Simvastatin Impairs Exercise Training Adaptations

Abstract

OBJECTIVES 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 the 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 We 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 per 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). CONCLUSION 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.

Cardiorespiratory Fitness and Incidence of Type 2 Diabetes in United States Veterans on Statin Therapy

“…Furthermore, some 20,21 but not all studies [22][23][24] suggest that improvements in cardiorespiratory fitness in response to exercise training may be blunted by statin therapy. Therefore, in the current study we sought to assess the impact of cardiorespiratory fitness on the incidence of type 2 diabetes in dyslipidemic patients treated with statins.…”

“…Cardiorespiratory fitness was assessed by a standard treadmill test using the Bruce protocol at the Veterans Affairs Medical Center in Washington, DC, and an individualized ramp protocol as described previously 20 for subjects assessed at the Veterans Affairs Health Care System Center in Palo Alto, CA. Peak exercise capacity (Metabolic Equivalents) was estimated by use of standardized equations.…”

“…Peak exercise capacity (Metabolic Equivalents) was estimated by use of standardized equations. 20,21 One…”

Statin intolerance: more questions than answers

“…Mikus et al reported recently that statin-treated subjects did not benefit from the training effect of a 12-week exercise program. In a randomized, placebo-controlled trial among 41 subjects, those treated with simvastatin showed significant failure to increase peak oxygen consumption and, in muscle biopsy specimens, a significant lack of increase in an enzyme marker of mitochondrial content [7].…”

“…Is there any interaction between statins and the natural decline of strength with aging? The recent data of Mikus et al may be pertinent [7]. What are optimal doses for lifelong statin treatment?…”