Investigating the combined effects of statins and exercise on skeletal muscle mitochondrial content and function, cardiorespiratory fitness and quality of life in individuals with dyslipidaemia: protocol for a randomised placebo-controlled trial
Introduction Dyslipidaemia, affecting approximately 39% of adults worldwide, is a major risk factor for cardiovascular disease. Individuals with dyslipidaemia are often prescribed statins, which effectively lower plasma low-density lipoprotein cholesterol (LDL-C), thereby reducing the risk of cardio...
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BMJ Publishing Group
2025-06-01
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| Online Access: | https://bmjopen.bmj.com/content/15/6/e101425.full |
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| author | Simon Birk Kjær Jensen Magni Mohr Jacob Bejder Nikolai B Nordsborg Jacobina Kristiansen Tórur Sjúrðarson Jan Rasmussen Helga Ellingsgaard Steen Larsen Sanna á Borg Jørgen Martin Meinhardsson Helgi Winther Olsen Jeppe F Vigh-Larsen |
| author_facet | Simon Birk Kjær Jensen Magni Mohr Jacob Bejder Nikolai B Nordsborg Jacobina Kristiansen Tórur Sjúrðarson Jan Rasmussen Helga Ellingsgaard Steen Larsen Sanna á Borg Jørgen Martin Meinhardsson Helgi Winther Olsen Jeppe F Vigh-Larsen |
| author_sort | Simon Birk Kjær Jensen |
| collection | DOAJ |
| description | Introduction Dyslipidaemia, affecting approximately 39% of adults worldwide, is a major risk factor for cardiovascular disease. Individuals with dyslipidaemia are often prescribed statins, which effectively lower plasma low-density lipoprotein cholesterol (LDL-C), thereby reducing the risk of cardiovascular events and mortality. Although statins lower LDL-C, emerging evidence suggests that they may counteract the beneficial adaptations to exercise in skeletal muscle mitochondria and whole-body aerobic capacity. The underlying mechanisms remain unclear, and there is a need for studies investigating how statins influence molecular adaptations to exercise. The primary objective of this study is to investigate the combined effects of statin therapy and focused exercise training on mitochondrial function and whole-body aerobic capacity in people with dyslipidaemia. The untargeted proteomic analysis will be incorporated to provide detailed insights into how statins may affect mitochondrial proteins and other muscle metabolic traits, offering molecular explanations for altered functional readouts at both the muscle and whole-body levels.Methods and analysis A total of 100 women and men (aged 40–65 years) diagnosed with dyslipidaemia without atherosclerotic cardiovascular disease will be enrolled in this 12-week, double-blinded, randomised, placebo-controlled trial. Participants will be randomised into one of four groups using a block randomisation approach to ensure an allocation ratio of 60:40 for exercise and non-exercise conditions, respectively. The four groups will be: (1) exercise+placebo, (2) exercise+atorvastatin (80 mg/day), (3) atorvastatin (80 mg/day) and (4) placebo. The primary outcome is mitochondrial function, measured by changes in skeletal muscle citrate synthase activity from baseline to post-intervention. Secondary outcomes include whole-body aerobic capacity (VO2peak) and proteomic analyses. Genetic analysis will be conducted to assess the role of genetic polymorphisms in individual responses to statins and exercise.Ethics and dissemination The trial has received ethical approval from the Faroe Islands Ethical Committee (2024-10) and adheres to the Declaration of Helsinki and General Data Protection Regulation (GDPR). Results will be published in peer-reviewed international journals.Trial registration number NCT06841536. |
| format | Article |
| id | doaj-art-1bb882be5f514c28b05483598ff43d9d |
| institution | Kabale University |
| issn | 2044-6055 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | BMJ Publishing Group |
| record_format | Article |
| series | BMJ Open |
| spelling | doaj-art-1bb882be5f514c28b05483598ff43d9d2025-08-20T03:26:09ZengBMJ Publishing GroupBMJ Open2044-60552025-06-0115610.1136/bmjopen-2025-101425Investigating the combined effects of statins and exercise on skeletal muscle mitochondrial content and function, cardiorespiratory fitness and quality of life in individuals with dyslipidaemia: protocol for a randomised placebo-controlled trialSimon Birk Kjær Jensen0Magni Mohr1Jacob Bejder2Nikolai B Nordsborg3Jacobina Kristiansen4Tórur Sjúrðarson5Jan Rasmussen6Helga Ellingsgaard7Steen Larsen8Sanna á Borg9Jørgen Martin Meinhardsson10Helgi Winther Olsen11Jeppe F Vigh-Larsen12Department of Biomedical Sciences, University of Copenhagen, Copenhagen, DenmarkFaculty of Health, University of the Faroe Islands, Tórshavn, Faroe IslandsDepartment of Nutrition, Exercise and Sports (NEXS), University of Copenhagen, Copenhagen, DenmarkDepartment of Nutrition, Exercise and Sports (NEXS), University of Copenhagen, Copenhagen, DenmarkDepartment of Medicine, National Hospital of the Faroe Islands, Tórshavn, Faroe IslandsFaculty of Health, University of the Faroe Islands, Tórshavn, Faroe IslandsDepartment of Medicine, National Hospital of the Faroe Islands, Tórshavn, Faroe IslandsCentre for Physical Activity Research, Rigshospitalet, University of Copenhagen, Copenhagen, DenmarkDepartment of Biomedical Sciences, University of Copenhagen, Copenhagen, DenmarkDepartment of Medicine, National Hospital of the Faroe Islands, Tórshavn, Faroe IslandsDepartment of Medicine, National Hospital of the Faroe Islands, Tórshavn, Faroe IslandsFaculty of Education, University of the Faroe Islands, Tórshavn, Faroe IslandsDepartment of Movement and Sports Sciences, Ghent University, Ghent, BelgiumIntroduction Dyslipidaemia, affecting approximately 39% of adults worldwide, is a major risk factor for cardiovascular disease. Individuals with dyslipidaemia are often prescribed statins, which effectively lower plasma low-density lipoprotein cholesterol (LDL-C), thereby reducing the risk of cardiovascular events and mortality. Although statins lower LDL-C, emerging evidence suggests that they may counteract the beneficial adaptations to exercise in skeletal muscle mitochondria and whole-body aerobic capacity. The underlying mechanisms remain unclear, and there is a need for studies investigating how statins influence molecular adaptations to exercise. The primary objective of this study is to investigate the combined effects of statin therapy and focused exercise training on mitochondrial function and whole-body aerobic capacity in people with dyslipidaemia. The untargeted proteomic analysis will be incorporated to provide detailed insights into how statins may affect mitochondrial proteins and other muscle metabolic traits, offering molecular explanations for altered functional readouts at both the muscle and whole-body levels.Methods and analysis A total of 100 women and men (aged 40–65 years) diagnosed with dyslipidaemia without atherosclerotic cardiovascular disease will be enrolled in this 12-week, double-blinded, randomised, placebo-controlled trial. Participants will be randomised into one of four groups using a block randomisation approach to ensure an allocation ratio of 60:40 for exercise and non-exercise conditions, respectively. The four groups will be: (1) exercise+placebo, (2) exercise+atorvastatin (80 mg/day), (3) atorvastatin (80 mg/day) and (4) placebo. The primary outcome is mitochondrial function, measured by changes in skeletal muscle citrate synthase activity from baseline to post-intervention. Secondary outcomes include whole-body aerobic capacity (VO2peak) and proteomic analyses. Genetic analysis will be conducted to assess the role of genetic polymorphisms in individual responses to statins and exercise.Ethics and dissemination The trial has received ethical approval from the Faroe Islands Ethical Committee (2024-10) and adheres to the Declaration of Helsinki and General Data Protection Regulation (GDPR). Results will be published in peer-reviewed international journals.Trial registration number NCT06841536.https://bmjopen.bmj.com/content/15/6/e101425.full |
| spellingShingle | Simon Birk Kjær Jensen Magni Mohr Jacob Bejder Nikolai B Nordsborg Jacobina Kristiansen Tórur Sjúrðarson Jan Rasmussen Helga Ellingsgaard Steen Larsen Sanna á Borg Jørgen Martin Meinhardsson Helgi Winther Olsen Jeppe F Vigh-Larsen Investigating the combined effects of statins and exercise on skeletal muscle mitochondrial content and function, cardiorespiratory fitness and quality of life in individuals with dyslipidaemia: protocol for a randomised placebo-controlled trial BMJ Open |
| title | Investigating the combined effects of statins and exercise on skeletal muscle mitochondrial content and function, cardiorespiratory fitness and quality of life in individuals with dyslipidaemia: protocol for a randomised placebo-controlled trial |
| title_full | Investigating the combined effects of statins and exercise on skeletal muscle mitochondrial content and function, cardiorespiratory fitness and quality of life in individuals with dyslipidaemia: protocol for a randomised placebo-controlled trial |
| title_fullStr | Investigating the combined effects of statins and exercise on skeletal muscle mitochondrial content and function, cardiorespiratory fitness and quality of life in individuals with dyslipidaemia: protocol for a randomised placebo-controlled trial |
| title_full_unstemmed | Investigating the combined effects of statins and exercise on skeletal muscle mitochondrial content and function, cardiorespiratory fitness and quality of life in individuals with dyslipidaemia: protocol for a randomised placebo-controlled trial |
| title_short | Investigating the combined effects of statins and exercise on skeletal muscle mitochondrial content and function, cardiorespiratory fitness and quality of life in individuals with dyslipidaemia: protocol for a randomised placebo-controlled trial |
| title_sort | investigating the combined effects of statins and exercise on skeletal muscle mitochondrial content and function cardiorespiratory fitness and quality of life in individuals with dyslipidaemia protocol for a randomised placebo controlled trial |
| url | https://bmjopen.bmj.com/content/15/6/e101425.full |
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