Review Article

Role of creatine in sensitivity and function of the auditory and vestibular system


Background and Aim: Creatine plays an important role in the regulation of cellular energy in high energy demand organs such as the inner ear. It is also believed to play a protective role. This article reviewed the mechanisms and effects of creatine on the auditory and vestibular systems.
Recent Findings: Creatine transporters and creatine kinase enzymes are involved in converting
creatine to creatine phosphate. Phosphate is a fuel cell available in the cochlear and vestibular hair cells and the protective cells, striavascularis, peripheral and central neural pathways to the auditory cortex. It provides essential ATP for auditory and vestibular system performance. Creatine kinase prevents cochlear damage by regulating the metabolism of energy in marginal layers of the striavascularis and preventing free radical production in stressful situations. It also plays an important role in vestibular compensation. Creatine kinase dysfunction leads to an increase in the threshold of auditory brainstem potentials and a reduction in vestibular performance. The use of creatine improves vestibular evoked myogenic potentials and neurologic symptoms.
Conclusion: Creatine and creatine kinase protein is essential for normal hearing and balance function and sensitivity. Creatine kinase deficiency impairs the functioning of these two systems; however, creatine consumption may boost the sensitivity of the vestibular system and neurological performance. Effects of the creatine consumption on the auditory system have not yet been examined.

1. Spillane M, Schoch R, Cooke M, Harvey T, Greenwood M, Kreider R, et al. 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. 2009;6:6.
2. Wallimann T, Dolder M, Schlattner U, Eder M, Hornemann T, O'Gorman E, et al. Some new aspects of creatine kinase (CK): compartmentation, structure, function and regulation for cellular and mitochondrial bioenergetics and physiology. Biofactors. 1998;8(3-4):229-34.
3. Snow RJ, McKenna MJ, Selig SE, Kemp J, Stathis CG, Zhao S. Effect of creatine supplementation on sprint exercise performance and muscle metabolism. J Appl Physiol (1985). 1998;84(5):1667-73.
4. van Leemputte M, Vandenberghe K, Hespel P. Shortening of muscle relaxation time after creatine loading. J Appl Physiol (1985). 1999;86(3):840-4.
5. Dunn-Meynell AA, Rawson NE, Levin BE. Distribution and phenotype of neurons containing the ATP-sensitive K+ channel in rat brain. Brain Res. 1998;814(1-2):41-54.
6. Clark JF. Creatine and phosphocreatine: a review of their use in exercise and sport. J Athl Train. 1997;32(1):45-51.
7. Kreider RB, Melton C, Rasmussen CJ, Greenwood M, Lancaster S, Cantler EC, et al. Long-term creatine supplementation does not significantly affect clinical markers of health in athletes. Mol Cell Biochem. 2003;244(1-2):95-104.
8. Shin JB, Streijger F, Beynon A, Peters T, Gadzala L, McMillen D, et al. Hair bundles are specialized for ATP delivery via creatine kinase. Neuron. 2007;53(3):371-86.
9. Gillespie PG, Cyr JL. Myosin-1c, the hair cell's adaptation motor. Annu Rev Physiol. 2004;66:521-45.
10. Spurr AR. A low-viscosity epoxy resin embedding medium for electron microscopy. J Ultrastruct Res. 1969;26(1):31-43.
11. Greenhaff PL, Bodin K, Soderlund K, Hultman E. Effect of oral creatine supplementation on skeletal muscle phosphocreatine resynthesis. Am J Physiol. 1994;266(5 Pt 1):E725-30.
12. Schlattner U, Tokarska-Schlattner M, Wallimann T. Mitochondrial creatine kinase in human health and disease. Biochim Biophys Acta. 2006;1762(2):164-80.
13. Kamber M, Koster M, Kreis R, Walker G, Boesch C, Hoppeler H. Creatine supplementation--part I: performance, clinical chemistry, and muscle volume. Med Sci Sports Exerc. 1999;31(12):1763-9.
14. Spicer SS, Schulte BA. Evidence for a medial K+ recycling pathway from inner hair cells. Hear Res. 1998;118(1-2):1-12.
15. Wong AC, Velamoor S, Skelton MR, Thorne PR, Vlajkovic SM. Expression and distribution of creatine transporter and creatine kinase (brain isoform) in developing and mature rat cochlear tissues. Histochem Cell Biol. 2012;137(5):599-613.
16. Ramírez-Camacho R, García-Berrocal JR, Trinidad A, González-García JA, Verdaguer JM, Ibáñez A, et al. Central role of supporting cells in cochlear homeostasis and pathology. Med Hypotheses. 2006;67(3):550-5.
17. Spicer SS, Schulte BA. Creatine kinase in epithelium of the inner ear. J Histochem Cytochem. 1992;40(2):185-92.
18. Minami SB, Yamashita D, Ogawa K, Schacht J, Miller JM. Creatine and tempol attenuate noise-induced hearing loss. Brain Res. 2007;1148:83-9.
19. Kaldis P, Hemmer W, Zanolla E, Holtzman D, Wallimann T. 'Hot spots' of creatine kinase localization in brain: cerebellum, hippocampus and choroid plexus. Dev Neurosci. 1996;18(5-6):542-54.
20. Brewer GJ, Wallimann TW. Protective effect of the energy precursor creatine against toxicity of glutamate and beta-amyloid in rat hippocampal neurons. J Neurochem. 2000;74(5):1968-78.
21. Wallimann T, Wegmann G, Moser H, Huber R, Eppenberger HM. High content of creatine kinase in chicken retina: compartmentalized localization of creatine kinase isoenzymes in photoreceptor cells. Proc Natl Acad Sci USA. 1986;83(11):3816-9.
22. Braissant O, Henry H, Loup M, Eilers B, Bachmann C. Endogenous synthesis and transport of creatine in the rat brain: an in situ hybridization study. Brain Res Mol Brain Res. 2001;86(1-2):193-201.
23. Andres RH, Ducray AD, Schlattner U, Wallimann T, Widmer HR. Functions and effects of creatine in the central nervous system. Brain Res Bull. 2008;76(4):329-43.
24. Karschin C, Ecke C, Ashcroft FM, Karschin A. Overlapping distribution of K(ATP) channel-forming Kir6.2 subunit and the sulfonylurea receptor SUR1 in rodent brain. FEBS Lett. 1997;401(1):59-64.
25. Wang WP, Qiu MD, Ren HJ, Zhang XH. Relations of intracranial pressure, creatine kinase and brainstem auditory evoked potential in patients with traumatic brain edema. Chin Med J (Engl). 1994;107(3):205-8.
26. Hiel H, Happe HK, Warr WB, Morley BJ. Regional distribution of a creatine transporter in rat auditory brainstem: an in-situ hybridization study. Hear Res. 1996;98(1-2):29-37.
27. Hetherington HP, Spencer DD, Vaughan JT, Pan JW. Quantitative (31)P spectroscopic imaging of human brain at 4 Tesla: assessment of gray and white matter differences of phosphocreatine and ATP. Magn Reson Med. 2001;45(1):46-52.
28. in 't Zandt HJ, Renema WK, Streijger F, Jost C, Klomp DW, Oerlemans F, et al. Cerebral creatine kinase deficiency influences metabolite levels and morphology in the mouse brain: a quantitative in vivo 1H and 31P magnetic resonance study. J Neurochem. 2004;90(6):1321-30.
29. Wyss M, Kaddurah-Daouk R. Creatine and creatinine metabolism. Physiol Rev. 2000;80(3):1107-213.
30. Zhu S, Li M, Figueroa BE, Liu A, Stavrovskaya IG, Pasinelli P, et al. Prophylactic creatine administration mediates neuroprotection in cerebral ischemia in mice. J Neurosci. 2004;24(26):5909-12.
31. Sullivan PG, Geiger JD, Mattson MP, Scheff SW. Dietary supplement creatine protects against traumatic brain injury. Ann Neurol. 2000;48(5):723-9.
32. Bürklen TS, Schlattner U, Homayouni R, Gough K, Rak M, Szeghalmi A, et al. The creatine kinase/creatine connection to Alzheimer's disease: CK-inactivation, APP-CK complexes and focal creatine deposits. J Biomed Biotechnol. 2006;2006(3):35936.
33. Ryu H, Rosas HD, Hersch SM, Ferrante RJ. The therapeutic role of creatine in Huntington's disease. Pharmacol Ther. 2005;108(2):193-207.
34. 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(1):69-76.
35. Bender A, Samtleben W, Elstner M, Klopstock T. Long-term creatine supplementation is safe in aged patients with Parkinson disease. Nutr Res. 2008;28(3):172-8.
36. Cui Y, Wang W, Fan Z. Cytoplasmic vestibule of the weak inward rectifier Kir6.2 potassium channel. J Biol Chem. 2002;277(12):10523-30.
37. Paterson JM, Short D, Flatman PW, Seckl JR, Aitken A, Dutia MB. Changes in protein expression in the rat medial vestibular nuclei during vestibular compensation. J Physiol. 2006;575(Pt 3):777-88.
38. LeMasurier M, Gillespie PG. Hair-cell mechanotransduction and cochlear amplification. Neuron. 2005;48(3):403-15.
39. Moradi V, Adel Ghahraman M, Pourbakht A, Naghdi S. Effects of short-term creatine supplement consumption on the cervical vestibular evoked myogenic potentials. [dissertation]. Tehran: School of Rehabilitation, Tehran University of Medical Sciences; 2014
IssueVol 23 No 6 (2015) QRcode
SectionReview Article(s)
Creatine creatine kinase vestibular system auditory system adenosine triphosphate

Rights and permissions
Creative Commons License This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
How to Cite
Moradi V, Adel Ghahraman M, Pourbakht A, Naghdi S, Jalaie S. Role of creatine in sensitivity and function of the auditory and vestibular system. Aud Vestib Res. 23(6):45-56.