GW501516/Cardarine is a nuclear hormone that activates the PPARδ genes involved in cell differentiation and exerts a primary regulation in maintaining health conditions and preventing diseases. PPARδ activation stimulates the mitochondrial function in various tissues improving lipid metabolism and energy homeostasis.

PPARδ receptors are expressed mainly in active metabolic tissues such as skeletal muscles, the heart, the liver, and neurons. PPARδ activation increases fatty acid oxidation, saving glycogen stores, so they find indications for the treatment of metabolic diseases, especially dyslipidemia and type-2 diabetes mellitus (T2DM), and hypertriglyceridemia. The pancreatic β-cell function is improved. In the heart, PPARδ improves cardiomyocytes function and reduces fibrosis. In the liver, it reduces the fat deposit, suppressing inflammation. Cardarine seems to be effective in preventing β-amyloid deposition and Alzheimer’s disease. In the skeletal muscles, cardarine induces a strong activation of mitochondrial biogenesis, increasing oxidative muscle capacity and endurance exercise capacity, and for this reason, it was included in the list of doping agents by WADA. However, some controversies on cancer risk stimulation exist. This review aims to evaluate the clinical benefits and side effects of GW501516/ cardarine.