Bile Acids 101: Testing, Interpreting, Treatment

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 potential roles of bile acids in supporting health within the functional medicine setting.

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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 suggests that elevated primary bile acids and their interactions with intestinal and immune cells may contribute to the inflammatory processes associated with inflammatory bowel conditions (8).

Elevated secondary bile acids have been associated with the following:

• Impaired gallbladder function and cholesterol gallstone formation (3, 4)
• Large intestinal inflammation, which may contribute to a compromised gut barrier and increased intestinal permeability (5, 6)
• Colon health concerns, especially with an elevated LCA:DCA ratio. Secondary bile acids have been associated with increased DNA damage and have been shown to have properties that may affect cellular health. LCA is thought to be more toxic than DCA due to its inhibitory effects on antioxidant pathways. (7)

Bile acid diarrhea (BAD) may contribute to up to 33% of chronic diarrhea cases. Poor bile acid reabsorption in the small intestine and excessive bile acid concentrations in the colon can lead to increased colonic motility and secretions, potentially 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 may be poorly absorbed, potentially 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, potentially contributing to elevated triglycerides, blood sugar, and fatty liver concerns.

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 individuals at increased risk for diabetes, liver concerns, and gallstones, a comprehensive metabolic panel (CMP) can monitor blood sugar and liver/gallbladder function.

A cholesterol panel can help assess cholesterol levels that may contribute 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 may help 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, which may lower intestinal pH and inhibit the enzyme that deconjugates bile salts, thereby potentially 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 may be used in various scenarios to support health.

• Ursodeoxycholic acid (UDCA) and/or CDCA are commonly prescribed to help manage gallstones (11).
• UDCA has been shown to be beneficial in supporting liver health in conditions like 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, may be managed with UDCA.
• Promising emerging evidence suggests that bile acid treatment may help manage inflammation associated with psoriasis.
• CA is approved for supporting health in rare bile acid synthesis disorders (13, 14).
• A growing body of evidence supports the potential benefits of tauroursodeoxycholic acid (TUDCA) in supporting fat digestion, microbiome diversity, reduction of cellular stress, liver health, and neurological well-being.

Summary

Bile acids support fat digestion, stimulate bile flow, and enhance cholesterol elimination. Imbalances in bile acid synthesis and metabolism may be associated with fat malabsorption, nutrient deficiencies, and metabolic concerns. Blood and stool tests can evaluate bile acid levels and ratios to help 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 potential 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.