Acute ketosis inhibits appetite and decreases plasma concentrations of acyl ghrelin in healthy humans

CONTEXT: Ketosis appears to decrease appetite and facilitate weight loss. Potential underlying mechanisms include decreases in plasma levels of the orexigenic hormone ghrelin and increases in appetite-inhibiting glucagon-like peptide-1 (GLP-1) levels. The effect of acute ketosis as compared to an isocaloric and isovolumetric beverage on both acyl ghrelin and total GLP-1 plasma concentrations has not been previously measured. OBJECTIVE: We aimed to investigate the acute effect of ketone ester (KE) ingestion on appetite and plasma concentrations of acyl ghrelin (AG), unacylated ghrelin (UAG), and GLP-1 secretion and to compare responses to those elicited by isocaloric glucose administration. METHODS: We examined ten healthy young males on three separate occasions using a placebo-controlled crossover design. INTERVENTIONS AND MAIN OUTCOME MEASURES: A KE vs. taste-matched isovolumetric and isocaloric 50% glucose (GLU) and taste-matched isovolumetric placebo vehicle (PBO) was orally administered. Our main outcome measures were plasma concentrations of AG, UAG, glucose-dependent insulinotropic polypeptide (GIP), and GLP-1 along with appetite sensation scores assessed by visual analogue scale . RESULTS: KE ingestion resulted in an average peak ꞵ-hydroxybutyrate concentration of 5.5 mM. AG and UAG were lowered by ~25% following both KE and GLU intake, compared with PBO. In the case of AG, the differences were - 52.1 [-79.4-24.8] for KE and - 48.4 [-75.4, -21.5] pg/mL for GLU intake, p