Gilbert's Syndrome - Symptoms, Triggers, Causes, and Treatment

Originally Medically Reviewed by Dr. Sony Sherpa, (MBBS) - November 16, 2023

Fact Checked and Updated by Dr. Rae Osborn, Ph.D. - July 14, 2026

Introduction

People who experience recurrent episodes of jaundice several times a year may, in some cases, have Gilbert’s syndrome. Find out more about the symptoms and causes of Gilbert’s syndrome below, as well as how to manage high bilirubin levels and when to seek treatment.

What Is Gilbert’s Syndrome?

Gilbert’s syndrome is a common disorder in which the person’s liver does not metabolize bilirubin properly, resulting in slower clearance of bilirubin from the system. Bilirubin is a waste product derived from dead red blood cells and hemoglobin. It contributes to the yellow-brown color of bile and, to a lesser degree, urine as well. The reduced bilirubin metabolism in Gilbert’s syndrome promotes high bilirubin levels in the blood that cause intermittent episodes of jaundice, also known as hyperbilirubinemia.

Prevalence

This condition is thought to affect between 4-16% of the population, with males being more commonly affected than females. This is possibly due to men having a higher baseline ‘bilirubin load’ due to more red blood cell mass and the differences in the effects of sex hormones. Diagnosis is common during adolescence when hormones begin to peak, and during young adulthood. Population-based studies also reveal a lower prevalence of Gilbert syndrome amongst East Asian individuals compared with Middle Eastern individuals. A study of 400 individuals found a higher prevalence of Gilbert syndrome amongst those with type 1 diabetes.

Is Gilbert's syndrome an autoimmune disease?

Gilbert syndrome is not an autoimmune disorder and is not related to excessive immune reactivity, autoimmunity, or inflammation. In fact, Gilbert syndrome may lessen the risk of developing autoimmune diseases due to the antioxidant properties of bilirubin. Patients with other autoimmune diseases, like lupus, may be prone to episodes of hyperbilirubinemia, but this is not the same as Gilbert syndrome.

What is the difference between Gilbert syndrome and Crigler-Najjar?

Crigler-Najjar syndrome is a similar condition to Gilbert’s syndrome, yet it is a lot rarer and more severe. In Crigler-Najjar syndrome, mutations in the UGT1A1 gene stop the enzyme from being produced entirely (type I) or cause a severe deficiency (type II). These result in more severe chronic hyperbilirubinemia as compared to that of Gilbert’s syndrome. Crigler-Najjar syndrome leads to a form of brain damage called kernicterus due to the high deposition of unconjugated bilirubin in the brain. This can be delayed till later in life with prompt treatment. While Gilbert’s syndrome is benign, Crigler-Najjar requires treatment and may even demand liver transplantation.

Gilbert’s Syndrome Symptoms

Generally, the elevated bilirubin levels seen in those with Gilbert syndrome are not enough to cause symptoms other than intermittent episodes of jaundice. Jaundice can cause the skin and whites of the eyes to turn yellow. This is due to the color of bilirubin and is often not a cause for concern in those with Gilbert syndrome.

People with GS occasionally report the following symptoms, particularly during the jaundice episodes:

• Fatigue
• Difficulty concentrating
• Abdominal discomfort
• Nausea or diarrhea
• Appetite loss
• Flu-like symptoms
• Dizziness / light-headedness

People with Gilbert syndrome may experience mild jaundice from time to time that typically resolves within a few days to weeks. The condition is not life-threatening and may even be asymptomatic for up to 33% of patients.

Severe jaundice can indicate the presence of liver disease, infections, or other problems. However, those with Gilbert syndrome are likely to be at a reduced risk of contracting metabolic syndrome or liver disease. If jaundice occurs with intense or unusual symptoms, it is important to go see a doctor to rule out other health conditions.

• Various Medication Sensitivities

Symptoms may become worse when those with the condition are exposed to triggers. This may predispose individuals with Gilbert’s syndrome to being more sensitive toward medications and foods that make use of the liver glucuronidase enzyme pathway in order to be metabolized. Some of these include general anesthetics, irinotecan, atazanavir, acetaminophen, menthol, lamotrigine, and rifamycin SV. These compounds may cause worse jaundice and may heighten toxic side effects in those with Gilbert syndrome, yet these effects are often negligible if present, and patients are not often advised to avoid medication. If toxic side effects develop in response to any medication, contact your healthcare provider immediately.

• Gallstone Risk

Chronic hyperbilirubinemia is a known risk factor for gallstone formation due to the way in which it combines with calcium to form calcium bilirubinate salts. Studies reveal that people with Gilbert syndrome have a higher prevalence of gallstones than people who are not affected.

• Infantile Gilbert Syndrome and Neurotoxicity Risk

In infants, hyperbilirubinemia is considered neurotoxic and, if high enough, potentially fatal. However, most newborns with Gilbert syndrome do not often have bilirubin levels high enough in order for them to be considered problematic, toxic, or fatal.

Triggers of Jaundice

As a result of having elevated bilirubin as a baseline, other factors that serve to increase blood bilirubin levels can cause episodes of mild jaundice in those with Gilbert syndrome.

Known triggers for jaundice in Gilbert syndrome include:

• Fasting or daily caloric intake of 400 kcal or less
• Dehydration
• Physical overexertion
• Stress
• Illness or infection
• Surgery
• Menstruation
• Sleep deprivation or disruption
• Alcohol consumption
• Medications that interfere with glucuronidation

Additionally, genetic comorbidities such as Thalassemia, Spherocytosis, Cystic Fibrosis, and other liver enzyme disorders may predispose those with Gilbert syndrome to severe hyperbilirubinemia.

Possible Benefits of Hyperbilirubinemia

Those with Gilbert syndrome and other conditions of hyperbilirubinemia may be predisposed to a lower risk for various chronic lifestyle diseases, such as cardiovascular disease, type 2 diabetes, autoimmune diseases, neurodegenerative diseases, and some types of cancer. Additionally, Gilbert syndrome is linked to a reduced risk of cardiovascular and all-cause mortality. These benefits are ascribed to the antioxidant, anti-thrombotic, and anticarcinogenic effects of bilirubin. Recent research revealed that those with Gilbert syndrome might also have better-than-average respiratory function, a lower risk for respiratory disease, and better outcomes for those with COVID-19, including protection from its negative metabolic effects.

Causes

Gilbert syndrome is caused by the combination of inherited genetics and factors that trigger jaundice.

• Bilirubin Conjugation and Disposal

Genetic underpinnings of Gilbert syndrome interfere with the metabolism of bilirubin, which is a by-product of red blood cell turnover. Bilirubin may be conjugated and water-soluble or unconjugated and water-insoluble. In the bloodstream, unconjugated bilirubin binds to albumin until it reaches the liver for conjugation prior to disposal. When absorbed by liver cells, bilirubin is conjugated by enzymes of the UGT (uridine diphosphate-glucuronosyltransferase) family prior to disposal. These enzymes form part of a major liver detoxification pathway known as glucuronidation. Conjugated bilirubin leaves the liver through the gallbladder in bile and can easily make its way to the colon without being reabsorbed. At the end of the ileum and in the colon, it gets deconjugated again by gut bacteria and transformed into metabolites that are even less absorbable and easily excreted.

• Genetic Conjugation Defects in Gilbert Syndrome

Most cases of Gilbert’s syndrome are caused by a mutation in the gene coding for the glucuronidation enzyme UGT1A1. The mutation affects the UGT1A1 promoter, referred to as A(TA)7TAA, and the mutated enzyme gene is known as UGT1A1*28. Those who are homozygous for UGT1A1*28 have a 70% reduction in the activity of the UGT1A1 enzyme, resulting in a lower conjugation rate. Studies on rodents found that hyperbilirubinemia reduces intestinal motility and increases gut permeability, resulting in a higher uptake of unconjugated bilirubin and slower bilirubin disposal, which could worsen Gilbert syndrome. Gilbert syndrome has been linked to delayed gastric emptying, and lab studies show unconjugated bilirubin may increase intestinal permeability. Researchers think this could create a cycle that keeps bilirubin levels elevated, though this hasn’t been confirmed in people with Gilbert’s syndrome specifically, and most of the evidence comes from animal or lab-based studies.

• Reduced Liver Cell Uptake of Bilirubin

Studies hint at a second genetic defect that reduces the ability of liver cells to absorb bilirubin. However, while the mechanisms involved in hepatic uptake of unconjugated bilirubin are better understood today, research is still ongoing regarding the precise roles and regulation of the transport pathways involved. The combination of reduced liver uptake and limited conjugation predisposes those with Gilbert syndrome to have higher-than-average blood bilirubin levels.

Diagnosis

A diagnosis of Gilbert syndrome is usually sought out after receiving a blood test for an unrelated complaint that reveals high unconjugated bilirubin levels. Bilirubin levels are often tested to assess overall liver function alongside several other blood markers. A physician will first rule out other causes of hyperbilirubinemia before diagnosing Gilbert syndrome, some of which include liver infections, liver disease, cancer, and other rare disorders of bilirubin metabolism.

Gilbert syndrome may be suspected if the patient’s other liver blood markers are normal, including red blood cell count and liver transaminases. In rare cases, confirmation of a Gilbert syndrome diagnosis may require genetic testing to see if the person has a specific mutation on the UGT1A1 gene (UGT1A1*28) – though this alone cannot confirm the condition, since carrying the mutation doesn’t guarantee that the phenotype (elevated bilirubin) will appear. It is important to have a history of hyperbilirubinemia prior to genetic testing, as not all individuals with UGT1A1*28 develop Gilbert syndrome.

When to Seek Treatment

As the condition is genetic and considered to be benign in most cases, Gilbert syndrome treatment is unnecessary. Episodes of jaundice usually give rise to harmless symptoms and are able to resolve on their own with bed rest and adequate hydration. Up to 33% of those with Gilbert syndrome do not ever have noticeable symptoms.

• Watching for Other Health Concerns

It is advisable to seek treatment if jaundice persists for longer than a few days, coupled with severe or unusual symptoms. This could be a sign of an infection or another health concern that can be treated.

• Communicating About Gilbert Syndrome With a Doctor or Surgeon

Although Gilbert syndrome is considered benign, it may be helpful to inform your healthcare practitioner about the condition before starting certain medications or undergoing surgery, as factors such as fasting, dehydration, and surgical stress may temporarily increase bilirubin levels.

Gilbert Syndrome Diet

There is no specific diet for Gilbert syndrome that is currently recommended by healthcare providers. Those with Gilbert syndrome are advised to consume a healthy, balanced diet, avoid alcohol, and keep well hydrated. Avoiding highly processed foods, foods high in sugar or carbs, and alcohol may help reduce jaundice severity.

Paleo-Keto Diet May Resolve Symptoms for Some

Some online references suggest going on a modified paleo-keto diet due to one case study in which a woman with Gilbert syndrome managed to normalize her bilirubin levels after being on a diet for over a year. Despite the good results, the diagnosis was never confirmed through genetic testing, the study was on a single individual, and there are no studies to confirm its efficacy for other individuals with chronically high bilirubinemia in the range seen in Gilbert syndrome.

Prognosis

Gilbert’s syndrome is not known to cause mortality or long-term health problems and often has an extremely favorable prognosis. While prone to occasional symptoms pertaining to jaundice and an elevated gallstone risk, those with the syndrome can lead long, healthy lives.

Conclusion

Gilbert’s syndrome is a genetic condition that affects the liver’s ability to process bilirubin, resulting in a slower clearance rate, higher-than-average blood bilirubin levels, and episodes of jaundice. Some people with Gilbert syndrome may experience non-specific (pre-diagnostic) symptoms such as fatigue and abdominal pain, though there isn't an established causal link between these symptoms and bilirubin levels. Intermittent jaundice tends to resolve within a few days of onset and may be triggered by various factors such as dehydration, medications, or fasting. Due to the antioxidant effects of bilirubin, Gilbert syndrome may reduce the risk of several chronic lifestyle diseases, yet can increase the risk of gallstone formation. No treatment is prescribed for Gilbert syndrome. However, those with the condition are advised to keep hydrated and consume a healthy diet low in refined, high-carb foods.

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Also Read:

• Alkaptonuria: The Rare Disease That Turns Urine Black
• Williams Syndrome: Causes, Symptoms, Treatment, Latest Research and More
• Wiskott-Aldrich Syndrome: Causes, Symptoms, and Treatments

 

First Published: July 26, 2023

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