Preprint Review Version 1 This version is not peer-reviewed

Creatine for Prevention of Statin Myopathy

Version 1 : Received: 11 August 2019 / Approved: 13 August 2019 / Online: 13 August 2019 (04:25:33 CEST)
Version 2 : Received: 10 September 2019 / Approved: 11 September 2019 / Online: 11 September 2019 (04:43:37 CEST)

A peer-reviewed article of this Preprint also exists.

Balestrino, M.; Adriano, E. Creatine as a Candidate to Prevent Statin Myopathy. Biomolecules 2019, 9, 496. Balestrino, M.; Adriano, E. Creatine as a Candidate to Prevent Statin Myopathy. Biomolecules 2019, 9, 496.

Journal reference: Biomolecules 2019, 9, 496
DOI: 10.3390/biom9090496

Abstract

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 may 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 adenosine triphosphate (ATP) would follow. Accordingly, ATP synthesis is decreased in statin-treated cells. In vitro, creatine supplementation prevents the opening of mitochondrial permeability transition pore 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 elder individuals. Thus, it should be trialed, under medical supervision, in patients who cannot assume statin due to the occurrence of muscular symptoms.

Subject Areas

creatine; statin; myopathy; muscle; myalgia; prevention; treatment; pathogenesis; pathophysiology; mitochondria

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