Essential Amino Acids and Protein Kinetics During Caloric Deprivation

• Sponsor: United States Army Research Institute of Environmental Medicine (U.S. Fed)
• Overall Status: Completed
• CT.gov ID: NCT03372928
• Collaborator: University of Arkansas (Other), Eastern Michigan University (Other)
• Enrollment: 20
• Location: 1
• Arms: 2
• Actual Duration (Months): 6.6
• Patients Per Site Per Month: 3

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Muscle Protein Synthesis; Whole-body Protein Balance	Dietary Supplement: Standard EAA; Dietary Supplement: High EAA	N/A

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 Design

• Study Type: Interventional
• Actual Enrollment: 20 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Intervention Model Description: Randomized, double-blind, cross-over controlled trialRandomized, double-blind, cross-over controlled trial
• Masking: Double (Participant, Investigator)
• Primary Purpose: Basic Science
• Official Title: The Effects of Varying Essential Amino Acid Intakes on Resting and Post-exercise Skeletal Muscle and Whole-body Protein Kinetics During Negative Energy Balance
• Actual Study Start Date: Sep 1, 2018
• Actual Primary Completion Date: Mar 20, 2019
• Actual Study Completion Date: Mar 20, 2019

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. Postprandial, Resting Muscle Protein Synthesis Rates [3 hour measure of muscle protein synthesis]

   Assessed using stable isotope infusions of phenylalanine.

2. Postprandial, Post-exercise Muscle Protein Synthesis Rates [3 hour measure of muscle protein synthesis]

   Assess using stable isotope infusions of phenylalanine.

3. 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 [3 hour measure of 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)

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 35 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	US Army Research Institute of Environmental Medicine	Natick	Massachusetts	United States	01760

Sponsors and Collaborators

• United States Army Research Institute of Environmental Medicine
• University of Arkansas
• Eastern Michigan University

Investigators

• Principal Investigator: Stefan M Pasiakos, PhD, Military Nutrition Division, USARIEM

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Jan 15, 2019
• Informed Consent Form - Oct 25, 2018

More Information

Publications

None provided.

• Responsible Party: United States Army Research Institute of Environmental Medicine
• ClinicalTrials.gov Identifier: NCT03372928
• Other Study ID Numbers: 17-32HC
• First Posted: Dec 14, 2017
• Last Update Posted: Nov 20, 2020
• Last Verified: Oct 1, 2020

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Study Results

Participant Flow

Pre-assignment Detail	This was a cross-over design study. 19 volunteers completed both the standard and high EAA testing phases.

Arm/Group Title	Low EAA First, Then High EAA	High EAA First, Then Low EAA
Arm/Group Description	Participants received EAA provided relative to body mass at a standard dose (0.10 g/kg; LOW)) during energy deprivation first, then received EAA provided relative to body mass at a high dose (0.3 g/kg; HIGH) during energy deprivation.	Participants received EAA provided relative to body mass at a high dose (0.30 g/kg; HIGH) during energy deprivation first, then received EAA provided relative to body mass at a low dose (0.1 g/kg; LOW) during energy deprivation.
Period Title: First Intervention (5 d Energy Deficit)
STARTED	10	10
COMPLETED	10	10
NOT COMPLETED	0	0
Period Title: First Intervention (5 d Energy Deficit)
STARTED	10	10
COMPLETED	10	9
NOT COMPLETED	0	1
Period Title: First Intervention (5 d Energy Deficit)
STARTED	10	9
COMPLETED	10	9
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	All Study Participants
Arm/Group Description	All participants were randomized to receive all interventions.
Overall Participants	19
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	23 (5)
Sex: Female, Male (Count of Participants)
Female	0 0%
Male	19 100%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	1 5.3%
Not Hispanic or Latino	18 94.7%
Unknown or Not Reported	0 0%
Body Mass Index (kilograms per meter squared) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kilograms per meter squared]	25.4 (2.7)

Outcome Measures

1. Primary Outcome

Title	Postprandial, Resting Muscle Protein Synthesis Rates
Description	Assessed using stable isotope infusions of phenylalanine.
Time Frame	3 hour measure of muscle protein synthesis

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Standard EAA Dose	High EAA Dose
Arm/Group Description	EAA dose provided at 0.10 g/kg body mass Standard EAA: EAA provided relative to body mass at a standard dose (0.10 g/kg) during energy deprivation	EAA dose provided at 0.30 g/kg body mass High EAA: EAA provided relative to body mass at a high dose (0.30 g/kg) during energy deprivation
Measure Participants	19	19
Mean (Standard Deviation) [percent per hour]	0.055 (0.01)	0.061 (0.02)

2. Primary Outcome

Title	Postprandial, Post-exercise Muscle Protein Synthesis Rates
Description	Assess using stable isotope infusions of phenylalanine.
Time Frame	3 hour measure of muscle protein synthesis

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Standard EAA	High EAA
Arm/Group Description	Arm: EAA dose provided at 0.10 g/kg body mass Standard EAA: EAA provided relative to body mass at a standard dose (0.10 g/kg) during energy deprivation	Arm: EAA dose provided at 0.30 g/kg body mass High EAA: EAA provided relative to body mass at a high dose (0.30 g/kg) during energy deprivation
Measure Participants	19	19
Mean (Standard Deviation) [percent per hour]	0.055 (0.01)	0.065 (0.02)

3. Primary Outcome

Title	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
Description	Assessed using stable isotope infusions of tyrosine. Net Whole-body Protein Balance is defined as whole-body protein synthesis - whole-body protein breakdown)
Time Frame	3 hour measure of whole-body protein balance

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Standard EAA	High EAA
Arm/Group Description	Arm: EAA dose provided at 0.10 g/kg body mass Low EAA: EAA provided relative to body mass at a standard dose (0.10 g/kg) during energy deprivation	Arm: EAA dose provided at 0.30 g/kg body mass High EAA: EAA provided relative to body mass at a high dose (0.30 g/kg) during energy deprivation
Measure Participants	19	19
Mean (Standard Deviation) [grams of protein per 180min]	2.7 (1.7)	21.3 (3.4)

Adverse Events

Time Frame	1 day
Adverse Event Reporting Description	non-serious adverse event
Arm/Group Title	Low EAA First, Then High EAA: Low EAA Treatment		High EAA First, Then Low EAA: Low EAA Treatment		Low EAA First, Then High EAA: High EAA Treatment		High EAA First, Then Low EAA: High EAA Treatment
Arm/Group Description	EAA dose provided at 0.10 g/kg body mass during first intervention, then EAA dose provided at 0.30 g/kg body mass during second intervention. Low EAA Treatment Period		EAA dose provided at 0.30 g/kg body mass during first intervention, then EAA dose provided at 0.10 g/kg body mass during second intervention. Low EAA Treatment Period		EAA dose provided at 0.10 g/kg body mass during first intervention, then EAA dose provided at 0.30 g/kg body mass during second intervention. High EAA Treatment Period		EAA dose provided at 0.30 g/kg body mass during first intervention, then EAA dose provided at 0.10 g/kg body mass during second intervention. High EAA Treatment Period
All Cause Mortality
	Low EAA First, Then High EAA: Low EAA Treatment		High EAA First, Then Low EAA: Low EAA Treatment		Low EAA First, Then High EAA: High EAA Treatment		High EAA First, Then Low EAA: High EAA Treatment
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/10 (0%)		0/10 (0%)		0/10 (0%)		0/10 (0%)
Serious Adverse Events
	Low EAA First, Then High EAA: Low EAA Treatment		High EAA First, Then Low EAA: Low EAA Treatment		Low EAA First, Then High EAA: High EAA Treatment		High EAA First, Then Low EAA: High EAA Treatment
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/10 (0%)		0/10 (0%)		0/10 (0%)		0/10 (0%)
Other (Not Including Serious) Adverse Events
	Low EAA First, Then High EAA: Low EAA Treatment		High EAA First, Then Low EAA: Low EAA Treatment		Low EAA First, Then High EAA: High EAA Treatment		High EAA First, Then Low EAA: High EAA Treatment
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/10 (0%)		0/10 (0%)		0/10 (0%)		1/10 (10%)
Skin and subcutaneous tissue disorders
mild erythema	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	1/10 (10%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.