search
Back to results

Leucine Co-ingestion and Myofibrillar Protein Synthesis in Older Adults

Primary Purpose

Aging, Sarcopenia

Status
Completed
Phase
Not Applicable
Locations
Canada
Study Type
Interventional
Intervention
Leucine
Placebo
Sponsored by
McMaster University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Aging focused on measuring Leucine, Protein, Diet, Muscle protein synthesis

Eligibility Criteria

65 Years - 85 Years (Older Adult)MaleAccepts Healthy Volunteers

Inclusion Criteria:

  • Body mass index (BMI) between 20-35 kg/m2
  • Non-smokers

Exclusion Criteria:

  • Diabetes mellitus, prediabetes and the metabolic syndrome
  • Cardiovascular disease
  • Neuromuscular problems or muscle wasting diseases
  • Renal disease
  • Gastrointestinal disease
  • Musculoskeletal conditions such as rheumatoid arthritis or osteoarthritis
  • Infectious disease
  • Cancer
  • Significant body mass loss in the 1 month period prior to the study
  • Vegetarianism
  • Use of medications known to interfere with muscle metabolism (i.e. beta-blockers, high dose non-steroidal anti-inflammatory drugs, corticosteroids, hormone replacement therapy, antiarrhythmic drugs, warfarin, prescription strength acne medications, oral hypoglycaemic agents and insulin)
  • Regular resistance training or daily step counts >9,000 or <3,500

Sites / Locations

  • McMaster University

Arms of the Study

Arm 1

Arm 2

Arm Type

Other

Other

Arm Label

Higher daily protein

Lower daily protein

Arm Description

Diets will provide protein intakes of 1.2 g/kg/d. Placebo with meals for 3 days, and leucine with meals for 3 days.

Diets will provide protein intakes of 0.8 g/kg/d. Placebo with meals for 3 days, and leucine with meals for 3 days.

Outcomes

Primary Outcome Measures

Myofibrillar protein fractional synthetic rate
The incorporation of a stable isotope (deuterium) into muscle tissue will allow for the determination of fractional synthetic rate, which is indicative of muscle protein synthesis.

Secondary Outcome Measures

Aminoacidemia in response to daily meals with and without leucine supplementation
Glycaemia in response to daily meals with and without leucine supplementation
Insulinemia in response to daily meals with and without leucine supplementation

Full Information

First Posted
February 13, 2015
Last Updated
March 14, 2016
Sponsor
McMaster University
Collaborators
Canadian Institutes of Health Research (CIHR)
search

1. Study Identification

Unique Protocol Identification Number
NCT02371278
Brief Title
Leucine Co-ingestion and Myofibrillar Protein Synthesis in Older Adults
Official Title
Influence of Leucine Co-ingestion With Mixed Meals on Integrative Myofibrillar Protein Synthesis in Older Adults
Study Type
Interventional

2. Study Status

Record Verification Date
March 2016
Overall Recruitment Status
Completed
Study Start Date
May 2015 (undefined)
Primary Completion Date
October 2015 (Actual)
Study Completion Date
October 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
McMaster University
Collaborators
Canadian Institutes of Health Research (CIHR)

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
The loss of muscle mass with aging is associated with a dysregulation of muscle protein synthesis (MPS) that is generally characterized by a suppressed MPS response to protein ingestion. This 'anabolic resistance' to protein feeding can be overcome with the ingestion of larger protein servings (~0.4g/kg/meal, equivalent to ~ 30 - 40g/meal); however, older adults would likely find it challenging to consume such quantities of protein on a per meal basis. The amino acid leucine has a unique role as a key 'activator' of MPS. Some research shows that increasing the leucine content of a suboptimal dose of a protein supplement can enhance the MPS response in older adults. However it is currently unknown whether the co-ingestion of leucine with normal, mixed meals can increase MPS. Furthermore, it has been suggested that leucine supplementation may only benefit older adults consuming suboptimal daily protein intakes. Therefore, the purpose of the current study is to examine the impact of leucine co-ingestion with mixed macronutrient meals on the myofibrillar protein synthetic response in older men consuming daily protein intakes at or below the current recommendations. A further objective is to determine whether the myofibrillar protein synthetic response to a session of resistance exercise is enhanced by leucine supplementation with meals. The investigators hypothesize that, in both the exercised and non-exercised condition, leucine co-ingestion at meals will enhance integrative myofibrillar protein synthesis in older adults consuming lower daily protein intakes, but will not augment MPS in those consuming higher daily protein. The investigators further hypothesize that the influence of leucine supplementation on MPS will be greater in the exercise condition than the non-exercise condition.
Detailed Description
At baseline, participants will be asked to wear a pedometer and to complete a physical activity and a weighed food record for 3 days. Resting energy expenditure (indirect calorimetry), body weight and body composition (DEXA) will be assessed in the fasted state. A strength test will be conducted to determine 1 repetition maximum (1-RM) and the maximum load that each participant can lift for 15 - 24 repetitions using a seated leg extension machine. Participants will then be randomized to one of two groups matched for age, activity level and BMI: higher (1.2 g/kg/d) or lower daily protein (0.8 g/kg/d). Participants will then commence a 9 day controlled diet (day -3 to 6) designed to meet energy requirements for weight maintenance and to provide a daily protein intake according to each participant's group allocation (i.e. 0.8 or 1.2 g/kg/d). All participants will be provided with flavored, supplemental beverages (Infinit Nutrition, Windsor, Ontario) and will be instructed to consume one beverage half way through each meal from day 0 - 5. Individual servings of the supplement will be packaged into a ziplocked pouch by Infinit Nutrition in power form. Participants will be required to add water to the power at home. During day 0 - 2 (unsupplemented period) the beverage will be a placebo (maltodextrin and sucrose), and during day 3 - 5 (leucine supplementation period) the beverage will contain crystalline leucine (5 g) with sucrose for flavour. The beverages will be provided in a single-blind manner, energy-matched and will be similar in odour, color, and taste. Participants will also be blinded to their group allocation. Aminoacidemia, insulinemia and glycaemia will be determined in response to breakfast, lunch and dinner ingestion during the unsupplemented (day 2) and leucine supplemented (day 5) periods. During each of these blood sampling trials blood samples will be obtained immediately before and 20, 40, 60, 90, 120, 180, 240 min following the ingestion of each meal (total of 25 x 4ml blood samples per participant per trial). Integrative MPS will be measured in the exercised and non-exercised leg over the unsupplemented (day 0 - 3) period and leucine supplemented (day 3 - 6) period using orally ingested deuterated water (D20) and muscle biopsies obtained from the vastus lateralis on days 0, 3 and 6. Participants will report to the laboratory in the fasted state on day 0 and, following a muscle biopsy from the vastus lateralis and saliva sample, participants will consume a single 100 ml oral bolus of D20 at approximately 0900. Immediately following the D20 bolus participants will perform a bout of unilateral leg extension exercise (3 sets to volitional failure at the maximum load they can lift for 15-24 repetitions (~40-50% 1-RM)). On day 3 participants will perform an identical resistance exercise session with the exception that repetitions will be clamped at the number achieved on day 0. Following both exercise sessions participants will consume their individualized breakfast (with the placebo beverage on day 0 and with the leucine beverage on day 3) in the laboratory before returning home. Bilateral muscle biopsies will be obtained prior to the exercise on day 3 (end of unsupplemented period) and on day 6 (end of leucine supplemented period). Total body water deuterium enrichment can be used as a surrogate for plasma alanine labelling and will be determined from saliva swabs collected by the participant every morning at 0900. Participants will be instructed to not eat or drink anything for 30 min before saliva sampling and samples will be stored in the participant's freezer before their next visit to the laboratory.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Aging, Sarcopenia
Keywords
Leucine, Protein, Diet, Muscle protein synthesis

7. Study Design

Primary Purpose
Prevention
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
Participant
Allocation
Randomized
Enrollment
20 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Higher daily protein
Arm Type
Other
Arm Description
Diets will provide protein intakes of 1.2 g/kg/d. Placebo with meals for 3 days, and leucine with meals for 3 days.
Arm Title
Lower daily protein
Arm Type
Other
Arm Description
Diets will provide protein intakes of 0.8 g/kg/d. Placebo with meals for 3 days, and leucine with meals for 3 days.
Intervention Type
Dietary Supplement
Intervention Name(s)
Leucine
Intervention Description
5 g leucine with sucrose and maltodextrin
Intervention Type
Dietary Supplement
Intervention Name(s)
Placebo
Intervention Description
5 g glycine with sucrose and maltodextrin
Primary Outcome Measure Information:
Title
Myofibrillar protein fractional synthetic rate
Description
The incorporation of a stable isotope (deuterium) into muscle tissue will allow for the determination of fractional synthetic rate, which is indicative of muscle protein synthesis.
Time Frame
3 days
Secondary Outcome Measure Information:
Title
Aminoacidemia in response to daily meals with and without leucine supplementation
Time Frame
3 days
Title
Glycaemia in response to daily meals with and without leucine supplementation
Time Frame
3 days
Title
Insulinemia in response to daily meals with and without leucine supplementation
Time Frame
3 days

10. Eligibility

Sex
Male
Minimum Age & Unit of Time
65 Years
Maximum Age & Unit of Time
85 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: Body mass index (BMI) between 20-35 kg/m2 Non-smokers Exclusion Criteria: Diabetes mellitus, prediabetes and the metabolic syndrome Cardiovascular disease Neuromuscular problems or muscle wasting diseases Renal disease Gastrointestinal disease Musculoskeletal conditions such as rheumatoid arthritis or osteoarthritis Infectious disease Cancer Significant body mass loss in the 1 month period prior to the study Vegetarianism Use of medications known to interfere with muscle metabolism (i.e. beta-blockers, high dose non-steroidal anti-inflammatory drugs, corticosteroids, hormone replacement therapy, antiarrhythmic drugs, warfarin, prescription strength acne medications, oral hypoglycaemic agents and insulin) Regular resistance training or daily step counts >9,000 or <3,500
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Stuart M Phillips, PhD
Organizational Affiliation
McMaster University
Official's Role
Principal Investigator
Facility Information:
Facility Name
McMaster University
City
Hamilton
State/Province
Ontario
ZIP/Postal Code
L8S 4K1
Country
Canada

12. IPD Sharing Statement

Citations:
PubMed Identifier
27935521
Citation
Murphy CH, Saddler NI, Devries MC, McGlory C, Baker SK, Phillips SM. Leucine supplementation enhances integrative myofibrillar protein synthesis in free-living older men consuming lower- and higher-protein diets: a parallel-group crossover study. Am J Clin Nutr. 2016 Dec;104(6):1594-1606. doi: 10.3945/ajcn.116.136424. Epub 2016 Nov 9.
Results Reference
derived

Learn more about this trial

Leucine Co-ingestion and Myofibrillar Protein Synthesis in Older Adults

We'll reach out to this number within 24 hrs