Bile Supplements

Dietary Supplements and especially bile supplements have received increased attention in recent years among consumers, researchers, and the media. Over the last decade, sales of bile supplements have remarkably raised. These supplements come in a variety of forms and are intended to confer healthy effects on the body. Continue reading this article to learn about the health effects of bile supplements.

Introduction

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Bile is a yellow-green liquid produced by the liver to digest fats in the small intestine (R).

It is constantly synthesized in the liver and stored in the gallbladder, a sac located below the liver. After food intake, the gallbladder delivers the bile into the small intestine where it aids in the digestion of lipids (R). 

In the body, bile acts as a biological detergent that emulsifies and dissolves fats (R).  

Bile is comprised of bile acids that play a key role in the digestion and absorption of fats and extract vitamins from that, also called fat-soluble vitamins like A, D, E, and K (RR).

Bile Induces its Effects Via Bile Acids

Bile acids are water soluble and readily excreted molecules that facilitate in the absorption of dietary lipid in the intestine and increase the biliary excretion of cholesterol.

In human, taurocholic acid and glycocholic acid are the primary bile acids, which are synthesized in the liver from cholesterol breakdown.

The conversion of cholesterol into these bile acids is a multistep process which involved many different enzymes (almost 17 enzymes) (R).

The actions of these enzymes are strictly controlled by factors, such as nuclear hormone receptors, which ensure continues delivery of bile acids in dynamic states of metabolism (R).

Soon after the synthesis in the liver, bile acids undergo numerous structural modification reactions, the most important of which is the conjugation reaction.

Bile acids conjugate with amino acids taurine or glycine and collectively formed bile salts. This reaction is catalyzed by an enzyme called n-acetyltransferase.

The conjugation reaction is important as its absence results in the release of free bile salts, which are incapable of solubilizing and absorbing lipids in the gut (R).  

The Liver is the primary site for bile salts synthesis, though small intestine also produces them up to some extent, hence considered as the secondary site for bile salts synthesis.

Bacteria play an important role in their synthesis in the small intestine (R).

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Functions of Bile Salts

1) Bile Salts Eliminate Cholesterol From the Body

The synthesis of bile salts from cholesterol in the key pathway in the removal of cholesterol from the body.

It has been estimated that about half of the total produced cholesterol in the body is consumed in the bile salts synthesis (R).

In addition, bile salts also help in maintaining the balance level of cholesterol in the body (R). 

2) Bile Salts Eliminate Bilirubin from the Body

Bile salts play a key role in the removal of bilirubin from the body (R).

Bilirubin is a useless breakdown product of hemoglobin (oxygen transporter in the blood), the accumulation of which may exert harmful effects on the body.

During hemoglobin breakdown, the globin part (chains of protein) efficiently recycled and reused, while the heme part (also called porphyrin) cannot be reused and converted into free bilirubin through a series of reactions (R).

The free form of bilirubin is then absorbed in the liver and subsequently conjugated with bile salts in the bile.

The bile salts facilitate its release into the small intestine where the action of bacteria converts it into small compounds, which are ultimately excreted out of the body in feces or in urine (R).

3) Bile Salts Cause Proteins and Starches Digestion

Bile acids of the bile salts have been shown to be essential for digestion of proteins and starches. Bile acids cause the digestion and assimilation of dietary protein by enhancing the activity of protease enzymes in the pancreas (R).

4) Bile Salts Assist the Bile to Remove Toxic Substances

Bile salts also help the bile to remove toxic substances or microbes from the body (R).

Furthermore, bile salts also facilitate the bile in the intestine to remove fecal substances out of the body.

What Happens When Bile Becomes Dysfunctional

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Bile plays a key role in the digestion of fats in the small intestine (R).

Accordingly, when bile becomes dysfunctional, the process of fats breakdown ceases. Consequently, the abnormal accumulation of fats starts in the intestine and reaches to a toxic level.

This ultimately leads to gastrointestinal problems in the body such as abdominal pain, loss of appetite, greasy or gray-colored stools, and light brown urine.

Weight loss and yellowing of the skin and eyes may also occur in some cases (R).       

Abnormal accumulation of bile cholesterol may also lead to the formation of stones in the gallbladder (gallstones), a disease condition called cholelithiasis (R).

The gallstones cause inflammation not only of the gallbladder but also of the liver and pancreas (R).

In such cases, the surgical removal of the gallbladder is recommended (R).

How Bile Supplements Cause Their Effects

When food is eaten, the gallbladder releases the stored bile containing bile salts into the small intestine. Here, the bile salts readily absorb and initiate fats breakdown (RR).

However, under abnormal condition, caused by disease condition or pancreatic insufficiency, the proper absorption of bile salts is disrupted, leading to the increased accumulation of fats in the intestinal region (RR).

Bile supplements usually act by restoring the cholesterol-lowering effect of bile salts in the body.

Once ingested, the bile supplement reaches the liver and immediately releases into the intestine, the place where bile supplements induce their action.

Here, the contents of the bile supplements (usually bile acids) are mixed up with stool and apparently excreted out of the body.

This loss of bile acids through the stool forces the liver to release more bile acids to compensate for the lost bile acids.

The resulting released bile acids by the liver then, in turn, mediate their cholesterol-lowering effects in the intestine. The outcome of this process is the result of the total cholesterol balance in the body (R).

Beneficial Effects of Bile Supplements

1) Bile Supplements Eliminate Gallstones in the Gallbladder

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Bile supplements can be used to treat patients with cholelithiasis (the presence of gallstones in the gallbladder) without the need for surgical removal of the gallbladder.

Clinical research on animal and human has shown that the use of bile supplements (in the form of bile acids at a dose of 3 mg/kg daily) can eliminate gallstones within 12 weeks (R).

Similar kind of study conducted on human also confirmed that the administration of bile supplements is effective in the treatment of cholelithiasis (R).    

In a clinical trial, the efficacy of chenodeoxycholic acid (primary form of bile acids) was tested in cholelithiasis patients. It was found that the ingestion of chenodeoxycholic acid eliminated cholesterol crystal.

In these patients. the chenodeoxycholic acid became the primary bile acid that effectively absorbed cholesterol (R).  

In another study conducted on seven women with gallstones revealed that the intake of chenodeoxycholic acid (0.75-4.5 g/day) for six months removed gallstones in these patients (RR).  

2) Bile Supplements Removes Toxic Substances From the Body

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Bile supplements assist in the removal of toxic substances from the body (R).

Toxins (toxic substances entered into the body externally or produced internally from the metabolic activity in the body) are usually broken down and removed by the liver.

This action is predominantly performed by the bile acids in the liverweight: 400;”>. However, the lack of adequate production of bile acids results in the accumulation of these toxins in the liver that apparently became the source of many chronic diseases (RR).

Bacteria are the most common and dangerous form of toxins (also called endotoxins).

Impairment in bile salts formation in the liver creates favorable conditions for intestinal bacterial propagation, leading to intestinal injury.

In some cases, these bacteria escape from intestinal barriers and enter into the blood circulation, thereby causing systemic infection (R).   

Bile salts have been shown to possess antimicrobial activity and thus can be used as a supplement to protect the body against the pathogenic effects of bacteria (RR).

Bile salts supplement is especially useful in patients with cirrhotic disease as these patients are usually very susceptible to bacterial infections (R).

The use of these supplements has been shown to protect cirrhotic patients against the harmful effects of bacteria. Laboratory research on cirrhotic rats has shown that ingestion of bile acids inhibits the growth and transport of bacteria in the blood and thereby protects the body from their infection (R).  

It was found that the oral administration of bile salts supplement inhibits the overgrowth of intestinal bacteria (R).

Further research on mice has revealed that the intake of bile salts supplement causes the expression of certain genes whose products elicit the activation of the body defense system against harmful bacteria, thereby prevent the body from the pathogenicity of these bacteria (R).

In some cases, these bacterial toxins entered into the bloodstream and are moved to the skin, another major route of toxin removal from the body.

Here, toxins excretion develops psoriasis (red, itchy, and scaly patches on the skin). The use of bile supplements can effectively treat this complication.

To test the efficacy of bile supplements against psoriasis, a clinical trial was performed in 800 patients with acute and chronic psoriasis. Patients were treated with oral bile acid supplementation for 1-8 weeks.

It was found that 78% of the patients became symptoms free following bile supplementation. It was further concluded that bile acid supplementation acts by increasing the availability of bile acid in the intestine that the bacteria and toxins released and their uptake in the gut (R).  

Laboratory research on rats has further highlighted the role of bile acid supplementation in the  treatment of psoriasis and many other diseases.

The results demonstrated that the intake of bile acid supplement causes the detoxification of toxins and inhibits their entrance into the blood circulation, thereby eliminates them from the body through gastrointestinal tract system (R).   

3) The Use of Bile Supplements in the Treatment of Liver Diseases

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Bile supplements can be used to treat a number of liver diseases including cystic fibrosis, primary biliary cirrhosis, and non-alcoholic fatty liver disease.

Bile Supplements as Effective Therapy for Cystic Fibrosis

Cystic fibrosis is an inherited disorder that affects many organs of the body including the liver. Patients with cystic fibrosis exhibit severe abnormalities in the structure and functions of the liver (R).   

Clinical trials have shown that oral supplementation of bile acids is useful in the treatment of cystic fibrosis.

In one clinical study, the efficacy of ursodeoxycholic acid (UDCA), a hydrophilic form of bile acid, was investigated in nine patients with cystic fibrosis.

The administration of UDCA (10 to 15 mg/kg body weight per day) in these patients significantly improved the liver function and reversed the pathology of cystic fibrosis (R).

Bile Supplements Can Treat Primary Biliary Cirrhosis

Primary biliary cirrhosis (also known as primary sclerosing cholangitis ) is a chronic liver disease in which the bile ducts in the liver become dysfunctional. Although the exact cause of the disease in unknown,

Although the exact cause of the disease in unknown, a problem in the immune system (the body’s natural defense system) has been linked to the pathogenesis of the disease (R).     

Clinical research has shown that bile supplementation can be effective in treating primary biliary cirrhosis

In one clinical trial, the efficacy of UDCA was tested in patients with primary biliary cirrhosis. It was found that the oral intake of UDCA at a dose of 13–16 mg/kg/day was very effective against the pathogenesis of primary biliary cirrhosis. 

Its administration not only delayed the progression but also reversed the symptoms of the disease (R).

The combination of UDCA with other supplements can further enhance the efficacy of UDCA.

One study concluded that the efficacy of UDCA against the primary biliary cirrhosis was strikingly increased when it was used in combination with s-adenosylmethionine, a naturally occurring molecule involved in the synthesis and breakdown of proteins and hormones in the body (R).

Beside UDCA, the use of docosahexaenoic acid (DHA) is another potential form of bile supplements that can be used for the treatment of primary sclerosing cholangitis.

DHA is a fatty acid usually found in fishes and are usually used in the diet to improve learning ability (R).    

In a clinical trial conducted on patients with primary sclerosing cholangitis has confirmed that the intake of DHA can efficiently reduce the symptoms associated with primary sclerosing cholangitis (R).    

Bile Supplementation is Effective in the Treatment of Non-alcoholic Fatty Liver Disease

Nonalcoholic fatty liver disease is a broad term for a range of liver conditions characterized by increased accumulation of fats in the liver. It usually occurs in children or in people who are non-alcoholic and obese.

The use of DHA has been shown to treat children with a non-alcoholic fatty liver disease.

A clinical study performed on 60 children with this disease has shown that the DHA reversed the pathological conditions of  the disease.

Following the oral intake of DHA (250 and 500 mg/day) for 6 months in had noticeably decreased the abnormal content of fat in the liver (R).  

4) The Use of Bile Supplements in the Treatment of Intestinal Diseases

Impairment in the intestinal function can cause fat malabsorption and results in the excess fat in feces, a condition called steatorrhea.

There are a number of intestinal diseases that are linked to steatorrhea including short bowel syndrome and cystic fibrosis. In addition, steatorrhea is also associated with pancreatic and liver diseases.

The use of bile supplements is an effective way of dealing with steatorrhea. In this regard, the efficacy of taurine has been extensively studied.

Taurine is an amino acid that conjugates with bile acids in the bile. The conjugation of taurine with bile acids is key in the digestive role of bile (RR) .

Laboratory experiments performed on rats demonstrated that taurine supplementation efficiently improves cholesterol level in the liver.

When rats were fed with a high dose of cholesterol, the total cholesterol level in the body was increased to 77%.

However, when the same diet was accompanied by taurine supplements, the cholesterol level was significantly lowered, especially in the liver which was 49% (R).

Similarly, the efficacy of taurine was also tested in many human clinical trials.  

One study has found that the use of taurine supplement (30 mg/kg/ day) over 6 months caused beneficial effects on fat malabsorption and thereby improved the pathological symptoms of an intestinal disease “cystic fibrosis” (R).

Further research has revealed taurine supplementation acts by enhancing the activity of the enzyme called 7α-hydroxylase in the body. This enzyme is responsible for the conversion of cholesterol into bile acids ((RR).

Beside taurine, the role of cholylsarcosine (a synthetic conjugated bile acid) as a bile supplement has also been studied, especially in people with short bowel syndrome.

A clinical trial performed on patients with short bowel syndrome has shown that intake of cholylsarcosine (2 g/meal) significantly improved fat absorption activity of the large intestine, thereby decreased steatorrhea and diarrhea in these patients (R).  

5) Bile Supplements Help People With Bile Gallbladder Removed

People after gallbladder removal suffer from a deficiency of bile acids.

Without the gallbladder, these patients are unable to control bile secretion to the intestine to properly regulate fats and fats soluble vitamins.

Consequently, many digestive problems (constipation, bloating, and diarrhea) develop in these people (RR).

The use of bile supplements is an effective way of dealing with these complications. The intake of bile supplements helps in the digestion of fats and further aid in the absorption of fat-soluble vitamins.

6) Bile Supplements for Eye Health

Bile supplements have positive effects on the health of the mouse retina, including a reduced accumulation of superoxide radicals, rod cell death, and the disruption of the inner and outer cone segments (R).

Adverse Effects of Bile Supplements

1) Bile Supplements Cause Digestive Problems

The use of bile supplements can cause a number of gastrointestinal complications such as diarrhea, constipation, abdominal pain, and vomiting.

Although bile supplements are recommended for diarrhea, in some cases their intake may worsen diarrhea.

In one clinical study, the use of natural conjugated acids (ox bile extracts) was shown to further exacerbate diarrhea in patients with short bowel syndrome (R).  

Chenodeoxycholic acid is the main constituent in most of the bile supplements.

Oral supplementation of bile supplements can abnormally elevate the concentration of chenodeoxycholic acid in the intestine. This abnormal level of chenodeoxycholic acid has been shown to cause diarrhea (R).

2) Bile Supplements Can Cause Inflammation of the Intestine

Excessive use of bile supplements may lead to inflammation of the large intestine.

Research on mice has shown that deoxycholate supplementation is strongly associated with intestinal inflammation. In these mice, the intake of deoxycholate caused damage of the colon (large intestine) and developed its inflammation.

This inflammation was characterized by angiogenesis (formation of new blood vessels), nitrosative stress (nitrogen stress that causes cell damage), and DNA/RNA damage.

Furthermore, these mice were also exhibiting abnormal expression of genes linked to various important functions of the cell (R).

3) Bile Supplements Can Cause Inflammation of the Skin  

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Exposure to bile supplements may cause skin inflammation.

Bile salt supplements contain digestive enzymes known as proteolytic and lipolytic enzymes, which are implicated in the breakdown of complex proteins and lipids.

In one study performed on human, the irritant potential in fecal concentration of these enzymes were investigated. It was found that prolonged exposure to these digestive enzymes cause skin erythema (redness of the skin) (R).  

Exposure to  bile salt supplements can also cause severe itching of the skin, a condition called pruritus.

In a clinical trial conducted on normal people (both men and women) revealed that direct exposure to bile salts, especially the conjugated form of bile salts, caused blisters on the skin (R).

4) Bile Supplements May Cause Cancer

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The excessive and long-term use of bile supplements may potentially cause cancer (R).

The bile acid form of bile supplements has been linked to a number of different serious cancers, such as cancer of the intestine, stomach, pancreas, breast, and cancer of the esophagus (RR).

The link between bile acids and cancer was first reported in 1939 when it was found that bile acids are carcinogenic, cancer-causing activity (R).

A latest research has confirmed the cancer promoter activity of bile acids (R).

Although the exact mechanism is unknown, several lines of evidence indicate that bile acids cause DNA damage (R) .

The damage of DNA is strongly associated with increased oxidative stress in the body (R).

Given the fact that bile acids cause DNA damage and that the DNA damage is usually linked to oxidative stress strongly suggests that bile acids induce their carcinogenic effects through oxidative stress production (R).   

Interaction with Other Drugs

When taken together with other drugs, bile supplements can interact with them and affect their absorption. This interaction may not only decrease the efficacy of those drugs but may also cause additional side effects.  

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