The DOI matches its Crossref record; 43 of the 43 references it cites were found in a registry or an index.
“Heads Up” for Creatine Supplementation and its Potential Applications for Brain Health and Function
Abstract
There is emerging interest regarding the potential beneficial effects of creatine supplementation on indices of brain health and function. Creatine supplementation can increase brain creatine stores, which may help explain some of the positive effects on measures of cognition and memory, especially in aging adults or during times of metabolic stress (i.e., sleep deprivation). Furthermore, creatine has shown promise for improving health outcome measures associated with muscular dystrophy, traumatic brain injury (including concussions in children), depression, and anxiety. However, whether any sex- or age-related differences exist in regard to creatine and indices of brain health and function is relatively unknown. The purpose of this narrative review is to: (1) provide an up-to-date summary and discussion of the current body of research focusing on creatine and indices of brain health and function and (2) discuss possible sex- and age-related differences in response to creatine supplementation on brain bioenergetics, measures of brain health and function, and neurological diseases.
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“This ensures protection against cell death and promotion of survival and differentiation of neurons [248].”
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Citations
Cites
Neurodegenerative diseases and oxidative stress
Barnham, K. J., Masters, C. L., & Bush, A. I. (2004) · Nature Reviews Drug Discovery · doi:10.1038/nrd1330 · Cited by 3,683 · cited 2×
“Neurodegenerative diseases are disabling conditions that progress slowly [65].”
BackgroundCipriani, A., Furukawa, T. A., Salanti, G., Chaimani, A., Atkinson, L. Z., Ogawa, Y., Leucht, S., Ruhe, H. G., Turner, E. H., Higgins, J. P. T., et al. (2018) · The Lancet · doi:10.1016/s0140-6736(17)32802-7 · Cited by 3,541
Creatine and Creatinine Metabolism
Wyss, M., & Kaddurah-Daouk, R. (2000) · Physiological Reviews · doi:10.1152/physrev.2000.80.3.1107 · Cited by 2,950
Dorsey, E. R., Elbaz, A., Nichols, E., Abbasi, N., Abd-Allah, F., Abdelalim, A., Adsuar, J. C., Ansha, M. G., Brayne, C., Choi, J.-Y. J., et al. (2018) · The Lancet Neurology · doi:10.1016/s1474-4422(18)30295-3 · Cited by 2,816
Brain Infarction and the Clinical Expression of Alzheimer Disease<subtitle>The Nun Study</subtitle>
Snowdon, D. A. (1997) · JAMA: The Journal of the American Medical Association · doi:10.1001/jama.1997.03540340047031 · Cited by 1,590
The clinical symptoms of Parkinson's disease.
Sveinbjornsdottir, S. (2016) · Journal of Neurochemistry · doi:10.1111/jnc.13691 · Cited by 1,410 · cited 1×
“In addition to motor impairments, such as resting tremors, slowness, rigidity, and impaired balance and gait [78], individuals with PD often experience apathy, mood swings, depression, and anxiety [79].”
BackgroundThe role of dopamine in the pathophysiology of depression
Dunlop, B. W., & Nemeroff, C. B. (2007) · Archives of General Psychiatry · doi:10.1001/archpsyc.64.3.327 · Cited by 1,244
Kreider, R. B., Kalman, D. S., Antonio, J., Ziegenfuss, T. N., Wildman, R., Collins, R., Candow, D. G., Kleiner, S. M., Almada, A. L., & Lopez, H. L. (2017) · Journal of the International Society of Sports Nutrition · doi:10.1186/s12970-017-0173-z · Cited by 1,057 · cited 1×
“Based on the accumulating body of research showing that creatine supplementation increases muscle performance and muscle accretion primarily in healthy individuals [98], creatine supplementation has been explored as a possible therapy for patients with ALS [99, 100].”
BackgroundSelf-citationPerez Ortiz, J. M., & Swerdlow, R. H. (2019) · British Journal of Pharmacology · doi:10.1111/bph.14585 · Cited by 426
Creatine in Huntington disease is safe, tolerable, bioavailable in brain and reduces serum 8OH2′dG
Hersch, S. M., Gevorkian, S., Marder, K., Moskowitz, C., Feigin, A., Cox, M., Como, P., Zimmerman, C., Lin, M., Zhang, L., et al. (2006) · Neurology · doi:10.1212/01.wnl.0000194318.74946.b6 · Cited by 313
Muscle composition in relation to age and sex
Forsberg, A. M., Nilsson, E., Werneman, J., Bergström, J., & Hultman, E. (1991) · Clinical Science · doi:10.1042/cs0810249 · Cited by 282
Long-term antidepressant use: patient perspectives of benefits and adverse effects
Cartwright, C., Gibson, K., Read, J., Cowan, O., & Dehar, T. (2016) · Patient Preference and Adherence · doi:10.2147/ppa.s110632 · Cited by 242
Parise, G., Mihic, S., MacLennan, D., Yarasheski, K. E., & Tarnopolsky, M. A. (2001) · Journal of Applied Physiology · doi:10.1152/jappl.2001.91.3.1041 · Cited by 236 · cited 1×
“…creatine stores [8], which may subsequently blunt their responsiveness to creatine supplementation [9]; no decrease in measures of muscle protein catabolism from creatine supplementation over time [10, 11]; and the possible influence that fluctuations in estrogen have on creatine homeostasis [5].”
BackgroundBrewer, G. J., & Wallimann, T. W. (2000) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2000.0741968.x · Cited by 230
Creatine in health and disease
Kreider, R. B., & Stout, J. R. (2021) · Nutrients · doi:10.3390/nu13020447 · Cited by 227
Increase of total creatine in human brain after oral supplementation of creatine-monohydrate
Dechent, P., Pouwels, P. J. W., Wilken, B., Hanefeld, F., & Frahm, J. (1999) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.1999.277.3.r698 · Cited by 221
Creatine monohydrate enhances strength and body composition in Duchenne muscular dystrophy
Tarnopolsky, M. A., Mahoney, D. J., Vajsar, J., Rodriguez, C., Doherty, T. J., Roy, B. D., & Biggar, D. (2004) · Neurology · doi:10.1212/01.wnl.0000125178.18862.9d · Cited by 216
Howes, O. D., Williams, M., Ibrahim, K., Leung, G., Egerton, A., McGuire, P. K., & Turkheimer, F. (2013) · Brain · doi:10.1093/brain/awt264 · Cited by 198
Creatine Supplementation and Brain Health
Roschel, H., Gualano, B., Ostojic, S. M., & Rawson, E. S. (2021) · Nutrients · doi:10.3390/nu13020586 · Cited by 174
Dolan, E., Gualano, B., & Rawson, E. S. (2019) · European Journal of Sport Science · doi:10.1080/17461391.2018.1500644 · Cited by 171
Creatine for treating muscle disorders
Kley, R. A., Tarnopolsky, M. A., & Vorgerd, M. (2013) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd004760.pub4 · Cited by 169
McMorris, T., Harris, R. C., Swain, J., Corbett, J., Collard, K., Dyson, R. J., Dye, L., Hodgson, C., & Draper, N. (2006) · Psychopharmacology · doi:10.1007/s00213-005-0269-z · Cited by 168
Candow, D. G., Forbes, S. C., Chilibeck, P. D., Cornish, S. M., Antonio, J., & Kreider, R. B. (2019) · Journal of Clinical Medicine · doi:10.3390/jcm8040488 · Cited by 149
Self-citationWiles, N. J., Thomas, L., Turner, N., Garfield, K., Kounali, D., Campbell, J., Kessler, D., Kuyken, W., Lewis, G., Morrison, J., et al. (2016) · The Lancet Psychiatry · doi:10.1016/s2215-0366(15)00495-2 · Cited by 139
Beneficial effects of creatine supplementation in dystrophic patients
Louis, M., Lebacq, J., Poortmans, J. R., Belpaire‐Dethiou, M., Devogelaer, J., Van Hecke, P., Goubel, F., & Francaux, M. (2003) · Muscle & Nerve · doi:10.1002/mus.10355 · Cited by 130
Sakellaris, G., Kotsiou, M., Tamiolaki, M., Kalostos, G., Tsapaki, E., Spanaki, M., Spilioti, M., Charissis, G., & Evangeliou, A. (2006) · The Journal of Trauma: Injury, Infection, and Critical Care · doi:10.1097/01.ta.0000230269.46108.d5 · Cited by 116
Creatine supplementation, sleep deprivation, cortisol, melatonin and behavior
McMorris, T., Harris, R. C., Howard, A. N., Langridge, G., Hall, B., Corbett, J., Dicks, M., & Hodgson, C. (2007) · Physiology & Behavior · doi:10.1016/j.physbeh.2006.08.024 · Cited by 115
Abdallah, C. G., Averill, C. L., Salas, R., Averill, L. A., Baldwin, P. R., Krystal, J. H., Mathew, S. J., & Mathalon, D. H. (2017) · Biological Psychiatry: Cognitive Neuroscience and Neuroimaging · doi:10.1016/j.bpsc.2017.04.006 · Cited by 111
CINRG randomized controlled trial of creatine and glutamine in Duchenne muscular dystrophy
Escolar, D. M., Buyse, G., Henricson, E., Leshner, R., Florence, J., Mayhew, J., Tesi‐Rocha, C., Gorni, K., Pasquali, L., Patel, K. M., et al. (2005) · Annals of Neurology · doi:10.1002/ana.20523 · Cited by 107
Cook, C. J., Crewther, B. T., Kilduff, L. P., Drawer, S., & Gaviglio, C. M. (2011) · Journal of the International Society of Sports Nutrition · doi:10.1186/1550-2783-8-2 · Cited by 104
Kreider, R. B., Jäger, R., & Purpura, M. (2022) · Nutrients · doi:10.3390/nu14051035 · Cited by 103
Cyclocreatine treatment improves cognition in mice with creatine transporter deficiency
Kurosawa, Y., DeGrauw, T. J., Lindquist, D. M., Blanco, V. M., Pyne-Geithman, G. J., Daikoku, T., Chambers, J. B., Benoit, S. C., & Clark, J. F. (2012) · Journal of Clinical Investigation · doi:10.1172/jci59373 · Cited by 98
Creatine for neuroprotection in neurodegenerative disease: end of story?
Bender, A., & Klopstock, T. (2016) · Amino Acids · doi:10.1007/s00726-015-2165-0 · Cited by 96
Creatine supplementation in women's health: a lifespan perspective
Smith-Ryan, A. E., Cabre, H. E., Eckerson, J. M., & Candow, D. G. (2021) · Nutrients · doi:10.3390/nu13030877 · Cited by 92
Balestrino, M., & Adriano, E. (2019) · Medicinal Research Reviews · doi:10.1002/med.21590 · Cited by 90
Can Creatine Combat the Mental Fatigue–associated Decrease in Visuomotor Skills?
VAN CUTSEM, J., ROELANDS, B., PLUYM, B., TASSIGNON, B., VERSCHUEREN, J., DE PAUW, K., & MEEUSEN, R. (2020) · Medicine & Science in Sports & Exercise · doi:10.1249/mss.0000000000002122 · Cited by 86
Creatine supplementation does not improve cognitive function in young adults
Rawson, E. S., Lieberman, H. R., Walsh, T. M., Zuber, S. M., Harhart, J. M., & Matthews, T. C. (2008) · Physiology & Behavior · doi:10.1016/j.physbeh.2008.05.009 · Cited by 77
Creatine for the Treatment of Depression
Kious, B. M., Kondo, D. G., & Renshaw, P. F. (2019) · Biomolecules · doi:10.3390/biom9090406 · Cited by 74 · cited 1×
“In addition, because ATP is used to convert creatine to phosphocreatine, low concentrations of creatine are associated with lower release of ATP from astrocytes, which is in turn considered to promote symptoms of depression and anxiety [158, 159].”
BackgroundClinical Use of Creatine in Neuromuscular and Neurometabolic Disorders
Tarnopolsky, M. A. (2007) · Subcellular Biochemistry · doi:10.1007/978-1-4020-6486-9_10 · Cited by 67
Effect of creatine supplementation and drop-set resistance training in untrained aging adults
Johannsmeyer, S., Candow, D. G., Brahms, C. M., Michel, D., & Zello, G. A. (2016) · Experimental Gerontology · doi:10.1016/j.exger.2016.08.005 · Cited by 59
Self-citationSaraiva, A. L. L., Ferreira, A. P. O., Silva, L. F. A., Hoffmann, M. S., Dutra, F. D., Furian, A. F., Oliveira, M. S., Fighera, M. R., & Royes, L. F. F. (2012) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2011.10.010 · Cited by 49
Involvement of hippocampal CAMKII/CREB signaling in the spatial memory retention induced by creatine
Souza, M. A., Magni, D. V., Guerra, G. P., Oliveira, M. S., Furian, A. F., Pereira, L., Marquez, S. V., Ferreira, J., Fighera, M. R., & Royes, L. F. F. (2012) · Amino Acids · doi:10.1007/s00726-012-1329-4 · Cited by 42
Allah Yar, R., Akbar, A., & Iqbal, F. (2015) · Brain Research · doi:10.1016/j.brainres.2014.11.017 · Cited by 30
Research works printed but not linked: 122
- Persky A, Brazeau G. Clinical pharmacology of the dietary supplement creatine monohydrate. Pharmacol Rev. 2001;53:161–76.
- Delpino FM, Figueiredo LM, Forbes SC, Candow DG, Santos HO. Influence of age, sex, and type of exercise on the efficacy of creatine supplementation on lean body mass: a systematic review and meta-analysis of randomized clinical trials. Nutrition. 2022;103–104:111791. · DOI · Paper page
- Syrotuik D, Bell G. Acute creatine monohydrate supplementation: a descriptive physiological profile of responders vs nonresponders. J Strength Cond Res. 2004;18:610–7.
- Forbes SC, Cordingley DM, Cornish SM, Gualano B, Roschel H, Ostojic SM, et al. Effects of creatine supplementation on brain function and health. Nutrients. 2022;14:921. · DOI · Paper page
- Wallimann T, Tokarska-Schlattner M, Schlattner U. The creatine kinase system and pleiotropic effects of creatine. Amino Acid. 2011;40:1271. · DOI · Paper page
- Raichle ME, Gusnard DA. Appraising the brain’s energy budget. Proc Natl Acad Sci U S A. 2002;99:10237–9. · DOI · Paper page
- De Graaf RA. In vivo NMR spectroscopy: principles and techniques. 2018. Available from: https://www.wiley.com/en-us/In+Vivo+NMR+Spectroscopy%3A+Principles+and+Techniques%2C+3rd+Edition-p-9781119382515. Accessed 18 Dec 2022.
- Fons C, Campistol J. Creatine defects and central nervous system. Semin Pediatr Neurol. 2016;23:285–9. · DOI
- Ostojic SM. Low tissue creatine: a therapeutic target in clinical nutrition. Nutrients. 2022;14:1230. · DOI
- Braissant O, Bachmann C, Henry H. Expression and function of AGAT, GAMT and CT1 in the mammalian brain. Subcell Biochem. 2007;46:67–81. · DOI
- Ohtsuki S, Tachikawa M, Takanaga H, Shimizu H, Watanabe M, Hosoya KI, et al. The blood-brain barrier creatine transporter is a major pathway for supplying creatine to the brain. J Cereb Blood Flow Metab. 2002;22:1327–35. · DOI
- Yazigi Solis M, De Salles PV, Artioli GG, Roschel H, Otaduy MC, Gualano B. Brain creatine depletion in vegetarians? A cross-sectional 1H-magnetic resonance spectroscopy (1H-MRS) study. Br J Nutr. 2014;111:1272–4. · DOI
- Kondo DG, Forrest LN, Shi X, Sung Y-H, Hellem TL, Huber RS, et al. Creatine target engagement with brain bioenergetics: a dose-ranging phosphorus-31 magnetic resonance spectroscopy study of adolescent females with SSRI-resistant depression. Amino Acids. 2016;48:1941–54. · DOI · Paper page
- Fernandes-Pires G, Braissant O. Current and potential new treatment strategies for creatine deficiency syndromes. Mol Genet Metab. 2022;135:15–26. · DOI · Paper page
- Braissant O, Henry H. AGAT, GAMT and SLC6A8 distribution in the central nervous system, in relation to creatine deficiency syndromes: a review. J Inherit Metab Dis. 2008;31:230–9. · DOI
- Christie DL. Functional insights into the creatine transporter. Subcell Biochem. 2007;46:99–118. · DOI
- Snow RJ, Murphy RM. Creatine and the creatine transporter: a review. Mol Cell Biochem. 2001;224:169–81. · DOI
- Ostojic SM. Modulation of CT1 function: from klotho protein to ammonia and beyond. Front Nutr. 2021;8:660021. · DOI
- Stead LM, Au KP, Jacobs RL, Brosnan ME, Brosnan JT. Methylation demand and homocysteine metabolism: effects of dietary provision of creatine and guanidinoacetate. Am J Physiol Endocrinol Metab. 2001;281:E1100. · DOI
- Ostojic SM, Stojanovic M, Drid P, Hoffman JR, Sekulic D, Zenic N. Supplementation with guanidinoacetic acid in women with chronic fatigue syndrome. Nutrients. 2016;8:72. · DOI
- Bender A, Samtleben W, Elstner M, Klopstock T. Long-term creatine supplementation is safe in aged patients with Parkinson disease. Nutr Res. 2008;28:172–8. · DOI · Paper page
- Snow WM, Cadonic C, Cortes-Perez C, Adlimoghaddam A, Roy Chowdhury SK, Thomson E, et al. Sex-specific effects of chronic creatine supplementation on hippocampal-mediated spatial cognition in the 3xTg mouse model of Alzheimer’s disease. Nutrients. 2020;12:3589. · DOI
- Snow WM, Cadonic C, Cortes-Perez C, Roy Chowdhury SK, Djordjevic J, Thomson E, et al. Chronic dietary creatine enhances hippocampal-dependent spatial memory, bioenergetics, and levels of plasticity-related proteins associated with NF-κB. Learn Mem. 2018;25:54–66. · DOI · Paper page
- Kaltschmidt B, Ndiaye D, Korte M, Pothion S, Arbibe L, Prüllage M, et al. NF-kappaB regulates spatial memory formation and synaptic plasticity through protein kinase A/CREB signaling. Mol Cell Biol. 2006;26:2936–46. · DOI
- Mao X, Kelty TJ, Kerr NR, Childs TE, Roberts MD, Booth FW. Creatine supplementation upregulates mTORC1 signaling and markers of synaptic plasticity in the dentate gyrus while ameliorating LPS-induced cognitive impairment in female rats. Nutrients. 2021;13:2758. · DOI
- AliMohammadi M, Eshraghian M, Zarindast MR, Aliaghaei A, Pishva H. Effects of creatine supplementation on learning, memory retrieval, and apoptosis in an experimental animal model of Alzheimer disease. Med J Islam Repub Iran. 2015;29:273.
- Ramesh V, Nair D, Zhang SXL, Hakim F, Kaushal N, Kayali F, et al. Disrupted sleep without sleep curtailment induces sleepiness and cognitive dysfunction via the tumor necrosis factor-α pathway. J Neuroinflamm. 2012;9:1–15. · DOI
- D’Rozario AL, Bartlett DJ, Wong KKH, Sach T, Yang Q, Grunstein RR, et al. Brain bioenergetics during resting wakefulness are related to neurobehavioral deficits in severe obstructive sleep apnea: a 31P magnetic resonance spectroscopy study. Sleep. 2018;41:zsy117. · DOI
- Dworak M, Kim T, Mccarley RW, Basheer R. Creatine supplementation reduces sleep need and homeostatic sleep pressure in rats. J Sleep Res. 2017;26:377–85. · DOI
- McMorris T, Mielcarz G, Harris RC, Swain JP, Howard A. Creatine supplementation and cognitive performance in elderly individuals. Neuropsychol Dev Cogn B Aging Neuropsychol Cogn. 2007;14:517–28. · DOI · Paper page
- Merege-Filho CAA, Otaduy MCG, De Sá-Pinto AL, De Oliveira MO, De Souza GL, Hayashi APT, et al. Does brain creatine content rely on exogenous creatine in healthy youth? A proof-of-principle study. Appl Physiol Nutr Metab. 2017;42:128–34. · DOI · Paper page
- Turner CE, Byblow WD, Gant N. Creatine supplementation enhances corticomotor excitability and cognitive performance during oxygen deprivation. J Neurosci. 2015;35:1773. · DOI · Paper page
- Watanabe A, Kato N, Kato T. Effects of creatine on mental fatigue and cerebral hemoglobin oxygenation. Neurosci Res. 2002;42:279–85. · DOI · Paper page
- Ainsley Dean PJ, Arikan G, Opitz B, Sterr A. Potential for use of creatine supplementation following mild traumatic brain injury. Concussion. 2017;2:CNC34. · DOI · Paper page
- Vedung F, Fahlström M, Wall A, Antoni G, Lubberink M, Johansson J, et al. Chronic cerebral blood flow alterations in traumatic brain injury and sports-related concussions. Brain Inj. 2022;36:948–60. · DOI
- Sullivan P, Geiger J, Mattson M, Scheff S. Dietary supplement creatine protects against traumatic brain injury. Ann Neurol. 2000;48:723–9. · DOI
- Scheff SW, Dhillon HS. Creatine-enhanced diet alters levels of lactate and free fatty acids after experimental brain injury. Neurochem Res. 2004;29:469–79. · DOI
- Dong XX, Wang Y, Qin ZH. Molecular mechanisms of excitotoxicity and their relevance to pathogenesis of neurodegenerative diseases. Acta Pharmacol Sin. 2009;30:379. · DOI · Paper page
- Masse I, Moquin L, Bouchard C, Gratton A, De Beaumont L. Efficacy of prophylactic versus therapeutic administration of the NMDA receptor antagonist MK-801 on the acute neurochemical response to a concussion in a rat model combining force and rotation. J Neurosurg. 2021;136:1–10.
- Genius J, Geiger J, Bender A, Möller HJ, Klopstock T, Rujescu D. Creatine protects against excitoxicity in an in vitro model of neurodegeneration. PLoS ONE. 2012;7: e30554. · DOI
- Sakellaris G, Nasis G, Kotsiou M, Tamiolaki M, Charissis G, Evangeliou A. Prevention of traumatic headache, dizziness and fatigue with creatine administration: a pilot study. Acta Paediatr. 2008;97:34. · DOI
- Chaychi S, Valera E, Tartaglia MC. Sex and gender differences in mild traumatic brain injury/concussion. Int Rev Neurobiol. 2022;164:349–75. · DOI
- Ravina BM, Fagan SC, Hart RG, Hovinga CA, Murphy DD, Dawson TM, et al. Neuroprotective agents for clinical trials in Parkinson’s disease: a systematic assessment. Neurology. 2003;60:1234–40. · DOI · Paper page
- Ostojic SM. Creatine and multiple sclerosis. Nutr Neurosci. 2022;25:912–9. · DOI
- Soria Lopez JA, González HM, Léger GC. Alzheimer’s disease. Handb Clin Neurol. 2019;167:231–55. · DOI · Paper page
- Rijpma A, van der Graaf M, Meulenbroek O, Olde Rikkert MGM, Heerschap A. Altered brain high-energy phosphate metabolism in mild Alzheimer’s disease: a 3-dimensional 31P MR spectroscopic imaging study. NeuroImage Clin. 2018;18:254–61. · DOI
- Pettegrew JW, Panchalingam K, Klunk WE, McClure RJ, Muenz LR. Alterations of cerebral metabolism in probable Alzheimer’s disease: a preliminary study. Neurobiol Aging. 1994;15:117–32. · DOI
- Aksenov MY, Aksenova MV, Payne RM, Smith CD, Markesbery WR, Carney JM. The expression of creatine kinase isoenzymes in neocortex of patients with neurodegenerative disorders: Alzheimer’s and Pick’s disease. Exp Neurol. 1997;146:458–65. · DOI
- Laakso MP, Hiltunen Y, Könönen M, Kivipelto M, Koivisto A, Hallikainen M, et al. Decreased brain creatine levels in elderly apolipoprotein E ε4 carriers. J Neural Transm. 2003;110:267–75. · DOI
- Alimohammadi-Kamalabadi M, Eshraghian M, Zarindast M, Aliaghaei A, Pishva H. Effect of creatine supplementation on cognitive performance and apoptosis in a rat model of amyloid-beta-induced Alzheimer’s disease. Iran J Basic Med Sci. 2016;19:1159–65.
- Sagna A, Gallo JJ, Pontone GM. Systematic review of factors associated with depression and anxiety disorders among older adults with Parkinson’s disease. Parkinsonism Relat Disord. 2014;20:708–15. · DOI
- Matthews RT, Ferrante RJ, Klivenyi P, Yang L, Klein AM, Mueller G, et al. Creatine and cyclocreatine attenuate MPTP neurotoxicity. Exp Neurol. 1999;157:142–9. · DOI · Paper page
- Klein AM, Ferrante RJ. The neuroprotective role of creatine. Subcell Biochem. 2007;46:205–43. · DOI
- Bender A, Koch W, Elstner M, Schombacher Y, Bender J, Moeschl M, et al. Creatine supplementation in Parkinson disease: a placebo-controlled randomized pilot trial. Neurology. 2006;67:1262–4. · DOI
- Li Z, Wang P, Yu Z, Cong Y, Sun H, Zhang J, et al. The effect of creatine and coenzyme q10 combination therapy on mild cognitive impairment in Parkinson’s disease. Eur Neurol. 2015;73:205–11. · DOI
- Ravina B, Kieburtz K, Tilley B, Shannon K, Tanner C, Frederick Wooten G, et al. A randomized, double-blind, futility clinical trial of creatine and minocycline in early Parkinson disease. Neurology. 2006;66:664–71. · DOI · Paper page
- Kieburtz K, Tilley B, Ravina B, Galpern WR, Shannon K, Tanner C, et al. A pilot clinical trial of creatine and minocycline in early Parkinson disease: 18-month results. Clin Neuropharmacol. 2008;31:141–50. · DOI
- Kieburtz K, Tilley BC, Elm JJ, Babcock D, Hauser R, Ross GW, et al. Effect of creatine monohydrate on clinical progression in patients with Parkinson disease: a randomized clinical trial. JAMA. 2015;313:584–93. · DOI · Paper page
- Alonso A, Hernán MA. Temporal trends in the incidence of multiple sclerosis: a systematic review. Neurology. 2008;71:129–35. · DOI · Paper page
- Goldenberg MM. Multiple sclerosis review. Pharm Ther. 2012;37:175.
- Dalgas U, Langeskov-Christensen M, Stenager E, Riemenschneider M, Hvid LG. Exercise as medicine in multiple sclerosis: time for a paradigm shift: preventive, symptomatic, and disease-modifying aspects and perspectives. Curr Neurol Neurosci Rep. 2019;19:1–12. · DOI · Paper page
- Taul-Madsen L, Connolly L, Dennett R, Freeman J, Dalgas U, Hvid LG. Is aerobic or resistance training the most effective exercise modality for improving lower extremity physical function and perceived fatigue in people with multiple sclerosis? A systematic review and meta-analysis. Arch Phys Med Rehabil. 2021;102:2032–48. · DOI
- Beer M, Sandstede J, Weilbach F, Spindler M, Buchner S, Krug A, et al. Cardiac metabolism and function in patients with multiple sclerosis: a combined 31P-MR-spectroscopy and MRI study. Rofo. 2001;173:399–404. · DOI
- Arnold DL, Riess GT, Matthews PM, Francis GS, Collins DL, Wolfson C, et al. Use of proton magnetic resonance spectroscopy for monitoring disease progression in multiple sclerosis. Ann Neurol. 1994;36:76–82. · DOI
- Lynch J, Peeling J, Auty A, Sutherland G. Nuclear magnetic resonance study of cerebrospinal fluid from patients with multiple sclerosis. Can J Neurol Sci. 1993;20:194–8. · DOI
- Lambert CP, Archer RL, Carrithers JA, Fink WJ, Evans WJ, Trappe TA. Influence of creatine monohydrate ingestion on muscle metabolites and intense exercise capacity in individuals with multiple sclerosis. Arch Phys Med Rehabil. 2003;84:1206–10. · DOI
- Malin SK, Cotugna N, Fang CS. Effect of creatine supplementation on muscle capacity in individuals with multiple sclerosis. J Diet Suppl. 2008;5:20–32. · DOI
- Zucchi E, Bonetto V, Sorarù G, Martinelli I, Parchi P, Liguori R, et al. Neurofilaments in motor neuron disorders: towards promising diagnostic and prognostic biomarkers. Mol Neurodegener. 2020;15:1–20. · DOI
- Gittings LM, Sattler R. Recent advances in understanding amyotrophic lateral sclerosis and emerging therapies. Fac Rev. 2020;9:12. · DOI
- Tarnopolsky MA, Beal MF. Potential for creatine and other therapies targeting cellular energy dysfunction in neurological disorders. Ann Neurol. 2001;49:561–74. · DOI · Paper page
- Wyss M, Schulze A. Health implications of creatine: can oral creatine supplementation protect against neurological and atherosclerotic disease? Neuroscience. 2002;112:243–60. · DOI · Paper page
- Beal MF. Neuroprotective effects of creatine. Amino Acids. 2011;40:1305–13. · DOI
- Klopstock T, Elstner M, Bender A. Creatine in mouse models of neurodegeneration and aging. Amino Acids. 2011;40:1297–303. · DOI
- Hervias I, Beal MF, Manfredi G. Mitochondrial dysfunction and amyotrophic lateral sclerosis. Muscle Nerve. 2006;33:598–608. · DOI
- Klivenyi P, Kiaei M, Gardian G, Calingasan NY, Beal MF. Additive neuroprotective effects of creatine and cyclooxygenase 2 inhibitors in a transgenic mouse model of amyotrophic lateral sclerosis. J Neurochem. 2004;88:576–82. · DOI
- Klivenyi P, Ferrante RJ, Matthews RT, Bogdanov MB, Klein AM, Andreassen OA, et al. Neuroprotective effects of creatine in a transgenic animal model of amyotrophic lateral sclerosis. Nat Med. 1999;5:347–50. · DOI · Paper page
- Andreassen OA, Jenkins BG, Dedeoglu A, Ferrante KL, Bogdanov MB, Kaddurah-Daouk R, et al. Increases in cortical glutamate concentrations in transgenic amyotrophic lateral sclerosis mice are attenuated by creatine supplementation. J Neurochem. 2001;77:383–90. · DOI
- Derave W, Van Den Bosch L, Lemmens G, Eijnde BO, Robberecht W, Hespel P. Skeletal muscle properties in a transgenic mouse model for amyotrophic lateral sclerosis: effects of creatine treatment. Neurobiol Dis. 2003;13:264–72. · DOI
- Mazzini L, Balzarini C, Colombo R, Mora G, Pastore I, De Ambrogio R, et al. Effects of creatine supplementation on exercise performance and muscular strength in amyotrophic lateral sclerosis: preliminary results. J Neurol Sci. 2001;191:139–44. · DOI
- Groeneveld GJ, Veldink JH, Van der Tweel I, Kalmijn S, Beijer C, De Visser M, et al. A randomized sequential trial of creatine in amyotrophic lateral sclerosis. Ann Neurol. 2003;53:437–45. · DOI · Paper page
- Rosenfeld J, King RM, Jackson CE, Bedlack RS, Barohn RJ, Dick A, et al. Creatine monohydrate in ALS: effects on strength, fatigue, respiratory status and ALSFRS. Amyotroph Lateral Scler. 2008;9:266–72. · DOI
- Shefner JM, Cudkowicz ME, Schoenfeld D, Conrad T, Taft J, Chilton M, et al. A clinical trial of creatine in ALS. Neurology. 2004;63:1656–61. · DOI · Paper page
- Drory VE, Gross D. No effect of creatine on respiratory distress in amyotrophic lateral sclerosis. Amyotroph Lateral Scler Other Motor Neuron Disord. 2002;3:43–6. · DOI
- Tarnopolsky M, Parise G. Direct measurement of high-energy phosphate compounds in patients with neuromuscular disease. Muscle Nerve. 1999;22:1228–33. · DOI
- Fitch CD, Moody LG. Creatine metabolism in skeletal muscle. V. An intracellular abnormality of creatine trapping in dystrophic muscle. Proc Soc Exp Biol Med. 1969;132:219–22. · DOI
- Passamano L, Taglia A, Palladino A, Viggiano E, D’Ambrosio P, Scutifero M, et al. Improvement of survival in Duchenne muscular dystrophy: retrospective analysis of 835 patients. Acta Myol. 2012;31:125.
- Passaquin AC, Renard M, Kay L, Challet C, Mokhtarian A, Wallimann T, et al. Creatine supplementation reduces skeletal muscle degeneration and enhances mitochondrial function in mdx mice. Neuromuscul Disord. 2002;12:174–82. · DOI · Paper page
- Ogborn DI, Smith KJ, Crane JD, Safdar A, Hettinga BP, Tupler R, et al. Effects of creatine and exercise on skeletal muscle of FRG1-transgenic mice. Can J Neurol Sci. 2012;39:225–31. · DOI · Paper page
- Davidson ZE, Hughes I, Ryan MM, Kornberg AJ, Cairns AG, Jones K, et al. Effect of a multicomponent nutritional supplement on functional outcomes for Duchenne muscular dystrophy: a randomized controlled trial. Clin Nutr. 2021;40:4702–11. · DOI
- Tarnopolsky M, Mahoney D, Thompson T, Naylor H, Doherty TJ. Creatine monohydrate supplementation does not increase muscle strength, lean body mass, or muscle phosphocreatine in patients with myotonic dystrophy type 1. Muscle Nerve. 2004;29:51–8. · DOI · Paper page
- Walter MC, Reilich P, Lochmüller H, Kohnen R, Schlotter B, Hautmann H, et al. Creatine monohydrate in myotonic dystrophy: a double-blind, placebo-controlled clinical study. J Neurol. 2002;249:1717–22. · DOI · Paper page
- Schneider-Gold C, Beck M, Wessig C, George A, Kele H, Reiners K, et al. Creatine monohydrate in DM2/PROMM: a double-blind placebo-controlled clinical study. Proximal myotonic myopathy. Neurology. 2003;60:500–2. · DOI · Paper page
- McCorquodale D, Pucillo EM, Johnson NE. Management of Charcot–Marie–Tooth disease: improving long-term care with a multidisciplinary approach. J Multidiscip Healthc. 2016;9:7–19.
- Doherty TJ, Lougheed K, Markez J, Tarnopolsky MA. Creatine monohydrate does not increase strength in patients with hereditary neuropathy. Neurology. 2001;57:559–60. · DOI
- Chetlin RD, Gutmann L, Tarnopolsky MA, Ullrich IH, Yeater RA. Resistance training exercise and creatine in patients with Charcot-Marie-Tooth disease. Muscle Nerve. 2004;30:69–76. · DOI · Paper page
- Smith CA, Chetlin RD, Gutmann L, Yeater RA, Alway SE. Effects of exercise and creatine on myosin heavy chain isoform composition in patients with Charcot–Marie–Tooth disease. Muscle Nerve. 2006;34:586–94. · DOI · Paper page
- Jung WY, Jang SH, Kim SG, Jae YM, Kong BG, Kim HC, et al. Times to discontinue antidepressants over 6 months in patients with major depressive disorder. Psychiatry Investig. 2016;13:440–6. · DOI
- Moncrieff J, Cooper RE, Stockmann T, Amendola S, Hengartner MP, Horowitz MA. The serotonin theory of depression: a systematic umbrella review of the evidence. Mol Psychiatry. 2022. https://doi.org/10.1038/s41380-022-01661-0. · DOI · Paper page
- Parsey RV, Oquendo MA, Ogden RT, Olvet DM, Simpson N, Huang YY, et al. Altered serotonin 1A binding in major depression: a [carbonyl-C-11]WAY100635 positron emission tomography study. Biol Psychiatry. 2006;59:106–13. · DOI · Paper page
- Persson J, Wall A, Weis J, Gingnell M, Antoni G, Lubberink M, et al. Inhibitory and excitatory neurotransmitter systems in depressed and healthy: a positron emission tomography and magnetic resonance spectroscopy study. Psychiatry Res Neuroimaging. 2021;315: 111327. · DOI
- Kumar A, Thomas A, Lavretsky H, Yue K, Huda A, Curran J, et al. Frontal white matter biochemical abnormalities in late-life major depression detected with proton magnetic resonance spectroscopy. Am J Psychiatry. 2002;159:630–6. · DOI
- Li BSY, Wang H, Gonen O. Metabolite ratios to assumed stable creatine level may confound the quantification of proton brain MR spectroscopy. Magn Reson Imaging. 2003;21:923–8. · DOI
- Chang L, Mehringer CM, Ernst T, Melchor R, Myers H, Forney D, et al. Neurochemical alterations in asymptomatic abstinent cocaine users: a proton magnetic resonance spectroscopy study. Biol Psychiatry. 1997;42:1105–14. · DOI
- Faulkner P, Lucini Paioni S, Kozhuharova P, Orlov N, Lythgoe DJ, Daniju Y, et al. Daily and intermittent smoking are associated with low prefrontal volume and low concentrations of prefrontal glutamate, creatine, myo-inositol, and N-acetylaspartate. Addict Biol. 2021;26:e12986. · DOI
- Prescot AP, Locatelli AE, Renshaw PF, Yurgelun-Todd DA. Neurochemical alterations in adolescent chronic marijuana smokers: a proton MRS study. Neuroimage. 2011;57:69–75. · DOI
- Öngür D, Prescot AP, Jensen JE, Cohen BM, Renshaw PF. Creatine abnormalities in schizophrenia and bipolar disorder. Psychiatry Res. 2009;172:44–8. · DOI
- Auer DP, Pütz B, Kraft E, Lipinski B, Schill J, Holsboer F. Reduced glutamate in the anterior cingulate cortex in depression: an in vivo proton magnetic resonance spectroscopy study. Biol Psychiatr. 2000;47:305–13. · DOI · Paper page
- Mirza Y, O’Neill J, Smith EA, Russell A, Smith JM, Banerjee SP, et al. Increased medial thalamic creatine-phosphocreatine found by proton magnetic resonance spectroscopy in children with obsessive-compulsive disorder versus major depression and healthy controls. J Child Neurol. 2006;21:106–11. · DOI
- Faulkner P, Paioni SL, Kozhuharova P, Orlov N, Lythgoe DJ, Daniju Y, et al. Relationship between depression, prefrontal creatine and grey matter volume. J Psychopharmacol. 2021;35:1464–72. · DOI
- Yue Q, Liu M, Nie X, Wu Q, Li J, Zhang W, et al. Quantitative 3.0T MR spectroscopy reveals decreased creatine concentration in the dorsolateral prefrontal cortex of patients with social anxiety disorder. PLoS ONE. 2012;7:e48105. · DOI
- Lyoo IK, Yoon S, Kim TS, Hwang J, Kim JE, Won W, et al. A randomized, double-blind placebo-controlled trial of oral creatine monohydrate augmentation for enhanced response to a selective serotonin reuptake inhibitor in women with major depressive disorder. Am J Psychiatry. 2012;169:937–45. · DOI · Paper page
- Nemets B, Levine J. A pilot dose-finding clinical trial of creatine monohydrate augmentation to SSRIs/SNRIs/NASA antidepressant treatment in major depression. Int Clin Psychopharmacol. 2013;28:127–33. · DOI
- Braissant O. Creatine and guanidinoacetate transport at blood-brain and blood-cerebrospinal fluid barriers. J Inherit Metab Dis. 2012;35:655–64. · DOI · Paper page
- van de Kamp JM, Pouwels PJW, Aarsen FK, ten Hoopen LW, Knol DL, de Klerk JB, et al. Long-term follow-up and treatment in nine boys with X-linked creatine transporter defect. J Inherit Metab Dis. 2012;35:149. · DOI · Paper page
- Pazini FL, Cunha MP, Rosa JM, Colla ARS, Lieberknecht V, Oliveira Á, et al. Creatine, similar to ketamine, counteracts depressive-like behavior induced by corticosterone via PI3K/Akt/mTOR pathway. Mol Neurobiol. 2016;53:6818–34. · DOI
- Assis LC, Rezin GT, Comim CM, Valvassori SS, Jeremias IC, Zugno AI, et al. Effect of acute administration of ketamine and imipramine on creatine kinase activity in the brain of rats. Rev Bras Psiquiatr. 2009;31:247–52. · DOI
- Mirowsky J, Ross CE. Age and depression. J Health Soc Behav. 1992;33:187–205. · DOI · Paper page
- Lind A, Boraxbekk CJ, Petersen ET, Paulson OB, Siebner HR, Marsman A. Regional myo-inositol, creatine, and choline levels are higher at older age and scale negatively with visuospatial working memory: a cross-sectional proton MR spectroscopy study at 7 Tesla on normal cognitive ageing. J Neurosci. 2020;40:8149–59. · DOI
- Brown MS, Singel D, Hepburn S, Rojas DC. Increased glutamate concentration in the auditory cortex of persons with autism and first-degree relatives: a (1)H-MRS study. Autism Res. 2013;6:1–10. · DOI
- Nagae-Poetscher LM, Bonekamp D, Barker PB, Brant LJ, Kaufmann WE, Horská A. Asymmetry and gender effect in functionally lateralized cortical regions: a proton MRS imaging study. J Magn Reson Imaging. 2004;19:27–33. · DOI
- Pouwels PJW, Frahm J. Regional metabolite concentrations in human brain as determined by quantitative localized proton MRS. Magn Reson Med. 1998;39:53–60. · DOI · Paper page
- Tayoshi S, Sumitani S, Taniguchi K, Shibuya-Tayoshi S, Numata S, Iga J, et al. Metabolite changes and gender differences in schizophrenia using 3-Tesla proton magnetic resonance spectroscopy (1H-MRS). Schizophr Res. 2009;108:69–77. · DOI
Cited by
Creatine monohydrate supplementation for older adults and clinical populations
Candow, D. G., Ostojic, S. M., Chilibeck, P. D., Longobardi, I., Gualano, B., Tarnopolsky, M. A., Wallimann, T., Moriarty, T., Kreider, R. B., Forbes, S. C., et al. (2025) · Journal of the International Society of Sports Nutrition · doi:10.1080/15502783.2025.2534130 · Cited by 43
Self-citationAntonio, J., Brown, A. F., Candow, D. G., Chilibeck, P. D., Ellery, S. J., Forbes, S. C., Gualano, B., Jagim, A. R., Kerksick, C., Kreider, R. B., et al. (2025) · Journal of the International Society of Sports Nutrition · doi:10.1080/15502783.2024.2441760 · Cited by 33
Self-citation
Metadata
- Authors
- Candow, D. G., Forbes, S. C., Ostojic, S. M., Prokopidis, K., Stock, M. S., Harmon, K. K., & Faulkner, P.
- Venue
- Sports Medicine
- Published
- 2023-06-27
- Volume
- 53
- Issue
- S1
- Pages
- 49-65
- ISSN
- 0112-1642
- 1179-2035
- Cited by
- 78
- References
- 43
- Language
- en
- Update notices
- correction (2023-07-10)
- Licence
- creativecommons.org/licenses/by/4.0 (tdm)
- creativecommons.org/licenses/by/4.0 (vor)
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