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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Old Bolus | Experimental | 15g EAA bolus |
|
| Old Arginine | Experimental | 15g EAA Bolus supplemented with 3g Arginine |
|
| Young Bolus | Experimental | 15g EAA bolus |
|
| Young Pulse | Experimental | 4 x 3.75g Mixed EAA Pulses |
|
| Old Pulse | Experimental | 4 x 3.75g Mixed EAA Pulses |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 15g EAA bolus | Dietary Supplement | Oral; in aqueous solution |
|
| 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 |
| 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. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Philip J Atherton, PhD | University of Nottingham | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Nottingham School of Graduate Entry Medicine and Health | Derby | DE23 6PF | United Kingdom |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 25644339 | Derived | Mitchell WK, Phillips BE, Williams JP, Rankin D, Lund JN, Smith K, Atherton PJ. A dose- rather than delivery profile-dependent mechanism regulates the "muscle-full" effect in response to oral essential amino acid intake in young men. J Nutr. 2015 Feb;145(2):207-14. doi: 10.3945/jn.114.199604. Epub 2014 Dec 10. |
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| 4 x 3.75g Mixed EAA Pulses | Dietary Supplement | Oral; in aqueous solution |
|
| 15g EAA Bolus supplemented with 3g Arginine | Dietary Supplement | Oral; in aqueous solution |
|
| 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 |
| ID | Term |
|---|---|
| D055948 | Sarcopenia |
| ID | Term |
|---|---|
| D009133 | Muscular Atrophy |
| D020879 | Neuromuscular Manifestations |
| D009461 | Neurologic Manifestations |
| D009422 | Nervous System Diseases |
| D001284 | Atrophy |
| D020763 | Pathological Conditions, Anatomical |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D012816 | Signs and Symptoms |
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| ID | Term |
|---|---|
| D001120 | Arginine |
| ID | Term |
|---|---|
| D024361 | Amino Acids, Basic |
| D000596 | Amino Acids |
| D000602 | Amino Acids, Peptides, and Proteins |
| D000599 | Amino Acids, Diamino |
| D000601 | Amino Acids, Essential |
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