Statin muscle side effects linked to calcium channel disruption
Using cryo-electron microscopy, researchers found that statins bind to the ryanodine receptor RyR1 in muscle cells and keep its calcium channel open. The resulting continuous calcium leak can injure muscle tissue and may explain pain, weakness, and rare severe damage. The team says the mechanism could help design cholesterol drugs with fewer muscle effects.
Statins are widely prescribed to cut cholesterol and lessen the chance of cardiovascular events, yet some users develop aching muscles or reduced strength, and a rare few suffer serious muscle injury that can harm the kidneys. Researchers at UBC and the University of Wisconsin–Madison used cryo-electron microscopy and published in Nature Communications.
Focusing on atorvastatin, they found three drug molecules occupying a pocket on RyR1, a calcium channel. One binds while the channel is shut, making opening more likely; two more then help hold it open, producing sustained calcium leakage. The team suggests other statins may behave similarly.
For patients who need statins, this finding may help explain puzzling muscle symptoms and could support better conversations with clinicians about risks and adherence. Drug developers might use the structural details to design cholesterol-lowering medicines that avoid RyR1, potentially reducing muscle-related side effects. Because severe muscle damage is rare, the broader societal effect may be modest but could still matter for confidence in preventive treatment and for people who currently stop or avoid statins due to muscle concerns.