Bile | Vitabase

Other Names

Animal gallBile acidsBile extractBile saltsBile soapBile, powderBilis BovisBos taurus bileBovine bileBovine bile concentrateBovine bile, desiccatedBovine bile, powderBovine ox bile extractBovine/ovine bile concentrateCholerConjugated bile acidsDesiccated ox bileDesiccated ox bile powderDried ox gallFel BovisFel TauriFellis BoviniGallGall soapGrassfed ox bileNiu DanOvine bile concentrateOx (Bos taurus) bileOx bileOx bile concentrateOx bile extractOx bile powderOx bile, desiccatedOx gallOx gall powderOxbileOxbile extractOxbile substancePorcine bile extractPorcine bile, powderPurified bile saltsSus scrofa domestica bileTotal bile acidsXiongdan

Synopsis

Bile (Ox Bile / Bile Acids / Bile Salts)

1. Identity: Chemical Names, Natural Sources, and Common Preparations

1.1 Definition and General Chemistry

Bile is a physiological aqueous solution produced and secreted by the liver. It consists mainly of bile salts, phospholipids, cholesterol, conjugated bilirubin, electrolytes, and water. In the supplemental and pharmacological context, the term "bile" most often refers to concentrated preparations of ox bile (bovine bile extract) or to isolated bile acid molecules such as ursodeoxycholic acid (UDCA) and tauroursodeoxycholic acid (TUDCA).

The family of bile acids includes a group of molecular species of acidic steroids with very peculiar physical-chemical and biological characteristics. They are synthesized by the liver from cholesterol through several complementary pathways that are controlled by mechanisms involving fine-tuning by the levels of certain bile acid species.

The first description of a bile acid was made in 1848 when cholic acid (CA) was discovered in ox-gall. Subsequent studies in the early 1900s identified additional bile acids including lithocholic acid (LCA), chenodeoxycholic acid (CDCA), ursodeoxycholic acid (UDCA), and muricholic acid (MCA) from ox, goose, bear, and rodents respectively, as described by Wieland in his 1928 Nobel Lecture. More sophisticated methodologies subsequently led to the identification of multiple additional species of bile acids, including deoxycholic acid (DCA), that contribute to the "bile acid pool" (2–4 g in humans).

1.2 Classification of Bile Acids

Bile acids are systematically classified by their biosynthetic origin and structural modification:

Primary bile acids: The immediate products of the bile acid synthetic pathways are referred to as primary bile acids. Cholic acid (CA) and chenodeoxycholic acid (CDCA) are the primary bile acids formed in humans.
Secondary bile acids: The action of intestinal bacterial flora on primary bile acids results in the formation of secondary bile acid species: deoxycholic acid and lithocholic acid, derived from cholic acid and chenodeoxycholic acid, respectively.
Conjugated bile acids (bile salts): CA and CDCA are conjugated to glycine or taurine, giving rise to glycocholic (GCA), taurocholic (TCA) acids and glycochenodeoxycholic (GCDCA), taurochenodeoxycholic (TCDCA) acids, respectively.
Hydrophilicity spectrum: The increase in the hydrophobic character, moving from primary to secondary bile acids, affects the bile acid chemical–physical and physiological properties, making them differently active in the diverse parts of the enterohepatic circuit.

1.3 Natural Sources and Supplemental Forms

Ox bile is an extract of exactly what its name suggests — the bile of an ox. Ox bile, in particular, is the most common supplemental form of bile because it is so chemically similar to what our bodies naturally make. Ox bile for supplements is typically obtained through a process known as "bovine bile harvesting." During this process, the bile is extracted from the gallbladder or liver of bovines used for meat after their death. The collected bile is then processed and purified to remove impurities and ensure safety for consumption.

The extract is a potent source of bile acids, primarily chenodeoxycholic and cholic acid. These acids are essential for absorption and emulsifying lipids in the small intestine.

Common supplemental and pharmaceutical forms include:

Ox bile extract (desiccated/lyophilized): Available in various forms, including capsules, tablets, and powders, making it easier for individuals to incorporate them into their daily health regimen.
Ursodeoxycholic acid (UDCA): An isolated secondary bile acid — a film-coated tablet available for oral administration.
Tauroursodeoxycholic acid (TUDCA): The taurine-conjugated form of UDCA. TUDCA has been licensed for the treatment of cholesterol gallstones and for therapy of chronic cholestatic liver disease in Europe since 1991 and is used at a dose of 10–20 mg/kg/day depending on the indication.

2. Traditional and Historical Use

2.1 Traditional Chinese Medicine (TCM)

Forty-four different animal biles obtained from both invertebrates and vertebrates (including human bile) have been used for centuries for a host of maladies in traditional Chinese medicine (TCM) beginning with dog, ox and common carp biles approximately in the Zhou dynasty (c. 1046–256 BCE).

There was a wide assortment of animal biles for medicinal use, the total number adding up to 44, of which ox bile was perhaps the most important one. The first mention of bile in TCM dates back to scriptures from 500 BC that mention the use of ox and dog bile for therapeutic purposes. Biles mentioned in other TCM books are from: the common carp fish, goat, sheep, mouse, shark, wild boar, elephant, tiger, and even bile from pythons and venomous vipers.

Overall, different animal biles were prescribed principally for the treatment of liver, biliary, skin (including burns), gynecological and heart diseases, as well as diseases of the eyes, ears, nose, mouth and throat. These bile acids were used for the treatment of gallstones, infectious skin diseases or burns, vision and eye conditions, respiratory infections, and even coma and epilepsy.

Ox bile was used in combination with gentian root, other herbs, and honey to combat jaundice or used on the skin for hemorrhoids. In Traditional Chinese Medicine, animal bile is also used to form an "artificial skin" to dress and cover burns and wounds.

2.2 European and Western Traditions

Bile has been used in traditional medicine for centuries. In Chinese medicine, bile from various animals is used to treat digestive and liver issues, whereas in European herbal medicine, it is used for its digestive and purgative properties.

As global trade and medical knowledge expanded, the use of animal-derived bile spread to other cultures. In the 19th and 20th centuries, Western medicine began to investigate the physiological role of bile acids, leading to the development of purified bile extracts for therapeutic use. Early pharmaceutical preparations often included ox bile or bile salts to assist with fat digestion, especially for patients with liver or gallbladder issues.

3. Key Constituents and Active Compounds

3.1 Composition of Bile

Bile is a natural substance produced by the liver, which then accumulates in the gallbladder. It consists of bile salts, cholesterol, water, bile acids, and bilirubin (the pigment that gives it that greenish-yellowish color).

The principal individual bile acids identified in mammalian bile include:

Cholic acid (CA): A primary bile acid with three hydroxyl groups; the most abundant bile acid in human bile.
Chenodeoxycholic acid (CDCA): A primary bile acid; CDCA has the strongest effect on FXR activation.
Deoxycholic acid (DCA): A secondary bile acid derived from CA by bacterial action.
Lithocholic acid (LCA): LCA, also known as 3α-hydroxy-5β-cholan-24-oic acid, is a monohydroxy bile acid produced from chenodeoxycholic acid (CDCA) or ursodeoxycholic acid (UDCA) by the action of intestinal bacteria. LCA has the highest capacity to activate TGR5.
Ursodeoxycholic acid (UDCA): A secondary bile acid found in high concentrations in bear bile; the most hydrophilic of the common bile acids.
TUDCA: UDCA is a secondary bile acid produced by gut bacteria, and TUDCA is its taurine-conjugated form.

According to the biochemical compounds and pharmacological activities of bile, such as specific bile salts, the bile pigment bilirubin and its glucuronides, secondary bile ingredients such as Vitamins A, D, E, K and melatonin synthetic ingredients, animal bile, such as cow and sheep, are promising candidates for bear bile's similar and alternative therapeutic purposes.

3.2 Biosynthesis

The steps leading to formation of primary bile acids include hydroxylation of cholesterol, catalyzed by the cytochrome P450 enzyme cholesterol 7α-hydroxylase (CYP7A1), the first and rate-limiting step of the so-called classic or neutral pathway of bile acid biosynthesis. Bile acid synthesis can also occur by an "alternative" or "acidic" pathway, which is governed by the enzyme CYP27A1 and converts oxysterols to bile acids.

Conjugation of bile acids increases ionization and solubility at physiological pH, prevents Ca²⁺ precipitation, minimizes passive absorption, and renders them resistant to cleavage by pancreatic carboxypeptidases.

4. Mechanisms of Action

4.1 Digestive / Detergent Role

Enzymatic oxidation of cholesterol generates numerous distinct bile acids that function both as detergents that facilitate digestion and absorption of dietary lipids, and as hormones that activate four distinct receptors.

Cholic acid (CA) and chenodeoxycholic acid (CDCA) are the major primary bile acids synthesized in human livers, and are conjugated with taurine or glycine for secretion into bile. Bile salts form mixed micelles with phospholipids and cholesterol, stored in the gallbladder, and secreted into the intestinal tract to facilitate digestion and absorption of nutrients.

Bile salt anions promote lipid absorption, enhance tryptic cleavage of dietary proteins, and have antimicrobial effects.

4.2 Enterohepatic Circulation

Bile salts have an enterohepatic circulation resulting from efficient vectorial transport of bile salts through the hepatocyte and the ileal enterocyte; such transport leads to the accumulation of a pool of bile salts that cycles between the liver and intestine.

Enterohepatic circulation of bile acids from the liver to intestine and back to the liver plays a central role in nutrient absorption and distribution, and metabolic regulation and homeostasis. This physiological process is regulated by a complex membrane transport system in the liver and intestine regulated by nuclear receptors.

Bile acid synthesis is naturally regulated by feedback inhibition from bile acids being recirculated to the liver. Bile salts inhibit cholesterol 7α-hydroxylase, decreasing the synthesis of bile acids.

4.3 Nuclear Receptor and GPCR Signaling

Bile salts are signaling molecules, activating nuclear receptors in the hepatocyte and ileal enterocyte, as well as an increasing number of G-protein coupled receptors.

Bile acids play an important role in the digestion and absorption of dietary fats and fat-soluble vitamins and act as signaling molecules that regulate metabolic homeostasis through activation of bile acid receptors such as Farnesoid X receptor (FXR) and G protein-coupled bile acid receptor (TGR5).

Studies in the past decades revealed that bile acids are signaling molecules that regulate lipid, glucose and energy metabolism. This regulatory function of bile acids is predominantly mediated by the bile acid-activated nuclear receptor farnesoid X receptor (FXR) and G protein-coupled receptor TGR5.

Bile acids activate farnesoid X receptor (FXR) and G protein-coupled bile acid receptor-1 (TGR5) to regulate bile acid metabolism and glucose and insulin sensitivity. FXR and TGR5 are coexpressed in the enteroendocrine L cells, but their roles in integrated regulation of metabolism are not completely understood. Activation of FXR induces TGR5 to stimulate glucagon-like peptide-1 (GLP-1) secretion to improve insulin sensitivity and hepatic metabolism.

4.4 Intestinal Immune Modulation

Besides being regulators of metabolic homeostasis, FXR and TGR5 are also expressed by cells belonging to both the innate and adaptive immune system, suggesting a role for bile acids in immune cell homeostasis and function.

LCA and DCA derivatives act as important signaling molecules that regulate the differentiation of TH17 and Treg cells, which further remodel intestinal inflammation. 3-OxoLCA directly binds to RORγt and inhibits the differentiation of TH17 cells, while isoalloLCA enhances the differentiation of anti-inflammatory Treg cells through the production of mitochondrial reactive oxygen species that increase FOXP3 expression.

Since the identification of the bile acid receptor FXR, there has been a growing interest in the role of bile acids as signaling molecules that influence cell growth and immune responses. The interaction between bile acids and their key receptors, FXR and TGR5, along with the intestinal barrier, is crucial for maintaining intestinal barrier integrity. This article reviews the functions of bile acid metabolism and the intestinal barrier, detailing the regulatory mechanisms by which bile acids and their primary receptors, FXR and TGR5, influence the mechanical, mucosal, microbial, and immune barriers of the intestine.

5. Scientific Evidence by Area of Use

5.1 Fat Digestion and Lipid Malabsorption

Mechanism and plausibility: The mechanistic plausibility is real. Biliary-related complications after cholecystectomy include fat malabsorption and bile acid diarrhea, and post-cholecystectomy syndrome prevalence in real-world cohorts is meaningful.

Clinical evidence: The most relevant guideline evidence comes from the management of short bowel syndrome, where bile acid depletion creates a similar physiological challenge to post-cholecystectomy states: ox bile supplements have been studied and found to improve fat absorption in patients with depleted bile salt pools, specifically in those who have lost more than 100 cm of ileum, without reports of significant adverse effects. The 2022 AGA guidelines note that ox bile supplements were given to improve fat absorption in bile acid-depleted states, though they acknowledge availability is limited.

A 1993 controlled clinical trial using tauroursodeoxycholic acid (TUDCA, a bile acid component) in 203 cholecystectomy patients demonstrated prompt regression of dyspeptic symptoms.

Evidence strength: Formal randomized controlled trials of OTC ox bile supplements specifically for post-cholecystectomy fat malabsorption are sparse. The clinical-management literature addresses bile acid diarrhea with prescription bile acid sequestrants and dietary fat modification, not OTC ox bile. Functional plausibility is good; trial-level evidence for ox bile as a treatment is weak.

5.2 Gallstone Dissolution (UDCA)

UDCA has been shown to decrease the biliary cholesterol saturation markedly and has found use as an alternative to cholecystectomy in patients with gallstone disease. Currently, gallstone disease is not an FDA-approved indication for UDCA use.

UDCA is FDA-approved for two specific indications: dissolution of radiolucent, noncalcified gallbladder stones smaller than 20 mm in patients with increased surgical risk, and prevention of gallstone formation in obese patients experiencing rapid weight loss.

Dosage from studies: The dosing of UDCA is as follows: for gallstone dissolution, 8 to 10 mg/kg/day orally divided into 3 or 4 doses; for gallstone prophylaxis, 300 mg orally twice daily.

Despite the extensive evidence accumulated regarding the possible use of UDCA in various types of diseases, the largest amount of evidence still remains the beneficial effect of UDCA in dissolution of cholesterol gallstones.

Evidence strength: Strong for cholesterol gallstone dissolution; this is one of the most well-documented applications with multiple randomized clinical trials and FDA recognition.

5.3 Primary Biliary Cholangitis (PBC)

UDCA is commonly used to treat patients with primary biliary cholangitis (formerly known as primary biliary cirrhosis), an immune-mediated cholestatic liver disease characterized by the destruction of intrahepatic bile ducts.

Ursodeoxycholic acid (UDCA) has been recommended as the first-line therapy for PBC patients according to guidelines since its approval by the Food and Drug Administration (FDA) in 1977, as it benefits biochemical mitigation and transplantation-free survival. UDCA was also found to slow the patient's histological progress compared with a placebo.

Dosage from studies: UDCA at 13–15 mg/kg/day is the established first-line treatment for PBC, supported by multiple randomized controlled trials and international guidelines. Dosing of 13–15 mg/kg/day divided into 2–3 doses is recommended by hepatology guidelines, though the FDA-approved dose is 8–10 mg/kg/day.

The optimum dose of UDCA has been identified in studies as 900 mg/day (equivalent to 13.5 mg/kg/day). Ursodeoxycholic acid improves liver function tests and prolongs survival in primary biliary cirrhosis. The dose of 10–15 mg/kg/day used in the large trials has largely been based on that used for gallstone dissolution.

Despite the efficacy, it was estimated that nearly 40% of PBC patients on standard UDCA therapy did not achieve a complete response.

Evidence strength: Strong and consistent; multiple large RCTs support UDCA for PBC, and it represents the standard of care in this indication.

5.4 Post-Cholecystectomy Syndrome

A clinical trial using tauroursodeoxycholic acid (a bile acid) at 500 mg per day showed reduced dyspepsia in cholecystectomized patients. Post-cholecystectomy patients lose the gallbladder's bile-concentrating and metered-release function; undigested fats reach the colon, where they stimulate water secretion and speed up transit time. This is why post-cholecystectomy diarrhea is common, especially after meals rich in fat. Bile acids that are not reabsorbed in the small intestine also contribute to this, a condition called bile acid diarrhea.

Evidence strength: The TUDCA trial at 500 mg/day is a controlled study, but the overall evidence base for broad-spectrum OTC ox bile supplementation in this population remains limited and requires larger confirmatory trials.

5.5 Metabolic Regulation: Glucose, Insulin, and Obesity

Research in the past two decades has unveiled important roles for bile acids in the regulation of hepatic lipid, glucose and energy metabolism. Small molecule ligands that target TGR5 and FXR have shown promise in treating various metabolic and inflammation-related human diseases.

Bile acids can affect glucose and energy metabolism by activating TGR5, and are involved in anti-inflammatory immune regulation.

Several studies indicate that 1.75 g/day of TUDCA is a safe and likely effective dose for insulin resistance. In a recent study, 10 obese, insulin-resistant adults received 1.75 g/day of TUDCA for 4 weeks with no adverse events.

Evidence strength: Preclinical evidence is substantial; human clinical evidence is preliminary and based on small studies. Larger RCTs are needed to confirm metabolic benefits in humans.

5.6 Cholestatic Liver Disease and Liver Protection

Bile acids are used therapeutically to correct deficiency states, to decrease the cholesterol saturation of bile, or to decrease the cytotoxicity of retained bile acids in cholestatic liver disease.

TUDCA has been licensed for the treatment of cholesterol gallstones and for therapy of chronic cholestatic liver disease in Europe since 1991. A cohort of subjects with primary biliary cirrhosis were treated with 500–1500 mg/day of TUDCA for 6 months, with diarrhea reported as the only side effect.

Previous studies have demonstrated that about 65% of the oral dose of TUDCA is absorbed and then undergoes first-pass metabolism in the liver followed by extensive enterohepatic circulation. Administration of bile acids such as UDCA and TUDCA results in a change in the overall serum bile acid concentration — between 1.9 and 8-fold — and alters the composition of the bile acid pool.

Evidence strength: Well-supported for UDCA in PBC; supportive for TUDCA in cholestatic conditions, particularly in Europe where it holds regulatory approval.

5.7 Gut Microbiome, Intestinal Immunity, and Inflammatory Bowel Disease

Evidence shows that changes in bile salt pool and composition due to changes in gut microbial composition contribute to the pathogenesis of inflammatory bowel disease and metabolic disease, possibly through altered activation of TGR5 and FXR.

Animals lacking the nuclear receptor FXR or the membrane receptor TGR5 are more susceptible to colitis, indicating that bile acid-triggered receptors are essential for sustaining intestinal homeostasis.

Protective bile acids (TCDCA, UDCA) attenuate chronic inflammation by inhibiting NF-κB through the FXR/TGR5 axis.

Evidence strength: Primarily preclinical (animal models and in vitro). Human data on bile acid supplementation as a direct treatment for IBD are limited; translation to clinical practice is still under investigation.

5.8 Colorectal and Hepatocellular Cancer Risk

In colorectal cancer (CRC), microbially produced secondary bile acids like deoxycholic acid (DCA) and LCA can activate TGR5 on tumor cells, leading to CCL28-mediated recruitment of immunosuppressive Tregs into the tumor, thereby fostering tumor progression. Specific intratumoral bile acid profiles in CRC correlate with high Treg abundance and poor patient outcomes, and bile acid dysregulation in hepatocellular carcinoma is linked to Th17/Treg imbalances potentially affecting immunotherapy responses.

In a nested case-control study within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort, pre-diagnostic plasma levels of seven conjugated bile acid metabolites including GCA, TCA, GCDCA, TCDCA, GHCA, GDCA, and TDCA were found to be associated with cancer risk.

Evidence strength: Epidemiological associations exist, and mechanistic data are emerging; however, no controlled clinical trials support the use of supplemental bile as a cancer preventive or treatment. The relationship between secondary bile acids and cancer risk is an area of active investigation.

5.9 Colonic Transit and IBS-D

Two randomized, double-blind, placebo-controlled studies were performed. In healthy volunteers (20/group), investigators evaluated effects of oral placebo, 500 mg, or 1000 mg of sodium chenodeoxycholate (CDC) given for 4 days on gastrointestinal and colonic transit. In healthy volunteers, CDC significantly accelerated colonic transit at 24h and 48h (p=0.01 and p<0.0001, respectively), increased stool frequency, and ease of passage.

Evidence strength: Moderate; small controlled trials confirm that oral bile acid administration accelerates colonic transit. These findings explain both the potential use in constipation-predominant conditions and the risk of diarrhea as an adverse effect.

6. Body Systems and Health Areas Associated with Bile

Hepatobiliary system: Bile is produced in the liver; UDCA and TUDCA are directly used to treat cholestatic liver diseases, and bile acids regulate cholesterol homeostasis.
Gastrointestinal tract: Fat emulsification and digestion, intestinal transit modulation, and antimicrobial effects in the gut lumen. Bile salt anions promote lipid absorption, enhance tryptic cleavage of dietary proteins, and have antimicrobial effects.
Metabolic system: Research has unveiled important roles for bile acids in the regulation of hepatic lipid, glucose, and energy metabolism.
Immune system: Bile acids act as signaling molecules that regulate metabolic homeostasis through activation of FXR and TGR5. FXR and TGR5 are also expressed by cells belonging to both the innate and adaptive immune system, suggesting a role in immune cell homeostasis and function.
Gut microbiome: Bile acid synthesis is naturally regulated by feedback inhibition from bile acids being recirculated to the liver; conversely, the gut microbiota transforms primary into secondary bile acids, creating a bidirectional interaction with the microbiome.
Fat-soluble vitamin absorption: Vitamins A, D, E, and K require fat for absorption. They dissolve in dietary fat, which is then emulsified by bile and absorbed in the small intestine along with the fat. Without adequate bile to emulsify fat, these vitamins hitch a ride on fat that never gets absorbed. Over time, this can lead to deficiencies.

7. Dosage Forms and Dosages Reported in Studies

The following dosages are drawn directly from cited human studies and clinical protocols:

UDCA — gallstone dissolution: 8 to 10 mg/kg/day orally divided into 3 or 4 doses.
UDCA — gallstone prophylaxis: 300 mg orally twice daily.
UDCA — primary biliary cholangitis: 13–15 mg/kg/day divided into 2–3 doses is recommended by hepatology guidelines. A dose-optimization study identified 900 mg/day (equivalent to 13.5 mg/kg/day) as the optimum dose.
TUDCA — cholestatic liver disease: 10–20 mg/kg/day depending on the indication.
TUDCA — insulin resistance (pilot study): 10 obese, insulin-resistant adults received 1.75 g/day of TUDCA for 4 weeks.
TUDCA — primary biliary cirrhosis cohort: 500–1500 mg/day for 6 months.
TUDCA — post-cholecystectomy dyspepsia trial: 500 mg per day.
Sodium chenodeoxycholate — colonic transit study: 500 mg or 1000 mg delayed-release, given for 4 days.

No standardized dosage has been established by regulatory agencies for over-the-counter bovine ox bile extracts. Mechanistically, bile salts function in the presence of dietary fat in the small intestine; ox bile products are therefore typically formulated for use with meals.

8. Safety Considerations and Known Interactions

8.1 Cytotoxicity of Hydrophobic Bile Acids

In vitro cytotoxicity of bile salts is positively proportional to their detergent effect, which is related to their hydrophobic-hydrophilic balance. In vivo liver injury can also occur when the liver is perfused by a high proportion of strongly detergent bile salts.

Within each class, the following order of decreasing detergent power can be indicated: lithocholic greater than deoxycholic greater than chenodeoxycholic greater than cholic greater than ursodeoxycholic acid.

8.2 Lithocholic Acid Toxicity

LCA is a monohydroxy bile acid produced from chenodeoxycholic acid (CDCA) or ursodeoxycholic acid (UDCA) by the action of intestinal bacteria. LCA acts as a detergent to solubilize fat for absorption in the intestine, but is considered to be toxic for hepatocytes.

Older studies showed that the species-specific toxicity of lithocholic acid could be explained by efficient sulfation of lithocholic acid in man and in chimpanzee, but not in the rabbit, rhesus monkey, or baboon. Recent studies suggest that lithocholic acid induces its own detoxification by activating nuclear receptors to promote transcription of genes encoding sulfotransferase.

8.3 Bile Acid Diarrhea

Increased colonic delivery of bile acids in conditions of bile acid malabsorption leads to what is referred to as "bile acid diarrhoea." The dihydroxy bile acids chenodeoxycholic acid and deoxycholic acid have been blamed for this phenomenon.

It is generally perceived that bile salts accelerate colonic transit by causing secretion. This perception is reinforced by observations of diarrhea post-cholecystectomy and the assumption that this results from bile salt loss. However, fewer than 20% of patients develop diarrhea post-cholecystectomy.

8.4 High-Dose UDCA in Primary Sclerosing Cholangitis

Ursodeoxycholic acid (UDCA) in a dose of 28–30 mg/kg/day increases the likelihood of clinical deterioration of primary sclerosing cholangitis (PSC) patients. There was an increased development of clinical endpoints amongst patients using UDCA vs. placebo with early histologic disease (stage 1–2). The increased risk of adverse events with UDCA treatment as compared to placebo is only apparent in patients with early histologic stage disease or normal total bilirubin. This finding highlights that the use of bile acid therapy at high doses may be contraindicated in specific patient populations.

8.5 General Adverse Effects

Side effects include diarrhea, nausea and vomiting, rash, and newly developed high blood pressure, which were mild and tolerated.

Based on available animal and human data, other than the potential for diarrhea, TUDCA appears to be very well tolerated even at doses 30-fold greater than the proposed therapeutic dose.

Hypertransaminasemia is a frequent side effect during chenodeoxycholic acid administration for gallstone dissolution. Evidence suggests that this effect is not mediated by lithocholic acid, the intestinal metabolite of chenodeoxycholic acid, but that toxicity is due to the chenodeoxycholic acid itself.

8.6 Product Quality Variability

Ox bile supplements are classified as dietary supplements, not medications, which means they are not regulated with the same rigor as prescription drugs. Quality can vary between brands. The bile acid composition in commercially available ox bile powders has been shown to differ from one manufacturer to another.

8.7 Drug Interactions

As a class consideration relevant to bile acid sequestrants (which work oppositely by binding bile in the gut): cholestyramine can interfere with the absorption of many medications such as digitalis glycosides, propranolol, thiazides, warfarin, tetracycline, iron salts, statins, ezetimibe, and phenobarbital. Supplemental bile acids themselves could, in principle, enhance the absorption of fat-soluble drugs; there are no known interactions between bile acids and antiretroviral drugs based on TUDCA pharmacokinetic studies. Bile acid absorption itself is enhanced by co-ingestion with food: the absorption of UDCA is enhanced by other bile acids; therefore, it is recommended to take the drug during meals with food to facilitate biliary secretion by the gallbladder.

References

Health Conditions

Health conditions that Bile may help support.

No conditions available.

Body Systems

Body systems that Bile may help support.

No body systems available.