Review
Version 2
This version is not peer-reviewed
Creatine as a Candidate to Prevent 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)
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.
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.
Keywords
creatine; statin; myopathy; muscle; myalgia; prevention; treatment; pathogenesis; pathophysiology; mitochondria
Subject
Medicine and Pharmacology, Clinical Medicine
Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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Commenter: Maurizio Balestrino
Commenter's Conflict of Interests: Author
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”.
The commenter has declared there is no conflict of interests.