Millions of people take statins to lower cholesterol and reduce their risk of heart attacks and strokes. For some, however, the drugs cause muscle pain, weakness and difficulty exercising — side effects that lead many patients to quit treatment. Now researchers at McMaster University say they have found a biological pathway that could help explain why these symptoms develop, and possibly a way to prevent them.
The study, published in Science Advances, points to a previously unrecognized interaction between the immune system and muscle cell metabolism. Statins can interfere with the way muscle cells generate energy, the team found, and that disruption activates an immune response inside the cells that leads to tissue damage. In experiments with muscle cells and mouse models, blocking that immune response prevented much of the damage.
An estimated 7 to 29 percent of statin users experience muscle-related symptoms. "Statins are among the most effective medications we have for reducing cardiovascular disease risk and preventing early death," said Jonathan Schertzer, a professor at McMaster and senior author of the study. "Unfortunately, muscle side-effects lead some people to reduce their dose or stop taking the medication altogether."
One of the most promising findings: the mechanism causing the 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," Schertzer said.
The research also revealed a surprising link between metabolism and immunity: changes in how muscle cells processed energy caused the cells to activate their own immune response, offering new insight into how inflammation may contribute to medication side effects. The work involved researchers from France, Australia, Canada and the UK, and was funded by Canada's Natural Sciences and Engineering Research Council. More research is needed before the findings become treatments, but the newly identified pathway provides several possible drug targets to make statins easier to tolerate.
