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Creatine as a Candidate to Prevent Statin Myopathy

Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics and Maternal and Child Sciences (DINOGMI), University of Genoa, Largo Daneo 3, 16132 Genova, Italy
Author to whom correspondence should be addressed.
Biomolecules 2019, 9(9), 496;
Received: 2 July 2019 / Revised: 10 September 2019 / Accepted: 10 September 2019 / Published: 17 September 2019
(This article belongs to the Special Issue Creatine as a Therapeutic Strategy)
Statins prevent cardiovascular diseases, yet their use is limited by the muscle disturbances they cause. Rarely, statin-induced myopathy is autoimmune, but more commonly it is due to direct muscle toxicity. Available evidence suggests that statin-induced creatine deficiency might be a major cause of this toxicity, and that creatine supplementation prevents it. Statins inhibit guanidinoacetate methyl transferase (GAMT), the last enzyme in the synthesis of creatine; thus, they decrease its intracellular content. Such decreased content could cause mitochondrial impairment, since creatine is the final acceptor of the phosphate group of adenosine triphosphate (ATP) at the end of mitochondrial oxidative phosphorylation. Decreased cellular synthesis of ATP would follow. Accordingly, ATP synthesis is decreased in statin-treated cells. In vitro, creatine supplementation prevents the opening of the mitochondrial permeability transition pore that is caused by statins. Clinically, creatine administration prevents statin myopathy in statin-intolerant patients. Additional research is warranted to hopefully confirm these findings. However, creatine is widely used by athletes with no adverse events, and has demonstrated to be safe even in double-blind, placebo-controlled trials of elderly individuals. Thus, it should be trialed, under medical supervision, in patients who cannot assume statin due to the occurrence of muscular symptoms. View Full-Text
Keywords: creatine; statin; myopathy; muscle; myalgia; prevention; treatment; pathogenesis; pathophysiology; mitochondria creatine; statin; myopathy; muscle; myalgia; prevention; treatment; pathogenesis; pathophysiology; mitochondria
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Balestrino, M.; Adriano, E. Creatine as a Candidate to Prevent Statin Myopathy. Biomolecules 2019, 9, 496.

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