The Effect of Repeated Whole-body NMES Sessions With or Without Protein Intake on Muscle Protein Synthesis During 3 Days of Bed Rest in Healthy Young Volunteers

Patients admitted to the hospital often experience prolonged bed rest, which can lead to rapid muscle loss and weakness. In the intensive care unit (ICU), this condition, known as ICU-acquired weakness (ICU-AW), affects up to 50% of patients and can lead to longer mechanical ventilation times, increased morbidity, and a reduced quality of life after hospital discharge. One of the key reasons for muscle loss during bed rest is an impaired response to dietary protein, which normally helps maintain muscle mass.

Neuromuscular electrical stimulation (NMES) is a method that uses small electrical currents to stimulate muscle contractions, potentially counteracting muscle loss during periods of inactivity. Previous research has shown that NMES applied to the quadriceps muscles can reduce muscle loss in sedated patients and improve muscle protein synthesis in individuals with type 2 diabetes. However, the effects of whole-body NMES in combination with timed protein intake on muscle protein metabolism during bed rest are still unknown.

This study aims to investigate the impact of both a single session and repeated sessions of whole-body NMES, with or without subsequent protein intake, on muscle protein synthesis rates, muscle mass, and function during 3 days of bed rest in healthy young adults.

Study Design:

This is a randomized, placebo-controlled clinical trial with three parallel groups. Participants will be randomly assigned to one of the following groups:

• Control Group (CON): Sham-NMES + standard nutrition
• NMES Group (NMES): Whole-body NMES + standard nutrition
• NMES + Protein Group (NMES+PRO): Whole-body NMES + 20g protein bolus

Study Procedures:

Participants will be healthy adults (18-35 years, male and female) and will undergo the following procedures:

• 3 days of strict bed rest to simulate hospitalization-related muscle disuse
• Neuromuscular electrical stimulation (NMES) sessions to assess its effect on muscle metabolism
• Muscle biopsies to measure changes in muscle protein synthesis at the molecular level
• Consumption of deuterium oxide (D₂O or "heavy water") to track muscle protein turnover
• Multiple blood and saliva samples to analyze protein metabolism markers
• Leg extension tests to assess changes in muscle function
• Quadriceps muscle thickness measurements via ultrasound
• Calf circumference measurements to assess muscle mass changes

This study will provide critical insights into how NMES and protein intake can help counteract muscle loss and weakness during hospitalization and may contribute to the development of more effective rehabilitation strategies for ICU and bedridden patients.

Inclusion criteria

• Aged from 18-35 years
• 18.5 < BMI < 30 kg·m2
• Recreationally active (performing non-competitive physical exercise at least one time per week for minimally 30 minutes)

Exclusion criteria

• Employed or undertaking a thesis or internship at the department of Human and Animal Physiology at Wageningen University
• 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 (excluding oral contraceptives and contraceptive devices)
• Known allergy to lidocaine
• Prone to keloid forming (i.e. hyperplastic growth of scars)
• All co-morbidities interacting with mobility and muscle metabolism of the lower limbs (e.g.

arthritis, spasticity/rigidity, all neurological disorders and paralysis)

• 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)
• A personal or family history of thrombosis (clots), epilepsy, seizures, or schizophrenia
• Any previous motor disorders or disorders in muscle and/or lipid metabolism
• Any back, leg, knee, neck, shoulder or postural complaints
• Presence of an ulcer in the stomach or gut and/or strong history of indigestion
• Contra-indications for DXA scans (e.g. undergoing radiologic examination)
• Lactose intolerance
• Known severe kidney problems
• Pregnant or breastfeeding
• Unable to give consent