By Barry Keate
One of the most common questions asked by both the ENT physicians who direct their tinnitus patients to take Arches Tinnitus Formula™ and our customers who use it is, “what is the mechanism of action?” How exactly does Arches Tinnitus Formula™ lower tinnitus sounds. In this article we will look at the specific pharmacological actions of this product and explain exactly how it helps in reducing tinnitus.
There is an abundance of clinical studies that show the efficacy of the components used in Arches Tinnitus Formula when used for a period of 3-4 months (4-5 bottles). We have collected 35 studies, conducted around the world, that show the ingredients used to be effective in reducing tinnitus. Arches Tinnitus Formula™ contains three primary ingredients; pharmaceutical-grade Ginkgo biloba Extract, zinc picolinate and deodorized garlic. I will discuss the various actions of each of these individually.
Ginkgo biloba Extract (GbE)
Ginkgo biloba is the most extensively studied herb in the world. It exhibits a phenomenal variety of pharmacological actions and is one of the healthiest herbs to take, with literally no side effects. Its medicinal uses can be traced back over 4,000 years to the Chen Noung Pen T’sao, China’s first pharmacopoeia in the third millennium, BC. The extract of the herb has been clinically studied since the 1960’s when it was first extracted and defined by the Dr. Willmar Schwabe Company in Germany. To date there have been over 400 published studies showing the many benefits of GbE including; cerebral insufficiency, memory improvement, depression, dizziness, tinnitus and headache.
There is a complex array of flavonoids, lactones and bilobalide in GbE. These components work synergistically to produce a multitude of vascular and neurological effects. The array is so complex that despite 20 years of effort, it is impossible to synthesize in a laboratory.
N. Holstein conducted a literature survey of 19 clinical trials investigating the effects of tinnitus treatment with GbE.1 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 7 studies showed clear improvement with ginkgo over placebo or other referenced medications 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.
There are three primary mechanisms of action of GbE for tinnitus:
1 – Glutamate Antagonism and Neuroprotection.
The primary reason GbE is helpful for tinnitus is because of its glutamate antagonism and neuroprotection. Before we proceed, it is necessary to know a little about the action of neurotransmitters in the brain and auditory pathway.
Neurotransmitters facilitate the transfer of chemical information between synapses in the brain and auditory nerve. There are many neurotransmitters in the brain but two of the primary workhorse transmitters are glutamate and GABA (gamma-amino-butyric acid). Glutamate is an excitatory neurotransmitter and GABA is an inhibitory neurotransmitter. It is important for excitation and inhibition to be in balance, otherwise a person becomes neurologically unbalanced. Too much excitation creates an increase in electrical and chemical activity that can lead to neurological disease. Too much inhibition makes a person slow and sluggish.
Glutamate is a neurotransmitter used by the cochlea to transmit signals across the synapse leading to the brain. It is produced by the hair cells of the inner ear when converting vibrational sound into electrical signals. When the hair cells are damaged, they produce excess glutamate which floods the neuro-receptors in the auditory nerve and brain. Excess glutamate overexcites the receptors and causes them to fire continuously until they become depleted and eventually die. This process is known as glutamate neurotoxicity and is responsible for many neurological diseases such as Parkinson’s disease, Alzheimer’s disease, ALS, epilepsy and tinnitus. Tinnitus caused by glutamate toxicity is called Cochlear-Synaptic Tinnitus.
Ginkgo biloba Extract is a powerful glutamate antagonist and neuroprotector. 2 3 4 5 Bilobalide, one of the constituents of GbE, has been found to be a potent antagonist to glutamate release. It has also been shown to reduce the rate of GABA uptake, meaning it keeps GABA active in the system to reduce the effects of increased glutamate. Bilobalide is potently therapeutic in cerebrovascular and neurodegenerative disorders such as tinnitus.
2 – Antioxidant Properties
Free radicals, also known as Reactive Oxygen Species (ROS), are produced in normal metabolism when oxygen is used to burn food for energy. They are also produced in certain disease states and in response to environmental pollution and toxins. A free radical is a molecule with an unpaired electron. This makes the molecule unstable and highly reactive, trying to capture an electron that will stabilize it. By capturing electrons from nearby molecules, the free radical converts other molecules to free radicals, thereby initiating a destructive chain reaction.
Untold damage is caused to the body by free radicals. These dangerous molecules are one of the leading causes of age-related disease, being directly responsible for over 100 human diseases including many types of cancer. Antioxidants neutralize free radicals and preserve tissues from their damaging effects.
In the biochemical process leading to neuroreceptor death, free radicals are generated in very large amounts. Antioxidants can prevent free radical damage in the receptors. The antioxidants can eventually be overwhelmed, however, and the damage continues, eventually leading to the death of the receptor.
The ginkgo flavonoids in GbE are powerful antioxidants and help prevent free radical damage to the auditory pathway.6
The United States Navy has conducted a major clinical study on the use of anti-oxidants to prevent noise-induced hearing loss and tinnitus from occurring in Navy personnel subjected to high noise levels. This study has shown positive effects in sustaining hearing thresholds if antioxidants are given before or shortly after noise exposure occurs. 7
3 – Increased Circulation
GbE increases circulation, especially in the microcapillaries feeding the brain, ears and eyes. It accomplishes this by acting as a vasodilator, allowing the capillaries to carry more blood. It also inhibits Platelet Aggravating Factor (PAF) which causes the blood platelets to clump together and slows circulation. 8 9 PAF is a major factor leading to stroke and inhibiting its effect reduces the likelihood of a stroke.
There has been a lot of misinformation on this point in the past. Several years ago there was a widely circulated paper warning of the possibility of internal bleeding due to the use of GbE. This paper purported to show that a single, anecdotal episode of bleeding in the brain was reason to be cautious about using GbE. This idea has since been discredited by two large clinical trials that show GbE does not increase bleeding time and does not lead to reduced coagulation or hemorrhage even when taken in large doses, up to 600 mg/day. 10 11
By increasing circulation within the inner ear, GbE promotes the uptake of nutrients, primarily glucose and oxygen, and allows built-up toxins to be flushed away, speeding the healing process.
Not all Ginkgo extracts are alike
A word about over-the-counter ginkgo products: Every bottle of Ginkgo biloba sold in the US will state that their product is a “standardized extract” and contains at least 24% Ginkgo Flavone Glycosides and 6% Terpene Lactones. This is the general description of GbE as defined by the German Commission E. However, the commission also specifically defined exact minimum requirements for individual glycosides, lactones and Bilobalide. Consumer Labs has done independent testing of a large number of over-the-counter products and found more than 77% of these products “lacked adequate levels of one or more important compounds expected of clinically effective ginkgo.” Of particular importance is that 67% of these products contained less than 20% of the specified amount of bilobalide. This is the compound most important for the reduction of glutamate toxicity and neuroprotection!
The Commission E has specified bilobalide must be present in the amount of at least 2.6% to be a standardized extract. The great majority of retail ginkgo products in the US contain less than 0.5%. The ginkgo used in Arches Tinnitus Formula contains 3.6% Bilobalide. This is part of the reason so many people who try over-the-counter ginkgo for their tinnitus do not experience satisfactory results. It also explains why our customers who try to substitute retail products for ours, invariably return. Superior products will produce superior results.
GbE is a very expensive product and many unscrupulous manufacturers have begun adulterating their raw material with rutin. Rutin is an extremely inexpensive extract of buckwheat that contains ineffective, but similar, compounds to GbE. It is impossible to tell the two apart through standardized testing measures. They can be distinguished through advanced diagnostics but many retail distributors are only interested in buying inexpensive products and do not ask too many questions. Until regulations in the US catch up with the detailed level of the Germans and European Union, we will continue to have problems of adulterated herbs in the US.
Arches Tinnitus Formula™ uses the highest quality, pharmaceutical-grade Ginkgo biloba Extract found anywhere in the world. It can be demonstrated by its Certificate of Analysis to be free of adulteration. It is naturally grown without the use of fertilizers or pesticides. It is picked by hand which reduces the chance of scraping or breaking the leaves. When leaves are scratched or torn, the terpene lactones immediately begin to oxidize and lose potency. It is extracted only with ethyl alcohol and water. Many producers extract with less expensive petroleum distillates which leave toxic residues. Finally our ginkgo is processed to remove Ginkgolic Acid, a powerful allergen that can cause gastric upset and skin rashes. There is no better ginkgo found in the world than that in Arches Tinnitus Formula.
Zinc is thought by nutritionists to be the single most important mineral supplement because it is commonly deficient in the diet and is essential for normal functioning of the immune system. It is a strong antioxidant and is famously used, in lozenge form, for helping the body fight off colds and the flu and to recover from illness, injury and surgery.
Previously, the eye was thought to contain the highest concentration of zinc but in recent years it has been found that the highest concentration is found in the cochlea. Zinc deficiency can lead to a multitude of problems including a weakened immune system, poor healing, loss of appetite and sense of taste and smell. Slight to moderate zinc deficiency is known cause tinnitus. 12
Several studies have clearly shown the link between zinc deficiency and tinnitus and also that zinc supplementation is helpful for it. 13 14
The most important clinical study on zinc and tinnitus was published in the Journal of Otology and Neurotology in January, 2003. The researchers measured zinc levels of tinnitus patients before and after treatment. They treated the patients with 50 mg of zinc daily for three months. At the end of treatment they found 82% of tinnitus patients reported their tinnitus had improved by an average of 45%. They found that even those patients who were not zinc deficient had improvement from the treatment. It is believed that this effect is due to the antioxidant properties of zinc. 15
It is very important to use a form of zinc that is bioavailable and easy to absorb. Zinc in its basic form is extremely difficult to absorb from the stomach or intestines. Many inferior forms of zinc are available and used in less expensive over-the-counter multivitamins. These products use zinc oxide of which only about 35% is absorbed. The use of zinc picolinate improves this absorption rate to around 90%.
Zinc is one of those supplements about which you must be careful. Amounts up to 100 mg per day can be used for a short period of time to correct imbalances. However zinc should not be consumed over about 50 mg per day continuously. It competes with copper and manganese for absorption and a person can become deficient in these two important minerals. Copper deficiency can combine with iron deficiency to cause anemia. This leads to fatigue, skin rashes and hair loss. Manganese deficiency can lead to bone loss. Any usage of zinc above 50 mg daily should be supplemented with 2-3 mg copper and 5-10 mg manganese.
The study cited above used 50 mg daily. We intended to use that dosage in our Tinnitus Formula but Dr. Seidman warned us to be careful. Since many people take other supplements containing zinc he advised we set our dosage at a therapeutic 30 mg. We recommend if people are not taking other zinc products they can add up to 20 mg to their daily regimen.
The main benefits of garlic for tinnitus are its ability to improve blood circulation, reduce plaque buildup on the walls of blood vessels, prevent arteriosclerosis (hardening of the arteries) and to lower lipid (fat) levels in the blood.
Garlic has a myriad of beneficial effects. It is antibiotic and antiviral, aids digestion and enhances the body’s absorption of nutrients and it may help in preventing cancer. It is strongly protective of the cardiovascular system and is reported to reduce heart attacks.
Blood flow to the cochlea is supplied by the cochlear artery. Plaque formations in this artery will severely reduce blood flow which is necessary to repair damage and flush toxins from the cochlea. Several studies have shown that garlic reduces plaque and improves blood flow. It also improves the antioxidant properties of the blood. 16 17
Clinical studies show that the ingredients used in Arches Tinnitus Formula™ are an effective and very well tolerated treatment which can be applied for the condition of ear noises of varying origin and duration. Holstein found in his overview that the prognosis was more favorable for recent onset tinnitus. He concludes, “The clinically relevant conclusion to be drawn from this is to begin treatment as early as possible.”
1 – Holstein, N. Ginkgo Special Extract EGb 761 in the Treatment of Tinnitus. Fortschr. Med. 118 (2000), p. 157-164.
2 – Chandrasekaran, K. Mahrabian, Z. et al. Neuroprotective effects of bilobalide, a component of the Ginkgo biloba extract (EGb 761), in gerbil global brain ischemia. Brain Research, Volume 922, Issue 2, 20 December 2001, Pages 282-292.
3 – Ahlemeyer, B. Krieglestein, J. Neuroprotective effects of Ginkgo biloba extract. Cellular and Molecular Life Sciences (2003) September;60(9):1779-92.
4 – Davies, JA. Johns, L. Jones, FA. Effects of Bilobalide on cerebral amino acid neurotransmission. Pharmacopsychiatry 2003;36 Suppl 1:584-588.
5 – 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 (1996)Mar;50(3):131-139.
6 – Marcossi, L. Packer, L. et al. Antioxidant action of Ginkgo biloba extract EGb 761. Methods Enzymol. 1994;234:462-75.
7 – Kopke, R. Bielefeld, E. et al. Prevention of impulse noise-induced hearing loss with antioxidants. Acta Otolaryngol. 2005 Mar;125(3):235-43.
8 – P. Halama et al. Gingko Biloba Extract with Cerebral Insufficiency. Fortschr. Med. vol. 106, no. 19 (1988).
9 – 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.
10 – Kohler, S. Funk, P. Kieser, M. Influence of a 7-day treatment with Ginkgo biloba special extract on bleeding time and coagulation. Blood Coagulation & Fibrinolysis: Volume 15(4) June 2004 pp 303-309.
11 – Sollier, CBD. Caplain, H. Drouet, L. No alteration in platelet function or coagulation induced by EGb761 in a controlled study. Clin Lab Haematol. 2003 Aug;25(4):251-3.
12 – Shambaugh, G. Zinc: The neglected nutrient. The American Journal of Otology Volume 10, Number 2 – March 1989.
13 – Ochi, K. Ohashi, T. et al. Serum Zinc Levels in Patients with Tinnitus. Nippon Jibiinkoka Gakkai Kaiho 100: 915–919, 1997.
14 – Ochi, K. Kinoshita, H. et al. Zinc deficiency and tinnitus. Auris, Nasus, Larynx Volume: 30; Issue: Supl; February 2003; Pages: S25-8.
15 – Arda, HN. Et al. The Role of Zinc in the Treatment of Tinnitus. Otol Neurotol 2003 Jan;24(1):86-89.
16 – 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.
17 – Durak, I. Kavutcu, M. et al. Effects of Garlic Extract Consumption on Blood Lipid and Oxidant/Antioxidant Parameters in Humans with High Blood Cholesterol. The Journal of Nutritional Biochemistry Volume: 15; Issue: 6; Month/Year: June 2004; Pages: 373-77.