For more than three decades, doctors have prescribed statins to millions of patients while observing a troubling phenomenon: about 10% discontinue treatment because of unexplained muscle pains and weakness. A research team from Columbia University and the University of Rochester has now solved this medical puzzle by identifying the precise biological mechanism behind these side effects. Their discovery, published in the Journal of Clinical Investigation, opens up new therapeutic avenues for people facing this intolerance.
Statins Cause Health Problems for Millions of Patients
In France, 6 million and in the United States, 40 million adults take statins daily to lower their LDL cholesterol and prevent cardiovascular disease. Among them, four million develop statin-associated muscle symptoms (SAMS), ranging from mild pains to disabling weakness. These manifestations occur irrespective of age or sex, but individuals carrying genetic mutations in the ryanodine receptor (RyR1) face an elevated risk, including the possibility of malignant hyperthermia during surgical procedures.
Andrew Marks, a cardiologist and chair of the Department of Physiology and Cellular Biophysics at Columbia University, emphasizes the scale of the problem: “I’ve treated patients who were prescribed statins and simply refused to take them because of the side effects. It’s the most common reason patients stop statins, and it’s a very real problem that needs a solution.”
The Ryanodine Receptor 1 (RyR1) is an essential calcium channel in skeletal muscle cells. Located in the sarcoplasmic reticulum, it regulates the release of calcium necessary for muscle contraction. Under normal conditions, this channel opens briefly to trigger contraction, then closes tightly to maintain intracellular calcium stores. Any dysfunction of this receptor compromises muscular mechanics and can lead to progressive tissue degeneration.
Researchers demonstrated that statin molecules, notably simvastatin, bind directly to two specific sites on RyR1. This molecular binding, documented through cryo-electron microscopy, alters the channel’s conformation and prevents its normal closing. The receptor then remains partially open, creating a continuous leak of calcium from the intracellular stores into the muscle cytoplasm. This excess calcium in the cytoplasm of muscle cells triggers two destructive processes simultaneously. On one hand, the calcium overload weakens the contractile capacity of muscle fibers. On the other hand, it activates proteolytic enzymes, notably calpains, which gradually degrade the structural proteins of the muscle tissue.
What to Take Away
- About 10% of people taking statins report muscle symptoms.
- Simvastatin can bind to the RyR1 muscle receptor.
- This interaction causes a calcium leak that can weaken muscles.
- This mechanism would likely affect only a subset of patients.
- Never stop a statin without consulting your doctor.
Also read
- Cholesterol: Why our bodies need it
- Blood tests: how to understand your cholesterol level
- https://www.cuimc.columbia.edu/news/how-statins-cause-muscle-aches
