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

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.