Essential Amino Acids and Protein Kinetics During Caloric Deprivation

Study Overview
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Brief Summary
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The amount of essential amino acids (EAA) necessary to maximally stimulate muscle protein synthesis and optimize whole-body net protein balance during caloric deprivation has not been determined. This study will address that gap in knowledge by examining the resting and post-exercise muscle and whole-body protein kinetic responses to ingesting varying amounts of EAA after a 5 day period of negative energy balance. This study will provide the initial evidence to support the development of a recovery-based food product for military combat rations.

Detailed Description
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Short-term negative energy balance downregulates muscle protein synthesis and upregulates whole-body proteolysis and amino acid (AA) oxidation, thereby increasing nitrogen excretion and exacerbating whole-body and skeletal muscle protein loss. Consumption of quality proteins high in essential amino acid (EAA) content may attenuate protein loss during energy deficit by restoring whole-body and skeletal muscle anabolic potential to that observed in a eucaloric state. During energy balance, muscle protein synthesis appears to be maximally stimulated after consuming 15 g of EAA at rest and after conventional resistance-type exercise. In response to a short-term energy deficit that downregulated basal muscle protein synthesis by as much as 27%, consuming 15 g ( 7.5 g EAA) and 30 g ( 15 g EAA) of whey protein after a bout of resistance exercise restored muscle protein synthesis rates to resting, fasted rates observed in the eucaloric state in a dose dependent manner. The effect of EAA intakes above 15 g on resting and post-exercise muscle protein synthesis and the whole-body protein anabolic response during acute energy deficit has not been determined. This study will assess resting and post-resistance exercise whole-body and skeletal muscle protein synthesis responses to across a spectrum of EAA intakes following a well-controlled, short-term (5-d) energy deficit (30% energy deficit). Using a randomized, double-blind, cross-over design, 20 resistance trained (≥ 2 d/wk for the past 6 mo) adults will undergo two, non-consecutive 5-d energy deficit periods, separated by a 14-d washout period. Resting and post-resistance exercise (single leg exercise model) whole-body protein turnover and skeletal muscle protein synthesis responses to two different doses of EAA (standard, 0.10 g/kg vs high, 0.30 g/kg) will be determined the morning after completing the 5-d energy deficit. This design will test the hypothesis that higher absolute doses of EAA are required to maintain resting and post-exercise anabolic responses during energy deficit.

Official Title
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The Effects of Varying Essential Amino Acid Intakes on Resting and Post-exercise Skeletal Muscle and Whole-body Protein Kinetics During Negative Energy Balance

Conditions
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Muscle Protein Synthesis, Whole-body Protein Balance

Intervention / Treatment
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* Dietary Supplement: Standard EAA
* Dietary Supplement: High EAA


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men and women aged 18 - 35 years Body mass index < 30.0 kg/m2 Healthy without evidence of chronic illness or musculoskeletal injury as determined by the USARIEM Office of Medical Support and Oversight (OMSO) Resistance exercise trained defined by self-report as performing ≥ 2 sessions/wk for previous 6 mo Refrain from taking any nonsteroidal anti-inflammatory drugs (e.g., aspirin, Advil®, Aleve®, Naprosyn®), or any other aspirin-containing product for 10 days before starting and at least 5 days after completing the study Willing to refrain from alcohol, smoking any nicotine product (includes e-cigarettes); vaping, chewing tobacco, caffeine, and dietary supplement use throughout the entire study period Supervisor approval for federal civilian employees and non-HRV active duty military personnel working within the US Army Natick Soldier Systems Center Exclusion Criteria: Musculoskeletal injuries that compromise exercise capability as determined by the USARIEM Office of Medical Support and Oversight (OMSO) Metabolic or cardiovascular abnormalities, gastrointestinal disorders (e.g., kidney disease, diabetes, cardiovascular disease, etc.) Abnormal PT/PTT test or problems with blood clotting History of complications with lidocaine Present condition of alcoholism, anabolic steroids, or other substance abuse issues Blood donation within 8-wk of beginning the study Pregnancy (self-report or results of urine pregnancy test before body composition testing) Unwillingness or inability to consume study diets or foods provided

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

Sexes Eligible for Study
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All

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: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: Randomized, double-blind, cross-over controlled trial
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Standard EAA Dose<br>EAA dose provided at 0.10 g/kg body mass | Dietary Supplement: Standard EAA<br>* EAA provided relative to body mass at a standard dose (0.10 g/kg) during energy deprivation<br>|
| Experimental: High EAA Dose<br>EAA dose provided at 0.30 g/kg body mass | Dietary Supplement: High EAA<br>* EAA provided relative to body mass at a high dose (0.30 g/kg) during energy deprivation<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Postprandial, Resting Muscle Protein Synthesis Rates | Assessed using stable isotope infusions of phenylalanine. | 3 hour measure of muscle protein synthesis | 
| Postprandial, Post-exercise Muscle Protein Synthesis Rates | Assess using stable isotope infusions of phenylalanine. | 3 hour measure of muscle protein synthesis | 
| How Well Participants Suppress the Degradation of Body Proteins While Stimulating the Growth of New Proteins After Ingesting Varying Doses of EAA at Rest and After Exercise. Net Whole-body Protein Balance | Assessed using stable isotope infusions of tyrosine. Net Whole-body Protein Balance is defined as whole-body protein synthesis - whole-body protein breakdown) | 3 hour measure of whole-body protein balance |