Essential Amino Acids and Protein Kinetics During Caloric Deprivation

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

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.

Study Overview

• Status: Completed
• Conditions: Muscle Protein Synthesis; Whole-body Protein Balance
• Intervention / Treatment: Dietary supplement: Standard EAA; Dietary supplement: High EAA

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Natick, Massachusetts, United States, 01760
      • US Army Research Institute of Environmental Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 33 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Standard EAA Dose; EAA dose provided at 0.10 g/kg body mass	Dietary supplement: Standard EAA; EAA provided relative to body mass at a standard dose (0.10 g/kg) during energy deprivation
Experimental: High EAA Dose; EAA dose provided at 0.30 g/kg body mass	Dietary supplement: High EAA; EAA provided relative to body mass at a high dose (0.30 g/kg) during energy deprivation

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: United States Army Research Institute of Environmental Medicine
• Collaborators: University of Arkansas; Eastern Michigan University
• Investigators: Principal Investigator: Stefan M Pasiakos, PhD, Military Nutrition Division, USARIEM

Publications and helpful links

General Publications

• Gwin JA, Church DD, Hatch-McChesney A, Howard EE, Carrigan CT, Murphy NE, Wilson MA, Margolis LM, Carbone JW, Wolfe RR, Ferrando AA, Pasiakos SM. Effects of high versus standard essential amino acid intakes on whole-body protein turnover and mixed muscle protein synthesis during energy deficit: A randomized, crossover study. Clin Nutr. 2021 Mar;40(3):767-777. doi: 10.1016/j.clnu.2020.07.019. Epub 2020 Jul 22.

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2018
• Primary Completion (Actual): March 20, 2019
• Study Completion (Actual): March 20, 2019

Study Registration Dates

• First Submitted: October 31, 2017
• First Submitted That Met QC Criteria: December 8, 2017
• First Posted (Actual): December 14, 2017

Study Record Updates

• Last Update Posted (Actual): November 20, 2020
• Last Update Submitted That Met QC Criteria: October 28, 2020
• Last Verified: October 1, 2020

More Information

Terms related to this study

• Other Study ID Numbers: 17-32HC

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No