Gallbladder Disease: Causes, Risk Factors, and Treatments

Gallbladder disease affects a significant number of people in the U.S. An estimated 1.8 million ambulatory care visits and 6.2 billion health care dollars are spent annually on this disease, which has increased by 20% over the last three decades (1). Alternative lifestyle changes such as eating hygiene, decreasing stress, and supplements and nutrients may be options to explore for supporting gallbladder health.

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What is Gallbladder Disease?

The gallbladder is an organ that sits under the liver. It is responsible for storing bile concentrates, which is digestive juice produced in the liver. Bile aids in the digestion of fats and is released from the gallbladder into the small intestines when certain foods are eaten. Gallbladder disease includes inflammation, infection, stones, or gallbladder blockage. (2)

Cholecystitis

Cholecystitis is the most common type of gallbladder disease, which causes swelling or inflammation of the gallbladder. This happens when the digestive juice, bile, gets blocked from the tube that drains it into the intestines. Usually, this happens from gallstones, but it can also be caused by a bacterial infection, a tumor of the pancreas or liver, reduced blood supply to the liver, or a thick material called sludge. (3)

Gallstones

Gallstones affect 10-15% of the population. (1). Gallstones form when bile stored in the gallbladder forms into a stone-like material. These are formed when too much cholesterol, bile salts, or bilirubin (bile salts) block the ducts that go to and from the liver, pancreas, and intestines. (4)

Acalculous gallbladder disease

Acalculous cholecystitis is an inflammatory disease that causes inflammation of the gallbladder without the presence of gallstones. This is usually associated with critical illness and can be triggered by complications from other medical conditions, trauma, or long-term illness. It is commonly associated with a higher incidence of gangrene and perforation.

Gangrene or Abscesses

When cholecystitis is not addressed, it can cause the gallbladder tissue to die, known as gangrene. An abscess is a swollen tissue area with an accumulation of pus.

Polyps

Extra tissue, such as polyps (mucosal projections), can grow in the gallbladder. These typically do not cause symptoms, and only 5% are cancerous.

Congenital Defects of the Gallbladder:

Congenital means a condition you were born with. For the gallbladder, these defects include cystic and non-cystic. Cysts are sac-like formations that can fill with fluid or pus. These can block or impair different parts of the digestive tract involving the gallbladder. Non-cystic congenital anomalies are biliary structures (parts of the gallbladder) abnormalities. (6)

Sclerosing Cholangitis

Sclerosing Cholangitis is when inflammation from chronic gallbladder disease causes scarring and eventual narrowing of the ducts, leading to severe liver damage. In most people, this progresses slowly. A liver transplant is the only option for advanced sclerosing cholangitis.

Tumors of the Gallbladder and Bile Ducts:

Along with polyps, there can be tumors of the gallbladder and bile ducts. Cholangiosarcoma and other bile duct tumors are rare but are usually malignant. Gallbladder carcinoma is uncommon. Worldwide the highest mortality rate is in the Asian population. In the U.S., it is more common in the African American population.

Gallbladder Disease Signs and Symptoms

The most common symptom is called biliary colic. It is usually intermittent (comes and goes) and is described as a gnawing or steady gripping pain in the upper right abdomen near the rib cage. It can be severe and can radiate to the upper back. Nausea or vomiting can also occur. (2)

Symptoms of chronic gallbladder disease (gallstones and inflammation) include symptoms of:

• Gas
• Nausea
• Abdominal discomfort after meals
• Chronic diarrhea. (2)
  

Stones lodged in the common bile duct can cause the following symptoms: (2)

• Jaundice
• Dark urine
• Rapid heart rate
• Fevers, chills, nausea, vomiting, with severe pain in the right upper abdomen

What Causes Gallbladder Disease?

Gallbladder disease begins either in the gallbladder itself or in the bile ducts connected to it. Any infection or blockage in these ducts can back up into your gallbladder, causing inflammation. Gallstones are the most common cause of gallbladder problems, although other possible reasons exist.

Gallbladder Disease Risk Factors

Risk factors for gallstones can be modifiable or not modifiable.

Modifiable risk factors: poor diet, rapid weight loss, and obesity.

Non-modifiable risk factors: being female, ethnicity, advancing age, and genetics.

Gallstone Risk Factors

You are more likely to have gallbladder disease if you have gallstones.

• High cholesterol diet: The most common type of gallstones are cholesterol gallstones. These gallstones are composed mainly of undissolved cholesterol.
• Overweight and obesity: Obesity is an established risk for gallstone disease. At least 25% of morbidly obese individuals have evidence of gallstone disease (1).
• Age greater than 60: The frequency of gallstones increases with age, escalating after age 40 to become 10-40 times more likely in older adults (1).
• Assigned female sex: The female sex is almost twice as likely to form gallstones until menopause, and then men start to catch up. The underlying mechanism is the female sex hormones. Female hormones may impact bile secretion from the liver and gallbladder function. Estrogens may increase cholesterol secretion and diminish bile salt secretion, while progestins may reduce bile salt secretion and impair gallbladder emptying, leading to periods of inactivity for the gallbladder. Oral contraceptives and estrogen replacement therapy are established risk factors for cholesterol gallstone formation. (1).
• Family history of gallbladder disease: Family history and genetics significantly influence gallstone risk factors. Familial studies reveal an increased frequency of nearly five times elevated risk in relatives of gallstone patients (1).
• Native American or Mexican American heritage: These ethnicities have an up to 70% likelihood of developing gallstones.
• Diabetes: Diabetes mellitus and metabolic syndrome are risk factors for gallstone disease. Metabolic syndrome and insulin resistance have been associated with cholesterol gallstone formation, suggesting altered cholesterol and bile salt metabolism (1).
• Underlying Chronic Diseases: Chronic diseases can cause gallstones, such as advanced cirrhosis, chronic hepatitis C viral infection, and non-alcoholic fatty liver disease. There is a two to a three-fold risk of gallstones in Crohn's disease. In cystic fibrosis, the evidence of gallstones is 10-30% (1)
• Cirrhosis of the liver: This late-stage liver disease can slow bile flow from the liver to the gallbladder, causing buildup.
• Sickle cell disease: This condition causes a buildup of bilirubin in the gallbladder, leading to the less-common pigmented type gallstones.
• Total parenteral nutrition: Individuals on total parenteral nutrition (TPN) is a well-known risk factor for sludge developing in the gallbladder (1). This is from the lack of activity in the digestive system.
• Pharmaceuticals: Certain medications can cause gallstones. These are Ceftriaxone (an antibiotic), thiazide diuretics, and statins. These all interfere with the metabolism of bile or cholesterol. (1)
• Rapid Weight Loss: Rapid weight loss or bariatric surgery is associated with gallstones developing in 30-71% of such individuals (1).
  

How is Gallbladder Disease Diagnosed?

A thorough history and exam is the first step to diagnosing gallbladder disease. During the history (interview), your medical provider will ask you questions about your symptoms and how you feel. Depending on the specific gallbladder issue, your symptoms may vary. A physical exam can be used to diagnose by palpating the abdomen. There is a special exam called "murphy's sign," which is positive when the patient takes a deep breath, and as they are doing that, the medical provider deeply palpates the right upper abdomen. If the patient stops breathing as this is happening, it is considered positive.

Abdominal Ultrasound

This test is used to look for gallstones. This is when ultrasound sound waves show the structures in the abdomen onto a computer screen. Identifying gallstones can aid in understanding gallbladder symptoms.

Endoscopic Ultrasound

‍This procedure can help identify smaller stones missed by standard ultrasound. This is when a small, flexible tube enters your mouth into the digestive tract. Then, a small ultrasound device produces sound waves to get an accurate picture of the surrounding tissue.

Other Imaging Tests

Oral cholecystography, a hepatobiliary iminodiacetic acid scan (HIDA), magnetic resonance cholangiopancreatography (MRCP), or endoscopic retrograde cholangiopancreatography (ERCP) may be used to diagnose gallbladder disease. During an ERCP, the gallstones can be removed. (8)

When ordering and interpreting functional medicine labs, it is essential to order labs that will help determine the root cause of symptoms and analyze with optimal values. Optimal values are a narrow range of lab values, meaning anything outside those values tends to show patterns toward disease progression. Functional medicine providers can then catch these markers early on and have a chance at reversing or stopping disease progression altogether.

Blood tests can be used to check for liver abnormalities, infection, gallbladder function, and pancreatitis related to gallbladder disease.

Commonly Ordered Blood Labs

• ​​Complete blood count: This test looks for high levels of white blood cells, which can indicate infection or inflammation.
• Liver function tests: These blood tests can help detect blockages in the bile ducts.
• Pancreas function tests:These blood tests can help detect a blockage of the pancreatic duct.

Functional Medicine Testing for Gallbladder Disease Prevention & Support

If you are looking for a root cause of gallbladder disease, the following tests may help to understand where the imbalance could be coming from.

Comprehensive Hormone Panel

DUTCH test: Women are twice as likely as men to develop gallstones. Extra estrogen may increase cholesterol and slow gallbladder emptying. The DUTCH test is an extensive hormone panel that looks for metabolites of sex hormones. By understanding these levels, you can understand how the sex hormones may impact bile secretion, impacting gallstone formation.

Comprehensive Stool Test

A comprehensive stool panel can identify dysbiosis (imbalance of good and bad bacteria), fat absorption, pancreatic enzyme production, pathogens, and much more for an accurate picture of your gastrointestinal health. All of these factors may contribute to gallbladder disease.

Cholesterol Balance Test

The Cholesterol Balance Test is a proprietary lipid extraction method that measures markers of cholesterol production and gastrointestinal cholesterol absorption. Our total body cholesterol comes from both what we make in our cells and what we absorb from our gastrointestinal tract.

Lipid Panel

This test can help identify metabolic syndrome, a known cause of gallbladder disease.  

Conventional Treatment for Gallbladder Disease

Pain medications are commonly used when gallbladder pain, or biliary colic, is most severe. If the gallbladder is infected, antibiotics may be used to address the infection. Some individuals may need their gallbladder removed- a cholecystectomy. This is typically performed as a laparoscopic procedure. If there is a tumor or gallstones, endoscopic intervention can be done to remove these blockages, place a stent, or open up the bile ducts. (11)

Functional Medicine Support for Gallbladder Health

The first goal is to find the root cause of the individual's gallbladder issues. Then once you know the cause, you can target that specific issue. Some different targets your medical provider may have are the following:

Nutrition

You can support your gallbladder health by maintaining a healthy diet. The modern western diet is high in fatty processed foods and cholesterol and low in fiber. This type of diet doesn't clear excess fats and cholesterol from the body, allowing them to impact gallbladder health. A lower fat fiber-rich whole foods diet is commonly suggested for gallbladder health. (11)

Exercise

Exercise promotes movement of the digestive system, therefore aiding in the movement of bile out of the gallbladder for digestion. Exercise also helps to maintain a healthy weight and may help manage insulin resistance and obesity (two significant risk factors for gallbladder disease).

Supplements

D-limonene: is a substance found in citrus peels and used as a solvent to support gallbladder health. It has studies dating back to the 1980s. (12)

Artichoke: A significant reduction in weight, cholesterol, liver function tests, blood sugar, and blood pressure occurred using artichoke as a supplement for liver health.

*Note: Artichoke can increase gastric emptying, which may need to be put on hold if there are active gallstones.

Milk thistle: is used for liver and gallbladder support. It has been shown to aid in decreasing the severity of liver and biliary issues, including non-alcoholic fatty liver, hepatitis, insulin resistance, and obesity- all risk factors for gallbladder disease. Milk thistle is an antioxidant, anti-inflammatory, and anti-fibrotic (decreasing injury to cells) agent. (13)

Fat Soluble Vitamins: As gallbladder function is supported, replenishing fat-soluble vitamins (after your medical provider checks the lab values) may be necessary. When the gallbladder is not functioning optimally, fats are not broken down, and vitamins that need fat to be absorbed are not. The fat-soluble vitamins are A, D, E, and K.

Address Hormone Imbalances

As mentioned above, women are twice as likely as men to develop gallstones. This can be due to the link between estrogen and the increase in cholesterol and slower gallbladder emptying. Estrogen replacement and oral contraceptives are risk factors for developing gallstones.

Addressing hormone imbalances may aid in getting your gallbladder health under control. To do this, most practitioners suggest a whole foods diet consisting of fruits, vegetables, locally sourced meat, nuts, and seeds, which gives you the vitamins and minerals needed for good hormone balance.

Post-Gallbladder Removal Nutrition

According to the National Institute of Diabetes and Digestive and Kidney Diseases, foods high in fiber and healthy fats may help support gallbladder health. Saturated fat, refined grains, and sugary sweets are associated with a higher risk of gallbladder issues.

Without your gallbladder, bile flows directly into your intestines and acts as a laxative. This may cause loose stools. Limiting the amount of high-fat foods (less than 3 grams of fat per serving) in your diet post gallbladder removal is suggested.

Some foods that generally make diarrhea worse are caffeine, dairy products, and processed sugary foods.  

Post Gallbladder Removal Supplements

Bile Salts: If the patient has had gallbladder issues and had the organ removed, Functional medicine practitioners may suggest the patient supplement with bile salts to aid digestion. Bile salts help with the digestion of fats. They also help the body absorb fat-soluble vitamins, like vitamins A, D, E, and K.

TUDCA: tauroursodeoxycholic acid is a bile acid found in small quantities in the body. This study showed prompt regression in dyspepsia symptoms after gallbladder removal (cholecystectomy) when supplementing TUDCA.

Can Gallbladder Disease Be Prevented?

Certain risk factors for gallbladder disease cannot be changed, including age, genetics, and being female.

Risk factors that can be managed or addressed include obesity, metabolic syndrome, and diet.

Choosing to eat a whole foods diet low in cholesterol and processed fats may help support gallbladder health and non-alcoholic fatty liver health. Making sure to get the appropriate amount of fiber may help improve the movement of unwanted fats out of the digestive tract. Choosing a diet low in sugar can also aid in prevention as a way to help manage insulin resistance, which may impact gallbladder health. The earlier gallbladder problems are recognized and addressed, the less likely complications of gallbladder issues occur.

Summary

Gallstones, a significant cause of gallbladder issues, affect 10-15% of the population. There are thorough ways to investigate and understand gallbladder issues and support them. Functional lab testing is available to assist in understanding and finding the underlying root cause. There are many functional medicine approaches available to aid in supporting gallbladder health.