health.* Ox bile, in particular, was one of the earliest forms used in TCM, containing many bile acids similar to those found in human bile.
Bile Acid Metabolism and Receptor Interactions
The human bile acid pool primarily consists of cholic acid (CA), chenodeoxycholic acid (CDCA), and deoxycholic acid (DCA), with smaller amounts of lithocholic acid (LCA) and ursodeoxycholic acid (UDCA).[7],[8] CA and CDCA, the primary bile acids, are synthesized in the liver from cholesterol. Before being excreted from the liver, these bile acids are conjugated with glycine or taurine, enhancing their water solubility. Once in the digestive tract, specific gut microbes further modify these bile acids, producing secondary bile acids such as DCA and LCA.
Bile acids exert numerous effects throughout the body through interactions with various receptors, including the farnesoid X receptor (FXR), pregnane X receptor (PXR), and vitamin D receptor, as well as several G-protein-coupled receptors (GPCRs) found in cell membranes.[9],[10] In the liver, most bile acid functions are mediated by FXR, which plays a role in the synthesis, transport, and enterohepatic circulation of bile acids. Through these interactions, bile acids help regulate their own levels, protecting the liver from potential damage caused by excessive bile accumulation.[11],[12]
Activation of FXR by bile acids also induces genes involved in detoxification processes, helping protect liver cells from potential toxicity.[13] This is one reason why bile acids are used in individuals who need support for bile acid synthesis.*[14] In such cases, cholic acid (CA), the main bile acid in ox bile, is commonly used.
FXR is expressed in various tissues, including the liver, pancreas, ileum, kidney, and adrenal glands, and to a lesser extent in the heart, central nervous system, adipose tissue, and arterial walls. The ability of different bile acids to activate FXR varies, with CDCA being the most potent activator. Basic science research suggests that FXR activation by bile acids may positively impact metabolic health by supporting lipid metabolism, gluconeogenesis, and insulin receptor activity.*[15],[16]
Another key pathway through which bile acids exert their metabolic effects is the activation of the G-protein-coupled bile acid receptor, TGR5. This receptor, found in brown adipose tissue, pancreatic beta cells, and the biliary tract, influences metabolic health by enhancing energy production and insulin secretion.*[17],[18],[19]
Metabolic Health
Research indicates that altered bile acid homeostasis is often observed in some individuals.*[20] Some studies suggest that the weight loss and improved glycemic control seen after bariatric surgery may be linked to changes in bile acid availability.[21]
In patients who have undergone gastric bypass surgery, elevated levels of total bile acids and specific bile acid subfractions have been observed. [22] These increases have been associated with various markers of metabolic health.*
Some individuals have lower fasting serum levels of CDCA, the most potent FXR activator, and FGF19, a marker of FXR activation. These findings suggest a potential link between bile acid metabolism.*[23],[24]
Conclusion
Bile acids have a rich history of use, and current research continues to uncover their broad therapeutic potential. However, much of the focus remains on synthetic derivatives or isolated fractions of bile acids. While these may offer potent effects, a natural blend of bile acids, similar to those produced by the body, may provide a more balanced and gentle approach to supporting metabolic health.*
The information provided is for educational purposes only. Consult your physician or healthcare practitioner if you have specific questions before instituting any changes in your daily lifestyle including changes in diet, exercise, and supplement use.