Botanical name: Ginkgo biloba, Ginkgoaceae

Common names: Ginkgo, Maidenhair tree

Plant description: Ginkgo grows to become a medium to large deciduous tree, with narrow spreading braches and a pyramidal shape when young, but after hundred years or so becoming more widely branched with a large or upright oval crown.  The bark is light brown to brownish-gray, and becomes deeply furrowed with age.  The characteristic bi-lobed leaves have forked veins that radiate outward from the stem.  Ginkgo is dioecious, and like the conifers, wind is required to carry the pollen to female trees. The fruit is a large woody stone enclosed in a green edible flesh.

Habitat, ecology and distribution: Ginkgo biloba is the only living representative of the order Ginkgoales, a group of gymnosperms comprised of the family Ginkgoaceae, which 200-300 million years ago consisted of some 18 members.  Fossil records indicate there were at least two different species of Ginkgo.  Today, Ginkgo has been found growing wild in the warm, mountainous regions of central and western China, but it is unknown whether these specimens are truly wild or are derived from cultivated specimens.  Despite being confined to China and Japan less than a few hundred years ago, Ginkgo is now widely cultivated all over the world as a tree of commerce.

Part used: Dried leaf; fresh and dried fruit (nuts).

History: Ginkgo is one of the oldest living tree species in the world, extending more than 200 million years into the past, first appearing in the Carboniferous.   During the Jurassic period Ginkgo was widespread throughout Asia, Europe and North America, and even survived the Cretaceous that marked the end of the dinosaurs.  From the fossil record it appears that Ginkgo disappeared from North America about 7 million years ago, in Europe by about 2.5 - 3 million years ago, and was next to non-existent in most of Asia.  Most European botanists had begun to think that Ginkgo was extinct, but in 1691 the German botanist Engelbert Kaempfer discovered it growing in the courtyards of Buddhist temples in Japan. These specimens had been cultivated by Buddhist monks since the 12th century, taken from older specimens found in China.  Ginkgo was highly revered by the ancient Chinese, the characteristic bi-lobed leaf said to represent the duality of yin and yang within the unity of the tao.   It was these same Taoist, Buddhist and Shaolin monks that appeared to have protected Ginkgo from complete extinction - the wide crown of these ancient trees spreading over the quietude of temple courtyards, some specimens today more than a thousand years old. The oldest European ginkgo was sown in 1730 in the Utrecht Botanical Gardens, and later in 1762 in the Kew Botanical Garden in London, both of which are still living.  Ginkgo was a favorite tree of the American architect Frank Lloyd Wright, and since this time Ginkgo has become popular ornamental in North America.  Ginkgo is particularly noted for its ability to withstand adversity, as evidenced by the survival of a specimen after the bombing of Hiroshima in 1945.  After all plant life had been reduced to ash from the bombing, the following spring a Ginkgo was seen to sprout from the charred earth ground, and since that time a temple has been constructed around it as a memorial.  This ability to withstand mutagens like radiation has encouraged urban planners to plant Ginkgo trees in polluted, high traffic areas (Kwant 2003).

  Ginkgo is an important plant in China, the nuts mentioned as food as early as the Han dynasty (206BCE-220CE), still popular today in Chinese cuisine. As a medicine the nuts were first mentioned in Li Tung-wan's Shih Wu Pen Ts'ao ('Edible Herbal') that dates from the Yuan Dynasty (1280-1368 CE).  Later, in 1505, the leaves were mentioned by Liu Wen-Tai as a treatment for diarrhea. In 1932 the Japanese first isolated terpene lactones called the ginkgolides, and later during the 1960's German researchers discovered that the flavonoid glycosides were particularly active in circulatory problems In 1965 the Dr. Willmar Schwabe company produced and marketed a high-potency extract standardized to its flavonoid constituents called EGb 761.  In 1990 Elias Corey of Harvard University received the Nobel prize for chemistry for the synthesis of ginkgolide B and other organic molecules (Kwant 2003).

Constituents: The primary constituents of interest in Ginkgo are the flavonoids and lactone diterpenes that have been the subject of a significant amount of scientific research during the last forty years.  The diterpenes are comprised of bilobalide and ginkgolides A, B, C, J and M.  Among the flavonoid constituents of interest are dimeric flavones such as bilobetin, ginkgetin, iosginkgetin, and sciadopitysin, as well as the flavones quercitin, kaempferol, and isorhamnetin.  Also found in Ginkgo are a range of proanthocyanidins, sterols, ginkolic acids, amino acids (e.g. 6-hydroxykynurenic acid, a metabolite of tryptophan), and polysaccharides.  Today most extracts on the market are standardized to at least 24% flavone glycosides and 6% diterpenes, sometimes referred to in shorthand as EGb. (Mills and Bone 2000, 405; Newall et al 1996, 138).

Medical Research:  As stated, Ginkgo has been the subject of a significant amount of research over the last while, particularly by the Germans and the French, and has become one of the most popular herbal remedies in the market place, first in Europe and now in North America.  Describing Ginkgo as a herbal remedy is somewhat of a misnomer, as the strength of the standardized extract cannot be obtained in traditional herbal preparations such as an infusion or tincture.  Furthermore, because Ginkgo leaf has weak traditional usage it is unclear if many of the benefits indicated in experimental research trials apply to actual clinical usage.  Indeed, upon cursory examination, the number of pharmacological activities described for EGb appear to suggest that Ginkgo is a kind of panacea, which is unlikely.  Many studies have shown that EGb has many beneficial effects, especially upon the cardiovascular system, with data obtained from in vitro studies, experimental animal models, and human clinical trials. 
•Cardiovascular: The ginkolides have been shown to antagonize platelet-activating factor (PAF), a potent vasoactive mediator released by all activated inflammatory cells, inducing platelet aggregation, vascular permeability, arachidonic acid metabolism and anaphylaxis (Mills and Bone 2000, 405).  The ginkgolides have also been shown to prevent metabolic damage in experimental cerebral ischemia, significantly reducing arrhythmia and infarct size in myocardial occlusion.  Overall, much of the evidence suggests that Ginkgo has a neuroprotective effect in ischemic and hypoxic conditions, increasing tolerance of the ischemic state and limiting the damage of reperfusion, inhibiting vasospasm and thrombus formation, and scavenging reactive oxygen species (Mills and Bone 2000, 405-407).  Randomized placebo-controlled clinical trials in patients with peripheral arterial disease have consistently indicated an overall benefit with EGb, improving walking performance and cognitive function, decreasing ischemia and decreasing pain (Mills and Bone 2000, 413).
•Cerebral insufficiency: Cerebral insufficiency (CI) is a collection of symptoms that are associated with mental deterioration, typically found in elderly people, manifesting as poor concentration, absentmindedness, confusion, fatigue, anxiety, dizziness, tinnitus and headaches (Mills and Bone 2000, 409).  Although not widely accepted as a medical condition per se, recent research indicates that these symptoms can be correlated with low attenuation of the white matter of the brain, a feature often seen in head injuries and stroke.  The efficacy of Ginkgo extracts in CI-related symptoms demonstrated in clinical trials suggests that Ginkgo may help prevent damage to the white matter by improving local blood supply (Mills and Bone 2000, 409-411).
•Central nervous system: Ginkgo extract has been shown to promote a significant increase in dopamine synthesis, enhance the release of the catecholamines epinephrine and norepinepherine, and increase the number of cholinergic receptors in the brain in experimental animal models (Le Poncin-Lafitte et al 1982; Auguet et al 1982; Taylor et al 1986).
•Neuroprotective: Ginkgo has also been shown to reduce brain edema by stabilizing the blood brain barrier (BBB), reducing ion-exchange problems and the accumulation of neurotoxins (Eteinne et al 1986).
•Tinnitus and vertigo: Researchers examined the efficacy of a Ginkgo extract in conjunction with physical therapy (kinezytherapy) in 45 persons aged between 35 and 48 years with clinical symptoms of peripheral vestibular lesion. After 30 days of administration almost all cases showed improvement, with or without the Ginkgo extract (i.e. kinezytherapy alone), although the group taking the extract with physical therapy were shown to gain full vestibular compensation sooner (Orendorz-Fraczkowska et al 2002).  An open, controlled study of 44 patients complaining of vertigo and dizziness caused by vascular vestibular disorders examined the efficacy of EGb 761, 80 mg twice daily for 3 months. A complete neuro-otologic and equilibrimetric examination was performed at baseline and after 3 months of treatment, the results indicating that EGb 761 can considerably improve oculomotor and vestibular function (Cesarani et al 1998). The efficacy of a Ginkgo biloba extract was examined in a double-blind placebo-controlled clinical trial of 70 patients with vertiginous syndrome of recent onset and undetermined origin over a 3-month period.  At the end of the trial, 47% of the patients treated with Ginkgo had found their symptoms completely ameliorated, compared with 18% in the placebo group (Haguenauer et al 1986).
•Cognition: Reseachers in Australia conducted a 30 day randomized, double-blind, placebo-controlled clinical trial of 61 healthy participants prescribed a standardized extract of Ginkgo (EGb) to determine its nootropic potential.  The results indicated that EGb promotes significant improvements in the speed of information processing, working memory and executive processing (Stough et al 2001).  Other clinical trials support the nootropic properties of Ginkgo as well, but not when taken for short periods of time, even at high doses (Mills and Bone 2000, 407).
•Alzheimer's disease: A 52-week, randomized, double-blind, placebo-controlled, parallel-group, multicenter research trial studied the benefit of a 120 mg standardized Ginkgo extract (EGb) in Alzheimer's disease.  The results of the study suggested that the Ginkgo extract could enhance cognitive performance and social functioning regardless of whether the dementia was mild or moderately severe. The greatest improvements in cognitive impairment occurred in patients with only mild impairment (LeBars et al 2002).  A 24-week, randomized, double-blind, placebo-controlled, parallel-group, multicenter trial studied the benefits of Ginkgo biloba extract EGb 761 in older people with dementia or age-associated memory impairment. The results indicated that  Ginkgo has little effect in patients with with mild to moderate dementia or age-associated memory impairment (van Dongen et al 2000).  An uncontrolled clinical trial comprised of 18 elderly subjects with light to moderate dementia compared the efficacy of 40 mg of the drug tacrine, which is approved for use in the treatment of Alzheimer's disease, with 240 mg of EGb 761.  Outcomes were based on computer-analyzed EEGs (CEEGs) after administration, which looked for a relative increase of 7.5 to 13 Hz ("alpha") and decrease of 1.3 to 7.5 Hz ("delta" and "theta") activity, an event characterized by the term "cognition activation." The results indicated that EGb achieved typical cognitive activator CEEG profiles in more subjects (8 of 18) than 40 mg tacrine (3 of 18 subjects) (Itil et al 1998). Researchers studied the influence of a daily dose of 240 mg of EGb 761 in a double-blind, randomized, placebo-controlled study of 20 outpatients with Alzheimer-induced dementia over a 3 month period.  Outcomes were based on the sum score of the SKT-test for the determination of attention and memory, as well as other psychometric tests (i.e. trailmaking test, ADAS, CGI) and electrophysiological investigations (EEG topography).  Overall, the active-treatment group experienced a greater improvement in measured parameters in the SKT-test, with similar indications of efficacy in psychometric tests (Maurer et al 1997). A 52-week, randomized double-blind, placebo-controlled, parallel-group, multicenter study examined the efficacy of EGb in 202 mild to severely demented outpatients with Alzheimer disease or multi-infarct dementia.   Outcomes were assessed by the Alzheimer's Disease Assessment Scale-Cognitive subscale (ADAS-Cog), Geriatric Evaluation by Relative's Rating Instrument (GERRI), and Clinical Global Impression of Change (CGIC).  The results indicated that EGb group had an ADAS-Cog score 1.4 points better than the placebo group (P=.04) and a GERRI score 0.14 points better than the placebo group (P=.004). No difference was seen in the CGIC.  The tolerability of EGb was similar to placebo. Overall EGb appeared to be a safe remedy to improve cognitive performance, with the changes of significant enough to be recognized by caregivers (LeBars et al. 1997).
•Asthma: A standardized extract of Ginkgo was shown to improve peak flow rates in asthmatic children and promote a significant clinical improvement in adult asthmatics (Mills and Bone 2000, 412).
•Altitude sickness: A randomized placebo-controlled clinical trial studied the preventative effects of a Ginkgo extract, dosed at 160 mg daily, during a Himalayan mountaineering expedition.  Results indicate that Ginkgo can prevent altitude sickness at moderate altitudes (5400 m) and decrease vasomotor disorders in the extremities (Mills and Bone 2000, 413).
•Ophthalmological disorders: In 24 patients suffering from a blockage of the veins of the retina a Ginkgo extract was shown to improve blood vessel integrity, visual acuity and enhance the field of vision (near and far vision and colour recognition).  An uncontrolled trial with 120 mg of EGb over a three month period was shown to improve symptoms in 86% of patients with impaired vision (Mills and Bone 2000, 413).

Toxicity: A standardized extract of Ginkgo was shown to have an oral LD50 value of 7.7g/kg in mice.  Chronic toxicity studies of oral doses up to 1600 mg/kg daily in rodents showed no evidence of organ damage or teratogenic effects.  The seeds of Ginkgo nut contain the toxin 4'-O-methylpyroxidine, which can cause symptoms of a vitamin B6 deficiency.  There have been cases of poisoning reported in Japan and China, with children apparently more susceptible.  The acute oral dose is listed as 11 mg/kg in guinea pigs, and the toxin has been measured at levels up to 42 mcg per gram of fresh weight Ginkgo stem (Mills and Bone 2000, 414).  The fruit pulp is reported to cause severe allergic reactions when applied to exposed skin, including erythema, edema, blisters and itching (Newall et al 139, 1996).

Herbal action: antioxidant, circulatory stimulant, cerebrovascular stimulant, geriatric restorative; the nuts are used in China as an expectorant and antitussive.

Indications: cerebrovascular insufficiency, vertigo, tinnitus, age-related macular degeneration, age-related deafness, dementia, mental confusion, memory loss, Alzheimer's disease, altitude sickness

Contraindications and cautions: Ginkgo may potentiate the effects of warfarin and aspirin.

Medicinal uses: Ginkgo is an unusual example of a herbal product that has little basis in tradition, its modern clinical usage derived almost entirely from research conducted on the standardized extract.  On the whole the research suggests that Ginkgo is a useful plant in age-related disorders, used primarily to enhance blood flow and oxygen utilization, inhibit inflammation and scavenge free radicals.  Even though the extract EGb represents a ratio of 50 parts plant to one part extract (50:1), more closely resembling what might be called a 'neutraceutical,' it has been remarkably well-tolerated in clinical trials.  Despite the safety of the extract, some herbalists prefer to make their own, typically as a fresh or dry plant tincture.  Limited clinical experience suggests that the tincture is probably active, although most practitioners will probably combine it with other, similarly acting herbs such as Crataegus.  In Chinese medicine both the nut and the leaf are used cough, wheezing and lung pain from Lung deficiency syndromes.  The nut is also used in incontinence and spermatorrhea, excessive vaginal discharges and turbid urine (Bensky and Gamble 1986, 309).

Pharmacy and dosage:
•Fresh Plant Tincture: fresh leaf, 1:2, 95% alcohol, 3-10 mL
•Dry Plant Tincture: recently dried leaf, 1:5, 25%, 3-10 mL
•Standardized extract: 24% flavonoids, 6% diterpenes, 80-240 mg

REFERENCES

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Etienne A et al. 1986. Mechanism of action of Ginkgo biloba extract in experimental cerebral edema Presse Med. Sep 25;15(31):1506-10.
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Weiss, Rudolf. 1988. Herbal Medicine. Translated by A.R. Meuss. Beaconsfield, England: Beaconsfield Publishers