Journal Article Randomized Controlled Trial Ppublish 1 citation
PubMed: 42779476 DOI: 10.1152/ajpregu.00073.2026
Ketone monoester intake affects the ventilatory response to O 2 and CO 2 in healthy individuals at high altitude.
Am J Physiol Regul Integr Comp Physiol 331(5):R671-R681
Authors: Myrthe Stalmans, Domen Tominec, Benjamin J Narang, Giorgio Manferdelli, Grégoire P Millet, Tadej Debevec, Chiel Poffé
Affiliations
- Exercise Physiology Research Group, Department of Movement Sciences, KU Leuven, Leuven, Belgium. Department of Cellular and Physiological Sciences, Faculty of Medicine, University of British Columbia, Vancouver, British Columbia, Canada.
- Faculty of Sport, University of Ljubljana, Ljubljana, Slovenia.
- Faculty of Sport, University of Ljubljana, Ljubljana, Slovenia. Department for Automatics, Biocybernetics and Robotics, Jožef Stefan Institute, Ljubljana, Slovenia.
- Institute of Exercise and Environmental Medicine, Texas Health Presbyterian Hospital Dallas, Dallas, Texas, United States. Department of Internal Medicine, The University of Texas Southwestern Medical Center, Dallas, Texas, United States.
- Institute for Sport Sciences, University of Lausanne, Lausanne, Switzerland.
- Exercise Physiology Research Group, Department of Movement Sciences, KU Leuven, Leuven, Belgium. REVAL-Rehabilitation Research Center, Faculty of Rehabilitation Sciences, Hasselt University, Diepenbeek, Belgium.
Abstract
Both cerebral blood flow (CBF) and ventilation ([Formula: see text]) respond to systemic O 2 and CO 2 levels. Ketone ester (KE) ingestion elicits hyperventilation, thereby increasing blood oxygenation in hypoxia while reducing blood buffering capacity and inducing hypocapnia-mediated CBF reductions. We aimed to characterize the impact of KE on [Formula: see text] and CBF at terrestrial altitude, as well as their reactivity to O 2 and CO 2 [[Formula: see text]R and cerebrovascular reactivity (CVR), respectively]. Thirty-four participants performed a double-blind, placebo-controlled study consisting of a normoxic and a hypobaric hypoxic session. The latter was performed after 20 h at terrestrial altitude (3,375 m). Although no supplements were provided at sea level, the altitude session involved regular ingestion of KE or placebo drinks. Middle cerebral artery velocity (MCAv) was measured using transcranial Doppler ultrasonography. Using a steady-state protocol, [Formula: see text]R and CVR were calculated as respectively Δ[Formula: see text] or ΔMCAv per Δ[end-tidal CO 2 pressure ([Formula: see text])] while breathing ambient air (i.e., baseline stage), 3% or 6% hyperoxic CO 2, or during hyperventilation-induced hypocapnia. Blood acid-base balance was evaluated from an arterialized capillary blood sample. KE intake increased blood [β-hydroxybutyrate] and reduced blood pH, arterial CO 2 partial pressure, and bicarbonate concentrations. KE induced hyperventilation and reduced [Formula: see text]R, mostly originating from the baseline-to-3%-CO 2 transition. KE did not affect MCAv or CVR. The effect of KE on [Formula: see text]R presumably resulted from hyperventilation while breathing ambient air, rather than reflecting altered [Formula: see text]R to O 2 and CO 2, but the underlying mechanisms remain uncertain. Despite acid-base dysregulations with KE intake, cerebrovascular outcomes remained unaltered.NEW & NOTEWORTHY Ketone ester (KE) intake attenuates the ventilatory response to O 2 and CO 2 after 20 h at 3,375 m, and this most likely results from hyperventilation induced by KE intake, rather than reflecting altered ventilatory reactivity to O 2 and/or CO 2 per se. Conversely, despite accentuated acid-base disruptions, ketosis did not affect cerebrovascular parameters.
MeSH
Blood, Hypocapnia, Respiration, Hyperventilation, Ketones, Air, Altitude, Hypoxia, Ventilation