Development of Oral Amino Acid Tracers to Study Protein Turnover in Humans
- Conditions
- Healthy Adult Males
- Interventions
- Dietary Supplement: Crystalline amino acids to assess myofibrillar protein synthesis ratesDietary Supplement: Crystalline amino acids to assess whole-body protein turnover, amino acid oxidation, and net protein balance
- Registration Number
- NCT04887727
- Lead Sponsor
- University of Toronto
- Brief Summary
Previous studies have used a combination of oral L-\[1-13C\]leucine and intravenous labeled L-\[5,5,5-2H3\]leucine to assess the acute postprandial changes in whole-body protein turnover (12, 19). Intravenous and dietary-labeled amino acid tracers have also been used in tandem to assess rates of myofibrillar protein synthesis in response to bolus protein ingestion and resistance exercise (46). By validating whole-body net balance to myofibrillar protein synthesis, our proposed multi-tracer approach will develop minimally invasive models to study protein turnover in a variety of populations in which traditional infusions and/or repeated blood samples are not possible (i.e. pediatric, free-living populations).
- Detailed Description
The primary objective of the proposed study is to validate the use of a novel oral tracer model to accurately and reliably measure myofibrillar protein synthesis. It is hypothesized that oral L-\[1-13C\]leucine and L-\[ring-2H5\]phenylalanine, ingested as a bolus to mimic an intravenous 'pulse dose' administration (51, 65), will reveal similar rates of myofibrillar protein synthesis when compared to traditional intravenous L-\[5,5,5-2H3\]leucine infusion. Moreover, it is hypothesized that both methods will reveal the expected graded changes in myofibrillar protein synthesis in response to feeding and resistance exercise (i.e. fasted\<feeding\<exercise \& feeding).
The secondary objective of the proposed study is to develop and validate non-invasive models to measure whole-body amino acid oxidation and net balance in response to feeding and resistance exercise. It is hypothesized that whole-body net balance, as determined by a novel oral tracer model (i.e. L-\[1-13C\]leucine) , will align with traditional intravenous tracer methodology (i.e. L-\[5,5,5-2H3\]leucine) and reveal the expected physiological changes in whole-body protein turnover in response to feeding and resistance exercise (i.e. fasted\<feeding\<exercise \& feeding).
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Male
- Target Recruitment
- 22
- Male
- Currently performing structured physical activity 2-5 days per week
- Unable to safely perform exercise as per PARQ+ guidelines
- Currently using tobacco products
- Currently using or have history of anabolic steroid use
- Diagnosed with medical condition including type 2 diabetes, cancer, heart disease
- Unable to abstain from supplement use (HMB, branched chain amino acids, phosphatidic acid) for at least three weeks prior to trial
- currently using medications known to affect protein metabolism e.g. corticosteroids, NSAID, prescription-strength acne medication
- allergic to local anesthetics
- female: Hormonal fluctuations associated with the menstrual cycle have been reported to alter protein metabolism during exercise and may influence indices of the post-exercise myofibrillar protein synthetic response. Accordingly, the study will include males to ensure a stable hormonal environment and to increase the homogeneity of the physiological response.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Healthy, recreationally-active adult males - Muscle Trial Crystalline amino acids to assess myofibrillar protein synthesis rates Subjects receive 0.25g/kg crystalline amino acids modelled after egg protein, enriched with L-\[1-13C\]leucine and L-ring-\[2H5\]phenylalanine with a primed-constant infusion of L-\[555-2H3\]leucine to assess myofibrillar protein synthesis rates Healthy, recreationally-active adult males - Whole Body Trial Crystalline amino acids to assess whole-body protein turnover, amino acid oxidation, and net protein balance Subjects receive 0.25g/kg crystalline amino acids modelled after egg protein, enriched with L-\[1-13C\]leucine with a primed-constant infusion of L-\[555-2H3\]leucine to whole-body protein turnover, amino acid oxidation, and net protein balance
- Primary Outcome Measures
Name Time Method Myofibrillar protein synthesis rates 5 hours Myofibrillar protein synthesis rates assessed by oral and intravenous tracers during Fast, Fed, and Ex-Fed
- Secondary Outcome Measures
Name Time Method Muscle anabolic signalling 2 and 5 hours Immunoblotting for mTORC1/key downstream targets of mTORC1
Whole-body protein turnover 5 hours Whole-body protein turnover assessed by oral and intravenous tracers during Fast, Fed, and Ex-Fed
Amino acid oxidation and net protein balance 5 hours Amino acid oxidation and net protein balance assessed by oral tracers during Fast, Fed, and Ex-Fed. Net protein balance is derived from the difference between amino acid intake (known) and total amino acid oxidation over the 5h measurement period.
Amino acid transporter expression 2 and 5 hours Immunoblotting for amino acid transporters LAT1/SNAT2
Trial Locations
- Locations (1)
Goldring Centre for High Performance Sport at the University of Toronto
🇨🇦Toronto, Ontario, Canada