BILIRUBIN AS A MARKER OF OXIDATIVE STRESS AND NON-COMMUNICABLE DISEASE: CHICKEN OR THE EGG?
Oxidative stress has been implicated in most non-communicable diseases: that is, metabolic syndrome (MetS), atherosclerosis and cancer. LDL cholesterol is rendered more atherogenic by oxidative modification  and many carcinogens create free oxygen radicals that damage DNA and other cellular structures, initiating and promoting tumor development . Therefore, antioxidant agents have been extensively evaluated in the prevention of cardiovascular disease and cancer.Vitamin E has been shown to reduce atherosclerotic lesions in animals , smooth muscle cell proliferation , platelet adherence and aggregation . Epidemiological data indicate an inverse association between cardiovascular or cancer risk and vitamin E intake from dietary sources and/or supplements . However, most randomized controlled trials have failed to confirm a role for vitamin E supplementation in cardiovascular prevention [7-11]. Vitamin E had no significant effect on myocardial infarction, stroke, cardiovascular death, unstable angina, revascularization, and total mortality.Trials of cancer chemoprevention have also been disappointing [12, 13].
Â Bilirubin has been recognized as a potent antioxidant. Bilirubin suppresses the oxidation of lipid in liposomes more than vitamin E, which is regarded as the best antioxidant of lipid peroxidation [14, 15]. The water-soluble glutathione primarily protects water soluble proteins, whereas the lipophilic bilirubin protects lipids from oxidation . Serum bilirubin has been demonstrated to be a major contributor to the total antioxidant capacity in blood plasma  and proven to haveanti-inflammatory properties . Serum bilirubin was shown to be cross-sectionaly associated with MetS in Chinese children, adolescents and adults [19, 20] as well as Korean men and women [21, 22]. Patients with Gilbert syndrome had low levels of oxidative stress associated with enhancement of endothelium-dependent vasodilation .Serum bilirubin has been demonstrated to be negatively associated with cardiovascular disease [24-26], hemoglobin A1c  and albuminuria . The authorpreviously suggested that serum bilirubin might be a negative predictor of end-stage kidney disease .Others reported that serum bilirubin predicted MetS [30, 31]. However, the author demonstrated that serum bilirubin cannot predict the development of MetS and suggested that a decreased serum bilirubin was not a cause of MetS but a marker of oxidative stress  which is closely related to inflammation  and endothelial dysfunction , both of which are thought to be underlying mechanisms of MetS .So, further prospective studies are required to conclude whether a decrease in serum bilirubin is a risk factor of non-communicable disease such as MetS .
The author received no financial support and has no conflict of interest.Â