Healthy
Conditions
Brief summary
The present study will investigate the impact of dietary branched chain amino acid restriction on muscle atrophy, insulin sensitivity and muscle protein synthesis following short-term forearm immobilization
Detailed description
Twenty-four healthy young volunteers will undergo 2 days of forearm immobilization in combination with either a branched chain amino acid restricted diet or a control diet. Before and after immobilization, they will receive a stable isotope tracer infusion (5.5 h) combined with repeated blood and muscle sampling under insulin clamp conditions, in order to measure insulin sensitivity and muscle protein synthesis in the fasted and fed state.
Interventions
BEHAVIORALForearm immobilization
Two days of forearm immobilization
Sponsors
Wellcome Trust
University of Exeter
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
DOUBLE (Subject, Investigator)
Masking description
Double blinded
Eligibility
Sex/Gender
ALL
Age
18 Years to 40 Years
Healthy volunteers
Yes
Inclusion criteria
* Males and females 18-40 years of age * Body mass index between 18.5 and 30 kg/m2
Exclusion criteria
* Smoking * Any diagnosed metabolic impairment (e.g. type 1 or 2 diabetes) * Any diagnosed cardiovascular disease * Hypertension (≥140 mmHg systolic and/or ≥90 mmHg diastolic) * Chronic use of any prescribed or over the counter pharmaceuticals (excluding oral contraceptives and contraceptive devices) * Regular use of nutritional supplements * Currently involved in a structured progressive resistance training programme (\>3 times per week) * A personal or family history of thrombosis, epilepsy, seizures or schizophrenia * Any previous motor disorders or disorders in muscle and/or lipid metabolism * Known hypokalaemia * Presence of an ulcer in the stomach or gut and/or strong history of indigestion * Known severe kidney problems * Pregnant or breastfeeding * Unable to give consent
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Forearm glucose uptake | Hyperinsulinaemic-euglycaemic clamps are performed before and immediately after 2 days of forearm immobilisation. Forearm glucose uptake is measured during the steady state period of the clamp. | Insulin sensitivity, measured as forearm glucose uptake, under hyperinsulinaemic-euglycaemic conditions |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Muscle protein synthesis rates | During 3 hours of hyperinsulinaemic-euglycaemic clamped conditions before and after 2 days of immobilisation | Muscle protein synthesis rates are measured using an intravenously infused stable isotope labelled amino acid tracer, combined with repeated blood and muscle tissue sampling. |
| Intramuscular BCAA concentration | Before and after 3 hours of hyperinsulinaemic-euglycaemic clamped conditions | Intramuscular BCAA concentration measured using mass spectrometry |
| BCAA concentrations between forearm arterialized venous and deep venous blood | Fasted and during the steady-state phase of the insulin clamp (i.e. last 30 minutes) | Arterialized venous-deep venous forearm balance of BCAA, in the fasted state and during a hyperinsulinaemic-euglycaemic clamp |
| Whole-body substrate oxidation | Hyperinsulinaemic-euglycaemic clamps are performed before and immediately after 2 days of forearm immobilisation. Whole-body substrate oxidation is measured before the commencement of, and during the steady state period of the clamp (last 30 minutes) | Whole-body substrate oxidation measured using indirect calorimetry |
Countries
United Kingdom
Outcome results
None listed