Impact of Varying Doses of Amino Acids on Exercise, Muscular and Mental Performance
Condition: Psychological Phenomena: Central Fatigue
MeSH terms: Fatigue
Study type: Interventional
Phase: Phase 1

Summary: 
      A number of studies have shown that ingestion of crystalline amino acids, in particular
      branched chain amino acids (BCAA) can affect endurance performance, markers of muscle damage,
      and possibly mental focus. It seems that the longer and lower intensity events are affected
      more by consumption of BCAA. This study will test the hypothesis that BCAA availability
      limits central fatigue (the feeling of tiredness). While various aspects of performance have
      been tested no study to date has tested multiple exercise, muscular, and mental performance
      aspects in a single study. Thus, the overall purpose of this study is to determine whether an
      amino acid supplement changes the mental and physical response to prolonged exercise versus a
      placebo (carbohydrate drink).

      This nutritional supplement could be useful on two levels. Improved mental focus and
      endurance performance and decreased central fatigue and muscle soreness could be valuable for
      enhancing athlete performance. Similarly, decreased central fatigue and muscle soreness may
      increase the willingness of the general public to exercise which could translate into
      decreased health risks and increased health benefits.
    

Detailed description: 
      Specific Purpose and Hypotheses

      In the current proposal we outline a study that will examine a comprehensive battery of tests
      to assess the efficacy of Amino Vital's Amino Acid (AA) formulation to improve physical and
      mental performance after exercise.

      We hypothesize:

        1. Ingestion of the Amino Acid (AA) formula will improve cognitive, motor, and physical
           performance on the post-exercise tasks in a hierarchical manner: 2AA > AA > placebo

        2. Blood concentrations of amino acids will be higher in the AA trials in a hierarchical
           manner: 2AA >AA > placebo

        3. Markers of muscle damage will be lower than placebo in a hierarchical manner: placebo >
           AA > 2AA

      Recruitment Methods and Process Recruitment methods will be passive. Participants will be
      made aware of the study through the use of Hamilton Health Science/Faculty of Health Sciences
      Research Ethics Board (HHS/FHS REB) approved posted flyers at McMaster University and will
      voluntarily initiate contact with the study team. A recruitment poster will also be submitted
      for posting on the McMaster Daily News webpage.

      Research Design and Methodology This study will use a double-blind repeated measures study
      design in which subjects will complete 7 sessions. The sessions consist of familiarization
      and the completion of three trials (placebo, AA, 2AA of AminoVital's formulation). Trials
      will be completed in a randomized, counterbalanced and blocked fashion such that with 12
      subjects, 2 participants complete each trial order: ABC, ACB, BCA, BAC, CAB, CBA.

      In the first session, participants will be screened using a standard health questionnaire.
      Interested participants will sign a consent form. They will then undergo testing of maximal
      oxygen consumption (VO2peak) using a treadmill. Subjects will also familiarize themselves
      with the physical and mental performance tests: Stroop test, profile of mood states (POMS),
      isometric strength test and an isokinetic muscle fatigue test. Following this initial
      session, participants will complete 3 trials (placebo, AA or 2AA drink formula) in random
      order.

      On the first day of a trial, participants will arrive at the lab in the morning after a day
      of dietary control and a standardized breakfast including the treatment beverage. Prior to
      beginning exercise, participants will complete the physical and mental performance tests. A
      small catheter (flexible plastic tube) will be inserted into a forearm vein by Dr. Phillips
      or a medically trained and qualified member of the laboratory group; Dr. Tarnopolsky is
      responsible for the individuals inserting the venous catheters. The needle will be removed
      promptly after the insertion of each catheter; only the catheters will remain in their arms
      until the end of the trial. The catheter will be used for repeated blood sampling over the
      next six hours (see Figure 1). Additionally, breath samples will be taken at the same time as
      the blood samples. Following the performance tests, and prior to the start of exercise, a
      baseline blood sample will be drawn. Participants will then perform a bout of endurance
      exercise that consists of treadmill walking for 180 minutes at 40% of their peak VO2.
      Following the start of exercise, participants will consume a treatment beverage (or placebo)
      every 20 minutes after the start of exercise and continuing until 20 minutes after exercise
      (see Figure 1). Following the exercise bout, participants will repeat the physical and mental
      performance tests.

      On the second day of a trial, participants will arrive after having consumed a standard
      breakfast including the treatment beverage. They will complete the physical and mental
      performance tests and one blood sample (4 mL) will be taken.

      The trial day breakfast will consist of energy estimated for each subject based on the
      Harris-Benedict equation with an activity factor of 30%. The diet will be 55:30:15 in terms
      of percent energy from carbohydrate:fat:protein. Subjects will consume the same diet on the
      days prior to each exercise trial to control for pre-study calorie and carbohydrate/fat
      intake, which could affect substrate oxidation. Subjects will refrain from consumption of
      alcohol and caffeine on the day of the trial. Trials will take place at least 5d (but no more
      than 10d) apart and will commence at a time between ~6-10am and will proceed according to the
      schematic timeline shown in figure 1. The testing time for subjects will remain consistent
      throughout the study. We also believe that it is prudent for subjects to consume a fixed and
      constant volume of water (500 ml with breakfast) during all trials to prevent dehydration and
      to allow subjects to complete the exercise in safe manner.

      Data Analyses/Statistics All data will be analyzed using a repeated measures two-way analysis
      of variance with time as a within factor and dose as a between factor. Significant ANOVA
      effects will be further scrutinized using Tukey's test as a post-hoc procedure. Where
      significant correlation of one variable with another exists, an analysis of covariance may
      also be performed. Significance will be accepted at P<0.05.

      Instrumentation Sample analysis will be carried out using a microplate reader/ELISA for
      creatine kinase (CK), C-reactive protein (CRP), lactate dehydrogenase (LDH) and myoglobin,
      glucose and lactate auto-analyzers, High Performance Liquid Chromatography (HPLC) for amino
      acids as well as a metabolic cart gas analyzer to analyze breath samples.
    

Intervention name(s): AminoVital Amino Acid formulation; Amino Vital Amino Acid formulation; Amino Vital Amino Acid formulation
Intervention type(s): Dietary Supplement; Dietary Supplement; Dietary Supplement
Intervention description(s): Contains minerals, vitamin C, flavour and sweetener.; Contains minerals, vitamin C, flavour and sweetener and an amino acid mixture (2.4g of AA as: leucine, isoleucine, valine, arginine and glutamine).; Contains minerals, vitamin C, flavour and sweetener and a double dose of the amino acid mixture (4.8 g of AA as: leucine, isoleucine, valine, arginine and glutamine).
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Treatment
Keywords: Branched Chain Amino Acids; Mental Performance; Muscular Performance; Central Fatigue Theory