Simvastatin impairs exercise training adaptations

Catherine R. Mikus, Leryn J. Boyle, Sarah J. Borengasser, Douglas J. Oberlin, Scott P. Naples, Justin Fletcher, Grace M. Meers, Meghan Ruebel, M. Harold Laughlin, Kevin C. Dellsperger, Paul J. Fadel, John P. Thyfault

Research output: Contribution to journalArticlepeer-review

179 Scopus citations


Objectives 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)

Original languageEnglish (US)
Pages (from-to)709-714
Number of pages6
JournalJournal of the American College of Cardiology
Issue number8
StatePublished - Aug 20 2013
Externally publishedYes


  • aerobic fitness
  • metabolic syndrome
  • obesity
  • skeletal muscle mitochondria
  • statin

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine


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