Bilirubin may mediate the anti-inflammatory effects of aerobic exercise habits: implications for the antiatherosclerotic effects of aerobic exercise

Background Moderately elevated serum bilirubin levels and aerobic exercise effectively reduce the risk of coronary artery disease (CAD). However, the relationships among aerobic exercise, total serum bilirubin (TSB), and inflammation remain unclear. We investigated the associations among aerobic exercise, TSB, and inflammatory response, with TSB as a mediator of this association. Methods This cross-sectional study included 8290 participants registered at the Health Planning Center of Nihon University Hospital in 2019. We defined aerobic exercise as 30 min of sweating at least twice a week for over a year. Results In this cohort (average age, 46.7±13.0 years; 59% men), participants who undertook habitual aerobic exercise (n=2131) had significantly higher TSB levels [0.78 (0.91/0.99) mg/dl vs. 0.74 (0.58/0.95) mg/dl, P<0.0001] than those who did not (n=6159). Multivariable logistic regression analysis demonstrated that aerobic exercise independently predicted higher TSB levels (>50^th percentile set as the dependent variable). Participants with habitual aerobic exercise had significantly lower inflammatory blood cell components, including leukocyte, neutrophil, and platelet counts, than those who did not (all P<0.0001). The levels of these inflammatory markers significantly decreased with increasing TSB levels. Mediation analysis indicated that higher TSB levels partially mediated the association between aerobic exercise and lower counts of inflammatory markers. Conclusion Habitual aerobic exercise was associated with lower levels of inflammatory markers and higher TSB levels, which mediated the anti-inflammatory effects of aerobic exercise. These associations potentially elucidate the preventive effects of aerobic exercise on CAD risk.