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Research Article

The Effect of Novel Exogenous Ketone Supplements on Blood Beta-Hydroxybutyrate and Glucose

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Pages 38-52 | Published online: 27 Feb 2023
 

Abstract

Exogenous ketone monoesters can raise blood β-OHB and lower glucose without other nutritional modifications or invasive procedures. However, unpleasant taste and potential gastrointestinal discomfort may make adherence to supplementation challenging. Two novel ketone supplements promise an improved consumer experience but differ in their chemical properties; it is currently unknown how these affect blood β-OHB and blood glucose compared to the ketone monoester. In a double-blind randomized cross-over pilot study, N=12 healthy individuals (29 ± 5 years, BMI = 25 ± 4 kg/m2, 42% female) participated in three experimental trials with a different ketone supplement providing 10 grams of active ingredient in each; (i) the monoester (R)-3-hydroxybutyl (R)-3-hydroxybutyrate, (ii) D-β-hydroxybutyric acid with R-1,3-butanediol, and (iii) R-1,3-butanediol. Blood β-OHB and glucose were measured via finger prick capillary blood samples at baseline and across 240 minutes post-supplementation. Supplement acceptability, hunger, and gastrointestinal distress were assessed via questionnaires. β-OHB was elevated compared to baseline in all conditions. Total and incremental area under the curve (p < 0.05) and peak β-OHB (p  < 0.001) differed between conditions with highest values seen in the ketone monoester condition. Blood glucose was reduced after consumption of each supplement, with no differences in total and incremental area under the curve across supplements. Supplement acceptability was greatest for D-β-hydroxybutyric acid with R-1,3-butanediol, with no effect on hunger or evidence of gastrointestinal distress across all supplements. All ketone supplements tested raised β-OHB with highest values seen after ketone monoester ingestion. Blood glucose was lowered similarly across the assessed time frame with all three supplements.

Authors’ contributions

Conceptualization, all authors; methodology, K.F., J.P.L.; formal analysis, K.F.; investigation, all authors; data curation, K.F., A.D.; writing – original draft preparation, K.F.; writing – review and editing, all authors; visualization, K.F.; supervision, J.P.L.; project administration, K.F., J.P.L.; funding acquisition, J.P.L. All authors have read and agreed to the published version of the manuscript

Disclosures statement

J.P.L. is volunteer Chief Scientific Officer for the not-for-profit Institute for Personalized Therapeutic Nutrition. J.P.L. holds founder shares in Metabolic Insights Inc., a for-profit company that developed noninvasive metabolic monitoring devices.

Institutional review board statement

The study was approved by the clinical ethics board of the University of British Columbia (H22-00083) and preregistered (NCT05273411).

Data availability statement

Data and corresponding code are publicly available under this link: https://osf.io/wvxf4/?view_only=2a2bc242fabd41babeba1b41d04652a5.

Additional information

Funding

J.P.L. is supported by a Michael Smith Foundation for Health Research (MSFHR) Scholar Award (16890) and a Killam Accelerator Research Fellowship. This work was funded by a Canadian Institutes of Health Research (CIHR) Project Grant to J.P.L. (PJT-169116).

Notes on contributors

Kaja Falkenhain

Kaja Falkenhain, is a PhD student at the University of British Columbia, investigating the effects of endogenous and exogenous ketosis on cardiometabolic health.

Ali Daraei

Ali Daraei, is a PhD student in the School of Health and Exercise Sciences at the University of British Columbia. His research interests include exercise immunology, exercise & respiratory system, ketone bodies and COPD.

Jonathan P. Little

Jonathan P. Little, is Professor in the School of Health and Exercise Sciences at the University of British Columbia. He leads the Exercise, Metabolism, and Inflammation Laboratory and conducts research with the goals of optimizing exercise and diet interventions for the prevention, treatment, and reversal of type 2 diabetes.

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