Exogenous Ketosis and Muscle Protein Synthesis During Exercise Recovery

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

NA

Total Enrollment

48 participants

Study Classification

INTERVENTIONAL

Study Start Date

2025-01-10

Study Completion Date

2025-10-30

Brief Summary

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An acute bout of resistance exercise stimulates muscle protein synthesis (MPS) rates for up to 24-48 hours, supporting muscle growth and repair. To optimize the anabolic effects of resistance exercise, the provision of dietary amino acids (i.e., proteins) is essential. Dietary protein intake provides the body with necessary amounts of essential and non-essential amino acids, which represent the building blocks for muscle proteins, enhancing anabolic muscle growth. The ingestion of dietary protein, such as whey protein, is well established to stimulate an increase in the rate of protein synthesis in skeletal muscle following resistance exercise. Research has demonstrated a dose-dependent relationship between protein intake and MPS rate, with 25 grams being the optimal dose to maximally stimulate MPS rates in younger adults with excess protein oxidized as a fuel source.

Determining whether this maximally stimulated MPS response can be further heightened during post-exercise recovery using non-protein dietary factors is yet to be explored. Recently, it has been shown that novel orally ingested ketone body supplements can stimulate MPS rates in younger adults at rest.

Ketone bodies (β-OHB) are lipid- derived molecules normally produced under conditions of glucose deprivation (i.e., fasting/starvation, or a low carbohydrate 'ketogenic' diet). However, these orally ingested ketone supplements rapidly increase blood ketone levels without the need for dietary restriction6. In vitro research showed that the combination of leucine and ketone bodies stimulated a 2-fold increase in MPS, compared to the leucine group alone, indicating synergistic effects of protein and ketone bodies on MPS. However, the effect of ketone supplementation, with and without dietary protein co-ingestion, on MPS rate during post-exercise recovery is yet to be investigated. If ketone bodies can amplify the anabolic response to dietary protein, they may provide a novel approach to maximizing muscle adaptation during post-exercise recovery.

Therefore, the purpose of this study is to evaluate the effects of ketone monoester intake on postprandial muscle protein synthesis rates when consumed alone and when co-ingested with an optimal dose (25 g) of whey protein during recovery after resistance exercise compared to 1) an optimal dose of whey protein (25 g), and 2) a control flavored water. It is hypothesized that muscle protein synthesis rates will be stimulated following the ingestion of the ketone body beverage. Further, muscle protein synthesis rates will be further enhanced when the ketone-containing beverage and an optimal dose are taken together.

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Detailed Description

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A parallel group design will be used for this randomized double-blind, placebo-controlled study in healthy adults to investigate the effects of ketone monoester on myofibrillar protein synthesis rates during post-exercise recovery. There are 4 groups in this trial, including one ketone group (0.36g/kg body weight) (KET), one protein group (25 g whey protein) (PRO), a combination of ketone and protein (KET+PRO), and a placebo group (flavoured water) (CON). A total of 48 participants will be enrolled in this trial (n=12 per group).

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 the exercise protocol, and the experimental trial (visit 3).

During the experimental trials, participants will arrive to the laboratory in a fasted state, and a prime dose of the L-\[ring-2H5\]-phenylalanine will be administered followed by a continuous infusion at a rate 0.05 μmol/kg of body weight/min. Then, participants will perform a unilateral lower-body resistance exercise, consisting of 8 sets of 10 reps of unilateral leg extension at 90% of their 10-RM with 90 seconds rest in between sets. Following exercise, the nutritional treatment will be administered.

Arterialized blood will be collected at baseline and 13 postprandial timepoints across 9 hours for plasma amino acid, glucose, and insulin quantitation.

Additionally, changes in capillary blood β-HB concentration will be assessed throughout the trial by collecting capillary blood samples at baseline and 10 postprandial timepoints. Finally, muscle biopsy samples from both the exercised leg and the rested leg will be collected prior to beverage intake and at the 5-hour mark of the postprandial post-recovery period to assess myofibrillar protein synthesis rates.

Conditions

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Ketosis Muscle Protein Synthesis Dietary Proteins Resistance Exercise

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

BASIC_SCIENCE

Blinding Strategy

TRIPLE

Participants Investigators Outcome Assessors

Participants, Investigators and Outcome Accessors will be blinded to the intervention and control drinks. The drinks will be flavor matched and provided in an opaque bottle. An individual not involved with the study data collection, analysis and interpretation will be designated as a study blinder and randomizer.

Study Groups

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Ketone Monoester (KET)

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

Group Type EXPERIMENTAL

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

\- 8 sets of 10 reps at 90% of 10- repetition maximum (10-RM) of unilateral leg extension with 90 seconds rest in between sets.

Ketone Monoester + Whey Protein (KET+PRO)

Ketone monoester supplement (R)-3-hydroxybutyl (R)-3-hydroxybutyrate based on participants' body weight (0.36g/kg body weight) and 25g of whey protein.

Group Type EXPERIMENTAL

Ketone Monoester + Whey Protein (KET+PRO)

Intervention Type DIETARY_SUPPLEMENT

* Ketone monoester supplement (R)-3-hydroxybutyl (R)-3-hydroxybutyrate based on participants' body weight (0.36g/kg body weight)
* 25g Whey Protein
* L-\[ring-2H5\]-phenylalanine tracer (enriched to 4%)

Resistance exercise

Intervention Type OTHER

\- 8 sets of 10 reps at 90% of 10- repetition maximum (10-RM) of unilateral leg extension with 90 seconds rest in between sets.

Whey Protein (PRO)

25g of whey protein.

Group Type EXPERIMENTAL

Whey Protein (PRO)

Intervention Type DIETARY_SUPPLEMENT

* 25g Whey Protein
* L-\[ring-2H5\]-phenylalanine tracer (enriched to 4%)

Resistance exercise

Intervention Type OTHER

\- 8 sets of 10 reps at 90% of 10- repetition maximum (10-RM) of unilateral leg extension with 90 seconds rest in between sets.

Placebo drink (CON)

Flavoured water.

Group Type PLACEBO_COMPARATOR

Flavour matched placebo (CON)

Intervention Type DIETARY_SUPPLEMENT

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

Resistance exercise

Intervention Type OTHER

\- 8 sets of 10 reps at 90% of 10- repetition maximum (10-RM) of unilateral leg extension with 90 seconds rest in between sets.

Interventions

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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

Ketone Monoester + Whey Protein (KET+PRO)

* Ketone monoester supplement (R)-3-hydroxybutyl (R)-3-hydroxybutyrate based on participants' body weight (0.36g/kg body weight)
* 25g Whey Protein
* L-\[ring-2H5\]-phenylalanine tracer (enriched to 4%)

Intervention Type DIETARY_SUPPLEMENT

Whey Protein (PRO)

* 25g Whey Protein
* L-\[ring-2H5\]-phenylalanine tracer (enriched to 4%)

Intervention Type DIETARY_SUPPLEMENT

Flavour matched placebo (CON)

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

Intervention Type DIETARY_SUPPLEMENT

Resistance exercise

\- 8 sets of 10 reps at 90% of 10- repetition maximum (10-RM) of unilateral leg extension with 90 seconds rest in between sets.

Intervention Type OTHER

Eligibility Criteria

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Inclusion Criteria

* Healthy adult female or male participants who are 18-40 years of age (inclusive) BMI \>18.5 and \<30.0 kg/m2
* Moderately active (i.e., ≥ 1 session of lower-body weightlifting /week for the previous 2 months).

Exclusion Criteria

* Be willing to entirely avoid alcohol consumption 48hr prior to the experimental test day.
* 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.

* Females who are lactating or pregnant
* Females using third-generation oral contraceptives (including: Desogen®, Ortho-Cept, Ortho-Cyclen, Ortho Tri-Cyclen) as these are known to affect protein metabolism in females.
* Individuals with metabolic disorders including: Type I or Type II diabetes
* Individuals with a history of thrombosis / cardiovascular disease
* Individuals who use of anticoagulants
* Individuals with musculoskeletal / orthopedic disorders
* Individuals with knee injuries (i.e., ACL injuries).
* Individuals who have used tobacco products within the last 6 months
* Individuals with a history of neuromuscular problems
* Chronic usage of medications known to modulate skeletal muscle metabolism (i.e. corticosteroids, hormone replacement therapy (HRT), and over-the-counter supplements including creatine monohydrate) in the last 6 months.
* Individuals with allergies to milk proteins (whey or casein).
* Individuals with lactose intolerance
* Individuals with Phenylketonuria (PKU)
* Previous participation in amino acid tracer studies.
* Adherence to a vegetarian or vegan diet
* Current use of ketone supplements or adherence to a ketogenic diet
* Individuals who train more than ≥ 5 sessions of lower-body weightlifting /week for the previous 4 months

Minimum Eligible Age

18 Years

Maximum Eligible Age

40 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes