Validating IAAO for Muscle Outcomes

Trial statusRecruiting
Trial phaseNot applicable
Trial typeInterventional
Biological sexAll
Age18-35
SponsorUniversity of Toronto

About this trial

Consuming dietary protein stimulates whole-body and muscle protein synthesis, the latter of which is typically measured using invasive primed constant infusions of stable isotopes with concurrent muscle biopsies. Alternative non-invasive methodologies have been developed (namely the indicator amino acid oxidation (IAAO) technique) to estimate the impact of protein ingestion on whole-body protein synthesis as a proxy for determining dietary protein requirements. Given that the IAAO technique is based on principles of protein metabolism which occur in the liver, it is unclear how representative the IAAO outcomes of whole-body protein synthesis is to skeletal muscle protein synthesis. Validation of the IAAO technique against gold-standard, biopsy-derived measures of muscle metabolism (i.e., muscle protein synthesis) would assist in mitigating the invasiveness of muscle physiology and nutrition research.

Eligibility criteria

This trial accepts healthy volunteers

Qualifiers

Participants will be aged 18-35 years old

Participants will have a BMI within the normal range (i.e., 18.5-24.9) and waist-to-hip circumference ratio of <0.95 for males and <0.8 for circumference for females to ensure homogeneity of the sample population

Participants are willing to abide by the compliance rules of this study (e.g., abstain from extraneous physical activity 48h prior to session 4

Self-reported regular menstrual cycle (25-35d) within the last 3 months (female participants)

Disqualifiers

Inability to adhere to any of the compliance rules judged by principal investigator

Self-reported regular tobacco or illicit drug use (e.g., growth hormone or testosterone)

Current use of hormonal contraceptives

Individuals with a history of allergy to local anesthetics (e.g., lidocaine)

Trial design

Design model

Single group

Treatments tested in this trial

  • Protein + Stable Isotope Tracer Beverage

    Dietary supplement

    Participants will consume 12 half-hourly (6 hours) isoenergetic, isonitrogenous beverages containing 0.9g/kg fat-free mass/day protein. Drinks will be enriched with stable isotopes \[2H5\]Phenylalanine and \[1-13C\]Phenylalanine, which will respectively allow for determination of muscle protein synthesis and whole-body protein synthesis over the subsequent 6 hours of feeding

Treatment groups

8 Participants
are divided into 1 treatment group
Group A: Protein + Stable Isotope Tracer BeverageExperimental treatment 1 intervention

Trial outcomes

Primary outcomes

1

Phenylalanine excretion (umol/kg/h)

Rate of whole-body phenylalanine excretion following orally ingested amino acid tracer \[1-13C\]Phenylalanine determined from the product of breath 13CO2 enrichment and carbon dioxide production rate (VCO2).

Time frame
6.5 hours
2

Phenylalanine oxidation (umol/kg/h)

Rate of whole-body phenylalanine oxidation following orally ingested amino acid tracer \[1-13C\]Phenylalanine determined from the correction of phenylalanine excretion by the phenylalanine precursor enrichment via urine enrichment.

Time frame
6.5 hours
3

Myofibrillar protein synthesis (%/hr)

Rate of myofibrillar fractional synthesis is determined by rate of incorporation of orally ingested tracer \[2H5\]Phenylalanine into myofibrillar proteins (isolated from skeletal muscle biopsies) and the enrichment of \[2H5\]Phenylalanine in plasma collected over the 6 hours protein consumption period. Enrichment will be quantified via tandem LC-MS/MS to derive a rate of incorporation over the 6-hour period.

Time frame
6.5 hours
4

Sarcoplasmic protein synthesis (%/hr)

Rate of sarcoplasmic fractional synthesis is determined by rate incorporation of orally ingested tracer \[2H5\]Phenylalanine into sarcoplasmic (ie., soluble) proteins (isolated from skeletal muscle biopsies) and the enrichment of \[2H5\]Phenylalanine in plasma collected over the 6 hours protein consumption period. Enrichment will be quantified via tandem LC-MS/MS to derive a rate of incorporation over the 6-hour period.

Time frame
6.5 hours

Secondary outcomes

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.