Scientists Explain Why Cholesterol Drugs Can Trigger Painful Side Effects in Some People

Statins are among the most commonly prescribed medications in the United States for treating high cholesterol, but they do not work smoothly for everyone. A meaningful share of patients stop taking them because of painful side effects known as statin-associated muscle symptoms, or SAMS. Although many people tolerate statins well, up to 10% develop muscle aches and discomfort.

Researchers may now have a clearer explanation for these long-mysterious reactions, which could open the door to new ways of preventing them.

Meet the experts: Catherine Benziger, M.D., member of the American College of Cardiology Prevention of Cardiovascular Diseases Council; Cheng-Han Chen, M.D., board-certified interventional cardiologist and medical director of the Structural Heart Program at MemorialCare Saddleback Medical Center in Laguna Hills, CA

A preliminary study published in the Journal of Clinical Investigation examined mice and pointed to a possible biological pathway behind SAMS, as well as why certain people may be more vulnerable than others. The issue may not be the statin itself, but a gene mutation in the person taking it.

In the study, researchers compared two groups of mice: one wild-type group and another with a genetic mutation affecting skeletal muscle receptors. After both groups received simvastatin, a type of statin, the mice with the mutation were more likely to show SAMS. The mutation appears to alter calcium release when statins are introduced, allowing excess calcium to enter muscle cells and leading to pain or discomfort.

Cardiologists explain what this could mean for people who take statins or are considering them.

What the research suggests

Even though some patients struggle with side effects, statins remain one of the most effective ways to lower LDL, or “bad,” cholesterol. Understanding why symptoms occur is important, says Catherine Benziger, M.D., member of the American College of Cardiology Prevention of Cardiovascular Diseases Council. “Statins are an incredibly effective and proven therapy to lower cholesterol and reduce the risk of heart attacks and strokes,” she explains. “But I see many patients who complain of muscle aches and cramps after starting a statin in my clinic... Sometimes this is minor, and the medication can be continued, but other times it is severe, and the medication must be stopped.”

“Statin-associated muscle symptoms are the most common reason people stop their statins,” says Cheng-Han Chen, M.D., board-certified interventional cardiologist and medical director of the Structural Heart Program at MemorialCare Saddleback Medical Center in Laguna Hills, CA. “Better understanding the cause of these symptoms can potentially help us find ways to reduce these effects and help patients to stay on these important medications.”

The findings matter, Dr. Benziger says, because they point to a specific biological mechanism that may explain SAMS. “When a mechanism is backed up by basic science and clinical research, it makes it easier to counsel patients and educate them about what the side effects they have might be caused by,” she explains. “It also can improve our knowledge of who might be more likely to be affected, specifically those with genetic mutations, and how we can possibly prevent them.”

Dr. Chen adds that the work also suggests a medication aimed at this mutation could potentially prevent symptoms. That, he says, “could potentially help us treat these side effects and help patients stay on the statins that they need.”

What this means for you

If you are starting a statin or already taking one, do not stop on your own. Watch for side effects and tell your doctor about them. “If a patient has muscle side effects, I tell [them] to stop taking the statin for five to seven days and make sure the muscle side effects go away, and then restart it,” says Dr. Benziger. If symptoms return, she recommends working with your doctor to try a different strain or lower the dose.

If statins are hard to tolerate, are there other options?

According to Dr. Chen, side effects often improve after switching to a different strain. Still, some people may not tolerate statins at all. That does not mean cholesterol treatment should stop, Dr. Benziger cautions. “The key is getting the LDL to goal! It is critically important not to overlook managing cholesterol, particularly in someone who has diabetes mellitus, kidney disease, a history of heart disease, an elevated coronary artery calcium score, or other risk factors.” If statins are not an option, Dr. Chen and Dr. Benziger recommend talking with a doctor about alternatives such as a PCSK9 inhibitor or bempedoic acid.

The bottom line

The study offers a promising explanation for why some people experience SAMS, but there are still important unknowns. “These findings have only been studied in a mouse model. Future research will be needed to determine whether the findings translate to humans as well,” Dr. Chen points out.

If later studies confirm the results, Dr. Benziger says the findings could help shape new therapies for people who qualify for statins. The research, she notes, offers “a hypothesis for future therapies that could reduce these side effects or lead to improved treatments without this limitation.”