Scientists identify how statins trigger muscle pain, paving way for safer cholesterol drugs

Molecular mechanism discovered using advanced imaging could help design medications without debilitating side effects

By LineZotpaper

Published20 October 2026

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Researchers at the University of British Columbia (UBC) and the University of Wisconsin-Madison have identified the molecular mechanism by which statins, a class of drugs used by more than 200 million people worldwide, cause muscle pain and damage, according to a study published in Nature Communications. The discovery could lead to safer cholesterol-lowering medications that preserve cardiovascular benefits without the risk of muscle injury.

Statins are among the most widely prescribed medications for preventing heart attacks and strokes by lowering cholesterol. While they have saved millions of lives, some patients experience muscle pain, weakness or, in rare cases, severe muscle breakdown that can lead to kidney failure. The side effects often cause people to stop taking the drugs, losing protection against cardiovascular disease.

Using cryo-electron microscopy, the team examined the ryanodine receptor (RyR1), a protein that controls calcium movement within muscle cells. Under normal conditions, RyR1 acts as a regulated gateway, releasing calcium when muscles need to contract. The researchers found that statins interfere with this process by holding the channel open, causing a continuous leak of calcium into areas where it should be tightly controlled. That leak injures muscle tissue.

"We were able to see, almost atom by atom, how statins latch onto this channel," said lead author Dr. Steven Molinarolo, a postdoctoral researcher at UBC. "That leak of calcium explains why some patients experience muscle pain or, in extreme cases, life-threatening complications."

The study focused on atorvastatin, a commonly prescribed statin, but the authors suggest similar interactions may occur with other drugs in the same family. One striking finding was that three statin molecules bind together in a specific pocket within the RyR1 protein. The first molecule binds while the channel is closed, making it more likely to open. Two additional molecules then enter the pocket and hold the channel open, sustaining the calcium leak.

"This is the first time we've had a clear picture of how statins activate this channel," said senior author Dr. Filip Van Petegem, professor at UBC's Life Sciences Institute. "It's a big step forward because it gives us a roadmap for designing statins that don't interact with muscle tissue."

Although severe muscle injury affects only a small percentage of statin users, milder symptoms like soreness, weakness and fatigue are more common. The structural insights could help drug developers modify statin molecules to avoid these interactions while maintaining cholesterol-lowering effects. Further research and development will be needed before new treatments reach patients.

"Statins have been a cornerstone of cardiovascular care for decades," Dr. Van Petegem said. "Our goal is to make them even safer, so patients can benefit without fear of serious side effects."

Analysis

Why This Matters

Statins are used by over 200 million people worldwide, and muscle side effects are a common reason for discontinuation, which increases cardiovascular risk.
Identifying the specific molecular pathway (the RyR1 calcium channel) gives drug developers a clear target to avoid, potentially leading to next-generation statins with fewer side effects.
The research could also improve quality of life for patients who experience milder but disruptive symptoms like soreness and fatigue.

Background

Statins work by inhibiting an enzyme involved in cholesterol production in the liver. They have been prescribed for decades as a cornerstone of cardiovascular disease prevention. However, muscle-related side effects have been a persistent clinical challenge, affecting adherence. Previous theories about the cause included mitochondrial dysfunction or genetic predispositions, but a clear molecular explanation at the protein level was lacking. The use of cryo-electron microscopy, which won the Nobel Prize in Chemistry in 2017, has enabled researchers to visualize protein structures at near-atomic resolution, making this discovery possible.

Key Perspectives

Patients and Prescribers: For the millions who take statins, the finding offers hope for future medications that reduce cholesterol without causing pain or weakness. Clinicians may be able to reassure patients that safer alternatives are being developed. Drug Developers: Pharmaceutical companies have a defined molecular target to modify in existing statins or design new compounds. The study identifies a specific binding pocket where three statin molecules interact with RyR1, providing a structural basis for chemical modification. Researchers: The work demonstrates the power of structural biology to solve long-standing drug safety questions. It also raises questions about whether other drugs with muscle side effects interact similarly with calcium channels.

What to Watch

Preclinical studies testing modified statin molecules in animal models to see if they maintain cholesterol-lowering efficacy while reducing calcium leak.
Clinical trials of any candidate drugs that emerge from this structural insight; the research is early-stage, and translation to approved medications could take years.
Whether similar mechanisms are found for other statin types beyond atorvastatin, which would broaden the potential impact.

Sources

Scientists finally uncover why statins can cause muscle pain · Latest Science News -- ScienceDaily

Checked

10 claims in this story checked against 1 source: 6 supported.

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SupportedScientists identified how statins trigger muscle pain and are paving the way for safer cholesterol drugs.Latest Science News -- ScienceDaily: “Scientists have uncovered why life-saving statins can damage muscles, opening the door to safer cholesterol drugs with fewer side effects.”
Partly supportedAdvanced imaging could help design medications without debilitating side effects.Latest Science News -- ScienceDaily: “These structural insights connect a longstanding drug safety concern to a specific molecular process, providing valuable information for future medication development.”
Partly supportedThe researchers identified the molecular mechanism by which statins cause muscle pain and damage.Latest Science News -- ScienceDaily: “Scientists at the University of British Columbia (UBC), working with colleagues at the University of Wisconsin-Madison, have identified a molecular mechanism that helps explain these complications.”
SupportedMolinarolo said, “We were able to see, almost atom by atom, how statins latch onto this channel.”Latest Science News -- ScienceDaily: “"We were able to see, almost atom by atom, how statins latch onto this channel," said lead author Dr. Steven Molinarolo, a postdoctoral researcher in UBC's department of biochemistry and molecular biology.”
SupportedMolinarolo said, “That leak of calcium explains why some patients experience muscle pain or, in extreme cases, life-threatening complications.”Latest Science News -- ScienceDaily: “"That leak of calcium explains why some patients experience muscle pain or, in extreme cases, life-threatening complications."”
SupportedVan Petegem said, “This is the first time we've had a clear picture of how statins activate this channel.”Latest Science News -- ScienceDaily: “"This is the first time we've had a clear picture of how statins activate this channel," said Dr. Filip Van Petegem, senior author and professor at UBC's Life Sciences Institute.”
SupportedVan Petegem called the finding “a big step forward” because it provides “a roadmap for designing statins that don't interact with muscle tissue.”Latest Science News -- ScienceDaily: “"It's a big step forward because it gives us a roadmap for designing statins that don't interact with muscle tissue."”
SupportedVan Petegem said, “Statins have been a cornerstone of cardiovascular care for decades,” and that the goal is to make them safer so patients can benefit without fear of serious side effects.Latest Science News -- ScienceDaily: “"Statins have been a cornerstone of cardiovascular care for decades," Dr. Van Petegem said. "Our goal is to make them even safer, so patients can benefit without fear of serious side effects."”
Partly supportedStatin side effects often cause people to stop taking the drugs.Latest Science News -- ScienceDaily: “These symptoms can be disruptive enough that some people discontinue their medication, potentially losing important protection against cardiovascular disease.”
Partly supportedThe discovery could lead to medications that preserve cardiovascular benefits without the risk of muscle injury.Latest Science News -- ScienceDaily: “Their findings, published in Nature Communications , could guide the development of safer statins that maintain their cholesterol-lowering benefits while minimizing muscle damage.”