Cutting edge concepts: Does bilirubin enhance exercise performance?

Abstract

Exercise performance is dependent on many factors, such as muscular strength and endurance, cardiovascular capacity, liver health, and metabolic flexibility. Recent studies show that plasma levels of bilirubin, which has classically been viewed as a liver dysfunction biomarker, are elevated by exercise training and that elite athletes may have significantly higher levels. Other studies have shown higher plasma bilirubin levels in athletes and active individuals compared to general, sedentary populations. The reason for these adaptions is unclear, but it could be related to bilirubin's antioxidant properties in response to a large number of reactive oxygen species (ROS) that originates from mitochondria during exercise. However, the mechanisms of these are unknown. Current research has re-defined bilirubin as a metabolic hormone that interacts with nuclear receptors to drive gene transcription, which reduces body weight. Bilirubin has been shown to reduce adiposity and improve the cardiovascular system, which might be related to the adaption of bilirubin increasing during exercise. No studies have directly tested if elevating bilirubin levels can influence athletic performance. However, based on the mechanisms proposed in the present review, this seems plausible and an area to consider for future studies. Here, we discuss the importance of bilirubin and exercise and how the combination might improve metabolic health outcomes and possibly athletic performance.

Cardiovascular and metabolic effects of hyperbilirubinemia in a cohort of Italian Olympic athletes

“…9,10 This may reflect an underlying bilirubin's role as a signaling molecule, which stimulates gene transcription, such as peroxisome proliferator-activated receptor alpha (PPARα), related to fatty acid oxidative and mitochondrial capacities, important mediators in muscle function. 6 Moreover, an increase in bilirubin seems to result from strenuous exercise since physical activity deeply increases oxygen consumption in skeletal muscles and stimulates an inflammatory response with high oxidative stress. 11 Higher serum bilirubin concentrations in elite athletes are directly related to serum values of total antioxidants available in the organism.…”

“…Our results show that endurance athletes presented higher serum bilirubin values, which may account for two main pathophysiological mechanisms. 6 The first is a short-term adaptation related to heme catabolism, where muscle strain and repetitive foot strikes during exercise cause myoglobin release, erythrocytes lysis, and consequently, heme release. The second mechanism is an additional long-term adaptation pathway that further increases exercise-induced hyperbilirubinemia and seems more related to an upregulation of the antioxidant mechanisms.…”

“…The second mechanism is an additional long-term adaptation pathway that further increases exercise-induced hyperbilirubinemia and seems more related to an upregulation of the antioxidant mechanisms. 6,11 By both mechanisms, endurance represents the sports category with the strongest trigger for hyperbilirubinemia.…”

“…6 Indeed, a negative relationship and a better prognosis have been reported in patients with previous CV events with mildly increased serum bilirubin levels. [6][7][8][9][10] In the general population, mild hyperbilirubinemia is consistently associated with a reduced incidence of all-cause mortality. 7 Elite athletes present significantly higher concentrations of serum bilirubin, and the prevalence of GS syndrome has been reported to be higher than in the general population, although mechanisms are still poorly known.…”

“…11 Although no study demonstrated an unequivocal fitness improvement in subjects with GS, evidence suggests that higher bilirubin levels may contribute to increased athletic performance by improving muscular, vascular, and cardiac efficiency. 6 Bilirubin also has a role in cardiac remodeling: a previous study demonstrated a lower degree of left ventricular hypertrophy in hypertensive patients with higher serum total bilirubin. 12 Therefore, in the present study, we sought to evaluate the prevalence of GS in Olympic athletes engaged in different sports disciplines, focusing on the effects of hyperbilirubinemia on biological markers and CV remodeling.…”