The Impact of Energy Intake and Short-term Disuse on Muscle Protein Synthesis Rates and Skeletal Muscle Mass in Middle-aged Adults.

Study Overview
=================
Brief Summary
-----------------
In healthy middle-aged men and women, what is the effect of dietary energy restriction and energy surplus on daily muscle protein synthesis rates and muscle morphology, compared to energy balance, during free-living and immobilisation?

Detailed Description
-----------------
Background Age related muscle tissue loss, which is associated with a number of negative health outcomes is partially caused by blunted muscle protein synthesis rates (MPS) in response to food ingestion, which is exacerbated by muscle disuse. Concomitantly, consuming an energy balanced diet appears to become more challenging with advancing age, due to a reduction in appetite. Of concern is that the impact of energy intake on muscle protein metabolism during ageing is poorly characterised. Objective To determine daily MPS and muscle morphology in response to differing energy intakes, in free-living conditions and during immobilisation. Methods Healthy middle-aged volunteers will consume a hypocaloric, energy-balanced, or hypercaloric diet (providing 1.4 g.kg.day protein) over a three-day free-living period, and a three day period of single leg immobilisation. Deuterium oxide and MRI scans will be used to measure daily MPS and muscle size, respectively. Value The study will determine the effect of energy intake per se on daily muscle protein synthesis rates and muscle size, in free-living and immobilised conditions. This will inform how energy provision modulates tissue loss with ageing, and how this interacts with the catabolic stress of muscle disuse.

Official Title
-----------------
The Impact of Energy Intake and Short-term Disuse on Muscle Protein Synthesis Rates and Skeletal Muscle Mass in Middle-aged Adults.

Conditions
-----------------
Muscle Atrophy, Aging, Energy Malnutrition Protein

Intervention / Treatment
-----------------
* Other: Energy status


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Age 35-65 Healthy Non-smoker Recreationally active Exclusion Criteria: Any diagnosed metabolic impairment (e.g. type 1 or 2 Diabetes) Any diagnosed cardiovascular disease or hypertension Elevated blood pressure at the time of screening. (An average systolic blood pressure reading of ≥150mmHg over two or more measurements and an average diastolic blood pressure of ≥90mmHg over two or more measurements.) Chronic use of diabetic medication. A personal or family history of epilepsy, seizures or schizophrenia. Allergic to mycoprotein / Quorn, penicillin, or cow's milk. Any musculoskeletal injury that may impair their use of crutches. Any diagnosed severe digestive illness. Any diagnosed severe autoimmune disease. Any diagnosed cancer. Any metal fragments in the eyes, a pacemaker, or metal implants in the body that preclude MRI scanning.

Ages Eligible for Study
-----------------
Minimum Age: 35 Years
Maximum Age: 65 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Basic Science
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Hypocaloric<br>Participants placed in energy restriction. | Other: Energy status<br>* Varying conditions of energy intake, thereby manipulating whether participants are in a state of energy restriction, balance, or surplus.<br>|
| Experimental: Energy Balance<br>Participants placed in energy balance. | Other: Energy status<br>* Varying conditions of energy intake, thereby manipulating whether participants are in a state of energy restriction, balance, or surplus.<br>|
| Experimental: Hypercaloric<br>Participants placed in energy surplus. | Other: Energy status<br>* Varying conditions of energy intake, thereby manipulating whether participants are in a state of energy restriction, balance, or surplus.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Muscle protein synthesis (MPS) | Daily muscle protein synthesis rates, expressed as fractional synthetic rate (FSR) (%/day) | 6 days (3 days free-living, 3 days immobilised) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Muscle morphology. | Changes in muscle size, measured via MRI scanning, during immobilisation. | 3 day immobilisation phase. | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Muscle protein synthesis, Ageing, Dietary protein, Disuse