The Effect of Acute Exogenous Oral Ketone Supplementation on Diurnal and Nocturnal Blood Pressure and Glucose Homeostasis

The goal of this clinical trial is to determine the effect of acute consumption of a ketone monoester supplement in healthy male adults.

The main questions it aims to answer are:

• To determine if acute consumption of a ketone monoester supplement modulates diurnal (measured in lab) and nocturnal blood pressure (assessed by ambulatory blood pressure monitoring; ABPM) compared to a taste-matched placebo. The investigators hypothesize that a ketone monoester supplement will acutely decrease systolic and diastolic blood pressure compared to the placebo. The same results are expected for diurnal and nocturnal blood pressure.
• To determine if acute consumption of a ketone monoester supplement improves glucose control measured with continuous glucose monitoring (CGM) following a standardized meal consumed 90 minutes after ingestion of the ketone supplement. The investigators hypothesize that a ketone monoester supplement, consumed 90 minutes before a meal, will decrease the 2-hour postprandial glucose incremental area under the curve (iAUC) and peak glucose compared to a placebo.
• To assess IL-10's ability to inhibit proinflammatory cytokine production (TNF- α and IL-1β) in LPS-stimulated whole blood cultures following the ingestion of β-OHB and placebo. The investigators hypothesize that β-OHB will augment the ability of IL-10 to inhibit TNF-α and IL-1β production compared to placebo.

Using a double-blind placebo-controlled randomized crossover study design, 15 adults will participate in two experimental conditions. Participants will be recruited using a local recruitment database (Nabû), during presentations in community organizations, with posters at the University of Sherbrooke and from word of mouth. Following screening, eligible participants will be invited for one baseline and two experimental conditions at the Research Centre on Aging (CdRV). During the baseline visit, the following assessments and tests will be conducted: 1) resting heart rate (HR) and blood pressure; 2) anthropometry and body composition; 3) medical history and questionnaires on physical activity levels, dietary habits and anxiety symptoms; 4) explanation of the dietary and physical activity logs; 5) installation of accelerometers to control physical activity levels and sedentary behaviours over 10 days and CGM to assess glucose control over the subsequent 10 consecutive days. Informed consent will be obtained from all participants involved in the study before participating in any assessments or tests. The participant will then be invited to our lab for two non-consecutive days for the experimental condition (at least 48 hours apart).

The first visit will take place at the CdRV (Sherbrooke, QC) on a Thursday or Friday morning. Once the informed consent has been obtained, a medical history and a physical activity questionnaire (International Physical Activity Questionnaire) will be completed by the participant. Body weight, height, and waist circumference will then be measured using standardized procedures. Body composition will be assessed using Dual Energy X-ray absorptiometry (DXA). A CGM will be installed at the abdominal region by the participant himself with the supervision of an experienced exercise physiologist. To limit compensatory behaviours in response to observed blood glucose levels, CGM will be blinded to participants. Finally, participants will be outfitted with a thigh-worn activPAL4 and a hip-worn ActiGraph wGT3X-BT accelerometer to wear for the following 10 days. Wearing the accelerometers will allow for comparing physical activity levels and sedentary behaviours on the days before and after each condition. To ensure that both accelerometers provide reliable data, standardized tests will be performed in our laboratory during the baseline condition. While wearing the activPAL4 and ActiGraph, participants will walk on the treadmill (Life Fitness, Club Series, FlexDeck®; Rosemont, IL, USA) at 3.0, 5.0 and 7.0 km/h for 6 minutes at each intensity. Participants will also have to be in a seated, recline and lying position for 5 minutes each and perform non-ambulatory tasks (washing dishes - 6 minutes and setting the table - 3 minutes). All participants will wear the Xsens motion system during these tasks to capture movement and inform us of the activity profile for better data analysis.