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.

Sham-NMES with standard nutrition

Other: Sham (No Treatment) · Other: Standard nutrition

Whole-body NMES stimulation with standard nutrition

Other: NMES · Other: Standard nutrition

Whole-body NMES with a 20g protein bolus on top of the standard nutrition

Other: NMES · Dietary Supplement: Protein bolus (20g) · Other: Standard nutrition

A placebo treatment in which no actual electrical stimulation is delivered, serving as a control for the active NMES.

Active neuromuscular electrical stimulation applied to the entire body to induce muscle contractions through small electric currents.

A bolus dose of 20 grams of protein provided after the NMES intervention to assess the combined effect of muscle stimulation and protein intake on muscle protein metabolism.

Provision of a normal Western standardized diet.

Plazo: Habitual MPS (Day -2 to Day 0), Acute effect of NMES (+protein bolus) (0 hours to 5 hours on Day 0), Bedrest MPS (Day 0 to Day 3),

A measure of muscle protein synthesis between two given time points.

Plazo: Between Day -21 and Day -5, Day 0, Day 3, Day 6, Week 6

Assessed using ultrasound, this measures changes in muscle size, indicating muscle loss or preservation during bed rest and NMES intervention.

Plazo: Day 0 and Day 3.

Evaluates muscle mass to determine overall changes.

Plazo: Time Frame: Day 0 and Day 3.

Evaluates fat distribution to determine overall changes.

Plazo: Between Day -21 and Day -5, Day 0, Day 3, Day 6, Week 6

Assessed via a leg dynamometer.

Plazo: Between Day -21 and Day -5, Day 0, Day 3, Day 6, Week 6

Assessed via a leg dynamometer.

Plazo: Between Day -21 and Day -5, Day 0, Day 3, Day 6, Week 6

Assessed via a hand dynamometer.

Plazo: Day 0 to Day 3

The balance between nitrogen intake (from dietary protein) and nitrogen loss (through urine and other excretions)

The Effect of Repeated Sessions of Whole-body Neuromuscular Electrical Stimulation (NMES), With or Without Subsequent Intake of a Protein Bolus, on Muscle Protein Synthesis in Healthy, Young Volunteers During 3 Days of Bed Rest