The effects of 2 days of intermittent exogenous ketosis at high altitude on baroreflex sensitivity and ventilation under hypoxic and hypercapnic conditions

Narang, Benjamin J. (author), Tominec, Domen (author), Stalmans, Myrthe (author), Millet, Grégoire P. (author), Poffé, Chiel (author), Debevec, Tadej (author)

High-altitude (HA) exposure induces an integrated physiological response to mitigate hypoxemia. Exogenous ketosis at simulated HA was previously shown to accentuate sympathetic activation and attenuate pulse oxygen saturation (Sp$_{O2}$) decreases through hyperventilation. The aim of this study was to extend these findings by investigating the effects of intermittent exogenous ketosis (IEK) across 2 days at terrestrial HA (3,375 m) on baroreflex sensitivity, heart rate variability, and hypoxic/hypercapnic ventilatory responses. Thirty-four healthy active adults completed neutral, hypoxic, and hypercapnic (0.03 FI$_{CO2}$) exposures, each comprising 6 min of seated rest, once at sea level (SL) and once after 2 days at HA. Across the 2 days, participants intermittently ingested either ketone monoester supplements (IEK) or placebo (PLA). During each exposure, blood pressure, ventilation, Sp$_{O2}$, and end-tidal CO$_2$ pressure (PET$_{CO2}$) were continuously recorded, and arterialized capillary blood gas content was measured in the final 30 s. Baroreflex sensitivity and time-domain metrics of heart rate variability were reduced at HA (P = 0.006–0.043) but unaffected by group (P = 0.288–0.525). However, ventilation at HA under all three conditions was significantly higher in IEK compared with PLA (all P < 0.001). In hypoxia, this induced a higher Sp$_{O2}$ (P = 0.038) and capillary O$_2$ pressure (P = 0.003). In hypercapnia, this induced a lower PET$_{CO2}$ and capillary CO$_2$ tension (both P < 0.001). These results extend previous findings, suggesting that IEK enhances ventilation at terrestrial HA after 2 days of exposure, with this effect being independent from baroreflex sensitivity or heart rate variability changes.

• Language: English
• Keywords: automatic control, blood pressure, hypobaric hypoxia, ketone bodies, sympathetic nervous system, high altitude
• 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. R350-R362
• Numbering: Vol. 329, iss. 2
• PID: 20.500.12556/RUL-183685
• UDC: 612
• ISSN on article: 1522-1490
• DOI: 10.1152/ajpregu.00125.2025
• COBISS.SI-ID: 243716867
• Publication date in RUL: 17.06.2026

Record is a part of a journal

• Title: American journal of physiology : Regulatory, integrative and comparative physiology
• Shortened title: Am. j. physiol. Regul., integr. comp. physiol.
• Publisher: American Physiological Society
• ISSN: 1522-1490
• COBISS.SI-ID: 3394580

Licences

• License: CC BY 4.0, Creative Commons Attribution 4.0 International
• Link: http://creativecommons.org/licenses/by/4.0/
• Description: This is the standard Creative Commons license that gives others maximum freedom to do what they want with the work as long as they credit the author.

Secondary language

• Language: Slovenian
• Keywords: anoksija, krvni tlak, avtomatski nadzor, ketoza, ketonska telesa, hipobarična hipoksija, simpatično živčevje, visoka nadmorska višina