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

Stalmans, Myrthe (author), Tominec, Domen (author), Lauriks, Wout (author), Robberechts, Ruben (author), Ramaekers, Monique (author), Debevec, Tadej (author), Poffé, Chiel (author)

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 (~6,100 m). 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 postexercise circulating [erythropoietin] ([EPO]) at sea level, we also assessed if KE might augment the blood [EPO] response after hypoxic exercise. In a double-blind, cross-over design, 13 healthy, male participants completed two 5.5-h sessions at 4,000-m simulated altitude while receiving either KE or placebo (CON). Throughout a graded exercise test (EX $_{MAX}$) after 1.5 h, and a submaximal exercise bout (EX $_{SUBMAX}$) after 3 h, blood and tissue oxygenation, ventilatory parameters, and acid-base balance were evaluated. Other measurements included cognitive function and blood [EPO]. KE reduced power output achieved during EX $_{MAX}$ by 3.6%, whereas blood and cerebral oxygenation were similar. KE ingestion lowered blood pH, [HCO$_3$], pCO $_2$, and [glucose], but did not impact cognitive function. In both KE and CON, circulating [EPO] increased by ~56% after 5 h. 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].

• Language: English
• Keywords: sport, altitude, cognition, erythropoietin (EPO), exercise performance, hypoxia, ketones
• Work type: Article
• Typology: 1.01 - Original Scientific Article
• Organization: FŠ - Faculty of Sport
• Publication status: Published
• Publication version: Version of Record
• Year: 2025
• Number of pages: Str. 1309-1320
• Numbering: Vol. 138, iss. 6
• PID: 20.500.12556/RUL-185594
• UDC: 796.01
• ISSN on article: 1522-1601
• DOI: 10.1152/japplphysiol.00097.2025
• COBISS.SI-ID: 236890371
• Publication date in RUL: 11.08.2026

Record is a part of a journal

• Title: Journal of applied physiology
• Shortened title: J. appl. physiol.
• Publisher: American Physiological Society
• ISSN: 1522-1601
• COBISS.SI-ID: 522932761

Licences

• License: CC BY-NC 4.0, Creative Commons Attribution-NonCommercial 4.0 International
• Link: http://creativecommons.org/licenses/by-nc/4.0/
• Description: A creative commons license that bans commercial use, but the users don’t have to license their derivative works on the same terms.

Secondary language

• Language: Slovenian
• Keywords: šport, nadmorska višina, višinske prilagoditve, kognitivne funkcije, eritropoetin (EPO), hipoksija, hipoksična izpostavljenost, ketoni