Statins are effective drugs to reduce cardiovascular events secondary to dyslipidemia;
however, they cause frequent undesirable side effects. The incidence of statin-induced
myotoxicity (SIM) is presented by 7 to 29% of patients, depending upon the report.
SIM may develop in presence of abnormally high concentrations of statins in the myocyte
and/or in presence of muscular conditions that may predispose to SIM. High concentrations
of statins in the myocyte may occur whenever the activity of liver influx membrane
transporters, namely OATP1B1, of drug metabolizing enzymes, and of liver and muscular
efflux transporters, MDR1 and BCRP, is reduced. In the muscle, conditions that may
predispose to SIM include mitochondrial damage with disruption of the mitochondrial
respiratory chain and decreased production of ATP, increase of ROS, and leak of cytochrome
c and Ca(2+). In the sarcoplasma, statins activate MAPK and diminish the RhoA/AKT/mTOR/PGC-1α
pathway. All these effects contribute to activate apoptosis, proteolysis, and muscle
remodeling. Moreover, in the sarcoplasma, statins can reduce the resting chloride
channel conductance, as well as lactate efflux. These changes will be responsible
of fatigue, cramps, myalgia and elevation of serum CK. To date, besides avoiding drug-drug
interactions and alcohol consumption, and correcting hypothyroidism, two strategies
could be useful to prevent/diminish SIM, e.g. gradual dose titration with statins
less prone to produce SIM, and high supplements of vitamin D in subjects with low
plasma concentrations of 25(OH) D3.