Effect of Acute Ketone Monoester Ingestion on Cardiorespiratory Responses to Exercise and the Influence of Blood Acidosis
Abstract
Purpose This study aimed to examine the effect of KE ingestion on exercise cardiac output ( Q˙ ) and the influence of blood acidosis. We hypothesized that KE versus placebo ingestion would increase Q ˙, and coingestion of the pH buffer bicarbonate would mitigate this effect. Methods In a randomized, double-blind, crossover manner, 15 endurance-trained adults (peak oxygen uptake (V̇O 2peak ), 60 ± 9 mL·kg -1 ·min -1 ) ingested either 0.2 g·kg -1 sodium bicarbonate or a salt placebo 60 min before exercise, and 0.6 g·kg -1 KE or a ketone-free placebo 30 min before exercise. Supplementation yielded three experimental conditions: basal ketone bodies and neutral pH (CON), hyperketonemia and blood acidosis (KE), and hyperketonemia and neutral pH (KE + BIC). Exercise involved 30 min of cycling at ventilatory threshold intensity, followed by determinations of V̇O 2peak and peak Q ˙. Results Blood [β-hydroxybutyrate], a ketone body, was higher in KE (3.5 ± 0.1 mM) and KE + BIC (4.4 ± 0.2) versus CON (0.1 ± 0.0, P Conclusions KE ingestion did not increase Q ˙ during submaximal exercise despite a modest elevation of HR. This response occurred independent of blood acidosis and was associated with a lower workload at V̇O 2peak .
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Studies that did not use 0.3 g/kg provided 0.2 g/kg or 0.4 g/kg doses.
“Those that did not provided 0.2 g/kg (Gough et al. 2022; D. G. McCarthy et al. 2023) or 0.4 g/kg (Durkalec‐Michalski et al. 2023) doses.”
From Gastrointestinal Symptoms Associated With Sodium Bicarbonate Supplementation Protocols: A Systematic Review (2026) · cites this paper as D. G. McCarthy et al. 2023
Six of 35 studies stated there were no apparent or significant differences in GIS between conditions.
“Alternatively, six of 35 studies stated there were no apparent or significant differences in GIS between conditions”
From Gastrointestinal Symptoms Associated With Sodium Bicarbonate Supplementation Protocols: A Systematic Review (2026) · cites this paper as D. G. McCarthy et al. 2023
Cites
Nutritional Ketosis Alters Fuel Preference and Thereby Endurance Performance in Athletes
Cox, P. J., Kirk, T., Ashmore, T., Willerton, K., Evans, R., Smith, A., Murray, A. J., Stubbs, B., West, J., McLure, S. W., et al. (2016) · Cell Metabolism · doi:10.1016/j.cmet.2016.07.010 · Cited by 530 · see citing works
Gender differences in leucine kinetics and nitrogen balance in endurance athletes
Phillips, S. M., Atkinson, S. A., Tarnopolsky, M. A., & MacDougall, J. D. (1993) · Journal of Applied Physiology · doi:10.1152/jappl.1993.75.5.2134 · Cited by 281 · see citing works
O’Malley, T., Myette-Cote, E., Durrer, C., & Little, J. P. (2017) · Applied Physiology, Nutrition, and Metabolism · doi:10.1139/apnm-2016-0641 · Cited by 106 · see citing works
No Benefit of Ingestion of a Ketone Monoester Supplement on 10-km Running Performance
EVANS, M., MCSWINEY, F. T., BRADY, A. J., & EGAN, B. (2019) · Medicine & Science in Sports & Exercise · doi:10.1249/mss.0000000000002065 · Cited by 82 · see citing works
Changes induced by exercise in rates of turnover and oxidation of ketone bodies in fasting man
Balasse, E. O., Fery, F., & Neef, M. A. (1978) · Journal of Applied Physiology · doi:10.1152/jappl.1978.44.1.5 · Cited by 68 · see citing works
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Winter, I. P., Sarac, P., & Wilson, P. B. (2026) · European Journal of Sport Science · doi:10.1002/ejsc.70225
- Authors
- MCCARTHY, D. G., BOSTAD, W., BONE, J., POWLEY, F. J., RICHARDS, D. L., & GIBALA, M. J.
- Affiliations
- McMaster University (CA)
- Venue
- Medicine & Science in Sports & Exercise
- Published
- 2023-02-21
- Volume
- 55
- Issue
- 7
- Pages
- 1286-1295
- ISSN
- 0195-9131 (ISSN-L)
- 1530-0315
- OpenAlex
- W4322485665
- Cited by
- 23
- References
- 5
- Citations by year
- 2026: 5 · 2025: 8 · 2024: 5 · 2023: 5
- FWCI
- 4.06
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Medicine & Science in Sports & Exercise (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Physiology › Diet and metabolism studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Muscle metabolism and nutrition
- Health Sciences › Medicine › Complementary and alternative medicine › Cardiovascular and exercise physiology
- Keywords
- ketone monoester, hyperketonemia, bicarbonate buffer, cardiac output, heart rate, peak oxygen uptake, ventilatory threshold, endurance exercise, beta-hydroxybutyrate, exercise performance, ventilatory response to exercise, blood pH
- MeSH terms
- Acidosis, Adult, Double-Blind Method, Eating, Humans, Ketones, Oxygen Consumption, Physical Endurance, Exercise
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