Many people start a cholesterol pill and, within a few weeks, feel their legs ache or stiffen when they stand up. Some push through it. Others quit, worried but unsure what to do next.
That nagging side effect has puzzled doctors for decades. Researchers at the University of British Columbia and the University of Wisconsin-Madison now say they can finally see what statins actually do inside muscle cells. Their findings were published in Nature Communications.
Using cryo-electron microscopy, a technique that photographs proteins almost atom by atom, the team watched statins latch onto a protein called RyR1.
The protein acts as a gate. It releases calcium inside muscle cells when you contract a muscle, and closes again when you relax.
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The images showed something unusual. Three statin molecules clustered together inside a pocket of the protein and wedged the gate open. Calcium then kept leaking out when it should have stayed locked away.
The leaking calcium, lead author Steven Molinarolo said, explains both the muscle pain many patients report and the rare but life-threatening complications that occasionally follow.
How common the muscle problem actually is
Statins are one of the most widely used classes of drugs in the world. More than 200 million people take them, and most do fine. But a sizeable minority report aches, cramps or weakness, and that is often why they stop.
In a 2022 clinical statement, the National Lipid Association estimated that muscle symptoms are reported by about 10 percent of statin users.
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A smaller slice, roughly 1 to 2 percent, is thought to be truly caused by the drug itself.
Muscle symptoms are also the single most common reason patients give for stopping their statin, according to the same statement.
In rare cases the damage escalates to rhabdomyolysis, a severe breakdown of muscle tissue that can injure the kidneys.
Why this matters for future drugs
Earlier research had already hinted that calcium signaling was involved. Welltica has reported before on work suggesting that statins disturb calcium handling in muscle, but no one had actually caught the drug binding to RyR1 in the act.
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That is what the new structural work shows. Senior author Filip Van Petegem, a professor at UBC's Life Sciences Institute, said the detailed picture gives chemists a map to work from.
The hope is that drug designers can tweak the statin molecule so it still blocks cholesterol production but no longer snaps onto RyR1.
That redesign has not been done yet. The statins on pharmacy shelves today are the same ones that have been in use for years.
Anyone struggling with muscle symptoms should talk to their doctor before stopping the medication, as a dose change or a switch to a different statin often helps.
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This article is made and published by Mie Hermansen, who may have used AI in the preparation.