Bilirubin: The yellow hormone?

Bilirubin is a tetrapyrrolic compound originating from heme catabolism. Although originally considered only a potentially dangerous waste product, it has become increasingly evident that this molecule represents an important modulator of various biological functions in the human body. Bilirubin appears to have versatile functions, from cell signaling (behaving almost like a “real” hormonal substance), modulation of metabolism, to immune regulation, affecting biological activities with apparent clinical and even therapeutic consequences. These activities may be the reason for the lower incidence of diseases of civilisation (cardiovascular diseases, arterial hypertension, diabetes, obesity, metabolic syndrome, certain cancers, autoimmune, and neurodegenerative diseases) observed in individuals with a chronic mild unconjugated hyperbilirubinemia, a typical sign of Gilbert’s syndrome. While higher serum concentrations of unconjugated bilirubin may serve as an important protective factor against these diseases, low levels of bilirubin are associated with the opposite effect.