ECSS Paris 2023: CP-PN25
INTRODUCTION: Ingestion of exogenous ketones monoester (Kme) provides a rapid increase in circulating [β-hydroxybutyrate] (β-HB) [1]. Kme induced elevations in [β-HB] are associated with increased endothelial nitric oxide bioavailability and vascular function in healthy individuals [2]. However, the dose–response effects of Kme intake and endothelial function has yet to be established. We assessed the dose-response effects of Kme doses on circulating [β-HB] and endothelial function, serially across 24h. METHODS: Thirteen healthy adults (age 21 ± 2 y; BMI 25.6 ± 3.4 kg·m2) completed a double-blind, randomised, placebo-controlled, crossover trial, with a 7-day washout. Participants attended the laboratory on four separate occasions and ingested a Kme supplement ((R)-3-hydroxybutyl (R)-3-hydroxybutyrate, Delta®, Oxford, UK) of 0.1 g/kg, 0.4 g/kg, 0.8 g/kg or a placebo drink in a randomised order. Subsequently, participants underwent measurements of circulating venous [β -Hb] and flow mediated dilatation (FMD) via ultrasound at 30 min, 1h, 2h, 3h, 6h, 12h and 24h after ingestion. RESULTS: Following 0.4 g/kg Kme ingestion, [β-HB] increased compared to placebo, remaining elevated for 3h, with the peak at 1h post-ingestion (mean difference: 2.1 mM; 95%CI 1.7 to 2.5; P=0.001). In comparison 0.8 g/kg Kme ingestion, produced a prolonged [β-HB] response remaining elevated for 6h and peaking at 2h post-ingestion compared to placebo (mean difference: 4.1 mM; 95%CI 3.6 to 4.5; P=0.001) compared to placebo. In addition, [β-HB] was higher until the 6h timepoint after 0.8 g/kg Kme ingestion compared to 0.4 g/kg condition, with the peak mean difference at 3h (3.0 mM; 95%CI, 2.6 to 3.5, P=0.001). No changes were observed following 0.1 g/kg Kme ingestion compared to placebo (P=0.124). Increases in FMD were observed following 0.8 g/kg Kme ingestion at 1h (mean difference 2.16%; 95%CI 1.7 to 2.3; P=0.001) and 2h post-ingestion (mean difference: 2.82%; 95%CI 2.1 to 3.1; P=0.001) compared to placebo. No effect on FMD was observed at any time point after 0.1 g/kg (P=0.354) and 0.4 g/kg (P=0.112) Kme ingestion. CONCLUSION: Conclusion In healthy young adults, ingestion of 0.4 and 0.8 g/kg of Kme demonstrated a dose-dependent increase in circulating [β-HB] compared to placebo. Ingestion of 0.8 g/kg of Kme was associated with significant acute increases in FMD compared to placebo, indicating a potential vascular health benefit at higher doses. Further research is warranted to determine whether the optimal dosage of Kme, administered at its peak time point (2h post ingestion), can elicit improved cardiovascular and cardiorespiratory response during exercise. 1. Cox, P.J., et al., Nutritional Ketosis Alters Fuel Preference and Thereby Endurance Performance in Athletes. Cell Metab, 2016. 24(2): p. 256-68. 2. Walsh, J.J., H. Neudorf, and J.P. Little, 14-Day Ketone Supplementation Lowers Glucose and Improves Vascular Function in Obesity: A Randomized Crossover Trial. J Clin Endocrinol Metab, 2021. 106(4): p. e1738-e175
Read CV Maria PerissiouECSS Paris 2023: CP-PN25
INTRODUCTION: Exogenous ketone ester (KE) ingestion elevates circulating beta hydroxybutyrate (BHB) and alters substrate availability during exercise, yet performance effects remain equivocal and may depend on habitual diet. This study tested whether acute R-3-hydroxybutyl R-3-hydroxybutyrate affects aerobic capacity, submaximal physiological responses, and repeated sprint performance in recreationally active adults habitually consuming either a ketogenic diet (KD) or a high carbohydrate diet (HC). METHODS: Recreationally active adults (n=19) completed a randomised, single blind, placebo controlled, crossover design. Participants ingested KE (330 mg/kg) or placebo (PLA) prior to a cycling maximal oxygen uptake test (VO2max). Capillary blood glucose, lactate, and BHB were sampled pre exercise, at 5 min intervals during the VO2max test, and immediately post exercise. On a separate visit, supplementation was repeated before 60 min cycling at 55% of WMax followed immediately by 5 x 10 s Wingate sprints. During the 60 min bout, blood variables were sampled at 0, 20, 40, and 60 min. During the Wingate protocol, blood measures were obtained after each sprint. Two-way mixed ANOVA tested Condition (KE vs PLA), Diet (KD vs HC), and Condition x Diet. Significance was set at p<0.05. RESULTS: No significant main or interaction effects were observed for VO2max. During 60 min cycling, KE increased BHB at 0 min (p=0.015), 20 min (p<0.001), 40 min (p<0.001), and 60 min (p<0.001). A Condition x Diet interaction was observed for BHB at 20 min only (p<0.001). Blood glucose was reduced at 40 min (p=0.002) and blood lactate was reduced at 40 min (p=0.003) and 60 min (p=0.003). Mean respiratory exchange ratio (RER) decreased (p=0.016) and mean VO2 increased (p=0.042) during the 60 min bout. In the Wingate test, peak cadence demonstrated a Condition x Diet interaction (p=0.007), while no significant interactions were observed for peak power, mean power, power per kg, speed, or distance. CONCLUSION: Acute KE ingestion produced significant metabolic alterations during submaximal exercise, with diet specific effects confined to early BHB kinetics and peak cadence. These changes did not translate into improvements in VO2max or repeated sprint power, suggesting diet dependent metabolic effects without clear performance enhancement.
Read CV Richard PhillipsECSS Paris 2023: CP-PN25
INTRODUCTION: Mitochondria are responsible for energy production in cells. Altering the quantity and function of mitochondria in skeletal muscles contributes to improved exercise capacity and metabolic health. In recent years, ketone bodies have gained attention as signaling molecules potentially involved in metabolic adaptations. One study reported that chronic administration of ketone bodies increased the protein levels of certain mitochondrial components in the skeletal muscle (Monsalves-Alvarez et al. 2020). Conversely, it has also been reported that post-exercise ketone body intake reduces the active form of AMP-activated protein kinase (AMPK), which is known to promote mitochondrial biogenesis, in skeletal muscles (Vandoorne et al. 2017; Takahashi et al. 2025). As the combined effect of ketone body intake and training on skeletal muscle mitochondrial adaptation remains unproven, we investigated the effects of ketone monoester ((R)-3-hydroxybutyl (R)-3-hydroxybutyrate, KE) intake with endurance training on the protein levels of mitochondrial components. METHODS: Male Institute of Cancer Research mice aged 10 weeks were divided into four groups: a sedentary-control group (Sed-Con, n = 10), a sedentary-KE group (Sed-KE, n = 9), a training-control group (Tr-Con, n = 10), and a training-KE group (Tr-KE, n = 10). All mice orally administered either KE (2.0 g/kg body weight [BW]) solution or an isocaloric control (triolein, 1.11 g/kg BW) solution. The training groups underwent treadmill running at a speed of 25 m/min for 60 minutes. Administrations and training sessions were conducted five times a week for four weeks. The training groups received the solution immediately after running. We harvested the soleus muscle (SOL), which is predominantly composed of slow-twitch fibers, and the plantaris muscle (PLA), which is predominantly composed of fast-twitch fibers. We measured the maximal activity of citrate synthase (CS), a widely used quantitative indicator of mitochondrial content, and protein levels of oxidative phosphorylation (OXPHOS) complexes in the SOL and PLA. RESULTS: In both SOL and PLA, a significant positive main effect of training on maximal CS activities were observed (p < 0.05 in SOL; p < 0.01 in PLA). Meanwhile, no significant main effect of KE intake was observed on maximal CS activity in either muscle. Regarding OXPHOS complex proteins, there was a significant negative main effect of KE intake on complex II protein levels in SOL (p < 0.05). In PLA, significant positive main effects of training were observed in complex I and IV protein levels (p < 0.05). However, there were no significant main effect of KE intake was observed in OXPHOS complex proteins. These results suggest that long-term ketone body intake combined with endurance training may partially influence changes in mitochondrial OXPHOS protein levels in skeletal muscle predominantly composed of slow-twitch fibers. CONCLUSION: These results suggest that chronic ketone body intake combined with endurance training may influence changes in mitochondrial OXPHOS protein levels in skeletal muscle.
Read CV Yumiko TAKAHASHIECSS Paris 2023: CP-PN25