Exogenous Ketosis and Muscle Protein Synthesis During Exercise Recovery

NCT06769100 | Completed

• 1 other identifier: A00-M15-24A
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Ketosis; Muscle Protein Synthesis; Dietary Proteins; Resistance Exercise

Keywords

Ketosis; Regulation of Muscle Protein Synthesis; Resistance Exercise; Post-Exercise Recovery; Whey Protein

Outcome Measures

Primary Outcomes (1)

• Myofibrillar fractional synthesis rate

  Quantification of changes in basal myofibrillar fractional synthetic rate (%/hour) in the rested and exercised limbs.

  0 - 5 hours in the postprandial period.

Secondary Outcomes (14)

• Time-course data for plasma enrichments (in moles percent excess) of L-[ring-2H5]-phenylalanine

  Baseline, 3 hours pre-prandial, and 5 hours into the postprandial period.

• Incremental area under the curve for total amino acid concentration

  3 hours pre-prandial to 5 hours postprandial

• Time-course data for total amino acid concentration

  Baseline, 3 hours pre-prandial, and 5 hours into the postprandial period.

• Incremental area under the curve for essential amino acid concentration

  3 hours pre-prandial to 5 hours postprandial

• Time-course data for essential amino acid concentration

  Baseline, 3 hours pre-prandial, and 5 hours into the postprandial period.

Study Arms (4)

Ketone Monoester (KET)

EXPERIMENTAL

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

Dietary Supplement: Ketone Monoester (KET); Other: Resistance exercise

Ketone Monoester + Whey Protein (KET+PRO)

EXPERIMENTAL

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

Dietary Supplement: Ketone Monoester + Whey Protein (KET+PRO); Other: Resistance exercise

Whey Protein (PRO)

EXPERIMENTAL

25g of whey protein.

Dietary Supplement: Whey Protein (PRO); Other: Resistance exercise

Placebo drink (CON)

PLACEBO COMPARATOR

Flavoured water.

Dietary Supplement: Flavour matched placebo (CON); Other: Resistance exercise

Interventions

Ketone Monoester (KET) 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

Ketone Monoester (KET)

Ketone Monoester + Whey Protein (KET+PRO) 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%)

Ketone Monoester + Whey Protein (KET+PRO)

Whey Protein (PRO) DIETARY_SUPPLEMENT

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

Whey Protein (PRO)

Flavour matched placebo (CON) DIETARY_SUPPLEMENT

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

Placebo drink (CON)

Resistance exercise 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 (KET); Ketone Monoester + Whey Protein (KET+PRO); Placebo drink (CON); Whey Protein (PRO)

Eligibility Criteria

• Age: 18 Years - 40 Years
• Gender Eligibility Details: Cis males and Cis females
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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).

You may not qualify if:

• 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)

Sponsors & Collaborators

• McGill University: lead

Study Sites (1)

McGill University

Montreal, Quebec, H2W 1S4, Canada

Location

MeSH Terms

Conditions

Ketosis

Interventions

Whey Proteins; Resistance Training

Condition Hierarchy (Ancestors)

Acidosis; Acid-Base Imbalance; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Milk Proteins; Animal Proteins, Dietary; Dietary Proteins; Proteins; Amino Acids, Peptides, and Proteins; Whey; Milk; Dairy Products; Food; Diet, Food, and Nutrition; Physiological Phenomena; Food and Beverages; Exercise Therapy; Rehabilitation; Aftercare; Continuity of Patient Care; Patient Care; Therapeutics; Physical Therapy Modalities; Physical Conditioning, Human; Exercise; Motor Activity; Movement; Musculoskeletal Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena

Study Officials

• Tyler Churchward-Venne, PhD

  Department of Kinesiology and Physical Education, McGill University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: 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.
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: January 6, 2025
• First Posted: January 10, 2025
• Study Start: January 10, 2025
• Primary Completion: March 2, 2026
• Study Completion: March 2, 2026
• Last Updated: March 23, 2026

Record last verified: 2026-03

Locations

CA (1)