The Effect of Ketone Monoesters on Skeletal Muscle Protein Synthesis and Whole-body Protein Metabolism.

NCT07082309 | Recruiting

• 1 other identifier: 9482953
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

The ketone β-hydroxybutyrate (BHB) is endogenously produced during periods of low glucose availability, serving as an alternative metabolic fuel. Beyond its role as an energy substrate, BHB acts as a pleiotropic signalling molecule, modulating various physiological processes across multiple tissues. BHB can also be ingested orally as a ketone monoester, transiently elevating plasma concentrations of BHB to a level similar to those seen following several days of fasting, thereby obviating the need for dietary manipulation. The influence of BHB on human skeletal muscle protein metabolism remains poorly understood, although emerging evidence suggests that BHB may play a role in regulating muscle protein turnover. As such, BHB supplementation may support skeletal muscle remodelling and offer therapeutic benefits, and investigating this is of considerable interest. This study will investigate the ability of oral BHB ingestion - co-ingested with protein - to stimulate skeletal muscle anabolism in young healthy adults. A dual amino acid stable isotope tracer approach will be utilised to determine postprandial (i.e., fed state) muscle protein synthesis (MPS) rates and whole-body amino acid kinetics, given BHBs systemic effects. This research will advance our understanding of the fundamental biology of exogenous ketosis and provide insight into the potential of BHB supplementation as a novel nutritional strategy to optimise muscle mass and quality.

Conditions

Healthy Participants

Keywords

ketone monoesters; muscle protein synthesis; amino acid metabolism

Outcome Measures

Primary Outcomes (1)

• Skeletal muscle protein synthesis rates (FSR)

  Skeletal muscle protein synthesis rates

  5 hours (2 hours postabsorptive, 3 hours postprandial)

Secondary Outcomes (4)

• Plasma amino acid concentrations

  5 hours

• Whole-body phenylalanine kinetics assessed by stable isotope tracer methodology, including rate of appearance (Ra), rate of disappearance (Rd), hydroxylation rate, and net balance.

  5 hours (2 hours postabsorptive, 3 hours postprandial)

• Serum insulin concentrations

  5 hours

• Plasma beta hydroxybutyrate concentrations

  5 hours

Study Arms (2)

Control

ACTIVE COMPARATOR

Placebo with bitter agent (Bitrex), to flavour match to ketone condition, whey protein (0.3 g/kg), and milk fat (to match the caloric content of the ketone condition).

Dietary Supplement: Control

Ketone monoester

EXPERIMENTAL

Ketone monoester ((R)-3-hydroxybutyl (R)-3-hydroxybutyrate) and whey protein (0.3 g/kg)

Dietary Supplement: Ketone Monoester (KE) and whey protein beverage

Interventions

Ketone Monoester (KE) and whey protein beverage DIETARY_SUPPLEMENT

Ketone monoester ((R)-3-hydroxybutyl (R)-3-hydroxybutyrate) and whey protein (0.3 g/kg)

Ketone monoester

Control DIETARY_SUPPLEMENT

Placebo with bitter agent (Bitrex), to flavour match to ketone condition, whey protein (0.3 g/kg), and milk fat (to match the caloric content of the ketone condition).

Control

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• BMI 18-30

You may not qualify if:

• Body mass index (BMI) \< 18.5 or \> 30 kg/m2
• Age \< 18 or \> 40
• Regularly smokes
• Type 2 diabetes
• Cardiovascular disease, metabolic disease and hypertension (≥ 140/90 mmHg)
• Gastrointestinal disorders
• Use medicines that may impact protein metabolism or that are anti-inflammatory (determined at the screening)
• Pregnancy

Sponsors & Collaborators

• University of Exeter: lead

Study Sites (1)

Health and Life Sciences

Exeter, Devon, EX1 2LU, United Kingdom

RECRUITING

Central Study Contacts

Alistair Monteyne, PhD

CONTACT

+44 (0)1392 72 4774; a.monteyne2@exeter.ac.uk

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 3, 2025
• First Posted: July 24, 2025
• Study Start: June 4, 2025
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): July 1, 2027
• Last Updated: July 24, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)