Simvastatin impairs exercise training adaptations

Abstract

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).

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.

Figure 1. Cardiorespiratory fitness (VO_2peak)

(A) VO_2peak before (Pre) and after (Post) 12 weeks of supervised aerobic exercise training (Ex) or combination exercise plus statin therapy (St+Ex). (B) VO_2peak presented as within group change (Δ) from baseline. Data are expressed as means±SE. * P<0.005 for within-group change from baseline. § P<0.005 for between-group difference in change from baseline.

Figure 2. Citrate synthase activity, a marker of skeletal muscle mitochondrial content

(A) Citrate synthase activity before (Pre) and after (Post) 12 weeks of supervised aerobic exercise training (Ex) or combination exercise plus statin therapy (St+Ex). (B) Citrate synthase activity presented as within group change (Δ) from baseline. Data are expressed as means±SE. * P<0.05 for within-group change from baseline. § P<0.05 for between-group difference in change from baseline.