Effective in the Treatment of Central Tinnitus: Ginkgo Special Extract EGb 761(R)

Link​

Ginkgo for Tinnitus again? Keep in mind this study was only done on Gerbils, with

Tebonin(R) a patented high dose concentrated Ginkgo and done by Pharma company.​

Effective in the treatment of central tinnitus: Ginkgo special extract EGb 761(R) increases neuronal plasticity Retraining therapy: EGb 761(R) can help to "unlearn" tinnitus / animal model demonstrates protective effect against tinnitus​

MAINZ, Germany, Jul 17, 2012 (BUSINESS WIRE) -- Around three million Germans permanently suffer from tinnitus, which can cause some considerable impairment in daily life. According to the most recent research findings, tinnitus results from maladaptive learning processes. The pharmacological reinforcement of neuronal plasticity to promote "unlearning" is therefore a new therapeutic approach. Ginkgo special extract EGb 761(R) (Tebonin(R)) is suitable for this, as studies show that it increases neuronal plasticity.(1) At the ENT Congress in Mainz, experts described the current status of research during a satellite symposium organised by Dr. Willmar Schwabe and chaired by Prof. Norbert Holstein, Karlsruhe.(2) His conclusion: "The clinical data show that EGb 761(R) is an effective and well-tolerated option to help in the treatment of various forms of tinnitus." In an animal model, a protective effect against the development of central tinnitus was found with EGb 761(R).(3)

The pathogenesis of acute tinnitus was long thought to be of vascular origin. However, research over the past few years shows that tinnitus can be described as "phantom pain" of the inner ear. "Tinnitus arises as a central phenomenon with a predominantly peripheral trigger - hearing loss - based on maladaptive learning processes in the auditory cortex", explained Prof. Christo Pantev, Munster. The maladaptive neuronal plasticity leads to the formation of a cortical tinnitus network - tinnitus is "learnt" and can therefore also be "unlearnt". According to Prof. Holger Schulze, University of Erlangen-Nuremberg, so-called retraining therapies have been shown to be particularly promising for the treatment of central tinnitus. The aim is to reverse the neuroplastic changes underlying the tinnitus. "Studies suggest that EGb 761(R) can further support specific retraining programmes by promoting the renewed neuroplastic development" according to Schulze.

Effects of EGb 761(R) on facilitation of learning
The facilitating effects of Ginkgo special extract on learning could be shown in animal models using auditory discrimination learning, as Schulze demonstrated: Over 15 days, Mongolian gerbils learnt to discriminate between different tones. The animals were given EGb 761(R) or placebo every day two weeks before and during training. "The animals treated with EGb 761(R) learnt much faster than the control group", according to Schulze. The constituents in EGb 761(R) promote neuronal plasticity by increasing neurite proliferation and synapse formation. Owing to the neuroprotective properties, the special extract can also protect the sensory cells of the cochlea from damage.
Protective effect against tinnitus

A protective effect of EGb 761(R) against acoustic trauma was also demonstrated in an animal model.(3) This consequently led to protection against the development of central tinnitus, according to Schulze: "This protective effect is probably based on an increased recruitment of global inhibition in the auditory cortex of the animals treated with EGb 761(R)." Mongolian gerbils were given EGb 761(R) or placebo every day from 12 to 43 days before and up to 14 days after being exposed to acoustic trauma. Result: The animals treated with EGb(R) 761 had slightly improved auditory thresholds even before acoustic trauma and a clearly lower auditory threshold loss overall after acoustic trauma. Of the gerbils treated, only 34 percent developed tinnitus after the acoustic trauma, in the control group it was 83 percent.

EGb 761(R) effective for several forms of tinnitus
Apart from improving circulation, EGb 761(R) primarily has neuroprotective properties, protects energy generation in neuronal mitochondria and promotes dopaminergic neurotransmission and neuroplasticity, as Schulze explained. Dieter Schneider, assistant professor at the University of Wurzburg, presented data on the therapeutic benefits of EGb 761(R) in tinnitus from a recent review with eight placebo-controlled studies and a total of 1,199 patients. "In all studies, EGb 761(R) was better than placebo." In particular, the Ginkgo special extract was shown to be effective against very different forms of tinnitus: Acute to subchronic or chronic tinnitus, cerebrovascular insufficiency with concomitant tinnitus and dementia with concomitant tinnitus. In the studies, EGb 761(R) was well tolerated and the rate of adverse events was at the placebo level. Schneider remarked that "Different Ginkgo extracts can differ considerably owing to different manufacturing processes." The positive study data on EGb 761(R) therefore cannot simply be transferred to other preparations. Vice versa, the studies with other Ginkgo preparations that were not able to demonstrate any effects do not call the results presented here into question.

Combination therapy for an intractable clinical picture
Chronic tinnitus is a challenge for the therapist, as every individual measure can only have a limited effect. For this reason, multimodal treatment concepts have become established in practice over the past few years, as explained by Prof. Holstein. Based on the new neurobiological findings, which have identified learning processes as an important element for tinnitus therapy, it appears appropriate to complement this approach with EGb 761(R) in order to promote neuroplasticity and thus to facilitate the "unlearning" of tinnitus.

About Tebonin(R)
Tebonin(R) intens 120 mg (high-dose patented EGb 761(R) Ginkgo biloba extract) is approved for adjuvant therapy of tinnitus of vascular and involutional origin. The recommended daily dose is 120 to 240 mg, corresponding to one or two film-coated tablets of Tebonin(R) intens.

Tebonin(R) contains Ginkgo biloba special extract EGb 761(R) as active ingredient, standardised by means of an additional patented extraction stage during manufacture to 22.0 - 27.0 % Ginkgo flavone glycosides and 5.0 - 7.0 % terpene lactones. For more than 20 years, the action, efficacy and tolerability of EGb 761(R) has been systematically investigated, so that today EGb 761(R) is the best researched and documented plant extract worldwide.

Dr. Willmar Schwabe
Over the 140 years since being founded, the Dr. Willmar Schwabe company has reached a leading position worldwide in the development and manufacture of phytopharmaceuticals. The high quality of our herbal medicines and dietary supplements and the scientific documentation of our special extracts are the reasons why Schwabe enjoys the reputation of being the "specialist for phytopharmaceuticals". www.schwabepharma.com

Sources:
1) Tchantchou et al. Journal of Alzheimer`s Disease, 2009
2) Symposium "Tinnitus - 'Phantomschmerz' der Cochlea. Moderne Konzepte zu Tinnitusentstehung und -therapie", veranstaltet von Dr. Willmar Schwabe am 17. Mai 2012 in Mainz anlasslich der 83. Jahresversammlung der Deutschen Gesellschaft fur Hals-Nasen-Ohrenheilkunde, Kopf- und Halschirurgie e.V.
3) Schulze H. et al.: Med Review 2011,11:5
4) Von Boetticher A.: Neuropsychiatric Disease and Treatment 2011:7,441-447
SOURCE: Dr. Willmar Schwabe GmbH & Co. KG

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Tebonin page link

Tebonin® - EGb 761®​

for the symptomatic treatment of mental losses due to organic brain syndrome within the framework of a general therapeutic concept in case of progressive impairment or loss of mental capacities (dementia syndrome) having as major symptoms: Deficient memory, disturbances of concentration, depressive mood, dizziness, tinnitus and headache. The primary target group includes patients with demential syndrome in primary degenerative dementia, vascular dementia and mixed forms of both. Individual response to the treatment cannot be predicted. Prior to starting treatment with this preparation, clarification should be obtained as to whether the pathological symptoms encountered are not based on an underlying disease requiring a specific treatment.​

Improvement of the pain-free walking distance in peripheral arterial occlusive disease in FONTAINE stage II (intermittent claudication) within the framework of physical therapeutic measures, in particular walking training.​

Vertigo of vascular and involutional origin.​

Supportive treatment in case of tinnitus of vascular and involutional origin.​

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Active ingredient:​

Ginkgo biloba extract EGb 761®​

Tebonin® contains Schwabe’s unique and patented Ginkgo biloba extract EGb 761®. Since its launch in 1975 EGb 761® has been an outstanding success in numerous countries. In several countries including Germany it is approved for the treatment of dementia and for vascular disorders such as tinnitus, vertigo and peripheral arterial occlusive disease. EGb 761® is manufactured in a patented multi-stage process. One ton (1,000 kg) of the dried leaves yields only 20 kg of EGb 761®. During the production process, the concentrations of active principles are increased by a factor of up to 100. In addition, potentially harmful ingredients are eliminated from the final product.​

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Approved indication in Germany:​

For the symptomatic treatment of mental losses due to organic brain syndrome within the framework of a general therapeutic concept in case of progressive impairment or loss of mental capacities (dementia syndrome) having as major symptoms: Deficient memory, disturbances of concentration, depressive mood, dizziness, tinnitus and headache. The primary target group includes patients with demential syndrome in primary degenerative dementia, vascular dementia and mixed forms of both. Individual response to the treatment cannot be predicted. Prior to starting treatment with this preparation, clarification should be obtained as to whether the pathological symptoms encountered are not based on an underlying disease requiring a specific treatment.​

Improvement of the pain-free walking distance in peripheral arterial occlusive disease in FONTAINE stage II (intermittent claudication) within the framework of physical therapeutic measures, in particular walking training.​

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Vertigo of vascular and involutional origin.​

Supportive treatment in case of tinnitus of vascular and involutional origin.​

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Note: If conditions persist, are unclear or new, consult a doctor as diseases requiring medical clarification might be involved.​

For information on precautions for use, side effects and contra-indications see the package leaflet or contact your doctor or pharmacist.​

 

Calin, I emailed the company with some questions about availability in the USA. Just waiting for a response.

 

Update: Just got a reply from the company about availability in the USA.

Here it is:

Thank you very much for your inquiry. Our standardized Ginkgo biloba extract EGb 761®, which is the active ingredient in Tebonin®, is sold in the USA under the trade name Ginkgold® from our subsidiary Nature's Way at quality health food stores.

You will find more information about Ginkgold® online by clicking here.


With best regards,

Andrea Hainz
Assistant International Marketing
_______________________________
Dr. Willmar Schwabe GmbH & Co. KG
Willmar-Schwabe-Straße 4
76227 Karlsruhe
Germany

 

You can get it from iHerb, Swanson, Amazon and other vitamin places. iHerb has it here.

 

I have sent a follow up asking more about this....I'll let you know when I hear back.

 

Ginkgold..

The generic Ginkgo is cheaper than Ginkgold, in essence I'd classify Ginkgold as a marketer's item/brand, it likely contains 100% the same stuff than any other Ginkgo product.

And from what I can find, the generic stuff contains the same amount/percentage of active ingredients (glycosides etc.).

Call me crazy, but I'm such a nut that I wouldn't be surprised if Ginkgold was made in the same factories than most other brands' Ginkgo, but only slapped a different etiquette on the bottle and box.

Pessimistic much, huh?

to be honest I've read people trying both, usual Ginkgo products and Ginkgold, without any effect or difference whatsoever.

And it wouldn't be the first time someone marketed some generic stuff as their own special working thing and slapped 3x the price of others.

 

The patent for Ginkgold was issued back in the 90s.
If it worked, we'd know about it, what with Ginkgo being the go-to supplement for new tinnitus sufferers (even tho' with its extremely limited success) and Ginkgold being on the market for several, several years.

http://www.google.com/patents/US5399348

Claims

1. An extract comprising 20 to 30 weight percent flavone glycosides, 2.5 to 4.5 weight percent of ginkogolides A, B, C and J, 2.0 to 4.0 weight percent bilobalide, less than 10 ppm alkylphenol compounds and less than 10 weight percent proanthocyanidins.
2. The extract of claim 1 containing about 22 to 26% by weight flavone glycosides.
3. The extract of claim 1 containing less than 1 ppm alkylphenol compounds.
4. A pharmaceutical composition useful for the treatment of peripheral and cerebral arterial circulatory disorders comprising a Ginkgo biloba extract of claim 1 in a pharmaceutical carrier wherein the extract concentration is sufficient to alleviate the circulatory disorders.
5. A method of preparing an extract from the leaves of Ginkgo biloba which is substantially free of alkylphenol compounds and having a high content of flavone glycosides and comprising substantially all of the ginkgolides and bilobalide originally present in the leaves, the method comprising the steps of
a) extracting the leaves with an organic solvent selected from the group consisting of aqueous acetone, an aqueous alkanol having one to three carbon atoms and anhydrous methanol;
b) separating most of the organic solvent from the extract of step (a) to form an aqueous solution;
c) diluting the aqueous solution with water to a solids content of 5 to 25 weight percent;
d) cooling the diluted aqueous solution to precipitate and separate lipophilic components from the diluted aqueous solution;
e) treating the aqueous solution from step (d) with ammonium sulfate and and then extracting the aqueous solution with methylethylketone, acetone, or a mixture of methylethylketone and acetone;
f) diluting the extract from step (e) with water and alcohol to form an aqueous alcohol solution;
g) treating the aqueous alcohol solution with a lead compound or an insoluble polyamide;
h) extracting the treated aqueous alcohol solution with an aliphatic or cycloaliphatic solvent having a boiling point of about 60.degree.-100.degree. C. to further remove the alkylphenol compounds; and
i) recovering a dry extract.
6. The method of claim 5 wherein the solids content of step (c) is about 15 to 20% by weight.
7. A method of preparing an extract from Ginkgo biloba leaves, containing 20 to 30 weight percent flavone glycosides, 2.5 to 4.5 weight percent of ginkgolides selected from ginkgolide A, B, C and J or mixtures thereof, 2.0 to 4.0 weight percent bilobalide, less than 10 ppm alkylphenol compounds and less than 10 weight percent proanthocyanidins comprising the steps of:
(a) extracting fresh or dried green leaves of Ginkgo biloba at a temperature of approximately 40.degree. to 100.degree. C. with an organic solvent selected from the group consisting of aqueous acetone, an aqueous alkanol of 1 to 3 C-atoms and anhydrous methanol,
(b) distilling the extract from step (a) to remove the organic solvent to a maximum content of 10 weight percent to form a concentrated aqueous solution,
(c) diluting the concentrated aqueous solution with water to a solids content of 5 to 25 weight percent and then cooling the diluted aqueous solution to a temperature below 25.degree. C. to precipitate and separate the lipophilic components from the diluted aqueous solution,
(d) adding ammonium sulfate to the aqueous solution from step (c) to a concentration of 30 weight percent and extracting said solution with methylethylketone or a mixture containing methylethylketone and acetone in a ratio from about 9:1 to 4:6,
(e) concentrating the extract from step (d) to a solids content of 50 to 70% and then diluting with water and ethanol to form an aqueous alcohol solution containing about 50 weight percent of water and about 50 weight percent of ethanol with a solids content of about 10 weight percent,
(f) adding an aqueous solution of a lead salt or an aqueous suspension of lead hydroxide to the aqueous alcohol solution of step (e) until a change in color from brown to umber takes place and precipitate is formed and separated,
(g) extracting the aqueous alcohol solution from step (f) with an aliphatic or cycloaliphatic solvent having a boiling point of about 60.degree. to 100.degree. C. to further remove alkylphenol compounds,
(h) concentrating the aqueous alcohol solution from step (g) under reduced pressure to a maximum ethanol content of about 5% and then adding ammonium sulfate up to about 20 weight percent,
(i) extracting the aqueous alcohol solution from step (h) with a mixture of methylethylketone and ethanol in a ratio from about 8:2 to 5:5 to form an organic phase extract,
(j) concentrating the organic phase extract to a solids content of 50 to 70 weight percent, and
(k) drying the resultant concentrate from step (j) under reduced pressure at a maximum temperature of 60.degree. to 80.degree. C. to form a dry extract with a water content of less than 5%.
8. The method of claim 7 wherein the prepared extract contains about 22 to 26% by weight flavone glycosides.
9. The method of claim 7 wherein the prepared extract contains less than 1 ppm alkylphenol compounds.
10. The method of claim 7 wherein the extract of step (b) contains a maximum of 5 weight percent organic solvent.
11. The method of claim 7 wherein the solids content of step (c) is about 15 to 20% by weight.
12. The method of claim 7 wherein the extract of step (c) is cooled to about 10.degree. to 12.degree. C.
13. The method of claim 7 wherein the methylethylketone and acetone mixture of step (d), step (i), or step (d) and step (i) is in a ratio of 6 to 4.
14. The method of claim 7 wherein the lead salt in step (f) is selected from the group consisting of lead acetate, lead hydroxide acetate and lead nitrate.
15. The method of claim 7 wherein lead hydroxide acetate is added to the aqueous solution of step (f).
16. A pharmaceutical composition comprising a Ginkgo biloba extract prepared according to the process of claim 5, 6, 7, 8, 9, 10, 11, 12, 13, or 14 in a pharmaceutical carrier wherein the extract concentration is sufficient to alleviate circulatory disorders.

 

Thanks for your comments Markku, interesting point.

UPDATE #1: I did get response from company...

Dear Erik,

thank your for writing us again.

I just learned from my colleague who is the regulatory affairs manager for EGb 761® that the retraining programs were not specified since Ginkgo special extract EGb 761® supports every retraining program. Thus we cannot give a recommendation for a specific retraining program because every tinnitus is different and needs an individual therapy. As an example he mentioned the "notched sound therapy" (i.e. TNMN = tailor made notched music) is only applicable for a specific tinnitus typus, the "tonal" tinnitus typus.

So unfortunately, we cannot give any recommendation.

With best regards and good wishes,

Andrea

_______________________________
Dr. Willmar Schwabe GmbH & Co. KG
Willmar-Schwabe-Straße 4
76227 Karlsruhe
Germany

 

UPDATE #2: I also contacted Dr Schulze from Univ of Erlangen-Nuremberg who was quoted in the article

"The maladaptive neuronal plasticity leads to the formation of a cortical tinnitus network – tinnitus is “learnt” and can therefore also be “unlearnt”. According to Prof. Holger Schulze, University of Erlangen-Nuremberg, so-called retraining therapies have been shown to be particularly promising for the treatment of central tinnitus. The aim is to reverse the neuroplastic changes underlying the tinnitus. “Studies suggest that EGb 761® can further support specific retraining programmes by promoting the renewed neuroplastic development” according to Schulze.

I asked him the methods used to "unlearn" tinnitus. What are the retraining programs that could be implemented along with the Ginkgo extract? Are we talking TRT (tinnitus retraining therapy), Neuromodulation, Vagus Nerve Stimulation, Notched Music Therapy etc? His reply was as follows...

We are currently running a study looking for the potential effect of EGb 761 in tinnitus retraining therapies. Actually I believe that it might be helpful in all the strategies you mentioned because of its known effect on learning and memory and the enhanced dopamine levels in prefrontal cortex after EGb 761 administration. But currently this is just our working hypothesis and we do not know if this will prove true. We still have to try…

Sincerely
Holger Schulze

 

There may very well be a difference in types of Gingko and thus why the results vary from it works to not at all. Most of the prior studies on Ginkgo and Tinnitus were done prior to 2008. I am not saying that for sure that ginkgo works because I am not qualified to make that statement (I have not tried Ginkgo), but as with most supplements there are good and bad choices. Consumerlab, which I pay a yearly subscription for and is worth it, is an independent tester of nutritional supplements in the USA. This is what they had to say about Ginkgo...

Neither the U.S. government nor any other agency is responsible for routinely testing dietary supplements for their contents or quality. In order to help consumers identify products of better quality, ConsumerLab.com purchased and tested ginkgo supplements for the quality of their ingredients and other relevant parameters as described below. See Testing Method for more details.
ConsumerLab.com's review of ginkgo products in 1999 found that nearly one quarter of the thirty brands tested did not have the expected levels of chemical marker compounds, despite claims to have been "standardized." Even worse, testing in 2003 found that seven of nine ginkgo products lacked adequate levels of certain marker
compounds, and six products failed testing for the same reason in 2005. Five of seven gingko supplements failed
CL testing in 2008.
To reduce their costs, some manufacturers (or their ingredient suppliers) provide less ginkgo than claimed or use material that has been adulterated or “spiked” with one or more compounds that can trick simple chemical tests.This makes a product with little or no real ginkgo appear to be real thing. In fact, it is now believed that ginkgo is among the most adulterated herbs.
To better understand how ginkgo can be adulterated, it is important to know that Ginkgo†biloba†extract (GBE)
used in most clinical trials contains two major groups of phytochemicals called flavonol glycosides and terpene
lactones. Specifically, the extracts shown to work in clinical trials have contained at least 5% terpene
lactones (consisting of bilobalide (2.6%) and ginkgolides A, B and C (2.8%)) and at least 22% flavonol glycosides
(consisting of quercetin (min. 9.5%), kaempferol (min. 10.5%), and isorhamnetin (min. 2.0%)). The flavonol
glycosides are believed to confer antioxidant activity and the terpene lactones may be responsible for a dilatory
effect on blood vessels. Bilobalide, one of the terpene lactones, may also increase brain activity by affecting
GABA receptors and enhancing the excitability of neurons in the hippocampus of the brain, which is associated
with learning and memory.
One way of adulterating ginkgo is to use little actual ginkgo extract and spike it with less expensive sources of
flavonol glycosides, such as rutin (from buckwheat) which is rich in quercetin. This will trick a test that looks only
at the total amount of flavonol glycosides and not the spectrum specific to ginkgo. The tests used by
ConsumerLab.com reveal this type of adulteration by showing the ratios of specific flavonal glycosides and
comparing them to established standards. [For more on this subject, see the Natural Products Insider article
Adulteration Stifles the Ginkgo Biloba Market].
ConsumerLab.com’s past tests have also detected lead contamination in some ginkgo products made with leaf
powder. Lead is a potential contaminant in natural products. In children, infants, and fetuses, even low levels of
lead can adversely affect neurobehavioral development and cognitive function. In adults, lead at somewhat higher levels can cause elevated blood pressure, anemia, and adversely affect the nervous and reproductive systems. Lead is of particular concern during pregnancy as the mother can transfer it to the fetus. All ginkgo products were tested for lead.

Consumers seeking products most similar to those used in clinical studies should seek those containing Ginkgo
biloba†leaf extract (GBE). The plant chemicals in the extract are about 50 times more concentrated than in dried
ginkgo leaf. Contamination with lead is also uncommon with extracts, as the extraction process may remove
impurities. The extract should be standardized for the specific compounds tested for in this study. This is often
summarized as 24% flavonol glycosides and 6% terpene lactones, or in terms of milligrams for a 40 mg pill, 9.6
mg and 2.4 mg, of each respectively. Although rarely listed on labels, products should ideally also be
standardized for the following specific flavonol glycosides and terpene lactones: quercetin (minimum 9.5%),
kaempferol (minimum 10.5%), isorhamnetin (minimum 2.0%), ginkgolides A, B, C (minimum 2.8%), and bilobalide(minimum 2.6%). These specifications are based on those for EGb761 (Schwabe Pharmaceuticals), the most studied form of ginkgo extract.