Author + information
- Received December 3, 2012
- Revision received February 6, 2013
- Accepted February 14, 2013
- Published online August 20, 2013.
- Catherine R. Mikus, PhD∗,
- Leryn J. Boyle, MSc†,
- Sarah J. Borengasser, PhD‡,
- Douglas J. Oberlin, MSc†,
- Scott P. Naples, MSc†,
- Justin Fletcher, MSc†,
- Grace M. Meers, BSc§,
- Meghan Ruebel, MA⋮,
- M. Harold Laughlin, PhD¶,
- Kevin C. Dellsperger, MD, PhD§,
- Paul J. Fadel, PhD# and
- John P. Thyfault, PhD†,‡∗∗∗ ()
- ∗Division of Cardiology, Duke University Medical Center, Durham, North Carolina
- †Department of Nutrition and Exercise Physiology, University of Missouri, Columbia, Missouri
- ‡Department of Pediatrics, Arkansas Children's Nutrition Center, University of Arkansas for Medical Sciences, Little Rock, Arkansas
- §Division of Gastroenterology and Hepatology, Department of Medicine, University of Missouri, Columbia, Missouri
- ⋮Division of Cardiovascular Medicine, Department of Medicine, University of Missouri, Columbia, Missouri
- ¶Department of Biomedical Sciences, University of Missouri, Columbia, Missouri
- #Department of Medical Pharmacology and Physiology, University of Missouri, Columbia, Missouri
- ∗∗Research Service, Harry S Truman Memorial Veteran's Hospital, Columbia, Missouri
Reprint requests and correspondence:
Dr. John P. Thyfault, Clinical Research Center, Medical Sciences Building NW502, University of Missouri School of Medicine, Columbia, Missouri 65211.
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)
Funding for this study was provided by the University of Missouri Research Board Grant (to Dr. Thyfault), Veterans Affairs Career Development Award (to Dr. Thyfault), American Heart Association Midwest Affiliate Clinical Research Award#09CRP2260136 (to Dr. Thyfault), and National Institutes of Health grant #T32 AR048523 (to Dr. Mikus). This work was also supported with resources and the use of facilities at the Harry S Truman Memorial Veterans Hospital. The authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- Received December 3, 2012.
- Revision received February 6, 2013.
- Accepted February 14, 2013.
- American College of Cardiology Foundation