A Ketone Ester Drink Lowers Human Ghrelin and Appetite

Abstract

Objective: The ketones d-β-hydroxybutyrate (BHB) and acetoacetate are elevated during prolonged fasting or during a "ketogenic" diet. Although weight loss on a ketogenic diet may be associated with decreased appetite and altered gut hormone levels, it is unknown whether such changes are caused by elevated blood ketones. This study investigated the effects of an exogenous ketone ester (KE) on appetite.

Methods: Following an overnight fast, subjects with normal weight (n = 15) consumed 1.9 kcal/kg of KE, or isocaloric dextrose (DEXT), in drinks matched for volume, taste, tonicity, and color. Blood samples were analyzed for BHB, glucose, insulin, ghrelin, glucagon-like peptide 1 (GLP-1), and peptide tyrosine tyrosine (PYY), and a three-measure visual analogue scale was used to measure hunger, fullness, and desire to eat.

Results: KE consumption increased blood BHB levels from 0.2 to 3.3 mM after 60 minutes. DEXT consumption increased plasma glucose levels between 30 and 60 minutes. Postprandial plasma insulin, ghrelin, GLP-1, and PYY levels were significantly lower 2 to 4 hours after KE consumption, compared with DEXT consumption. Temporally related to the observed suppression of ghrelin, reported hunger and desire to eat were also significantly suppressed 1.5 hours after consumption of KE, compared with consumption of DEXT.

Conclusions: Increased blood ketone levels may directly suppress appetite, as KE drinks lowered plasma ghrelin levels, perceived hunger, and desire to eat.

© 2017 The Authors. Obesity published by Wiley Periodicals, Inc. on behalf of The Obesity Society (TOS).

Figures

Figure 1

(A) Schematic illustrating the study protocol. (B) Blood BHB kinetics following isocaloric KE and DEXT drinks in 15 subjects at rest. Values are means ± SEM. *P < 0.05 difference between KE and DEXT.

Figure 2

Changes in VAS responses from baseline, correlation between BHB and VAS score, and levels of plasma glucose, insulin, ghrelin, GLP‐1, and PYY following isocaloric KE and DEXT drinks in 15 subjects at rest. Panels 2D‐2F show data from the KE visit only: each point is one of the time series points between 30 and 240 minutes (seven time points) for each participant (n = 15), giving a total of 105 points. Values are means ± SEM. r = Pearson's r. *P < 0.05 difference between KE and DEXT; †P < 0.05 difference from baseline value.