Post‐exercise ketone supplementation improves endurance performance and mitochondrial adaptations during an 8‐week endurance training intervention

Post-exercise ketone supplementation (PEKS) previously improved endurance performance and muscular adaptations during overload training. However, whether and how PEKS improves endurance performance during a periodised endurance training period remains unclear. Twenty-eight trained males completed 8 weeks of supervised cycling, receiving either 25 g of the ketone monoester (R)-hydroxybutyl (R)-hydroxybutyrate (KE, n = 14) or isocaloric placebo (CON, n = 14) post-exercise and before sleep. Outcomes included exercise performance and muscular/cardiac adaptations assessed at baseline (PRE), week 3 (MID) and 7 (POST), and following a taper week (POST_+1week). The training intervention improved 30 min time trial performance (TT_30min), absolute and relative <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"> <mml:semantics> <mml:msub><mml:mover><mml:mi>V</mml:mi> <mml:mo>̇</mml:mo></mml:mover> <mml:mrow><mml:msub><mml:mi>O</mml:mi> <mml:mn>2</mml:mn></mml:msub> <mml:mi>peak</mml:mi></mml:mrow> </mml:msub> <mml:annotation>${\dot V_{{{\mathrm{O}}_{\mathrm{2}}}{\mathrm{peak}}}}$</mml:annotation></mml:semantics> </mml:math> , peak power output during the <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"> <mml:semantics> <mml:msub><mml:mover><mml:mi>V</mml:mi> <mml:mo>̇</mml:mo></mml:mover> <mml:mrow><mml:msub><mml:mi>O</mml:mi> <mml:mn>2</mml:mn></mml:msub> <mml:mi>peak</mml:mi></mml:mrow> </mml:msub> <mml:annotation>${\dot V_{{{\mathrm{O}}_{\mathrm{2}}}{\mathrm{peak}}}}$</mml:annotation></mml:semantics> </mml:math> test (PPO <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"> <mml:semantics> <mml:msub><mml:mover><mml:mi>V</mml:mi> <mml:mo>̇</mml:mo></mml:mover> <mml:mrow><mml:msub><mml:mi>O</mml:mi> <mml:mn>2</mml:mn></mml:msub> <mml:mi>peak</mml:mi></mml:mrow> </mml:msub> <mml:annotation>${\dot V_{{{\mathrm{O}}_{\mathrm{2}}}{\mathrm{peak}}}}$</mml:annotation></mml:semantics> </mml:math> ), citrate synthase (CS) activity, and peak cardiac output (all P < 0.05 PRE vs. POST). Notably, TT_30min (CON: 291 ± 27 W vs. KE: 302 ± 28 W, P < 0.001, Hedges' g = 0.40) was 4% higher in KE compared to CON at POST. Although peak cardiac output was similar, relative <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"> <mml:semantics> <mml:msub><mml:mover><mml:mi>V</mml:mi> <mml:mo>̇</mml:mo></mml:mover> <mml:mrow><mml:msub><mml:mi>O</mml:mi> <mml:mn>2</mml:mn></mml:msub> <mml:mi>peak</mml:mi></mml:mrow> </mml:msub> <mml:annotation>${\dot V_{{{\mathrm{O}}_{\mathrm{2}}}{\mathrm{peak}}}}$</mml:annotation></mml:semantics> </mml:math> increased more in KE (+12%) than CON (+6%, ΔP < 0.001), suggesting enhanced peripheral oxygen utilisation. Accordingly, CS activity was at POST 14% higher in KE (9.37 ± 1.36 mol h^-1 kg protein^-1) compared to CON (8.21 ± 0.97 mol h^-1 kg protein^-1, P = 0.035, Hedges' g = 0.98) and OXPHOS complex II muscle protein content remained unaltered in CON while increasing by 25% in KE (P = 0.030 vs. PRE). In conclusion, these findings establish PEKS as a nutritional strategy to enhance endurance performance and mitochondrial adaptations during periodised endurance training. KEY POINTS: Previous research showed that post-exercise ketone ester (KE) supplementation improves endurance performance and muscle adaptations during 3 weeks of excessive endurance exercise. Whether KE ingestion enhances performance, muscular and cardiac adaptations during a periodised endurance training intervention remained unknown. We demonstrate that KE supplementation post-exercise and before sleep during an 8 week periodised endurance training period enhances endurance performance and peak oxygen uptake rate in trained male participants. These performance improvements were mediated by muscular adaptations (e.g. increased mitochondrial content), while cardiac adaptations were not affected by KE. Our findings show that KE enhances endurance performance primarily by muscular adaptations, indicating that post-exercise KE supplementation is effective to amplify endurance exercise training adaptations.