Exogenous ketosis mitigates hypoxia-induced neural signaling alterations and cerebral oxygenation decline at rest in healthy males

Abstract

Intensive exercise and high-altitude exposure can disrupt neural activity and impair cognitive functioning. Previous research suggests that ketone ester (KE) ingestion may counteract cognitive impairments, however, its impact on neural activity during exercise and hypoxia remains unclear. Therefore, we investigated the impact of KE on electroencephalography (EEG) patterns and cognition during hypoxia and exercise. Twelve healthy males completed three randomized crossover sessions: i) normoxia + placebo, ii) hypoxia + placebo, and iii) hypoxia + KE. Each session included normoxic endurance (ET120’) and high-intensity interval training (HIIT80’), followed by a 16-h period including sleep in either normoxia or hypoxia. The next day, participants performed a normoxic 30-min all-out time-trial (TT30’). EEG was recorded during rest and exercise, while cerebral tissue oxygenation index (cTOI) and cognitive performance were evaluated during rest. At rest, KE attenuated hypoxia-induced increases in alpha and beta power and cTOI declines. Nonetheless, cognitive performance remained unaffected. Brain activity rose throughout ET120’ and normalized during recovery, while HIIT80’ elicited a fluctuating neural response but normalized during recovery. Following TT30’, theta, alpha, and gamma power remained elevated during recovery. Altogether, these data, obtained in healthy males, show the potential of KE to stabilize resting-state EEG patterns in hypoxia. Moreover, they shed light on how EEG patterns vary with exercise intensity, with sustained post-exercise increases in theta, alpha, and gamma power following high-intensity efforts. These findings suggest that KE can help to preserve neural stability under hypoxia and highlight EEG’s potential for monitoring fatigue and tailoring training or recovery strategies.