New Aspects of Bilirubin Effects in Health and Disease: a Review

Bilirubin belongs to a phylogenetically old superfamily of tetrapyrrolic compounds. Although for decades bilirubin was believed to be only a waste product of the heme catabolic pathway and a potentially toxic compound; recent data has convincingly demonstrated that mildly elevated serum bilirubin levels are strongly associated with a lower prevalence of oxidative stress-mediated diseases, such as cardiovascular diseases (CVD), diabetes, cancer and all-cause mortality. Therefore, bilirubin is emerging as a ‘health- promoting’ molecule and the role of bilirubin as a biological predictor in the risk assessment of chronic disorders is of great medical and economic importance. In the present review, detailed information on the association between bilirubin and all-cause mortality, as well as the pathological conditions of CVD, cancer, diabetes, neurodegenerative diseases, non-alcoholic fatty liver disease and organ transplantation is provided. All of these pathological conditions represent an important threat to human civilization, being the major killers in developed countries, with a steadily increasing prevalence. Thus, it is extremely important to search for novel markers of these diseases, as well as for finding new therapeutic modalities to reverse this unfavorable situation. Thus, it is suggested to consider bilirubin in clinical trials as a molecule which may be involved in resistance to diseases.