Scientists Uncover Why Statins Cause Muscle Pain — Opening Door to Safer Drugs
Researchers at the University of British Columbia used cryo-electron microscopy to show that statin molecules force open a calcium channel in muscle cells, explaining the side effects that cause millions of patients to stop taking the life-saving cholesterol drugs.
Scientists at the University of British Columbia, working with collaborators at the University of Wisconsin-Madison, have identified the precise molecular mechanism behind one of the most common side effects of statins — muscle pain, weakness, and in rare cases severe muscle damage — publishing their findings in Nature Communications in 2025. Using cryo-electron microscopy, the team showed that statin molecules bind to a protein in muscle cells called the ryanodine receptor (RyR1), which normally acts as a tightly controlled gate regulating the flow of calcium within muscle fibres. The researchers found that three statin molecules act together in an unusual pattern: the first makes the gate more likely to open, and the remaining two hold it open, allowing calcium to leak continuously into parts of the cell where it should not accumulate. This sustained calcium leakage damages muscle tissue over time. More than 200 million people worldwide take statins to lower cholesterol and reduce the risk of heart attacks and strokes, making them among the most widely prescribed drugs globally. Muscle-related side effects are common enough that a significant proportion of patients discontinue the medication, often leaving cardiovascular risk unmanaged. The discovery is expected to guide the development of next-generation statins engineered to avoid binding to RyR1, preserving the cholesterol-lowering benefit while eliminating the muscle toxicity.
