Ginkgo biloba, commonly referred to as Ginkgo or maidenhair tree, is a member of the Ginkgoaceae family.  Botanically, Ginkgo is a deciduous tree growing up to 100m in height.  It is a dioecious plant, meaning the male and female flowers grow on separate trees. The leaves have a characteristic fan-like appearance, bi-lobed, and appear with a dichotomous venation. The naked seed of the Ginkgo tree is a nut which is edible and was used in the past as a medicinal agent. However, the leaves of younger trees are now the part of the plant that used for medicinal application. Extracts of Ginkgo exhibit a slightly sour taste.
Ginkgo is an ancient tree that has remained virtually unchanged for approximately 150 million years. It can live up to 1000 years and is considered a living fossil, being the world’s oldest living tree species. The Chinese are credited with saving this tree from extinction as they planted it around holy sights as a revered specimen. Ginkgo was used medicinally by the Chinese over 5000 years ago, where it was prescribed for some of the same conditions it is used for today, including enhancement of cognitive ability in the aging population.
There are two main categories of active constituents, responsible for the remedial powers of Ginkgo: Ginkgo flavone glycosides (flavonoid glycosides), and Terpene lactones (terpenoids). [3, 4] Extracts of ginkgo are standardized to contain 24% ginkgo flavone glycosides and 6% terpenoids. The flavone glycosides include quercetin, kaempferol, isorhamnetin (including coumaric acid esters of flavonoids). These important constituents contribute to the antioxidant activity and mild platelet aggregation inhibitory activity of ginkgo.
The terpene lactones comprise the Ginkgolides and bilobalide(s) A, B, C, and J.  Terpenoids are associated with increased circulatory activity to the brain and other parts of the body; as well as protective properties for neurons (nerve cells). Other constituents found in the leaves of Ginkgo trees include; biflavonoids, sterols, ginkgolic acids, procyanadins, and polysaccharides.
The standardized Ginkgo extract is the form used for clinical application and in research studies. It is often considered the most effective and beneficial form of Ginkgo, as it contains significant amounts of the medicinally active compounds. Ginkgo extract was actually patented in Germany, and is prepared over a 2 week period where more than 50 pounds of Ginkgo leaves are converted into one pound of extract.  If one was to use preparations that were not standardized, the volume of extract needed to be effective would contain high levels of undesirable compounds. Furthermore, the sheer volume of extract required would not be practical to prescribe.
Medicinal actions ascribed to Ginkgo include; [1, 2, 6, 7]
- PAF (platelet activating factor)
- tissue perfusion enhancer
- circulatory stimulant
- nootropic (means “acting on the mind”)
A large collection of evidence exists for the use of Ginkgo as a medicinal agent. Ginkgo is one of the most intensely researched herbal medicines, beginning with the German investigations in the late 1950s and early 1960s. Ginkgo is widely known for its use in the elderly for the treatment of age related-cognitive decline (ARCD), or memory impairment in healthy individuals; as well as cerebrovascular insufficiency.
Ginkgo extract for the treatment of cerebrovascular insufficiency has been extensively studied. This term refers to a diminished flow of blood to the brain, common in the elderly, resulting in symptoms such as; memory loss, disorientation, fatigue, anxiety, dizziness and depression. The pharmacologic action of Ginkgo extract equals enhancing circulation to the brain and inhibiting platelet aggregation; making it a prime candidate for treatment of this such cognitive disorders. Trials have consistently shown results that support Ginkgo’s use in cerebrovascular insufficiency. A meta-analysis of 11 double-blind, placebo-controlled trials concluded that Ginkgo extract provides a better therapeutic effect than placebo for the treatment of this condition. 
An important trial was conducted in the United States to examine the safety and efficacy of Ginkgo extract for patients with mild to severe Alzheimer's disease or multi-infarct dementia.  A large randomized double-blind, placebo-controlled clinical trial (which is the gold standard) lasting one year investigated the administration of a 120 milligram daily dose of standardized (50:1) extract or placebo. Patients were assessed using standardized evaluations, including the Geriatric Evaluation by Relative’s Rating Instrument (GERRI). The results showed that patients taking the standardized Ginkgo extract had significant improvements over placebo in two out of three of the evaluation tools. As well, the standardized ginkgo extract produced no significant difference in adverse effects over placebo. The authors concluded that for patients with dementia, standardized ginkgo extract is a safe and effective therapy for stabilizing and improving cognitive performance and social function. Numerous other studies have exhibited similar findings. [10, 11]
Ginkgo is also an efficacious treatment for intermittent claudication, which is classified as a peripheral arterial disease (PAD). Patients generally experience bouts of severe pain in their legs due to poor circulation to the extremities. Randomized double-blind, placebo-controlled clinical trials have demonstrated the benefit of Ginkgo for patients suffering from this painful disease. [12-14] A meta-analysis of these trials was performed, concluding that the use of standardized Ginkgo extract is similar to clinical outcomes of specific drug therapies, namely pentoxifylline.  Other clinical trials have demonstrated improved walking performance, improvement in rapid anti-ischemic activity, and reduced pain severity. [16-17]
Another possible application for Ginkgo extract is for sexual dysfunction of vascular etiology. A small, open study of 30 men showed that Ginkgo can reduce sexual problems caused by antidepressants like fluoxetine, bupropion, venlafaxine, and nefazodone.  The results revealed that approximately 200 milligrams (mg) of supplemental Ginkgo per day had a positive effect on sexual function in 76% of the men. This effect is likely caused by Ginkgo’s activity in enhancing blood flow.
In addition, Ginkgo may be beneficial for the treatment of early-stage macular degeneration, asthma symptoms, atherosclerosis, migraines, vertigo, premenstrual syndrome, cochlear deafness, and diabetic retinopathy. [19, 20]
As mentioned, preparations of Ginkgo should only be utilized if they are of the 50:1 standardized extract type, specifically containing 24% flavone glycosides and 6% terpenoids. All of the research concerning the efficacy and safety of Ginkgo extracts were conducted using this potency of standardized extract. Furthermore, this extract eliminates many other constituents, including bioflavonoids, ginkolic acids, and sterols, which may cause adverse effects.
Typical dosages of the 50:1 standardized Ginkgo extract exist as 120 mg daily, administered in divided doses (equivalent to 27 - 30 mg Ginkgo flavone glycosides and 10 mg terpenoids per day). Generally, 40 mg tablets and 40 mg/ml liquids are available. Ginkgo should be administered for at least 6 weeks before being reassessed. This time frame may, however, vary depending on the condition being treated. Combination products on the market include Tanakan, Rkan, Ginkgobil, Kaveri, and Tebonin. 
Caution must be taken in patients with blood clotting disorders. Three case reports of spontaneous bleeding with Ginkgo use have been reported (both standardized and non-standardized preparations).  Cases where there is excessive bleeding may also be contraindicated, such as menorrhagia. Ginkgo may be contraindicated in anovulatory amenorrhea.
Ginkgo may interact with a number of prescription medications.  Ginkgo should be avoided in patients taking anticoagulant or antiplatelet medications like warfarin, heparin and aspirin. Other drug interactions include possible potentiation of MAO inhibitors and potentiation of papaverine.
The raw seeds, stems and leaves contain 4’-O-methylpyroxidine which can cause vitamin B6 deficiency symptoms including convulsions. [22, 23] The stems have been measured to contain 42 mg per gram fresh weight. The oral toxic dose in guinea pigs was 11 mg/kg. Bilobalide appears to decrease the toxic affect. Side effects from the consumption of the leaf include gastrointestinal discomfort, headaches and dizziness; from the fruit/nut includes erythema, edema, vesicles and severe gastrointestinal irritation. No overdose cases have been documented with use of the standardized extract.
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