Sex Differences in Muscle Damage Following Resistance Exercise at Low or High Intensity

Study Overview
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Brief Summary
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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.

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

Conditions
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Muscle Damage

Intervention / Treatment
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* Other: Resistance Exercise


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 35 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

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

What is the study measuring?
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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 | 
| 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 | 
| 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 |