Quercetin as an Exercise Mimetic: Enhancing Mitochondrial Biogenesis and Physical Performance

Mitochondrial function is central to physical endurance, metabolic health, and brain performance. Declines in mitochondrial number and efficiency are closely linked to fatigue, physical inactivity, metabolic disorders, cardiovascular disease, and neurodegenerative conditions. While regular exercise is the most effective stimulus for mitochondrial biogenesis, not all individuals can engage in sufficient physical activity due to illness, aging, or injury. For this reason, there has been strong scientific interest in identifying “exercise mimetics”—compounds that can reproduce key biological effects of exercise without physical training. One such candidate is quercetin, a naturally occurring flavonoid found in onions, apples, berries, and tea.

In a controlled 7-day animal experiment, researchers investigated whether short-term quercetin supplementation could stimulate mitochondrial biogenesis and improve physical performance in the absence of exercise. Mice received daily quercetin doses equivalent to approximately 12.5 or 25 mg/kg body weight in humans. Despite the brief intervention period and the absence of any exercise training, the results revealed profound molecular and functional adaptations typically associated with endurance exercise.

At the molecular level, quercetin supplementation significantly increased markers of mitochondrial biogenesis in both skeletal muscle and brain tissue. Messenger RNA expression of PGC-1α, the master regulator of mitochondrial biogenesis, and SIRT1, a key longevity- and metabolism-associated enzyme, rose by approximately 50–200%. These signaling changes were accompanied by structural adaptations: mitochondrial DNA content nearly doubled at the higher quercetin dose, and cytochrome c protein—an essential component of the mitochondrial electron transport chain—increased by 18–32%. Together, these findings indicate a robust increase in both mitochondrial number and functional capacity.

Importantly, these molecular changes translated directly into measurable improvements in physical performance. Without any exercise training, mice receiving quercetin showed a roughly 37% increase in maximal treadmill running time to exhaustion. In addition, voluntary wheel-running activity increased substantially, with total distance, time spent running, and peak running speed rising by up to 35–40%. Notably, some of these performance benefits persisted even after supplementation ended, suggesting that quercetin induced lasting physiological adaptations rather than short-lived stimulation.

The authors concluded that quercetin functions as a potent, short-term exercise mimetic by activating mitochondrial biogenesis pathways in both muscle and brain. By stimulating PGC-1α– and SIRT1-dependent signaling, quercetin appears to reproduce a core molecular signature of endurance exercise, leading to enhanced oxidative capacity and improved physical performance. Unlike stimulants, which increase performance through acute nervous system activation, quercetin’s effects were rooted in fundamental changes to cellular energy metabolism.

The potential implications of these findings are wide-ranging. In athletic and military settings, quercetin could theoretically enhance endurance and physical readiness when training opportunities are limited. In clinical contexts, boosting mitochondrial function may help counteract diseases associated with physical inactivity and mitochondrial dysfunction, including type 2 diabetes, cardiovascular disease, sarcopenia, and neurodegenerative disorders. The observed effects in brain tissue further suggest possible cognitive or neuroprotective benefits linked to improved neuronal energy metabolism.

Nevertheless, important limitations must be acknowledged. The study was conducted in mice, and the duration was short. While the doses used were adjusted to human-equivalent levels, human physiology may respond differently, and long-term safety and efficacy remain uncertain. Additionally, exercise provides numerous benefits beyond mitochondrial biogenesis—such as mechanical, cardiovascular, and psychosocial effects—that cannot be fully replicated by a supplement.

In conclusion, this experimental study demonstrates that short-term quercetin supplementation can dramatically increase mitochondrial biogenesis and improve physical performance without exercise, supporting its classification as an exercise mimetic (Proceedings of the National Academy of Sciences, year of publication). Although human trials are required to confirm these effects, the findings highlight quercetin as a promising tool for enhancing mitochondrial health and physical capacity in situations where exercise is limited or impossible.