Ketone ester ingestion impairs exercise performance without impacting cognitive function or circulating EPO during acute hypoxic exposure

Abstract

Background: Altitude-induced hypoxemia impairs exercise performance and cognition. Interestingly, ketone ester (KE) ingestion may attenuate hypoxemia, which likely explains the observation that KE impairs high-intensity exercise performance in normoxia but not in hypoxia. Moreover, KE was reported to attenuate cognitive decline at extreme altitudes (~6,100m). Given that hypoxemia is unaffected by KE in milder conditions, the impact of KE on cognition and performance in the absence of elevated oxygenation remains unknown. As KE may increase post-exercise circulating [erythropoietin] ([EPO]) at sea level, we also assessed if KE might augment the blood [EPO] response after hypoxic exercise. Methods: In a double-blind, cross-over design, thirteen healthy, male participants completed two 5.5-h sessions at 4,000m simulated altitude while receiving either KE or placebo (CON). Throughout a graded exercise test (EXMAX) after 1.5h, and a submaximal exercise bout (EXSUBMAX) after 3h, blood and tissue oxygenation, ventilatory parameters, and acid-base balance were evaluated. Other measurements included cognitive function, and blood [EPO]. Results: KE reduced power output achieved during EXMAX by 3.6%, while blood and cerebral oxygenation were similar. KE ingestion lowered blood pH, [HCO3-], pCO2 and [glucose], but did not impact cognitive function. In both KE and CON, circulating [EPO] increased by ~56% after 5h. Conclusions: These results indicate that KE ingestion impairs high-intensity exercise performance, at least if not compensated by elevated oxygenation. A progressively increasing oxygenation upon KE was unable to protect against hypoxia-induced cognitive declines, and potentially counteracted a KE-induced augmentation of circulating [EPO].