Dysfunction of Nutritive Blood Flow as a Determinant of Anabolic Resistance With Age; the Role of Amino Acids in Modulating Muscle Metabolism

Study Overview
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Brief Summary
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The investigators plan to measure changes in muscle protein metabolism in response to feeding, comparing between a single large essential amino acid (EAA) feed (the normal building blocks of protein) and the provision of the same dose in 4 smaller feeds at 45min intervals. The investigators will perform this study in healthy older (65-75y) and younger (18-28) men. The investigators will also explore how feeding affects muscle blood flow as this is important in the delivery of the nutrients we eat to the muscle where they are used. The investigators plan to supplement the feed with arginine, a safe and widely found non-essential amino acid, to explore if this can improve muscle blood flow.

Detailed Description
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We will provide a 15g mixed essential amino acid feed or 4 x 3.75g. There is sexual dimorphism thus initially we will just recruit males. Powering calculations dictate n=8 in each group. We will use well established stable isotope tracer techniques (with 13C6 Phenylalanine) to measure muscle protein synthesis and breakdown by Gas Chromatography - combustion - isotope ratio mass spectroscopy. We will measure leg blood flow by phase shift Doppler and muscle microvascular flow by contrast enhanced ultrasound.

Official Title
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Dysfunction of Nutritive Blood Flow as a Determinant of Anabolic Resistance in Older People; The Role of Essential Amino Acids in Modulating Muscle Protein Metabolism; Bolus vs. Pulse Feeding Strategies and the Ability of Arginine to Rejuvenate Microvascular Responsiveness.

Conditions
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Old Age (Focus; Not a Recognized Condition)

Intervention / Treatment
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* Dietary Supplement: 15g EAA bolus
* Dietary Supplement: 4 x 3.75g Mixed EAA Pulses
* Dietary Supplement: 15g EAA Bolus supplemented with 3g Arginine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: age 65-75 or 18-28 Exclusion Criteria: BMI >30 Diabetes Beta blocker or steroid use Established cerebrovascular, peripheral vascular or ischaemic heart disease.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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Male

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: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Old Bolus<br>15g EAA bolus | Dietary Supplement: 15g EAA bolus<br>* Oral; in aqueous solution<br>* Other names: Mixed Essential Amino Acids;|
| Experimental: Old Arginine<br>15g EAA Bolus supplemented with 3g Arginine | Dietary Supplement: 15g EAA Bolus supplemented with 3g Arginine<br>* Oral; in aqueous solution<br>|
| Experimental: Young Bolus<br>15g EAA bolus | Dietary Supplement: 15g EAA bolus<br>* Oral; in aqueous solution<br>* Other names: Mixed Essential Amino Acids;|
| Experimental: Young Pulse<br>4 x 3.75g Mixed EAA Pulses | Dietary Supplement: 4 x 3.75g Mixed EAA Pulses<br>* Oral; in aqueous solution<br>|
| Experimental: Old Pulse<br>4 x 3.75g Mixed EAA Pulses | Dietary Supplement: 4 x 3.75g Mixed EAA Pulses<br>* Oral; in aqueous solution<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Muscle Protein Synthesis (FSR, fractional synthetic rate, %/hr) | We measure FSR when fasted and again 0-90, 90-180 and 180-240 post feed. | Across 6hr study | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Muscle Protein Breakdown (MPB) | MBP is measured during fasting and 0-90, 90-180 and 180-240mins post feed. | Across 6hr study | 
| Whole leg blood flow | We measure common femoral blood flow by doppler ultrasound when fasted and again 0-90, 90-180 and 180-240 post feed. | Across a 6hr study | 
| Muscle Microvascular Blood flow | We measure muscle microvascular flow using contrast enhanced ultrasound when fasted and again 0-90, 90-180 and 180-240 post feed. | Across a 6hr study | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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old age, sarcopenia, essential amino acid, arginine, contrast enhanced ultrasound, muscle microcirculation, muscle protein synthesis