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No. 26 October 2002
Ginkgo and Ear Disorders
by Kerry Bone
Ginkgo biloba extract (GBE) is the most clinically-tested
herbal therapy for disorders involving the ear. However,
results from clinical trials have not always been consistent.
This article reviews the available clinical trials under the
headings hearing loss, vestibular disorders and tinnitus.
Those trials for which outcomes for more than one of these
disorders were examined have been included under
tinnitus.
Hearing Loss
Deafness of sudden onset (acute cochlear deafness) is
often due to ischemia of the cochlea and the metabolic
derangement which accompanies it. The first study on the
use of GBE in acute cochlear deafness was published 16
years ago in 1986.1 The author suggested that the
prognosis in acute cochlear deafness is entirely dependent
on the rapid initiation of an effective treatment. Hence a
relatively high dose of GBE of 320 mg/day (corresponding
to around 16 g/day of Ginkgo leaf) was employed in the
study. The efficacy of GBE was compared to nicergoline an
α-adrenoreceptor blocker. The study involved 18 patients
in a double-blind design over 30 days. Audiometric
analyses and labyrinth tests demonstrated that all of the
patients in the GBE group had normal values at the end of
the trial, whereas one-third of the patients in the
nicergoline group still had inconclusive tests. The
significance of this trial was hampered by the small patient
numbers.
In another trial, standardized Ginkgo extract (intravenous
200 mg/day for 9 days, followed by oral 160 mg/day for
6 weeks) was found to be superior to the drug piracetam
for the treatment of sudden deafness (one-sided hearing
loss).2 Median values for hearing thresholds in the range
250 to 3000 Hz were significantly lower with GBE
treatment.
In a randomized comparative study published in 1994, 80
patients with idiopathic sudden hearing loss existing no
longer than 10 days were treated with either standardized
Ginkgo extract or naftidrofuryl (a vasodilator). After one
week, 40% of patients in each group experienced a
complete remission. After 3 weeks there was a significant
borderline benefit for Ginkgo over naftidrofuryl. Ginkgo
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treatment was preferred due to a lack of side effects,
unlike the naftidrofuryl.3
It appears that interest has been rekindled in this
important but uncommon application for Ginkgo, with
three clinical trials published in the past two years. One
study conducted in India examined the value of GBE
compared to a combined drug treatment for acquired
sensorineural hearing loss in 52 patients.4 Probable
etiologies included presbycusis (36.5%) followed by
unknown causes (28.8%). Outcomes for GBE were better
than the conventional treatment in responding patients.
Response rates were similar between the two treatments.
In a relatively large trial involving 106 patients, the
efficacies of two different doses of GBE for unilateral
idiopathic sudden hearing loss were compared in a
randomized double-blind design.5 The higher dosage of
GBE appeared to accelerate and secure the recovery of
patients, with a good chance for complete recovery.
Positive results were observed after one week of
treatment.
In a randomized, prospective, double-blind study involving
72 patients, the therapeutic efficacy of GBE (n=37) was
compared to that of pentoxifylline (n=35) for the
treatment of sudden deafness.6 The two treatments were
equally well tolerated and showed a statistically significant
equivalence either in improvement or in return to normal
of the auditory thresholds in the two patient groups.
Subjective assessment of the treatment (with regard to
improvement in hearing and reduction in tinnitus)
suggested that Ginkgo biloba extract was more beneficial
than pentoxifylline.
Vestibular Disorders
Most of the trials assessing the value of GBE in vertigo
date back to the 1980s, although there is one trial of
recent origin. In one early trial, which had an open phase
with GBE followed by a double-blind placebo-controlled
phase, results were compiled for 50 patients complaining
of dizziness. These results showed a clear benefit for GBE
in the open phase as well as over the placebo except for
patients with Ménière’s disease.7
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A randomized, placebo-controlled, double-blind trial in 35
patients assessed the value of GBE at 160 mg/day for
vestibular vertigo.8 The primary outcome measured was
performance using posturography (assessment of body
sway with eyes open or closed etc) and there was a
statistically significant benefit from baseline observed for
therapy with GBE, which was also superior to placebo.
A study conducted in three centers included 70 patients
with vertigo of recent and idiopathic onset in a doubleblind, placebo-controlled trial.9 The efficacy of GBE on both
the frequency and duration of vertigo achieved statistical
significance, with 47% of patients in the Ginkgo group free
of symptoms at the end of the trial compared to 18% for
the placebo group.
The most recent trial conducted in Poland compared GBE
therapy plus physical therapy against physical therapy
alone for the treatment of vestibular organ peripheral
lesion syndrome in an open design.10 Patients in both
groups improved, but improvement was more clear and
faster, as assessed by dynamic posturography, for the
group receiving GBE.
Tinnitus or Combined Syndromes
Tinnitus is one of the most important symptoms in the
field of disorders of the ear, after vertigo, nausea and
hearing loss. In most cases the origin of the tinnitus is not
identifiable although it is recognized that it can arise in
any part of the hearing pathway. It is frequently associated
with vertigo, nausea and hearing loss. An age
predominance exists and identifiable causes include
presbycusis, atherosclerosis, chronic otitis media,
otosclerosis, acoustic trauma, Ménière’s disease and
ototoxicity. Given such a wide range of causes, known and
unknown, it is likely that clinical trials in this field will be
fraught with difficulties and prone to conflicting results.
This is certainly the case for trials involving Ginkgo
treatment.
An early trial conducted in 1979 included 60 patients with
hearing loss and/or vertigo and tinnitus.11 GBE
(120 mg/day) was compared with nicergoline and found
to be superior. Another early open design trial found good
efficacy for GBE in patients with hearing impairment and
tinnitus due to a variety of causes, mainly involving
ischemia.12
Sixteen years ago, Meyer conducted a defining study on
103 patients which clearly established a reputation for
Ginkgo in the treatment of tinnitus (deserved or
otherwise).13 A randomized, double-blind, placebocontrolled trial was conducted with GBE including only
patients with tinnitus of recent onset (less than one year).
Improvement or cure was observed after an average of 70
days in patients treated with Ginkgo compared with 119
days in patients receiving placebo. Tinnitus which was of
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recent onset, unilateral and intermittent seemed to be
particularly responsive to Ginkgo.
Soft laser therapy in combination with GBE for the
treatment of tinnitus was found to be effective in one
open trial14 and ineffective in another.15 In a double-blind,
placebo-controlled trial involving 100 elderly patients
(with at least four symptoms out of poor memory, anxiety,
vertigo, tinnitus and headaches), therapy with GBE
(112 mg/day) or placebo was assessed after 12 weeks.16
Improvement for tinnitus from baseline was 37% for the
Ginkgo group versus 12% for the placebo group.
The 20 patients reporting a positive effect on persistent
severe tinnitus in an open study involving 80 patients
were included in a double-blind placebo-controlled
crossover study.17 They received either Ginkgo extract
(29.2 mg per day, 2 weeks) or placebo. The success of the
treatment was based on patient preference (as there is no
objective measurement) and on this basis Ginkgo did not
demonstrate a significant effect. However, the dosage of
Ginkgo extract used was probably subtherapeutic.
Again there has been recent interest in assessing the value
of Ginkgo for tinnitus. A study published last year in the
BMJ found no effect for GBE (150 mg/day) in treating
tinnitus in a double-blind, placebo-controlled trial using
mail questionnaires in 1121 healthy people with a
comparatively stable condition.18
In contrast, a trial published this year involving 60 patients
with chronic tinnitus found a positive result for GBE
(200 mg/day by intravenous infusion for 10 days followed
by oral therapy of 160 mg/day) compared with a placebo
after 12 weeks of therapy.19 While results achieved
statistical significance, the absolute difference between
the two treatment groups was only moderate.
A systematic search of the literature identified 19 clinical
trials (many early and not including the two above)
investigating the effect of GBE on tinnitus.20 The results of
eight controlled studies were found for the most part to
show a statistically significant superiority of GBE over
placebo or reference drugs. Tinnitus of recent onset had a
better prognosis.
Conclusions
Clinical trials demonstrate that Ginkgo biloba can play a
valuable role in the management of disorders involving
the inner ear and related neural pathways. Unilateral
conditions of recent and sudden onset, possibly involving
an ischemic etiology, would appear to respond best to this
form of therapy.
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REFERENCES
1
Dubreuil C. [Therapeutic trial in acute cochlear deafness. A comparative
study of Ginkgo biloba extract and nicergoline]. Presse Med 1986; 15
(31): 1559-1561
2
Baschek V, Steinert W. In: Claussen CF, Kirtane MV, Schlitter K. (eds).
Vertigo, Nausea, Tinnitus and Hypoacusia, in Metabolic Disorders. Elsevier,
Amsterdam, 1988: pp 575-582
3
Hoffmann F, Beck C, Schutz A. et al. [Ginkgo extract EGb 761
(tenobin)/HAES versus naftidrofuryl (Dusodril)/HAES. A randomized study
of therapy of sudden deafness]. Laryngorhinootologie 1994; 73(3): 149152
4
Kumar A, Raizada RM, Chaturvedi VN. Role of Ginkgo biloba extract in
acquired sensorineural hearing loss. Indian J Otolaryngol Head Neck Surg
2000; 52(3): 212-219
5
Burschka MA, Hassan HA, Reineke T 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
outpatients. Eur Arch Otorhinolaryngol 2001; 258(5): 213-219
6
Reisser CH, Weidauer H. Ginkgo biloba extract Egb 761 or pentoxifylline
for the treatment of sudden deafness: a randomized, referencecontrolled, double-blind study. Acta Otolaryngol 2001; 121(5): 579-584
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Schwerdtfeger F. Elektronystagmographisch und klinisch dokumentierte
Therapie-erfahrungen mit rokan bei Schwindelsymptomatick.
Therapiewoche 1981; 31: 8658-8667. In: DeFeudis FV. Ginkgo biloba
Extract (EGb 761): Pharmacological Activities and Clinical Applications.
Elsevier, Paris, 1991.
8
Hamann KF. Physikalische Therapie des vestibularen Schwindels in
Verbindung mit GBE. Therapiewoche1985; 35: 4586-4590. In: DeFeudis
FV. Ginkgo biloba Extract (EGb 761): Pharmacological Activities and
Clinical Applications. Elsevier, Paris, 1991.
9
Haguenauer JP, Cantenot F, Koskas H et al. [Treatment of equilibrium
disorders with Ginkgo biloba extract. A multicenter double-blind drug vs.
placebo study]. Presse Med 1986; 15(31): 1569-1572
10
Orendorz-Fraczkowska K, Pospiech L, Gawron W. [Results of combined
treatment for vestibular receptor impairment with physical therapy and
Ginkgo biloba extract (Egb 761)]. Otolaryngol Pol 2002; 56(1): 83-88
11
Chesseboeuf L, Herard J, Trevin J. Etude comparative de deux
vasoregulaterus dans les hypoacousies et les syndromes vertigineux. Med
Nord Est 1979; 3; 534-539. In: DeFeudis FV. Ginkgo biloba Extract (EGb
761): Pharmacological Activities and Clinical Applications. Elsevier, Paris,
1991.
12
Artieres J. Effets therapeutiques du Tanakan sur les hypoacousies et les
acouphenes. Lyon Mediterr Med 1978; 14: 2503-2515. In: DeFeudis FV.
Ginkgo biloba Extract (EGb 761): Pharmacological Activities and Clinical
Applications. Elsevier, Paris, 1991.
13
Meyer B. [Multicenter randomized double-blind drug vs. placebo study
of the treatment of tinnitus with Ginkgo biloba extract]. Presse Med 1986;
15(31): 1562-1564
14
Plath P, Olivier J. Results of combined low-power laster therapy and
extracts of Ginkgo biloba in cases of sensorineural hearing loss and
tinnitus. Adv Otorhinolaryngol 1995; 49: 101-104
15
Partheniadis-Stumpf M, Maurer J, Mann W. [Soft laser therapy in
combination with tebonin i.v. in tinnitus]. Laryngorhinootologie 1993;
72(1): 28-31
16
Vorberg G, Schenk N, Schmidt U. Herz Gefasse 1989; 9: 936-941
17
Holgers KM, Azelsson A, Pringle I. Ginkgo biloba extract for the
treatment of tinnitus. Audiology 1994; 33(2): 85-92
18
Drew S, Davies E. Effectiveness of Ginkgo biloba in treating tinnitus:
double blind, placebo controlled trial. BMJ 2001; 322(7278): 73
19
Morgenstern C, Biermann E. The efficacy of Ginkgo special extract EGb
761 in patients with tinnitus. Int J Clin Pharmacol Ther 2002; 40(5): 188197
20
Holstein N. [Ginkgo special extract EGb 761 in tinnitus therapy. An
overview of results of completed clinical trials]. Fortschr Med Orig 2001;
118(4): 157-164
This article was originally printed in the Townsend Letter for
Doctors and Patients, #231, October 2002.
See www.tldp.com
Reprinted with permission.
Not for Public Distribution. For Education of Health Care Professionals Only.
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