Prior ingestion of a ketone monoester supplement reduces postprandial glycemic responses in young healthy-weight individuals

Greaves, Grant; Xiang, Richard F.; Rafiei, Hossein; Malas, Adeeb; Little, Jonathan P.

doi:10.1139/apnm-2020-0644

Cited by 19 publications

(12 citation statements)

References 52 publications

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“…Additionally, in this study the carbohydrate content of the provided breakfast choices was highly variable which might confound the observation. As ketone esters have been demonstrated to lower blood glucose responses following an oral glucose tolerance test and a mixed meal in acute and multi-day studies [ 26 , 27 , 28 , 62 ], the effect of BH-BD on blood glucose concentrations is a promising area for future investigation.…”

Section: Discussionmentioning

confidence: 99%

Tolerability and Safety of a Novel Ketogenic Ester, Bis-Hexanoyl (R)-1,3-Butanediol: A Randomized Controlled Trial in Healthy Adults

et al. 2021

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Nutritional ketosis is a state of mildly elevated blood ketone concentrations resulting from dietary changes (e.g., fasting or reduced carbohydrate intake) or exogenous ketone consumption. In this study, we determined the tolerability and safety of a novel exogenous ketone diester, bis-hexanoyl-(R)-1,3-butanediol (BH-BD), in a 28-day, randomized, double-blind, placebo-controlled, parallel trial (NCT04707989). Healthy adults (n = 59, mean (SD), age: 42.8 (13.4) y, body mass index: 27.8 (3.9) kg/m2) were randomized to consume a beverage containing 12.5 g (Days 0–7) and 25 g (Days 7–28) of BH-BD or a taste-matched placebo daily with breakfast. Tolerability, stimulation, and sedation were assessed daily by standardized questionnaires, and blood and urine samples were collected at Days 0, 7, 14, and 28 for safety assessment. There were no differences in at-home composite systemic and gastrointestinal tolerability scores between BH-BD and placebo at any time in the study, or in acute tolerability measured 1-h post-consumption in-clinic. Weekly at-home composite tolerability scores did not change when BH-BD servings were doubled. At-home scores for stimulation and sedation did not differ between groups. BH-BD significantly increased blood ketone concentrations 1-h post-consumption. No clinically meaningful changes in safety measures including vital signs and clinical laboratory measurements were detected within or between groups. These results support the overall tolerability and safety of consumption of up to 25 g/day BH-BD.

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Section: Discussionmentioning

confidence: 99%

Tolerability and Safety of a Novel Ketogenic Ester, Bis-Hexanoyl (R)-1,3-Butanediol: A Randomized Controlled Trial in Healthy Adults

et al. 2021

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“…Ketones from exogenous sources can act as a fuel and signal, through the same pathways as endogenously derived ketones, and therefore may benefit health and performance. One class of exogenous ketones, called ketone esters, has been investigated for their impact on multiple endpoints, including physical and cognitive performance, [7][8][9][10][11][12][13] blood glucose regulation [14][15][16][17] and cardiac function. 18,19 There is a previously developed novel ketone di-ester that induces nutritional ketosis within 30 min: bis-hexanoyl (R)-1,3-butanediol (BH-BD, common name: C6 ketone diester).…”

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

A randomized, open-label, cross-over pilot study investigating metabolic product kinetics of the palatable novel ketone ester, bis-octanoyl (R)-1,3-butanediol, and bis-hexanoyl (R)-1,3-butanediol ingestion in healthy adults

Stubbs,

Cook,

Blonquist

et al. 2023

Toxicology Research and Application

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Introduction Bis-octanoyl (R)-1,3-butanediol (BO-BD) is a novel, palatable ketone ester that, when consumed, is hydrolyzed in the gastrointestinal tract into octanoic acid (OCT) and (R)-1,3-butanediol (BDO) which are subsequently metabolized into beta-hydroxybutyrate (BHB). Metabolism of BO-BD is hypothesized to be similar to bis-hexanoyl (R)-1,3-butanediol (BH-BD), apart from release of octanoic acid instead of hexanoic acid (HEX). Methods As part of the safety assessment for BO-BD a randomized, cross-over, open-label study in middle-aged, healthy adults ( n = 12) was undertaken to provide a qualitative comparison of plasma BHB, OCT, HEX and BDO concentrations for 8 h following consumption of 12.5 or 25 g of BO-BD and 12.5 g of BH-BD. Results All study products increased plasma BHB and BDO up to 4 h post-consumption. BH-BD increased HEX, whereas BO-BD increased OCT. All kinetic parameters for BHB and BDO were similar between 12.5 g servings of BH-BD and BO-BD while Cmax and AUC for OCT were higher following 12. 5 g servings of BO-BD as compared to HEX with 12.5 g of BH-BD. All metabolites returned to baseline by 8 h post-consumption. BHB, BDO and OCT Cmax and AUC were increased with serving size of BO-BD from 12.5 to 25 g. Sensory acceptability scores of BO-BD were significantly higher than for BH-BD. An in vitro hydrolysis experiment using human blood plasma further confirmed that plasma esterases possess the ability to break down the novel ketone esters into BDO, and OCT or HEX. Discussion The two novel ketone ester molecules exhibit similar metabolic breakdown to BHB and BDO and result in transiently higher concentrations of the plasma fatty acids, OCT and HEX, in vivo. Conclusions Given the similar ketone delivery with greater acceptability, BO-BD may offer a more broadly translatable tool to induce physiologic ketosis than BH-BD.

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“…The effect of acute ketosis on free fatty acids – another risk factor for cardiovascular disease – could be of interest. However, investigating these in the present study would have been redundant as several previous RCTs found free fatty acids to be significantly reduced following acute ketosis (whereas no previous RCT used the standard lipid panel as an outcome) [ 11 , 60 – 62 ]. Last, lipid profile is altered in individuals with remnant removal disease or lipoprotein lipase deficiency (which were not our exclusion criteria).…”

Section: Discussionmentioning

confidence: 99%

Effect of acute ketosis on lipid profile in prediabetes: findings from a cross-over randomized controlled trial

Liu

Bharmal

Kimita

et al. 2022

Cardiovasc Diabetol

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Background Ketone monoester β-hydroxybutyrate (KEβHB) ingestion has emerged as an effective method of inducing acute ketosis. Although evidence suggests that KEβHB can offer several therapeutic benefits, whether KEβHB affects lipid profile is still unknown. Aims The primary aim was to study the effect of KEβHB on plasma lipid profile in individuals with prediabetes. The secondary aim was to investigate the role of saturated fat intake in that effect. Methods This study was a randomized controlled trial with cross-over design. Following an overnight fast, 18 adults (six women and 12 men) with prediabetes (diagnosed based on the American Diabetes Association criteria) ingested a single dose of KEβHB drink or placebo drink. Blood samples were collected every 30 min, from baseline to 150 min. Outcome variables included changes in total cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, remnant cholesterol, triglycerides, and the triglycerides to HDL cholesterol ratio. The area under the curve (AUC) over 150 min was calculated for each outcome following ingestion of the drinks. Habitual saturated fat intake was ascertained using the EPIC-Norfolk food frequency questionnaire. Results Significant elevation of blood β-hydroxybutyrate from 0.2 mmol/L to 3.5 mmol/L (p < 0.001) was achieved within 30 min. Acute ketosis resulted in significantly lower AUCs for remnant cholesterol (p = 0.022) and triglycerides (p = 0.022). No statistically significant differences in the AUCs for total cholesterol, HDL cholesterol, LDL cholesterol, and the triglycerides to HDL cholesterol ratio were found. The changes in remnant cholesterol and triglycerides were statistically significant in individuals with high, but not low, habitual saturated fat intake. Conclusion Acute ketosis had no untoward effect on plasma lipid profile. Moreover, it led to significantly reduced circulating levels of remnant cholesterol and triglycerides. This paves the way for investigating whether exogenous ketone supplementation reduces cardiovascular disease risk (via its actions on triglyceride-rich lipoproteins) in at-risk populations. Trial registration: ClinicalTrials.gov, NCT03889210.

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Prior ingestion of a ketone monoester supplement reduces postprandial glycemic responses in young healthy-weight individuals

Cited by 19 publications

References 52 publications

Tolerability and Safety of a Novel Ketogenic Ester, Bis-Hexanoyl (R)-1,3-Butanediol: A Randomized Controlled Trial in Healthy Adults

Tolerability and Safety of a Novel Ketogenic Ester, Bis-Hexanoyl (R)-1,3-Butanediol: A Randomized Controlled Trial in Healthy Adults

A randomized, open-label, cross-over pilot study investigating metabolic product kinetics of the palatable novel ketone ester, bis-octanoyl (R)-1,3-butanediol, and bis-hexanoyl (R)-1,3-butanediol ingestion in healthy adults

Effect of acute ketosis on lipid profile in prediabetes: findings from a cross-over randomized controlled trial

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