Author(s): PERISSIOU, M., ZIA, F., PRASKACOVA, V., SHEPHERD, A.I., Institution: UNIVERSITY OF PORTSMOUTH, Country: UNITED KINGDOM, Abstract-ID: 2014

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