Creatine for treating muscle disorders

Kley, Rudolf A.; Vorgerd, Matthias; Tarnopolsky, Mark A.

doi:10.1002/14651858.cd004760.pub2

Cited by 69 publications

(80 citation statements)

References 66 publications

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“…These changes in mtDNA maintenance diseases point to a challenged glutathione supply and suggest that N-acetyl-cysteine supplementation, providing cysteine for glutathione and taurine synthesis, could be tried as a metabolic bypass therapy. Our unbiased screen identified creatine depletion in NMD patients, which was an interesting proof of principle, as a Cochrane review found creatine supplementation to be useful for muscle dystrophies (Kley et al, 2013). However, similarly low global creatine pool, represented by the blood creatine/creatinine ratio, was found to be present in IBM and also in IOSCA, despite the fact that IOSCA patients do not show any muscle phenotype (Lönnqvist et al, 1998) or low muscle mass (Park et al, 2013).…”

Section: Discussionmentioning

confidence: 81%

Metabolomes of mitochondrial diseases and inclusion body myositis patients: treatment targets and biomarkers

et al. 2018

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Mitochondrial disorders (MDs) are inherited multi‐organ diseases with variable phenotypes. Inclusion body myositis (IBM), a sporadic inflammatory muscle disease, also shows mitochondrial dysfunction. We investigated whether primary and secondary MDs modify metabolism to reveal pathogenic pathways and biomarkers. We investigated metabolomes of 25 mitochondrial myopathy or ataxias patients, 16 unaffected carriers, six IBM and 15 non‐mitochondrial neuromuscular disease (NMD) patients and 30 matched controls. MD and IBM metabolomes clustered separately from controls and NMDs. MDs and IBM showed transsulfuration pathway changes; creatine and niacinamide depletion marked NMDs, IBM and infantile‐onset spinocerebellar ataxia (IOSCA). Low blood and muscle arginine was specific for patients with m.3243A>G mutation. A four‐metabolite blood multi‐biomarker (sorbitol, alanine, myoinositol, cystathionine) distinguished primary MDs from others (76% sensitivity, 95% specificity). Our omics approach identified pathways currently used to treat NMDs and mitochondrial stroke‐like episodes and proposes nicotinamide riboside in MDs and IBM, and creatine in IOSCA and IBM as novel treatment targets. The disease‐specific metabolic fingerprints are valuable “multi‐biomarkers” for diagnosis and promising tools for follow‐up of disease progression and treatment effect.

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Section: Discussionmentioning

confidence: 81%

Metabolomes of mitochondrial diseases and inclusion body myositis patients: treatment targets and biomarkers

et al. 2018

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“…It can also enhance muscle strength in certain myopathies, such as muscular dystrophy [3]. Creatine cannot be synthesized in skeletal muscle cells and is transported into skeletal muscle by a Na + -dependent transmembrane protein [4].…”

Section: Introductionmentioning

confidence: 99%

Incubating Isolated Mouse EDL Muscles with Creatine Improves Force Production and Twitch Kinetics in Fatigue Due to Reduction in Ionic Strength

2011

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BackgroundCreatine supplementation can improve performance during high intensity exercise in humans and improve muscle strength in certain myopathies. In this present study, we investigated the direct effects of acute creatine incubation on isolated mouse fast-twitch EDL muscles, and examined how these effects change with fatigue.Methods and ResultsThe extensor digitorum longus muscle from mice aged 12–14 weeks was isolated and stimulated with field electrodes to measure force characteristics in 3 different states: (i) before fatigue; (ii) immediately after a fatigue protocol; and (iii) after recovery. These served as the control measurements for the muscle. The muscle was then incubated in a creatine solution and washed. The measurement of force characteristics in the 3 different states was then repeated. In un-fatigued muscle, creatine incubation increased the maximal tetanic force. In fatigued muscle, creatine treatment increased the force produced at all frequencies of stimulation. Incubation also increased the rate of twitch relaxation and twitch contraction in fatigued muscle. During repetitive fatiguing stimulation, creatine-treated muscles took 55.1±9.5% longer than control muscles to lose half of their original force. Measurement of weight changes showed that creatine incubation increased EDL muscle mass by 7%.ConclusionAcute creatine application improves force production in isolated fast-twitch EDL muscle, and these improvements are particularly apparent when the muscle is fatigued. One likely mechanism for this improvement is an increase in Ca2+ sensitivity of contractile proteins as a result of ionic strength decreases following creatine incubation.

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“…The therapeutic role of creatine supplementation has been largely investigated 72,73 in this regard; there are studies showing that this compound may counteract muscle wasting in animal models, 4 as well as in dystrophic patients. 74,14,75,27 Furthermore, it has been observed that creatine improves glycemic control in diabetic subjects, most likely by enhancing GLUT-4 translocation to the sarcolemma. 76 Studies also suggest that creatine supplementation has a beneficial effect on glucoregulation in skeletal muscle, which may be due to an increase in insulin secretion, activating GLUT-4.…”

Section: Discussionmentioning

confidence: 99%

“…For the measurement CO 2 production, gastrocnemius muscle slices (~100 mg) were incubated in 1.0 ml of Dulbecco buffer (pH 7.4), containing either 5.0 mM of D-glucose + 0.2 mCi D-[U- 14 C] glucose. Before incubation, the reaction medium was gassed with oxygen for 30 s. Flasks were sealed with rubber caps and parafilm.…”

Section: Subjects and Reagentsmentioning

confidence: 99%

“…Impaired energy metabolism may trigger proapoptotic signalling (programmed cell death), oxidative damage to lipids, protein and DNA, and impair mitochondrial DNA repair. 14,15 It has been demonstrated that alterations in energy metabolism seem to be implicated in the pathogenesis of a number of muscle and neurological complications, [16][17][18] metabolic disorders, [19][20][21][22] aging [23][24][25] and neuromuscular diseases. 26,27 Mitochondrial function and structure/integrity is crucial to maintaining the energy supply for optimal function and maintenance of homeostasis in some tissues.…”

Section: Introductionmentioning

confidence: 99%

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Homocysteine induces energy imbalance in rat skeletal muscle: Is creatine a protector?

Kolling¹,

Scherer²,

Siebert³

et al. 2012

Cell Biochemistry & Function

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Homocystinuria is a neurometabolic disease caused by a severe deficiency of cystathionine beta-synthase activity, resulting in severe hyperhomocysteinemia. Affected patients present several symptoms including a variable degree of motor dysfunction. In this study, we investigated the effect of chronic hyperhomocysteinemia on the cell viability of the mitochondrion, as well as on some parameters of energy metabolism, such as glucose oxidation and activities of pyruvate kinase, citrate synthase, isocitrate dehydrogenase, malate dehydrogenase, respiratory chain complexes and creatine kinase in gastrocnemius rat skeletal muscle. We also evaluated the effect of creatine on biochemical alterations elicited by hyperhomocysteinemia. Wistar rats received daily subcutaneous injections of homocysteine (0.3-0.6 µmol/g body weight) and/or creatine (50 mg/kg body weight) from the 6th to the 28th days of age. The animals were decapitated 12 h after the last injection. Homocysteine decreased the cell viability of the mitochondrion and the activities of pyruvate kinase and creatine kinase. Succinate dehydrogenase was increased other evaluated parameters were not changed by this amino acid. Creatine, when combined with homocysteine, prevented or caused a synergistic effect on some changes provoked by this amino acid. Creatine per se or creatine plus homocysteine altered glucose oxidation. These findings provide insights into the mechanisms by which homocysteine exerts its effects on skeletal muscle function, more studies are needed to elucidate them. Although creatine prevents some alterations caused by homocysteine, it should be used with caution, mainly in healthy individuals because it could change the homeostasis of normal physiological functions.

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Creatine for treating muscle disorders

Cited by 69 publications

References 66 publications

Metabolomes of mitochondrial diseases and inclusion body myositis patients: treatment targets and biomarkers

Metabolomes of mitochondrial diseases and inclusion body myositis patients: treatment targets and biomarkers

Incubating Isolated Mouse EDL Muscles with Creatine Improves Force Production and Twitch Kinetics in Fatigue Due to Reduction in Ionic Strength

Homocysteine induces energy imbalance in rat skeletal muscle: Is creatine a protector?

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