Summary of Clinical Studies for Tinnitus

By Barry Keate
Barry Keate, has lived with tinnitus over 40 years and has published 150+ research articles on numerous aspects of tinnitus. He is an expert on the condition and a well-known advocate for those with tinnitus.

There are many products for tinnitus advertised on the internet, in magazines, and on late night television. Most of these products promise instant gratification, miracle cures and complete cessation of tinnitus sounds. So how is the cautious consumer supposed to navigate the marketing hype of these competing products and find out which ones are truly helpful?

I suggest a look at the science behind the products to find out what medical researchers are saying. It is also very important to know that there is no cure for tinnitus. If there was a cure, it would spread world-wide in no time and doctors would be joyfully prescribing it.

The great majority of competing products are advertised as homeopathic products. Homeopathy is an offshoot of 19th century medicine. The basic premise is “Like cures like,” meaning that if you take a poison that will make you sick and dilute it to the point where there is hardly any poison to be found, it will cure you of the same sickness.

While there remain many adherents of homeopathy for general health, there is not a shred of scientific evidence that homeopathy has any affect on tinnitus. There has not been a single clinical study conducted on homeopathy and tinnitus because there are no researchers who believe it to be effective.

On the other hand, there are 35 positive clinical studies, and only one negative study, on the effects of the ingredients used in Arches Tinnitus Formula™ on tinnitus. These ingredients are Ginkgo Biloba Extract, zinc picolinate and deodorized garlic. These studies have been conducted by scientists around the world and span at least the last 20 years. They are almost universally in favor of these ingredients as a viable treatment option for tinnitus.

There is a lot of dry and detailed information in these pages. For the casual reader, I recommend reading the Group Summation at the beginning of each category. For those who wish to dig deeper, all the details are right here.

Ginkgo Biloba Extract and Tinnitus

Note: The Term GBE is used throughout this text to indicate standardized Ginkgo Biloba Extract.

Group Summation

This grouping includes the recommendation of the German Commission E. Similar to our FDA, the Commission E is a panel of noted physicians and scientists having expertise in herbal medicine and related disciplines. The Commission E recommends GBE for the treatment of tinnitus.

This grouping also includes 15 double-blind, placebo controlled studies with a total of 1,066 patients. All studies showed statistically significant improvement using GBE with one exception; a single study of 60 patients showed the same improvement with GBE as with nicergoline, a vaso-active medication that increases arterial blood flow in the brain.

This grouping also includes 16 open studies involving 4,581 patients. All studies were positive regarding GBE for tinnitus with one exception; a single study of 23 patients showed no improvement.

This grouping also includes one study of an animal model of tinnitus. Administration of GBE resulted in a significant decrease of the behavioral manifestation of tinnitus.

Individual Studies

1 – The German Commission E recommends GBE for tinnitus in the dosage of 120-240 mg taken 2 or 3 times daily.1

2 – N. Holstein conducted a literature survey of 19 clinical trials investigating the effects of tinnitus treatment with GBE.2 Eight of the studies were controlled with placebo or reference medications and eleven did not have reference groups.

The eight controlled studies included 687 patients. Those in placebo controlled studies numbered 348 patients. Those who controlled with nicergoline, a vasodilator, numbered 319 and those who controlled with cinnarizine, an antihistamine, numbered 20.

One study of 60 patients using nicergoline as a control found improvement in both groups with no difference between them. The other seven studies showed clear improvement with ginkgo over placebo or other referenced medication including one study of 259 patients who controlled with nicergoline.

The eleven studies that were open included 5 that were multi-center. The total number of patients was 3,244. One study with 23 patients using a low dosage of 120 mg showed no improvement. All other studies showed improvement varying from a low of 18 out of 68 patients to a high of 82% good or very good efficacy.

3 – B. Meyer conducted a multicenter study of 103 tinnitus patients using double-blind, placebo control.3 The GBE treatment improved the condition of all the tinnitus patients, irrespective of the prognostic factor.

4 – C. Morganstern and E. Biermann conducted a study on 60 tinnitus patients.4 They underwent 10 days of in-patient infusion treatment after which they were randomized to double-blind oral outpatient treatment with either GBE or placebo. They concluded a combination of infusion therapy followed by oral administration of GBE appears to be effective and safe in alleviating symptoms associated with tinnitus.

5 – Abraham Shulman, Claus-F. Claussen and colleagues conducted a clinical trial on 20 tinnitus patients who also suffered other vestibular disturbances such as vertigo and nausea.5 They concluded GBE influenced excitatory states of the vestibuloacoustic system and is effective in the treatment of central excitatory tinnitus.

6 – Pawel Jastreboff and associates conducted a trial on an animal model of tinnitus.6 Tinnitus was induced by daily administration of sodium salicylate. Administration of GBE resulted in a statistically significant decrease of the behavioral manifestation of tinnitus.

7 – Claus-F Claussen conducted a study on 50 patients in a Berlin ENT practice suffering from dizziness and concomitant tinnitus.7 A definite improvement in the dizziness and tinnitus symptoms of the 50 patients treated with GBE was observed. However, patients who were not treated and received follow-up examinations for diagnostic purposes alone showed only a minor spontaneous remission.

8 – An open Spanish study of GBE for 70 patients with cochlea-vestibular pathologies, including tinnitus, was conducted in 1995.8 After six months of Ginkgo biloba therapy, statistically significant changes regarding the decrease of intensity of tinnitus and vertigo were confirmed.

9 – An open Brazilian study was conducted to determine the effectiveness of GBE on 885 patients with cerebral vascular insufficiency.9 At the completion of the 60 day study there was statistically significant improvement of symptoms related to changes in the internal ear including dizziness, disturbed equilibrium, and tinnitus.

10 – Enrique Gomez conducted a prospective, open and multicenter trial to test the efficacy and safety of GBE in the treatment of memory loss, vertigo and tinnitus.10 Two hundred two patients were studied. Most of the patients with tinnitus mentioned the absence or significant reduction of the symptom.

11 – G. Vorberg conducted a long-term study of GBE on chronic cerebral insufficiency in geriatric patients.11 One hundred twelve patients were treated in an open, one-year trial in several German test centers. Results showed a statistically significant regression of major symptoms of vertigo, headache and tinnitus.

12 – P. Halama and associates conducted a placebo controlled, randomized, double-blind trial with GBE on 40 outpatients with cerebrovascular insufficiency.12 Superior effects were shown in the symptoms of headaches and tinnitus.

13 – F. Eckmann and H. Schlag conducted a controlled, double-blind study to prove the efficacy of GBE in patients with cerebral insufficiency.13 A total of 50 patients were studied. After the treatment, tinnitus has been eliminated in the test drug group but could not be eliminated in the placebo group.

14 – An open study of 68 patients with hearing problems, including tinnitus, was conducted in France.14 Overall, 70% had very positive results with GBE while 13% had no improvement at all.

15 – P. Albernaz conducted a double-blind, placebo controlled study of 56 patients presenting with symptoms of labyrinthopathies including vertigo, hearing loss, nausea and tinnitus. 31.3% of those with tinnitus (n=16) became either asymptomatic or significantly improved following treatment with GBE.15

Ginkgo Biloba Extract and Hearing Loss

Group Summation

This grouping includes two double-blind, placebo controlled studies of 124 patients on GBE and sudden hearing loss and acute deafness. Conclusions showed greater recovery using GBE than placebo.

This grouping also includes 1 open study of 350 hearing impaired elderly people. Hearing improved in 82% of the patients and lasted from 5 to 7 years.

This grouping also includes two studies of GBE and hearing loss using an animal model. Animals were exposed to acoustic trauma or an ototoxic medication to damage hearing. Both studies showed GBE reduced damage.

Individual Studies

16 – Martin Burschka and associates conducted a randomized, double-blind study of GBE on 106 patients who had experienced unilateral idiopathic sudden hearing loss less than 10 days before study inclusion.16 They concluded that a dose-dependent recovery was significant and most respondents recovered completely.

17 – C. Dubreuil conducted a comparative study in 18 patients of GBE and nicergoline on acute cochlear deafness.17 At the end of the trial improvement was distinctly better in the Ginkgo biloba group.

18 – A study from the labs of the Dr. Willmar Schwabe Co in Karlsruhe, Germany was conducted on GBE treatment for hearing impaired elderly people.18 A total of 350 elderly patients with hearing loss were treated with GBE. Findings improved in 287 patients (82%). Of the 287 improved patients, 127 had a high degree of hearing loss. After five years, 92 of the 137 of the improved patients had better hearing than at the beginning of the trial. After 7 years, 63 of these 92 patients had better hearing than at the beginning.

19 – Strange and Benning conducted trials of an animal model to compare GBE and no treatment on laboratory guinea pigs who were subjected to acoustic noise trauma.19 They found a significant influence of the GBE in the sense of a reduction in acoustic damage to the cochlea of the guinea pigs.

20 – Fukaya and Sugano conducted trials of an animal model to compare GBE and no treatment on the mitigating effects of treatment with cisplatin, an ototoxic anti-tumor medication.20 They found elevation in the Cochlear nerve threshold values were significantly less when compared to the group treated with cisplatin without Ginkgo biloba.

Ginkgo Biloba Extract and Neuroprotection

Group Summation

This grouping contains two studies on an animal model to determine if GBE exhibits neuroprotective activities. Both showed that GBE protects against ischemia and had a potent inhibitory effect on glutamate release.

This grouping also includes two reviews of over 150 clinical studies relating to the neuroprotective effects of GBE. They conclude that GBE is neuroprotective.

Individual Studies

21 – K. Chandrasekaran and associates conducted trials on laboratory gerbils of the protective effect of bilobalide, a GBE component, against ischemic injury.21 They found oral administration of EGb 761 for 7 days before ischemia progressively protected CA1 neurons from death and from ischemia-induced reductions in COX III mRNA.

22 – JA Davies and associates conducted an animal study on laboratory animals to determine the effect of bilobalide, a GBE component, on neuroprotective activities.22 Bilobalide was shown to reduce glutamate and aspartate release. In addition, bilobalide had a very potent effect on glutamate release elicited by hypoxia/hypoglycemia-induced release from rat cortical slices. Bilobalide also decreased the frequency of y-aminobutyric acid (GABA) uptake inhibitor-induced depolarization in mouse cortical slices.

23 – B. Ahlemeyer and J. Krieglstein performed a review of over 100 clinical studies relating to the neuroprotective effects of GBE.23 They conclude that constituents of GBE have neuroprotective properties. PAF antagonism, free radical and NO scavenging, interaction with neurotransmitters and even induction of growth factors are possible mechanisms of action.

24 – Paul Smith and associates performed a review of over 50 clinical studies on the neuroprotective effect of various fractions of GBE. 24 They concluded there is sufficient experimental evidence to support the view that extracts of Ginkgo biloba have neuroprotective properties under conditions such as hypoxia/ischemia, seizure activity and peripheral nerve damage.

Ginkgo Biloba Extract and Bleeding Potential

Group Summation

This grouping includes three double-blind, placebo controlled studies involving 106 patients to determine whether GBE causes increased bleeding. Doses of 120 mg to 480 mg per day were used. The studies did not reveal any alteration of platelet function or coagulation, nor did they show any causal relationships between the use of GBE and hemorrhagic complications.

This grouping also includes one overview of 40 clinical studies conducted on GBE and the risk of hemorrhage. They concluded there was nothing in case history to indicate a risk potential for GBE.

Individual Studies

25 – C. Bal Dit Sollier and associates conducted a placebo-controlled double-blind study on 32 healthy male volunteers to evaluate the effect of three doses of GBE (120, 240 and 480 mg/day for 14 days) on hemostasis, coagulation and fibrinolysis.25 The study did not reveal any alteration of platelet function or coagulation.

26 – Kohler and associates conducted a crossover study on 50 healthy male volunteers to determine if there was a causal relationship between hemorrhagic complications and the intake of GBE.26 Among the 29 coagulation and bleeding parameters assessed, none showed any evidence of an inhibition of blood coagulation and platelet aggregation through GBE. Furthermore, the study did not reveal any evidence to substantiate a causal relationship between the administration of GBE and hemorrhagic complications.

27 – J. Juretzek, in a review article, described 40 clinical studies conducted on GBE and the risk of hemorrhage.27 In one study, a 52-week placebo-controlled double-blind study of 309 patients suffering from dementia, a subdural hematoma was observed with placebo, but not with ingestion of GBE. Another study showed even a dose of 600 mg did not change bleeding time and coagulation parameters. The conclusion was there is nothing in documented case reports to indicate a risk potential of GBE.

28 – J. Engelsen and associates conducted a double-blind, placebo controlled crossover study on 24 patients who were treated long-term with warfarin and also given GBE.28 INR was kept between 2.0 and 4.0 by appropriate adjustment of the warfarin dosage. Major bleedings or thromboembolic events were not observed.

Zinc and Tinnitus

Group Summation

This grouping includes one double-blind, placebo controlled study on 41 patients treated with zinc for tinnitus. Results were 46% of patients improved and subjective tinnitus decreased by 82%.

This grouping also includes three open studies of 174 patients treated with zinc for tinnitus. Results showed that zinc is involved in the generation of tinnitus and can be helpful in reducing it. In one study, 52% of patients were improved.

This grouping also includes a clinical vignette on zinc deficiency. The author concludes that chronic zinc deficiency contributes to presbycusis and zinc treatment can reduce it.

Individual Studies

29 – Arda and associates in Ankara, Turkey conducted a randomized, placebo-controlled study on 41 patients for effectiveness of zinc treatment for tinnitus.29 Clinically favorable progress was detected in 46% of patients given zinc. The severity of subjective tinnitus decreased in 82% of the patients receiving zinc.

30 – Ochi and associates studied 73 patients to determine if serum zinc levels affected hearing and tinnitus.30 There was a significant correlation between average hearing sensitivity and serum zinc level. Conclusions suggest that zinc is involved in the generation of tinnitus, especially in patients whose hearing is relatively normal.

31 – Ochia and associates conducted another study on 74 individuals by measuring serum zinc levels to determine who could be improved with zinc treatment.31 After zinc treatment, 10 patients showed significant improvement in tinnitus and 1 patient had no change.

32 – Gersdorff studied 27 patients with tinnitus and hypozincemia.32 Overall, 52% of patients experienced positive effects from zinc treatment.

33 – George Shambaugh, Jr. addressed zinc deficiency in a Clinical Vignette.33 He has determined that chronic deficiency of zinc probably induces some cases of presbycusis. Correcting the deficiency improves the clarity of hearing and arrests hearing deterioration.

Garlic and Plaque Formation

Group Summation

This grouping includes one open study on blood lipid levels of 23 patients. They show that garlic supplementation improves lipid profile and leads to reduction in blood pressure.

This grouping also includes one in vitro study on garlic and arteriosclerotic plaque formation. Garlic extract significantly inhibits the formation of plaque.

Individual Studies

34 – Durak and associates studied the effect of garlic supplementation on 23 subjects for blood lipid levels, antioxidant activity and blood pressure levels.34 They concluded that garlic extract supplementation improves blood lipid profile, strengthens blood antioxidant potential and causes significant reductions in systolic and diastolic blood pressures.

35 – Siegel and associates conducted in vitro experiments on how garlic affects arteriosclerotic nanoplaque formation and size.35 They concluded that garlic supplementation strongly inhibits the formation of nanoplaque and ultimately arteriosclerotic plaque generation.

Negative Ginkgo Biloba Study

In addition to the two small studies under Holstein, above, that did not show efficacy, a large double blind, placebo-controlled study did not show GBE to be effective in treating tinnitus.36 The Birmingham study was published in 2001 and included 978 patients. While the methodology, generally speaking, was appropriate, there were two serious flaws in the study.

1 – Only 150 mg of GBE was used daily, less than 1/3 the German Commission E recommended 480 mg. This is a serious flaw and is akin to treating any condition with 1/3 the effective dosage;

2 – The study was conducted entirely by postal questionnaire, with no personal interface with any health care provider. This leaves open the very real possibility of non-compliance by many participants.

The authors acknowledge this by saying, “A weakness of this approach, however, was that contact with participants was minimal and participants were probably provided with less support than offered in other trials.”

The authors expected this study to show improvement in cerebral insufficiency, which has been shown in many previous GBE trials. However, this trial did not show any improvement. This is an outcome that could have come about through an ineffective dosage and/or non-compliance on the part of many participants.

References:

1. 1 – The Complete Commission E Monographs: Therapeutic Guide to Herbal Medicine. Published July 19, 1994. American Botanical Council, Boston, MA. Edited by Mark Blumenthal.
2. 2 – Holstein, N. Ginkgo Special Extract EGb 761 in the Treatment of Tinnitus. Fortschr. Med. 118 (2000), p. 157-164.
3. 3 – Meyer, B. A multicenter Randomized Double-Blind Study of Ginkgo Biloba Extract Versus Placebo in the Treatment of Tinnitus. Press Med 1986 (in French), Sept. 25; 15(31):1562-4.
4. 4 – Morganstern, C. Biermann, E. The Efficacy of Ginkgo Special Extract EGb 761 in Patients with Tinnitus. International Journal Clinical Pharmacol Therapeutics. Volume 40: Issue 5; May 2002; pages 188-97.
5. 5 – Schneider, D. Schneider, L. Shulman, A. Claussen, C-F. et al. Ginkgo biloba (Rokan) Therapy in Tinnitus Patients and Measurable Interactions between Tinnitus and Vestibular Disturbances. International Tinnitus Josurnal. Volume6; Issue 1; 2000; pages 56-62.
6. 6 – Jastreboff, P. Zhou, S. et al. Attenuation of Salicylate-Induced Tinnitus by Ginkgo biloba Extract in Rats. Audiol Neurotology. 1997;2:197-212.
7. 7 – Claussen, C-F. Claussen, E. A comparative Study of Treatment of Dizziness and Tinnitus with Rokan. Verhandlungen der Gesellschaft Fur Neurootologie. 1981: S( ): 471-485.
8. 8 – Cano Cuenza, B. Algarra, JM. Del Valle, BP. Pascual, FJP. The Effect of Ginkgo Biloba on Cochlestibulary Pathology of Vascular Origin. Anales Otorrinolaringologicos Ibero-Americanos, Barcelona. XXII, 6:619-629 (1995).
9. 9 – D’Avila, JL. Multicenter Study of the Efficacy of Ginkgo Biloba Extract in Patients with Cerebral Vascular Insufficiency. Arquinvos Brasilerios de Medcina – Rio De Janiero. 1992: 66( ): 87-91.
10. 10 – Gomez, E. Multicenter Study of Standized Ginkgo Biloba Extract in the Treatment of Memory Loss, Vertigo and Tinnitus. Investigation Medica Internacional (1997)24 ( ): 31-39.
11. 11 – Vorberg, G. Ginkgo Biloba Extract (GBE): A Long-Term Study of Chronic Cerebral Insufficiency in Geriatric Patients. Clinical Trials Journal. 1985; Volume 22; No. 2; Pages 149-157.
12. 12 – Halama, P. Bartsch, G. Meng, G. Cerebrovascular Insufficiency: Placebo-Controlled, Randomized, Double-Blind Trial on the Effect of Ginkgo Biloba Extract. Fortschr. Med. Vol. 106, No. 19 (1988).
13. 13 – Eckmann, F. Schlag, H. Controlled Double-Blind Study to Prove the Efficacy of Tebonin forte in Patients with Cerebrovascular Insufficiency. Advances in Therapy. From the Schleswig State Hospital, Psychiatric and Neurological Hospital for the University of Kiel, Germany.
14. 14 – Natalie, R. Rachinel, J. Pouyat, PM. Tanakan in Cochleo-Vestibular Syndromes. Gazette Medicale de France. 1997 Vol. 86, Pages 1381-1384.
15. 15 – Albernaz, PLM. Et al. Double-Blind Study of the Activity of Gingko Biloba Extract in the Treatment of Labyrinthopathies. E Med (BR), 93 (5-8), 375-377, 1986.
16. 16 – Burschka, M. et al. Effect of Treatment with Ginkgo Biloba Extract EGb 761 (oral) on Unilateral Idiopathic Sudden Hearing Loss in a Prospective Randomized Double-Blind Study of 106 Patients. European Archives of Otorhinolaryngology. Volume 258: Issue 5; July 2001: Pages 213-219.
17. 17 – Dubreuil, C. Therapeutic Trial in Acute Cochlear Deafness: A Comparative Study of Ginkgo Biloba Extract and Nicergoline. Presse Med. 1986, 15, pp. 1559-1561.
18. 18 – Koeppel, FW. Tebonin Treatment of Hearing Impaired Elderly. Therapiewoche 30, 6443-6446 (1980).
19. 19 – Strange, G. Benning, CD. Influencing Acoustic Trauma with a Ginkgo Biloba Extract. Arch. Oto-Rhino-Laryng. 209, 203-215 (1975).
20. 20 – Fukaya, K. Sugano, H. Experimental Studies of the Mitigating Effect of Ginkgo Biloba Extract on Cisplatin Toxicity in Rats. Nippon Jibiinkoka Gakkai Kaiho, 102: 907-917, 1999.
21. 21 – Chandrasekaran, K., Mahrabian, Z. et al. Neuroprotective Effects of Bilobalide, a Component fo the Ginkgo Biloba Extract (EGb 761), in Gerbil Global Brain Ischemia. Brain Research. Volume 922, Issue 2, 20 December 2001, Pages 282-292.
22. 22 – Davies, JA. Johns, L. Jones, FA. Effects of Bilobalide on Cerebral Amino Acid Neurotransmission. Pharmacopsychiatry 2003; 36 Suppl 1: 584-588.
23. 23 – Ahlemeyer, B. Krieglstein, J. Neuroprotective Effects of Ginkgo Biloba Extract. Cell. Mol. Life Sci. 60 (2003) 1779-1792.
24. 24 – Smith, PF, Kaclennan, K. Darlington, C. The Neuroprotective Properties of the Ginkgo Biloba Leaf: a Review of the Possible Relationship to Platelet-Activating Factor (PAF). Journal of Ethnopharmacology 50 (1996) 131-139.
25. 25 – Sollier, CBD. Caplain, H. Drouet, L. No Alteration in Platelet Function or Coagulation Induced by EGb 761 in a controlled study. Clin. Lab. Haem. 2003, 25, 251-253.
26. 26 – Kohler, S. Funk, P. Kieser, M. Influence of a 7-Day treatment with Ginkgo Biloba Special Extract EGb 761 on Bleeding Time and Coagulation: a Randomized, Placebo-Controlled, Double-Blind Study in Healthy Volunteers. Blood Coagulation and Fibrinolysis 2004, 15:303-309.
27. 27 – Juretzek, W. Risk of Hemorrhaging with Ginkgo? Hausarzt; Volume 19, 2002.
28. 28 – Englesen,J. et al. Effect of CoQ10 and Ginkgo Biloba on Warfarin Dosage in Stable, Long-Term Treated Outpatients. A Randomized, Double-blind, Placebo-Crossover Trial. Thromb. Haemost., 2002; 87: 1075-6.
29. 29 – Arda, HN, et al. The Role of Zinc in the Treatment of Tinnitus. Otol Neurotol 2003 Jan;24(1):86-89.
30.  30 – Ochi, K. Kinoshita, H. et al. Zinc Deficiency and Tinnitus. Aurus, Nasus, Larynx Volume 30; Issue Supl; February 2003; Pages S25-8.
31. 31 – Ochi, K. Ohashi, T. et al. Serum Zinc Levels in Patients with Tinnitus. Nippon Jibiinkoka Gakkai Kaiho 100: 915-919, 1997.
32. 32 – Gersdorff, M. Robillard, T. Stein,f. et al. Zinc Sulfate Overload Test in Patients Suffering from Tinnitus Associated with Hypozincemia. Acta Oto-Rhino-Laryngologica Belgica. Volume 41, Brochure 3, 1987.
33. 33 – Shambaugh, G, Jr. Zinc: The Neglected Nurtrient. Am J of Otology Volume 10, Number 2 – March 1989.
34. 34 – Durak, I. Kavutcu, M. et al. Effects of Garlic Extract Consumption on Blood Lipid and Oxidant/Antioxidant Parameters in Humans with High Blood Cholesterol. Journal of Nutritional Biochemistry. Volume 15; Issue 6; June 2004; Pages 373-77.
35. 35 – Siegel, G. Malmsten, M. et al.The Effect of Garlic on Arteriosclerotic Nanoplaque Formation and Size. Phytomedicine Volume 11; Issue 1; January 2004; Pages 24-35.
36. 36 – Drew, S. Davies, E. Effectiveness of Gingko Biloba in Treating Tinnitus: Double Blind, Placebo-Controlled Trial. British Medical Journal Volume 322: pages 1-6.

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