Scientists Identify Mechanism Behind Statin-Related Muscle Pain

Research from Columbia University Irving Medical Center has unveiled a potential explanation for the muscle pain experienced by many individuals taking statins, medications widely prescribed to lower cholesterol levels. The study, published on December 15, 2025, in the Journal of Clinical Investigation, highlights how certain statins can interact with muscle cells, leading to harmful calcium leaks that may cause pain and weakness.

Many patients discontinue statin therapy due to adverse effects, with muscle-related symptoms being a primary concern. Approximately 40 million adults in the United States rely on statins, yet an estimated 10 percent report experiencing muscle discomfort. This new research sheds light on a long-standing issue that has puzzled scientists since statins first became available in the late 1980s.

Understanding the Mechanism

The research team, led by Andrew Marks, chair of the Department of Physiology and Cellular Biophysics at the Vagelos College of Physicians and Surgeons, utilized advanced imaging techniques such as cryo-electron microscopy. This method allowed them to observe how simvastatin, a commonly prescribed statin, binds to the ryanodine receptor, a key protein in muscle cells.

The binding of simvastatin to the ryanodine receptor opens a channel that causes calcium to leak into muscle cells. Marks explains that this unregulated calcium flow can weaken muscle fibers directly or activate enzymes that progressively degrade muscle tissue. The findings suggest that even if this mechanism does not apply to every patient, it could potentially help a significant number of individuals suffering from statin-related muscle pain.

Implications for Future Treatments

The discovery opens avenues for developing statins that retain their cholesterol-lowering efficacy while minimizing muscle-related side effects. Marks is collaborating with chemists to redesign statins, aiming to prevent them from binding to the ryanodine receptor in muscle cells.

Another promising strategy involves addressing the calcium leak itself. In preliminary studies with mice, an experimental drug developed in Marks’ laboratory successfully closed the calcium leak associated with statin use. According to Marks, if this drug proves effective for patients with rare muscle diseases, it could also be tested for those experiencing myopathies induced by statins.

The research not only aims to improve the experience of patients on statins but also addresses a significant public health concern. As Marks highlights, “It’s the most common reason patients quit statins, and it’s a very real problem that needs a solution.”

Funding for this research was provided by various grants from the National Institutes of Health, underscoring its scientific credibility. Marks, who holds shares in RyCarma Therapeutics Inc., is also a co-inventor on patents related to treatments targeting the ryanodine receptor.

As this important research progresses, it may pave the way for safer cholesterol management options, potentially allowing millions to benefit from statin therapy without the burden of debilitating side effects.