Exogenous Beta-Hydroxybutyrate Ketone Salts Elevate Circulating Acetoacetate Levels

Angelia Holland-Winkler, Andrew Moore, Jenna Ansley
2021 Current Developments in Nutrition  
Objectives Ketones are compounds that provide both fuel and protection against various diseases; they are produced naturally by the liver or exogenously to be ingested. Beta-hydroxybutyrate is the most stable ketone and therefore, often used in ketone supplements. Beta-hydroxybutyrate interconverts with acetoacetate, the least stable ketone. Acetoacetate may offer greater neuroprotection than beta-hydroxybutyrate. Therefore, it is important to find methods to increase acetoacetate levels. The
more » ... rpose of this study was to determine if exogenous beta-hydroxybutyrate salts significantly elevate blood acetoacetate levels 30-minutes after consumption. Methods Sixteen young adults participated in this randomized, triple-blinded, cross-over, placebo-controlled study and met for three laboratory visits: 1) familiarization visit, and 2–3) data collection visits separated by at least one week for washout. During visits two and three, blood samples were collected at baseline and again 30-minutes after consuming either the racemic ketone-salt supplement or placebo. Acetoacetate was stabilized in the blood samples and analyzed via mass spectrophotometry. A two-way repeated-measures ANOVA was conducted to determine the effects of drink and time on blood acetoacetate levels. Results There was a significant (p = .008) interaction between drink and time. Bonferroni-adjusted simple main effects tests demonstrated that between baseline and 30-minutes post drink, blood acetoacetate was not different (p = .50) for the placebo but was significantly increased (p = .001) for the ketone salt supplement. The gain score analysis from a paired samples t-test demonstrated that the increase in acetoacetate after ingestion of ketone salts was significantly (p = .01) and substantially (d = .842) larger than the increase following ingestion of the placebo drink. Conclusions Blood acetoacetate levels can be significantly elevated by exogenous ketone salts, demonstrating a quick interconversion of exogenous beta-hydroxybutyrate to acetoacetate. More studies are needed to determine if this acute increase in acetoacetate is great enough to confer protective benefits demonstrated in previous studies. Funding Sources Augusta University and Keto-Mojo, inc.
doi:10.1093/cdn/nzab041_017 fatcat:cql7buddercn3o5kytgytrtgim