The Hidden Reason Statins Can Cause Muscle Pain

Statins have long been prescribed to lower cholesterol and reduce heart disease risk, but muscle-related side effects like pain, weakness, or fatigue have puzzled doctors for years. Now, researchers from the University of British Columbia and University of Wisconsin–Madison have uncovered a key mechanism behind these side effects, publishing their findings in *Nature Communications*. Using cryo-electron microscopy, the team examined how statins interact with the RyR1 protein, which regulates calcium release in muscle cells. Normally, RyR1 opens only when muscles contract, but statins bind to it, causing the protein to remain stuck in an open state. This leads to a continuous calcium leak, stressing muscle cells and potentially triggering pain or damage. The study focused on atorvastatin, one of the most widely prescribed statins, but the researchers believe similar effects may apply to other statin drugs. They discovered that three statin molecules cluster together on RyR1, with the first molecule increasing the likelihood of the channel opening, while the next two force it to stay open permanently. Lead researcher Dr. Steven Molinarolo explained that this mechanism explains why some patients experience muscle issues while others do not. Senior researcher Dr. Filip Van Petegem noted the findings could guide the development of safer statins that lower cholesterol without disrupting muscle function. The breakthrough offers hope for reducing statin-related muscle complications, which range from mild discomfort to severe damage like kidney failure. By redesigning statins to avoid interfering with RyR1, scientists may preserve their heart-protective benefits while eliminating muscle side effects, potentially improving treatment for millions of patients worldwide.