When my mother first started taking statins for her high cholesterol, she was blindsided by absolutely crippling pain deep in her leg muscles. It was so bad that she stopped taking the medication without talking to her doctor first (never a good idea).
Yet, when my husband had to start taking a statin because of his cholesterol, he didn’t have any muscle pain at all.
I wondered what the difference was. Why do statins cause muscle pain in some people and not others?
I’m not the only one who was curious. A team of researchers at Columbia University decided to put statins under the microscope — literally….
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A tiny leak in muscle cells
About 10 percent of the 40 million U.S. adults who take statins to lower cholesterol experience side effects such as muscle aches, weakness and fatigue.
“I’ve had patients who’ve been prescribed statins, and they refused to take them because of the side effects,” says Dr. Andrew Marks of Columbia University. “It’s the most common reason patients quit statins, and it’s a very real problem that needs a solution.”
Statins lower cholesterol by binding to an enzyme involved in synthesizing cholesterol. Unfortunately, they also bind to other so-called “off-target” molecules. Previous studies have suggested that muscular side effects occur when statins bind to a specific protein in muscle.
The researchers employed cryo-electron microscopy, a technique that can image molecules down to individual atoms. Using this technology, they documented the binding of the statin simvastatin to muscle protein and uncovered the specific details of the interaction.
They found simvastatin molecules bind to two locations on a muscle protein called the ryanodine receptor, opening a channel through which calcium ions flow. The researchers note that patients with mutations in the ryanodine receptor 1/calcium release channel can be especially intolerant of statins.
Marks says this tiny calcium “leak” could explain the muscular side effects of statins by weakening the muscle directly or by activating enzymes that degrade the muscle tissue.
“It is unlikely that this explanation applies to everyone who experiences muscular side effects with statins, but even if it explains a small subset, that’s a lot of people we could help if we can resolve the issue,” he says.
Even though the study tested one of the older statins from a group referred to as type 1, the researchers observed that both type 1 and the newer type 2 statins have a similar effect on the ryanodine receptor.
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Potential fixes for statin-driven muscle pain
The new images also suggest statins could be redesigned to avoid binding to the ryanodine receptor while retaining their cholesterol-lowering ability. Marks is now collaborating with chemists to create such a statin.
Another option could be to plug the calcium leak. The researchers showed statin-induced calcium leaks in mice can be closed with an experimental drug developed in Marks’ lab for other conditions involving calcium leaks.
“[This drug is] currently being tested in people with rare muscle diseases,” Marks says. “If it shows efficacy in those patients, we can test it in statin-induced myopathies.”
According to cardiologist Dr. Elizabeth Klodas, who was not involved in the study, “Diet is a major driver of high cholesterol, but instead of changing the food, we prescribe medications. This never seemed logical to me.”
If you battle muscle pain from statins, check out her post on three specific foods that can yield as much as a 40% reduction in LDL cholesterol.
Sources:
How Statins Cause Muscle Aches — Columbia University Irving Medical Center
Scientists finally uncover why statins cause muscle pain — ScienceDaily
Structural basis for simvastatin-induced skeletal muscle weakness associated with type 1 ryanodine receptor T4709M mutation — The Journal of Clinical Investigation
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