Introduction: Ketone bodies (KB) are oxidative fuel substrates and metabolic signals produced in response to starvation or a high fat low carbohydrate diet. Recently we developed a ketone ester (KE) that, when consumed as a drink, rapidly increased circulating KB [1]. However, the effect of concomitant meal ingestion on the absorption kinetics of this nutritional ketone ester is unknown. This aim of this study was to characterize the kinetics of blood KB following a standard meal and on an empty stomach. Methods: Following favorable ethical review , healthy, non-obese volunteers (n = 16) completed a randomized, cross over study. Following an overnight fast, subjects consumed 395 mg.kg KE, on an empty stomach (CON) or immediately following a standard meal (FED). The standardised meal consisted of 600 kCal of carbohydrate, fat and protein (ratio: 2:4:1), 600g in mass. Blood samples were obtained via an intravenous catheter at baseline (BL) and at regular interval post-drink/meal. Samples were analyzed for β-hydroxybutyrate (BHB), acetoacetate (AcAc) and insulin. Breath acetone was measured using a handheld analyzer (NNT DOCOMO).Values are means ± SEM. 2-way repeated measures ANOVA with Sidak Post Hoc corrections were performed. Significance was taken at p<0.05. Peak BHB concentration (1h post KE) was lower on FED vs. CON (2.1 mM ± 0.2 mM vs. 3.1 mM ± 0.1 mM). AcAc concentrations followed a similar time course to BHB, and were unchanged in both CON and FED. BHB:AcAc was therefore significantly greater between 0.5-2h in CON vs FED (p<0.05). BHB area under the curve (AUC) was ~ 60% lower in FED vs. CON (p<0.05). Breath acetone reached a peak after 3h, and was not different between conditons. Peak insulin concentration and AUC was ~ 3-fold greater in FED vs. CON (3500 mU/L min-1 vs. 1077 mU/L min-1). Conclusions: The ingestion of KE immediately following a meal reduced peak BHB and AUC, but did not influence AcAc or acetone kinetics. This may be due to lower gut absorption [2] or increased metabolic disposal mediated by higher insulin levels [3] in the FED vs. CON state. BHB conversion to AcAc may have been affected by the higher BHB concentration in the fasted state or alteration of the hepatic redox state. These data demonstrate the importance of considering meal ingestion when planning dosing regimes to induce or maintain ketosis following KE.
Physiology 2015 (Cardiff, UK) (2015) Proc Physiol Soc 34, PC235
Poster Communications: Concomitant meal ingestion alters levels of circulating ketone bodies following a ketone ester drink
B. J. Stubbs1, K. Willerton1, S. Hiyama2, K. Clarke1, P. J. Cox1
1. Department of Physiology Anatomy and Genetics, Oxford University, Oxford, United Kingdom. 2. NNT DOCOMO, Kanagawa, Japan.
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Where applicable, experiments conform with Society ethical requirements.