4 min readFOR PEOPLE WITH high cholesterol, statins are a game-changing medication. So why are a chunk of medicated users quitting them after a while?
Up to 10 percent of people who take them end up dealing with muscle pain and weakness as a side effect. Things can get so intense that some people stop taking the medication altogether.
Doctors are aware of the situation, but for decades it's been a mystery why it happens. Now, we might have answers via a recent study published in The Journal of Clinical Investigation that could lay a path for preventing it altogether.
When a Statin Is Also a Double-Edged Sword
Scientists in the 60s and 70s had found more evidence that high cholesterol levels were directly contributing to heart disease. When statins were first approved in 1987, the medications seemed promising. They work by binding an enzyme involved in the breakdown of cholesterol in the body.
Here's where it gets tricky: Statins also bind to other molecules.
One of statins' unintended targets is a protein called ryanodine receptor 1 (RyR1). RyR1 acts as a gate, opening or closing the entryway for calcium ions to get into the muscles. Having a flow of calcium is important for muscle contractions.
A few studies have suggested that the muscular side effects of statins—which can range from muscle stiffness and cramps to rare cases of rhabdomyolysis—may have something to do with a calcium 'leak.'
“These muscle cramps are probably just as painful as any muscle cramp,” says Jamie Alan, PhD, associate professor of pharmacology and toxicology at Michigan State University. “However, because the statin is everywhere in the body, sometimes more muscles end up cramping and that causes more pain.”
Nailing down the exact molecular mechanism behind this has stumped scientists for decades. Until now.
What Did The New Study Find?
In the December 2025 study, scientists used mice to see what was going on at the molecular level. They genetically engineered a mutation—taken from an actual person with a statin intolerance— into the animals. Their water was infused with a type of statin called simvastatin (Zocor), which they drank freely for 6 weeks.
Using a tool called cryo-electron microscopy, scientists then flash froze several samples of muscle tissue from the mice, which allowed them to preserve its structure without creating large ice crystals. The tissue samples were then hit with an electron beam to make detailed 3D images of molecules—down to their individual atoms. Putting thousands of these frame-by-frame shots together created a cellular stop-motion movie.
The team watched the interaction between statins and RyR1 and found two 'scenes' worth analyzing. First, the moment when simvastatin bound to the pore region of RyR1. The lock-and-key binding opened up the RyR1 channel and allowed calcium ions to flow through. According to the researchers, simvastatin kept the gate open for an extended period, which could be what's causing the direct weakening of the muscle—or activation of enzymes that break down muscle tissue.
A Potential Treatment for Statin-Induced Muscle Pain
People sometimes get relief if they stop taking the statins, says Kelly Johnson-Arbor, MD, a toxicologist at MedStar Health. “But discontinuation of statins is associated with detrimental outcomes, including an increased risk of heart problems and hospital admission.”
Now that scientists have found the likely cause of muscle pain, they have started working with a drug called Rycal, which is already used in people with rare muscle conditions. Results from mice already look promising.
In a separate experiment, scientists also gave a group of mice a mixture of simvastatin and Rycal in their drinking water for 6 weeks. Those who also had Rycal in their water did not show signs of statin-induced muscle weakness. Further analysis of the tissue showed Rycal helped stabilize and close the RyR1 channel.
What Can You Do Now, Though?
The findings suggest a few different ways that doctors could prevent or treat statin side effects in the future. One is to redesign statins to avoid binding to RyR1. Another is Rycal.
That said, Rycal is not currently approved for use in cases of statin-induced muscle weakness. In the meantime, Alan says there are other viable options currently available. These include switching to other cholesterol-lowering medications like ezetimibe (Zetia), lowering the statin dose, or switching to a lower-potency statin.
If you get muscle cramps on a statin, it’s important to talk to your healthcare provider. “There is a chance that this could progress to rhabdomyolysis, which can be fatal,” Alan says. Once that’s ruled out, Johnson-Arbor says you can work with your healthcare provider to go over your dosage, physical activity level, vitamin deficiencies, and other factors that might be leading to muscle soreness.
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Jocelyn Solis-Moreira, MS is the associate health & fitness for Men's Health and has previously written for CNN, Scientific American, Popular Science, and National Geographic before joining the brand. When she's not working, she's doing circus arts or working towards the perfect pull-up.
