Scientists have recently found one possible reason why.<\/p>\n
Research from Columbia University and the University of Rochester in the US revealed a potential culprit: a tiny calcium gate inside muscle cells that statins may force open.<\/p>\n
The resulting calcium leak can damage muscle tissue, offering a new explanation for at least some cases of statin-associated muscle symptoms (SAMS).<\/p>\n
“I’ve had patients who’ve been prescribed statins, and they refused to take them because of the side effects,” said<\/a> lead author Andrew Marks, a cardiologist at the Columbia University Vagelos College of Physicians and Surgeons.<\/p>\n Statins work by blocking an enzyme that’s required for the biosynthesis of cholesterol in the liver.<\/p>\n As a result, levels of ‘bad’ LDL cholesterol<\/a> are reduced in the blood<\/a>, helping to prevent one of America’s top killers<\/a>: cardiovascular diseases like atherosclerosis, the buildup of fatty deposits in blood vessels.<\/p>\n But statins also affect “off-target” molecules, including a protein called ryanodine receptor 1<\/a> (RyR1). RyR1 is a mushroom-shaped channel, or gate, located on the sarcoplasmic reticulum<\/a>, a web-like structure that surrounds muscle fibers.<\/p>\n RyR1 acts like a bouncer at a club, opening or closing the door to let calcium ions flow into the muscles. This calcium flow is an essential process that mediates muscle contractions.<\/p>\n Using mice as models, the researchers observed the precise way statins bind to RyR1, using an imaging technique called cryo-electron microscopy<\/a> (cryo-EM).<\/p>\n Cryo-EM involves flash-freezing biological samples and then blasting them with electron beams. The deflection pattern of the electrons reveals tiny structures, allowing scientists to create highly detailed 3D images<\/a> of things like proteins and view their constituent molecules.<\/p>\n Yet cholesterol-lowering drugs like simvastatin<\/a> may keep these gates open, allowing calcium ions to leak into muscle cells, which can either directly damage muscles or trigger enzymes that degrade them.<\/p>\n As a result, statin users may experience persistent pain, weakness, tenderness, and cramps<\/a>.<\/p>\n The issue is exacerbated in individuals with RyR1 mutations, who may also experience episodes of malignant hyperthermia<\/a> (a severe overheating triggered by medication) or weakness in the diaphragm<\/a> that leads to reduced lung function and respiratory disorders.<\/p>\n In rare but potentially life-threatening cases, the side effects of statins can induce rhabdomyolysis<\/a>, a serious syndrome in which muscle tissues rupture and leak into the bloodstream, culminating in kidney failure<\/a>.<\/p>\n The equally gruesome autoimmune-mediated necrotizing myositis<\/a> may also rarely occur, a condition in which the immune system turns against its own tissues and kills muscle tissue.<\/p>\n The leaky calcium gate explanation may not apply to all cases of SAMS, but now that we understand this mechanism, it could help identify people at risk of statin intolerance.<\/p>\n Around 40 million adults take statins in the US alone, and approximately 10 percent of treated individuals experience SAMS.<\/p>\n “It’s the most common reason patients quit statins, and it’s a very real problem that needs a solution,” said<\/a> Marks.<\/p>\n Related: US Cardiologists Have Published New Guidelines For Managing Cholesterol<\/a><\/p>\n The researchers highlight two promising options. The first is to redesign statins so they don’t bind to RyR1 but still inhibit cholesterol production in the liver.<\/p>\n Alternatively, when the researchers treated statin-intolerant mice with Rycal<\/a>, an experimental class of drug used to treat patients with rare muscle diseases, they were able to close the leaky RyR1 calcium gates and prevent simvastatin-induced muscle weakness.<\/p>\n “It is unlikely that this explanation applies to everyone who experiences muscular side effects with statins,” Marks explained<\/a>.<\/p>\n “But even if it explains a small subset, that’s a lot of people we could help if we can resolve the issue.”<\/p>\n![\"YouTube](\"https:\/\/www.newsbeep.com\/ie\/wp-content\/uploads\/2026\/06\/1780363813_905_0.jpg\")
frameborder=”0\u2033 allow=”accelerometer; autoplay; clipboard-write; encrypted-media; gyroscope; picture-in-picture; web-share” referrerpolicy=”strict-origin-when-cross-origin” allowfullscreen><\/p>\n![\"protein](\"https:\/\/www.newsbeep.com\/ie\/wp-content\/uploads\/2026\/06\/ry_r1_protein_642.jpg\")
Structure of RyR1, a protein channel that allows calcium to leak into muscles. (Wenbo Chen<\/a>\/Chen & Kudryashev, EMBO Rep., 2020<\/a>)<\/p>\n![\"Subscribe](\"https:\/\/www.newsbeep.com\/ie\/wp-content\/uploads\/2026\/05\/1779408609_365_FOMO-1200x628-_Dont-miss-the-next-breakthrough_-cosmic-colourful-642x336.jpg\")
<\/a><\/p>\n![\"Cryo-EM](\"https:\/\/www.newsbeep.com\/ie\/wp-content\/uploads\/2026\/06\/marks_statin_binding_to_ryanodine_receptor-642x236.jpg\")
Simvastatin molecules bind to ryanodine receptors on a muscle protein. The flow of calcium through the opened channels in the receptors could explain the muscular side effects of statins. (Columbia University<\/a>)<\/p>\n