The Role of Bilirubin in Obesity Prevention

• January 31, 2024

The British Medical Journal and British Cardiovascular Society’s Open Heart journal recently published an article underscoring the multifaceted benefits of bilirubin in obesity prevention and metabolic health. Elevated unconjugated bilirubin levels, particularly observed in Gilbert syndrome (GS), demonstrate significant health protection, with a relative risk for all-cause mortality as low as 0.5. This protection is attributed to bilirubin’s unique role as a ‘source antioxidant,’ suppressing superoxide generation at its origin and distinguishing itself from traditional ‘scavenging antioxidants.’ 

Clinical strategies, including ‘iatrogenic Gilbert syndrome,’ are discussed to boost bilirubin levels for health benefits. The study explores GS’s link to lower fat gain during aging, potentially associated with bilirubin’s role in preserving hypothalamic leptin sensitivity. Moreover, bilirubin exhibits direct protective effects on adipocytes, enhancing insulin sensitivity and reducing metabolic syndrome risks. The protective influence of bilirubin extends to liver function, reducing liver fat content and inflammation in metabolic syndrome, as well as preserving vascular endothelial function to potentially lower cardiovascular event risks. 

Prospective epidemiological studies underscore the links between higher plasma bilirubin and reduced risks of various cardiovascular conditions. In the context of diabetes, bilirubin emerges as a preventive factor, inhibiting beta-cell dysfunction induced by glucolipotoxicity and correlating inversely with the risk of diabetic complications. The article emphasizes the profound implications of safely moderating NADPH oxidase activity through bilirubin for preserving metabolic and vascular health, providing physicians with valuable insights into potential patient interventions.

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