Effectiveness of Exogenous Ketone Salts in Enhancing Circulating Acetoacetate Levels—A Pilot Study in Healthy Adults

TL;DR

This study shows that exogenous ketone salts significantly increase acetoacetate levels in healthy adults, suggesting they can serve as an effective energy source.

Contribution

The study demonstrates a strong correlation between ketone salt consumption and increased acetoacetate levels in a placebo-controlled trial.

Findings

Ketone salt consumption significantly increased plasma acetoacetate levels compared to placebo.

The increase in acetoacetate was strongly correlated with changes in beta-hydroxybutyrate levels.

Ketone salts appear to enhance ketone body interconversion for energy supply in peripheral tissues.

Abstract

Background/Objectives: Ketone salt (KS) containing a racemic beta-hydroxybutyrate mixture is commonly used as an alternative fuel source as it may lead to improved health and/or performance. We postulate that KS will raise acetoacetate levels and represent the effectiveness of exogenous KS as an energy source. We conducted a pilot study to quantify changes in the circulating acetoacetate following KS and to determine if any changes in acetoacetate were associated with the changes in circulating beta-hydroxybutyrate. Methods: Thirteen adults (21.6 ± 4.3 years old; seven males/six females) completed this randomized, triple-blinded, placebo-controlled, cross-over design study. Participants consumed either KS or flavor-matched placebo with a one-week washout period between supplements. Blood samples were taken before and 30 min after consuming each supplement, and plasma acetoacetate and beta-hydroxybutyrate levels were measured by gas chromatography/mass spectrometry. Results: The consumption of KS resulted in a significant increase in acetoacetate from baseline. The increase in acetoacetate after the KS supplement was significantly greater than that following the consumption of a placebo (↑ 0.57 ± 0.44 mM vs. ↑ 0.07 ± 0.23 mM, p = 0.009, d = 0.86), and significantly and strongly related to the change in blood beta-hydroxybutyrate (r = 0.757, p < 0.001). Conclusions: Our findings indicate that KS markedly increases plasma ketone body interconversion, presumably to supply peripheral tissues for ATP generation.

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