McMaster Team Uncovers Pathway Behind Statin Muscle Side-Effects

Millions of people take statins to lower cholesterol and reduce the risk of heart attack and stroke, but for some patients, the drugs bring on muscle pain, weakness and exercise intolerance severe enough to make continuing treatment difficult. Statin-associated muscle symptoms affect an estimated seven to 29 per cent of people who take the drugs, and until now, the biological mechanisms behind these effects have remained unclear.

A study published in Science Advances by researchers at McMaster University has identified an immune and metabolic mechanism that drives statin-induced muscle damage, challenging longstanding assumptions about how these side-effects develop.

Led by first authors Nazli Robin and Nicole Barra of the Schertzer Lab at McMaster, the research team found that statins can disrupt how muscle cells produce energy, triggering an immune response that damages muscle tissue. Using muscle cells and mouse models, the researchers were able to prevent much of that damage by blocking the immune response.

According to senior author Jonathan Schertzer, statins remain among the most effective medications available for reducing cardiovascular disease risk and preventing early death. “Unfortunately, muscle side-effects lead some people to reduce their dose or stop taking the medication altogether. We wanted to understand why this happens and whether it might be possible to separate the side-effects from the benefits,” he said.

The findings suggest that may be possible. Schertzer said that one of the most exciting results is that the mechanism causing muscle side-effects appears to be separate from the mechanism that lowers cholesterol. “That suggests it may one day be possible to target the side-effects without interfering with the cardiovascular benefits that make statins so valuable,” he said.

The study also revealed an unexpected link between metabolism and immunity, showing that changes in muscle-cell metabolism triggered an immune response within the cells themselves. This provides new insight into how inflammation can contribute to drug side-effects more broadly.

While additional research is needed before the findings can be translated into therapies for patients, the discovery points to several potential targets for future drug development aimed at preventing statin intolerance. As Schertzer put it, “These findings give us a clearer understanding of why some patients experience muscle symptoms and provide promising directions for making these important medications safer and more effective in the future.”