Looking to the horizon: the role of bilirubin in the development and prevention of age-related chronic diseases

Abstract

Bilirubin, the principal tetrapyrrole, bile pigment and catabolite of haem, is an emerging biomarker of disease resistance, which may be related to several recently documented biological functions. Initially believed to be toxic in infants, the perception of bilirubin has undergone a transformation: it is now considered to be a molecule that may promote health in adults. Data from the last decade demonstrate that mildly elevated serum bilirubin levels are strongly associated with reduced prevalence of chronic diseases, particularly cardiovascular diseases (CVDs), as well as CVD-related mortality and risk factors. Recent data also link bilirubin to other chronic diseases, including cancer and Type 2 diabetes mellitus, and to all-cause mortality. Therefore, there is evidence to suggest that bilirubin is a biomarker for reduced chronic disease prevalence and a predictor of all-cause mortality, which is of important clinical significance. 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 and neurodegenerative diseases, is provided. The mechanistic background concerning how bilirubin and its metabolism may influence disease prevention and its clinical relevance is also discussed. Given that the search for novel biomarkers of these diseases, as well as for novel therapeutic modalities, is a key research objective for the near future, bilirubin represents a promising candidate, meeting the criteria of a biomarker, and should be considered more carefully in clinical practice as a molecule that might provide insights into disease resistance. Clearly, however, greater molecular insight is warranted to support and strengthen the conclusion that bilirubin can prevent disease, with future research directions also proposed.

Parameters of liver function in patients with psoriasis vulgaris

“…Similar observations were made in obese persons in whom bilirubin concentration was lower than in the group of individuals with normal BMI [22]. Wagner et al [23] observed a beneficial influence of bilirubin on lipid concentrations in the blood. A negative correlation was observed between bilirubin level and LDL dodatnio koreluje ze stężeniem cholesterolu całko-witego i apoB.…”

“…Wagner i wsp. [23] potwierdzili korzystny wpływ bilirubiny na stężenie lipidów we krwi. Wykazano ujemną korelację między stę-żeniem bilirubiny a LDL oraz dodatnią zależność między stężeniem bilirubiny a lipoproteinami o dużej gęstości (high density lipoprotein -HDL).…”

Association of serum bilirubin levels with mortality in patients with diabetes initiating chronic hemodialysis: a competing risks analysis of a single-center cohort

“…Cohort studies examining the association of bilirubin with incidence of and mortality from cancer have resulted in conflicting findings [26][27][28]. In our study, there were only eight cases with cancer-related mortality, limiting meaningful analysis to determine the cause-specific associations.…”

Hyperbilirubinemia in Preterm Neonates

“…51 A negative correlation between TB concentrations and common carotid intima media thickness was reported in children who had undergone kidney transplantation and peritoneal dialysis, suggesting bilirubin may protect from vascular complications. 52 Bilirubin is also regarded as an in important multipoint inhibitor of atherosclerosis 50,53,54 and may protect from vascular damage via its antioxidant properties, thus protecting from free radical-induced damage to lipids and proteins. [55][56][57] Yet another example is of individuals with Gilbert syndrome who have unconjugated hyperbilirubinemia (!1 mg/dL or 17.1 mmol/L) and whose reduced oxidative stress and inflammatory status might prevent glomerular dysfunction and vascular complications.…”