Metabolomic impacts of branched-chain amino acid supplementation during endurance exercise: a crossover study

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Abstract
BackgroundSerotonin syntheses in the brain requires a steady supply of tryptophan. Branched chain amino acids (BCAA) and tryptophan are transported across the blood-brain barrier by the amino acid transporter LAT1. BCAA supplementation is predicted to decrease serotonin biosynthesis through LAT1 competition and reduce central fatigue during exercise. Despite a strong theoretical basis for BCAA to attenuate serotonin production and fatigue during exercise, a number of human clinical trials have failed to demonstrate these benefits. To shed light on this discrepancy, we measured the impact of BCAA supplementation on serotonin and associated metabolites during exercise.MethodsA cohort of endurance runners (n=10) participated in a randomized, placebo-controlled, crossover trial to determine impact of BCAA supplementation during a 60-minute run at 65% of VO₂ max. Metabolomic analysis targeted for serotonin and untargeted analysis for biomarkers of BCAA supplementation using LCMS were performed on serum samples collected immediately before and after exercise.ResultsSerum BCAA levels were greater in the supplement group compared to placebo (p<0.05). Serum serotonin was lower immediately after BCAA supplementation and before exercise (p<0.05) but not after exercise. L-ornithine increased during exercise with BCAA treatment compared to placebo. Ratings of perceived exertion were no different in BCAA and placebo groups.ConclusionsBCAA supplementation led to a rapid decrease in serum serotonin concentration relative to placebo, which may be indicative of a central nervous system (CNS) mediated process. After exercise with BCAA supplementation, endurance athletes did not show lower serum serotonin concentration, but did present an almost three-fold increase in L-ornithine which has metabolic connections to cortisol and central fatigue.Trial Registration: ClinicalTrials.gov NCT04969536, retrospectively registered 20 July 2021, https://clinicaltrials.gov/ct2/show/NCT04969536