Millions of people take statins to lower cholesterol and reduce their chances of having a heart attack or stroke. For some patients, however, the medications can cause muscle pain, weakness, and difficulty exercising, making it harder to stay on treatment.
Researchers at McMaster University have now identified a biological pathway that could help explain why these muscle symptoms develop. The finding may eventually lead to treatments that make statins easier to tolerate without reducing their important cardiovascular benefits.
Published in Science Advances, the study points to a previously unrecognized interaction between the immune system and muscle cell metabolism. The mechanism appears to contribute to muscle damage caused by statins and challenges earlier ideas about the origins of these side effects.
Why Statin Side Effects Matter
“Statins are among the most effective medications we have for reducing cardiovascular disease risk and preventing early death,” said Jonathan Schertzer, professor in McMaster’s Department of Biochemistry and Biomedical Sciences and senior author of the study.
“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.”
An estimated seven to 29 percent of statin users experience muscle-related symptoms. Although the connection between statins and muscle problems has been recognized for years, scientists have not fully understood the biological processes responsible.
Statins Can Disrupt Muscle Cell Energy
The research was led by first authors Nazli Robin and Nicole Barra of the Schertzer Lab at McMaster. Their team found that statins can interfere with the way muscle cells generate energy.
That disruption appears to activate an immune response inside the muscle cells, leading to tissue damage. In experiments involving muscle cells and mouse models, the researchers prevented much of the damage by blocking the immune response.
“One of the most exciting findings of the research is that the mechanism causing muscle side-effects appears to be separate from the mechanism that lowers cholesterol,” said Schertzer. “That suggests it may one day be possible to target the side-effects without interfering with the cardiovascular benefits that make statins so valuable.”
A Surprising Connection Between Immunity and Metabolism
The findings also uncovered an unexpected relationship between metabolism and the immune system. Changes in the way muscle cells processed energy caused the cells to activate their own immune response.
This discovery offers new insight into how inflammation may contribute to medication side effects. It also suggests that scientists could potentially protect muscle tissue by targeting the immune pathway while leaving the cholesterol-lowering effects of statins intact.
More research is needed before the findings can be developed into treatments for patients. Still, the newly identified pathway provides several possible targets for medications designed to prevent statin intolerance.
“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,” added Schertzer.
An International Research Collaboration
The project involved researchers from the Centre International de Recherche en Infectiologie (CIRI) in Lyon, France; the Centre for Muscle Research at the University of Melbourne, Australia; the Murdoch Children’s Research Institute and The Royal Children’s Hospital in Australia; York University in Canada; and McMaster’s Department of Pathology and Molecular Medicine.
The research was funded by the Natural Sciences and Engineering Research Council of Canada (NSERC).