Does serum bilirubin prevent cardiovascular disease?

Bilirubin possesses potent antioxidant, anti-inflammatory, anti-platelet, anti-hypercholesterolemic and anti-adiposity properties. Cross-sectional studies have demonstrated negative associations between serum bilirubin and metabolic syndrome (MetS), diabetes and atherosclerotic cardiovascular diseases (CVDs). However, longitudinal studies show conflicting results. Serum bilirubin levels are determined both genetically and environmentally, and fluctuate throughout one’s life. Longitudinal data suggest that some genetically hyperbilirubinemic individuals may have a lower CVD risk than the general population. However, the reverse may be also true; that is, postnatal metabolic or atherosclerotic diseases may cause oxidative stress and reduce serum bilirubin levels. Therefore, baseline serum bilirubin levels may not always be associated with future metabolic or atherosclerotic diseases. This situation resembles a phenomenon called antioxidant paradox; that is, randomized controlled trials have failed to confirm a role for antioxidant supplementation in CVD prevention, although oxidative stress is involved in the pathogenesis of CVD. Further prospective studies are required to confirm whether serum bilirubin prevents metabolic and atherosclerotic diseases.