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 Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
15
Participants will consume 15g of the oral ketone monoester supplement 15 minutes prior to each meal of the day for 14 days. All meals will be provided throughout the 14-day supplementation period.
Participants will consume an equivalent volume (30ml) of the active intervention supplement 15 minutes prior to each meal for 14 days. All meals will be provided throughout the 14-day placebo supplementation period.
University of British Columbia Okanagan
Kelowna, British Columbia, Canada
Glucose Control: Change in Fructosamine
Change in glucose control (from pre-intervention Day 0) will be quantified by serum fructosamine obtained by fasting blood sample in both conditions.
Time frame: Day 14 (post-intervention)
Vascular function
Vascular function will be assessed by flow mediated dilation of the brachial artery using vascular ultrasound. A cuff will affixed on the forearm, distal to the brachial artery and will be inflated for 5 minutes. Flow mediation dilation will be measured over a 3-minute period following cuff release.
Time frame: Day 0 (Pre-intervention) and Day 14 (post-intervention)
Cognition: N-back test
Cognition will be assessed using a customized battery of psychometrically validated tests within the domain of executive functions using the computer-based app Inqisit6 Lab (Millisecond). The test will be the n-back test.
Time frame: Day 0 (Pre-intervention) and Day 14 (post-intervention)
Cognition: Digit-symbol substitution test
Cognition will be assessed using a customized battery of psychometrically validated tests within the domain of executive functions using the computer-based app Inquisit6 Lab (Millisecond). The test will be the digit-symbol substitution test.
Time frame: Day 0 (Pre-intervention) and Day 14 (post-intervention)
Change from baseline plasma insulin at 14 days
Plasma insulin from venous blood samples will be measured using a high-sensitivity human insulin enzyme-like immunosorbent assay (ELISA) run in duplicate.
Time frame: Day 0 (Pre-intervention) and Day 14 (post-intervention)
Change from baseline plasma free fatty acids at 14 days
Free fatty acids from venous blood samples will be measured by colorimetric assay run in duplicate.
Time frame: Day 0 (Pre-intervention) and Day 14 (post-intervention)
Change from baseline circulating inflammatory cytokines at 14 days
Key inflammatory cytokines including CRP will be quantified by Mesoscale Discovery U-PLEX run in duplicate.
Time frame: Day 0 (Pre-intervention) and Day 14 (post-intervention)
Phagocytosis
Phagocytosis of fluorescent-labelled E. coli by immune cells from whole blood will be quantified by flow cytometry
Time frame: Day 0 (Pre-intervention) and Day 14 (post-intervention)
Oxidative Burst
LPS-stimulated oxidative burst by immune cells from whole blood will be quantified by flow cytometry
Time frame: Day 0 (Pre-intervention) and Day 14 (post-intervention)
Degranulation
Immune cell degranulation will be quantified by enzyme-linked immunosorbent assay run in duplicate (quantifying myeloperoxidase and elastase in whole blood cell culture supernatants).
Time frame: Day 0 (Pre-intervention) and Day 14 (post-intervention)
Immune Cell Phenotyping
Phenotyping of macrophages and T cells will be quantified by surface and intracellular staining by flow cytometry.
Time frame: Day 0 (Pre-intervention) and Day 14 (post-intervention)
Complete blood count
A 5-part white blood cell differential and complete blood count will be quantified by hematology analyzer.
Time frame: Day 0 (Pre-intervention) and Day 14 (post-intervention)
Glycemic Control: 2hr postprandial hyperglycemia
Glycemic control will be measured by continuous glucose monitoring using the G6 CGM (Dexcom) in both the active and placebo supplement conditions. Glycemic control will be quantified by assessing 2hr postprandial hyperglycemia.
Time frame: Day 1 through to Day 10
Glycemic Control: 24hr average glucose area under the curve (AUC)
Glycemic control will be measured by continuous glucose monitoring using the G6 CGM (Dexcom) in both the active and placebo supplement conditions. Glycemic control will be quantified by assessing 24hr average glucose AUC.
Time frame: Day 1 through to Day 10
Glycemic Control: Fasting glucose
Glycemic control will be measured by continuous glucose monitoring using the G6 CGM (Dexcom) in both the active and placebo supplement conditions. Glycemic control will be quantified by assessing fasting plasma glucose.
Time frame: Day 1 through to Day 10
Glycemic Control: Change in Fasting Plasma glucose
Change in fasting plasma glucose (from pre-intervention Day 0) will be measured by fasting blood sample in both the active and placebo supplement conditions.
Time frame: Day 14
Glycemic Control: Glycemic variability
Glycemic control will be measured by continuous glucose monitoring using the G6 CGM (Dexcom) in both the active and placebo supplement conditions. Glycemic control will be quantified by assessing glycemic variability.
Time frame: Day 1 through to Day 10
Glycemic Control: Time in Target Range
Glycemic control will be measured by continuous glucose monitoring using the G6 CGM (Dexcom) in both the active and placebo supplement conditions. Glycemic control will be quantified by assessing time in target range.
Time frame: Day 1 through to Day 10
Glycemic Control: HbA1c
Glycemic control will be measured by assessing HbA1c using a point-of-care analyzer.
Time frame: Day 0 (pre-intervention) and Day 14 (post-intervention)
Lipid Panel
Lipid panel (total cholesterol, high-density cholesterol, low-density cholesterol, triglycerides, non-HDL cholesterol, cholesterol/HDL ratio) will be measured using a point-of-care analyzer.
Time frame: Day 0 (pre-intervention) and Day 14 (post-intervention)
Body weight
Change in body weight will be measured using a body weight scale.
Time frame: Day 0 (pre-intervention) and Day 14 (post-intervention)
Blood pressure
Change in blood pressure will be measured using an automated blood pressure device. Both systolic and diastolic blood pressure will be measured.
Time frame: Day 0 (pre-intervention) and Day 14 (post-intervention)
Blood beta-hydroxybutyrate
Change in fasting blood beta-hydroxybutyrate will be measured using a standard assay.
Time frame: Day 0 (pre-intervention) and Day 14 (post-intervention)
Physical activity
Physical activity will be assessed using an accelerometer (activePal) worn throughout the entire intervention period.
Time frame: Day 0 (pre-intervention) to Day 14 (post-intervention)
Sedentary time
Sedentary time will be assessed using an accelerometer (activePal) worn throughout the entire intervention period.
Time frame: Day 0 (pre-intervention) to Day 14 (post-intervention)
Sleeping time
Sleeping time will be assessed using an accelerometer (activePal) worn throughout the entire intervention period.
Time frame: Day 0 (pre-intervention) to Day 14 (post-intervention)
Resting heart rate
Change resting heart rate will be measured using an automated heart rate monitor device.
Time frame: Day 0 (pre-intervention) and Day 14 (post-intervention)
Waist circumference
Change in waist circumference will be measures using a measurement tape.
Time frame: Day 0 (pre-intervention) and Day 14 (post-intervention)
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