Selenoprotein synthesis and side-effects of statins

Lancet. 2004 Mar 13;363(9412):892-4. doi: 10.1016/S0140-6736(04)15739-5.


Statins are possibly the most effective drugs for the prevention and treatment of hypercholesterolaemia and coronary heart disease. They are generally well tolerated, however, they do cause some unusual side-effects with potentially severe consequences, most prominently myopathy or rhabdomyolysis and polyneuropathy. We noted that the pattern of side-effects associated with statins resembles the pathology of selenium deficiency, and postulated that the mechanism lay in a well established, but often overlooked, biochemical pathway--the isopentenylation of selenocysteine-tRNA([Ser]Sec). A negative effect of statins on selenoprotein synthesis does seem to explain many of the enigmatic effects and side-effects of statins, in particular, statin-induced myopathy.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Coronary Disease / drug therapy
  • Coronary Disease / prevention & control
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / adverse effects*
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use
  • Hypercholesterolemia / drug therapy
  • Hypercholesterolemia / prevention & control
  • Models, Biological
  • Muscular Diseases / chemically induced*
  • Muscular Diseases / metabolism
  • Polyneuropathies / chemically induced
  • Polyneuropathies / metabolism
  • Protein Biosynthesis*
  • Proteins / metabolism
  • Rhabdomyolysis / chemically induced
  • Rhabdomyolysis / metabolism
  • Selenium / deficiency
  • Selenium / metabolism
  • Selenoproteins


  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Proteins
  • Selenoproteins
  • Selenium