Gingko Biloba Introduction   Gingko biloba, commonly referred to as gingko or maidenhair tree, is a member of the Gingkoaceae family. [1]  Botanically, gingko is a deciduous tree growing up to 100m in height. [2]  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 Gingko 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 Gingko exhibit a slightly sour taste.   Gingko 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.  Gingko 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 Gingko: Ginkgo flavone glycosides (flavonoid glycosides), and Terpene lactones (terpenoids). [3, 4]  Extracts of gingko 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 Gingko.    The terpene lactones comprise the Ginkgolides and bilobalide(s) A, B, C, and J. [5]  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 Gingko trees include; biflavonoids, sterols, gingkolic acids, procyanadins, and polysaccharides.     The standardized Gingko extract is the form used for clinical application and in research studies.  It is often considered the most effective and beneficial form of Gingko, as it contains significant amounts of the medicinally active compounds.  Gingko extract was actually patented in Germany, and is prepared over a 2 week period where more than 50 pounds of Gingko leaves are converted into one pound of extract. [5]  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 Gingko include; [1, 2, 6, 7] PAF (platelet activating factor) antagonist antioxidant anti-atherosclerotic tissue perfusion enhancer circulatory stimulant nootropic (means "acting on the mind") anti-inflammatory anti-thrombotic     Gingko Biloba Uses   A large collection of evidence exists for the use of Gingko as a medicinal agent.  Gingko is one of the most intensely researched herbal medicines, beginning with the German investigations in the late 1950s and early 1960s.  Gingko 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.   Gingko 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 Gingko 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 Gingko's use in cerebrovascular insufficiency.  A meta-analysis of 11 double-blind, placebo-controlled trials concluded that Gingko extract provides a better therapeutic effect than placebo for the treatment of this condition. [8]   An important trial was conducted in the United States to examine the safety and efficacy of Gingko extract for patients with mild to severe Alzheimer's disease or multi-infarct dementia. [9]  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 gingko extract had significant improvements over placebo in two out of three of the evaluation tools.  As well, the standardized gingko extract produced no significant difference in adverse effects over placebo.  The authors concluded that for patients with dementia, standardized gingko 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]   Gingko 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 Gingko for patients suffering from this painful disease. [12-14]  A meta-analysis of these trials was performed, concluding that the use of standardized Gingko extract is similar to clinical outcomes of specific drug therapies, namely pentoxifylline. [15]  Other clinical trials have demonstrated improved walking performance, improvement in rapid anti-ischemic activity, and reduced pain severity. [16-17]   Another possible application for Gingko 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. [18]  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 Gingko's activity in enhancing blood flow.         In addition, Gingko 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]     Gingko Biloba Dosages   As mentioned, preparations of Gingko 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 Gingko 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 Gingko extract exist as 120 mg daily, administered in divided doses (equivalent to 27 - 30 mg Gingko flavone glycosides and 10 mg terpenoids per day).  Generally, 40 mg tablets and 40 mg/ml liquids are available.  Gingko 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. [4]     Gingko Biloba Toxicities and Contraindications   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). [2] Cases where there is excessive bleeding may also be contraindicated, such as menorrhagia. Ginkgo may be contraindicated in anovulatory amenorrhea.   Gingko may interact with a number of prescription medications. [21] Gingko 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.[4] No overdose cases have been documented with use of the standardized extract.     Gingko Biloba Products   The following table lists various products that contain a safe and reliable source of Gingko Biloba:   Manufacturer Ingredient Amount US RDA Learn More NSI Ginkgo Biloba Extract 120mg -- Click Here Kyolic Ginkgo Biloba Leaf Extract 50:1 40mg -- Click Here

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