Dysfunction of Nutritive Blood Flow as a Determinant of Anabolic Resistance With Age; the Role of Amino Acids in Modulating Muscle Metabolism (Ajinomoto1A)

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.

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.

Study Overview

• Status: Unknown
• Conditions: Old Age (Focus; Not a Recognized Condition)
• Intervention / Treatment: Dietary supplement: 15g EAA bolus; Dietary supplement: 15g EAA Bolus supplemented with 3g Arginine; Dietary supplement: 4 x 3.75g Mixed EAA Pulses

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Anticipated): 40
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United Kingdom
  • Derby, United Kingdom, DE23 6PF
    • University of Nottingham School of Graduate Entry Medicine and Health

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Old Bolus; 15g EAA bolus	Dietary supplement: 15g EAA bolus; Oral; in aqueous solution; Other Names: Mixed Essential Amino Acids
Experimental: Old Arginine; 15g EAA Bolus supplemented with 3g Arginine	Dietary supplement: 15g EAA Bolus supplemented with 3g Arginine; Oral; in aqueous solution
Experimental: Young Bolus; 15g EAA bolus	Dietary supplement: 15g EAA bolus; Oral; in aqueous solution; Other Names: Mixed Essential Amino Acids
Experimental: Young Pulse; 4 x 3.75g Mixed EAA Pulses	Dietary supplement: 4 x 3.75g Mixed EAA Pulses; Oral; in aqueous solution
Experimental: Old Pulse; 4 x 3.75g Mixed EAA Pulses	Dietary supplement: 4 x 3.75g Mixed EAA Pulses; Oral; in aqueous solution

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University of Nottingham
• Investigators: Principal Investigator: Philip J Atherton, PhD, University of Nottingham

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: December 1, 2011
• Primary Completion (Actual): January 1, 2014
• Study Completion (Anticipated): January 1, 2014

Study Registration Dates

• First Submitted: November 22, 2012
• First Submitted That Met QC Criteria: November 27, 2012
• First Posted (Estimate): November 28, 2012

Study Record Updates

• Last Update Posted (Estimate): January 17, 2014
• Last Update Submitted That Met QC Criteria: January 16, 2014
• Last Verified: January 1, 2014

More Information

Terms related to this study

• Keywords: sarcopenia; old age; essential amino acid; arginine; contrast enhanced ultrasound; muscle microcirculation; muscle protein synthesis
• Other Study ID Numbers: UNottingham F/3/2009

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