Effects of olive leaf extract on exercise performance and muscle mitochondrial response in young healthy adults

Introduction Sprint interval training (SIT) can elicit similar or even higher skeletal muscle mitochondrial adaptations than moderate-intensity continuous training (MICT) despite a lower training volume. We have previously shown that this is at least partially driven by improved skeletal muscle mitochondrial bioenergetics with increased mitochondrial Ca2+ uptake and pyruvate dehydrogenase (PDH) activation after a single session of SIT but not MICT [1]. Olive leaf extract (OLE) is a natural compound that triggers mitochondrial Ca2+ uptake and activates PDH in mouse skeletal muscle [2]. Here we tested the hypothesis that OLE would contribute to exercise performance improvement by increasing muscle mitochondrial response and PDH activation in human participants performing MICT. Methods In a crossover (OLE vs. placebo), double-blind study, eleven healthy males performed a single session of MICT (1h at 50% maximal aerobic power). Knee extensor neuromuscular tests and vastus lateralis muscle biopsies were performed before (Pre), immediately after (Post), and 24 hours after (24h Post) MICT. Results Compared to placebo, OLE reduced average heart rate in MICT while the extent and origin of knee extensor fatigability was unchanged. Targeted investigation of selected proteins involved in the oxidative phosphorylation pathway showed an overall decrease of expression immediately after exercise but did not reveal any differences between placebo and OLE. The Pre to Post change in PDH activity was different with a decrease in placebo versus an increase in OLE. Transcriptomic analyses showed a potentiation of the exercise effect on mitochondrial genes by OLE 24h after exercise. In addition, OLE potentiated several pathways involved in inflammation and immune response immediately after exercise. Discussion/Conclusion Altogether, these results suggest that OLE can modulate skeletal muscle response to exercise and pave the way for future investigations aiming to investigate the chronic effect of combining OLE and exercise training. References Zanou, N., Dridi, H., Reiken, S., Imamura de Lima, T., Donnelly, C., De Marchi, U., et al. (2021). Acute RyR1 Ca²⁺ leak enhances NADH-linked mitochondrial respiratory capacity. Nature Communications, 12(1), 7219. https://doi.org/10.1038/s41467-021-27422-1 Gherardi, C., Rossi, L., Bianchi, M., & Ferri, P. (2024). Mitochondrial calcium uptake declines during aging and is directly activated by oleuropein to boost energy metabolism and skeletal muscle performance. Cell Metabolism. https://doi.org/10.1016/j.cmet.2024.10.021