Creatine has no beneficial effect on skeletal muscle energy metabolism in patients with single mitochondrial DNA deletions: a placebo‐controlled, double‐blind ³¹P‐MRS crossover study

Abstract

The purpose of our randomized, double-blind, placebo-controlled crossover study in 15 patients with chronic progressive external ophthalmoplegia (CPEO) or Kearns-Sayre syndrome (KSS) because of single large-scale mitochondrial (mt) DNA deletions was to determine whether oral creatine (Cr) monohydrate can improve skeletal muscle energy metabolism in vivo. Each treatment phase with Cr in a dosage of 150 mg/kg body weight/day or placebo lasted 6 weeks. The effect of Cr was estimated by phosphorus-31 magnetic resonance spectroscopy ((31)P-MRS), clinical and laboratory tests. (31)P-MRS analysis prior to treatment showed clear evidence of severe mitochondrial dysfunction. However, there were no relevant changes in (31)P-MRS parameters under Cr. In particular, phosphocreatine (PCr)/ATP at rest did not increase, and there was no facilitation of post-exercise PCr recovery. Clinical scores and laboratory tests did not alter significantly under Cr, which was tolerated without major side-effects in all patients. Cr supplementation did not improve skeletal muscle oxidative phosphorylation in our series of patients. However, one explanation for our negative findings may be the short study duration or the limited number of patients included.

Effect of creatine and pioglitazone on Hk-2 cell line cisplatin nephrotoxicity

“…In addition, authors showed that mitochondrial mutagenesis could be normalized by creatine supplementation. On the contrary of this in a limited number of patients (n ¼ 15), Kornblum et al 28 reported that high dose creatine treatment has no beneficial effect on skeletal muscle energy metabolism in patients with genetically proven single mitochondrial DNA deletion.…”

Review of Clinical Trials for Mitochondrial Disorders: 1997–2012

“…The third study, conducted at the University of Bonn, was, again, a double-blind, placebo-controlled, randomized crossover trial type [47]. The design was to randomize the patient to initially receive either creatine, 150 mg/kg d (= 7.5 g/d for 70 kg) or placebo for 6 weeks, followed by a 4-week washout, before crossing over to the alternative of creatine or placebo for 6 weeks ( Table 1).…”

Síndrome de Kearns-Sayre: relato de dois casos

“…Um estudo randomizado, prospectivo, duplo-cego com 15 pacientes portadores de síndrome de KearnsSayre e oftalmoplegia externa crônica progressiva utilizou o monoidrato de creatina oral. Uma dosagem de 150 mg/kg versus placebo não demonstrou melhora nos sintomas clínicos musculares na série (10) . Também a coenzima Q (10) não apresentou resultados satisfatórios na disfunção muscular em um pequeno grupo de pacientes com a síndrome.…”

“…Uma dosagem de 150 mg/kg versus placebo não demonstrou melhora nos sintomas clínicos musculares na série (10) . Também a coenzima Q (10) não apresentou resultados satisfatórios na disfunção muscular em um pequeno grupo de pacientes com a síndrome.…”