Effect of Knee Position on Muscle Loss During Leg Immobilization

Short periods of physical inactivity, as occur during illness, surgery, or injury, lead to rapid and substantial losses of muscle mass, strength, and metabolic health, often with incomplete recovery in vulnerable individuals. In older adults, repeated bouts of disuse are thought to contribute significantly to age-related sarcopenia. Despite decades of research, the underlying mechanisms remain incompletely elucidated, and effective therapeutic interventions are lacking.

Mechanistically, any muscle atrophy must occur due to a negative muscle protein net balance (MPNB), which can be caused by a decline in muscle protein synthesis (MPS), an increase in muscle protein breakdown (MPB), or a combination of both. Normally, exercise and dietary protein stimulate MPS and maintain muscle mass. During disuse, however, exercise is often impossible, and inactive muscle shows a blunted response to dietary protein. Consequently, these potent strategies become ineffective or even harmful in inactive individuals, highlighting the need for alternative approaches.

Animal studies indicate that immobilizing a muscle in a lengthened (stretched) position can attenuate disuse-induced muscle atrophy and functional decline compared to a shortened position. Whether this phenomenon also occurs in humans, and whether passive muscle length and tension influence muscle metabolism during disuse, remain unexplored.

The objective of this study is to assess whether immobilizing the quadriceps in a lengthened versus neutral position during disuse attenuates losses of muscle mass, function, and metabolic health.

In this randomized, controlled human intervention study with 2 parallel groups 30 healthy, normal weight males and females (18-40 years old, BMI between 18 and 30 kg·m-2) will undergo 5 days of unilateral leg immobilization using a knee brace that prevents voluntary quadriceps contraction. In the neutral group, the leg is fixed in full extension (0° flexion), while in the lengthened group it is fixed at 60° flexion, stretching the quadriceps.

The effects on muscle protein net balance (MPNB), quadriceps muscle volume , muscle quality, muscle strength, fatigue resistance, and muscle mitochondrial bioenergetics will be assessed.

Inclusion criteria

• Healthy males and females
• Aged from 18-40 years at the time of signing informed consent
• 18.5 < BMI < 30 kg·m-2
• Must be willing and able to communicate and participate in the whole study

Exclusion criteria

• Smoking
• Diabetes (Type 1, Type 2, or genetic form of diabetes)
• Any diagnosed cardiovascular (heart) disease or high blood pressure (≥140 mmHg systolic and/or ≥90 mmHg diastolic)
• Chronic use of any prescribed or over the counter pharmaceuticals that may modulate muscle protein metabolism (excluding oral contraceptives and contraceptive devices).
• A personal or family history of thrombosis, epilepsy, seizures or schizophrenia.
• Prone to keloid forming (i.e. hyperplastic growth of scars).
• Any known disorders in muscle metabolism
• Regular use of dietary protein and/or amino acid supplements (>3 times per week)
• Currently involved in a structured progressive resistance training programme (>3 times per week)
• Known allergy to lidocaine
• Known severe kidney problems
• Allergy to one or multiple amino acids
• Recent (within the last 6 months) or current musculoskeletal injury (e.g. leg fracture)
• Having received or ingested a stable isotope tracer containing 15N in the past
• Contra-indications for MRI such as incompatible metal objects in the body and claustrophobia.
• Currently taking part in other scientific research
• Pregnant or breastfeeding
• Unable to give consent