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Clinical Use of Creatine in Neuromuscular and Neurometabolic Disorders

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Creatine and Creatine Kinase in Health and Disease

Part of the book series: Subcellular Biochemistry ((SCBI,volume 46))

Abstract

Many of the neuromuscular (e.g., muscular dystrophy) and neurometabolic (e.g., mitochondrial cytopathies) disorders share similar final common pathways of cellular dysfunction that may be favorably influenced by creatine monohydrate (CrM) supplementation. Studies using the mdx model of Duchenne muscular dystrophy have found evidence of enhanced mitochondrial function, reduced intra-cellular calcium and improved performance with CrM supplementation. Clinical trials in patients with Duchenne and Becker’s muscular dystrophy have shown improved function, fat-free mass, and some evidence of improved bone health with CrM supplementation. In contrast, the improvements in function in myotonic dystrophy and inherited neuropathies (e.g., Charcot-Marie-Tooth) have not been significant. Some studies in patients with mitochondrial cytopathies have shown improved muscle endurance and body composition, yet other studies did not find significant improvements in patients with mitochondrial cytopathy. Lower-dose CrM supplementation in patients with McArdle’s disease (myophosphorylase deficiency) improved exercise capacity, yet higher doses actually showed some indication of worsened function. Based upon known cellular pathologies, there are potential benefits from CrM supplementation in patients with steroid myopathy, inflammatory myopathy, myoadenylate deaminase deficiency, and fatty acid oxidation defects. Larger randomized control trials (RCT) using homogeneous patient groups and objective and clinically relevant outcome variables are needed to determine whether creatine supplementation will be of therapeutic benefit to patients with neuromuscular or neurometabolic disorders. Given the relatively low prevalence of some of the neuromuscular and neurometabolic disorders, it will be necessary to use surrogate markers of potential clinical efficacy including markers of oxidative stress, cellular energy charge, and gene expression patterns

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References

  • Adcock, K.H., Nedelcu, J., Loenneker, T., Martin, E., Wallimann, T., and Wagner, B.P., 2002, Neuroprotection of creatine supplementation in neonatal rats with transient cerebral hypoxia-ischemia. Dev. Neurosci. 24: 382–388.

    Article  PubMed  CAS  Google Scholar 

  • Alexanderson, H., 2005, Exercise: an important component of treatment in the idiopathic inflammatory myopathies. Curr, Rheumatol. Rep. 7: 115–124.

    Article  Google Scholar 

  • Andreassen, O.A., Dedeoglu, A., Ferrante, R.J., Jenkins, B.G., Ferrante, K.L., Thomas, M., Friedlich, A., Browne, S.E., Schilling, G., Borchelt, D.R., Hersch, S.M., Ross, C.A., and Beal, M.F., 2001, Creatine increases survival and delays motor symptoms in a transgenic animal model of Huntington’s disease. Neurobiol. Dis. 8: 479–491.

    Article  PubMed  CAS  Google Scholar 

  • Argov, Z., De Stefano, N., and Arnold, D.L., 1996, ADP recovery after a brief ischemic exercise in normal and diseased human muscle – a 31P MRS study. NMR Biomed. 9: 165–172.

    Article  PubMed  CAS  Google Scholar 

  • Arnardottir, S., Alexanderson, H., Lundberg, I.E., and Borg, K., 2003, Sporadic inclusion body myositis: pilot study on the effects of a home exercise program on muscle function, histopathology and inflammatory reaction. J. Rehabil. Med. 35: 31–35.

    Article  PubMed  Google Scholar 

  • Baker, S.K., and Tarnopolsky, M.A., 2001, Statin myopathies: pathophysiologic and clinical perspectives. Clin. Invest. Med. 24: 258–272.

    PubMed  CAS  Google Scholar 

  • Baker, S.K., and Tarnopolsky, M.A., 2003, Targeting cellular energy production in neurological disorders. Expert Opin. Investig. Drugs 12: 1655–1679.

    Article  PubMed  CAS  Google Scholar 

  • Baker, S.K., and Tarnopolsky, M.A., 2005, Statin-associated neuromyotoxicity. Drugs Today (Barc.) 41: 267–293.

    Article  CAS  Google Scholar 

  • Barisic, N., Bernert, G., Ipsiroglu, O., Stromberger, C., Muller, T., Gruber, S., Prayer, D., Moser, E., Bittner, R.E., and Stöckler-Ipsiroglu, S., 2002, Effects of oral creatine supplementation in a patient with MELAS phenotype and associated nephropathy. Neuropediatrics 33: 157–161.

    Article  PubMed  CAS  Google Scholar 

  • Benedict, J.D., Kalinsky, H.J., Scarrone, L.A., Wertbeim, A.R., and Stetten, D., Jr., 1955, The origin of urinary creatine in progressive muscular dystrophy. J. Clin. Invest. 34: 141–145.

    PubMed  CAS  Google Scholar 

  • Borchert, A., Wilichowski, E., and Hanefeld, F., 1999, Supplementation with creatine monohydrate in children with mitochondrial encephalomyopathies. Muscle Nerve 22: 1299–1300.

    Article  PubMed  CAS  Google Scholar 

  • Brooke, M.H., Fenichel, G.M., Griggs, R.C., Mendell, J.R., Moxley, R., Florence, J., King, W.M., Pandya, S., Robison, J., Schierbecker, J., et al., 1989, Duchenne muscular dystrophy: patterns of clinical progression and effects of supportive therapy. Neurology 39: 475–481.

    PubMed  CAS  Google Scholar 

  • Brooke, M.H., Griggs, R.C., Mendell, J.R., Fenichel, G.M., and Shumate, J.B., 1981a, The natural history of Duchenne muscular dystrophy: a caveat for therapeutic trials. Trans. Am. Neurol. Assoc. 106: 195–199.

    CAS  Google Scholar 

  • Brooke, M.H., Griggs, R.C., Mendell, J.R., Fenichel, G.M., Shumate, J.B., and Pellegrino, R.J., 1981b, Clinical trial in Duchenne dystrophy. I. The design of the protocol. Muscle Nerve 4: 186–197.

    Article  CAS  Google Scholar 

  • Brose, A., Parise, G., and Tarnopolsky, M.A., 2003, Creatine supplementation enhances isometric strength and body composition improvements following strength exercise training in older adults. J. Gerontol. A Biol. Sci. Med. Sci. 58: 11–19.

    PubMed  Google Scholar 

  • Burke, D.G., Chilibeck, P.D., Parise, G., Candow, D.G., Mahoney, D., and Tarnopolsky, M., 2003a, Effect of creatine and weight training on muscle creatine and performance in vegetarians. Med. Sci. Sports Exerc. 35: 1946–1955.

    Article  CAS  Google Scholar 

  • Burke, D.G., Chilibeck, P.D., Parise, G., Tarnopolsky, M.A., and Candow, D.G., 2003b, Effect of alpha-lipoic acid combined with creatine monohydrate on human skeletal muscle creatine and phosphagen concentration. Int. J. Sport Nutr. Exerc. Metab. 13: 294–302.

    CAS  Google Scholar 

  • Campos, A.R., Serafini, L.N., Sobreira, C., Menezes, L.G., and Martinez, J.A., 2006, Creatine intake attenuates corticosteroid-induced impairment of voluntary running in hamsters. Appl. Physiol. Nutr. Metab. 31: 490–494.

    Article  PubMed  CAS  Google Scholar 

  • Carter, A.J., Muller, R.E., Pschorn, U., and Stransky, W., 1995, Preincubation with creatine enhances levels of creatine phosphate and prevents anoxic damage in rat hippocampal slices. J. Neurochem. 64: 2691–2699.

    Article  PubMed  CAS  Google Scholar 

  • Casey, A., Constantin-Teodosiu, D., Howell, S., Hultman, E., and Greenhaff, P.L., 1996, Creatine ingestion favorably affects performance and muscle metabolism during maximal exercise in humans. Am. J. Physiol. 271: E31–E37.

    PubMed  CAS  Google Scholar 

  • Chang, C.T., Wu, C.H., Yang, C.W., Huang, J.Y., and Wu, M.S., 2002, Creatine monohydrate treatment alleviates muscle cramps associated with haemodialysis. Nephrol. Dial. Transplant. 17: 1978–1981.

    Article  PubMed  CAS  Google Scholar 

  • Chetlin, R.D., Gutmann, L., Tarnopolsky, M.A., Ullrich, I.H., and Yeater, R.A., 2004, Resistance training exercise and creatine in patients with Charcot-Marie-Tooth disease. Muscle Nerve 30: 69–76.

    Article  PubMed  CAS  Google Scholar 

  • Chilibeck, P.D., Chrusch, M.J., Chad, K.E., Shawn Davison, K., and Burke, D.G., 2005, Creatine monohydrate and resistance training increase bone mineral content and density in older men. J. Nutr. Health Aging 9: 352–353.

    PubMed  CAS  Google Scholar 

  • Dedeoglu, A., Kubilus, J.K., Yang, L., Ferrante, K.L., Hersch, S.M., Beal, M.F., and Ferrante, R.J., 2003, Creatine therapy provides neuroprotection after onset of clinical symptoms in Huntington’s disease transgenic mice. J. Neurochem. 85: 1359–1367.

    Article  PubMed  CAS  Google Scholar 

  • Doherty, T.J., Lougheed, K., Markez, J., and Tarnopolsky, M.A., 2001, Creatine monohydrate does not increase strength in patients with hereditary neuropathy. Neurology 57: 559–560.

    PubMed  CAS  Google Scholar 

  • Duke, A.M., and Steele, D.S., 1999, Effects of creatine phosphate on Ca2+ regulation by the sarcoplasmic reticulum in mechanically skinned rat skeletal muscle fibres. J. Physiol. 517: 447–458.

    Article  PubMed  CAS  Google Scholar 

  • Escolar, D.M., Buyse, G., Henricson, E., Leshner, R., Florence, J., Mayhew, J., Tesi-Rocha, C., Gorni, K., Pasquali, L., Patel, K.M., McCarter, R., Huang, J., Mayhew, T., Bertorini, T., Carlo, J., Connolly, A.M., Clemens, P.R., Goemans, N., Iannaccone, S.T., Igarashi, M., Nevo, Y., Pestronk, A., Subramony, S.H., Vedanarayanan, V.V., and Wessel, H., 2005, CINRG randomized controlled trial of creatine and glutamine in Duchenne muscular dystrophy. Ann. Neurol. 58: 151–155.

    Article  PubMed  CAS  Google Scholar 

  • Escolar, D.M., Henricson, E.K., Mayhew, J., Florence, J., Leshner, R., Patel, K.M., and Clemens, P.R., 2001, Clinical evaluator reliability for quantitative and manual muscle testing measures of strength in children. Muscle Nerve 24: 787–793.

    Article  PubMed  CAS  Google Scholar 

  • Gerber, I., ap Gwynn, I., Alini, M., and Wallimann, T., 2005, Stimulatory effects of creatine on metabolic activity, differentiation and mineralization of primary osteoblast-like cells in monolayer and micromass cell cultures. Eur. Cells Mater. 10: 8–22.

    CAS  Google Scholar 

  • Gordon, A., Hultman, E., Kaijser, L., Kristjansson, S., Rolf, C.J., Nyquist, O., and Sylven, C., 1995, Creatine supplementation in chronic heart failure increases skeletal muscle creatine phosphate and muscle performance. Cardiovasc. Res. 30: 413–418.

    Article  PubMed  CAS  Google Scholar 

  • Granchelli, J.A., Pollina, C., and Hudecki, M.S., 2000, Pre-clinical screening of drugs using the mdx mouse. Neuromusc. Disord. 10: 235–239.

    Article  PubMed  CAS  Google Scholar 

  • Hespel, P., Op’t Eijnde, B., and Van Leemputte, M., 2002, Opposite actions of caffeine and creatine on muscle relaxation time in humans. J. Appl. Physiol. 92: 513–518.

    PubMed  CAS  Google Scholar 

  • Isenberg, D.A., Allen, E., Farewell, V., Ehrenstein, M.R., Hanna, M.G., Lundberg, I.E., Oddis, C., Pilkington, C., Plotz, P., Scott, D., Vencovsky, J., Cooper, R., Rider, L., and Miller, F., 2004, International consensus outcome measures for patients with idiopathic inflammatory myopathies. Development and initial validation of myositis activity and damage indices in patients with adult onset disease. Rheumatology (Oxford) 43: 49–54.

    Article  CAS  Google Scholar 

  • Johansen, K.L., Doyle, J., Sakkas, G.K., and Kent-Braun, J.A., 2005, Neural and metabolic mechanisms of excessive muscle fatigue in maintenance hemodialysis patients. Am. J. Physiol. Regul. Integr. Comp. Physiol. 289: R805–R813.

    PubMed  CAS  Google Scholar 

  • Klein, A.M., and Ferrante, R.J., 2007, The neuroprotective role of creatine. Subcell. Biochem. 46: 205–243.

    Article  PubMed  Google Scholar 

  • Kley, R., Vorgerd, M., and Tarnopolsky, M., 2007, Creatine for treating muscle disorders. Cochrane Database Syst. Rev. CD004760.

    Google Scholar 

  • Klivenyi, P., Calingasan, N.Y., Starkov, A., Stavrovskaya, I.G., Kristal, B.S., Yang, L., Wieringa, B., and Beal, M.F., 2004, Neuroprotective mechanisms of creatine occur in the absence of mitochondrial creatine kinase. Neurobiol. Dis. 15: 610–617.

    Article  PubMed  CAS  Google Scholar 

  • Klivenyi, P., Ferrante, R.J., Matthews, R.T., Bogdanov, M.B., Klein, A.M., Andreassen, O.A., Mueller, G., Wermer, M., Kaddurah-Daouk, R., and Beal, M.F., 1999, Neuroprotective effects of creatine in a transgenic animal model of amyotrophic lateral sclerosis. Nat. Med. 5: 347–350.

    Article  PubMed  CAS  Google Scholar 

  • Klopstock, T., Querner, V., Schmidt, F., Gekeler, F., Walter, M., Hartard, M., Henning, M., Gasser, T., Pongratz, D., Straube, A., Dieterich, M., and Muller-Felber, W., 2000, A placebo-controlled crossover trial of creatine in mitochondrial diseases. Neurology 55: 1748–1751.

    PubMed  CAS  Google Scholar 

  • Komura, K., Hobbiebrunken, E., Wilichowski, E.K., and Hanefeld, F.A., 2003, Effectiveness of creatine monohydrate in mitochondrial encephalomyopathies. Pediatr. Neurol. 28: 53–58.

    Article  PubMed  Google Scholar 

  • Korenke, G.C., Wanders, R.J., and Hanefeld, F., 2003, Striking improvement of muscle strength under creatine therapy in a patient with long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency. J. Inherit. Metab. Dis. 26: 67–68.

    Article  PubMed  CAS  Google Scholar 

  • Kornblum, C., Schroder, R., Muller, K., Vorgerd, M., Eggers, J., Bogdanow, M., Papassotiropoulos, A., Fabian, K., Klockgether, T., and Zange, J., 2005, 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. Eur. J. Neurol. 12: 300–309.

    Article  PubMed  CAS  Google Scholar 

  • Kuethe, F., Krack, A., Richartz, B.M., and Figulla, H.R., 2006, Creatine supplementation improves muscle strength in patients with congestive heart failure. Pharmazie 61: 218–222.

    PubMed  CAS  Google Scholar 

  • Lawler, J.M., Barnes, W.S., Wu, G., Song, W., and Demaree, S., 2002, Direct antioxidant properties of creatine. Biochem. Biophys. Res. Commun. 290: 47–52.

    Article  PubMed  CAS  Google Scholar 

  • Louis, M., Lebacq, J., Poortmans, J.R., Belpaire-Dethiou, M.C., Devogelaer, J.P., Van Hecke, P., Goubel, F., and Francaux, M., 2003, Beneficial effects of creatine supplementation in dystrophic patients. Muscle Nerve 27: 604–610.

    Article  PubMed  CAS  Google Scholar 

  • Louis, M., Raymackers, J.M., Debaix, H., Lebacq, J., and Francaux, M., 2004, Effect of creatine supplementation on skeletal muscle of mdx mice. Muscle Nerve 29: 687–692.

    Article  PubMed  CAS  Google Scholar 

  • Mahoney, D.J., Parise, G., and Tarnopolsky, M.A., 2002, Nutritional and exercise-based therapies in the treatment of mitochondrial disease. Curr. Opin. Clin. Nutr. Metab. Care 5: 619–629.

    Article  PubMed  CAS  Google Scholar 

  • Malcon, C., Kaddurah-Daouk, R., and Beal, M.F., 2000, Neuroprotective effects of creatine administration against NMDA and malonate toxicity. Brain Res. 860: 195–198.

    Article  PubMed  CAS  Google Scholar 

  • Mallouk, N., Jacquemond, V., and Allard, B., 2000, Elevated subsarcolemmal Ca2+ in mdx mouse skeletal muscle fibers detected with Ca2+-activated K+ channels. Proc. Natl. Acad. Sci. USA 97: 4950–4955.

    Article  PubMed  CAS  Google Scholar 

  • Menezes, L.G., Sobreira, C., Neder, L., Rodrigues-Junior, A.L., and Martinez, J.A., 2007, Creatine supplementation attenuates corticosteroid-induced muscle wasting and impairment of exercise performance in rats. J. Appl. Physiol. 102: 698–703.

    Article  PubMed  CAS  Google Scholar 

  • Mihic, S., MacDonald, J.R., McKenzie, S., and Tarnopolsky, M.A., 2000, Acute creatine loading increases fat-free mass, but does not affect blood pressure, plasma creatinine, or CK activity in men and women. Med. Sci. Sports Exerc. 32: 291–296.

    Article  PubMed  CAS  Google Scholar 

  • Milhorat, A.T., 1953, Creatine and creatinine metabolism and diseases of the neuromuscular system. Res. Publ. Assoc. Res. Nerv. Ment. Dis. 32: 400–421.

    PubMed  CAS  Google Scholar 

  • Moxley, R.T., 3rd, Ashwal, S., Pandya, S., Connolly, A., Florence, J., Mathews, K., Baumbach, L., McDonald, C., Sussman, M., and Wade, C., 2005, Practice parameter: corticosteroid treatment of Duchenne dystrophy: report of the Quality Standards Subcommittee of the American Academy of Neurology and the Practice Committee of the Child Neurology Society. Neurology 64: 13–20.

    PubMed  CAS  Google Scholar 

  • Parise, G., Mihic, S., MacLennan, D., Yarasheski, K.E., and Tarnopolsky, M.A., 2001, Effects of acute creatine monohydrate supplementation on leucine kinetics and mixed-muscle protein synthesis. J. Appl. Physiol. 91: 1041–1047.

    PubMed  CAS  Google Scholar 

  • Park, J.H., Niermann, K.J., Ryder, N.M., Nelson, A.E., Das, A., Lawton, A.R., Hernanz-Schulman, M., and Olsen, N.J., 2000, Muscle abnormalities in juvenile dermatomyositis patients: P-31 magnetic resonance spectroscopy studies. Arthritis Rheum. 43: 2359–2367.

    Article  PubMed  CAS  Google Scholar 

  • Park, J.H., Olsen, N.J., King, L., Jr., Vital, T., Buse, R., Kari, S., Hernanz-Schulman, M., and Price, R.R., 1995, Use of magnetic resonance imaging and P-31 magnetic resonance spectroscopy to detect and quantify muscle dysfunction in the amyopathic and myopathic variants of dermatomyositis. Arthritis Rheum. 38: 68–77.

    Article  PubMed  Google Scholar 

  • Park, J.H., Vital, T.L., Ryder, N.M., Hernanz-Schulman, M., Partain, C.L., Price, R.R., and Olsen, N.J., 1994, Magnetic resonance imaging and P-31 magnetic resonance spectroscopy provide unique quantitative data useful in the longitudinal management of patients with dermatomyositis. Arthritis Rheum. 37: 736–746.

    Article  PubMed  CAS  Google Scholar 

  • Passaquin, A.C., Renard, M., Kay, L., Challet, C., Mokhtarian, A., Wallimann, T., and Ruegg, U.T., 2002, Creatine supplementation reduces skeletal muscle degeneration and enhances mitochondrial function in mdx mice. Neuromusc. Disord. 12: 174–182.

    Article  PubMed  Google Scholar 

  • Payne, E.T., Yasuda, N., Bourgeois, J.M., Devries, M.C., Rodriguez, M.C., Yousuf, J., and Tarnopolsky, M.A., 2006, Nutritional therapy improves function and complements corticosteroid intervention in mdx mice. Muscle Nerve 33: 66–77.

    Article  PubMed  CAS  Google Scholar 

  • Piccolo, G., Banfi, P., Azan, G., Rizzuto, R., Bisson, R., Sandona, D., and Bellomo, G., 1991, Biological markers of oxidative stress in mitochondrial myopathies with progressive external ophthalmoplegia. J. Neurol. Sci. 105: 57–60.

    Article  PubMed  CAS  Google Scholar 

  • Pulido, S.M., Passaquin, A.C., Leijendekker, W.J., Challet, C., Wallimann, T., and Ruegg, U.T., 1998, Creatine supplementation improves intracellular Ca2+ handling and survival in mdx skeletal muscle cells. FEBS Lett. 439: 357–362.

    Article  PubMed  CAS  Google Scholar 

  • Raha, S., and Robinson, B.H., 2000, Mitochondria, oxygen free radicals, disease and ageing. Trends Biochem. Sci. 25: 502–508.

    Article  PubMed  CAS  Google Scholar 

  • Rindfleisch, J.A., and Muller, D., 2005, Diagnosis and management of rheumatoid arthritis. Am. Fam. Physician 72: 1037–1047.

    PubMed  Google Scholar 

  • Rodriguez, M.C., MacDonald, J.R., Mahoney, D.J., Parise, G., Beal, M.F., and Tarnopolsky, M.A., 2007, Beneficial effects of creatine, CoQ10, and lipoic acid in mitochondrial disorders. Muscle Nerve 35: 235–242.

    Article  PubMed  CAS  Google Scholar 

  • Roy, B.D., Bourgeois, J.M., Mahoney, D.J., and Tarnopolsky, M.A., 2002, Dietary supplementation with creatine monohydrate prevents corticosteroid-induced attenuation of growth in young rats. Can. J. Physiol. Pharmacol. 80: 1008–1014.

    Article  PubMed  CAS  Google Scholar 

  • Scaglia, F., Towbin, J.A., Craigen, W.J., Belmont, J.W., Smith, E.O., Neish, S.R., Ware, S.M., Hunter, J.V., Fernbach, S.D., Vladutiu, G.D., Wong, L.J., and Vogel, H., 2004, Clinical spectrum, morbidity, and mortality in 113 pediatric patients with mitochondrial disease. Pediatrics 114: 925–931.

    Article  PubMed  Google Scholar 

  • Schneider-Gold, C., Beck, M., Wessig, C., George, A., Kele, H., Reiners, K., and Toyka, K.V., 2003, Creatine monohydrate in DM2/PROMM: a double-blind placebo-controlled clinical study. Proximal myotonic myopathy. Neurology 60: 500–502.

    Article  PubMed  CAS  Google Scholar 

  • Schneider-Gold, C., Gajdos, P., Toyka, K.V., and Hohlfeld, R.R., 2005, Corticosteroids for myasthenia gravis. Cochrane Database Syst. Rev. CD002828.

    Google Scholar 

  • Smith, C.A., Chetlin, R.D., Gutmann, L., Yeater, R.A., and Alway, S.E., 2006, Effects of exercise and creatine on myosin heavy chain isoform composition in patients with Charcot-Marie-Tooth disease. Muscle Nerve 34: 586–594.

    Article  PubMed  CAS  Google Scholar 

  • Sullivan, P.G., Geiger, J.D., Mattson, M.P., and Scheff, S.W., 2000, Dietary supplement creatine protects against traumatic brain injury. Ann. Neurol. 48: 723–729.

    Article  PubMed  CAS  Google Scholar 

  • Taivassalo, T., and Haller, R.G., 2005, Exercise and training in mitochondrial myopathies. Med. Sci. Sports Exerc. 37: 2094–2101.

    Article  PubMed  CAS  Google Scholar 

  • Tarnopolsky, M.A., Roy, B.D., and MacDonald, J.R., 1997, A randomized, controlled trial of creatine monohydrate in patients with mitochondrial cytopathies. Muscle Nerve 20: 1502–1509.

    Article  PubMed  CAS  Google Scholar 

  • Tarnopolsky, M., and Martin, J., 1999, Creatine monohydrate increases strength in patients with neuromuscular disease. Neurology 52: 854–857.

    PubMed  CAS  Google Scholar 

  • Tarnopolsky, M.A., and Parise, G., 1999, Direct measurement of high-energy phosphate compounds in patients with neuromuscular disease. Muscle Nerve 22: 1228–1233.

    Article  PubMed  CAS  Google Scholar 

  • Tarnopolsky, M.A., Parise, G., Yardley, N.J., Ballantyne, C.S., Olatinji, S., and Phillips, S.M., 2001, Creatine-dextrose and protein-dextrose induce similar strength gains during training. Med. Sci. Sports Exerc. 33: 2044–2052.

    Article  PubMed  CAS  Google Scholar 

  • Tarnopolsky, M.A., and Beal, M.F., 2001, Potential for creatine and other therapies targeting cellular energy dysfunction in neurological disorders. Ann. Neurol. 49: 561–574.

    Article  PubMed  CAS  Google Scholar 

  • Tarnopolsky, M., Parise, G., Fu, M.H., Brose, A., Parshad, A., Speer, O., and Wallimann, T., 2003, Acute and moderate-term creatine monohydrate supplementation does not affect creatine transporter mRNA or protein content in either young or elderly humans. Mol. Cell. Biochem. 244: 159–166.

    Article  PubMed  CAS  Google Scholar 

  • Tarnopolsky, M., 2004, Exercise testing as a diagnostic entity in mitochondrial myopathies. Mitochondrion 4: 529–542.

    Article  PubMed  CAS  Google Scholar 

  • Tarnopolsky, M., Mahoney, D., Thompson, T., Naylor, H., and Doherty, T.J., 2004a, Creatine monohydrate supplementation does not increase muscle strength, lean body mass, or muscle phosphocreatine in patients with myotonic dystrophy type 1. Muscle Nerve 29: 51–58.

    Article  CAS  Google Scholar 

  • Tarnopolsky, M.A., Mahoney, D.J., Vajsar, J., Rodriguez, C., Doherty, T.J., Roy, B.D., and Biggar, D., 2004b, Creatine monohydrate enhances strength and body composition in Duchenne muscular dystrophy. Neurology 62: 1771–1777.

    CAS  Google Scholar 

  • Tarnopolsky, M.A., Simon, D.K., Roy, B.D., Chorneyko, K., Lowther, S.A., Johns, D.R., Sandhu, J.K., Li, Y., and Sikorska, M., 2004c, Attenuation of free radical production and paracrystalline inclusions by creatine supplementation in a patient with a novel cytochrome b mutation. Muscle Nerve 29: 537–547.

    Article  Google Scholar 

  • Tarnopolsky, M.A., and Raha, S., 2005, Mitochondrial myopathies: diagnosis, exercise intolerance, and treatment options. Med. Sci. Sports Exerc. 37: 2086–2093.

    Article  PubMed  CAS  Google Scholar 

  • Tartaglia, M.C., Chen, J.T., Caramanos, Z., Taivassalo, T., Arnold, D.L., and Argov, Z., 2000, Muscle phosphorus magnetic resonance spectroscopy oxidative indices correlate with physical activity. Muscle Nerve 23: 175–181.

    Article  PubMed  CAS  Google Scholar 

  • Terjung, R.L., Clarkson, P., Eichner, E.R., Greenhaff, P.L., Hespel, P.J., Israel, R.G., Kraemer, W.J., Meyer, R.A., Spriet, L.L., Tarnopolsky, M.A., Wagenmakers, A.J., and Williams, M.H., 2000, American College of Sports Medicine roundtable. The physiological and health effects of oral creatine supplementation. Med. Sci. Sports Exerc. 32: 706–717.

    Article  PubMed  CAS  Google Scholar 

  • Vorgerd, M., Grehl, T., Jager, M., Muller, K., Freitag, G., Patzold, T., Bruns, N., Fabian, K., Tegenthoff, M., Mortier, W., Luttmann, A., Zange, J., and Malin, J.P., 2000, Creatine therapy in myophosphorylase deficiency (McArdle disease): a placebo-controlled crossover trial. Arch. Neurol. 57: 956–963.

    Article  PubMed  CAS  Google Scholar 

  • Vorgerd, M., Zange, J., Kley, R., Grehl, T., Husing, A., Jager, M., Muller, K., Schroder, R., Mortier, W., Fabian, K., Malin, J.P., and Luttmann, A., 2002, Effect of high-dose creatine therapy on symptoms of exercise intolerance in McArdle disease: double-blind, placebo-controlled crossover study. Arch. Neurol. 59: 97–101.

    Article  PubMed  Google Scholar 

  • Whittingham, T.S., and Lipton, P., 1981, Cerebral synaptic transmission during anoxia is protected by creatine. J. Neurochem. 37: 1618–1621.

    Article  PubMed  CAS  Google Scholar 

  • Wilken, B., Ramirez, J.M., Probst, I., Richter, D.W., and Hanefeld, F., 2000, Anoxic ATP depletion in neonatal mice brainstem is prevented by creatine supplementation. Arch. Dis. Child. Fetal Neonatal Ed. 82: F224–F227.

    Article  PubMed  CAS  Google Scholar 

  • Zhu, S., Li, M., Figueroa, B.E., Liu, A., Stavrovskaya, I.G., Pasinelli, P., Beal, M.F., Brown, R.H., Jr., Kristal, B.S., Ferrante, R.J., and Friedlander, R.M., 2004, Prophylactic creatine administration mediates neuroprotection in cerebral ischemia in mice. J. Neurosci. 24: 5909–5912.

    Article  PubMed  CAS  Google Scholar 

  • Ziegler, D., 2004, Thioctic acid for patients with symptomatic diabetic polyneuropathy: a critical review.Treat. Endocrinol. 3: 173–189.

    CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Pediatrics and Medicine (Neurology and Rehabilitation), Neuromuscular and Neurometabolic Clinic, Rm 2H26, McMaster University Medical Center, 1200 Main St. W., Hamilton, Ontario, Canada,L8N 3Z5

    Mark A. Tarnopolsky

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  1. Mark A. Tarnopolsky
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Editors and Affiliations

  1. VU University Medical Center, Amsterdam, The Netherlands

    Gajja S. Salomons

  2. DSM Nutritional Products Ltd, Basel, Switzerland

    Markus Wyss

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Tarnopolsky, M.A. (2007). Clinical Use of Creatine in Neuromuscular and Neurometabolic Disorders. In: Salomons, G.S., Wyss, M. (eds) Creatine and Creatine Kinase in Health and Disease. Subcellular Biochemistry, vol 46. Springer, Dordrecht. https://doi.org/10.1007/978-1-4020-6486-9_10

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  • DOI: https://doi.org/10.1007/978-1-4020-6486-9_10

  • Publisher Name: Springer, Dordrecht

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  • Online ISBN: 978-1-4020-6486-9

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