Scientists from Columbia University have found that statins may cause muscle pain due to a “leak” of calcium within muscle cells. The findings were published in the Journal of Clinical Investigation (JCI).

Statins are widely used to lower cholesterol levels, but some patients discontinue them because of muscle pain, weakness, and chronic fatigue. Despite decades of use, the underlying causes of these side effects have remained unclear.

In the new study, researchers showed that in at least some patients the problem may arise from an unintended interaction between statins and the ryanodine receptor. This key protein in muscle cells regulates the movement of calcium ions.

Using cryo-electron microscopy, the scientists closely examined how the drug simvastatin interacts with this receptor and effectively pries open the calcium channel. As a result, calcium begins to flow uncontrollably into the cells. Such leakage can directly weaken muscles or activate enzymes that break down muscle tissue, leading to pain and weakness.

According to the authors, this mechanism is unlikely to explain all cases of statin-associated myopathy, but even if it applies to only a small fraction of patients, it would still affect millions of people.

Experiments in mice showed that statin-induced calcium leakage can be prevented with an experimental drug previously developed for other disorders involving disrupted calcium signaling. These compounds are currently being tested in people with rare muscle diseases.