Skeletal Muscle Protein Synthetic Response to Amino Acid and Peptides

Study Overview
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Brief Summary
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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.

Official Title
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Skeletal Muscle Protein Synthetic Response to Amino Acid and Peptides

Conditions
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Protein Metabolism

Intervention / Treatment
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* Behavioral: Resistance Exercise
* Behavioral: No Resistance Exercise
* Dietary Supplement: Leucine
* Dietary Supplement: Dileucine


Participation Criteria
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Eligibility Criteria
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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

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
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Leucine<br>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<br>* 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.<br>Behavioral: No Resistance Exercise<br>* 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.<br>Dietary Supplement: Leucine<br>* 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.<br>|
| Experimental: Leucine Peptide (Dileucine)<br>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<br>* 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.<br>Behavioral: No Resistance Exercise<br>* 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.<br>Dietary Supplement: Dileucine<br>* 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.<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Metabolism, Amino Acid Peptides, Muscle Protein Synthesis, Muscle Protein Breakdown