GINKGO-BILOBA-CLINICAL-REFERENCES

  GINKGO BILOBA CLINICAL REFERENCES

Hi all,

Many people have waited patiently (and some impatiently) for me to catalog all the clinical research and studies I have on Ginkgo Biloba after promising to make these available to those who wanted it. It is now on disk and ready to email!

!WARNING!: THE FILE IS HUGE. It is 26 pages in length and contains the clinical references to 283 clinical studies and trials (which is why this has taken so long!). It is organized alphabetically by author and contains the author's name, the title of the study/report, the date it was published and where it was published. It does NOT contain abstracts. PLEASE don't ask me to send information just pertaining to a specific illness/disease, as it is NOT organized in this manner, and would be impossible for me to provide. Ginkgo has been researched and studied extensively in Europe and about 1/3 of the research titles have not been translated from German or French.

So if you still want this, just email me and let me know. I'll email it out in ascii format to any who want it.

As this may be a little much for the average consumer to consume, I have provided below some excerpts from literature concerning Ginkgo, its uses, and an overview of some of the clinical research as it pertains to specific illnesses and conditions all written by others more well informed than myself. Sorry if it gets a little technical, this is the best I could provide without trying to author something with my own limited non-medical (lowly researcher) opinions. Maybe some of the more professional readers can provide any medical interpretations necessary.

Hope this is helpful.

Leslie Taylor The Raintree Group (who sells no Ginkgo - so can provide this info without any problem)

For information purposes only.... "GINKGO BILOBA (Family Ginkgoaccae) Common Name: Ginkgo tree

GENERAL INFORMATION: Ginkgo biloba is a deciduous tree which may live as long as 1,000 years, growing to a height of l00-122 feet and a diameter of 34 feet. The leaf resembles a fan or the maidenhair fern. Because of this the ginkgo has also been called the 'maidenhair tree.' It is the leaves of the ginkgo which are used medicinally. Ginkgo bears a foul-smelling fruit that is non-edible and an ivory-colored inner seed that resembles an almond. The seed is edible and is sold in marketplaces in the Orient.

CHEMICAL COMPOSITION: The active components of ginkgo leaves are the so called ginkgo heterosides or ginkgo-flavone glycosides (flavonoid molecules which are unique to the ginkgo), several terpene molecules unique to ginkgo (ginkgolides and bilobalide), and organic acids. Ginkgo biloba extract (GBE) marketed In Europe under the trade names Tanakan, Rokan, and Tebonin is a very well-defined and complex product prepared from the green leaves. The mode of culture, harvesting, and extraction are standardized and controlled in Europe and the Orient. GBE is standardized to contain 24% flavonoid glycosides. This product is available in the US under various labels in the health food stores and should state that its a "24% standardized extract" on the label.

The three major aglycones are quercetin, kaempferol and isorhamnetin. The glucosidic components are glucose and rhamnose present as monoglucosides or diglucosides in esterified as well as non-esterified forms.

Other significant flavonoid components of the extract include proanthocyanidins largely composed of dimers and oligomers of delphinidine and cyanidin. (Antioxidants)

HISTORY AND USE Ginkgo biloba is the world's oldest living tree species. The ginkgo tree can be traced back more than 200 million years to the fossils of the Permian Period and for this reason is often referred to as "the living fossil". In the late 17th century, Dr. Kaempfer, a German physician and botanist, became the first European to discover and catalog the ginkgo tree. Ginkgo's medicinal use can be traced back to the oldest Chinese materia medica (2800 BC). The ginkgo leaves have been used in traditional Chinese medicine for their ability to "benefit the brain",, relieve the symptoms of asthma and coughs, and help the body eliminate filaria. Ginkgo leaf extracts arc now the leading prescription medicines in both Germany and France. The extracts account for 1.%. and 1.5% of total prescription sales in Germany and France respectively.

PHARMACOLOGY: The standardized concentrated extract of the leaves of Ginkgo biloba (24% ginkgo heteroside content) has demonstrated remarkable pharmacologic effects. According to Drieu, the total extract is more active than single isolated components.

I have found more than 250 clinical and experimental studies utilizing the extract and will attempt to give you a broad overview of them concerning the areas, illnesses and conditions studied with Ginkgo. The studies included human, animal and in vitro studies. The human studies are widespread and included double-blind, randomized and placebo controlled studies.

GENERAL TISSUE EFFECTS Ginkgo biloba Extract (GBE) has been found to exert profound general tissue effects including membrane stabilizing, anti-oxidant, and free radical scavenging effects. GBE also enhances the utilization of oxygen and glucose. GBE has shown to be an extremely effective inhibitor of lipid peroxidation of cellular membranes. Erythrocyte studies utilizing GBE have demonstrated that in addition to stabilizing membrane structures directly and its free radical scavenging effects, GBE also activates membranal Na+K+ATP-ase or sodium pump. This enzyme Is responsible for the exchange of intracellular sodium for extracellular potassium. In essence, GBE leads to better membranal polarization. This is of importance in excitable tissues, particularly nerve tissues.

NEURONAL CELLS Briefly: GBE promotes increased nerve transmission rate, improved synthesis and turnover of cerebral neurotransmitters, and promotion of acetylcholine receptors in the hippocampus. Not so briefly: GBE's membrane stabilizing and free radical scavenging effects are perhaps most evident In the central nervous system. Brain cells contain the highest percentage of unsaturated phospholipids in their membranes of any cells in the body, making them extremely susceptible to lipid peroxidation. GBE has the ability to prevent metabolic and neuronal disturbances In experimental models of cerebral ischemia and hypoxia. It accomplishes these positive results largely via its ability to enhance the utilization of oxygen and Increase the cellular uptake or glucose, thus restoring aerobic glycolysis. More specifically, GBE improves mitochondrial respiration, diminishes cerebral edema, improves membranal dynamics including collection of ionic disturbances, stabilizes lysosomal membranes, and inhibits the action of proteolytic enzymes. GBE also has the ability to reestablish effective tissue perfusion and to normalize the circulation in the areas most affected by microembolization, namely the hippocampus and striatum.

VASCULAR EFFECTS: The mechanisms of GBE's vascular effects have been investigated in a number of in vitro and invito studies. Briefly: GBE exerts its vascular effects primarily by affecting the vascular endothelium and the adrenergic vasoregulatory system. Its vasodilating action is explained by direct stimulation of the release of endothelium-derived relaxing factor (EDRF) and prostacyclin. In addition, GBE inhibits phosphodiesterase, thereby increasing the intracellular concentration of cyclic-AMP which leads lo smooth muscle cell relaxation in the intima of the vessel. GBE has evidenced tonic effects which are capable of restoring circulation in cases of vasomotor paralysis as well as relaxant effects in cases of vasomotor spasm.

PLATELET EFFECTS GBE and isolated Ginkgolides have demonstrated profound effects on platelet function including inhibition of platelet aggregation, adhesion, and degranulation.These effects appear lo be due to direct membranal and antioxidant effects, increased synthesis of prostacyclin, inhibition of phosphodiesterase, and antagonism of platelet activating factor (PAF).

CLINICAL APPLICATIONS: Ginkgo biloba extract's primary clinical application has been in the treatment of vascular insufficiency. In numerous clinical trials, both patients with chronic cerebral arterial insufficiency and peripheral arterial insufficiency have responded favorably to GBE.

GBE IN CEREBRAL VASCULAR INSUFFICIENCY AND IMPAIRED CEREBRAL PERFORMANCE: In 20 human studies, GBE has displayed a statistically significant regression of the major symptoms of cerebral vascular Insufficiency and impaired cerebral performance. These symptoms included: short-term memory loss, vertigo, headache, ringing in the ears, lack of vigilance and depression. The significant regression of these symptoms offered by GBE suggests that vascular Insufficiency may indeed be the major causative factor accounting for these so called 'age-related cerebral disorders' versus a true degenerative process. As well as improving blood supply to the brain, Ginkgo biloba extract also increases the rate at which information is transmitted at the nerve cell level. This has been demonstrated in experimental and clinical studies. In another double-blind clinical study, Ginkgo biloba extract was shown to induce in elderly patients a restoration of vigilance towards normal levels and improved mental performance. The findings at the behavioral level correlated with improvements in EEG tracings. The patients with a more unfavorable initial situation as measured in resting EEG activity displayed the greatest improvement. The conclusion or the study was 'the results show that chronic GBE medication has a positive effect in geriatric subjects with deterioration of mental performance and vigilance, and this effect is reflected at the behavioral level." It must be pointed out that it says GBE should be taken consistently for at least 12 weeks In order to determine effectiveness. Although most people report benefits within a 2 to 3 week period, some individuals may take longer to respond. Warburton reviewed 20 carefully conducted studies involving a total of 770 patients observed for an average period of 4 months (ranging from 2 weeks to I year) and concluded: "It seems that the longer the treatment is continued, the more obvious and lasting the result. Even at the end of a year, it was found that improvement was continuing and adherence to the treatment was good. At least eight days are necessary before the first clinical effects are manifested."

GBE IN ALZHEIMER'S DISEASE: Ginkgo biloba extract is showing great benefit in many cases of senility including Alzheimer's. In addition to GBE's ability to increase the functional capacity of the brain via the mechanisms described above, it also has been shown to normalize the muscarinic acetylcholine receptors in hippocampus in aged animals and increase cholinergic transmission as well as address many of the other major elements of Alzheimer's disease. Although preliminary studies in established Alzheimer's patients are quite promising, at this little it appears that GBE can only help delay clinical deterioration in the early stages of Alzheimer's disease.

GBE IN TINNITUS: GBE has demonstrated favorable improvements in patients suffering from tinnitus in several clinical trials including 2 double-blind clinical studies. In one study, GBE improved the condition regardless of prognostic factor while another reported the complete abolition of tinnitus in 12 of 33 patients and improvement in five more.

GBE IN COCHLEAR DEAFNESS: Ischemia is usually the pathogenic factor in acute cochlear deafness. GBE was shown to improve recovery in cases of acute cochlear deafness due to idiopathic sudden deafness or deafness due to sound trauma or barotrauma.

GBE IN SENILE MACULAR DEGENERATION AND DIABETIC RETINOPATHY: In a small double-blind study, GBE demonstrated a statistically significant improvement in long distance visual acuity. In 4 studies GBE demonstrated impressive protective effects against free radical damage to the retina. In another study, GBE has been shown to prevent diabetic retinopathy in alloxan induced diabetic rats suggesting it may have a protective effect in human diabetics.

GBE IN PERIPHERAL ARTERIAL INSUFFICIENCY: In 3 double-blind randomized clinical trials of Ginkgo biloba extract versus a placebo in two parallel groups of patients with peripheral arterial insufficiency of the leg, Ginkgo biloba extract was shown to be quite active and superior to placebo. Not only were measurements of pain-free walking distance and maximum walking distance dramatically increased, but plethysmographic and doppler ultrasound measurements (after exercise) were also increased reflecting increased blood flow through the affected limb. GBE IN ERECTILE DYSFUNCTION:

A preliminary clinical study indicated GBE may be effective in impotency due to arterial insufficiency. In the study, sixty patients with proven arterial erectile dysfunction who hadn't reacted to papaverine injections up to 50 mg., were treated with Ginkgo biloba extract in a dose of 60 mg. per day for 12 to 18 months. The penile arterial blood flow was reevaluated by duplex sonography every four weeks.The first signs of improved blood supply were seen after six to eight weeks; after six months therapy 50% of the patients had regained potency and in 20% a new trial of papaverine injection was then successful; 25% of the patients showed an improved arterial inflow, but papaverine was still not successful. The remaining five percent were unchanged. The improvement of the arterial inflow is assumed to be due to the known direct effect of Ginkgo on endothelial cells which enhances blood flow of both arteries and veins without any change in systemic blood pressure.

DOSAGE Most of the clinical research on Ginkgo biloba has utilized a standardized extract, containing 24% Ginkgo heterosides (flavoglycosides), at a dose or 40 mg. three times a day. The 24% Standardized extract is sold in most health foods stores under several labels. It is difficult to devise a dosage schedule using other forms of ginkgo due to extreme variation in content of active compounds in dried leaf and crude extracts.

If by chance a standard 1:5 tincture was obtained from the highest possible flavonoid content crude ginkgo leaf, it would require 1 ounce of the tincture per day to approach the equivalent dosage level of the standardized extract used in the clinical studies.

To prepare a at-home Ginkgo tincture, read the article written by P. Berger, titled "Ginkgo Biloba" in Medical Herbalism 2:1,5,6, 1990.