Bile is a vital fluid the body makes to digest fats and absorb fat-soluble vitamins. Bile supplements can eliminate gallstones, help the body detox, and improve liver and gut diseases. They come in a variety of forms, of which ox bile is the most common. Continue reading to learn about the function of bile and the health effects of bile supplements.
What is Bile?
Digests Fats
Bile is a complex, vital, and unique fluid produced by the liver to aid in the digestion of fats in the small intestine. The components of bile are actually quite eclectic. It’s yellow-green in color and composed of 95% water in which the following compounds are dissolved, such as [1, 2, 3]:
- Bile acids and salts
- Phospholipids, cholesterol, and steroid hormones
- Pigments and amino acids
- Electrolytes and vitamins
- Antioxidants like melatonin and glutathione
- Antibodies like IgA
- Heavy metals, drugs, and environmental toxins
The liver secretes about 600 ml of bile every day, which amounts to almost 3 cups [4].
Removes Toxins
Bile is the body’s main way of eliminating harmful fat-soluble substances like toxins, drugs, and heavy metals. It’s also the main pathway for eliminating excessive cholesterol from the body [1].
Helps You Absorb Nutrients
Bile dissolves dietary fats so that they can be more easily broken down by lipases. Bile acids enable the digestion and absorption of fats and fat-soluble vitamins like A, D, E, and K in the gut. Bile also protects the gut from infection by stimulating the gut immune system [5, 6, 7].
Bile Production
Signals from the Gallbladder
The liver constantly makes bile that’s transported to the gallbladder via bile ducts. The gallbladder, a small sac-like organ located below the liver, stores and concentrates bile. After food intake, the gallbladder delivers bile into the small intestine where it aids in the digestion of fats [8].
The main signal in the body for the gallbladder to contract and release bile is cholecystokinin. Others include secretin, gastrin, and somatostatin and the vagus nerve [4, 9].
Bile salts are resistant to strong digestive enzymes in the gut are mostly reabsorbed after they achieve their effects. This way, the body recycles bile salts, which can be stored and used again [10].
Bile Acids & Bile Salts
Bile acids are made in the liver from cholesterol [4].
The 2 main bile acids made in the liver are cholic acid and chenodeoxycholic acid. Gut bacteria can modify these into 2 slightly different bile acids (into deoxycholic acid and lithocholic acid), but the liver still makes most bile acids overall [4].
Transforming cholesterol into bile acids is a multistep process that involves many different liver enzymes. Many of these enzymes are part of cytochrome P450, the body’s key detox pathway [11].
These are the most important cytochrome P450 enzymes for bile production [12]:
- CYP7A1
- CYP8B1
- CYP27A1
Bile acids can affect their own production in the body. If they increase too much, they stop their own production. If they’re not produced enough, low levels activate receptors that tell the body to make more bile. The most important one is called the bile acid receptor (FXR) [12].
The activity of these enzymes is also strictly controlled by hormone and drug levels in the body. Hormones, toxins, and drugs can activate certain receptors (so-called nuclear receptors, which include VDR) that affect gene expression. By turning on key genes, they help lower blood lipids, cholesterol, and detox drugs and toxins [13, 14, 15].
When bile acids are taken back to the liver and bound to the amino acids glycine or taurine when they become bile salts. An enzyme called n-acetyltransferase is crucial for this step known as conjugation [4].
If this enzyme is not working properly, free bile acids are released instead of bile salts. Bile acids are incapable of digesting fats. Only bile salts act as natural gut detergents – they have the power to emulsify, dissolve and digest fats in the gut [4].
Function
1) Bile Salts Remove Excess Cholesterol
Bile salts are crucial for maintaining balanced cholesterol levels in the body [16].
Producing bile acids from cholesterol is the key pathway for removing cholesterol from the body. About half of the total cholesterol produced in the body is used to make bile acids [17].
2) Bile Eliminates Bilirubin From the Body
Bile salts play a key role in the removal of bilirubin from the body [18].
Bilirubin is the main pigment in bile. It’s a waste product of hemoglobin breakdown and has harmful effects in the body if accumulated. Bilirubin buildup in the body causes jaundice [19].
The liver takes bilirubin bound to proteins from the bloodstream and then modifies it to make it into a yellow water-soluble form. It then secretes this bilirubin into bile with bile salts. The gut microbiome then breaks down it down into its basic form (free bilirubin) that is darker in color and can finally be eliminated in the stool [4, 20].
3) Bile Salts Digest Proteins and Starches
Bile salts are essential for digesting proteins and starches. They help break down dietary proteins by enhancing the digestive activity of protease enzymes in the pancreas [21].
4) Bile Salts Help Remove Toxins
Bile salts help the bile remove toxic substances from the body [22].
This includes drugs, environmental pollutants, and heavy metals such as mercury, lead, silver, and cadmium [1].
Scientists are still debating exactly how bile salts are able to do this. Toxins can activate genes that help make bile and phase II detox enzymes. Once the bile is produced, toxins are modified and added to bile along with bile salts. They travel along the gut and can be eliminated through the stool [15].
5) Bile Salts Help Absorb Fat-Soluble Vitamins
Without bile salts, fat-soluble vitamins (Vitamin A, D, E, and K) cannot be absorbed. Bile salts break down fats and the vitamins dissolved in it into small particles called “micelles”. This allows cells in the gut lining to transport them into the body [15].
And it’s not just that bile salts affect vitamin absorption. Some fat-soluble vitamins themselves can have an effect on the amount of bile the body makes. This way, vitamins regulate their own levels [23].
When the dietary intake of fat-soluble vitamins is high, Vitamin A and vitamin D can deactivate genes that make bile to reduce their own absorption and vice versa. Vitamin A and vitamin D have a strong effect on the receptors that affect bile gene expression (via RAR, RXR, and VDR). This prevents a buildup or deficiency of vitamins A, D, E, and K under normal conditions [23].
In fact, vitamin A may have specific therapeutic potential. It can help the bile re-establish its own feedback loops if it was interrupted for any reason. For example, vitamin A may help in cases when the body stops re-absorbing bile salts from the gut, which is needed to recycle bile salts that are re-used [23].
6) Bile Protects the Gut from Infections
Bile protects the organism from gut infections by [1]:
- Making immunoglobulin A (IgA), the first line of defense against harmful microbes
- Stimulating the gut immune system
On the other hand, chronic inflammation reduces bile production in the body. Increased inflammatory substances ( IL-1 beta, IL-6, TNF-alpha, and nitric oxide) all reduce bile secretion, this way making the gut vulnerable to infections [1].
When Bile Flow Becomes Dysfunctional
Dysfunctional bile flow reduces the digestion of fats, absorption of vitamins, and toxins detox in the small intestine [24].
This leads to a condition known as cholestasis, which means “blocked bile flow”. Dysfunctional bile flow causes [25]:
- Fats to build up in the gut instead of being broken down, which causes indigestion, stomach pain, loss of appetite, and greasy or gray-colored stools
- Vitamin A, D, E, and K deficiencies
- A buildup of toxic substances such as bilirubin. Increased bilirubin causes jaundice – itchy yellow-colored skin and eyes. Bilirubin has to be eliminated via urine, coloring it light-brown.
- Bile acid buildup increases oxidative stress, which can damage the liver and may even increase the risk of cancer [12]
- Bile cholesterol buildup that forms gallstones in the gallbladder
- Gallstones cause inflammation not only of the gallbladder but also of the liver and pancreas. In such cases, the surgical removal of the gallbladder is recommended [26, 27].
- Increased susceptibility to gut infections
Bile production and flow can become dysfunctional due to various causes. Some conditions that worsen the flow of bile salts include chronic inflammation, liver diseases such as hepatitis or cirrhosis, cystic fibrosis, and diabetes [12].
Bile Supplements: What Are the Options?
How They Work
Under normal conditions, the gallbladder releases the stored bile into the small intestine in response to food. Bile, containing bile salts, initiates the breakdown and absorption of fats [8].
But under abnormal conditions caused by diseases of the pancreas, liver, or hormones, bile salts are not properly absorbed, leading to the increased accumulation of fats in the gut [28, 29].
Bile supplements (like ox bile, other animal biles, UDCA, TUDCA, or other bile acids) act to counter bile salts deficiency in the gut and may [30]:
- Break down and eliminate cholesterol gallstones [3].
- Protect the gut from damage and infections [31, 3].
- Protect the liver and restore natural bile acid production and bile flow [32].
- Help absorb fats and fat-soluble vitamins, reducing symptoms of indigestion and greasy stools [33].
- Restore the cholesterol-lowering effect of bile salts. Once supplemented bile is mixed up with gut contents, it’s removed with the stool. This loss of bile acids forces the liver to release more bile acids to compensate, transforming more cholesterol to bile acids.
- Reduce cholesterol production in the liver mediating the cholesterol-lowering effects [34, 35, 36].
- Reduce anxiety and promote sleep, due to their melatonin content [3].
Types of Supplements
Various types of bile supplements are available, including all of the following:
- Ox bile
- Ox bile combined with various digestive enzymes (such as Pancrelipase, Pancreatic Protease, Pancreatic Amylase, Pancreatic Lipase, Papain, Bromelain) and/or Betaine HCl
- Ox bile combined with herbs such as dandelion root or artichoke
- Ox bile in combination with probiotics
- Ox bile combined with Taurine
- Purified bile salts such as TUDCA, ursodeoxycholic acid (Ursodiol or UDCA), cholic acid
- TCM bile supplements (see below)
In most supplements, the dosage of ox bile varies between 100 – 500 mg.
The content of pure bile acids in ox bile is about 40%. Some supplements may be purified to contain higher amounts [37].
In Traditional Chinese Medicine
Ox bile and other animal bile supplements were an important part of Traditional Chinese Medicine (TCM) since ancient times. 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 [3].
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 [3]!
Interestingly, python bile was traditionally used to eliminate parasites and reduce gum inflammation and tooth cavities.
Ox bile was used in combination with gentian root, other herbs, and honey to combat jaundice or used on the skin for hemorrhoids.
A recent analysis showed that different animal biles have different components. Accordingly, specific animal bile supplements are used for a variety of acute and chronic diseases in TCM [3].
Only pig, ox and bear biles are extensively used in China today.
Health Benefits of Ox Bile Supplements
1) Eliminate Gallstones
Bile supplements may reduce cholesterol gallstones in the gallbladder (cholelithiasis), potentially reducing the need for surgical removal of the gallbladder.
In one clinical trial of 24 people, bile acids (UDCA up to 1,000 mg/day) reduced cholesterol in gallstones after one month [38].
Bile acids (UDCA) reduced gallstones in 6 people with hepatitis B after 3 – 20 months (daily dose of 8 – 11 mg/kg). It completely dissolved the stones in 5 people and reduced liver enzymes. They remained gallstone free for at least 2 years [39].
The primary bile acid chenodeoxycholic acid (0.75 – 4.5 g/day) eliminated gallstones in a trial of 7 women with 6 – 22 months. It also restored bile acid production in the liver [40, 41].
2) Help Remove Toxic Substances From the Body
Bile supplements assist in the removal of toxic substances from the body [42].
Toxins that enter the body via pollution, food, or medications, as well as those that build up in the body, are usually broken down by the liver. They are then combined with bile salts, secreted into the gut as bile, and removed through the stool. However, they lack bile salt production results in the accumulation of these toxins in the liver, which can trigger many chronic diseases [43, 44].
Bile acids and toxins activate the same receptors in the body, which increase liver detox pathways. In a way, the body views all fat-soluble pollutants (and the majority of environmental pollutants and drugs are fat-soluble) as “toxic bile acids”, which triggers the detox process [45, 46].
Aside from bile supplements themselves, herbal supplements that activate this pathway (PXR activators) may also be useful for people with bile issues [46].
3) May Help Clear Gut Infections and SIBO
Impaired bile salts production creates favorable conditions for intestinal bacterial overgrowth. Bacterial toxins, known as endotoxins, can damage the gut. If the gut damage is severe enough and gut immunity low, the result is a leaky gut barrier that can cause bacteria to enter the bloodstream and cause a systemic infection. On the other hand, lack of bile salts can also cause small intestinal overgrowth (SIBO) [47].
Bile salts have antimicrobial activity and protect the body against harmful bacteria [48, 44].
Bile salt supplements may be especially useful for people with liver cirrhosis who are very susceptible to SIBO and bacterial infections [42].
In several studies of rats with liver damage, bile acids supplements reduced bacterial overgrowth and prevented the bacteria and their toxins from entering the blood [49, 50].
In mice, bile salt supplements could turn on genes that activate the defense system against harmful bacteria [51].
4) May Help with Psoriasis
Bacterial endotoxins might play a role in developing psoriasis. People with psoriasis have detectable levels of endotoxins in the blood, which can cause or worsen inflammation. Bile deficiency may be the underlying cause, as it allows endotoxin to enter the blood and reach the skin. People with psoriasis also often complain of gut and gallbladder problems [52+].
The buildup of toxins and inflammatory substances in the skin can cause red, itchy, and scaly skin patches in psoriasis. Bile acids can balance the gut microbiome, protect from bacterial gut endotoxins, and reduce inflammation [52+].
In a large clinical trial of 800 patients with psoriasis, oral bile acid supplementation (dehydrocholic acid) resolved psoriasis symptoms in 79% of all cases after 1 – 8 weeks. It had even better results in people with acute psoriasis, clearing symptoms in 95% of the cases. Two years later, 58% of chronic psoriasis patients were also symptom-free, compared to only 6% of those on conventional treatment [52].
In bile-deficient rats, bile acid supplements caused helped blocked gut toxins from entering the blood and helped detox them from the body. Enhancing detox with bile salts may also be useful for viral infections, herpes, and clogged arteries in heart disease – all conditions in which bacterial toxins build up in the body [53].
5) May Improve Liver Disease
Bile supplements are used for a number of diseases including cystic fibrosis (a genetic disease) and chronic liver diseases such as primary biliary cirrhosis and non-alcoholic fatty liver disease.
Cystic fibrosis is a genetic disease that affects many organs of the body including the liver. It leads to an abnormal structure and function of the liver [54].
In one clinical study, the bile acid UDCA improved liver function, reduced liver enzymes, and reversed damage in people with cystic fibrosis. All participants were also supplementing with pancreatic enzymes and taurine [55].
Primary biliary cirrhosis is a chronic liver disease in which the bile ducts become dysfunctional.
Immune system dysfunction has been linked to its development. Bile supplements may help reduce and reverse the symptoms and bile duct damage [56].
In one clinical trial, the bile acid UDCA (13 – 16 mg/kg/day) prevented the worsening, improved symptoms, and prolonged survival in people with primary biliary cirrhosis [57].
In one study, UDCA had even more striking benefits when combined with s-adenosylmethionine (SAM-e) in 19 people with this disease. The combination of prolonged remission, reduced elevated liver enzymes, bilirubin, and cholesterol [58].
Non-alcoholic fatty liver disease happens when the liver can’t break down fats, so fat builds up in the liver. It’s not caused by alcohol use and is most common in obese people. People with this disease don’t have functional bile salts, which worsens inflammation and damage. Bile supplements may help, but more research is needed [59, 60].
6) Help with Diarrhea and Fatty Stool
Disrupted bile flow leads to fat buildup in the gut and stool, which causes diarrhea and stomach pain. This condition is known as steatorrhea.
Several diseases are linked to it: gut diseases like Celiac and Crohn’s, cystic fibrosis, kidney, pancreas, and liver diseases. A diet high in hard-to-digest fats, fibers, grains, and excessive drinking can also trigger it.
Bile supplements can help make up for the lack of bile salts and reduce steatorrhea.
A synthetic bile salt cholylsarcosine (2 g/meal) greatly improved fat absorption in the gut and reduced steatorrhea and diarrhea in a clinical trial of 4 people who had part of their bowel surgically removed (short bowel syndrome). In comparison, natural bile salts improved steatorrhea but worsened diarrhea [61].
Taurine, an amino acid that conjugates with bile acids in the bile, can also help the body make more bile salts. It’s needed to conjugate bile acids into bile salts, which is key for their digestive action [62, 63].
In one clinical trial, taurine (30 mg/kg/day) increased fat digestion and absorption in 22 children with cystic fibrosis over six months [64].
Taurine supplementation enhanced the activity of the key enzyme needed to convert cholesterol into bile acids (called 7α-hydroxylase) in animals. That’s why it’s also used for people with heart disease and high cholesterol levels [65].
7) Help People without a Gallbladder
People who have had their gallbladder removed suffer from a deficiency of bile acids.
Without the gallbladder, they are unable to control bile secretion to the intestines. This causes many digestive problems such as constipation, bloating, and diarrhea [66, 67].
The use of bile supplements can make up for the lack of bile, helps in the digestion of fats and absorption of fat-soluble vitamins.
The bile acid TUDCA reduced indigestion and improved symptoms in one trial of 203 people without a gallbladder [68].
8) May Improve Eye Health
The bile acid TUDCA improved eye health in mice and reduced the buildup of harmful free radicals. It may help prevent eye damage [69].
9) May Enhance Weight Loss
Bile acids may help prevent or reverse obesity by enhancing fat-burning. In animal studies, they helped with weight loss, improved insulin sensitivity and protected the heart.
In fat cells, the bile acid chenodeoxycholic acid increased fat breakdown and energy use. This bile acid also reversed obesity in mice fed a high-fat diet by reducing food intake [70, 71].
In obese mice fed a high-fat diet, bile acids increased energy use, fat-burning, lowered glucose and improved the gut microbiome. They improved the overall metabolic profile [72].
Another bile acid – deoxycholic acid – helps break down fat cells when injected directly under the skin into the fat tissue. Solutions of this bile acid are used in the USA and EU to improve the appearance of neck and chin fat. Several clinical trials proved its effectiveness in improving the appearance of neck and chin fullness. It seems to be a well-tolerated and safe option in plastic surgery [73].
10) Help Heal Skin Burns and Infections
In Traditional Chinese Medicine (TCM), animal bile is used to form an “artificial skin” to dress and cover burns and wounds. Bile fats are isolated from bile have unique properties, which enables them to form a protective layer on the damaged skin. They also act as an antioxidant and anti-inflammatory due to the fat-soluble vitamins content while bile acids can kill bacteria [3].
As appealing or repelling as it may sound, bile has some great potential for repairing damaged skin. These studies are still limited to TCM, though, and more research is needed.
Limitations and Caveats
Although the knowledge about the function of bile and various bile salts is growing, the information about bile supplements themselves is limited. The additional difficulty is that there are big differences between various bile acids as well as between different types of animal bile supplements.
Some studies are limited to specific bile salts or TCM observations. Proper, larger, clinical trials are needed, especially with popular ox bile supplements.
Side Effects of Bile Supplements
Considerations
It’s important to note these side effects really depend on the exact composition of bile salts and other ingredients in the supplement. Taking purified bile salts is not the same as taking mixed salts or various animal bile supplements.
The side effects also depend on your health condition. The side effects in people with a surgically removed gallbladder or bowel part will not necessarily be the same as in someone with mild indigestion.
Digestive Problems
Bile supplements can cause digestive problems such as diarrhea, constipation, stomach pain, and vomiting. Although recommended for diarrhea, some natural bile salts may worsen diarrhea, as was the case with ox bile in people with a short bowel [61].
Chenodeoxycholic acid, present in some bile supplements, can too much water to be secreted into the gut, worsening diarrhea. It may even impair the gut barrier [74].
Gut Inflammation
Some components in bile supplements may cause gut inflammation.
Deoxycholic acid is a bile acid produced by gut bacteria and an ingredient in some supplements. In IBS, this acid is probably elevated, which worsens inflammation. In mice, deoxycholate supplementation triggered IBS and DNA/RNA damage [75].
Skin Inflammation (Rare)
In one clinical trial of 24 people, direct exposure to bile salts caused skin itching and blisters [76].
Oral bile supplements probably can’t cause skin inflammation, but skin application of the purified salts or their waste products found in the stool can. Purified digestive enzymes from the stool caused redness and irritation in a skin study. However, the mixture used also contained protein-degrading (proteolytic) and fat-degrading (lipolytic) enzymes that are not found in pure bile [77].
Also, this would be relevant perhaps only if applying bile supplements to the skin, which is not typical. Bile supplements that are applied to the skin are only occasionally used in China and specially modified and prepared.
Possible Cancer Risk
In a mice study, excessive and long-term exposure to bile salts caused colon cancer [78].
Some bile acids have been linked to a number of different cancers in animal studies, such as intestinal, stomach, pancreas, breast, and esophageal cancer [79, 80].
It was first reported that bile acids may be carcinogenic in the 1930s [81].
Recent reports point to the cancer-promoting activity of bile acids [82, 83, 84].
Evidence suggests that high amounts of bile acids in the gastrointestinal tract might increase oxidative stress and DNA damage. High exposure to bile acids also happens in people with high dietary fat intake. However, the exact mechanism of how bile salts may promote cancer upon chronic exposure remains unknown [85].
A clear link between supplementing with bile salts and cancer is missing, though. A lot of the studies looked at high bile acid production caused by a high-fat diet in people, not at the use of bile supplements [82].
Bile acids can cause damage if they accumulate in the gut or liver. But a lot of the seen cancer-promoting effects could be a result of factors that cause increased bile acid production in the first place – such as a high-fat, unhealthy diet, or obesity – and not directly from bile salts themselves. More research is needed to shed light on this [12]
Genetic Factors
1% – 2% of bile duct disorders in children are caused by defects in bile acid production [12].
Some other genetic mutations in enzymes that make bile acids or aid in their activity can cause liver disease or fat-soluble vitamin deficiencies. Some examples include defects in the following genes [12]:
These variations may also affect the efficacy and side effects of bile supplements.
