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Articles

Beyond muscle: the effects of creatine supplementation on brain creatine, cognitive processing, and traumatic brain injury

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References

  • Allen, P. J. (2012). Creatine metabolism and psychiatric disorders: Does creatine supplementation have therapeutic value? Neuroscience & Biobehavioral Reviews, 36(5), 1442–1462. doi: 10.1016/j.neubiorev.2012.03.005
  • Alves, C. R., Merege Filho, C. A., Benatti, F. B., Brucki, S., Pereira, R. M., de Sa Pinto, A. L., … Gualano, B. (2013). Creatine supplementation associated or not with strength training upon emotional and cognitive measures in older women: A randomized double-blind study. PLoS One, 8(10), e76301. doi: 10.1371/journal.pone.0076301
  • Andres, R. H., Ducray, A. D., Schlattner, U., Wallimann, T., & Widmer, H. R. (2008). Functions and effects of creatine in the central nervous system. Brain Research Bulletin, 76(4), 329–343. doi: 10.1016/j.brainresbull.2008.02.035
  • Barrett, E. C., McBurney, M. I., & Ciappio, E. D. (2014). Omega-3 fatty acid supplementation as a potential therapeutic aid for the recovery from mild traumatic brain injury/concussion. Advances in Nutrition, 5(3), 268–277. doi: 10.3945/an.113.005280
  • Beard, E., & Braissant, O. (2010). Synthesis and transport of creatine in the CNS: Importance for cerebral functions. Journal of Neurochemistry, 115(2), 297–313. doi: 10.1111/j.1471-4159.2010.06935.x
  • Bender, A., & Klopstock, T. (2016). Creatine for neuroprotection in neurodegenerative disease: End of story? Amino Acids, 48(8), 1929–1940. doi: 10.1007/s00726-015-2165-0
  • Benton, D., & Donohoe, R. (2011). The influence of creatine supplementation on the cognitive functioning of vegetarians and omnivores. British Journal of Nutrition, 105(7), 1100–1105. doi: 10.1017/S0007114510004733
  • Braissant, O., Bachmann, C., & Henry, H. (2007). Expression and function of AGAT, GAMT and CT1 in the mammalian brain. Subcellular Biochemistry, 46, 67–81. doi: 10.1007/978-1-4020-6486-9_4
  • Branch, J. D. (2003). Effect of creatine supplementation on body composition and performance: A meta-analysis. International Journal of Sport Nutrition and Exercise Metabolism, 13(2), 198–226. doi: 10.1123/ijsnem.13.2.198
  • Candow, D. G., Chilibeck, P. D., & Forbes, S. C. (2014). Creatine supplementation and aging musculoskeletal health. Endocrine, 45(3), 354–361. doi: 10.1007/s12020-013-0070-4
  • Chilibeck, P. D., Kaviani, M., Candow, D. G., & Zello, G. A. (2017). Effect of creatine supplementation during resistance training on lean tissue mass and muscular strength in older adults: A meta-analysis. Open Access Journal of Sports Medicine, 8, 213–226. doi: 10.2147/OAJSM.S123529
  • Cook, C. J., Crewther, B. T., Kilduff, L. P., Drawer, S., & Gaviglio, C. M. (2011). Skill execution and sleep deprivation: Effects of acute caffeine or creatine supplementation – A randomized placebo-controlled trial. Journal of the International Society of Sports Nutrition, 8, 2. doi: 10.1186/1550-2783-8-2
  • Cox, G., Mujika, I., Tumilty, D., & Burke, L. (2002). Acute creatine supplementation and performance during a field test simulating match play in elite female soccer players. International Journal of Sport Nutrition and Exercise Metabolism, 12(1), 33–46. doi: 10.1123/ijsnem.12.1.33
  • Dean, P. J. A., Arikan, G., Opitz, B., & Sterr, A. (2017). Potential for use of creatine supplementation following mild traumatic brain injury. Concussion, 2(2), CNC34. doi. 10.2217/cnc-2016-0016
  • Dechent, P., Pouwels, P. J., Wilken, B., Hanefeld, F., & Frahm, J. (1999). Increase of total creatine in human brain after oral supplementation of creatine-monohydrate. American Journal of Physiology, 277(3 Pt 2), R698–R704.
  • Devries, M. C., & Phillips, S. M. (2014). Creatine supplementation during resistance training in older adults—A meta-analysis. Medicine & Science in Sports & Exercise, 46(6), 1194–1203. doi: 10.1249/MSS.0000000000000220
  • Greenhaff, P. L. (2001). The creatine-phosphocreatine system: There’s more than one song in its repertoire. The Journal of Physiology, 537(Pt 3), 657. doi: 10.1113/jphysiol.2001.013478
  • Greenhaff, P. L., Casey, A., Short, A. H., Harris, R., Söderlund, K., & Hultman, E. (1993). Influence of oral creatine supplementation of muscle torque during repeated bouts of maximal voluntary exercise in man. Clinical Science, 84(5), 565–571. doi: 10.1042/cs0840565
  • Gualano, B., Artioli, G. G., Poortmans, J. R., & Lancha Junior, A. H. (2010). Exploring the therapeutic role of creatine supplementation. Amino Acids, 38(1), 31–44. doi: 10.1007/s00726-009-0263-6
  • Gualano, B., de Salles Painelli, V., Roschel, H., Lugaresi, R., Dorea, E., Artioli, G. G., … Lancha Junior, A. H. (2011). Creatine supplementation does not impair kidney function in type 2 diabetic patients: A randomized, double-blind, placebo-controlled, clinical trial. European Journal of Applied Physiology, 111(5), 749–756. doi: 10.1007/s00421-010-1676-3
  • Gualano, B., Rawson, E. S., Candow, D. G., & Chilibeck, P. D. (2016). Creatine supplementation in the aging population: Effects on skeletal muscle, bone and brain. Amino Acids, 48(8), 1793–1805. doi: 10.1007/s00726-016-2239-7
  • Gualano, B., Roschel, H., Lancha, A. H., Jr., Brightbill, C. E., & Rawson, E. S. (2012). In sickness and in health: The widespread application of creatine supplementation. Amino Acids, 43(2), 519–529. doi: 10.1007/s00726-011-1132-7
  • Hamid, M., Rahnama, N., Moghadasi, M., & Ranjbar, K. (2012). Effect of creatine supplementation on sprint and skill performance in young soccer players. Middle East Journal of Scientific Research, 12(3), 397–401. doi: 10.5829/idosi.mejsr.2012.12.3.64214
  • Hammett, S. T., Wall, M. B., Edwards, T. C., & Smith, A. T. (2010). Dietary supplementation of creatine monohydrate reduces the human fMRI BOLD signal. Neuroscience Letters, 479(3), 201–205. doi: 10.1016/j.neulet.2010.05.054
  • Harris, R. C., Söderlund, K., & Hultman, E. (1992). Elevation of creatine in resting and exercised muscle of normal subjects by creatine supplementation. Clinical Science, 83(3), 367–374. doi: 10.1042/cs0830367
  • Hayashi, A. P., Solis, M. Y., Sapienza, M. T., Otaduy, M. C., de Sa Pinto, A. L., Silva, C. A., … Gualano, B. (2014). Efficacy and safety of creatine supplementation in childhood-onset systemic lupus erythematosus: A randomized, double-blind, placebo-controlled, crossover trial. Lupus, 23(14), 1500–1511. doi: 10.1177/0961203314546017
  • Heaton, L. E., Davis, J. K., Rawson, E. S., Nuccio, R. P., Witard, O. C., Stein, K. W., … Baker, L. B. (2017). Selected in-season nutritional strategies to enhance recovery for team sport athletes: A practical overview. Sports Medicine, 47(11), 2201–2218. doi: 10.1007/s40279-017-0759-2
  • Hellem, T. L., Sung, Y. H., Shi, X. F., Pett, M. A., Latendresse, G., Morgan, J., … Renshaw, P. F. (2015). Creatine as a novel treatment for depression in females using methamphetamine: A pilot study. Journal of Dual Diagnosis, 11(3–4), 189–202. doi: 10.1080/15504263.2015.1100471
  • Hultman, E., Söderlund, K., Timmons, J. A., Cederblad, G., & Greenhaff, P. L. (1996). Muscle creatine loading in men. Journal of Applied Physiology, 81(1), 232–237. doi: 10.1152/jappl.1996.81.1.232
  • Ipsiroglu, O. S., Stromberger, C., Ilas, J., Hoger, H., Muhl, A., & Stockler-Ipsiroglu, S. (2001). Changes of tissue creatine concentrations upon oral supplementation of creatine-monohydrate in various animal species. Life Sciences, 69(15), 1805–1815. doi: 10.1016/S0024-3205(01)01268-1
  • Kaldis, P., Hemmer, W., Zanolla, E., Holtzman, D., & Wallimann, T. (1996). ‘Hot spots’ of creatine kinase localization in brain: Cerebellum, hippocampus and choroid plexus. Developmental Neuroscience, 18(5-6), 542–554. doi: 10.1159/000111452
  • Kondo, D. G., Forrest, L. N., Shi, X., Sung, Y. H., Hellem, T. L., Huber, R. S., & Renshaw, P. F. (2016). Creatine target engagement with brain bioenergetics: A dose-ranging phosphorus-31 magnetic resonance spectroscopy study of adolescent females with SSRI-resistant depression. Amino Acids, 48(8), 1941–1954. doi: 10.1007/s00726-016-2194-3
  • Kondo, D. G., Sung, Y. H., Hellem, T. L., Fiedler, K. K., Shi, X., Jeong, E. K., & Renshaw, P. F. (2011). Open-label adjunctive creatine for female adolescents with SSRI-resistant major depressive disorder: A 31-phosphorus magnetic resonance spectroscopy study. Journal of Affective Disorders, 135(1-3), 354–361. doi: 10.1016/j.jad.2011.07.010
  • Kreider, R. B. (2003). Species-specific responses to creatine supplementation. American Journal of Physiology – Regulatory, Integrative and Comparative Physiology, 285(4), R725–R726. doi: 10.1152/ajpregu.00375.2003
  • Kreider, R. B., Kalman, D. S., Antonio, J., Ziegenfuss, T. N., Wildman, R., Collins, R., … Lopez, H. L. (2017). International society of sports nutrition position stand: Safety and efficacy of creatine supplementation in exercise, sport, and medicine. Journal of the International Society of Sports Nutrition, 14, 273. doi: 10.1186/s12970-017-0173-z
  • Laakso, M. P., Hiltunen, Y., Kononen, M., Kivipelto, M., Koivisto, A., Hallikainen, M., & Soininen, H. (2003). Decreased brain creatine levels in elderly apolipoprotein E epsilon 4 carriers. Journal of Neural Transmission, 110(3), 267–275. doi: 10.1007/s00702-002-0783-7
  • Ling, J., Kritikos, M., & Tiplady, B. (2009). Cognitive effects of creatine ethyl ester supplementation. Behavioural Pharmacology, 20(8), 673–679. doi: 10.1097/FBP.0b013e3283323c2a
  • Lugaresi, R., Leme, M., de Salles Painelli, V., Murai, I. H., Roschel, H., Sapienza, M. T., … Gualano, B. (2013). Does long-term creatine supplementation impair kidney function in resistance-trained individuals consuming a high-protein diet? Journal of the International Society of Sports Nutrition, 10(1), 26. doi: 10.1186/1550-2783-10-26
  • Lukaszuk, J. M., Robertson, R. J., Arch, J. E., Moore, G. E., Yaw, K. M., Kelley, D. E., … Moyna, N. M. (2002). Effect of creatine supplementation and a lacto-ovo-vegetarian diet on muscle creatine concentration. International Journal of Sport Nutrition and Exercise Metabolism, 12(3), 336–348. doi: 10.1123/ijsnem.12.3.336
  • Lukaszuk, J. M., Robertson, R. J., Arch, J. E., & Moyna, N. M. (2005). Effect of a defined lacto-ovo-vegetarian diet and oral creatine monohydrate supplementation on plasma creatine concentration. The Journal of Strength and Conditioning Research, 19(4), 735–740. doi: 10.1519/R-16224.1
  • Lyoo, I. K., Kong, S. W., Sung, S. M., Hirashima, F., Parow, A., Hennen, J., … Renshaw, P. F. (2003). Multinuclear magnetic resonance spectroscopy of high-energy phosphate metabolites in human brain following oral supplementation of creatine-monohydrate. Psychiatry Research: Neuroimaging, 123(2), 87–100. doi: 10.1016/S0925-4927(03)00046-5
  • McMorris, T., Harris, R. C., Howard, A. N., Langridge, G., Hall, B., Corbett, J., … Hodgson, C. (2007). Creatine supplementation, sleep deprivation, cortisol, melatonin and behavior. Physiology & Behavior, 90(1), 21–28. doi: 10.1016/j.physbeh.2006.08.024
  • McMorris, T., Harris, R. C., Swain, J., Corbett, J., Collard, K., Dyson, R. J., … Draper, N. (2006). Effect of creatine supplementation and sleep deprivation, with mild exercise, on cognitive and psychomotor performance, mood state, and plasma concentrations of catecholamines and cortisol. Psychopharmacology, 185(1), 93–103. doi: 10.1007/s00213-005-0269-z
  • McMorris, T., Mielcarz, G., Harris, R. C., Swain, J. P., & Howard, A. (2007). Creatine supplementation and cognitive performance in elderly individuals. Neuropsychology, Development and Cognition. Seciton B, Aging, Neuropsychology and Cognition, 14(5), 517–528. doi: 10.1080/13825580600788100
  • Merege-Filho, C. A., Otaduy, M. C., de Sa-Pinto, A. L., de Oliveira, M. O., de Souza Goncalves, L., Hayashi, A. P., … Gualano, B. (2017). Does brain creatine content rely on exogenous creatine in healthy youth? A proof-of-principle study. Applied Physiology, Nutrition, and Metabolism, 42(2), 128–134. doi: 10.1139/apnm-2016-0406
  • Nicastro, H., Gualano, B., de Moraes, W. M., de Salles Painelli, V., da Luz, C. R., dos Santos Costa, A., … Lancha, A. H., Jr. (2012). Effects of creatine supplementation on muscle wasting and glucose homeostasis in rats treated with dexamethasone. Amino Acids, 42(5), 1695–1701. doi: 10.1007/s00726-011-0871-9
  • Ostojic, S. M., Ostojic, J., Drid, P., & Vranes, M. (2016). Guanidinoacetic acid versus creatine for improved brain and muscle creatine levels: A superiority pilot trial in healthy men. Applied Physiology, Nutrition, and Metabolism, 41(9), 1005–1007. doi: 10.1139/apnm-2016-0178
  • Pan, J. W., & Takahashi, K. (2007). Cerebral energetic effects of creatine supplementation in humans. American Journal of Physiology-Regulatory, Integrative and Comparative Physiology, 292(4), R1745–R1750. doi: 10.1152/ajpregu.00717.2006
  • Pereira, R. T., Dorr, F. A., Pinto, E., Solis, M. Y., Artioli, G. G., Fernandes, A. L., … Gualano, B. (2015). Can creatine supplementation form carcinogenic heterocyclic amines in humans? The Journal of Physiology, 593(17), 3959–3971. doi: 10.1113/JP270861
  • Persky, A. M., & Rawson, E. S. (2007). Safety of creatine supplementation. Subcellular Biochemistry, 46, 275–289. doi: 10.1007/978-1-4020-6486-9_14
  • Rae, C. D., & Broer, S. (2015). Creatine as a booster for human brain function. How might it work? Neurochemistry International, 89, 249–259. doi: 10.1016/j.neuint.2015.08.010
  • Rae, C. D., Digney, A. L., McEwan, S. R., & Bates, T. C. (2003). Oral creatine monohydrate supplementation improves brain performance: A double-blind, placebo-controlled, cross-over trial. Proceedings of the Royal Society B: Biological Sciences, 270(1529), 2147–2150. doi: 10.1098/rspb.2003.2492
  • Rawson, E. S., Clarkson, P. M., & Tarnopolsky, M. A. (2017). Perspectives on exertional rhabdomyolysis. Sports Medicine, 47(Suppl 1), 33–49. doi: 10.1007/s40279-017-0689-z
  • Rawson, E. S., Lieberman, H. R., Walsh, T. M., Zuber, S. M., Harhart, J. M., & Matthews, T. C. (2008). Creatine supplementation does not improve cognitive function in young adults. Physiology & Behavior, 95(1–2), 130–134. doi: 10.1016/j.physbeh.2008.05.009
  • Rawson, E. S., Miles, M. P., & Larson-Meyer, D. E. (2018). Dietary supplements for health, adaptation, and recovery in athletes. International Journal of Sport Nutrition and Exercise Metabolism, 28, 188–199. doi: 10.1123/ijsnem.2017-0340
  • Rawson, E. S., & Venezia, A. C. (2011). Use of creatine in the elderly and evidence for effects on cognitive function in young and old. Amino Acids, 40(5), 1349–1362. doi: 10.1007/s00726-011-0855-9
  • Rawson, E. S., & Volek, J. S. (2003). Effects of creatine supplementation and resistance training on muscle strength and weightlifting performance. The Journal of Strength and Conditioning Research, 17(4), 822–831.
  • Sahlin, K., & Harris, R. C. (2011). The creatine kinase reaction: A simple reaction with functional complexity. Amino Acids, 40(5), 1363–1367. doi: 10.1007/s00726-011-0856-8
  • Sakellaris, G., Kotsiou, M., Tamiolaki, M., Kalostos, G., Tsapaki, E., Spanaki, M., … Evangeliou, A. (2006). Prevention of complications related to traumatic brain injury in children and adolescents with creatine administration: An open label randomized pilot study. The Journal of Trauma: Injury, Infection, and Critical Care, 61(2), 322–329. doi: 10.1097/01.ta.0000230269.46108.d5
  • Sakellaris, G., Nasis, G., Kotsiou, M., Tamiolaki, M., Charissis, G., & Evangeliou, A. (2008). Prevention of traumatic headache, dizziness and fatigue with creatine administration. A pilot study. Acta Paediatrica, 97(1), 31–34. doi: 10.1111/j.1651-2227.2007.00529.x
  • Salomons, G. S., van Dooren, S. J., Verhoeven, N. M., Marsden, D., Schwartz, C., Cecil, K. M., … Jakobs, C. (2003). X-linked creatine transporter defect: An overview. Journal of Inherited Metabolic Disease, 26(2-3), 309–318. doi: 10.1023/A:1024405821638
  • Solis, M. Y., Artioli, G. G., Otaduy, M. C. G., Leite, C. D. C., Arruda, W., Veiga, R. R., & Gualano, B. (2017). Effect of age, diet and tissue type on PCr response to creatine supplementation. Journal of Applied Physiology, 123, 407–414. doi: 10.1152/japplphysiol.00248.2017
  • Souza, M. A., Magni, D. V., Guerra, G. P., Oliveira, M. S., Furian, A. F., Pereira, L., … Royes, L. F. (2012). Involvement of hippocampal CAMKII/CREB signaling in the spatial memory retention induced by creatine. Amino Acids, 43(6), 2491–2503. doi: 10.1007/s00726-012-1329-4
  • Stöckler, S., Holzbach, U., Hanefeld, F., Marquardt, I., Helms, G., Requart, M., … Frahm, J. (1994). Creatine deficiency in the brain: A new, treatable inborn error of metabolism. Pediatric Research, 36(3), 409–413. doi: 10.1203/00006450-199409000-00023
  • Sullivan, P. G., Geiger, J. D., Mattson, M. P., & Scheff, S. W. (2000). Dietary supplement creatine protects against traumatic brain injury. Annals of Neurology, 48(5), 723–729. doi:10.1002/1531-8249(200011)48:5<723::AID-ANA5>3.0.CO;2-W
  • Swinton, P., Hemingway, B. S., Saunders, B., Gualano, B., & Dolan, E. (2018). A statistical framework to interpret individual response to intervention: Paving the way for personalized nutrition and exercise prescription. Frontiers in Nutrition, 5, 41–. doi: 10.3389/fnut.2018.00041
  • Tarnopolsky, M. A., Bourgeois, J. M., Snow, R., Keys, S., Roy, B. D., Kwiecien, J. M., & Turnbull, J. (2003). Histological assessment of intermediate- and long-term creatine monohydrate supplementation in mice and rats. American Journal of Physiology-Regulatory, Integrative and Comparative Physiology, 285(4), R762–R769. doi: 10.1152/ajpregu.00270.2003
  • Tomporowski, P. D., & Ellis, N. R. (1986). Effects of exercise on cognitive processes: A review. Psychological Bulletin, 99(3), 338–346. doi: 10.1037/0033-2909.99.3.338
  • Turner, C. E., Byblow, W. D., & Gant, N. (2015). Creatine supplementation enhances corticomotor excitability and cognitive performance during oxygen deprivation. Journal of Neuroscience, 35(4), 1773–1780. doi: 10.1523/JNEUROSCI.3113-14.2015
  • Turner, C. E., Russell, B. R., & Gant, N. (2015). Comparative quantification of dietary supplemented neural creatine concentrations with (1)H-MRS peak fitting and basis spectrum methods. Magnetic Resonance Imaging, 33(9), 1163–1167. doi: 10.1016/j.mri.2015.06.018
  • Vagnozzi, R., Signoretti, S., Floris, R., Marziali, S., Manara, M., Amorini, A. M., … Tavazzi, B. (2013). Decrease in N-acetylaspartate following concussion may be coupled to decrease in creatine. Journal of Head Trauma Rehabilitation, 28(4), 284–292. doi: 10.1097/HTR.0b013e3182795045
  • Walker, J. B. (1979). Creatine: Biosynthesis, regulation, and function. Advances in Enzymology and Related Areas of Molecular Biology, 50, 177–242.
  • Watanabe, A., Kato, N., & Kato, T. (2002). Effects of creatine on mental fatigue and cerebral hemoglobin oxygenation. Neuroscience Research, 42(4), 279–285. doi: 10.1016/S0168-0102(02)00007-X
  • Wilkinson, I. D., Mitchel, N., Breivik, S., Greenwood, P., Griffiths, P. D., Winter, E. M., & Van Beek, E. J. (2006). Effects of creatine supplementation on cerebral white matter in competitive sportsmen. Clinical Journal of Sport Medicine, 16(1), 63–67. doi: 10.1097/01.jsm.0000176372.67398.c8
  • Yazigi Solis, M., de Salles Painelli, V., Giannini Artioli, G., Roschel, H., Concepcion Otaduy, M., & Gualano, B. (2014). Brain creatine depletion in vegetarians? A cross-sectional (1)H-magnetic resonance spectroscopy ((1)H-MRS) study. British Journal of Nutrition, 111(7), 1272–1274. doi: 10.1017/S0007114513003802

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