Effects of Short-term Energy Deficit on Muscle Protein Turnover

March 14, 2016 updated by: Stuart M. Phillips, McMaster University
Weight loss through energy restriction results in the loss of both fat and muscle mass. Muscle mass is important for mobility, strength, glucose control and energy expenditure, and therefore the retention of muscle mass during energy restriction is an important goal. The retention of muscle mass depends on the balance between muscle protein synthesis (MPS) and muscle protein breakdown (MPB). It is well known that MPS is reduced during weight loss, however the effect of weight loss on MPB is currently a topic of debate. The purpose of this study is to assess the effect of short-term (10 day) weight loss (40% energy deficit) on both MPS and MPB in order to gain insight into the mechanisms causing muscle loss during energy restriction. In addition, the effect of resistance exercise and protein (both known to preserve muscle mass) on MPS and MPB will be examined

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

An undesirable consequence of energy restriction is the loss of muscle mass. Muscle mass is determined by the the rates of two processes: muscle protein synthesis and muscle protein breakdown. It has been consistently shown that a reduced rate of muscle protein synthesis exists during energy restriction. However, it is currently unclear whether an increase in muscle protein breakdown also contributes to muscle mass loss. In addition, the effect of high protein diets and resistance exercise on muscle protein turnover during energy restriction, two interventions known to preserve muscle, remains to be investigated.We aim to demonstrate that the decrease in muscle protein synthesis is the main contributor to a negative protein balance during energy restriction. In addition, we hope to show that a higher-protein diet (2.4g/kg/d versus 1.2g/kg/d) and the addition of resistance exercise can help to maintain the muscle protein synthesis rate and thereby improve negative protein balance.The present study will be designed as a parallel group randomized controlled trial. Subjects will be given pre-packaged diets (Copper County Foods) to consume which will put them in a relative energy deficit of 40% per day. Based on random assignment, these subjects will either consume an adequate protein diet (1.2g/kg/d) or a high protein diet (2.4g/kg/d) for 10 consecutive days. Participants in the adequate protein diet will consume a ratio of 50:35:15 (carbohydrates:fat:protein) while subjects within the high protein diet will consume a ratio of 50:15:35 (carbohydrates:fat:protein). Subjects will undergo testing at baseline and following a 10 day dietary and unilateral resistance exercise intervention. Testing will consist of muscle and blood samples. Muscle protein synthesis and muscle protein breakdown will be measured using stable isotope tracers that are orally ingested (deuterated water) or infused into an antecubital vein (labelled phenylalanine tracers) before and after the 10 day diet.

Study Type

Interventional

Enrollment (Actual)

24

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

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

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

20 years to 30 years (Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

Male

Description

Inclusion Criteria:

  • Between the ages of 20 and 30 years inclusive
  • Have a BMI between 25 and 33 inclusive

Exclusion Criteria:

  • Have a body mass index less than 25 kg/m2 or greater than 33 kg/m2.
  • Vegan
  • History of allergy, sensitivity, or strong dislike towards dairy protein
  • Smoker or user of tobacco products
  • High physical activity
  • Have health problems such as: renal or gastrointestinal disorders, metabolic disease, heart disease, vascular disease, rheumatoid arthritis, diabetes, poor lung function, uncontrolled blood pressure, dizziness, thyroid problems, or any other health conditions for which volunteers are being treated that might put them at risk for this study.
  • Taking anti-diabetic, anti-inflammatory, platelet inhibitor, or anti-coagulant medications
  • Use of an investigational drug product within the last 30 days
  • Have participated in an infusion protocol in the last year
  • Do not understand English or have a condition the PI believes would interfere with the ability to provide informed consent, comply with the study protocol, or which might confound the interpretation of the study results or put volunteers at undue risk

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: High Protein
2.4g protein/kg/d. The macronutrient composition will be 50:15:35 (carbohydrates:fat:protein) during Energy Restriction
Other: Energy Restriction
All meals will be provided for the duration of the energy restriction intervention and the energy deficit will be calculated based on estimated energy requirements by indirect calorimetry to provide 60% of energy requirements. In addition, one leg will be assigned to perform resistance exercise for 5 days during the 10 day energy deficit.
Experimental: Adequate Protein
1.2g protein/kg/d. The macronutrient composition will be 50:35:15 (carbohydrates:fat:protein) during Energy Restriction
Other: Energy Restriction
All meals will be provided for the duration of the energy restriction intervention and the energy deficit will be calculated based on estimated energy requirements by indirect calorimetry to provide 60% of energy requirements. In addition, one leg will be assigned to perform resistance exercise for 5 days during the 10 day energy deficit.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Muscle protein turnover
Time Frame: Baseline and 10 days
Change in muscle protein synthesis and muscle protein breakdown before and after the weight loss diet will be assessed. The relationship between high protein diets (parallel groups) and exercise (unilateral resistance exercise) on muscle protein turnover will also be examined. Muscle protein synthesis and muscle protein breakdown will be measured with stable isotope infusions of labelled phenylalanine tracers before and after the 10 day diet. In addition, long term muscle protein synthesis will be measured with orally ingested deuterated water.
Baseline and 10 days

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Molecular markers
Time Frame: Baseline and 10 days
Change in the the transcriptional expression of genes involved in the ubiquitin-proteasome pathway (main regulator of muscle protein breakdown) measured in muscle samples obtained at baseline and following the 10 day dietary intervention by quantitative polymerase chain reaction (qPCR). These same samples will be analyzed by western blot for the expression of active and inactive isoforms of caspase-3, an important component of muscle protein breakdown. Finally, immunoprecipitation and western blot will be used to examine the ubiquitination of translation initiation factors at baseline and following the 10 day intervention
Baseline and 10 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

McMaster University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

June 1, 2015

Primary Completion (Actual)

January 1, 2016

Study Completion (Actual)

January 1, 2016

Study Registration Dates

First Submitted

March 28, 2015

First Submitted That Met QC Criteria

March 28, 2015

First Posted (Estimate)

April 1, 2015

Study Record Updates

Last Update Posted (Estimate)

March 16, 2016

Last Update Submitted That Met QC Criteria

March 14, 2016

Last Verified

March 1, 2016

More Information

Terms related to this study

Keywords

Other Study ID Numbers

  • Not assigned (Charles A. Dana Foundation Brain and Immuno-Imaging Grant)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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