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).

An international research team led by The University of Manchester analyzed magma from the 2021 Tajogaite eruption on La Palma, Spain. The scientists found that “superheating,” which occurs when magma becomes hotter than the temperature at which crystals remain stable, can postpone crystal formation as the magma moves toward the surface.

Superheating Removes Crystal Seeds

The study, published in Nature Communications, found that intense heat can dissolve tiny existing crystals that normally act as “seeds” for the growth of new crystals.

Superheating also reorganizes the magma at a microscopic level, making its internal structure more uniform and less favorable for new crystals to develop. These changes can affect both the speed at which magma rises and the ease with which volcanic gases escape. Together, those factors can strongly influence whether an eruption produces dramatic lava fountains or a slower release of lava.

The results provide new insight into a long-running scientific question about how magma’s temperature history affects crystallization before and during an eruption.

Lead author, Dr. Barbara Bonechi, Research Associate at The University of Manchester, said: “The history of crystal and bubble growth can dramatically control how a magma erupts; in particular, as more crystals grow, they eventually have a dramatic effect on magma viscosity. Until now, we did not fully understand the dynamics of crystal growth for magmas that received an injection of superheat just before ascent. But using our exciting and newly developed X-ray transparent pressure vessel combined with synchrotron X-ray microtomography, we can actually observe these processes ‘in situ’.”

Recreating Volcanic Conditions in the Laboratory

To investigate the process, the researchers recreated conditions found inside a volcano using magma collected from the Tajogaite eruption. That magma may have been superheated before the eruption and while it was rising through the crust.

At Diamond Light Source, the team used synchrotron X-ray microtomography to watch crystals form inside the magma in real time. They also conducted complementary ex-situ experiments in Prague, which made it possible to observe the samples over longer periods.

Together, the experiments allowed the scientists to follow crystallization under carefully controlled conditions of intense heat and pressure.

Crystal Growth Delayed for More Than Eight Hours

The difference between the samples was striking. Magma that had not been superheated began forming crystals after about 20 minutes.

By comparison, strong superheating prevented crystal formation for more than eight hours.

The researchers used these experimentally measured nucleation delays in numerical models of magma ascent. These simulations were designed to show how magma moves and changes as it travels upward through Earth’s crust.

How Heat Can Change an Eruption

The models indicated that a long delay in crystallization can keep magma relatively fluid, allowing it to rise rapidly toward the surface. This fast-moving magma could help generate dramatic lava fountains.

When crystals begin forming earlier, however, the magma becomes thicker and more viscous. It then rises more slowly, giving volcanic gases additional time to escape and making a gentler, effusive eruption more likely.

The researchers say this newly recognized role of superheating could help volcanologists better interpret monitoring data and improve forecasts of eruption behavior.

Co-author Dr. Margherita Polacci, Senior Lecturer in Volcanology at The University of Manchester, said: “Current volcanic hazard models typically focus on magma chemistry, gas content and pressure changes. This work suggests that pre-eruptive thermal history and crystallization kinetics may also play an important role in controlling magma ascent and eruptive behavior, with implications for volcanic hazard assessment.”