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

This is the authors' abstract. We don't add key points for this paper.

Background: 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 to identify underlying physiological mechanisms. Methods: Fourteen healthy, male participants were enrolled in two 29h protocols (simulated altitude of 4,000-4,500m) receiving either KE or a placebo (CON) at regular timepoints throughout the protocol in a randomized, crossover manner. Physiological responses were characterized after 15min and 4h in hypoxia, and the protocol was terminated prematurely upon development of severe AMS (Lake Louise Score ≥ 10). Results: KE ingestion induced a consistent diurnal ketosis ([ßHB] of ~3 mM), whereas blood [ßHB] remained low (<0.6 mM) in CON. Each participant tolerated the protocol equally long or longer (n=6 or n=8, resp.) in KE. Protocol duration increased by 32% on average with KE, and doubled upon KE for severe AMS-developing participants (n=9). Relative to CON, KE induced a mild metabolic acidosis, hyperventilation, and relative sympathetic dominance. KE also inhibited the progressive hypoxemia that was observed between 15min and 4h in hypoxia in CON, while concomitantly increasing cerebral oxygenation and capillary pO 2 within this timeframe despite a KE-induced reduction in cerebral oxygen supply. Conclusions: These data indicate that exogenous ketosis attenuates AMS development. The key underlying mechanisms include improved arterial and cerebral oxygenation, in combination with lowered cerebral blood flow and oxygen delivery, and increased sympathetic dominance.