Scientists at Columbia University have identified a mechanism explaining why some people experience muscle pain from cholesterol-lowering statins. The study reveals that certain statins bind to a muscle protein, causing calcium leaks that weaken muscles. This discovery could lead to safer drugs for the millions who rely on these medications.
For decades, statins have been a cornerstone in managing high cholesterol, with about 40 million adults in the United States taking them. However, around 10 percent of users develop muscle-related side effects like pain, weakness, or fatigue, leading many to stop the treatment. This has puzzled researchers since the drugs emerged in the late 1980s.
A new study from Columbia University provides a breakthrough. Using cryo-electron microscopy, the team visualized how simvastatin, a common statin, attaches to two sites on the ryanodine receptor, a key protein in muscle cells. This binding opens a channel, allowing calcium ions to leak into areas where they disrupt normal function. The excess calcium can directly weaken muscle fibers or activate enzymes that break down tissue over time.
"It is unlikely that this explanation applies to everyone who experiences muscular side effects with statins, but even if it explains a small subset, that's a lot of people we could help if we can resolve the issue," said Andrew Marks, chair of the Department of Physiology and Cellular Biophysics at Columbia's Vagelos College of Physicians and Surgeons.
Marks, who has treated patients reluctant to continue statins due to these issues, emphasized the problem's prevalence. "I've had patients who've been prescribed statins, and they refused to take them because of the side effects. It's the most common reason patients quit statins, and it's a very real problem that needs a solution."
The findings, published on December 15, 2025, in the Journal of Clinical Investigation, suggest paths forward. Researchers are redesigning statins to avoid the ryanodine receptor interaction. In mouse models, an experimental drug from Marks' lab closed the calcium leaks. "These drugs are currently being tested in people with rare muscle diseases. If it shows efficacy in those patients, we can test it in statin-induced myopathies," Marks noted.
This work highlights unintended statin effects beyond cholesterol production and opens doors to muscle-friendly alternatives.
