Re-evaluation of the Muscle-full Effect During Continuously Elevated Amino Acid Availability in Healthy Young Males (Muscle-full)

Muscle tissue consists of proteins. These proteins are built up of a collection of smaller building blocks: amino acids. When protein is consumed, it gets digested and absorbed into the blood. The body can use these amino acids, by taking them up from thecirculation. By consuming sufficient protein through our diet, we ensure that the body is provided with enough amino acids to enable muscle protein building. Sufficient muscle protein synthesis is important for maintaining muscle function and strength.

Previous research has shown that when 20 to 25g of protein is eaten, muscle protein synthesis is maximized. It is therefore recommended to eat 20g of protein per meal. However, it is currently unclear what happens to muscle protein synthesis rates if multiple meals are eaten. When multiple meals are consumed, amino acids appear in the circulation for prolonged period of time.

Theoretically, when there are a high amino acid concentrations in the blood, muscle protein synthesis rates will increase. Contrary to this theory, a study more than 20 years ago showed otherwise. It was observed that muscle protein synthesis rates are only elevated for2 hours afterwhich they decrease again. This phenomenon was referred to as the "muscle-full" effect. Because this phenomenon is in contrast with more previous studies, the objective is to replicate that study. This is important so that nutritional advice for healthy, but also clinical populations in the future can be improved.

Study Overview

• Status: Not yet recruiting
• Conditions: Muscle Protein Synthesis
• Intervention / Treatment: Other: Continuous intravenous stable isotope amino acid tracer infusion; Other: Amino acid infusion

• Study Type: Interventional
• Enrollment (Estimated): 12
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Luc van Loon, PhD; Phone Number: 0031433881743; Email: l.vanloon@maastrichtuniversity.nl

Study Locations

• Netherlands
  • Limburg
    • Maastricht, Limburg, Netherlands, 6229ER
      • Maastricht University Medical Centre+
      • Contact: Noortje Boot, MSc

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Male sex
• Aged between 18 - 35 years
• Healthy (assessed based on routine medical questionnaire)
• BMI between 18.5 - 30 kg/m2

Exclusion Criteria:

A potential subject who meets any of the following criteria will be excluded from participation in this study:

• Smoking
• Involved in progressive exercise training
• A history of neuromuscular problems
• Use of anticoagulants
• Recent (<12 months) participation in amino acid tracer (L-[ring-13C6] phenylalanineand L-[3,5-2H2]-tyrosine) studies
• Use of medication known to affect (muscle) protein metabolism (e.g. corticosteroids, non-steroidal anti-inflammatory drugs, acne medication)
• Phenylketonuria
• Diagnosed with or history of liver damage
• Diagnosed with or history of severe kidney damage and/or malfunction
• Diagnosed with inability to break down amino acids

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Continuous amino acid infusion; Tracer infusions combined with infusion of a mixture of amino acids

Other: Continuous intravenous stable isotope amino acid tracer infusion; During the single 12 h trial day, a primed continuous stable isotope infusion will run in order to assess muscle protein synthesis in the basal (4 h) and post-prandial (8 h) state.; Other: Amino acid infusion; In order to assess muscle protein synthesis rates during continuous elevated plasma amino acid availability, the amino acid infusion solution Vamin®14 EF will be used. Vamin® 14EF contains 85g amino acids per liter and will be administered in the post-prandial period for 8 hours to ensure a constant rate of amino acid infusion over the full assessment period of the primary outcome measure.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Muscle protein synthesis during continuous elevated plasma amino acid avaialbility in healthy young males	The primary endpoint is muscle protein synthesis rates (in %/h) over the full assessment period (8 h) as determined with contemporary stable isotope tracer methodology combined with repeated blood and muscle sampling. Muscle protein synthesis are calculated using plasma as precursor pool and the tracer enrichment in the muscle (measured with UPLC and GC-IRMS).	8 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Basal muscle protein synthesis rates	Basal muscle protein synthesis rates (in %/h) will be assessed over a 3h period as determined with contemporary stable isotope tracer methodology combined with repeated blood and muscle sampling. Muscle protein synthesis are calculated using plasma as precursor pool and the tracer enrichment in the muscle biopsy (measured with UPLC and GC-IRMS).	3 hours
Whole-body protein kinetics	Including total rate of appearance, exogenous rate of appearance, endogenous rate of appearance, rate of disappearance based (all expressed as μmol/kg/min) on tracer plasma amino acid concentrations over time (measured with UPLC)	8 hours
Whole-body protein metabolism	synthesis, breakdown, oxidation, net balance (all expressed as μmol/kg/h). Based on amino acid concentrations in plasma and breath samples (measured with UPLC and GC-IRMS).	8 hours

Collaborators and Investigators

• Sponsor: Maastricht University Medical Center
• Investigators: Principal Investigator: Luc van Loon, PhD, Maastricht University

Study record dates

Study Major Dates

• Study Start (Estimated): March 1, 2025
• Primary Completion (Estimated): December 31, 2025
• Study Completion (Estimated): February 1, 2026

Study Registration Dates

• First Submitted: December 3, 2024
• First Submitted That Met QC Criteria: December 3, 2024
• First Posted (Actual): December 6, 2024

Study Record Updates

• Last Update Posted (Estimated): December 13, 2024
• Last Update Submitted That Met QC Criteria: December 10, 2024
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Keywords: muscle biopsy; amino acid infusion; tracer methodology
• Other Study ID Numbers: METC24-028

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: Data will be made available upon request

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No