Bile acids are a family of cholesterol-derived molecules made and secreted by the liver into the small intestine to support the digestion and absorption of fats. This article will discuss the symptoms and conditions associated with imbalances in bile acid metabolism and the therapeutic indications for bile acids in the functional medicine setting.
What are Bile Acids?
Bile acids are steroid acids found predominantly in bile, synthesized in the liver as end products of cholesterol metabolism. They are responsible for fat emulsification, aiding fat digestion and absorption in the small intestine. Additionally, bile salts help the body absorb fat-soluble vitamins A, D, E, and K. (1, 2)
Primary bile acids, chenodeoxycholic acid (CDCA), and cholic acid (CA) are derived from cholesterol in the liver. Liver cells then conjugate them by adding a glycine or taurine residue to form conjugated bile acids (or bile salts). Bile salts are secreted into the small intestine to aid fat digestion and absorption and travel to the large intestine. In the large intestine, commensal gut bacteria modify the bile salts by removing the glycine and taurine groups. This results in the formation of secondary bile acids, where CDCA is converted to lithocholic acid (LCA) and CA is converted to deoxycholic acid (DCA). Clostridium, Enterococcus, Bacteroides, and Lactobacillus bacteria are primarily responsible for deconjugating bile salts into secondary bile acids. All four bile acids can be absorbed by intestinal cells and recycled back to the liver. (1, 2)
Clinical Significance of Elevated Bile Acids
Emerging evidence supports the notion that elevated primary bile acids and their interactions with intestinal and immune cells contribute to the inflammatory process underlying inflammatory bowel disease (IBD) development and progression (8).
Elevated secondary bile acids have been associated with the following:
- Impaired gallbladder function and cholesterol gallstone formation (3, 4)
- Large intestinal inflammation, which contributes to a compromised gut barrier and increased intestinal permeability (5, 6)
- Colon cancer, especially with an elevated LCA:DCA ratio. Secondary bile acids have been associated with increased DNA damage and have been shown to have carcinogenic properties. LCA is thought to be more toxic than DCA due to its inhibitory effects on antioxidant pathways. (7)
Bile acid diarrhea (BAD) causes up to 33% of chronic diarrhea. Poor bile acid reabsorption in the small intestine and excessive bile acid concentrations in the colon lead to increased colonic motility and secretions, causing diarrhea, fecal urgency, and abdominal cramping.
Clinical Significance of Low Bile Acids
When bile acid production is insufficient, fat-soluble vitamins and fatty acids will be poorly absorbed, leading to nutrient deficiencies over time. Additionally, when these unabsorbed fatty nutrients travel to the colon, they can cause digestive symptoms like diarrhea, gas, and abdominal cramping.
Bile acids act as steroid hormones, having various direct metabolic actions in the body. Deficient bile salts can disrupt normal hormone synthesis and negatively impact metabolic function, contributing to elevated triglycerides, blood sugar, and fatty liver disease.
Bile supersaturated with cholesterol due to low concentration of bile acids is a primary cause of cholesterol gallstones.
Low secondary bile acids may result from the use of broad-spectrum antibiotics, causing intestinal dysbiosis, and reduced cholesterol intake or absorption.
Functional Medicine Labs to Test for Bile Acids
Bile acids can be measured through blood and stool samples. Blood testing is typically indicated for the assessment of liver and gallbladder health. Comprehensive stool testing also allows for an extensive evaluation of fat malabsorption, intestinal inflammation, and dysbiotic patterns of the intestinal microbiome, often accompanying bile acid imbalances.
For patients at increased risk for diabetes, liver disease, and gallstones, a comprehensive metabolic panel (CMP) can monitor blood sugar and liver/gallbladder function.
A cholesterol panel can diagnose high or low cholesterol contributing to abnormal bile acid levels. This Cholesterol Balance test can provide additional insight into the cause of abnormal cholesterol levels by measuring markers of endogenous synthesis and gastrointestinal absorption of cholesterol.
A nutrient panel can measure micronutrients and identify deficiencies if fat malabsorption is suspected.
Bile Acids in Functional Medicine Protocols
For those with bile acid imbalances, diet can significantly impact the gastrointestinal metabolism and regulation of bile acid levels. Resistant starch and insoluble fiber in the diet can reduce secondary bile acids in the stool by binding to them and increasing fecal elimination. Insoluble fiber also promotes short chain fatty acid production in the colon, lowering intestinal pH and inhibiting the enzyme that deconjugates bile salts, thereby reducing concentrations of LCA and DCA. High consumption of saturated fats and red meat is, conversely, associated with elevated secondary bile acid levels. (9, 10)
Bile acids and their derivatives can be used therapeutically and benefit human health in various scenarios.
- Ursodeoxycholic acid (UDCA) and/or CDCA are commonly prescribed to dissolve gallstones (11).
- UDCA has been proven to be especially beneficial in treating cholestatic liver diseases, including primary biliary cirrhosis, pediatric cholestatic disorders, primary sclerosing cholangitis, and drug-induced cholestasis (12).
- Some cases of bile reflux, backflow of bile from the small intestine into the stomach and esophagus, can be treated with UDCA.
- Promising emerging evidence suggests that bile acid treatment can downregulate inflammation associated with psoriasis.
- CA is approved for treating rare bile acid synthesis disorders (13, 14).
- A growing body of evidence supports the beneficial effects of tauroursodeoxycholic acid (TUDCA) in fat digestion, microbiome diversity, reduction of cellular stress, liver disease, and neurological concerns.
Bile acids support fat digestion, stimulate bile flow, and enhance cholesterol elimination. Imbalances in bile acid synthesis and metabolism are associated with fat malabsorption, nutrient deficiencies, and metabolic diseases like diabetes. Blood and stool tests can evaluate bile acid levels and ratios to determine underlying causes of digestive and metabolic symptoms. Addressing diet and the microbiome can support healthy bile acid levels. Emerging evidence supports a wide range of therapeutic uses for bile acids/salts. Working with a functional medicine doctor, you can learn how bile acids may affect your health and if you are a good candidate for bile acid supplementation.
Lab Tests in This Article
1. Staels, B., & Fonseca, V. (2009). Bile Acids and Metabolic Regulation. Diabetes Care, 32(suppl_2), S237–S245. https://doi.org/10.2337/dc09-s355
2. Hofmann, A.F. The Continuing Importance of Bile Acids in Liver and Intestinal Disease. Arch Intern Med. 1999;159(22):2647–2658. doi:10.1001/archinte.159.22.2647
3. Wang, D., Cohen, D., & Carey, M.C. (2009). Biliary lipids and cholesterol gallstone disease. Journal of Lipid Research, 50, S406–S411. https://doi.org/10.1194/jlr.r800075-jlr200
4. Wang, H.H., Portincasa, P., & Wang, D. (2008). Molecular pathophysiology and physical chemistry of cholesterol gallstones. Frontiers in Bioscience, 13(13), 401. https://doi.org/10.2741/2688
5. Kakiyama, G., Hylemon, P.B., Zhou, H., et al. (2014). Colonic inflammation and secondary bile acids in alcoholic cirrhosis. American Journal of Physiology-Gastrointestinal and Liver Physiology, 306(11), G929–G937. https://doi.org/10.1152/ajpgi.00315.2013
6. Ridlon, J.M., Alves, J., Hylemon, P.B., et al. (2013). Cirrhosis, bile acids and gut microbiota. Gut Microbes, 4(5), 382–387. https://doi.org/10.4161/gmic.25723
7. Nguyen, T.H.O., Ung, T.T., Kim, N., et al. (2018). Role of bile acids in colon carcinogenesis. World Journal of Clinical Cases, 6(13), 577–588. https://doi.org/10.12998/wjcc.v6.i13.577
8. Novel approaches to the diagnosis of bile acid diarrhea - Mayo Clinic. (2020, April 23). https://www.mayoclinic.org/medical-professionals/digestive-diseases/news/novel-approaches-to-the-diagnosis-of-bile-acid-diarrhea/mqc-20479822
9. Ajouz, H., Mukherji, D., & Shamseddine, A. (2014). Secondary bile acids: an underrecognized cause of colon cancer. World Journal of Surgical Oncology, 12(1). https://doi.org/10.1186/1477-7819-12-164
10. Van Munster, I.P., & Nagengast, F.M. (1993). The Role of Carbohydrate Fermentation in Colon Cancer Prevention. Scandinavian Journal of Gastroenterology, 28(sup200), 80–86. https://doi.org/10.3109/00365529309101581
11. Fromm, H. (1986). Gallstone dissolution therapy. Gastroenterology, 91(6), 1560–1567. https://doi.org/10.1016/0016-5085(86)90216-7
12. Achufusi, T.G.O, Safadi, A.O, & Mahabadi, N. (2022). Megaloblastic Anemia. StatPearls Publishing. https://www.ncbi.nlm.nih.gov/books/NBK545303/
13. FDA approves Cholbam to treat rare bile acid synthesis disorders. (2015, March 18). Fierce Biotech. https://www.fiercebiotech.com/biotech/fda-approves-cholbam-to-treat-rare-bile-acid-synthesis-disorders
14. National Organization for Rare Disorders. (2023, January 12). Bile Acid Synthesis Disorders - Symptoms, Causes, Treatment. https://rarediseases.org/rare-diseases/bile-acid-synthesis-disorders/