Exogenous ketosis attenuates acute mountain sickness and mitigates normobaric high-altitude hypoxemia

Acute mountain sickness (AMS) represents a considerable issue for individuals sojourning to high altitudes with systemic hypoxemia known to be intimately involved in its development. Based on recent evidence that ketone ester (KE) intake attenuates hypoxemia, we investigated whether exogenous ketosis might mitigate AMS development and identified underlying physiological mechanisms. Fourteen healthy, male participants were enrolled in two 29-h protocols (simulated altitude of 4,000-4,500 m) receiving either KE or a placebo (CON) at regular timepoints throughout the protocol in a randomized, crossover manner. Physiological responses were characterized after 15 min and 4 h in hypoxia, and the protocol was terminated prematurely upon development of severe AMS (Lake Louise Score ≥ 10). KE ingestion induced a consistent diurnal ketosis (d-β-hydroxybutyrate, [βHB] of ∼3 mM), whereas blood [βHB] remained low (