Life Extension Magazine April 2005
Anti-Aging Benefits of Creatine
By Will Brink
Creatine Improves Brain Function
Perhaps the most compelling case for creatine supplementation is its ability to modulate brain function and metabolism. Previous articles in Life Extension have examined some of creatine’s applications in promoting muscle, brain, and heart health.1,2 Ongoing research indicates that creatine is an important nutrient for brain function and metabolism in both healthy people and those who suffer from brain damage or brain-related disease. Traumatic brain injuries affect thousands each year. Adding to this tragedy is that much of the damage is caused not by the immediate injury to the brain, but by cell death caused by ischemia (lack of blood flow and oxygen to tissues), free radical damage, and oxidative stress.
A cell’s ability to function is directly related to its mitochondrial health and ATP status. Even small changes in ATP supply can have profound effects on the tissues’ ability to function properly. Heart tissue, brain neurons, and other highly active tissues are very sensitive to diminished ATP levels. Creatine appears to be among the most effective nutritional supplements for maintaining or raising ATP levels.
Recent research indicates that creatine affords the human nervous system significant protection against ischemic and oxidative insults.43-56 A study published in the Annals of Neurology examined creatine’s effects on brain tissue damage following simulated traumatic brain injury in animals.57 Administration of creatine ameliorated the extent of cortical damage by as much as 36% in mice and 50% in rats. The researchers noted that this protection may be tied to creatine-induced maintenance of mitochondrial bioenergetics. They concluded that creatine “. . . may provide clues to the mechanisms responsible for neuronal loss after traumatic brain injury and may find use as a neuroprotective agent against acute and delayed neurodegenerative processes.” This study suggests that creatine therapy should be initiated as soon as possible after traumatic brain injury. People who have already been using creatine regularly may be afforded considerable protection against additional brain damage following such an injury.
Research also indicates that creatine improves brain function in healthy adults. A recent double-blind, placebo-controlled crossover study examined how six weeks of creatine supplementation affected cognitive function in adult vegetarians.58 Subjects were given five grams of creatine daily. Following creatine supplementation, the study participants demonstrated improved scores on tests assessing intelligence and working memory. Creatine’s effects may be due to its ability to increase the cellular energy available to the brain. Although creatine supplementation may have a less dramatic effect on non-vegetarians who obtain some creatine from dietary sources such as meat, it is likely that creatine benefits brain function in meat eaters and vegetarians. Supplemental creatine thus appears to improve function and performance in healthy and injured brains alike.
Through its role in promoting an abundant pool of cellular energy, creatine helps support the healthy functioning of muscle, brain, and other body tissues. A substantial body of research demonstrates that creatine is a safe and effective tool for managing a wide range of pathologies, and may be a powerful anti-aging nutrient. Healthy adults may benefit from supplementing with two to three grams of creatine daily, while those seeking to address specific health concerns such as muscle loss or brain injury may benefit from five to ten grams of creatine daily.
Additional information on how creatine and other supplements may benefit athletes is available at www.MuscleBuildingNutrition.com.
1. Available at: http://www.lef.org/magazine/mag2003/mag2003_03.html. Accessed December 17, 2004.
2. Available at: http://www.lef.org/magazine/mag2003/mag2003_09.html. Accessed December 17, 2004.
3. Racette SB. Creatine supplementation and athletic performance. J Orthop Sports PhysTher. 2003 Oct;33(10):615-21.
4. Hespel P, Op’t EB, Van Leemputte M, et al. Oral creatine supplementation facilitates the rehabilitation of disuse atrophy and alters the expression of muscle myogenic factors in humans. J Physiol. 2001 Oct 15;536(Pt 2):625-33.
5. Jowko E, Ostaszewski P, Jank M, et al. Creatine and beta-hydroxy-beta-methylbutyrate (HMB) additively increase lean body mass and muscle strength during a weight-training program. Nutrition. 2001 Jul;17(7-8):558-66.
6. Tarnopolsky MA, Parise G, Yardley NJ, et al. Creatine-dextrose and protein-dextrose induce similar strength gains during training. Med Sci Sports Exerc. 2001 Dec;33(12):2044-52.
7. Becque MD, Lochmann JD, Melrose DR. Effects of oral creatine supplementation on muscular strength and body composition. Med Sci Sports Exerc. 2000 Mar;32(3):654-8.
8. Francaux M, Poortmans JR. Effects of training and creatine supplement on muscle strength and body mass. Eur J Appl Physiol Occup Physiol. 1999 Jul;80(2):165-8.
9. Clarkson PM, Rawson ES. Nutritional supplements to increase muscle mass. Crit Rev Food Sci Nutr. 1999 Jul;39(4):317-28.
10. Kreider RB, Ferreira M, Wilson M, et al. Effects of creatine supplementation on body composition, strength, and sprint performance. Med Sci Sports Exerc. 1998 Jan;30(1):73-82.
11. Vandenberghe K, Goris M, Van Hecke P, et al. Long-term creatine intake is beneficial to muscle performance during resistance training. J Appl Physiol. 1997 Dec;83(6):2055-63.
12. Balsom PD, Soderlund K, Sjodin B, Ekblom B. Skeletal muscle metabolism during short duration high-intensity exercise: influence of creatine supplementation. Acta Physiol Scand. 1995 Jul;154(3):303-10.
13. Harris RC, Soderlund K, Hultman E. Elevation of creatine in resting and exercised muscle of normal subjects by creatine supplementation. Clin Sci (Lond). 1992 Sep;83(3):367-74.
14. Fulle S, Protasi F, Di Tano G, et al. The contribution of reactive oxygen species to sarcopenia and muscle ageing. Exp Gerontol. 2004 Jan;39(1):17-24.
15. Yarasheski KE. Exercise, aging, and muscle protein metabolism. J Gerontol A Biol Sci Med Sci. 2003 Oct;58(10):M918-22.
16. Semba RD, Blaum C, Guralnik JM, et al. Carotenoid and vitamin E status are associated with indicators of sarcopenia among older women living in the community. Aging Clin Exp Res. 2003 Dec;15(6):482-7.
17. Volpi E, Kobayashi H, Sheffield-Moore M, Mittendorfer B, Wolfe RR. Essential amino acids are primarily responsible for the amino acid stimulation of muscle protein anabolism in healthy elderly adults. Am J Clin Nutr. 2003 Aug;78(2):250-8.
18. Doherty TJ. Invited review: Aging and sarcopenia. J Appl Physiol. 2003 Oct;95(4):1717-27.
19. Vanitallie TB. Frailty in the elderly: contributions of sarcopenia and visceral protein depletion. Metabolism. 2003 Oct;52(10 Suppl 2):22-6.
20. Kamel HK, Maas D, Duthie EH, Jr. Role of hormones in the pathogenesis and management of sarcopenia. Drugs Aging. 2002;19(11):865-77.
21. Lawler JM, Barnes WS, Wu G, Song W, Demaree S. Direct antioxidant properties of creatine. Biochem Biophys Res Commun. 2002 Jan 11;290(1):47-52.
22. Ji LL. Exercise-induced modulation of antioxidant defense. Ann NY Acad Sci. 2002 Apr;959:82-92.
23. Carmeli E, Coleman R, Reznick AZ. The biochemistry of aging muscle. Exp Gerontol. 2002 Apr;37(4):477-89.
24. Welle S. Cellular and molecular basis of age-related sarcopenia. Can J Appl Physiol. 2002 Feb;27(1):19-41.
25. Lio D, Scola L, Crivello A, et al. Allele frequencies of +874T: A single nucleotide polymorphism at the first intron of interferon-gamma gene in a group of Italian centenarians. Exp Gerontol. 2002 Jan;37(2-3):315-9.
26. Bonafe M, Olivieri F, Cavallone L, et al. A gender-dependent genetic predisposition to produce high levels of IL-6 is detrimental for longevity. Eur J Immunol. 2001 Aug;31(8):2357-61.
27. Bruunsgaard H, Pedersen M, Pedersen BK. Aging and proinflammatory cytokines. Curr Opin Hematol. 2001 May;8(3):131-6.
28. Marcell TJ, Harman SM, Urban RJ, et al. Comparison of GH, IGF-I, and testosterone with mRNA of receptors and myostatin in skeletal muscle in older men. Am J Physiol Endocrinol Metab. 2001 Dec;281(6):E1159-E64.
29. Persky AM, Brazeau GA. Clinical pharmacology of the dietary supplement creatine monohydrate. Pharmacol Rev. 2001 Jun;53(2):161-76.
30. Parise G, Mihic S, MacLennan D, Yarasheski KE, Tarnopolsky MA. Effects of acute creatine monohydrate supplementation on leucine kinetics and mixed-muscle protein synthesis. J Appl Physiol. 2001 Sep;91(3):1041-7.
31. Brod SA. Unregulated inflammation shortens human functional longevity. Inflamm Res. 2000 Nov;49(11):561-70.
32. Rogers MA, Evans WJ. Changes in skeletal muscle with aging: effects of exercise training. Exerc Sport Sci Rev. 1993;21:65-102.
33. Hutter E, Renner K, Pfister G, et al. Senescence-associated changes in respiration and oxidative phosphorylation in primary human fibroblasts. Biochem J. 2004 Jun 15;380(Pt 3):919-28.
34. Brose A, Parise G, Tarnopolsky MA. Creatine supplementation enhances isometric strength and body composition improvements following strength exercise training in older adults. J Gerontol A Biol Sci Med Sci. 2003 Jan;58(1):11-9.
35. Gotshalk LA, Volek JS, Staron RS, et al. Creatine supplementation improves muscular performance in older men. Med Sci Sports Exerc. 2002 Mar;34(3):537-43.
36. Candow DG, Chilibeck PD, Chad KE, et al. Effect of ceasing creatine supplementation while maintaining resistance training in older men. J Aging Phys Act. 2004 Jul;12(3):219-31.
37. Emerit J, Edeas M, Bricaire F. Neurodegenerative diseases and oxidative stress. Biomed Pharmacother. 2004 Jan;58(1):39-46.
38. Kang D, Hamasaki N. Mitochondrial oxidative stress and mitochondrial DNA. Clin Chem Lab Med. 2003 Oct;41(10):1281-8.
39. Szibor M and Holtz J. Mitochondrial ageing. Basic Res Cardiol. 2003 Jul;98(4):210-8.
40. Wei YH, Lee HC. Oxidative stress, mitochondrial DNA mutation, and impairment of antioxidant enzymes in aging. Exp Biol Med (Maywood.). 2002 Oct;227(9):671-82.
41. Waters DL, Brooks WM, Qualls CR, Baumgartner RN. Skeletal muscle mitochondrial function and lean body mass in healthy exercising elderly. Mech Ageing Dev. 2003 Mar;124(3):301-9.
42. Santos RV, Bassit RA, Caperuto EC, Costa Rosa LF. The effect of creatine supplementation upon inflammatory and muscle soreness markers after a 30km race. Life Sci. 2004 Sep 3;75(16):1917-24.
43. Klivenyi P, Calingasan NY, Starkov A, et al. Neuroprotective mechanisms of creatine occur in the absence of mitochondrial creatine kinase. Neurobiol Dis. 2004 Apr;15(3):610-7.
44. Zhu S, Li M, Figueroa BE, et al. Prophylactic creatine administration mediates neuroprotection in cerebral ischemia in mice. J Neurosci. 2004 Jun 30;24(26):5909-12.
45. Dedeoglu A, Kubilus JK, Yang L, et al. Creatine therapy provides neuroprotection after onset of clinical symptoms in Huntington’s disease transgenic mice. J Neurochem. 2003 Jun;85(6):1359-67.
46. Rabchevsky AG, Sullivan PG, Fugaccia I, Scheff SW. Creatine diet supplement for spinal cord injury: influences on functional recovery and tissue sparing in rats. J Neurotrauma. 2003 Jul;20(7):659-69.
47. Adcock KH, Nedelcu J, Loenneker T, et al. Neuroprotection of creatine supplementation in neonatal rats with transient cerebral hypoxia-ischemia. Dev Neurosci. 2002;24(5):382-8.
48. Hausmann ON, Fouad K, Wallimann T, Schwab ME. Protective effects of oral creatine supplementation on spinal cord injury in rats. Spinal Cord. 2002 Sep;40(9):449-56.
49. See D, Mason S, Roshan R. Increased tumor necrosis factor alpha (TNF-alpha) and natural killer cell (NK) function using an integrative approach in late stage cancers. Immunol Invest. 2002 May;31(2):137-53.
50. Andreassen OA, Dedeoglu A, Ferrante RJ, et al. Creatine increase survival and delays motor symptoms in a transgenic animal model of Huntington’s disease. Neurobiol Dis. 2001 Jun;8(3):479-91.
51. Tarnopolsky MA, Beal MF. Potential for creatine and other therapies targeting cellular energy dysfunction in neurological disorders. Ann Neurol. 2001 May;49(5):561-74.
52. Walter MC, Lochmuller H, Reilich P, et al. Creatine monohydrate in muscular dystrophies: A double-blind, placebo-controlled clinical study. Neurology. 2000 May 9;54(9):1848-50.
53. Tarnopolsky M, Martin J. Creatine monohydrate increases strength in patients with neuromuscular disease. Neurology. 1999 Mar 10;52(4):854-7.
54. Klivenyi P, Ferrante RJ, Matthews RT, et al. Neuroprotective effects of creatine in a transgenic animal model of amyotrophic lateral sclerosis. Nat Med. 1999 Mar;5(3):347-50.
55. Matthews RT, Ferrante RJ, Klivenyi P, et al. Creatine and cyclocreatine attenuate MPTP neurotoxicity. Exp Neurol. 1999 May;157(1):142-9.
56. Matthews RT, Yang L, Jenkins BG, et al. Neuroprotective effects of creatine and cyclocreatine in animal models of Huntington’s disease. J Neurosci. 1998 Jan 1;18(1):156-63.
57. Sullivan PG, Geiger JD, Mattson MP, Scheff SW. Dietary supplement creatine protects against traumatic brain injury. Ann Neurol. 2000 Nov;48(5):723-9.
58. Rae C, Digney AL, McEwan SR, Bates TC. Oral creatine monohydrate supplementation improves brain performance: a double-blind, placebo-controlled, cross-over trial. Proc R Soc Lond B Biol Sci. 2003 Oct 22;270(1529):2147-50.
59. Marshall K. Therapeutic applications of whey protein. Altern Med Rev. 2004 Jun;9(2):136-56.
60. Bounous G. Whey protein concentrate (WPC) and glutathione modulation in cancer treatment. Anticancer Res. 2000 Nov;20(6C):4785-92.
61. Bounous G, Gold P. The biological activity of undenatured dietary whey proteins: role of glutathione. Clin Invest Med. 1991 Aug;14(4):296-309.
62. Tsai WY, Chang WH, Chen CH, Lu FJ. Enchancing effect of patented whey protein isolate (Immunocal) on cytotoxicity of an anticancer drug. Nutr Cancer. 2000;38(2):200-8.
63. Baruchel S, Viau G. In vitro selective modulation of cellular glutathione by a humanized native milk protein isolate in normal cells and rat mammary carcinoma model. Anticancer Res. 1996 May;16(3A):1095-99.
64. McIntosh GH, Regester GO, Le Leu RK, Royle PJ, Smithers GW. Dairy proteins protect against dimethylhydrazine-induced intestinal cancers in rats. J Nutr. 1995 Apr;125(4):809-16.
65. Stumvoll M, Perriello G, Meyer C, Gerich J. Role of glutamine in human carbohydrate metabolism in kidney and other tissues. Kidney Int. 1999 Mar;55(3):778-92.
66. Walsh NP, Blannin AK, Robson PJ, Gleeson M. Glutamine, exercise and immune function. Links and possible mechanisms. Sports Med. 1998 Sep;26(3):177-91.
67. De Bandt JP, Cynober LA. Amino acids with anabolic properties. Curr Opin Clin Nutr Metab Care. 1998 May;1(3):263-72.
68. Balzola FA, Boggio-Bertinet D. The metabolic role of glutamine. Minerva Gastroenterol Dietol. 1996 Mar;42(1):17-26.
69. Roth E, Spittler A, Oehler R. Glutamine: effects on the immune system, protein balance and intestinal functions. Wien Klin Wochenschr. 1996;108(21):669-76.
70. Furst P, Albers S, Stehle P. Evidence for a nutritional need for glutamine in catabolic patients. Kidney Int Suppl. 1989 Nov;27:S287-92.
71. Available at: http://www.the-aps.org/press/conference/eb03/12.htm. Accessed December 17, 2004.