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Researchers have uncovered a biological pathway that may explain why statins cause muscle pain in some patients, a discovery that could pave the way for treatments that eliminate one of the drugs’ most common side effects without reducing their cholesterol-lowering benefits.

The study, led by researchers at McMaster University and published in Science Advances, found that statin-related muscle damage appears to result from an unexpected interaction between muscle cell metabolism and the immune system. The findings challenge previous theories about the cause of statin intolerance and could help millions of patients continue taking the life-saving medications.

Statins are widely prescribed to lower cholesterol and reduce the risk of heart attacks and strokes. However, muscle pain, weakness, and exercise intolerance affect an estimated 7 to 29 percent of users, causing many patients to reduce their dosage or stop treatment altogether.

The McMaster team discovered that statins can disrupt how muscle cells produce energy. This metabolic disruption triggers an immune response within the muscle tissue, leading to inflammation and damage. In experiments using muscle cells and mouse models, researchers were able to prevent much of the damage by blocking that immune response.

Senior author Jonathan Schertzer said the most significant finding was that the biological mechanism responsible for muscle side effects appears to be separate from the one that lowers cholesterol. If confirmed in future studies, this separation could allow scientists to develop therapies that target muscle symptoms while preserving the cardiovascular benefits of statins.

The research also revealed a previously unknown connection between cellular metabolism and the immune system. Changes in energy production caused muscle cells to activate their own immune defenses, offering new insight into how inflammation contributes to medication-related side effects.

Although the findings are still at the experimental stage and more research is needed before treatments become available, the newly identified pathway provides several promising drug targets for preventing statin intolerance. The international study involved researchers from Canada, France, and Australia and was funded by the Natural Sciences and Engineering Research Council of Canada.