Effect of 14 Days of Exogenous Ketone Supplementation on Glycemic Control in Type 2 Diabetes: a Randomized Placebo-controlled Crossover Trial
Trial Snapshot
- Phase
- Not Applicable
- Status
- Completed
- Enrollment
- 15
- Locations
- 1
- Primary Endpoint
- Glucose Control: Change in Fructosamine
Study Overview
Brief Summary
Ketone bodies are a fuel source and signaling molecule that are produced by the body during prolonged fasting or if an individuals consistently eats a low-carbohydrate "keto" diet. Blood ketones can be used as a source of energy by the body, but they may also act as signals that impact the functioning of different cells in the body. Recently, the availability of ketone supplements that can be taken orally allows for raising blood ketones without having to fast or eat a "keto" diet. The investigators' studies and those of other researchers have shown that ketone supplementation can lower blood sugar without having to make any other dietary changes. Oral ingestion of ketones may therefore be an effective strategy to improve blood sugar control and influence how cells function.
The main objective of this study is to determine if consuming a ketone supplement 3 times per day (before meals) for 14 days lowers blood sugar and impacts how the body's cells function. The results of this study will be used to guide future recommendations on the utility of ketone supplements for improving health in individuals with, or at elevated risk of, type 2 diabetes.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Crossover
- Primary Purpose
- Treatment
- Masking
- Triple (Participant, Investigator, Outcomes Assessor)
Eligibility Criteria
- Ages
- 30 Years to 69 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Have a type 2 diabetes diagnosis from a physician
- •Have stable use of glucose-lowering medications for at least 3 months
Exclusion Criteria
- •Are a competitively trained endurance athlete
- •Are actively attempting to gain or lose weight
- •Have a history of mental illness or existing neurological disease(s), cardiovascular events (i.e., heart attack, stroke) in the last 2 years
- •Have hypoglycemia, irritable bowel syndrome or inflammatory bowel disease
- •Are currently using insulin or SGLT2 inhibitors
- •Are using more than 2 classes of glucose-lowering medication
- •Are currently following a ketogenic diet or taking ketone supplements
- •Are unable to commit for a 29-day trial
- •Are unable to follow a controlled diet
Arms & Interventions
Experimental
Participants will consume 15 g of an active oral exogenous ketone monoester supplement 15 minutes prior to each meal of the day for a 14-day period.
Pre-intervention (baseline) and post-intervention measurements will be obtained before and immediately after the 14-day period.
All meals will be provided throughout the supplementation period Participants will wear a continuous glucose monitor for the first 10 consecutive days during the supplementation period.
Intervention: Exogenous Ketone Monoester (Dietary Supplement)
Placebo
Participants will consume a flavor-matched placebo drink and undergo the same procedures described in the Experimental Arm
Intervention: Placebo (Dietary Supplement)
Outcomes
Primary Outcomes
Glucose Control: Change in Fructosamine
Time Frame: Day 14 (post-intervention)
Change in glucose control (from pre-intervention Day 0) will be quantified by serum fructosamine obtained by fasting blood sample in both conditions.
Secondary Outcomes
- Change from baseline plasma free fatty acids at 14 days(Day 0 (Pre-intervention) and Day 14 (post-intervention))
- Phagocytosis(Day 0 (Pre-intervention) and Day 14 (post-intervention))
- Degranulation(Day 0 (Pre-intervention) and Day 14 (post-intervention))
- Glycemic Control: Fasting glucose(Day 1 through to Day 10)
- Glycemic Control: Change in Fasting Plasma glucose(Day 14)
- Glycemic Control: Glycemic variability(Day 1 through to Day 10)
- Lipid Panel(Day 0 (pre-intervention) and Day 14 (post-intervention))
- Physical activity(Day 0 (pre-intervention) to Day 14 (post-intervention))
- Sedentary time(Day 0 (pre-intervention) to Day 14 (post-intervention))
- Waist circumference(Day 0 (pre-intervention) and Day 14 (post-intervention))
- Body weight(Day 0 (pre-intervention) and Day 14 (post-intervention))
- Blood pressure(Day 0 (pre-intervention) and Day 14 (post-intervention))
- Vascular function(Day 0 (Pre-intervention) and Day 14 (post-intervention))
- Cognition: N-back test(Day 0 (Pre-intervention) and Day 14 (post-intervention))
- Cognition: Digit-symbol substitution test(Day 0 (Pre-intervention) and Day 14 (post-intervention))
- Change from baseline plasma insulin at 14 days(Day 0 (Pre-intervention) and Day 14 (post-intervention))
- Change from baseline circulating inflammatory cytokines at 14 days(Day 0 (Pre-intervention) and Day 14 (post-intervention))
- Oxidative Burst(Day 0 (Pre-intervention) and Day 14 (post-intervention))
- Glycemic Control: 2hr postprandial hyperglycemia(Day 1 through to Day 10)
- Glycemic Control: 24hr average glucose area under the curve (AUC)(Day 1 through to Day 10)
- Glycemic Control: Time in Target Range(Day 1 through to Day 10)
- Glycemic Control: HbA1c(Day 0 (pre-intervention) and Day 14 (post-intervention))
- Blood beta-hydroxybutyrate(Day 0 (pre-intervention) and Day 14 (post-intervention))
- Immune Cell Phenotyping(Day 0 (Pre-intervention) and Day 14 (post-intervention))
- Complete blood count(Day 0 (Pre-intervention) and Day 14 (post-intervention))
- Sleeping time(Day 0 (pre-intervention) to Day 14 (post-intervention))
- Resting heart rate(Day 0 (pre-intervention) and Day 14 (post-intervention))
Investigators
Jonathan Little
Associate professor
University of British Columbia