Prior ingestion of exogenous ketone monoester attenuates the glycemic response to an oral glucose tolerance test in healthy young individuals

Abstract

The main objectives of this study were threefold: (1) To determine whether acute ingestion of K_me; (R)-3-hydroxybutyl (R)-3-hydroxybutyrate impacts plasma glucose levels during a standardized oral glucose tolerance test (OGTT). (2) To compare changes in insulin concentrations and estimates of insulin sensitivity after acute K_me supplementation. Twenty healthy participants (n = 10 males/females) aged between 18–35 years took part in a randomized crossover study. After an overnight fast, participants consumed a K_me supplement (ΔG®; 0.45 ml kg⁻¹ body weight) or placebo (water) 30 min before completing a 75-gram OGTT. Blood samples were collected every 15–30 min over a period of 2.5 h. Participants and study personnel performing laboratory analyses were blinded to condition. K_me acutely raised blood D-beta-hydroxybutyrate (β-OHB) to 3.2±0.6 mm within 30 min with levels remaining elevated throughout the entire OGTT. Compared to placebo, K_me significantly decreased glucose area under the curve (AUC; −16%, P = 0.001), non-esterified fatty acid (NEFA) AUC (-44%, P < 0.001) and C-peptide incremental AUC (P = 0.005), while improving oral glucose insulin sensitivity index by ∼11% (P = 0.001). In conclusion, a K_me supplement that acutely increased β-OHB levels up to ∼3 mm attenuated the glycemic response to an OGTT in healthy humans. The reduction in glycemic response did not appear to be driven by an increase in insulin secretion, but was accompanied by improved markers of insulin sensitivity. These results suggest that ketone monoester supplements could have therapeutic potential in the management and prevention of metabolic disease.

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