metabolized by one of the other enzymes also deficient in some people with GS. A subset of people with GS may have an increased risk of paracetamol toxicity. Cardiovascular effects The mild increase in unconjugated bilirubin due to Gilbert syndrome is closely related to the reduction in the prevalence of chronic diseases, especially cardiovascular disease and type 2 diabetes, related risk factors, and all-cause mortality. Observational studies emphasize that the antioxidant effects of unconjugated bilirubin may bring survival benefits to patients. Several analyses have found a significantly decreased risk of coronary artery disease (CAD) in individuals with GS. Specifically, people with mildly elevated levels of bilirubin (1.1 mg/dl to 2.7 mg/dl) were at lower risk for CAD and at lower risk for future heart disease. These researchers went on to perform a meta-analysis of data available up to 2002, and confirmed the incidence of atherosclerotic disease (hardening of the arteries) in subjects with GS had a close and inverse relationship to the serum bilirubin. This beneficial effect was attributed to bilirubin IXα which is recognized as a potent antioxidant, rather than confounding factors such as high-density lipoprotein levels. This association was also seen in long-term data from the Framingham Heart Study. Moderately elevated levels of bilirubin in people with GS and the (TA)7/(TA)7 genotype were associated with one-third the risk for both coronary heart disease and cardiovascular disease as compared to those with the (TA)6/(TA)6 genotype (i.e. a normal, nonmutated gene locus). Platelet counts and MPV (mean platelet volume) are decreased in patients with Gilbert's syndrome. The elevated levels of bilirubin and decreasing levels of MPV and CRP in Gilbert's syndrome patients may have an effect on the slowing down of the atherosclerotic process. Other Symptoms, whether connected or not to GS, have been reported in a subset of those affected: fatigue (feeling tired all the time), difficulty maintaining concentration, unusual patterns of anxiety, loss of appetite, nausea, abdominal pain, loss of weight, itching (with no rash), and others, such as humor change or depression. But scientific studies found no clear pattern of adverse symptoms related to the elevated levels of unconjugated bilirubin in adults. However, other substances glucuronidized by the affected enzymes in those with Gilbert's syndrome could theoretically, at their toxic levels, cause these symptoms. Consequently, debate exists about whether GS should be classified as a disease. However, Gilbert syndrome has been linked to an increased risk of