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Balestrino and Adriano suggest that guanidinoacetate might explain the difference between AGAT- and GAMT-deficient mice in simvastatin-induced myopathy. We agree with Balestrino and Adriano that our data shows that (1) creatine possesses a protective potential to ameliorate statin-induced myopathy in humans and mice and (2) homoarginine did not reveal a beneficial effect in statin-induced myopathy. Third, we agree that guanidinoacetate can be phosphorylated and partially compensate for phosphocreatine. In our study, simvastatin-induced damage showed a trend to be less pronounced in GAMT-deficient mice compared with wildtype mice. Therefore, (phospo) guanidinoacetate cannot completely explain the milder phenotype of GAMT-deficient mice, but we agree that it might contribute to ameliorate statin-induced myopathy in GAMT-deficient mice compared with AGAT-deficient mice. Finally, we agree with Balestino and Adriano that AGAT metabolites should further be evaluated as potential treatments in statin-induced myopathy.<\/jats:p>","DOI":"10.1007\/s00726-020-02865-w","type":"journal-article","created":{"date-parts":[[2020,6,27]],"date-time":"2020-06-27T15:04:16Z","timestamp":1593270256000},"page":"1067-1069","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Creatine, guanidinoacetate and homoarginine in statin-induced myopathy"],"prefix":"10.1007","volume":"52","author":[{"given":"Axel","family":"Neu","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S\u00f6nke","family":"Hornig","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ali","family":"Sasani","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dirk","family":"Isbrandt","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christian","family":"Gerloff","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dimitris","family":"Tsikas","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Edzard","family":"Schwedhelm","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9154-8439","authenticated-orcid":false,"given":"Chi-un","family":"Choe","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2020,6,27]]},"reference":[{"issue":"Pt 2","key":"2865_CR1","doi-asserted-by":"publisher","first-page":"391","DOI":"10.1113\/jphysiol.2006.115006","volume":"576","author":"RR1 Alfieri","year":"2006","unstructured":"Alfieri RR1, Bonelli MA, Cavazzoni A, Brigotti M, Fumarola C, Sestili P, Mozzoni P, De Palma G, Mutti A, Carnicelli D, Vacondio F, Silva C, Borghetti AF, Wheeler KP, Petronini PG (2006) Creatine as a compatible osmolyte in muscle cells exposed to hypertonic stress. 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