Exogenous Ketones and Glucose Tolerance

The Effect of Exogenous Ketone Monoester Supplement on Glycemic Response to an Oral Glucose Tolerance Test

The ketone body beta-hydroxybutyrate is produced during prolonged fasting or when endogenous carbohydrate stores are depleted and can be used as an alternative fuel source. Exogenous beta-hydroxybutyrate, in the form of a ketone monoester, is proposed to have glucose-lowering potential but this has not been adequately studied. The purpose of this study is to determine whether supplementing with an acute dose of ketone monoester can improve the glycemic response to an oral glucose tolerance test in individuals with impaired fasting glucose.

Study Overview

• Status: Completed
• Conditions: Dietary Supplements; Ketones
• Intervention / Treatment: Dietary supplement: Ketone monoester; Dietary supplement: Placebo

• Study Type: Interventional
• Enrollment (Actual): 15
• Phase: Phase 1

Contacts and Locations

Study Locations

• Canada
  • British Columbia
    • Kelowna, British Columbia, Canada, V1V 1V7
      • University of British Columbia, Okanagan.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 30 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Not taking any medications affecting glucose metabolism.
• Elevated fasting glucose level (5.6-6.9 mmol/L) OR body mass index >28 kg/m2 OR elevated waist circumference (>102 cm for males, >88 cm for females)

Exclusion Criteria:

• Diagnosed with diabetes.
• Diagnosed with heart disease.
• Competitive endurance athlete (self-identified as engaged in specific endurance training in triathlon, cycling, or distance running and competing in races or competition)
• Recent (last 3 months) or current consumption of a low-carbohydrate ketogenic diet
• Current consumption of ketone supplements
• Pregnant or planning to become pregnant during the study (if female)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: BASIC_SCIENCE
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Ketone monoester; Acute morning dose of (R)-3-hydroxybutyl (R)-3-hydroxybutyrate (0.45 ml/kg body weight)	Dietary supplement: Ketone monoester; Acute ingestion of (R)-3-hydroxybutyl (R)-3-hydroxybutyrate prior a 2-hour oral glucose tolerance test.
PLACEBO_COMPARATOR: Placebo; Acute morning dose of flavour-matched placebo.	Dietary supplement: Placebo; Acute ingestion of a taste-matched placebo prior a 2-hour oral glucose tolerance test.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Glucose area under the curve	Area under the curve for glucose during oral glucose tolerance test	2-hour

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Insulin area under the curve	Insulin area under the curve during oral glucose tolerance test	2-hour
Free fatty acids area under the curve	Non-esterified fatty acids area under the curve during oral glucose tolerance test	2-hour
Caspase-1 activation	Caspase-1 activation assessed before and after ketone or placebo ingestion in the morning	15 minutes
Inflammatory cytokines	Inflammatory cytokines assessed before and after ketone or placebo ingestion in the morning	15 minutes
C-peptide area under the curve	C-peptide area under the curve during oral glucose tolerance test	2-hour
GLP-1 area under the curve	GLP-1 area under the curve during oral glucose tolerance test	2-hour
Glucagon area under the curve	Glucagon area under the curve during oral glucose tolerance test	2-hour
Glucose incremental area under the curve	Incremental area under the curve (above baseline) for glucose during oral glucose tolerance test	2-hour
Insulin incremental area under the curve	Incremental area under the curve (above baseline) for insulin during oral glucose tolerance test	2-hour
2-hr glucose level	Plasma glucose assessed 2-hr after oral glucose tolerance test.	2-hour
Oral glucose sensitivity index	Oral glucose sensitivity index derived from glucose and insulin values throughout the 2-hr oral glucose tolerance test	2-hour

Collaborators and Investigators

• Sponsor: University of British Columbia

Publications and helpful links

General Publications

• Myette-Cote E, Caldwell HG, Ainslie PN, Clarke K, Little JP. A ketone monoester drink reduces the glycemic response to an oral glucose challenge in individuals with obesity: a randomized trial. Am J Clin Nutr. 2019 Dec 1;110(6):1491-1501. doi: 10.1093/ajcn/nqz232.

Study record dates

Study Major Dates

• Study Start (ACTUAL): March 26, 2018
• Primary Completion (ACTUAL): October 3, 2018
• Study Completion (ACTUAL): October 15, 2018

Study Registration Dates

• First Submitted: March 4, 2018
• First Submitted That Met QC Criteria: March 8, 2018
• First Posted (ACTUAL): March 9, 2018

Study Record Updates

• Last Update Posted (ACTUAL): April 18, 2019
• Last Update Submitted That Met QC Criteria: April 17, 2019
• Last Verified: April 1, 2019

More Information

Terms related to this study

• Other Study ID Numbers: H16-01846

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No