Creatine as a Candidate to Prevent Statin Myopathy

Comment: We added to the second paragraph of the “Common hypothesis on pathogenesis” section the following text: “Specifically, several intermediates have been proposed as causes of statin-associated myopathy, including mevalonate pathway and its end products including non-sterol isoprenoids (farnesol, geranylgeraniol), heme, ubiquinone A, dolichol, squalene and more”. For better clarity and fluency, we moved after this statement, and slightly modified, the sentence that was previously preceding it. The latter now follows this added statement and reads “In fact, multiple pathophysiological mechanisms may perhaps contribute to this condition [24]”. We added to the paragraph describing our case report the following sentence: “Although we could not derive any statistics from this single patient, results of our crossover treatment is suggestive of efficacy, and it is consistent with Shewmon and Craig’s findings”. We expanded the fourth paragraph of the “Discussion”, that now reads “We acknowledge that further research should be done on these subjects. For example, muscle creatine in statin-induced myopathy should be measured, to possibly confirm its decrease. In fact, so far the only investigation that was carried out on this topic was done in liver cells [39]. Albeit positive (it found that atorvastatin did indeed decrease creatine content), it certainly needs confirmation in muscle cells or tissue. Furthermore, it should be noted that the fact that in statin myopathy there is a high urinary creatine/creatinine ratio [38] does not per se indicate decrease of creatine in the muscle. In theory, it might indicate either increased blood plasma creatine linked to higher excretion rate and/or lower formation and excretion of creatinine. Nevertheless, and pending future studies, the above findings suggest that creatine supplementation may be a simple way to prevent statin-induced myopathy”. We changed the title to “Creatine as a candidate to prevent statin myopathy”.