Creatine supplementation associated or not with strength training upon emotional and cognitive measures in older women: a randomized double-blind study

Christiano Robles Rodrigues Alves, Carlos Alberto Abujabra Merege Filho, Fabiana Braga Benatti, Sonia Brucki, Rosa Maria R Pereira, Ana Lucia de Sá Pinto, Fernanda Rodrigues Lima, Hamilton Roschel, Bruno Gualano, Christiano Robles Rodrigues Alves, Carlos Alberto Abujabra Merege Filho, Fabiana Braga Benatti, Sonia Brucki, Rosa Maria R Pereira, Ana Lucia de Sá Pinto, Fernanda Rodrigues Lima, Hamilton Roschel, Bruno Gualano

Abstract

Purpose: To assess the effects of creatine supplementation, associated or not with strength training, upon emotional and cognitive measures in older woman.

Methods: This is a 24-week, parallel-group, double-blind, randomized, placebo-controlled trial. The individuals were randomly allocated into one of the following groups (n=14 each): 1) placebo, 2) creatine supplementation, 3) placebo associated with strength training or 4) creatine supplementation associated with strength training. According to their allocation, the participants were given creatine (4 x 5 g/d for 5 days followed by 5 g/d) or placebo (dextrose at the same dosage) and were strength trained or not. Cognitive function, assessed by a comprehensive battery of tests involving memory, selective attention, and inhibitory control, and emotional measures, assessed by the Geriatric Depression Scale, were evaluated at baseline, after 12 and 24 weeks of the intervention. Muscle strength and food intake were evaluated at baseline and after 24 weeks.

Results: After the 24-week intervention, both training groups (ingesting creatine supplementation and placebo) had significant reductions on the Geriatric Depression Scale scores when compared with the non-trained placebo group (p = 0.001 and p = 0.01, respectively) and the non-trained creatine group (p < 0.001 for both comparison). However, no significant differences were observed between the non-trained placebo and creatine (p = 0.60) groups, or between the trained placebo and creatine groups (p = 0.83). Both trained groups, irrespective of creatine supplementation, had better muscle strength performance than the non-trained groups. Neither strength training nor creatine supplementation altered any parameter of cognitive performance. Food intake remained unchanged.

Conclusion: Creatine supplementation did not promote any significant change in cognitive function and emotional parameters in apparently healthy older individuals. In addition, strength training per se improved emotional state and muscle strength, but not cognition, with no additive effects of creatine supplementation.

Trial registration: Clinicaltrials.gov NCT01164020.

Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1. Experimental design.
Figure 1. Experimental design.
Figure 2. Fluxogram of subjects.
Figure 2. Fluxogram of subjects.
PL = placebo supplementation, CR = creatine supplementation, PL + ST = placebo supplementation associated with strength training and PL+ST = creatine supplementation associated with strength training group.
Figure 3. Delta changes in Geriatric Depression…
Figure 3. Delta changes in Geriatric Depression Scale at baseline and after 12 and 24 weeks of intervention.
* denotes statistically significant differences at 24 week in the comparisons between the trained versus non-trained groups (i.e., Placebo + Strength training and Creatine + Strength training versus Placebo and Creatine; p < 0.05).

References

    1. Van Gool CH, Kempen GI, Bosma H, van Boxtel MP, Jolles J et al. (2007) Associations between lifestyle and depressed mood: longitudinal results from the Maastricht Aging Study. Am J Public Health 97: 887-894. doi:10.2105/AJPH.2004.053199. PubMed: .
    1. Colcombe S, Kramer AF (2003) Fitness effects on the cognitive function of older adults: a meta-analytic study. Psychol Sci 14: 125–130. doi:10.1111/1467-9280.t01-1-01430. PubMed: .
    1. Parkin AJ, Java RI (1999) Deterioration of frontal lobe function in normal aging: Influences of fluid intelligence versus perceptual speed. Neuropsychology 13: 539–545. doi:10.1037/0894-4105.13.4.539. PubMed: .
    1. Cassilhas RC, Antunes HK, Tufik S, de Mello MT (2010) Mood, anxiety, and serum IGF-1 in elderly men given 24 weeks of high resistance exercise. Percept Mot Skills 110: 265-276. doi:10.2466/pms.110.1.265-276. PubMed: .
    1. Van Gool CH, Kempen GI, Penninx BW, Deeg DJ, Beekman AT et al. (2003) Relationship between changes in depressive symptoms and unhealthy lifestyles in late middle aged and older persons: results from the Longitudinal Aging Study Amsterdam. Age Ageing 32: 81-87. doi:10.1093/ageing/32.1.81. PubMed: .
    1. Wyss M, Kaddurah-Daouk R (2000) Creatine and creatinine metabolism. Physiol Rev 80: 1107-1213. PubMed: .
    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. Dev Neurosci 18: 542–554. doi:10.1159/000111452. PubMed: .
    1. Salomons GS, van Dooren SJ, Verhoeven NM, Marsden D, Schwartz C et al. (2003) X-linked creatine transporter defect: an overview. J Inherit Metab Dis 26: 309–318. doi:10.1023/A:1024405821638. PubMed: .
    1. Stöckler S, Hanefeld F, Frahm J (1996) Creatine replacement therapy in guanidinoacetate methyltransferase deficiency, a novel inborn error of metabolism. Lancet 348: 789–790. doi:10.1016/S0140-6736(96)04116-5. PubMed: .
    1. Lyoo IK, Kong SW, Sung SM, Hirashima F, Parow A et al. (2003) Multinuclear magnetic resonansce spectroscopy of high-energy phosphate metabolites in human brain following oral supplementation of creatinemonohydrate. Psychiatry Res Neuroimaging 123: 87–100. doi:10.1016/S0925-4927(03)00046-5.
    1. Dechent P, Pouwels PJ, Frahm J (1999) Neither short-term nor long-term administration of oral choline alters metabolite concentrations in human brain. Biol Psychiatry 46: 406-411. doi:10.1016/S0006-3223(98)00346-1. PubMed: .
    1. 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: R698-R704. PubMed: .
    1. Watanabe A, Kato N, Kato T (2002) Effects of creatine on mental fatigue and cerebral hemoglobin oxygenation. Neurosci Res 42: 279–285. doi:10.1016/S0168-0102(02)00007-X. PubMed: .
    1. McMorris T, Harris RC, Howard AN, Langridge G, Hall B et al. (2007) Creatine supplementation, sleep deprivation, cortisol, melatonin and behavior. Physiol Behav 90: 21-28. doi:10.1016/j.physbeh.2006.08.024. PubMed: .
    1. Roitman S, Green T, Osher Y, Karni N, Levine J (2007) Creatine monohydrate in resistant depression: a preliminary study. Bipol Disord 9: 754–758. doi:10.1111/j.1399-5618.2007.00532.x. PubMed: .
    1. Amital D, Vishne T, Roitman S, Kotler M, Levine J (2006) Open study of creatine monohydrate in treatment-resistant posttraumatic stress disorder. J Clin Psychiatry 67: 836–837. doi:10.4088/JCP.v67n0521c. PubMed: .
    1. Agren H, Niklasson F (1988) Creatinine and creatine in CSF: indices of brain energy metabolism in depression. J Neural Transm 74: 55–59. doi:10.1007/BF01243575. PubMed: .
    1. Kato T, Takahashi S (1994) Reduction of brain phosphocreatine in bipolar II disorder detected by phosphorus-31 magnetic resonance spectroscopy. J Affect Disord 31: 125–133. doi:10.1016/0165-0327(94)90116-3. PubMed: .
    1. Moore CM, Christensen JD, Lafer B, Fava M, Renshaw PF (1997) Lower levels of nucleoside triphosphate in the basal ganglia of depressed subjects: a phosphorous-31 magnetic resonance spectroscopy study. Am J Psychiatry 154: 116–118. PubMed: .
    1. Volz HP, Rzanny R, Riehemann S, May S, Hegewald H et al. (1998) 31P magnetic resonance spectroscopy in the frontal lobe of major depressed patients. Eur Arch Psychiatry Clin Neurosci 248: 289–295. doi:10.1007/s004060050052. PubMed: .
    1. Czéh B, Michaelis T, Watanabe T, Frahm J, de Biurrun G et al. (2001) Stress-induced changes in cerebral metabolites, hippocampal volume, and cell proliferation are prevented by antidepressant treatment with tianeptine. Proc Natl Acad Sci USA 98: 12796–12801. doi:10.1073/pnas.211427898. PubMed: .
    1. Iosifescu DV, Bolo NR, Nierenberg AA, Jensen E, Fava M et al. (2008) Brain bioenergetics and response to triiodothyronine augmentation in major depressive disorder. Biol Psychiatry 63: 1127–1134. doi:10.1016/j.biopsych.2007.11.020. PubMed: .
    1. Hillman CH, Erickson KI, Kramer AF (2008) Be smart, exercise your heart: exercise effects on brain and cognition. Nat Rev Neurosci 9: 58-65. doi:10.1038/nrn2298. PubMed: .
    1. Lautenschlager NT, Cox KL, Flicker L, Foster JK, van Bockxmeer FM et al. (2008) Effect of physical activity on cognitive function in older adults at risk for Alzheimer disease: a randomized trial. JAMA 300: 1027-1037. doi:10.1001/jama.300.9.1027. PubMed: .
    1. Larson EB, Wang L, Bowen JD, McCormick WC, Teri L et al. (2006) Exercise is associated with reduced risk for incident dementia among persons 65 years of age and older. Ann Intern Med 144: 73-81. doi:10.7326/0003-4819-144-2-200601170-00004. PubMed: .
    1. Etnier JL, Nowell PM, Landers DM, Sibley BA (2006) A meta-regression to examine the relationship between aerobic fitness and cognitive performance. Brain. Res Rev 52: 119–130. doi:10.1016/j.brainresrev.2006.01.002.
    1. Heyn P, Abreu BC, Ottenbacher KJ (2004) The effects of exercise training on elderly persons with cognitive impairment and dementia: a meta-analysis. Arch Phys Med Rehabil 84: 1694–1704. PubMed: .
    1. Spirduso WW (1975) Reaction and movement time as a function of age and physical activity level. J Gerontol 30: 435-440. doi:10.1093/geronj/30.4.435. PubMed: .
    1. Sofi F, Valecchi D, Bacci D, Abbate R, Gensini GF et al. (2011) Physical activity and risk of cognitive decline: a meta-analysis of prospective studies. J Intern Med 269: 107-117. doi:10.1111/j.1365-2796.2010.02281.x. PubMed: .
    1. Liu-Ambrose T, Nagamatsu LS, Graf P, Beattie BL, Ashe MC et al. (2010) Resistance training and executive functions: a 12-month randomized controlled trial. Arch Intern Med 170: 170-178. doi:10.1001/archinternmed.2009.494. PubMed: .
    1. Cassilhas RC, Viana VA, Grassmann V, Santos RT, Santos RF et al. (2007) The impact of resistance exercise on the cognitive function of the elderly. Med Sci Sports Exerc 39: 1401-1407. doi:10.1249/mss.0b013e318060111f. PubMed: .
    1. Perrig-Chiello P, Perrig WJ, Ehrsam R, Staehelin HB, Krings F (1998) The effects of resistance training on well-being and memory in elderly volunteers. Age Ageing 27: 469-475. doi:10.1093/ageing/27.4.469. PubMed: .
    1. Rawson ES, Venezia AC (2011) Use of creatine in the elderly and evidence for effects on cognitive function in young and old. Amino Acids 40: 1349-1362. doi:10.1007/s00726-011-0855-9. PubMed: .
    1. Almeida OP, Almeida SA (2003) Reliability of the Brazilian version of the abbreviated form of Geriatric Depression Scale (GDS) short form. Arq Neuropsiquiat 57: 421-426.
    1. Folstein MF, Folstein SE, McHugh PR. (1975) 1075) "Mini-mental state". A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 12: 189-198. doi:10.1016/0022-3956(75)90026-6. PubMed: .
    1. Brucki SM, Nitrini R, Caramelli P, Bertolucci PH, Okamoto IH (2003) Suggestions for utilization of the mini-mental state examination in Brazil. Arq Neuro Psiquiatr 61: 777-781. doi:10.1590/S0004-282X2003000500014.
    1. Spreen O, Strauss E (1998) A compendium of neuropsychological tests (2nd ed.). New York: Oxford University Press.
    1. Arbuthnott K, Frank J (2000) Trail making test, part B as a measure of executive control: validation using a set-switching paradigm. J Clin Exp Neuropsychol 22: 518-528. doi:10.1076/1380-3395(200008)22:4;1-0;FT518. PubMed: .
    1. Cronholm B, Viding G (1956) Digit span as a test of immediate memory. Nord Med 56: 1612-1614. PubMed: .
    1. Nitrini R, Caramelli P, Herrera Júnior E, Porto CS, Charchat-Fichman H et al. (2004) Performance of illiterate and literate nondemented elderly subjects in two tests of long-term memory. J Int Neuropsychol Soc 10: 634-638. doi:10.1017/S1355617704104062. PubMed: .
    1. Andres RH, Ducray AD, Schlattner U, Wallimann T, Widmer HR (2008) Functions and effects of creatine in the central nervous system. Brain. Res Bull 76: 329-343. doi:10.1016/j.brainresbull.2008.02.035.
    1. Gabbay V, Hess DA, Liu S, Babb JS, Klein RG et al. (2007) Lateralized caudate metabolic abnormalities in adolescent major depressive disorder: a proton MR spectroscopy study. Am J Psychiatry 164: 1881–1889. doi:10.1176/appi.ajp.2007.06122032. PubMed: .
    1. Kalia M (2005) Neurobiological basis of depression: an update. Metabolism 54: 24–27. doi:10.1016/j.metabol.2004.07.008. PubMed: .
    1. Manji HK, Drevets WC, Charney DS (2001) The cellular neurobiology of depression. Nat Med 7: 541–547. doi:10.1038/87865. PubMed: .
    1. McEwen BS (2005) Glucocorticoids, depression, and mood disorders: structural remodeling in the brain. Metabolism 54: 20–23. doi:10.1016/j.metabol.2005.01.008. PubMed: .
    1. Burroughs S, French D (2007) Depression and anxiety: role of mitochondria. Curr Anaesth Crit Care 18: 34–41. doi:10.1016/j.cacc.2007.01.007.
    1. Duman RS, Malberg J, Thome J (1999) Neural plasticity to stress and antidepressant treatment. Biol Psychiatry 46: 1181–1191. doi:10.1016/S0006-3223(99)00177-8. PubMed: .
    1. Manji HK, Moore GJ, Rajkowska G, Chen G (2000) Neuroplasticity and cellular resilience in mood disorders. Mol Psychiatry 5: 578–593. doi:10.1038/sj.mp.4000811. PubMed: .
    1. Moretti A, Gorini A, Villa RF (2003) Affective disorders, antidepressant drugs and brain metabolism. Mol Psychiatry 8: 773–785. doi:10.1038/sj.mp.4001353. PubMed: .
    1. McMorris T, Mielcarz G, Harris RC, Swain JP, Howard A (2007) Creatine supplementation and cognitive performance in elderly individuals. Neuropsychol Dev Cogn B Aging Neuropsychol Cogn 14: 517–528. doi:10.1080/13825580600788100. PubMed: .
    1. Benton D, Donohoe R (2010) The influence of creatine supplementation on the cognitive functioning of vegetarians and omnivores. BJ Nutr 105: 1-6
    1. 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 Biol Sci 270: 2147-2150. doi:10.1098/rspb.2003.2492. PubMed: .

Source: PubMed

3
Tilaa