Role of Leucine in the Regulation of Human Myofibrillar Protein Synthesis at Rest and Following Resistance Exercise

Muscle mass is normally maintained through the regulated balance between the processes of protein synthesis (i.e. making new muscle proteins) and protein breakdown (breaking down old muscle proteins). Proteins are composed of amino acids and we know that amino acids increase muscle protein synthesis. However, not all amino acids are the same. Essential amino acids are ones that must be consumed through food, while non-essential amino acids can be made by our body. Interestingly, the essential amino acids are all that are required to increase the rate of muscle protein synthesis. In addition, the essential amino acid leucine appears to be particularly important in regulating protein synthesis. However, how leucine is able to increase protein synthesis is not entirely understood. Previously, it has been shown that 20-25 g of high-quality protein, such as that found in milk, appears to be the amount of protein that maximizes the rate of muscle protein synthesis after performing a bout of resistance exercise. Thus, the aim is to measure the synthesis of new muscle proteins after ingesting the following:

1. 25g whey protein
2. 6.25g whey protein supplemented with leucine
3. 6.25g whey protein supplemented with essential amino acids but no leucine

The investigators will measure muscle protein synthesis after consumption of the above beverages in a leg that has done no exercise ( ie. a rested leg) and in the other leg that has done resistance exercise. The hypothesis is that 6.25g whey supplemented with leucine will stimulate muscle protein synthesis as effectively as 25g whey, but that 6.25g whey supplemented will all the essential amino acids except whey will be less effective at increasing muscle protein synthesis. Whey protein is a dairy-based protein found in cow's milk, thus when you drink a glass of milk you are consuming some whey protein. However, the investigators will be using an isolated form of whey protein, meaning it has been removed from milk. As mentioned previously, amino acids are 'strung-together' to make protein. The 'essential' amino acids must be consumed through food because our body cannot make them, thus they are consumed when you eat protein-rich foods like milk or chicken.

Study Overview

• Status: Completed
• Conditions: Regulation of Muscle Protein Synthesis
• Intervention / Treatment: Dietary supplement: whey protein; Dietary supplement: whey protein supplemented with leucine; Dietary supplement: whey protein supplemented with essential amino acids

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Hamilton, Ontario, Canada, L8S 4K1
      • Exercise Metabolism Research Laboratory, McMaster Univeristy

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 35 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• male
• 18-35 years of age
• non-smoker/ non-tobacco product user

Exclusion Criteria:

• heart disease
• vascular disease
• rheumatoid arthritis
• diabetes
• poor lung function
• uncontrolled blood pressure
• dizziness
• thyroid problems

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: SINGLE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: 25 g protein; 25 g whey protein	Dietary supplement: whey protein; 25 g whey protein; Other Names: whey protein powder
EXPERIMENTAL: 6.25 g protein supplemented with leucine	Dietary supplement: whey protein supplemented with leucine; 6.25 g whey protein supplemented with free form leucine; Other Names: whey protein powder supplemented with free-form leucine
EXPERIMENTAL: 6.25 g whey protein with EAA; 6.25 g protein supplemented with a mixture of essential amino acids devoid of leucine	Dietary supplement: whey protein supplemented with essential amino acids; 6.25 g whey protein supplemented with essential amino acids devoid of leucine; Other Names: whey protein supplemented with EAA devoid of leucine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Muscle protein synthesis	Muscle protein synthesis will be expressed as fractional synthetic rate (FSR) by dividing the increment in enrichment in the product, i.e. protein-bound C13phe, by the enrichment of the precursor (= intracellular availability).	5 hours postprandial

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Signaling molecule phosphorylation status	Western blot will be used to measure the phosphorylation status of signaling molecules involved in protein synthesis ie. mTOR, p70S6k, 4E-BP1.	1, 3, and 5 hours

Collaborators and Investigators

• Sponsor: McMaster University
• Collaborators: Canadian Institutes of Health Research (CIHR); University of California, Davis; Natural Sciences and Engineering Research Council, Canada

Publications and helpful links

General Publications

• Churchward-Venne TA, Burd NA, Mitchell CJ, West DW, Philp A, Marcotte GR, Baker SK, Baar K, Phillips SM. Supplementation of a suboptimal protein dose with leucine or essential amino acids: effects on myofibrillar protein synthesis at rest and following resistance exercise in men. J Physiol. 2012 Jun 1;590(11):2751-65. doi: 10.1113/jphysiol.2012.228833. Epub 2012 Mar 25.

Study record dates

Study Major Dates

• Study Start: June 1, 2010
• Primary Completion (ACTUAL): August 1, 2010
• Study Completion (ACTUAL): September 1, 2010

Study Registration Dates

• First Submitted: December 12, 2011
• First Submitted That Met QC Criteria: December 12, 2011
• First Posted (ESTIMATE): December 14, 2011

Study Record Updates

• Last Update Posted (ACTUAL): February 24, 2020
• Last Update Submitted That Met QC Criteria: February 21, 2020
• Last Verified: February 1, 2020

More Information

Terms related to this study

• Keywords: resistance exercise; skeletal muscle; protein; leucine; FSR
• Other Study ID Numbers: LEU-10-141