Dose response of a novel exogenous ketone supplement on physiological, perceptual and performance parameters

Abstract

Background: Interest into the health, disease, and performance impact of exogenous ketone bodies has rapidly expanded due to their multifaceted physiological and signaling properties but limiting our understanding is the isolated analyses of individual types and dose/dosing protocols.

Methods: Thirteen recreational male distance runners (24.8 ± 9.6 years, 72.5 ± 8.3 kg, VO_2max 60.1 ± 5.4 ml/kg/min) participated in this randomized, double-blind, crossover design study. The first two sessions consisted of a 5-km running time trial familiarization and a VO_2max test. During subsequent trials, subjects were randomly assigned to one (KS1: 22.1 g) or two (KS2: 44.2 g) doses of beta-hydroxybutyrate (βHB) and medium chain triglycerides (MCTs) or flavor matched placebo (PLA). Blood R-βHB, glucose, and lactate concentrations were measured at baseline (0-min), post-supplement (30 and 60 min), post-exercise (+ 0 min, + 15 min). Time, heart rate (HR), rating of perceived exertion (RPE), affect, respiratory exchange ratio, oxygen consumption (VO₂), carbon dioxide production, and ventilation were measured during exercise. Cognitive performance was evaluated prior to and post-exercise.

Results: KS significantly increased R-βHB, with more potent and prolonged elevations in KS2, illustrating an administrative and dosing effect. R-βHB was significantly decreased in KS1 compared to KS2 illustrating a dosing and exercise interaction effect. Blood glucose elevated post-exercise but was unchanged across groups. Blood lactate significantly increased post-exercise but was augmented by KS administration. Gaseous exchange, respiration, HR, affect, RPE, and exercise performance was unaltered with KS administration. However, clear responders and none-responders were indicated. KS2 significantly augmented cognitive function in pre-exercise conditions, while exercise increased cognitive performance for KS1 and PLA to pre-exercise KS2 levels.

Conclusion: Novel βHB + MCT formulation had a dosing effect on R-βHB and cognitive performance, an administrative response on blood lactate, while not influencing gaseous exchange, respiration, HR, affect, RPE, and exercise performance.

Keywords: Beta hydroxybutyrate; Cognition; Ketogenic; Ketone bodies; Medium chain triglycerides; Performance.

Fig. 1

Study design. Subjects consumed beta hydroxybutyrate (βHB)-salts and medium-chain triglycerides (MCTs; KS1 and KS2) or flavor match control (PLA). Capillary metabolites were assessed pre-drink (baseline), 30 min post-drink (30 min), 60 min post-drink (60 min), post-run (+ 0 min), and 15 min post-5 k TT (+ 15 min). Cognitive tests were performed 30 min post-drink (30 min) and 5 min after 5 k TT (+ 5 min). Heart rate (HR), affect, rate of perceived exertion (RPE), and gas exchange were evaluated during the 5 k TT. Beta Hydroxybutyrate, βHB; Medium Chain Triglycerides, MCT; KS1, one dose βHB-salts and MCTs; KS2, two doses βHB-salts and MCTs; Flavor Matched Control, PLA; Heart Rate, HR; Rate of Perceived Exertion (RPE)

Fig. 2

Blood metabolites. Impact of exogenous ketone supplementation on blood a R-β-hydroxybutyrate, b glucose, and c lactate (n = 13). Values are mean ± SE. One Dose Beta Hydroxybutyrate Salt and Medium Chain Triglycerides, KS1; Double Dose Beta Hydroxybutyrate Salt and Medium Chain Triglycerides, KS2; Flavored Matched Control, PLA; All Groups, ALL; *, significantly different from PLA (p < 0.05); **, significantly different from PLA (p < 0.001); ‡, significantly different between KS groups (p < 0.05); a, significantly different from baseline (p < 0.05); aaa, Significantly different from baseline (p < 0.0001); b, significantly different from 30-min (p < 0.05); c, significantly different from 60-min (p < 0.05); ccc, significantly different from 60-min (p < 0.0001); d, significantly different from + 0 min (p < 0.05); ddd, significantly different from + 0-min (p < 0.0001); e, significantly different from + 15-min (p < 0.05); eee, significantly different from + 15-min (p < 0.0001)

Fig. 3

5-km time trial performance. a Individual and average 5-km performance time responses to exogenous ketone supplements and placebo ingestion (n = 13). b Difference in 5 k time trial between ketone supplements and placebo ingestion with smallest worthwhile difference (SWD) range shaded in grey. Values are mean ± SD. One Dose Beta Hydroxybutyrate Salts and Medium Chain Triglycerides, KS1; Two Doses Beta Hydroxybutyrate Salts and Medium Chain Triglycerides, KS2; Flavored Matched Control, PLA

Fig. 4

Reaction time accuracy. Reaction time accuracy was assessed via Stroop incongruent assessment (n = 13). Values are mean ± SD. One Dose Beta Hydroxybutyrate Salt and Medium Chain Triglycerides, KS1; Double Dose Beta Hydroxybutyrate Salt and Medium Chain Triglycerides, KS2; Flavored Matched Control, PLA. ‡, significantly different between KS groups (p < 0.05); a, significantly different from Pre-TT (p < 0.05)