Exogenous Ketosis and Muscle Protein Synthesis During Exercise Recovery

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

Interventions

DIETARY_SUPPLEMENT

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

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%)

DIETARY_SUPPLEMENT

Whey Protein (PRO)

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

DIETARY_SUPPLEMENT

Flavour matched placebo (CON)

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

OTHER

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.

Sponsors & Collaborators

• McGill University

  lead OTHER

Principal Investigators

• Tyler Churchward-Venne, PhD · Department of Kinesiology and Physical Education, McGill University

Study Design

Allocation

RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

TRIPLE

Model

PARALLEL

Eligibility

Min Age

18 Years

Max Age

40 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2025-01-10

Primary Completion

2026-03-02

Completion

2026-03-02

Countries

• Canada

Study Locations