Ketone monoester attenuates oxygen desaturation during weighted ruck exercise under acute hypoxic exposure but does not impact cognitive performance

Abstract

Acute ingestion of exogenous ketone supplements in the form of a (R)-3-hydroxybutyl (R)-3-hydroxybutyrate (R-BD R-βHB) ketone monoester (KME) can attenuate declines in oxygen availability during hypoxic exposure and might impact cognitive performance at rest and in response to moderate-intensity exercise. In a single-blind randomized crossover design, 16 males performed assessments of cognitive performance before and during hypoxic exposure with moderate exercise [2 × 20 min weighted ruck (∼22 kg) at 3.2 km/h at 10% incline] in a normobaric altitude chamber (4572 m, 11.8% O₂). The R-BD R-βHB KME (573 mg/kg) or a calorie- and taste-matched placebo (∼50 g maltodextrin) were co-ingested with 40 g of dextrose before exposure to hypoxia. The R-βHB concentrations were rapidly elevated and sustained (>3 mM; P < 0.001) by KME. The decline in oxygen saturation during hypoxic exposure was attenuated in KME conditions by 2.4%-4.2% (P < 0.05) compared with placebo. Outcomes of cognitive performance tasks, in the form of the Defense Automated Neurobehavioral Assessment (DANA) code substitution task, the Stroop color and word task, and a shooting simulation, did not differ between trials before and during hypoxic exposure. These data suggest that the acute exogenous ketosis induced by KME ingestion can attenuate declining blood oxygen saturation during acute hypoxic exposure both at rest and during moderate-intensity exercise, but this did not translate into differences in cognitive performance before or after exercise in the conditions investigated.

Keywords: cognitive performance; exogenous ketones; heart rate variability; oxygen saturation; β‐hydroxybutyrate.

FIGURE 1

Schematic diagram of the experiment to investigate whether acute ingestion of (R)‐3‐hydroxybutyl (R)‐3‐hydroxybutyrate (R‐BD R‐βHB) ketone monoester (KME) impacts cognitive performance and oxygen saturation ($S_{\mathrm{p}{\mathrm{O}}_2}$) at rest and during moderate‐ to vigorous‐intensity exercise in the form of a weighted treadmill ruck during rapid‐onset acute hypoxic exposure. Abbreviations: GI/AMS, Gastrointestinal & Acute Mountain Sickness Questionnaire; HR/HRV, Heart Rate and Heart Rate Variability; KME, Ketone Monoester; PLA, Placebo; R1, Ruck 1; R2, Ruck 2; RPE, Rated Perceived Exertion; SpO2, Oxygen Satuation.

FIGURE 2

Blood R‐βHB (a), glucose (b) and lactate (c) concentrations during ketone monoester (KME) and placebo (PLA) conditions at Baseline, Pre‐chamber, after ruck 1 (R1 Post) and before and after ruck 2 (R2 Pre and R2 Post, respectively). Data are presented as the mean ± SD. Abbreviations: C, condition (KME vs. PLA); PLA, placebo; R‐βHB, (R)‐3‐hydroxybutyrate; T, time; T*C, time × condition interaction. ***P < 0.001 for KME versus PLA.

FIGURE 3

Cognitive performance assessed by Stroop interference score (a), Stroop incongruent correct reaction time (CRT) (b) and DANA code substitution delayed efficiency (c) during ketone monoester (KME) and placebo (PLA) conditions at Baseline, before ruck 1 (R1 Pre), after ruck 1 (R1 Post) and after ruck 2 (R2 Post). (d) The VirTra shoot simulation occurred only at Baseline, R1 Post and Post R2. Data are presented as the mean ± SD. Abbreviations: C, condition (KME vs. PLA); T, time; T*C, time × condition interaction.

FIGURE 4

Average oxygen saturation ($S_{\mathrm{p}{\mathrm{O}}_2}$) (a), and mean differences in $S_{\mathrm{p}{\mathrm{O}}_2}$ between trials (b), during ketone monoester (KME) and placebo (PLA) conditions at Pre‐chamber, and before (Pre) and during (10 and 20 min) ruck 1 (R1) and ruck 2 (R2). Data are presented as the mean ± SD in (a) and as the mean ± 95% confidence limits in (b). Abbreviations: C, condition (KME vs. PLA); T, time; T*C, time × condition interaction. *P < 0.05, **P < 0.01 and ***P < 0.001 for KME versus PLA.

FIGURE 5

Heart rate (HR) (a), room mean square of successive differences (RMSSD) (b) and parasympathetic (PNS) index (c) during ketone monoester (KME) and placebo (PLA) conditions Pre‐chamber and before (Pre) and during (10 and 20 min) ruck 1 (R1) and ruck 2 (R2). (d) Rating of perceived exertion (RPE) was taken at Baseline, Pre‐chamber, after ruck 1 (R1 Post) and before and after ruck 2 (R2 Pre and R2 Post, respectively). Data are presented as the mean ± SD. Abbreviations: C, condition (KME vs. PLA); T, time; T*C, time × condition interaction. *P < 0.05, **P < 0.01 and ***P < 0.001 for KME versus PLA.