Use of creatine in the elderly and evidence for effects on cognitive function in young and old

Abstract

The ingestion of the dietary supplement creatine (about 20 g/day for 5 days or about 2 g/day for 30 days) results in increased skeletal muscle creatine and phosphocreatine. Subsequently, the performance of high-intensity exercise tasks, which rely heavily on the creatine-phosphocreatine energy system, is enhanced. The well documented benefits of creatine supplementation in young adults, including increased lean body mass, increased strength, and enhanced fatigue resistance are particularly important to older adults. With aging and reduced physical activity, there are decreases in muscle creatine, muscle mass, bone density, and strength. However, there is evidence that creatine ingestion may reverse these changes, and subsequently improve activities of daily living. Several groups have demonstrated that in older adults, short-term high-dose creatine supplementation, independent of exercise training, increases body mass, enhances fatigue resistance, increases muscle strength, and improves the performance of activities of daily living. Similarly, in older adults, concurrent creatine supplementation and resistance training increase lean body mass, enhance fatigue resistance, increase muscle strength, and improve performance of activities of daily living to a greater extent than resistance training alone. Additionally, creatine supplementation plus resistance training results in a greater increase in bone mineral density than resistance training alone. Higher brain creatine is associated with improved neuropsychological performance, and recently, creatine supplementation has been shown to increase brain creatine and phosphocreatine. Subsequent studies have demonstrated that cognitive processing, that is either experimentally (following sleep deprivation) or naturally (due to aging) impaired, can be improved with creatine supplementation. Creatine is an inexpensive and safe dietary supplement that has both peripheral and central effects. The benefits afforded to older adults through creatine ingestion are substantial, can improve quality of life, and ultimately may reduce the disease burden associated with sarcopenia and cognitive dysfunction.

This is a preview of subscription content, log in to check access.

References

  1. Alexander BH, Rivara FP, Wolf ME (1992) The cost and frequency of hospitalization for fall-related injuries in older adults. Am J Public Health 82(7):1020–1023

    PubMed  CAS  Google Scholar 

  2. Angelie E, Bonmartin A, Boudraa A, Gonnaud PM, Mallet JJ, Sappey-Marinier D (2001) Regional differences and metabolic changes in normal aging of the human brain: proton MR spectroscopic imaging study. AJNR Am J Neuroradiol 22(1):119–127

    PubMed  CAS  Google Scholar 

  3. Angevaren M, Aufdemkampe G, Verhaar HJJ, Aleman A, Vanhees L (2008) Physical activity and enhanced fitness to improve cognitive function in older people without known cognitive impairment. Cochrane Database Syst Rev (2):2–9, Art No CD005381. doi:10.1002/14651858.CD005381.pub2

  4. Balsom PD, Söderlund K, Ekblom B (1994) Creatine in humans with special reference to creatine supplementation. Sports Med 18(4):268–280

    PubMed  CAS  Google Scholar 

  5. Bassit RA, Pinheiro CH, Vitzel KF, Sproesser AJ, Silveira LR, Curi R (2010) Effect of short-term creatine supplementation on markers of skeletal muscle damage after strenuous contractile activity. Eur J Appl Physiol 108(5):945–955

    PubMed  CAS  Google Scholar 

  6. Bemben MG, Witten MS, Carter JM, Eliot KA, Knehans AW, Bemben DA (2010) The effects of supplementation with creatine and protein on muscle strength following a traditional resistance training program in middle-aged and older men. J Nutr Health Aging 14(2):155–159

    PubMed  CAS  Google Scholar 

  7. Bender A, Auer DP, Merl T, Reilmann R, Saemann P, Yassouridis A et al (2005) Creatine supplementation lowers brain glutamate levels in Huntington’s disease. J Neurol 252(1):36–41

    PubMed  CAS  Google Scholar 

  8. Bender A, Koch W, Elstner M, Schombacher Y, Bender J, Moeschl M et al (2006) Creatine supplementation in Parkinson disease: a placebo-controlled randomized pilot trial. Neurology 67(7):1262–1264

    PubMed  CAS  Google Scholar 

  9. Bergström J (1962) Muscle electrolytes in man. Determination by neutron activation analysis on needle biopsy specimens. A study on normal subjects, kidney patients, and patients with chronic diarrhoea. Scand J Clin Lab Invest 14:1–110

    Google Scholar 

  10. Bermon S, Venembre P, Sachet C, Valour S, Dolisi C (1998) Effects of creatine monohydrate ingestion in sedentary and weight-trained older adults. Acta Physiol Scand 164(2):147–155

    PubMed  CAS  Google Scholar 

  11. Bessman SP, Carpenter CL (1985) The creatine-creatine phosphate energy shuttle. Annu Rev Biochem 54:831–862

    PubMed  CAS  Google Scholar 

  12. Bessman SP, Geiger PJ (1981) Transport of energy in muscle: the phosphorylcreatine shuttle. Science 211(4481):448–452

    PubMed  CAS  Google Scholar 

  13. Bhasin S, Storer TW (2009) Anabolic applications of androgens for functional limitations associated with aging and chronic illness. Front Horm Res 37:163–182

    PubMed  CAS  Google Scholar 

  14. Bixby WR, Spalding TW, Haufler AJ, Deeny SP, Mahlow PT, Zimmerman JB et al (2007) The unique relation of physical activity to executive function in older men and women. Med Sci Sports Exerc 39(8):1408–1416

    PubMed  Google Scholar 

  15. Bloch K, Schoenheimer R (1941) The biological precursors of creatine. J Biol Chem 138:167–194

    CAS  Google Scholar 

  16. Braissant O, Bachmann C, Henry H (2007) Expression and function of AGAT, GAMT and CT1 in the mammalian brain. Subcell Biochem 46:67–81

    PubMed  Google Scholar 

  17. Brose A, Parise G, Tarnopolsky MA (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(1):11–19

    PubMed  Google Scholar 

  18. Brown LA, Riby LM, Reay JL (2010) Supplementing cognitive aging: a selective review of the effects of ginkgo biloba and a number of everyday nutritional substances. Exp Aging Res 36(1):105–122

    PubMed  Google Scholar 

  19. Bugaiska A, Clarys D, Jarry C, Taconnat L, Tapia G, Vanneste S et al (2007) The effect of aging in recollective experience: the processing speed and executive functioning hypothesis. Conscious Cogn 16(4):797–808

    PubMed  Google Scholar 

  20. Burke DG, Chilibeck PD, Parise G, Candow DG, Mahoney D, Tarnopolsky M (2003) Effect of creatine and weight training on muscle creatine and performance in vegetarians. Med Sci Sports Exerc 35(11):1946–1955

    PubMed  CAS  Google Scholar 

  21. Calof OM, Singh AB, Lee ML, Kenny AM, Urban RJ, Tenover JL et al (2005) Adverse events associated with testosterone replacement in middle-aged and older men: a meta-analysis of randomized, placebo-controlled trials. J Gerontol A Biol Sci Med Sci 60(11):1451–1457

    PubMed  Google Scholar 

  22. Campbell WW, Barton ML Jr, Cyr-Campbell D, Davey SL, Beard JL, Parise G et al (1999) Effects of an omnivorous diet compared with a lactoovovegetarian diet on resistance-training-induced changes in body composition and skeletal muscle in older men. Am J Clin Nutr 70(6):1032–1039

    PubMed  CAS  Google Scholar 

  23. Candow DG, Chilibeck PD, Chad KE, Chrusch MJ, Davison KS, Burke DG (2004) Effect of ceasing creatine supplementation while maintaining resistance training in older men. J Aging Phys Act 12(3):219–231

    PubMed  Google Scholar 

  24. Candow DG, Little JP, Chilibeck PD, Abeysekara S, Zello GA, Kazachkov M et al (2008) Low-dose creatine combined with protein during resistance training in older men. Med Sci Sports Exerc 40(9):1645–1652

    PubMed  CAS  Google Scholar 

  25. Canete S, San Juan AF, Perez M, Gomez-Gallego F, Lopez-Mojares LM, Earnest CP et al (2006) Does creatine supplementation improve functional capacity in elderly women? J Strength Cond Res 20(1):22–28

    PubMed  Google Scholar 

  26. Census Bureau, U. S. (2010) Update world population: 1950-2050. From http://www.census.gov/ipc/www/idb/

  27. Chanutin A (1927) A study of the effect of creatine on growth and its distribution in the tissues normal rats. J Biol Chem 75:549–557

    CAS  Google Scholar 

  28. Chanutin A, Guy LP (1926) The fate of creatine when administered to man. J Biol Chem 67:29–37

    CAS  Google Scholar 

  29. Chevreul ME (1832) Sur une nouvelle substance contenue dans la chair de boeuf. Paris Mus Hist Nat N Ann I:306–316

    Google Scholar 

  30. Chilibeck PD, Chrusch MJ, Chad KE, Shawn Davison K, Burke DG (2005) Creatine monohydrate and resistance training increase bone mineral content and density in older men. J Nutr Health Aging 9(5):352–353

    PubMed  CAS  Google Scholar 

  31. Chrusch MJ, Chilibeck PD, Chad KE, Davison KS, Burke DG (2001) Creatine supplementation combined with resistance training in older men. Med Sci Sports Exerc 33(12):2111–2117

    PubMed  CAS  Google Scholar 

  32. Clark BC, Manini TM (2010) Functional consequences of sarcopenia and dynapenia in the elderly. Curr Opin Clin Nutr Metab Care 13(3):271–276

    PubMed  Google Scholar 

  33. Conley KE, Jubrias SA, Esselman PC (2000) Oxidative capacity and ageing in human muscle. J Physiol 526(Pt 1):203–210

    PubMed  CAS  Google Scholar 

  34. Dalbo VJ, Roberts MD, Lockwood CM, Tucker PS, Kreider RB, Kerksick CM (2009) The effects of age on skeletal muscle and the phosphocreatine energy system: can creatine supplementation help older adults. Dyn Med 8:6

    PubMed  Google Scholar 

  35. Dechent P, Pouwels PJ, Wilken B, Hanefeld F, Frahm J (1999) Increase of total creatine in human brain after oral supplementation of creatine-monohydrate. Am J Physiol 277(3 Pt 2):R698–R704

    PubMed  CAS  Google Scholar 

  36. Delanghe J, De Slypere JP, De Buyzere M, Robbrecht J, Wieme R, Vermeulen A (1989) Normal reference values for creatine, creatinine, and carnitine are lower in vegetarians. Clin Chem 35(8):1802–1803

    PubMed  CAS  Google Scholar 

  37. Deldicque L, Louis M, Theisen D, Nielens H, Dehoux M, Thissen JP et al (2005) Increased IGF mRNA in human skeletal muscle after creatine supplementation. Med Sci Sports Exerc 37(5):731–736

    PubMed  CAS  Google Scholar 

  38. Department of Health and Human Services, U. S. (2009) A profile of older Americans. U.S. Department of Health and Human Services, Washington, DC

  39. Eggleton P, Eggleton GP (1927) The inorganic phosphate and a labile form of organic phosphate in the gastrocnemius of the frog. Biochem J 21(1):190–195

    PubMed  CAS  Google Scholar 

  40. Eijnde BO, Van Leemputte M, Goris M, Labarque V, Taes Y, Verbessem P et al (2003) Effects of creatine supplementation and exercise training on fitness in men 55–75 yr old. J Appl Physiol 95(2):818–828

    PubMed  CAS  Google Scholar 

  41. Ferguson KJ, MacLullich AM, Marshall I, Deary IJ, Starr JM, Seckl JR et al (2002) Magnetic resonance spectroscopy and cognitive function in healthy elderly men. Brain 125(Pt 12):2743–2749

    PubMed  Google Scholar 

  42. Ferrier CH, Alarcon G, Glover A, Koutroumanidis M, Morris RG, Simmons A et al (2000) N-acetylaspartate and creatine levels measured by (1)H MRS relate to recognition memory. Neurology 55(12):1874–1883

    PubMed  CAS  Google Scholar 

  43. Fiske CH, Subbarow Y (1927) The nature of the “organic phosphate” in voluntary muscle. Science 65:401–403

    PubMed  CAS  Google Scholar 

  44. Forsberg AM, Nilsson E, Werneman J, Bergström J, Hultman E (1991) Muscle composition in relation to age and sex. Clin Sci 81(2):249–256

    PubMed  CAS  Google Scholar 

  45. Giannakouris K (2010) Regional population projections EUROP2008: Most EU regions face older population profile in 2030. European Commission & Eurostat. http://bookshop.europa.eu/is-bin/INTERSHOP.enfinity/WFS/EU-Bookshop-Site/en_GB/-/EUR/ViewPublication-Start?PublicationKey=KSSF10001. Accessed June 2010

  46. Giese MW, Lecher CS (2009a) Non-enzymatic cyclization of creatine ethyl ester to creatinine. Biochem Biophys Res Commun 388(2):252–255

    PubMed  CAS  Google Scholar 

  47. Giese MW, Lecher CS (2009b) Qualitative in vitro NMR analysis of creatine ethyl ester pronutrient in human plasma. Int J Sports Med 30(10):766–770

    PubMed  CAS  Google Scholar 

  48. Gotshalk LA, Volek JS, Staron RS, Denegar CR, Hagerman FC, Kraemer WJ (2002) Creatine supplementation improves muscular performance in older men. Med Sci Sports Exerc 34(3):537–543

    PubMed  CAS  Google Scholar 

  49. Gotshalk LA, Kraemer WJ, Mendonca MA, Vingren JL, Kenny AM, Spiering BA et al (2008) Creatine supplementation improves muscular performance in older women. Eur J Appl Physiol 102(2):223–231

    PubMed  CAS  Google Scholar 

  50. Greenhaff PL, Casey A, Short AH, Harris R, Söderlund K, Hultman E (1993) Influence of oral creatine supplementation of muscle torque during repeated bouts of maximal voluntary exercise in man. Clin Sci (Colch) 84(5):565–571

    CAS  Google Scholar 

  51. Greenhaff PL, Bodin K, Söderlund K, Hultman E (1994) Effect of oral creatine supplementation on skeletal muscle phosphocreatine resynthesis. Am J Physiol 266(5 Pt 1):E725–E730

    PubMed  CAS  Google Scholar 

  52. Harris RC, Hultman E, Nordesjö LO (1974) Glycogen, glycolytic intermediates and high-energy phosphates determined in biopsy samples of musculus quadriceps femoris of man at rest. Methods and variance of values. Scand J Clin Lab Invest 33(2):109–120

    PubMed  CAS  Google Scholar 

  53. Harris RC, Söderlund K, Hultman E (1992) Elevation of creatine in resting and exercised muscle of normal subjects by creatine supplementation. Clin Sci (Colch) 83(3):367–374

    CAS  Google Scholar 

  54. Hubal MJ, Gordish-Dressman H, Thompson PD, Price TB, Hoffman EP, Angelopoulos TJ et al (2005) Variability in muscle size and strength gain after unilateral resistance training. Med Sci Sports Exerc 37(6):964–972

    PubMed  Google Scholar 

  55. Hultman E, Söderlund K, Timmons JA, Cederblad G, Greenhaff PL (1996) Muscle creatine loading in men. J Appl Physiol 81(1):232–237

    PubMed  CAS  Google Scholar 

  56. Hunter A (1928) Creatine and creatinine. Longmans, Grenn, and Company, New York

    Google Scholar 

  57. Ipsiroglu OS, 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 Sci 69(15):1805–1815

    PubMed  CAS  Google Scholar 

  58. Jakobi JM, Rice CL, Curtin SV, Marsh GD (2001) Neuromuscular properties and fatigue in older men following acute creatine supplementation. Eur J Appl Physiol 84(4):321–328

    PubMed  CAS  Google Scholar 

  59. Kalinski MI (2003) State-sponsored research on creatine supplements and blood doping in elite Soviet sport. Perspect Biol Med 46(3):445–451

    PubMed  Google Scholar 

  60. Kato T, Takahashi S, Shioiri T, Inubushi T (1992) Brain phosphorous metabolism in depressive disorders detected by phosphorus-31 magnetic resonance spectroscopy. J Affect Disord 26(4):223–230

    PubMed  CAS  Google Scholar 

  61. Katseres NS, Reading DW, Shayya L, Dicesare JC, Purser GH (2009) Non-enzymatic hydrolysis of creatine ethyl ester. Biochem Biophys Res Commun 386(2):363–367

    PubMed  CAS  Google Scholar 

  62. Kent-Braun JA, Ng AV (2000) Skeletal muscle oxidative capacity in young and older women and men. J Appl Physiol 89(3):1072–1078

    PubMed  CAS  Google Scholar 

  63. Korzun WJ (2004) Oral creatine supplements lower plasma homocysteine concentrations in humans. Clin Lab Sci 17(2):102–106

    PubMed  Google Scholar 

  64. Laakso MP, Hiltunen Y, Kononen M, Kivipelto M, Koivisto A, Hallikainen M et al (2003) Decreased brain creatine levels in elderly apolipoprotein E epsilon 4 carriers. J Neural Transm 110(3):267–275

    PubMed  CAS  Google Scholar 

  65. Lanza IR, Befroy DE, Kent-Braun JA (2005) Age-related changes in ATP-producing pathways in human skeletal muscle in vivo. J Appl Physiol 99(5):1736–1744

    PubMed  CAS  Google Scholar 

  66. Larsson L, Grimby G, Karlsson J (1979) Muscle strength and speed of movement in relation to age and muscle morphology. J Appl Physiol 46(3):451–456

    PubMed  CAS  Google Scholar 

  67. Lexell J, Taylor CC (1991) Variability in muscle fibre areas in whole human quadriceps muscle: effects of increasing age. J Anat 174:239–249

    PubMed  CAS  Google Scholar 

  68. Ling J, Kritikos M, Tiplady B (2009) Cognitive effects of creatine ethyl ester supplementation. Behav Pharmacol 20(8):673–679

    PubMed  CAS  Google Scholar 

  69. Lukaszuk JM, Robertson RJ, Arch JE, Moore GE, Yaw KM, Kelley DE et al (2002) Effect of creatine supplementation and a lacto-ovo-vegetarian diet on muscle creatine concentration. Int J Sport Nutr Exerc Metab 12(3):336–348

    PubMed  CAS  Google Scholar 

  70. Lukaszuk JM, Robertson RJ, Arch JE, Moyna NM (2005) Effect of a defined lacto-ovo-vegetarian diet and oral creatine monohydrate supplementation on plasma creatine concentration. J Strength Cond Res 19(4):735–740

    PubMed  Google Scholar 

  71. Lyoo IK, Kong SW, Sung SM, Hirashima F, Parow A, Hennen J et al (2003) Multinuclear magnetic resonance spectroscopy of high-energy phosphate metabolites in human brain following oral supplementation of creatine-monohydrate. Psychiatry Res 123(2):87–100

    PubMed  CAS  Google Scholar 

  72. Maccormick VM, Hill LM, Macneil L, Burke DG, Smith-Palmer T (2004) Elevation of creatine in red blood cells in vegetarians and nonvegetarians after creatine supplementation. Can J Appl Physiol 29(6):704–713

    PubMed  CAS  Google Scholar 

  73. MacDougall JD, Ward GR, Sale DG, Sutton JR (1977) Biochemical adaptation of human skeletal muscle to heavy resistance training and immobilization. J Appl Physiol 43(4):700–703

    PubMed  CAS  Google Scholar 

  74. Massana G, Gasto C, Junque C, Mercader JM, Gomez B, Massana J et al (2002) Reduced levels of creatine in the right medial temporal lobe region of panic disorder patients detected with (1)H magnetic resonance spectroscopy. Neuroimage 16(3 Pt 1):836–842

    PubMed  Google Scholar 

  75. McCully KK, Forciea MA, Hack LM, Donlon E, Wheatley RW, Oatis CA et al (1991) Muscle metabolism in older subjects using 31P magnetic resonance spectroscopy. Can J Physiol Pharmacol 69(5):576–580

    PubMed  CAS  Google Scholar 

  76. McCully KK, Fielding RA, Evans WJ, Leigh JS Jr, Posner JD (1993) Relationships between in vivo and in vitro measurements of metabolism in young and old human calf muscles. J Appl Physiol 75(2):813–819

    PubMed  CAS  Google Scholar 

  77. McMorris T, Harris RC, Swain J, Corbett J, Collard K, Dyson RJ et al (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

    Google Scholar 

  78. McMorris T, Harris RC, Howard AN, Langridge G, Hall B, Corbett J et al (2007a) Creatine supplementation, sleep deprivation, cortisol, melatonin and behavior. Physiol Behav 90(1):21–28

    PubMed  CAS  Google Scholar 

  79. McMorris T, Mielcarz G, Harris RC, Swain JP, Howard A (2007b) Creatine supplementation and cognitive performance in elderly individuals. Neuropsychol Dev Cogn B Aging Neuropsychol Cogn 14(5):517–528

    PubMed  Google Scholar 

  80. Mihic S, MacDonald JR, McKenzie S, Tarnopolsky MA (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(2):291–296

    PubMed  CAS  Google Scholar 

  81. Möller P, Brandt R (1982) The effect of physical training in elderly subjects with special reference to energy-rich phosphagens and myoglobin in leg skeletal muscle. Clin Physiol 2(4):307–314

    PubMed  Google Scholar 

  82. Möller P, Bergström J, Fürst P, Hellström K (1980) Effect of aging on energy-rich phosphagens in human skeletal muscles. Clin Sci 58(6):553–555

    PubMed  Google Scholar 

  83. Montero-Odasso M, Wells JL, Borrie MJ, Speechley M (2009) Can cognitive enhancers reduce the risk of falls in older people with mild cognitive impairment? A protocol for a randomised controlled double blind trial. BMC Neurol 9:42

    PubMed  Google Scholar 

  84. Nelson AG, Arnall DA, Kokkonen J, Day R, Evans J (2001) Muscle glycogen supercompensation is enhanced by prior creatine supplementation. Med Sci Sports Exerc 33(7):1096–1100

    PubMed  CAS  Google Scholar 

  85. Olsen S, Aagaard P, Kadi F, Tufekovic G, Verney J, Olesen JL et al (2006) Creatine supplementation augments the increase in satellite cell and myonuclei number in human skeletal muscle induced by strength training. J Physiol 573(Pt 2):525–534

    PubMed  CAS  Google Scholar 

  86. Öngur D, Prescot AP, Jensen JE, Cohen BM, Renshaw PF (2009) Creatine abnormalities in schizophrenia and bipolar disorder. Psychiatry Res 172(1):44–48

    PubMed  Google Scholar 

  87. Pan JW, Takahashi K (2007) Cerebral energetic effects of creatine supplementation in humans. Am J Physiol Regul Integr Comp Physiol 292(4):R1745–R1750

    PubMed  CAS  Google Scholar 

  88. Persky AM, Rawson ES (2007) Safety of creatine supplementation. Subcell Biochem 46:275–289

    PubMed  Google Scholar 

  89. Rae C, Digney AL, McEwan SR, Bates TC (2003) Oral creatine monohydrate supplementation improves brain performance: a double-blind, placebo-controlled, cross-over trial. Proc R Soc Lond B Biol Sci 270(1529):2147–2150

    CAS  Google Scholar 

  90. Rango M, Castelli A, Scarlato G (1997) Energetics of 3.5 s neural activation in humans: a 31P MR spectroscopy study. Magn Reson Med 38(6):878–883

    PubMed  CAS  Google Scholar 

  91. Rawson ES, Clarkson PM (2000) Acute creatine supplementation in older men. Int J Sports Med 21(1):71–75

    PubMed  CAS  Google Scholar 

  92. Rawson ES, Clarkson PM (2004) Scientifically debatable: is creatine worth its weight? Gatorade Sports Sci Exch 16(4):1–6

    Google Scholar 

  93. Rawson ES, Persky AM (2007) Mechanisms of muscular adaptations to creatine supplementation. Int SportMed J 8(2):43–53

    Google Scholar 

  94. Rawson ES, Wehnert ML, Clarkson PM (1999) Effects of 30 days of creatine ingestion in older men. Eur J Appl Physiol 80(2):139–144

    CAS  Google Scholar 

  95. Rawson ES, Clarkson PM, Price TB, Miles MP (2002) Differential response of muscle phosphocreatine to creatine supplementation in young and old subjects. Acta Physiol Scand 174(1):57–65

    PubMed  CAS  Google Scholar 

  96. Rawson ES, Lieberman HR, Walsh TM, Zuber SM, Harhart JM, Matthews TC (2008) Creatine supplementation does not improve cognitive function in young adults. Physiol Behav 95(1–2):130–134

    PubMed  CAS  Google Scholar 

  97. Rawson ES, Stec MJ, Frederickson SJ, Miles MP (2011) Low dose creatine supplementation enhances fatigue resistance in the absence of weight gain. Nutrition (in press)

  98. Roitman S, Green T, Osher Y, Karni N, Levine J (2007) Creatine monohydrate in resistant depression: a preliminary study. Bipolar Disord 9(7):754–758

    PubMed  CAS  Google Scholar 

  99. Safdar A, Yardley NJ, Snow R, Melov S, Tarnopolsky MA (2008) Global and targeted gene expression and protein content in skeletal muscle of young men following short-term creatine monohydrate supplementation. Physiol Genomics 32(2):219–228

    PubMed  CAS  Google Scholar 

  100. Sappey-Marinier D, Calabrese G, Fein G, Hugg JW, Biggins C, Weiner MW (1992) Effect of photic stimulation on human visual cortex lactate and phosphates using 1H and 31P magnetic resonance spectroscopy. J Cereb Blood Flow Metab 12(4):584–592

    PubMed  CAS  Google Scholar 

  101. Shomrat A, Weinstein Y, Katz A (2000) Effect of creatine feeding on maximal exercise performance in vegetarians. Eur J Appl Physiol 82(4):321–325

    PubMed  CAS  Google Scholar 

  102. Smith SA, Montain SJ, Matott RP, Zientara GP, Jolesz FA, Fielding RA (1998) Creatine supplementation and age influence muscle metabolism during exercise. J Appl Physiol 85(4):1349–1356

    PubMed  CAS  Google Scholar 

  103. Spillane M, Schoch R, Cooke M, Harvey T, Greenwood M, Kreider R et al (2009) The effects of creatine ethyl ester supplementation combined with heavy resistance training on body composition, muscle performance, and serum and muscle creatine levels. J Int Soc Sports Nutr 6:6

    PubMed  Google Scholar 

  104. Stockler S, Schutz PW, Salomons GS (2007) Cerebral creatine deficiency syndromes: clinical aspects, treatment and pathophysiology. Subcell Biochem 46:149–166

    PubMed  Google Scholar 

  105. Stout JR, Sue Graves B, Cramer JT, Goldstein ER, Costa PB, Smith AE et al (2007) Effects of creatine supplementation on the onset of neuromuscular fatigue threshold and muscle strength in elderly men and women (64–86 years). J Nutr Health Aging 11(6):459–464

    PubMed  CAS  Google Scholar 

  106. Tarnopolsky M, Parise G, Fu MH, Brose A, Parshad A, Speer O et al (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(1–2):159–166

    PubMed  CAS  Google Scholar 

  107. Tarnopolsky M, Zimmer A, Paikin J, Safdar A, Aboud A, Pearce E et al (2007) Creatine monohydrate and conjugated linoleic acid improve strength and body composition following resistance exercise in older adults. PLoS One 2(10):e991

    PubMed  Google Scholar 

  108. Tesch PA, Thorsson A, Fujitsuka N (1989) Creatine phosphate in fiber types of skeletal muscle before and after exhaustive exercise. J Appl Physiol 66(4):1756–1759

    PubMed  CAS  Google Scholar 

  109. Tinetti ME, Speechley M, Ginter SF (1988) Risk factors for falls among elderly persons living in the community. N Engl J Med 319(26):1701–1707

    PubMed  CAS  Google Scholar 

  110. Tinetti ME, Gordon C, Sogolow E, Lapin P, Bradley EH (2006) Fall-risk evaluation and management: challenges in adopting geriatric care practices. Gerontologist 46(6):717–725

    PubMed  Google Scholar 

  111. Tucker KL, Qiao N, Scott T, Rosenberg I, Spiro A III (2005) High homocysteine and low B vitamins predict cognitive decline in aging men: the Veterans Affairs Normative Aging Study. Am J Clin Nutr 82(3):627–635

    PubMed  CAS  Google Scholar 

  112. Valenzuela MJ, Jones M, Wen W, Rae C, Graham S, Shnier R et al (2003) Memory training alters hippocampal neurochemistry in healthy elderly. Neuroreport 14(10):1333–1337

    PubMed  Google Scholar 

  113. Vandenberghe K, Goris M, Van Hecke P, Van Leemputte M, Vangerven L, Hespel P (1997) Long-term creatine intake is beneficial to muscle performance during resistance training. J Appl Physiol 83(6):2055–2063

    PubMed  CAS  Google Scholar 

  114. Volek JS, Duncan ND, Mazzetti SA, Staron RS, Putukian M, Gomez AL et al (1999) Performance and muscle fiber adaptations to creatine supplementation and heavy resistance training. Med Sci Sports Exerc 31(8):1147–1156

    PubMed  CAS  Google Scholar 

  115. Walker JB (1979) Creatine: biosynthesis, regulation, and function. Adv Enzymol Relat Areas Mol Biol 50:177–242

    PubMed  CAS  Google Scholar 

  116. Watanabe A, Kato N, Kato T (2002) Effects of creatine on mental fatigue and cerebral hemoglobin oxygenation. Neurosci Res 42(4):279–285

    PubMed  CAS  Google Scholar 

  117. Watt KK, Garnham AP, Snow RJ (2004) Skeletal muscle total creatine content and creatine transporter gene expression in vegetarians prior to and following creatine supplementation. Int J Sport Nutr Exerc Metab 14(5):517–531

    PubMed  CAS  Google Scholar 

  118. Wilkinson ID, Mitchel N, Breivik S, Greenwood P, Griffiths PD, Winter EM et al (2006) Effects of creatine supplementation on cerebral white matter in competitive sportsmen. Clin J Sport Med 16(1):63–67

    PubMed  Google Scholar 

  119. Willoughby DS, Rosene JM (2003) Effects of oral creatine and resistance training on myogenic regulatory factor expression. Med Sci Sports Exerc 35(6):923–929

    PubMed  CAS  Google Scholar 

  120. Wiroth JB, Bermon S, Andrei S, Dalloz E, Hebuterne X, Dolisi C (2001) Effects of oral creatine supplementation on maximal pedalling performance in older adults. Eur J Appl Physiol 84(6):533–539

    PubMed  CAS  Google Scholar 

  121. Wyss M, Felber S, Skladal D, Koller A, Kremser C, Sperl W (1998) The therapeutic potential of oral creatine supplementation in muscle disease. Med Hypotheses 51(4):333–336

    PubMed  CAS  Google Scholar 

  122. Yquel RJ, Arsac LM, Thiaudiere E, Canioni P, Manier G (2002) Effect of creatine supplementation on phosphocreatine resynthesis, inorganic phosphate accumulation and pH during intermittent maximal exercise. J Sports Sci 20(5):427–437

    PubMed  CAS  Google Scholar 

Download references

Author information

Affiliations

Authors

Corresponding author

Correspondence to Eric S. Rawson.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Rawson, E.S., Venezia, A.C. Use of creatine in the elderly and evidence for effects on cognitive function in young and old. Amino Acids 40, 1349–1362 (2011). https://doi.org/10.1007/s00726-011-0855-9

Download citation

Keywords

  • Dietary supplement
  • Ergogenic aid
  • Fatigue
  • Phosphocreatine
  • Aging