title: Simvastatin impairs exercise training adaptations.
abstract: OBJECTIVE
  This study sought to determine if simvastatin impairs exercise training adaptations.
  
  
  BACKGROUND
  Statins are commonly prescribed in combination with therapeutic lifestyle changes, including exercise, to reduce cardiovascular disease risk in patients with metabolic syndrome. Statin use has been linked to skeletal muscle myopathy and impaired mitochondrial function, but it is unclear whether statin use alters adaptations to exercise training.
  
  
  METHODS
  This study examined the effects of simvastatin on changes in cardiorespiratory fitness and skeletal muscle mitochondrial content in response to aerobic exercise training. Sedentary overweight or obese adults with at least 2 metabolic syndrome risk factors (defined according to National Cholesterol Education Panel Adult Treatment Panel III criteria) were randomized to 12 weeks of aerobic exercise training or to exercise in combination with simvastatin (40 mg/day). The primary outcomes were cardiorespiratory fitness and skeletal muscle (vastus lateralis) mitochondrial content (citrate synthase enzyme activity).
  
  
  RESULTS
  Thirty-seven participants (exercise plus statins: n = 18; exercise only: n = 19) completed the study. Cardiorespiratory fitness increased by 10% (p < 0.05) in response to exercise training alone, but was blunted by the addition of simvastatin resulting in only a 1.5% increase (p < 0.005 for group by time interaction). Similarly, skeletal muscle citrate synthase activity increased by 13% in the exercise-only group (p < 0.05), but decreased by 4.5% in the simvastatin-plus-exercise group (p < 0.05 for group-by-time interaction).
  
  
  CONCLUSIONS
  Simvastatin attenuates increases in cardiorespiratory fitness and skeletal muscle mitochondrial content when combined with exercise training in overweight or obese patients at risk of the metabolic syndrome. (Exercise, Statins, and the Metabolic Syndrome; NCT01700530).
authors.affiliation: Division of Cardiology, Duke University Medical Center, Durham, North Carolina, USA.
authors.forename: Catherine R
authors.initials: CR
authors.lastname: Mikus
authors.forename: Leryn J
authors.initials: LJ
authors.lastname: Boyle
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: Borengasser
authors.forename: Douglas J
authors.initials: DJ
authors.lastname: Oberlin
authors.forename: Scott P
authors.initials: SP
authors.lastname: Naples
authors.forename: Justin
authors.initials: J
authors.lastname: Fletcher
authors.forename: Grace M
authors.initials: GM
authors.lastname: Meers
authors.forename: Meghan
authors.initials: M
authors.lastname: Ruebel
authors.forename: M Harold
authors.initials: MH
authors.lastname: Laughlin
authors.forename: Kevin C
authors.initials: KC
authors.lastname: Dellsperger
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Fadel
authors.forename: John P
authors.initials: JP
authors.lastname: Thyfault
mesh_terms: D000222:Adaptation, Physiological; D000328:Adult; D000924:Anticholesteremic Agents / Q000627:therapeutic use*; D002318:Cardiovascular Diseases / Q000517:prevention & control; D002950:Citrate (si)-Synthase / Q000378:metabolism; D003131:Combined Modality Therapy; D015444:Exercise / Q000502:physiology*; D005081:Exercise Therapy; D005260:Female; D006801:Humans; D008074:Lipoproteins / Q000097:blood; D008297:Male; D024821:Metabolic Syndrome / Q000517:prevention & control; D008875:Middle Aged; D008931:Mitochondria, Muscle / Q000378:metabolism; D050177:Overweight / Q000503:physiopathology; D010809:Physical Fitness / Q000502:physiology; D019821:Simvastatin / Q000627:therapeutic use*
chemical_list: D000924:Anticholesteremic Agents; D008074:Lipoproteins; D019821:Simvastatin; D002950:Citrate (si)-Synthase
keywords: BMI; LDL-C; Vo(2)peak; aerobic fitness; body mass index; low-density lipoprotein cholesterol; metabolic syndrome; obesity; peak oxygen consumption; skeletal muscle mitochondria; statin