Exercise, Statins, and the Metabolic Syndrome

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).

Inclusion criteria

• Sedentary metabolic syndrome subjects will be 25-59 y of age
• overweight to Class I or II obese (BMI 25-39 kg/m2) men and women
• 2 of 4 other characteristics of the metabolic syndrome including fasting glucose of 100 to 125 mg/dl; waist circumference greater than 102 cm in men and 88 cm in women, serum triglyceride concentration greater than 150 mg/dl, HDL-C concentrations less than 40 mg/dl in men and 50 mg/dl in women, and blood pressure greater than 130/85 mmHG
• Women must be taking birth control or be postmenopausal.

Exclusion criteria

• Diagnosed cardiovascular disease or diabetes or disease
• Symptoms that could alter their ability to perform exercise
• Fasting blood glucose of greater than 126 mg/dl
• Smoking
• Taking any medications or supplements (e.g., statins, fibrates, metformin, thiazolidenediones, anti-hypertensives (ACE-inhibitors and angiotensin blockers) which could affect blood lipids or insulin sensitivity.
• Women who are pregnant or plan to become pregnant during the duration of the study
• Individuals exercising regularly (more than one 30 min session per week)
• Individuals with an orthopedic limitations for walking.
• Report any allergies to the medications (statins, lidocaine)