Dr. Bikman’s lecture this week explores the metabolic roles of bilirubin, a molecule typically associated with liver disease and jaundice but now emerging as a key player in metabolism, oxidative stress, and fat regulation.

Bilirubin is produced from the breakdown of red blood cells and is transported to the liver, where it undergoes conjugation to become water-soluble and is then excreted into bile.

While historically viewed as a waste product, recent research suggests that bilirubin plays a significant role in protecting against oxidative stress and inflammation, and may even contribute to metabolic flexibility and fat metabolism.

One of bilirubin’s most fascinating properties is its potent antioxidant effect. It neutralizes reactive oxygen species (ROS), helping to reduce oxidative stress—a key driver of chronic diseases, including insulin resistance, cardiovascular disease, and neurodegeneration. Bilirubin also acts as an anti-inflammatory agent, inhibiting key inflammatory pathways such as NF-kappa B, which is involved in obesity-related inflammation. Interestingly, individuals with Gilbert Syndrome, a genetic condition that causes mildly elevated bilirubin levels, have been shown to have a significantly lower risk of cardiovascular disease.

Beyond its antioxidant and anti-inflammatory roles, bilirubin also influences fat metabolism. Studies suggest that bilirubin enhances mitochondrial function and thermogenesis, particularly in brown and beige fat, by increasing UCP-1 (uncoupling protein 1) expression, which helps the body burn fat more efficiently.

Ben concludes by discussing ways to naturally increase bilirubin levels. Since bilirubin is excreted in bile, diets higher in fat may enhance enterohepatic recycling, allowing more bilirubin to re-enter circulation and exert its beneficial effects. While excessive bilirubin can be toxic, modestly elevated levels, as seen in Gilbert Syndrome, appear to provide metabolic advantages.

This growing body of research challenges the outdated view of bilirubin as a mere waste product and suggests that it may be a crucial player in metabolic health.

Show Notes/References:

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How Bilirubin Affects Fat Burning, Inflammation & Metabolic Health

The Metabolic Classroom with Dr. Ben Bikman