Development of Oral Amino Acid Tracers to Study Protein Turnover in Humans

University of Toronto

Status: Completed

Conditions: Healthy Adult Males

Treatments: Dietary Supplement: Crystalline amino acids to assess whole-body protein turnover, amino acid oxidation, and net protein balance; Dietary Supplement: Crystalline amino acids to assess myofibrillar protein synthesis rates

Study type: Interventional

Funder types: Other

Identifiers

NCT04887727

Connaught

Details and patient eligibility

About

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).

Full 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).

Enrollment: 22 patients

Sex: Male

Ages: 18 to 35 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

• Male
• Currently performing structured physical activity 2-5 days per week

Exclusion criteria

• 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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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22 participants in 2 patient groups

Healthy, recreationally-active adult males - Muscle Trial

Experimental group

Description:

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

Treatment:

Dietary Supplement: Crystalline amino acids to assess myofibrillar protein synthesis rates

Healthy, recreationally-active adult males - Whole Body Trial

Experimental group

Description:

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

Treatment:

Dietary Supplement: Crystalline amino acids to assess whole-body protein turnover, amino acid oxidation, and net protein balance