Scientists have uncovered how some statins may cause muscle pain by disrupting calcium balance in muscle cells, offering paths to safer therapies.
Many people discontinue cholesterol-lowering statins after developing muscle pain, weakness, or ongoing fatigue.
New research from scientists at Columbia suggests that, for some patients, these symptoms may occur when statins attach to a protein inside muscle cells, triggering an abnormal release of calcium ions within the cell.
“It is unlikely that this explanation applies to everyone who experiences muscular side effects with statins, but even if it explains a small subset, that’s a lot of people we could help if we can resolve the issue,” says Andrew Marks, chair of the Department of Physiology and Cellular Biophysics at the Vagelos College of Physicians and Surgeons.
Statins are widely prescribed, with roughly 40 million adults in the United States using them to reduce cholesterol levels. About one in ten of these patients report muscle-related side effects.
“I’ve had patients who’ve been prescribed statins, and they refused to take them because of the side effects. It’s the most common reason patients quit statins, and it’s a very real problem that needs a solution,” says Marks.
Electron microscopy pinpoints statin-muscle interaction
Scientists have been trying to understand statin-related muscle problems since these drugs were introduced in the late 80s. While statins are meant to reduce cholesterol by binding to an enzyme involved in its production, they can also attach to other unintended targets. Earlier research has hinted that muscle symptoms may appear when statins interact with a particular protein found in muscle tissue.
Using cryo-electron microscopy, which allows researchers to visualize molecular structures at extremely high resolution, the team behind the new study was able to directly observe this interaction and map out its exact structural details.
The images revealed two locations on the muscle protein, called the ryanodine receptor, where a statin called simvastatin binds, opening a channel in the receptor and allowing calcium to flow through.
The calcium leak could explain the muscular side effects of statins, Marks says, by weakening the muscle directly or by activating enzymes that degrade muscle tissue.
Building a better statin
The new images also suggest that statins could be redesigned so they do not bind the ryanodine receptor but retain their cholesterol-lowering ability.
Marks is now collaborating with chemists to create such a statin.
Plugging the calcium leak could be another option: Statin-induced calcium leaks in mice can be closed, the researchers showed, with an experimental drug developed in the Marks lab for other conditions involving calcium leaks.
“These drugs are currently being tested in people with rare muscle diseases. If it shows efficacy in those patients, we can test it in statin-induced myopathies,” Marks says
Reference: “Structural basis for simvastatin-induced skeletal muscle weakness associated with type 1 ryanodine receptor T4709M mutation” by Gunnar Weninger, Haikel Dridi, Steven Reiken, Qi Yuan, Nan Zhao, Linda Groom, Jennifer Leigh, Yang Liu, Carl Tchagou, Jiayi Kang, Alexander Chang, Estefania Luna-Figueroa, Marco C. Miotto, Anetta Wronska, Robert T. Dirksen and Andrew R. Marks, 15 December 2025, The Journal of Clinical Investigation.
DOI: 10.1172/JCI194490
Funding: The research was supported by grants from the NIH (R01HL145473, R01DK118240, R01HL142903, R01HL140934, R01NS114570, R01AR070194, R01AR078000 , R25HL156002, R25NS076445, P01HL164319, and T32HL120826.
Disclosure: Andrew Marks owns stock in RyCarma Therapeutics Inc., a company developing compounds targeting the ryanodine receptor, and a coinventor on U.S. patent nos. US8022058 and US8710045. Gunnar Weninger, Haikel Dridi, Marco Miotto, and Andrew Marks are inventors on the patent application entitled “STATIN INNOVATION FOR MUSCLE-FRIENDLY CHOLESTEROL MANAGEMENT” [Invention Report (IR) #CU24350] to be filed by Columbia University.
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19 Comments
I
Have been on statins for 40 years
I am on Cholman 20 at the moment
Do suffer from sore muscles on and off.
My cholesterol hereditary
Reading stays between 6 and 7.
Shirley le roux
Have tried 4 different statins.
Pain in my muscles has forced me to discontinue them.
I was on Rosuvastatin for 12 days in 2018. I have a myopathy from it, the myopathy caused breast cancer that was discovered in 2020. I reached my 5 year cancer free this year . The myopathy is awful. Is there a clinical trial for this med? I am very interested!
I’ve tried 4 different statins muscle pain and fatigue plus brain fog I decided to discontinue these drugs and feel a whole lot better for doing so
I heard that statins blocks the pathway to produce CoQ 10 and by supplementing with a high quality product like Ubiquinol can alleviate the muscle pain. Is there research to support this? I do not take statins btw.
What causes cognitive changes from statins or repatha with some people? Is our ability to differentiate healthful from harmful cholesterol ( remnant VLDL and chylomicrons) the real issue? Is the statin reduction quest relevant in its current form? Since 1948, we’ve learned a lot. Can we rethink Framingham?
The pain can be unbearable. I attribute it to arthritis but It was the side effect of the statin. I wonder why my physician never mentioned that it is a possibility that I could experience this pain.
I knew in first week no good. Did diet took care of it.more side effects to statins than listed .its just a money maker.i know 2 doctors that sued for unlisted side effects.plus you need cholesterol for brain and hormones. One reason why men are getting infertile
DO NOT TAKE STATINS, they are horrible for you and do not provide you with benefit. They make you diabetic, they waste your muscles and kill your good cholesterol which is needed for hormone production. The top cardiologist in the world do not put their patients that have already had a heart attack on these meds. I take all my patients off these meds the second we meet and I dont have any issues. Another exmaple of drug manufacturers infiltrating medicine to create an algorithm to make them money. You need serial cholesterol testing to have a good panel of understanding, not just a single fasting study. All statins are poison, do not take them
Definitely agree.
For every drug, there are side effects. But don’t worry, there are drugs to treat those side effects. If those cause side effects, there’s also a pill for those ……..
What causes cognitive changes from statins or repatha with some people? Is our ability to differentiate healthful from harmful cholesterol ( remnant VLDL and chylomicrons) the real issue? Is the statin reduction quest relevant in its current form? Since 1948, we’ve learned a lot. Can we rethink Framingham?
Forget muscle soreness, statins disrupt GLP-1 synthesis. This is why DIABETES is the side-effect people should be the most concerned about.
It’s all right here:
“Statins aggravate insulin resistance through reduced blood glucagon-like peptide‑1 levels in a microbiota‑dependent manner.” Cell Metabolism (2024), 36(2): 408–421.e5
DOI: 10.1016/j.cmet.2023.12.027
Yeah, whatever. Such is life. Been there, doing that.
Following Bypass Surgery in 2023 I found myself on a daily dose of 40mg Atvorvastin. 3mths, later calf muscle strain (blood beneath skin) daily nausea I’m on the edge of type 2 diabetes. Stopped taking it. Within weeks symptoms vanished. To me it’s obvious, for the vast majority of people the body creates the amount of cholesterol your body needs to operate. No more no less. Yes, it travels around the body via the cardiovascular system. This in turn will contribute to a build up of plaque as we age. The harsh reality is, there’s no free lunch in this life and taking another drug to minimize the effects of preventing your liver from doing it’s job, is like applying paint to rotten wood 🪵.
Regarding the CALCIUM LEAKS–
I’m a man in mid 50’s with OSTEOPOROSIS and always had a light frame. Wondering if a high percent of ppl who can’t tolerate statins also have bone loss generally?
Could this Calcium Leak be a clue about a failed mechanism that people have even when not on stains?
If there;s a connection between this receptor/enzyme and calcium/bone-related disorders, we may be a step closer to resolving Osteoporosis and calcium-related issues in a lot of people.
eg Besides statins causing muscle reactions, I had extremely high blood/urine CALCIUM levels when on bone meds like Forteo.
If you have myopathic reaction to statins AND bone or calcium-related issues, please share your experiences.
I have inherited cholesterol. Have had five different statins and every one of them have caused extremely sore muscles, I decided to stop them completely. I am 74 have a good diet and look after myself physically. I don’t feel that I need to take these statins that make me feel really ill when taking them.
I was on Rosuvostin for about 9 months, getting cramps, then muscle pain mainly calves with beach swimming, L>R. I stopped it. Slow improvement. No path test abnormalities. My Dr told me to restart which I did for 10 days – mowed the lawns, then muscle pains ++. It has been all down hill since, with increasing pain and weakness. MRI showed muscle oedema, and biopsy (1cm square x 2 cm long) showed necrotising myositis. No improvement in the following 28 months despite p[rednisolone, methotrxate and mycophenalate. Off everything now and possibly a little improvement, but hour to hour and day to day fluctuations. Have ditched the walking stick mostly. Did really need it.
When my husband was prescribed a statin, his heart specialist told him to take 200mg of Co-Enzyme Q10 every day. My research supports this. About a year or so later, an idiot GP told him to stop taking the Co-Enzyme Q10. He started having muscle problems within a few days. I had him restart taking the Co-Enzyme Q10 and the muscle pain went away. Co-Enzyme Q10 is a natural component in your cells, but the statins affect the amount that you have.
It’s not the whole picture. The best thing is to get to a point where you have low enough cholesterol to be able to lower and eventually stop taking the statins. Basically taking statins trades one problem for another. However the Co-Enzyme Q10 will help with the muscle pain.
Drug companies can’t conner the market for Co-Enzyme Q10 as it’s a popular supplement you can buy easily whenever you can get vitamins. It became popular because people believed that it was a miracle anti-aging supplement. It’s not, but it’s still easily accessible as a supplement to help with statin caused muscle pain.
More research is needed, but it should not exclude things that drug companies can patent.