Effect of Acute Ketone Monoester Ingestion on Cardiorespiratory Responses to Exercise and the Influence of Blood Acidosis

Abstract

Ketone monoester (KE) ingestion can induce hyperketonemia and blood acidosis. We previously found that acute ingestion of 0.6 g·kg−1 body mass KE increased exercise heart rate (HR) compared with placebo.PurposeThis 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.MethodsIn a randomized, double-blind, crossover manner, 15 endurance-trained adults (peak oxygen uptake (V̇O2peak), 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 V̇O2peak and peak Q˙.ResultsBlood [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 < 0.0001). Blood pH was lower in KE versus CON (7.30 ± 0.01 vs 7.34 ± 0.01, P < 0.001) and KE + BIC (7.35 ± 0.01, P < 0.001). Q˙ during submaximal exercise was not different between conditions (CON: 18.2 ± 3.6, KE: 17.7 ± 3.7, KE + BIC: 18.1 ± 3.5 L·min−1; P = 0.4). HR was higher in KE (153 ± 9 bpm) and KE + BIC (154 ± 9) versus CON (150 ± 9, P < 0.02). V̇O2peak (P = 0.2) and peak Q˙ (P = 0.3) were not different between conditions, but peak workload was lower in KE (359 ± 61 W) and KE + BIC (363 ± 63) versus CON (375 ± 64, P < 0.02).ConclusionsKE 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 V̇O2peak.

A Ketone Monoester with Carbohydrate Improves Cognitive Measures Post-Exercise, but not Performance in Trained Females

“…The present study found that in a trained female cohort, the acute ingestion of KME + CHO elicited similar 10-km TT completion times, average power output, and session RPE compared with CHO alone. Additionally, the responses observed between conditions in HR and RPE across the GXT intervals and each respective kilometer did not differ significantly, which are in contrast to more recent findings (24,25). These data were observed during the GXT despite significantly elevated βHB concentrations and lower glucose and lactate concentrations across the KME + CHO condition.…”

“…In fact, the seminal study conducted by Cox et al (5) demonstrated that the ingestion of a carbohydrate beverage with the (R)-1,3-hydroxybutyl R-3-hydroxybutrate KME did indeed lower glycolytic intermediates, although an improvement was still observed in cycling performance (~2%). Since then, studies incorporating various exogenous ketone esters with CHO or alone tend to demonstrate null findings in markers of performance (9,24,26–30) or a decrement to performance (25,31,32). Similarly, the present study demonstrated no benefits to physical performance with KME + CHO ingestion compared with CHO alone in a female cohort.…”

Acute Ketone Monoester Supplementation Impairs 20-min Time-Trial Performance in Trained Cyclists: A Randomized, Crossover Trial

“…The lower HR during the time trial after KE ingestion may relate to effects of KE ingestion on peak HR and/or perceived exertion or reflect the lower time-trial power output. Interpreting these HR data are challenging because ingestion of 0.6 g/kg KE increased HR during submaximal cycling at a constant workload that was equivalent to ventilatory threshold intensity (McCarthy et al, 2021(McCarthy et al, , 2023. It is unknown whether the comparatively lower dose of KE used in the current study would similarly affect exercise HR or whether HR responses to KE ingestion differ depending on relative exercise intensity.…”