In vitro stability and in vivo pharmacokinetics of the novel ketogenic ester, bis hexanoyl (R)-1,3-butanediol (original) (raw)

An open-label, acute clinical trial in adults to assess ketone levels, gastrointestinal tolerability, and sleepiness following consumption of (R)-1,3-butanediol (Avela™)

Frontiers in Physiology

Introduction: A study was undertaken to determine the acute effects of a beverage made with Avela™ (R)-1,3-butanediol, on blood beta-hydroxybutyrate (BHB) levels (using the Keto-Mojo monitor), gastrointestinal (GI) tolerability (using the modified visual analogue scale GI Symptoms Tool), and sleepiness (using the Stanford Sleepiness Scale).Methods: Following a 12-h overnight fast, 26 healthy adults consumed one beverage containing 11.5 g of (R)-1,3-butanediol at each of 0, 30, and 60 min, culminating in a total intake of 34.5 g of (R)-1,3-butanediol. Blood BHB levels, GI tolerability, and sleepiness were assessed at baseline (0 min), and at 30, 60, 90, 120, 180, 240, and 300 min. At 240 min, a protein bar was consumed.Results: The mean (±SD) BHB fasting baseline level, maximal concentration, time at maximal concentration, and incremental area under the curve over 300 min were 0.23 ± 0.21 mmol/L, 2.10 ± 0.97 mmol/L, 133.85 ± 57.07 min, and 376.73 ± 156.76 mmol/L*min, respectively. BH...

Effect of 1,3 butanediol on hepatic fatty acid synthesis and metabolite levels in the rat

Journal of Nutrition

The effect of 1,3-butanediol on hepatic fatty acid synthesis and metab olite levels in the rat was examined. Hepatic fatty acid synthesis was depressed in rats fed 1,3-butanediol. An intraperitoneal injection of 1,3-butanediol increased blood glucose levels but did not affect hepatic fatty acid synthesis in the rat. Addition of 1,3-bu tanediol to the incubation buffer depressed glucose, but not acetate, conversion to fatty acids by rat liver slices. Méthylène blue inhibition of hepatic fatty acid synthesis was partially reversed by the addition of 1,3-butanediol to the incubation buffer. Hepatic /3-hydroxybutyrate levels and the £-hydroxybutyrate:acetoacetate ratio were increased when 1,3-butanediol was fed. Lactate and pyruvate levels were lower in freeze-clamped liver preparations from rats fed 1,3-butanediol than those observed in control animals. Further, the lactate: pyruvate ratio was increased, suggesting that the hepatic cytoplasmic NADH/NAD+ ratio was increased. Hepatic long-chain acyl CoA levels were also increased when 1,3-butanediol was fed. It is suggested that the shift in the cytoplasmic redox state and the increase in hepatic long-chain acyl CoA levels are involved in the decrease in hepatic fatty acid synthesis observed when rats are fed 1,3-butanediol.