Metabolic Flexibility and Exercise Performance in Adults with Gilbert’s Syndrome–Associated Hyperbilirubinemia

BACKGROUND: Recent evidence suggests that moderately elevated bilirubin plasma concentrations possess protective effects against non-communicable diseases. One possible explanation for this might be that Gilbert's Syndrome (GS), a mildly hyperbilirubinaemic condition, leads to an enhanced lipid metabolism. Furthermore, there are first hints that individuals with GS may have a greater performance capacity. We hypothesize that GS participants have a greater maximal fat oxidation and performance capacity. METHODS: To test this, we conducted an age- and gender-matched human case-control study. We included 40 people with GS and 40 controls, aged 18-65 years, who were all moderately physically active. 50% of the participants were over the age of 35. Participants performed a FatMax test on a bicycle ergometer. The study was performed from March 2023 to December 2023 at the University of Vienna. RESULTS: The group of GS participants over the age of 35 had a significantly higher FatMax (GS: median = 1.03 [maximum = 0.44; minimum = 2.42] W/kg body weight; C: median = 0.48 [minimum = 0.33; maximum = 1.61] W/kg body weight, p = 0.002) and a significantly greater oxygen consumption (GS: mean = 30.2 ± standard diviation (sd) = 8.09 ml/min/ kg body weight; C: mean = 23.4 ± sd = 5.91 ml/min/kg body weight, p = 0.005) at the respiratory compensation point. CONCLUSION: This is the first study to demonstrate that older GS individuals can generate more power whilst harnessing fatty acid metabolism and this may enhance their performance over prolonged periods of sub-maximal exercise.