Effect of Vitamin D Supplementation on Exercise Adaptations in Patients on Statin Therapy

Statins along with lifestyle modifications including exercise are commonly prescribed to patients with type 2 diabetes. American diabetes association recommends using moderate-intensity statin and lifestyle therapy for patients with diabetes aged ≥40 years, even without additional cardiovascular disease(CVD) risk factors.. Myopathy is a well known adverse effect of statins, which occurs in 1-7% of patients. The spectrum of statin-related myopathy ranges from common benign myalgia to rare but life threatening rhabdomyolysis. Being lipophilic, simvastatin diffuses nonselectively into extrahepatic tissues such as muscle, leading to higher incidence of myopathy among statin users. In addition, simvastatin attenuates the exercise-induced increase in cardiorespiratory fitness, and reduces the skeletal muscle mitochondrial content and oxidative capacity in humans. Impaired cardiorespiratory fitness and mitochondrial function is possibly due to reduction in Coenzyme Q10, which is a component of the electron transport chain and is indispensable for generation of adenosine triphosphate (ATP) during oxidative phosphorylation in mitochondria. Statins or hydroxyl-methylglutaryl coenzyme A (HMA CoA) reductase inhibitors interfere with the production of mevalonic acid, which is a precursor in the synthesis of coenzyme Q10. Mitochondrial dysfunction has also been reported in vitamin D deficient individuals which has been attributed to intra-mitochondrial calcium deficiency or deficient enzyme function of the oxidative pathway ( by direct effect of vitamin D on enzyme gene or protein expression). Thus, vitamin D may improve the statin-mediated changes in cardiorespiratory fitness and mitochondrial function by improving the enzymatic machinery involved in oxidative phosphorylation which is blocked by statin. This study is being done to look for the effect of vitamin D supplementation on simvastatin-mediated change in exercise-mediated cardiorespiratory fitness and skeletal muscle mitochondrial content in adults with type 2 diabetes