Researchers at Columbia University Irving Medical Center have made a significant breakthrough in understanding why many individuals experience muscle pain when taking statins, a common class of cholesterol-lowering medications. Their study reveals that certain statins, particularly simvastatin, can bind to a crucial muscle protein, leading to harmful calcium leaks within muscle cells. This discovery may explain why approximately 10 percent of the 40 million adults in the United States who take statins discontinue their use due to muscle-related side effects.
The research, published on December 15, 2025, in the Journal of Clinical Investigation, highlights how the interaction between statins and muscle tissue proteins can disrupt normal muscle function. According to Andrew Marks, chair of the Department of Physiology and Cellular Biophysics at Columbia, the findings could help address a longstanding issue that has puzzled scientists since statins were first introduced in the late 1980s.
The study utilized advanced imaging techniques, specifically cryo-electron microscopy, to closely observe the interaction between statins and muscle cells. The researchers discovered that simvastatin attaches to two specific sites on the ryanodine receptor, a protein integral to muscle contraction. This binding action opens a channel, allowing calcium ions to leak into areas of the muscle cell where they typically do not flow. Marks suggests that this excess calcium may directly weaken muscle fibers or activate enzymes that lead to gradual muscle degradation.
“This explanation might not apply to every individual experiencing muscle pain from statins, but even if it helps a small subset, we can significantly improve their quality of life,” Marks stated. He noted that many patients refuse to take statins due to these adverse effects, emphasizing the urgency for a solution.
The study adds to a growing body of evidence indicating that while statins are effective in controlling cholesterol levels, they can also interact with unintended targets in the body, resulting in harmful side effects. Previous research hinted at this interaction, but the specific mechanisms were not clear until now.
Looking forward, the findings open new avenues for research aimed at minimizing the side effects associated with statin use. One potential approach involves redesigning statins to retain their cholesterol-lowering capabilities while preventing them from binding to the ryanodine receptor. Marks is collaborating with chemists to develop such modified statins.
Additionally, the researchers are exploring ways to halt the calcium leaks triggered by statins. Marks’ laboratory has developed an experimental drug that has shown promise in closing statin-related calcium leaks in animal models. If successful in humans with rare muscle diseases, this drug could also be tested for those suffering from statin-induced myopathies.
Andrew Marks holds multiple roles at Columbia University, including Clyde and Helen Wu Professor of Medicine and director of the Wu Center for Molecular Cardiology. Funding for this significant research was provided by the National Institutes of Health through various grants.
As research progresses, these insights could lead to safer alternatives for millions of people reliant on statins for managing their cholesterol levels while minimizing the impact of muscle pain and weakness.
