Related Terms

• Autosomal dominant, bilirubin, bilirubin-BUGT, bilirubin-uridine diphosphate glucuronyl transferase, jaundice, liver disorder, nonhemolytic jaundice, unconjugated bilirubin.

Background

• Gilbert's syndrome, also known as constitutional hepatic dysfunction, unconjugated benign bilirubinemia, and familial nonhemolytic jaundice, is an inherited disorder that occurs when the liver is unable to properly process the yellow-green pigments in bile (called bilirubin). The resulting increased levels of bilirubin in the bloodstream may lead to yellowing of the skin and eyes (jaundice), but the liver itself remains normal. In fact, this condition is so mild that doctors do not usually consider it a disease.

• Because jaundice is often a symptom of other, more serious liver conditions, people should visit their doctors if they experience symptoms. It is important to rule out other liver problems before Gilbert's syndrome is diagnosed.

• Researchers estimate that about 3-10% of Americans have Gilbert's syndrome. It is more common among males than females.

• Gilbert's syndrome does not require treatment. Even if a patient experiences periods of jaundice, each symptomatic episode is very mild and will go away in a few days.

Causes

• General: People with Gilbert's syndrome are born with a mutated gene. Normally, this gene provides the body with instructions on how to produce an enzyme called bilirubin-uridine diphosphate glucuronyl transferase (bilirubin-UGT). This enzyme breaks down bilirubin, a waste product from red blood cells in the liver. When a person inherits the mutated gene, the body does not produce enough of bilirubin-UGT, and high amounts of bilirubin build up in the bloodstream instead of being excreted from the body.

• Some experts believe that Gilbert's syndrome is simply a normal variation in the range of bilirubin levels.

• Inheritance: Gilbert's syndrome is passed down among families. The mutated gene that causes Gilbert's syndrome is inherited as an autosomal dominant trait. This means that if one parent has the disorder, there is a 50% chance that his/her child will have Gilbert's syndrome. If both parents have the disorder, there is a 75% chance that the child will inherit the condition.

• Factors that worsen symptoms: Several factors may worsen symptoms of Gilbert's syndrome by slightly increasing the amount of bilirubin in the blood. Examples include illnesses or infections (e.g. the common cold or the flu), fasting or skipping meals, menstruation, dehydration, or overexertion.

Signs and Symptoms

• Gilbert's syndrome rarely causes any symptoms. Even if symptoms are present, the condition is still considered harmless. When bilirubin builds up in the blood, some patients may experience episodes of mild jaundice, which causes the skin and eyes to appear yellow in color. Usually the whites of the eyes start to turn yellow before the skin starts to change color.

• Although some patients experience periods of fatigue and abdominal pain, it is unclear if they are related to Gilbert's syndrome.

Diagnosis

• Gilbert's syndrome is strongly suspected after a blood test. Patients with the condition will have more than 0.3-1.9 milligrams of total bilirubin per deciliter of blood and more than 0-0.3 milligrams of direct bilirubin per deciliter of blood. However, levels of bilirubin normally fluctuate throughout the day. Therefore, if Gilbert's syndrome is strongly suspected based on the person's symptoms, but initial results are normal, repeat testing may be recommended at a different time of day.

• If patients have high levels of bilirubin in their blood, a doctor may recommend additional tests to make sure the patient does not have a more serious liver condition. Once other liver conditions are ruled out, Gilbert's syndrome can be diagnosed.

Complications

• Patients with Gilbert's syndrome have low levels of a liver enzyme called bilirubin-uridine diphosphate glucuronyl transferase (bilirubin-UGT). People with low levels of bilirubin-UGT may experience increased side effects of certain medications, especially an anti-cancer (or antineoplastic) drug called irinotecan (Camptosar®). This is because bilirubin-UGT helps the body process medications. Therefore, patients should talk to their doctors before taking any new medications (prescription or over-the-counter), herbs, or supplements.

Treatment

• General: Gilbert's syndrome generally does not require treatment. Even if a patient experiences periods of jaundice, each symptomatic episode is very mild and will go away in a few days without treatment.

• However, if jaundice worsens or other symptoms develop, patients should visit their doctors. This may indicate an unrelated liver problem.

• Manage stress: Stress may trigger symptoms of Gilbert's syndrome. Managing stress with relaxation techniques may help prevent symptoms from occurring.

• Eat a healthy and regular diet: Fasting or skipping meals may trigger symptoms of Gilbert's syndrome. Therefore, it is recommended that individuals eat well-balanced meals regularly.

• Drink plenty of water: Individuals should drink plenty of fluids, especially water. This helps prevent dehydration, which may trigger symptoms of Gilbert's syndrome.

• Barbiturates: If a patient is distressed by the appearance of jaundice, a doctor may recommend a barbiturate medication, called phenobarbital (Solfoton®). This medication helps reduce the level of bilirubin in the blood.

Integrative Therapies

• Unclear or conflicting scientific evidence:

• Zinc: Zinc formulations have been used since ancient Egyptian times to enhance wound healing. Zinc sulfate supplementation seemed to decrease serum unconjugated bilirubin levels in limited available study. Well-designed clinical trials are needed to better understand the potential role of zinc in Gilbert's syndrome.

• Zinc is generally considered safe when taken at the recommended dosages. Avoid zinc chloride because studies have not evaluated its safety or effectiveness. While zinc appears safe during pregnancy in amounts lower than the established upper intake level, caution should be used because studies cannot rule out the possibility of harm to the fetus.

• Traditional or theoretical uses lacking sufficient evidence:

• SAMe: SAMe (S-adenosyl-L-methionine) is a natural substance that is found inside all cells in the body. Early laboratory evidence suggests that SAMe may reduce bilirubin levels in patients with Gilbert's syndrome. SAMe may improve the transport of bilirubin, which is impaired in people with Gilbert's syndrome. However, until studies are performed in humans, it remains unclear if SAMe supplements are a safe and effective therapy for this condition.

• Avoid if allergic or hypersensitive to SAMe. Avoid with bipolar disorder. Avoid during the first trimester of pregnancy or if breastfeeding. Use cautiously with diabetes, anxiety disorders, or during the third trimester of pregnancy.

Prevention

• There is currently no known method of prevention against Gilbert's syndrome. Individuals are not usually tested to determine if they carry the gene associated with the disease. However, if a person has Gilbert's syndrome or has a family history of the disorder, he/she can speak with a genetic counselor to learn about the chances of passing the disorder onto his/her children.

• Stress may trigger symptoms of Gilbert's syndrome. Managing stress with relaxation techniques may help prevent symptoms from occurring.

• Patients with Gilbert's syndrome are encouraged not to fast or skip meals because it may trigger symptoms.

• Individuals with Gilbert's syndrome should drink plenty of water to prevent dehydration. Dehydration has been shown to trigger symptoms of the disorder.

• Infections, such as the common cold, may trigger symptoms of Gilbert's syndrome. Therefore, preventing infections may help prevent symptoms from developing. To reduce the risk of infections, experts recommend regularly washing the hands with soap and warm water as well as avoiding close contact with individuals who have contagious illnesses.

Author Information

• This information has been edited and peer-reviewed by contributors to the Natural Standard Research Collaboration (www.naturalstandard.com).

Bibliography

Natural Standard developed the above evidence-based information based on a thorough systematic review of the available scientific articles. For comprehensive information about alternative and complementary therapies on the professional level, go to www.naturalstandard.com. Selected references are listed below.

1. American College of Gastroenterology (ACG). www.gi.org.

2. Gentile S, Persico M, Orlando C, et al. Effect of different doses of S-adenosyl-L-methionine (SAMe) on nicotinic acid-induced hyperbilirubinaemia in Gilbert's syndrome. Scand J Clin Lab Invest. 1988 Oct;48(6):525-9. View Abstract

3. Muchova L, Krasloa I, Lenicek M, et al. [Gilbert's syndrome--myths and reality.] [Article in Czech.] Cas Lek Cesk. 2004;143(6):375-80. View Abstract

4. National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). www2.niddk.nih.gov.

5. National Institutes of Health (NIH). www.nih.gov.

6. Natural Standard: The Authority on Integrative Medicine. www.naturalstandard.com.

7. Olsson R, Lindstedt G. Evaluation of tests for Gilbert's syndrome. Acta Med Scand. 1980;207(5):425-8. View Abstract

8. Radlovic N, Lekovic Z, Mladenovic M, et al. [Gilbert's syndrome in children--our experience.] [Article in Serbian.] Srp Arh Celok Lek. 2007 May-Jun;135(5-6):317-20. View Abstract

9. Sieg A, Stiehl A, Raedsch R. Gilbert's syndrome: diagnosis by typical serum bilirubin pattern. Clin Chim Acta. 1986 Jan 15;154(1):41-7. View Abstract