Ketones and Muscle Protein Synthesis

The Effects of Acute Nutritional Ketosis on Myofibrillar Protein Synthesis in Young Men

Ketones are natural substances normally produced by the body during prolonged fasting and starvation, or in response to a "ketogenic" diet to be used as fuel by the brain and muscles. Ketones are therefore similar to dietary proteins, carbohydrates and fats since they represent a source of energy for the body. In addition to serving as a source of energy, ketones have also been shown to stimulate increased rates of muscle protein synthesis in humans.

The ingestion of dietary protein is well established to stimulate an increase in the rate of protein synthesis in skeletal muscle. The rate of muscle protein synthesis can be maximized following the intake of 20g of protein. As a result, smaller doses of protein (i.e. 10g) represent a sub-optimal dose of protein because there is still room for improvement concerning muscle protein synthesis.

Recently ketone-containing food products have become available that elevate ketone levels in the body without the need for ketogenic diets or prolonged fasting. Therefore, the purpose of this study is to measure skeletal muscle protein synthesis rates after ingesting the following:

1. Ketone monoester
2. Ketone monoester supplemented with sub-optimal dose of whey protein
3. Sub-optimal dose of whey protein

It is hypothesized that muscle protein synthesis rates will increase following the ingestion of a ketone-containing beverage. Further, muscle protein synthesis rates will be enhanced when the ketone-containing beverage and sub-optimal protein dose are taken together.

Study Overview

• Status: Completed
• Conditions: Ketosis; Regulation of Muscle Protein Synthesis
• Intervention / Treatment: Dietary supplement: Ketone; Dietary supplement: Ketone + Protein; Dietary supplement: Protein

• Study Type: Interventional
• Enrollment (Actual): 36
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Canada
  • Quebec
    • Montreal, Quebec, Canada, H2W 1S4
      • Exercise Metabolism and Nutrition Research Laboratory

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 33 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Male
• Aged between 18-35 years inclusive
• Healthy, moderately active
• BMI < 30 kg/m2 and > 18.5 kg/m2
• Having given informed consent

Exclusion Criteria:

• Presence of any identified metabolic or intestinal disorders
• Use of tobacco products
• Allergies to milk proteins (whey or casein)
• Lactose intolerance
• Phenylketonuria (PKU)
• A history of neuromuscular problems
• Previous participation in amino acid tracer studies
• Adherence to a strict vegetarian or vegan diet
• Current use of ketone supplements or adherence to a ketogenic diet
• Use of medications known to affect protein metabolism
• Diagnosis of Diabetes
• Engagement in sports or physical exercise 5 or more days per week

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ketone; Ketone monoester supplement (R)-3-hydroxybutyl (R)-3-hydroxybutyrate based on participants' body weight (0.36g/kg body weight) and carbohydrate control.	Dietary supplement: Ketone; Ketone monoester supplement (R)-3-hydroxybutyl (R)-3-hydroxybutyrate based on participants' body weight (0.36g/kg body weight); Isocaloric carbohydrate control: dextrose + vanilla flavouring
Experimental: Ketone + Protein; Ketone monoester supplement (R)-3-hydroxybutyl (R)-3-hydroxybutyrate based on participants' body weight (0.36g/kg body weight) and 10g of whey protein.	Dietary supplement: Ketone + Protein; Ketone monoester supplement (R)-3-hydroxybutyl (R)-3-hydroxybutyrate based on participants' body weight (0.36g/kg body weight); 10g Whey Protein; L-[ring-2H5]-phenylalanine tracer (enriched to 4%)
Experimental: Protein; Carbohydrate control and 10g of whey protein.	Dietary supplement: Protein; Isocaloric carbohydrate control: dextrose + stevia; 10g Whey Protein; L-[ring-2H5]-phenylalanine tracer (enriched to 4%)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Fractional synthetic rate of muscle protein synthesis (myofibrillar)	0-5 hours in the post-prandial period

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Fractional synthetic rate of muscle protein synthesis (myofibrillar)		0-3 hours in the pre-prandial period; 0-2 hours, and 2-5 hours into the post-prandial period
Plasma enrichments (in moles percent excess) of L-[ring-2H5]-phenylalanine		3 hours pre-prandial to 5 hours post-prandial
Plasma glucose concentration (mmol/L)		3 hours pre-prandial to 5 hours post-prandial
Plasma insulin concentration (pmol/L)		3 hours pre-prandial to 5 hours post-prandial
Plasma amino acid concentrations (mmol/L)		3 hours pre-prandial to 5 hours post-prandial
Capillary blood Beta-OHB concentrations (mmol/L)		0-5 hours in the post-prandial period
Signaling molecule phosphorylation status	The use of Western blots to measure the phosphorylation status of signaling molecules involved in protein synthesis ie. mTOR, p70S6k, 4E-BP1	0, 2, and 5 hours into the post-prandial period

Collaborators and Investigators

• Sponsor: McGill University

Study record dates

Study Major Dates

• Study Start (Actual): September 21, 2020
• Primary Completion (Actual): May 14, 2021
• Study Completion (Actual): May 14, 2021

Study Registration Dates

• First Submitted: September 17, 2020
• First Submitted That Met QC Criteria: September 24, 2020
• First Posted (Actual): September 25, 2020

Study Record Updates

• Last Update Posted (Actual): May 18, 2021
• Last Update Submitted That Met QC Criteria: May 17, 2021
• Last Verified: May 1, 2021

More Information

Terms related to this study

• Keywords: muscle; protein metabolism; ketone
• Additional Relevant MeSH Terms: Metabolic Diseases; Acid-Base Imbalance; Acidosis; Ketosis
• Other Study ID Numbers: A11-M51-19A

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No