Standardized Ginkgo biloba extract (GBE) is an established herbal treatment used for
a variety of indications, including vertigo and/or tinnitus. The evidence base
in human clinical studies for a clear benefit of GBE in vertigo and/or tinnitus
is limited and contradictory due to poor reporting as well as variations in
study quality and outcome measures used. The aim of this review is to identify
and discuss the rationale for using GBE in the treatment of vertigo and/or
tinnitus based on the known pleiotropic actions of GBE and the pathophysiology
of vertigo and/or tinnitus. The rationale will be substantiated by a review of
the literature in order to identify and evaluate clinical trials investigating
the efficacy of GBE in individuals with vertigo and/or tinnitus. The review identified randomized
controlled trials (RCTs) investigating the effectiveness of GBE in vertigo
and/or tinnitus publishedin PubMed up to 1st January 2020.In
total, 17 RCTs were included 8 of the 9 studies investigating tinnitus and/or
vertigo/dizziness found improvements, and 6 of 8 included studies investigating
solely tinnitus showed positive effects. Based on the known mechanisms of
action of GBE as well as evidence from animal models and human clinical trials
identified in this review, GBEis a
rational alternative treatment that might provide benefits to individuals with
vertigo and/or tinnitus. However, further well-defined RCTs in patients with
defined pathological entities are necessary to further substantiate the
beneficial effects of GBE for vertigo
References
[1]
Cullen, K.E. (2012) The Vestibular System: Multimodal Integration and Encoding of Self-Motion for Motor Control. Trends in Neurosciences, 35, 185-196. https://doi.org/10.1016/j.tins.2011.12.001
[2]
Borel, L., Lopez, C., Péruch, P. and Lacour, M. (2008) Vestibular Syndrome: A Change in Internal Spatial Representation. Neurophysiologie Clinique, 38, 375-389. https://doi.org/10.1016/j.neucli.2008.09.002
[3]
Guerraz, M., Yardley, L., Bertholon, P., Pollak, L., Rudge, P., Gresty, M.A., et al. (2001) Visual Vertigo: Symptom Assessment, Spatial Orientation and Postural Control. Brain, 124, 1646-1656. https://doi.org/10.1093/brain/124.8.1646
[4]
Agrup, C., Gleeson, M. and Rudge, P. (2007) The Inner Ear and the Neurologist. Journal of Neurology, Neurosurgery, and Psychiatry, 78, 114-122. https://doi.org/10.1136/jnnp.2006.092064
[5]
Bisdorff, A., Bosser, G., Gueguen, R. and Perrin, P. (2013) The Epidemiology of Vertigo, Dizziness, and Unsteadiness and Its Links to Co-Morbidities. Frontiers in Neurology, 4, 29. https://doi.org/10.3389/fneur.2013.00029
[6]
Teggi, R., Manfrin, M., Balzanelli, C., Gatti, O., Mura, F., Quaglieri, S., et al. (2016) Point Prevalence of Vertigo and Dizziness in a Sample of 2672 Subjects and Correlation with Headaches. ACTA Otorhinolaryngologica Italica, 36, 215-219. https://doi.org/10.14639/0392-100X-847
[7]
Neuhauser, H.K. (2016) The Epidemiology of Dizziness and Vertigo. In: Furman, J.M. and Lempert, T., Eds., Handbook of Clinical Neurology, Vol. 137, Elsevier, Amsterdam, 67-82. https://doi.org/10.1016/B978-0-444-63437-5.00005-4
[8]
Neuhauser, H.K., Radtke, A., von Brevern, M., Lezius, F., Feldmann, M. and Lempert, T. (2008) Burden of Dizziness and Vertigo in the Community. Archives of Internal Medicine, 168, 2118-2124. https://doi.org/10.1001/archinte.168.19.2118
[9]
Henry, J.A., Dennis, K.C. and Schechter, M.A. (2005) General Review of Tinnitus: Prevalence, Mechanisms, Effects, and Management. Journal of Speech, Language, and Hearing Research, 48, 1204-1235. https://doi.org/10.1044/1092-4388(2005/084)
[10]
Jastreboff, P.J. and Hazell, J.W. (1993) A Neurophysiological Approach to Tinnitus: Clinical Implications. British Journal of Audiology, 27, 7-17. https://doi.org/10.3109/03005369309077884
[11]
Nondahl, D.M., Cruickshanks, K.J., Dalton, D.S., Klein, B.E.K., Klein, R., Schubert, C.R., et al. (2007) The Impact of Tinnitus on Quality of Life in Older Adults. Journal of the American Academy of Audiology, 18, 257-266. https://doi.org/10.3766/jaaa.18.3.7
[12]
Zeman, F., Koller, M., Langguth, B. and Landgrebe, M. (2014) Which Tinnitus-Related Aspects Are Relevant for Quality of Life and Depression: Results from a Large International Multicentre Sample. Health and Quality of Life Outcomes, 12, 7. https://doi.org/10.1186/1477-7525-12-7
[13]
Chung, J.H. and Lee, S.H. (2016) The Pathophysiologic Mechanism of Tinnitus. Hanyang Medical Reviews, 36, 81-85. https://doi.org/10.7599/hmr.2016.36.2.81
[14]
Muller, N., Lorenz, I., Langguth, B. and Weisz, N. (2013) rTMS Induced Tinnitus Relief Is Related to an Increase in Auditory Cortical Alpha Activity. PLoS ONE, 8, e55557. https://doi.org/10.1371/journal.pone.0055557
[15]
Adjamian, P., Hall, D.A., Palmer, A.R., Allan, T.W. and Langers, D.R.M. (2014) Neuroanatomical Abnormalities in Chronic Tinnitus in the Human Brain. Neuroscience & Biobehavioral Reviews, 45, 119-133. https://doi.org/10.1016/j.neubiorev.2014.05.013
[16]
Bhatt, J.M., Lin, H.W. and Bhattacharyya, N. (2016) Prevalence, Severity, Exposures, and Treatment Patterns of Tinnitus in the United States. JAMA Otolaryngology—Head & Neck Surgery, 142, 959-965. https://doi.org/10.1001/jamaoto.2016.1700
[17]
Coles, R.R. (1984) Epidemiology of Tinnitus: (1) Prevalence. Journal of Laryngology and Otology. Supplement, 9, 7-15. https://doi.org/10.1017/S1755146300090041
[18]
Bauch, C.D., Lynn, S.G., Williams, D.E., Mellon, M.W. and Weaver, A.L. (2003) Tinnitus Impact: Three Different Measurement Tools. Journal of the American Academy of Audiology, 14, 181-187. https://doi.org/10.1055/s-0040-1715725
[19]
Ramassamy, C., Longpré, F. and Christen, Y. (2007) Ginkgo Biloba Extract (EGb 761) in Alzheimer’s Disease: Is There Any Evidence? Current Alzheimer Research, 4, 253-262. https://doi.org/10.2174/156720507781077304
[20]
Mahadevan, S. and Park, Y. (2008) Multifaceted Therapeutic Benefits of Ginkgo biloba L.: Chemistry, Efficacy, Safety, and Uses. Journal of Food Science, 73, R14-R19. https://doi.org/10.1111/j.1750-3841.2007.00597.x
[21]
Spiegel, R., Kalla, R., Mantokoudis, G., Maire, R., Mueller, H., Hoerr, R., et al. (2018) Ginkgo biloba Extract EGb 761(®) Alleviates Neurosensory Symptoms in Patients with Dementia: A Meta-Analysis of Treatment Effects on Tinnitus and Dizziness in Randomized, Placebo-Controlled Trials. Clinical Interventions in Aging, 13, 1121-1127. https://doi.org/10.2147/CIA.S157877
[22]
Woelk, H., Arnoldt, K.H., Kieser, M. and Hoerr, R. (2007) Ginkgo biloba Special Extract EGb 761® in Generalized Anxiety Disorder and Adjustment Disorder with Anxious Mood: A Randomized, Double-Blind, Placebo-Controlled Trial. Journal of Psychiatric Research, 41, 472-480. https://doi.org/10.1016/j.jpsychires.2006.05.004
[23]
Chan, P.-C., Xia, Q. and Fu, P.P. (2007) Ginkgo biloba Leave Extract: Biological, Medicinal, and Toxicological Effects. Journal of Environmental Science and Health, Part C, 25, 211-244. https://doi.org/10.1080/10590500701569414
[24]
European Medicines Agency, Committee on Herbal Medicinal Products (HMPC) (2014) Assessment Report on Ginkgo biloba L., Folium. https://www.ema.europa.eu/en/documents/herbal-report/final-assessment-report-ginkgo-biloba-l-folium_en.pdf
[25]
European Medicines Agency (EMA). (2015) Overview of Comments Received on European Union Herbal Monograph on Ginkgo biloba L., Folium 2015. https://www.ema.europa.eu/en/documents/herbal-comments/final-overview-comments-received-european-union-herbal-monograph-ginkgo-biloba-l-folium_en.pdf
[26]
Khan, S. and Chang, R. (2013) Anatomy of the Vestibular System: A Review. NeuroRehabilitation, 32, 437-443. https://doi.org/10.3233/NRE-130866
[27]
Strupp, M., Dlugaiczyk, J., Ertl-Wagner, B.B., Rujescu, D., Westhofen, M. and Dieterich, M. (2020) Vestibular Disorders. Deutsches Ärzteblatt International, 117, 300-310. https://doi.org/10.3238/arztebl.2020.0300
[28]
Strupp, M., Arbusow, V., Maag, K.P., Gall, C. and Brandt, T. (1998) Vestibular Exercises Improve Central Vestibulospinal Compensation after Vestibular Neuritis. Neurology, 51, 838-844. https://doi.org/10.1212/WNL.51.3.838
[29]
Pajor, A.M., Ormezowska, E.A. and Jozefowicz-Korczynska, M. (2013) The Impact of Co-Morbid Factors on the Psychological Outcome of Tinnitus Patients. European Archives of Oto-Rhino-Laryngology, 270, 881-888. https://doi.org/10.1007/s00405-012-2079-3
[30]
Swain, S.K., Nayak, S., Ravan, J.R. and Sahu, M.C. (2016) Tinnitus and Its Current Treatment—Still an Enigma in Medicine. Journal of the Formosan Medical Association, 115, 139-144. https://doi.org/10.1016/j.jfma.2015.11.011
[31]
Mazurek, B., Stöver, T., Haupt, H., Gross, J. and Szczepek, A. (2007) The Role of Cochlear Neurotransmitters in Tinnitus. HNO, 55, 964-971. https://doi.org/10.1007/s00106-007-1624-7
[32]
Furman, A.C., Kujawa, S.G. and Liberman, M.C. (2013) Noise-Induced Cochlear Neuropathy Is Selective for Fibers with Low Spontaneous Rates. Journal of Neurophysiology, 110, 577-586. https://doi.org/10.1152/jn.00164.2013
[33]
Liberman, M.C. (2017) Noise-Induced and Age-Related Hearing Loss: New Perspectives and Potential Therapies. F1000Research, 6, 927. https://doi.org/10.12688/f1000research.11310.1
[34]
Barnea, G., Attias, J., Gold, S. and Shahar, A. (1990) Tinnitus with Normal Hearing Sensitivity: Extended High-Frequency Audiometry and Auditory-Nerve Brain-Ste-m-Evoked Responses. Audiology, 29, 36-45. https://doi.org/10.3109/00206099009081644
[35]
Baguley, D.M., McFerran, D. and Hall, D.A. (2013) Tinnitus. The Lancet (London, England), 382, 1600-1607. https://doi.org/10.1016/S0140-6736(13)60142-7
[36]
Jastreboff, P.J. (1990) Phantom Auditory Perception (Tinnitus): Mechanisms of Generation and Perception. Neuroscience Research, 8, 221-254. https://doi.org/10.1016/0168-0102(90)90031-9
[37]
Phillips, J.S. and McFerran, D. (2010) Neurophysiological Model-Based Treatments for Tinnitus. Cochrane Database of Systematic Reviews, No. 1, CD008248. https://doi.org/10.1002/14651858.CD008248
[38]
De Ridder, D., Elgoyhen, A.B., Romo, R. and Langguth, B. (2011) Phantom Percepts: Tinnitus and Pain as Persisting Aversive Memory Networks. Proceedings of the National Academy of Sciences of the United States of America, 108, 8075-8080. https://doi.org/10.1073/pnas.1018466108
[39]
Sedley, W., Friston, K.J., Gander, P.E., Kumar, S. and Griffiths, T.D. (2016) An Integrative Tinnitus Model Based on Sensory Precision. Trends in Neurosciences, 39, 799-812. https://doi.org/10.1016/j.tins.2016.10.004
[40]
DeFeudis, F. (1998) Ginkgo biloba Extract (EGb 761®). From Chemistry to the Clinic. Ullstein Medical, Wiesbaden.
[41]
Hamann, K.F. (2007) Ginkgo Special Extract EGb 761® in Vertigo: A Systematic Review of Randomised, Double-Blind, Placebo-Controlled Clinical Trials. The Internet Journal of Otorhinolaryngology, 7, 1-6. https://doi.org/10.5580/639
[42]
Lacour, M., Ez-Zaher, L. and Raymond, J. (1991) Plasticity Mechanisms in Vestibular Compensation in the Cat Are Improved by an Extract of Ginkgo biloba (EGb 761). Pharmacology Biochemistry and Behavior, 40, 367-379. https://doi.org/10.1016/0091-3057(91)90568-M
[43]
Maclennan, K., Smith, P.F. and Darlington, C.L. (1995) Ginkgolide B Accelerates Vestibular Compensation of Spontaneous Ocular Nystagmus in Guinea Pig Following Unilateral Labyrinthectomy. Experimental Neurology, 131, 273-278. https://doi.org/10.1016/0014-4886(95)90049-7
[44]
Tighilet, B., Leonard, J. and Lacour, M. (1995) Betahistine Dihydrochloride Treatment Facilitates Vestibular Compensation in the Cat. Journal of Vestibular Research, 5, 53-66. https://doi.org/10.1016/0957-4271(94)00023-U
[45]
Yabe, T., Chat, M., Malherbe, E. and Vidal, P.P. (1992) Effects of Ginkgo biloba Extract (EGb 761) on the Guinea Pig Vestibular System. Pharmacology Biochemistry and Behavior, 42, 595-604. https://doi.org/10.1016/0091-3057(92)90004-Y
[46]
Denise, P. and Bustany, P. (1989) The Effect of Extract of Ginkgo biloba (EGb 761®) on Central Compensation of a Total Unilateral Peripheral Vestibular Deficit in the Rat. In: Lacour, M., Toupet, M., Denise, P. and Christen, Y., Eds., Vestibular Compensation: Facts, Theories and Clinical Perspectives, Elsevier, Paris, 201-208.
[47]
Bustany, P., Denise, P., Pottier, M. and Moulin, M. (1992) Brain Protein Synthesis after Unilateral Labyrinthectomy: Natural One Month and EGb 761® Treatment Effect. In: Christen, Y., Costentin, J. and Lacour, M., Eds., Effects of Ginkgo biloba Extract on the Central Nervous System, Elsevier, Paris, 57-74.
[48]
Abdel-Kader, R., Hauptmann, S., Keil, U., Scherping, I., Leuner, K., Eckert, A., et al. (2007) Stabilization of Mitochondrial Function by Ginkgo biloba Extract (EGb 761). Pharmacological Research, 56, 493-502. https://doi.org/10.1016/j.phrs.2007.09.011
[49]
Eckert, A., Keil, U., Scherping, I., Hauptmann, S. and Muller, W.E. (2005) Stabilization of Mitochondrial Membrane Potential and Improvement of Neuronal Energy Metabolism by Ginkgo biloba Extract EGb 761. Annals of the New York Academy of Sciences, 1056, 474-485. https://doi.org/10.1196/annals.1352.023
[50]
DeFeudis, F.V. and Drieu, K. (2004) “Stress-Alleviating” and “Vigilance-Enhancing” Actions of Ginkgo biloba Extract (EGb 761). Drug Development Research, 62, 1-25. https://doi.org/10.1002/ddr.10351
[51]
Wu, Y., Li, S., Cui, W., Zu, X., Du, J. and Wang, F. (2008) Ginkgo biloba Extract Improves Coronary Blood Flow in Healthy Elderly Adults: Role of Endothelium-Dependent Vasodilation. Phytomedicine, 15, 164-169. https://doi.org/10.1016/j.phymed.2007.12.002
[52]
Müller, W.E. and Chatterjee, S.S. (2003) Cognitive and Other Behavioral Effects of EGb 761 in Animal Models. Pharmacopsychiatry, 36, S24-S31. https://doi.org/10.1055/s-2003-40459
[53]
Luo, Y., Smith, J.V., Paramasivam, V., Burdick, A., Curry, K.J., Buford, J.P., et al. (2002) Inhibition of Amyloid-Beta Aggregation and Caspase-3 Activation by the Ginkgo biloba Extract EGb761. Proceedings of the National Academy of Sciences of the United States of America, 99, 12197-121202. https://doi.org/10.1073/pnas.182425199
[54]
Massieu, L., Morán, J. and Christen, Y. (2004) Effect of Ginkgo biloba (EGb 761) on Staurosporine-Induced Neuronal Death and Caspase Activity in Cortical Cultured neurons. Brain Research, 1002, 76-85. https://doi.org/10.1016/j.brainres.2003.12.018
[55]
Schindowski, K., Leutner, S., Kressmann, S., Eckert, A. and Müller, W.E. (2001) Age-Related Increase of Oxidative Stress-Induced Apoptosis in Mice Prevention by Ginkgo biloba Extract (EGb761). Journal of Neural Transmission (Vienna), 108, 969-978. https://doi.org/10.1007/s007020170016
[56]
Wu, Y., Wu, Z., Butko, P., Christen, Y., Lambert, M.P., Klein, W.L., et al. (2006) Amyloid-Beta-Induced Pathological Behaviors Are Suppressed by Ginkgo biloba Extract EGb 761 and Ginkgolides in Transgenic Caenorhabditis elegans. Journal of Neuroscience, 26, 13102-13113. https://doi.org/10.1523/JNEUROSCI.3448-06.2006
[57]
Yang, T.H., Young, Y.H. and Liu, S.H. (2011) EGb 761 (Ginkgo biloba) Protects Cochlear Hair Cells against Ototoxicity Induced by Gentamicin via Reducing Reactive Oxygen Species and Nitric Oxide-Related Apoptosis. Journal of Nutritional Biochemistry, 22, 886-894. https://doi.org/10.1016/j.jnutbio.2010.08.009
[58]
Didier, A., Droy-Lefaix, M.T., Aurousseau, C. and Cazals, Y. (1996) Effects of Ginkgo biloba Extract (EGb 761) on Cochlear Vasculature in the Guinea Pig: Morphometric Measurements and Laser Doppler Flowmetry. European Archives of Oto-Rhino-Laryngology, 253, 25-30. https://doi.org/10.1007/BF00176698
[59]
Smith, G.S., Romanelli-Gobbi, M., Gray-Karagrigoriou, E. and Artz, G.J. (2013) Complementary and Integrative Treatments: Tinnitus. Otolaryngologic Clinics of North America, 46, 389-408. https://doi.org/10.1016/j.otc.2013.02.005
[60]
Sereda, M., Xia, J., Scutt, P., Hilton, M.P., El Refaie, A. and Hoare, D.J. (2019) Ginkgo biloba for Tinnitus. Cochrane Database of Systematic Reviews, No. 12, CD013514. https://doi.org/10.1002/14651858.CD013514
[61]
Jastreboff, P.J., Zhou, S., Jastreboff, M.M., Kwapisz, U. and Gryczynska, U. (1997) Attenuation of Salicylate-Induced Tinnitus by Ginkgo biloba Extract in Rats. Audiology and Neurotology, 2, 197-212. https://doi.org/10.1159/000259244
[62]
Krauss, P., Tziridis, K., Buerbank, S., Schilling, A. and Schulze, H. (2016) Therapeutic Value of Ginkgo biloba Extract EGb 761(R) in an Animal Model (Meriones unguiculatus) for Noise Trauma Induced Hearing Loss and Tinnitus. PLoS ONE, 11, e0157574. https://doi.org/10.1371/journal.pone.0157574
[63]
Tian, C.J., Kim, Y.J., Kim, S.W., Lim, H.J., Kim, Y.S. and Choung, Y.H. (2013) A Combination of Cilostazol and Ginkgo biloba Extract Protects against Cisplatin-Induced Cochleo-Vestibular Dysfunction by Inhibiting the Mitochondrial Apoptotic and ERK Pathways. Cell Death & Disease, 4, e509. https://doi.org/10.1038/cddis.2013.33
[64]
Tziridis, K., Korn, S., Ahlf, S. and Schulze, H. (2014) Protective Effects of Ginkgo biloba Extract EGb 761 against Noise Trauma-Induced Hearing Loss and Tinnitus Development. Neural Plasticity, 2014, Article ID: 427298. https://doi.org/10.1155/2014/427298
[65]
(ESCOP) ESCoP (2003) Gingko Folium. ESCOP Monograph: The Scientific Foundation for Herbal Medicinal Products. 2nd Edition, Thieme, Exeter, 178-210.
[66]
Sokolova, L., Hoerr, R. and Mishchenko, T. (2014) Treatment of Vertigo: A Randomized, Double-Blind Trial Comparing Efficacy and Safety of Ginkgo biloba Extract EGb 761 and Betahistine. International Journal of Otolaryngology, 2014, Article ID: 682439. https://doi.org/10.1155/2014/682439
[67]
Cesarani, A., Meloni, F., Alpini, D., Barozzi, S., Verderio, L. and Boscani, P.F. (1998) Ginkgo biloba (EGb 761) in the Treatment of Equilibrium Disorders. Advances in Therapy, 15, 291-304.
[68]
Haguenauer, J.P., Cantenot, F., Koskas, H. and Pierart, H. (1986) Treatment of Equilibrium Disorders with Ginkgo biloba Extract. A Multicenter Double-Blind Drug vs. Placebo Study. La Presse médicale, 15, 1569-1572.
[69]
Claussen, C.F. and Kirtane, M.V. (1985) Randomisierte Doppelblindstudie zur Wirkung von Extractum Gingko biloba bei Schwindel und Gangunsicherheit des älteren Menschen. Springer, Berlin. https://doi.org/10.1007/978-3-642-70035-4_4
[70]
European Medicines Agency (EMA) (2014) Assessment Report of Ginkgo biloba L., Folium. https://www.ema.europa.eu/en/documents/herbal-report/draft-assessment-report-ginkgo-biloba-l-folium_en.pdf
[71]
Halama, P., Bartsch, G. and Meng, G. (1988) Disorders of Brain Performance of Vascular Origin. Randomized Double-Blind Study of the Effectiveness of Ginkgo biloba Extract. Fortschritte der Medizin, 106, 408-412.
[72]
Morgenstern, C. and Biermann, E. (2002) The Efficacy of Ginkgo Special Extract EGb 761 in Patients with Tinnitus. International Journal of Clinical Pharmacology and Therapeutics, 40, 188-197. https://doi.org/10.5414/CPP40188
[73]
Prochazkova, K., Sejna, I., Skutil, J. and Hahn, A. (2018) Ginkgo biloba Extract EGb 761((R)) versus Pentoxifylline in Chronic Tinnitus: A Randomized, Double-Blind Clinical Trial. International Journal of Clinical Pharmacy, 40, 1335-1341. https://doi.org/10.1007/s11096-018-0654-4
[74]
Radunz, C.L., Okuyama, C.E., Branco-Barreiro, F.C.A., Pereira, R.M.S. and Diniz, S.N. (2019) Clinical Randomized Trial Study of Hearing Aids Effectiveness in Association with Ginkgo biloba Extract (EGb 761) on Tinnitus Improvement. Brazilian Journal of Otorhinolaryngology, 86, 734-742. https://doi.org/10.1016/j.bjorl.2019.05.003
[75]
Morgenstern, V.C. and Biermann, E. (1997) Long-Term Tinnitus Therapy with Ginkgo Special Extract EGb 761. Fortschritte der Medizin, 115, 57-58. (In German)
[76]
Meyer, B. (1986) A Multicentre, Randomized, Double-Blind Drug versus Placebo Study of Ginkgo biloba Extract in the Treatment of Tinnitus. La Presse médicale, 15, 1562-1564. (In French)
[77]
Drew, S. and Davies, E. (2001) Effectiveness of Ginkgo biloba in Treating Tinnitus: Double Blind, Placebo Controlled Trial. BMJ (Clinical Research ed), 322, 73. https://doi.org/10.1136/bmj.322.7278.73
[78]
Polanski, J.F., Soares, A.D. and de Mendonça Cruz, O.L. (2016) Antioxidant Therapy in the Elderly with Tinnitus. Brazilian Journal of Otorhinolaryngology, 82, 269-274. https://doi.org/10.1016/j.bjorl.2015.04.016
[79]
Kleijnen, J. and Knipschild, P. (1992) Ginkgo biloba for Cerebral Insufficiency. British Journal of Clinical Pharmacology, 34, 352-358. https://doi.org/10.1111/j.1365-2125.1992.tb05642.x
[80]
Rai, G.S., Shovlin, C. and Wesnes, K.A. (1991) A Double-Blind, Placebo Controlled Study of Ginkgo biloba Extract (“Tanakan”) in Elderly Outpatients with Mild to Moderate Memory Impairment. Current Medical Research and Opinion, 12, 350-355. https://doi.org/10.1185/03007999109111504
[81]
Janssen, I.M., Sturtz, S., Skipka, G., Zentner, A., Velasco Garrido, M. and Busse, R. (2010) Ginkgo biloba in Alzheimer’s Disease: A Systematic Review. Wiener Medizinische Wochenschrift, 160, 539-546. https://doi.org/10.1007/s10354-010-0844-8
[82]
Kanowski, S., Herrmann, W.M., Stephan, K., Wierich, W. and Hörr, R. (1996) Proof of Efficacy of the Ginkgo biloba Special Extract EGb 761 in Outpatients Suffering from Mild to Moderate Primary Degenerative Dementia of the Alzheimer Type or Multi-Infarct Dementia. Pharmacopsychiatry, 29, 47-56. https://doi.org/10.1055/s-2007-979544
[83]
Dai, C.-X., Hu, C.-C., Shang, Y.-S. and Xie, J. (2018) Role of Ginkgo biloba Extract as an Adjunctive Treatment of Elderly Patients with Depression and on the Expression of Serum S100B. Medicine (Baltimore), 97, e12421-e. https://doi.org/10.1097/MD.0000000000012421
[84]
Schneider, B. (1992) Ginkgo biloba Extract in Peripheral Arterial Diseases. Meta-Analysis of Controlled Clinical Studies. Arzneimittelforschung, 42, 428-436.
[85]
Jung, F., Mrowietz, C., Kiesewetter, H. and Wenzel, E. (1990) Effect of Ginkgo biloba on Fluidity of Blood and Peripheral Microcirculation in Volunteers. Arzneimittelforschung, 40, 589-593.
[86]
Janssens, D., Michiels, C., Guillaume, G., Cuisinier, B., Louagie, Y. and Remacle, J. (1999) Increase in Circulating Endothelial Cells in Patients with Primary Chronic Venous Insufficiency: Protective Effect of Ginkor Fort in a Randomized Double-Blind, Placebo-Controlled Clinical Trial. Journal of Cardiovascular Pharmacology, 33, 7-11. https://doi.org/10.1097/00005344-199901000-00002
[87]
Tang, Y., Xu, Y., Xiong, S., Ni, W., Chen, S., Gao, B., et al. (2007) The Effect of Ginkgo biloba Extract on the Expression of PKCα in the Inflammatory Cells and the Level of IL-5 in Induced Sputum of Asthmatic Patients. Journal of Huazhong University of Science and Technology, 27, 375-380. https://doi.org/10.1007/s11596-007-0407-4
[88]
Li, M.H., Zhang, H.L. and Yang, B.Y. (1997) Effects of Ginkgo Leave Concentrated Oral Liquor in Treating Asthma. Chinese Journal of Integrated Traditional and Western Medicine, 17, 216-218.
[89]
European Parliament (2017) Complementary and Alternative Therapies for Patients Today and Tomorrow. https://www.europarl.europa.eu/cmsdata/135562/ENVI%202017-10%20WS%20CAM%20%20PE%20614.180%20(Publication).pdf
[90]
von Boetticher, A. (2011) Ginkgo biloba Extract in the Treatment of Tinnitus: A Systematic Review. Neuropsychiatry Disease and Treatment, 7, 441-447. https://doi.org/10.2147/NDT.S22793
[91]
Napryeyenko, O. and Borzenko, I. (2007) Ginkgo biloba Special Extract in Dementia with Neuropsychiatric Features. A Randomised, Placebo-Controlled, Double-Blind Clinical Trial. Arzneimittelforschung, 57, 4-11. https://doi.org/10.1055/s-0031-1296579
[92]
Nikolova, G., Yancheva, S., Raychev, I. and Hoerr, R. (2013) PLAGIN Study Group Ginkgo biloba Extract in Dementia: A 22-Week Randomised, Placebo-Controlled, Double-Blind Trial. Bulgarian Neurology, 14, 139-143.
[93]
Ihl, R., Bachinskaya, N., Korczyn, A.D., Vakhapova, V., Tribanek, M., Hoerr, R., et al. (2011) Efficacy and Safety of a Once-Daily Formulation of Ginkgo biloba Extract EGb 761 in Dementia with Neuropsychiatric Features: A Randomized Controlled Trial. International Journal of Geriatric Psychiatry, 26, 1186-1194. https://doi.org/10.1002/gps.2662
[94]
Schneider, L.S., DeKosky, S.T., Farlow, M.R., Tariot, P.N., Hoerr, R. and Kieser, M. (2005) A Randomized, Double-Blind, Placebo-Controlled Trial of Two Doses of Ginkgo biloba Extract in Dementia of the Alzheimer’s Type. Current Alzheimer Research, 2, 541-551. https://doi.org/10.2174/156720505774932287
[95]
Herrschaft, H., Nacu, A., Likhachev, S., Sholomov, I., Hoerr, R. and Schlaefke, S. (2012) Ginkgo biloba Extract EGb 761(®) in Dementia with Neuropsychiatric Features: A Randomised, Placebo-Controlled Trial to Confirm the Efficacy and Safety of a daily Dose of 240 mg. Journal of Psychiatric Research, 46, 716-723. https://doi.org/10.1016/j.jpsychires.2012.03.003
[96]
Lindner, M., Gosewisch, A., Eilles, E., Branner, C., Krämer, A., Oos, R., et al. (2019) Ginkgo biloba Extract EGb 761 Improves Vestibular Compensation and Modulates Cerebral Vestibular Networks in the Rat. Frontiers in Neurology, 10, 147. https://doi.org/10.3389/fneur.2019.00147
[97]
Hamann, K.F. (2006) Special Ginkgo Extract in Cases of Vertigo: A Systematic Review of Randomised, Double-Blind, Placebo Controlled Clinical Examinations. HNO, 55, 258-263. https://doi.org/10.1007/s00106-006-1440-5
[98]
Ernst, E. (2001) Marketing Studies and Scientific Research Must Be Distinct. BMJ (Clinical Research ed), 322, 1249. https://doi.org/10.1136/bmj.322.7296.1249
[99]
Rejali, D., Sivakumar, A. and Balaji, N. (2004) Ginkgo biloba Does Not Benefit Patients with Tinnitus: A Randomized Placebo-Controlled Double-Blind Trial and Meta-Analysis of Randomized Trials. Clinical Otolaryngology and Allied Sciences, 29, 226-231. https://doi.org/10.1111/j.1365-2273.2004.00814.x
[100]
Food and Drug Administration (FDA). Vertigo Medications 2000-2020. https://www.drugs.com/search.php?searchterm=VERTIGO
[101]
European Medicines Agency (EMA). Trimetazidine 2012. https://www.ema.europa.eu/en/medicines/human/referrals/trimetazidine
[102]
McFerran, D.J., Stockdale, D., Holme, R., Large, C.H. and Baguley, D.M. (2019) Why Is There No Cure for Tinnitus? Frontiers in Neuroscience, 13, 802. https://doi.org/10.3389/fnins.2019.00802
[103]
Strupp, M. and Brandt, T. (2008) Diagnosis and Treatment of Vertigo and Dizziness. Deutsches Ärzteblatt International, 105, 173-180. https://doi.org/10.3238/arztebl.2008.0173
[104]
Cima, R.F.F., Mazurek, B., Haider, H., Kikidis, D., Lapira, A., Noreña, A., et al. (2019) A Multidisciplinary European Guideline for Tinnitus: Diagnostics, Assessment, and Treatment. HNO, 67, 10-42. https://doi.org/10.1007/s00106-019-0633-7
[105]
Cima, R.F., Maes, I.H., Joore, M.A., Scheyen, D.J., El Refaie, A., Baguley, D.M., et al. (2012) Specialised Treatment Based on Cognitive Behaviour Therapy versus Usual Care for Tinnitus: A Randomised Controlled Trial. The Lancet, 379, 1951-1959. https://doi.org/10.1016/S0140-6736(12)60469-3
[106]
Pantev, C., Wollbrink, A., Roberts, L.E., Engelien, A. and Lutkenhoner, B. (1999) Short-Term Plasticity of the Human Auditory Cortex. Brain Research, 842, 192-199. https://doi.org/10.1016/S0006-8993(99)01835-1
[107]
Strauss, D.J., Corona-Strauss, F.I., Seidler, H., Haab, L. and Hannemann, R. (2017) Notched Environmental Sounds: A New Hearing Aid-Supported Tinnitus Treatment Evaluated in 20 Patients. Clinical Otolaryngology, 42, 172-175. https://doi.org/10.1111/coa.12575
[108]
Tyler, R., Cacace, A., Stocking, C., Tarver, B., Engineer, N., Martin, J., et al. (2017) Vagus Nerve Stimulation Paired with Tones for the Treatment of Tinnitus: A Prospective Randomized Double-Blind Controlled Pilot Study in Humans. Scientific Reports, 7, Article No. 11960. https://doi.org/10.1038/s41598-017-12178-w
[109]
Guntensperger, D., Thuring, C., Kleinjung, T., Neff, P. and Meyer, M. (2019) Investigating the Efficacy of an Individualized Alpha/Delta Neurofeedback Protocol in the Treatment of Chronic Tinnitus. Neural Plasticity, 2019, Article ID: 3540898. https://doi.org/10.1155/2019/3540898
[110]
Cacace, A.T. (2003) Expanding the Biological Basis of Tinnitus: Cross-Modal Origins and the Role of Neuroplasticity. Hearing Research, 175, 112-132. https://doi.org/10.1016/S0378-5955(02)00717-7
[111]
Rajagopalan, A., Jinu, K.V., Sailesh, K.S., Mishra, S., Reddy, U.K. and Mukkadan, J.K. (2017) Understanding the Links between Vestibular and Limbic Systems Regulating Emotions. Journal of Natural Science, Biology and Medicine, 8, 11-15. https://doi.org/10.4103/0976-9668.198350
[112]
Smith, J.V. and Luo, Y. (2004) Studies on Molecular Mechanisms of Ginkgo biloba Extract. Applied Microbiology and Biotechnology, 64, 465-472. https://doi.org/10.1007/s00253-003-1527-9
[113]
Langguth, B., Kreuzer, P.M., Kleinjung, T. and De Ridder, D. (2013) Tinnitus: Causes and Clinical Management. The Lancet Neurology, 12, 920-930. https://doi.org/10.1016/S1474-4422(13)70160-1
[114]
Moher, D., Liberati, A., Tetzlaff, J., Altman, D.G. and The, P.G. (2009) Preferred Reporting Items for Systematic Reviews and Meta-Analyses: The PRISMA Statement. PLOS Medicine, 6, e1000097. https://doi.org/10.1371/journal.pmed.1000097