Ketones and Muscle Protein Synthesis

Study Overview
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Brief Summary
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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: Ketone monoester Ketone monoester supplemented with sub-optimal dose of whey protein 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.

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

Conditions
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Ketosis, Regulation of Muscle Protein Synthesis

Intervention / Treatment
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* Dietary Supplement: Ketone
* Dietary Supplement: Ketone + Protein
* Dietary Supplement: Protein


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 35 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ketone<br>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<br>* 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<br>|
| Experimental: Ketone + Protein<br>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<br>* 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%)<br>|
| Experimental: Protein<br>Carbohydrate control and 10g of whey protein. | Dietary Supplement: Protein<br>* Isocaloric carbohydrate control: dextrose + stevia 10g Whey Protein L-[ring-2H5]-phenylalanine tracer (enriched to 4%)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ketone, protein metabolism, muscle