Skeletal Muscle Protein Synthetic Response to Amino Acid and Peptides

Skeletal muscle quality is an important determinant of exercise performance and overall health. It is vital for not just movement, but also metabolizing nutrients. Protein from the diet can promote muscle protein synthesis for muscle recovery and growth. More importantly, doing so shifts net protein balance positively (e.g. protein synthesis is greater than protein breakdown) and promotes greater rates of muscle protein turnover. Leucine is an amino acid required to build muscle, but it also acts as a signaling molecule informing the muscle to start protein synthesis. Before reaching skeletal muscle, dietary protein is digested into small peptides and free amino acids. Rate of absorption from the intestine to the blood stream is significantly faster for peptides compared to amino acids. As amino acid availability in the blood is a precursor for muscle protein synthesis, our objective is to determine if the different absorption rates between free amino acid and peptides influence muscle protein synthetic and breakdown rates.

Study Overview

• Status: Completed
• Conditions: Protein Metabolism
• Intervention / Treatment: Behavioral: Resistance Exercise; Behavioral: No Resistance Exercise; Dietary supplement: Leucine; Dietary supplement: Dileucine

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Illinois
    • Urbana, Illinois, United States, 61801
      • Freer Hall

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 35 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Recreationally-active adults: ≥ 30 min of physical activity at moderate intensity ≥ 3 times per week
• Ages: 18-35 years old
• English fluency

Exclusion Criteria:

• Tobacco, nicotine (patch/gum) use (previous 6 mo)
• Alcohol consumption >10 drinks per week
• Metabolic disorders (e.g., Metabolic Syndrome, Diabetes, thyroid diseases)
• Cardiovascular disease, arrhythmias
• Hypogonadism
• Asthma
• History of uncontrolled hypertension
• Orthopedic injury/surgery (within 1 yr)
• Hepatorenal, musculoskeletal, autoimmune, or neurological disease
• History of neuromuscular problems
• Previous participation in amino acid tracer studies
• Predisposition to hypertrophic scarring or keloid formation
• Consumption of ergogenic-levels of dietary supplements that may affect muscle mass (e.g., creatine, HMB), insulin-like substances, or anabolic/catabolic pro-hormones (e.g., DHEA) within 6 weeks prior to participation
• Consumption of thyroid, androgenic, or other medications known to affect endocrine function
• Consumption of medications known to affect protein metabolism (e.g., prescription-strength corticosteroids, non-steroidal anti-inflammatories, or acne medication)
• Currently pregnant

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Leucine; Participants will be allocated to an exercise or non-exercise group. After resistance exercise (or equivalent time point for non-exercise group), participants will consume 2g leucine powder dissolved in 250 mL of water.	Behavioral: Resistance Exercise; Prior to protein consumption participants will perform an acute bout of resistance exercise. They will warm up with two sets of 10 repetitions at 35-75% working load respectively, then perform four working sets of 10-12 repetitions at 65-70% of 1-RM. 1 min, 30 sec rest periods will be implemented between each set.; Behavioral: No Resistance Exercise; Participants allocated to this group will not perform exercise prior to the administration of the nutritional intervention. Participants will remain at rest throughout the trial.; Dietary supplement: Leucine; Participants will be given 2g of leucine dissolved in 250mL of water. Drink will be consumed immediately after exercise or equivalent time point for non-exercise group.
Experimental: Leucine Peptide (Dileucine); Participants will be allocated to an exercise or non-exercise group. After resistance exercise (or equivalent time point for non-exercise group), participants will consume 2g protein peptide powder dissolved in 250 mL of water.	Behavioral: Resistance Exercise; Prior to protein consumption participants will perform an acute bout of resistance exercise. They will warm up with two sets of 10 repetitions at 35-75% working load respectively, then perform four working sets of 10-12 repetitions at 65-70% of 1-RM. 1 min, 30 sec rest periods will be implemented between each set.; Behavioral: No Resistance Exercise; Participants allocated to this group will not perform exercise prior to the administration of the nutritional intervention. Participants will remain at rest throughout the trial.; Dietary supplement: Dileucine; Participants will be given 2g of dileucine dissolved in 250mL of water. Drink will be consumed immediately after exercise or equivalent time point for non-exercise group.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Fractional Synthetic Rate of Mixed Muscle Proteins	Mixed muscle protein synthesis rates will be assessed during the 3.5hr Postabsorptive period (e.g. non-fed state) and the 3hr postprandial period (e.g. fed state) for both experimental interventions (e.g. leucine and leucine peptide). This will allow us to assess the change in fractional synthetic rate from the Postabsorptive period to the postprandial period.	Postabsorptive for 3.5 hours, Postprandial for 3 hours.
Fractional Synthetic Rate of Myofibrillar Proteins	Myofibrillar muscle protein synthesis rates will be assessed during the 3.5hr Postabsorptive period (e.g. non-fed state) and the 3hr postprandial period (e.g. fed state) for both experimental interventions (e.g. leucine and leucine peptide). This will allow us to assess the change in fractional synthetic rate from the Postabsorptive period to the postprandial period.	Postabsorptive for 3.5 hours, Postprandial for 3 hours.
Fractional Breakdown Rate of Mixed Muscle Proteins	Mixed muscle protein breakdown rates will be assessed during the first hour of the postprandial period (e.g. fed state) for both experimental interventions (e.g. leucine and leucine peptide). This will allow us to assess the change in fractional breakdown rate for each respective experimental intervention.	Postprandial for 1 hour

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phosphorylation of muscle anabolic signaling	Phosphorylation of anabolic signaling pathways will be assessed in the fasted state and after the ingestion of the experimental interventions.	Baseline, immediately after ingestion of leucine/leucine peptides, and 3 hours after ingestion of leucine/leucine peptides

Collaborators and Investigators

• Sponsor: University of Illinois at Urbana-Champaign
• Investigators: Principal Investigator: Nicholas A. Burd, Ph.D., University of Illinois at Urbana-Champaign

Study record dates

Study Major Dates

• Study Start (Actual): May 3, 2019
• Primary Completion (Actual): November 20, 2019
• Study Completion (Actual): November 20, 2019

Study Registration Dates

• First Submitted: May 8, 2019
• First Submitted That Met QC Criteria: May 14, 2019
• First Posted (Actual): May 16, 2019

Study Record Updates

• Last Update Posted (Actual): September 28, 2020
• Last Update Submitted That Met QC Criteria: September 24, 2020
• Last Verified: September 1, 2020

More Information

Terms related to this study

• Keywords: Metabolism; Muscle Protein Synthesis; Muscle Protein Breakdown; Amino Acid Peptides
• Other Study ID Numbers: 18897

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