Scientists have identified the mechanism behind statin-induced muscle weakness that leads many people with high cholesterol to drop or avoid the medications.

The new research, at Radboud University Nijmegen Medical Center in the Netherlands, suggests that muscle weakness and related side effects are likely due to statins’ effects on the energy production centers, or mitochondria, of muscle cells, Medical News Today reports.

Statins work by blocking the liver’s production of too much cholesterol, which is a major risk factor for heart disease and stroke. According to the Centers for Disease Control and Prevention, more than a quarter of American adults aged 40 and over use a prescription cholesterol-lowering medication, the vast majority of these being statins.

But for about 25 percent of patients, statins cause unpleasant side effects, including muscle weakness, pain and cramps, that can impair quality of life and often cause patients to stop taking the drugs.

Frans Russel, a professor in molecular pharmacology and toxicology who helped conduct the new research, noted statins exist in two forms: acid and lactone. Most statin drugs are of the acid form and target cholesterol production in the liver. But he said the team’s findings indicate the lactone form of statin interferes with mitochondrial function

Using muscle cells from mice, the team found statins of the lactone form are three times more powerful at disrupting mitochondria than those of the acid form.

Russel says additional studies are needed to look at the effects of different statins on mitochondrial function, and to confirm whether the mechanism they have identified could be a useful marker to predict which patients are likely to experience side effects from statin use.

The new findings were published in the journal Cell Metabolism.