Sex Differences in Muscle Damage Following Resistance Exercise at Low or High Intensity (EIMD-LOAD)

Sex Differences in Resistance Exercise-induced Muscle Damage: The Impact of Exercise Load

Purpose: To investigate the impact of exercise load on resistance exercise-induced muscle damage in untrained males and females.

Rationale: Unaccustomed resistance exercise can cause muscle damage, presenting as muscle soreness and reduced muscle function - such as loss of strength, power, and flexibility - for several days after the exercise bout. Therefore, individuals may require longer recovery periods before performing another exercise bout, and their performance may be impaired. Further, muscle soreness may reduce exercise compliance, particularly in novice individuals. Over time, this may compromise the gains in muscle mass and strength achieved through exercise training. Therefore, strategies to reduce the severity of exercise-induced muscle damage and/or to enhance post-exercise recovery processes are advantageous for exercising individuals.

One such strategy is to perform resistance exercise with lighter loads, i.e. <70% one repetition maximum (1RM). Low-load resistance training has shown to induce comparable gains in muscle mass and strength to high-load (≥70% 1RM), while being perceptively less exerting. Low-load resistance exercise may place less mechanical stress on muscle fibres and accordingly, its impact on muscle damage has been investigated. While several studies have reported less severe muscle damage, muscle soreness, and functional impairments with low-load resistance exercise compared to high-load, others have found no differences. Further, there is a lack of studies conducted solely in females or comparing between sexes. It has been suggested that males and females respond differently to muscle damage, and therefore, this research aims to provide a sex comparison in the muscle damage response to an acute bout of resistance exercise performed with low or high loads.

Therefore, 40 healthy, young (18-35 years) adults (20 males, 20 females) will be recruited to participate in this randomised controlled trial. Maximal leg strength and body composition (by dual-energy X-ray absorptiometry; DXA) will be conducted at baseline. In females, all primary outcome measures will be obtained during the late follicular phase of the menstrual cycle. Participants will then be randomised to a low-load (30% 1RM) or high-load (80% 1RM) exercise condition.

Three weeks later, participants will complete a resistance exercise session at their allocated intensity on leg extension and leg curl machines to induce muscle damage. Various measures of muscle damage (blood biomarkers, muscle soreness, flexibility, and swelling) will be obtained before, immediately after, and 24, 48, 72, and 168 h after the exercise protocol. The maximal strength test will be repeated 72 and 168 h after the exercise. Participants' habitual activity and dietary intake will be monitored and controlled throughout the study period.

Expected outcome: It is expected that the resistance exercise protocol will induce muscle damage, which will be less severe in the low-load exercise condition. It cannot be ascertained whether males and females will have the same responses to the exercise.

Study Overview

• Status: Suspended
• Conditions: Muscle Damage
• Intervention / Treatment: Other: Resistance Exercise

• Study Type: Interventional
• Enrollment (Anticipated): 40
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United Kingdom
  • County Durham
    • Durham, County Durham, United Kingdom, DH1 3HN
      • Durham University, The Graham Sports Centre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 35 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• BMI 18.5 - 25.0 kg/m2
• Untrained in resistance exercise
• No known chronic disease or current acute illness
• No current or recent (past 3 months) musculoskeletal injury
• No frequent use (2x per week for past month) of non-steroidal anti-inflammatory drugs, anti-oxidant supplements, polyunsaturated omega-3 fatty acids (and other substances that may alleviate muscle damage) and compliant to abstain from use during experimental period
• No recent or current engagement in massage or cryotherapy and compliant to abstain from use during experimental period
• Females will be eumenorrheic (regular menstrual cycle) >12 months
• Absence of pregnancy and breast-feeding

Exclusion Criteria:

• Underweight
• Overweight/obese
• Resistance trained
• Current or recent injury
• Pregnancy or breast-feeding
• Unwilling to provide blood samples, perform resistance exercise, or abstain from use of NSAID's and other substances (stated above)
• Unwilling to abstain from other forms of exercise during the experimental period

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Low-Load; Acute resistance exercise performed at 30% 1RM	Other: Resistance Exercise; Acute leg-based resistance exercise bout (3 sets performed to volitional failure on leg extension and leg curl machines)
Active Comparator: High-Load; Acute resistance exercise performed at 80% 1RM	Other: Resistance Exercise; Acute leg-based resistance exercise bout (3 sets performed to volitional failure on leg extension and leg curl machines)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximal Voluntary Contraction at baseline	One-repetition maximum (1RM) test: leg extension and leg curl machines	Baseline
Change from baseline Maximal Voluntary Contraction at 72-hours post-exercise	One-repetition maximum (1RM) test: leg extension and leg curl machines	72-hours after the exercise bout
Change from baseline Maximal Voluntary Contraction at 168-hours post-exercise	One-repetition maximum (1RM) test: leg extension and leg curl machines	168-hours after the exercise bout
Creatine kinase concentration at baseline	Serum concentration of creatine kinase from venous blood sampling	Immediately pre-exercise
Change from baseline in Creatine Kinase concentration immediately post-exercise	Serum concentration of creatine kinase from venous blood sampling	Immediately after the exercise bout
Change from baseline in Creatine Kinase concentration at 24-hours post-exercise	Serum concentration of creatine kinase from venous blood sampling	24-hours after the exercise bout
Change from baseline in Creatine Kinase concentration at 48-hours post-exercise	Serum concentration of creatine kinase from venous blood sampling	48-hours after the exercise bout
Change from baseline in Creatine Kinase concentration at 72-hours post-exercise	Serum concentration of creatine kinase from venous blood sampling	72-hours after the exercise bout
Change from baseline in Creatine Kinase concentration at 168-hours post-exercise	Serum concentration of creatine kinase from venous blood sampling	168-hours after the exercise bout
Interleukin-6 concentration at baseline	Serum concentration of Interleukin-6 from venous blood sampling	Immediately pre-exercise
Change from baseline in Interleukin-6 concentration immediately post-exercise	Serum concentration of Interleukin-6 from venous blood sampling	Immediately after the exercise bout
Change from baseline in Interleukin-6 concentration at 24-hours post-exercise	Serum concentration of Interleukin-6 from venous blood sampling	24-hours after the exercise bout
Change from baseline in Interleukin-6 concentration at 48-hours post-exercise	Serum concentration of Interleukin-6 from venous blood sampling	48-hours after the exercise bout
Change from baseline in Interleukin-6 concentration at 72-hours post-exercise	Serum concentration of Interleukin-6 from venous blood sampling	72-hours after the exercise bout
Change from baseline in Interleukin-6 concentration at 168-hours post-exercise	Serum concentration of Interleukin-6 from venous blood sampling	168-hours after the exercise bout
Muscle soreness (pressure algometry) at baseline	Self-perceived rating of muscle soreness with use of pressure algometry	Immediately pre-exercise
Change in muscle soreness (pressure algometry) immediately post-exercise	Self-perceived rating of muscle soreness with use of pressure algometry	Immediately after the exercise bout
Change in muscle soreness (pressure algometry) at 24-hours post-exercise	Self-perceived rating of muscle soreness with use of pressure algometry	24-hours after the exercise bout
Change in muscle soreness (pressure algometry) at 48-hours post-exercise	Self-perceived rating of muscle soreness with use of pressure algometry	48-hours after the exercise bout
Change in muscle soreness (pressure algometry) at 72-hours post-exercise	Self-perceived rating of muscle soreness with use of pressure algometry	72-hours after the exercise bout
Change in muscle soreness (pressure algometry) at 168-hours post-exercise	Self-perceived rating of muscle soreness with use of pressure algometry	168-hours after the exercise bout
Range of motion at baseline	Flexibility of the exercised limb as determined by goniometry	Immediately pre-exercise
Change in range of motion immediately post-exercise	Flexibility of the exercised limb as determined by goniometry	Immediately after the exercise bout
Change in range of motion at 24-hours post-exercise	Flexibility of the exercised limb as determined by goniometry	24-hours after the exercise bout
Change in range of motion at 48-hours post-exercise	Flexibility of the exercised limb as determined by goniometry	48-hours after the exercise bout
Change in range of motion at 72-hours post-exercise	Flexibility of the exercised limb as determined by goniometry	72-hours after the exercise bout
Change in range of motion at 168-hours post-exercise	Flexibility of the exercised limb as determined by goniometry	168-hours after the exercise bout
Limb circumference at baseline	Measure of leg circumference with use of standard anthropometric tape to indicate muscle swelling	Immediately pre-exercise
Change in limb circumference immediately post-exercise	Measure of leg circumference with use of standard anthropometric tape to indicate muscle swelling	Immediately after the exercise bout
Change in limb circumference at 24-hours post-exercise	Measure of leg circumference with use of standard anthropometric tape to indicate muscle swelling	24-hours after the exercise bout
Change in limb circumference at 48-hours post-exercise	Measure of leg circumference with use of standard anthropometric tape to indicate muscle swelling	48-hours after the exercise bout
Change in limb circumference at 72-hours post-exercise	Measure of leg circumference with use of standard anthropometric tape to indicate muscle swelling	72-hours after the exercise bout
Change in limb circumference at 168-hours post-exercise	Measure of leg circumference with use of standard anthropometric tape to indicate muscle swelling	168-hours after the exercise bout
Muscle soreness (visual analogue scale, VAS) at baseline	Self-perceived rating of muscle soreness while performing a bodyweight squat with use of a visual analogue scale (0 - not sore at all, 10 - extremely sore)	Immediately pre-exercise
Change in muscle soreness (visual analogue scale, VAS) immediately post-exercise	Self-perceived rating of muscle soreness while performing a bodyweight squat with use of a visual analogue scale (0 - not sore at all, 10 - extremely sore)	Immediately after the exercise bout
Change in muscle soreness (visual analogue scale, VAS) at 24-hours post-exercise	Self-perceived rating of muscle soreness while performing a bodyweight squat with use of a visual analogue scale (0 - not sore at all, 10 - extremely sore)	24-hours after the exercise bout
Change in muscle soreness (visual analogue scale, VAS) at 48-hours post-exercise	Self-perceived rating of muscle soreness while performing a bodyweight squat with use of a visual analogue scale (0 - not sore at all, 10 - extremely sore)	48-hours after the exercise bout
Change in muscle soreness (visual analogue scale, VAS) at 72-hours post-exercise	Self-perceived rating of muscle soreness while performing a bodyweight squat with use of a visual analogue scale (0 - not sore at all, 10 - extremely sore)	72-hours after the exercise bout
Change in muscle soreness (visual analogue scale, VAS) at 168-hours post-exercise	Self-perceived rating of muscle soreness while performing a bodyweight squat with use of a visual analogue scale (0 - not sore at all, 10 - extremely sore)	168-hours after the exercise bout

Collaborators and Investigators

• Sponsor: Durham University

Study record dates

Study Major Dates

• Study Start (Anticipated): January 1, 2023
• Primary Completion (Anticipated): January 1, 2024
• Study Completion (Anticipated): January 1, 2024

Study Registration Dates

• First Submitted: October 27, 2021
• First Submitted That Met QC Criteria: October 27, 2021
• First Posted (Actual): November 8, 2021

Study Record Updates

• Last Update Posted (Actual): November 16, 2021
• Last Update Submitted That Met QC Criteria: November 8, 2021
• Last Verified: November 1, 2021

More Information

Terms related to this study

• Other Study ID Numbers: 290580-LOAD

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No