Statin-induced muscle weakness mechanism revealed

The muscle weakness and related side effects of statin is likely due to the effects on the energy production centers of muscle cells.

  • The Dutch scientists reported the new mechanism behind muscle-related side effects of statins in the journal Cell Metabolism.

Previous studies have linked side effects of HMG-CoA reductase inhibitors and other drugs to mitochondria, but the underlying mechanisms are often unknown. The researchers noted that statins exist in two chemical forms, acid and lactone. Most statin drugs are of the acid form and target cholesterol production in the liver.

The study findings showed that statins of the lactone form are three times more powerful at disrupting mitochondria, the powerhouse of cells, than those of the acid form. They confirmed this finding in cells taken from muscle biopsies of patients experiencing statin-induced side effects.

The investigators also found that cells of the patients had reduced ATP production compared with cells from healthy volunteers. The lactone form of statins appears to reduce activity in a protein structure known as “complex III.”

Prof. Frans Russel, a lead researcher, said further 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 proteins are likely to experience side effects from statin use.

Statins are a class of cholesterol lowering drugs that work by inhibiting the enzyme HMG-CoA reductase. The enzyme plays a central role in the production of cholesterol. About 25 percent of statin users complain muscle weakness, pain and cramps.

Other side effects include increased concentrations of liver enzymes, increased risk of diabetes mellitus, neuropathy, pancreatic and hepatic dysfunction. Cholesterol is a major risk factor for myocardial infarction, ischemic heart disease, atherosclerosis and cerebrovascular accident. IMAGE/Schirris et al./Cell Metabolism 2015

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