The Impact of Ketone Monoester Intake on Post-exercise Hormonal Responses After Resistance Exercise in Young Males

NCT ID: NCT06683547

Last Updated: 2025-09-02

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 12 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-01-06
• Study Completion Date: 2025-07-27

Brief Summary

This study investigates how orally ingested exogenous ketone monoester supplements affect circulating hormone concentrations in healthy young adult males after a single session of resistance exercise. Resistance exercise is known to stimulate an acute increase in the circulating concentration of various hormones that are involved in the regulation of muscle mass, including testosterone, growth hormone (GH), and insulin-like growth factor-1 (IGF-1).

Recently, there has been growing interest in how nutritional supplements impact these natural hormone responses at rest. One such intervention is the oral ingestion of exogenous ketone body supplements. Ketone bodies (i.e., β-hydroxybutyrate (β-HB), acetoacetate (AcAc), and acetone) are naturally occurring compounds that are normally produced by the body during prolonged fasting/starvation, or in response to a "ketogenic" diet (a diet very high in fat and very low in carbohydrates). These ketone body supplements taken in the form of a ketone monoester can quickly raise blood ketone levels without needing to change your diet.

Recent research has shown that the ingestion of exogenous ketone supplements or following a 'ketogenic diet' can alter the concentration of certain hormones measured in blood samples at rest. However, the effects of ketone monoester intake on the exercise-induced elevation in circulating hormones is yet to be explored.

Therefore, the purpose of this study is to examine how elevated β-HB, induced via the ingestion of the ketone monoester (R)-3-hydroxybutyl-(R)-3-hydroxybutyrate, affects blood concentrations of various anabolic hormones, during post-exercise recovery in healthy young adult males, compared to a placebo drink (flavoured water).

Detailed Description

A within-subject crossover design will be used for this randomized, double-blind, placebo-controlled study in healthy males to investigate the impact of ketone monoester (KET) intake on circulating (blood) concentrations of 'anabolic' and other hormones. There are two treatment arms in this crossover trial, including one KET arm and one placebo group. A total of 12 participants will be enrolled and undergo both treatment phases with a minimum 7-day washout period between lab visits.

The study will include a screening visit (Visit 1), 10-repetition maximum (10-RM) testing (visit 2), where participants' 10-RM will be determined for each exercise machine used, experimental trial (visit 3), minimum 7-day washout, followed by the phase 2 of the experimental trial (visit 4).

During the experimental trials, participants will arrive to the laboratory in an overnight fasted state, and the KET or placebo drink will then be administered following basal blood collection. Then, participants will perform a lower-body resistance exercise session consisting of 5 sets of 10 repetitions of leg press and 3 sets of 12 repetitions of leg extension/leg curl supersets at 95% of their determined 10-RM. Following exercise, another dose of the nutritional treatment will be administered.

Arterialized blood samples will then be collected at 13 postprandial timepoints during the 1-hour rested period and the 4-hour post-exercise recovery period to measure changes in plasma glucose and insulin concentration. Arterialized blood samples will also be utilized for quantitation of anabolic hormones, including testosterone, IGF-1, GH, cortisol, luteinizing hormone, sex-hormone binding globulin, dehydroepiandrosterone, estrogen, progesterone, and follicle-stimulating hormone.

Additionally, changes in capillary blood β-HB concentration will be assessed throughout the trials by collecting capillary blood samples at baseline and 11 postprandial timepoints during the 1-hour rested period and the 4-hour post-exercise recovery period.

Conditions

Ketosis; Blood Hormones; Testing Effect of Intervention; Resistance Exercise; Ketone Body

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: TRIPLE

Study Groups

Ketone Monoester (KET)

Ketone monoester supplement: (R)-3-hydroxybutyl (R)-3-hydroxybutyrate dosed based on participants' body weight (0.36g/kg body weight).

The nutritional beverage will be consumed twice: 30 minutes prior to the exercise workout (t = -60 min) and immediately following the completion of the exercise protocol (t = 0 min).

Group Type: ACTIVE_COMPARATOR

Ketone Monoester (KET)

Intervention Type: DIETARY_SUPPLEMENT

Ketone monoester supplement (R)-3-hydroxybutyl (R)-3-hydroxybutyrate based on participants' body weight (0.36g/kg body weight). The ketone brand name: delta G Oxford Ketone Ester.

Resistance Exercise

Intervention Type: OTHER

\- 5 sets of 10 repetitions of leg press and 3 sets of 12 repetitions of leg extension/leg curl 'supersets' (1 set of each back to back with no rest in between sets) at 95% of their 10-RM. Between-set rest intervals for the leg exercises will be 60 seconds.

Placebo drink

Flavoured water. Participants will consume this beverage twice: 30 minutes prior to the exercise workout (t = -60 min) and immediately following the completion of the exercise protocol (t = 0 min).

Group Type: PLACEBO_COMPARATOR

Flavour matched placebo drink (CON)

Intervention Type: DIETARY_SUPPLEMENT

\- Flavoured water (non-caloric bitter + citrus flavours)

Resistance Exercise

Intervention Type: OTHER

\- 5 sets of 10 repetitions of leg press and 3 sets of 12 repetitions of leg extension/leg curl 'supersets' (1 set of each back to back with no rest in between sets) at 95% of their 10-RM. Between-set rest intervals for the leg exercises will be 60 seconds.

Interventions

Ketone Monoester (KET)

Ketone monoester supplement (R)-3-hydroxybutyl (R)-3-hydroxybutyrate based on participants' body weight (0.36g/kg body weight). The ketone brand name: delta G Oxford Ketone Ester.

Intervention Type: DIETARY_SUPPLEMENT

Flavour matched placebo drink (CON)

\- Flavoured water (non-caloric bitter + citrus flavours)

Intervention Type: DIETARY_SUPPLEMENT

Resistance Exercise

\- 5 sets of 10 repetitions of leg press and 3 sets of 12 repetitions of leg extension/leg curl 'supersets' (1 set of each back to back with no rest in between sets) at 95% of their 10-RM. Between-set rest intervals for the leg exercises will be 60 seconds.

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• Healthy adult male participants who are 18-40 years of age (inclusive).
• BMI >18.5 and <30.0 kg/m2
• Recreationally active (at least of 150 minutes of activity/week).

Exclusion Criteria

• Be willing to entirely avoid alcohol consumption 48 hours prior to the test days.
• Willing and able to agree to the requirements and restrictions of this study, be willing to give voluntary consent, be able to understand and read the questionnaires, and carry out all study-related procedures.

• Individuals with metabolic disorders including: Type I or Type II diabetes.
• Individuals with a history of thrombosis / cardiovascular disease, endocrine disorders
• Individuals with knee injuries (i.e., ACL injuries).
• Individuals with a positive medical history of unstable thyroid disease (i.e., hypothyroidism, hyperthyroidism, hyperparathyroidism, and hypoparathyroidism) and immune disorders.
• Individuals who have used tobacco products within the last 6 months.
• Chronic usage of medications known to modulate hormone levels (i.e. corticosteroids and hormone replacement therapy (HRT)) in the last 6 months.
• Current use of ketone supplements or adherence to a ketogenic diet.
• Formal or regular weightlifting activity within the last year.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 40 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: Yes

Sponsors

McGill University

OTHER

Sponsor Role: lead

Responsible Party

Tyler Churchward-Venne

Associate Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Tyler Churchward-Venne, PhD

Role: PRINCIPAL_INVESTIGATOR

Department of Kinesiology and Physical Education, McGill University

Locations

McGill University

Montreal, Quebec, Canada

Countries

Canada

Other Identifiers

A00-M69-24B

Identifier Type: -

Identifier Source: org_study_id