Ginkgo

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Ginkgo biloba L.

[Fam. Ginkgoaceae]

Overview

Ginkgo is the oldest living species of tree on earth, dating back to the Paleozoic period, over 225 million years ago. The medicinal use of ginkgo leaf is first mentioned in Chinese medicine in the Ming dynasty in 1436 (Foster, 1996). A standardized extract of ginkgo leaf is one of the most clinically tested and frequently prescribed phytomedicines in Europe, and has been one of the 10 best-selling herbal dietary supplements in the U.S. for about six years (Blumenthal et al., 1998, 2001). Ginkgo biloba extract (GBE) is approved in Germany for the treatment of cerebral insufficiency (memory loss that occurs with conditions such as Alzheimer’s disease, vascular or multi-infarct dementia, and other conditions), tinnitus (ringing in the ears), vertigo, and intermittent claudication (poor circulation to the lower legs). In the U.S, ginkgo is used widely as a complementary therapy for Alzheimer’s disease and vascular dementia (Oken et al., 1998). For comprehensive detailed reviews, see DeFeudis (1998) and McKenna et al. (2001).

Description

Ginkgo preparations are derived from the dried, green leaf of Ginkgo biloba L. [Fam. Ginkgoaceae]. Ginkgo extracts are usually manufactured using acetone and water, and subsequent purification steps, without addition of concentrates or isolated ingredients. The dry extract is prepared pharmaceutically using a 35–67:1 ratio of dried leaves to final extract (50:1 is the average level at which the leading German product is based). Standardization is carried out to 22–27% ginkgo flavonol glycosides (e.g., the flavones quercetin, kaempferol, and isorhamnetin) and 5–7% terpene lactones (ginkgolides and bilobalide). In Germany, the content of ginkgolic acid is limited to a concentration of 5 parts per million (ppm). Scientific literature gives little or no support of the clinical benefits of other dosage forms of crude ginkgo leaf or low concentration extracts made from the leaf (Blumenthal et al., 2000).

Primary Uses

Neurology

Cerebral insufficiency:

The German Commission E approved ginkgo for the following symptoms resulting from demential syndromes: memory deficit, poor concentration, depression, dizziness, tinnitus, and headache (Blumenthal et al.,1998)

Treatment of attention and memory loss that occur with Alzheimer’s disease and multi-infarct dementia (Arrigo, 1986; Brautigam et al., 1998; Grässel, 1992; Halama et al., 1988; Hofferberth, 1994; Hofferberth, 1989; Kanowski et al., 1997; Kleijnen and Knipschild, 1992; Le Bars et al., 1997; Oken et al., 1998; Rigney et al., 1999; Taillandier et al., 1986; Vesper and Hansgen, 1994; Wesnes et al., 1987)

Vertigo and tinnitus (ringing in the ear) of vascular and involutional origin (Morgenstern and Biermann, 2002; Meyer, 1986; Dubreuil, 1986)

Vascular Disease

Peripheral vascular disease: improvement of pain-free walking distance in Peripheral Arterial Occlusive Disease in Stage II according to Fontaine (intermittent claudication) in a regimen of physical therapeutic measures, in particular walking exercise (Bauer, 1984; Peters et al., 1998; Schweizer and Hautmann, 1999; Pittler and Ernst, 2000) approved by Commission E (Blumenthal et al., 1998)

Other Potential Uses

Sexual dysfunction secondary to selective serotonin reuptake inhibitor (SSRI) use (Cohen and Bartlik,1998)

Control of acute altitude sickness and vascular reactivity to cold exposure (Leadbetter et al., 2001; Roncin et al., 1996)

Protective action in hypoxia (Schaffler and Reeh, 1985)

Acute cochlear deafness (Dubreuil, 1986)

Dosage

Internal

Standardized Preparations

Dry extract: total of 120–240 mg solid pharmaceutical form per day, administered in small doses (e.g., 40–60 mg) 2–3 times daily to treat dementia syndromes (Blumenthal et al., 1998), or total of 120–160 mg dry extract per day, administered in doses of 40–60 mg 2–3 times daily to treat intermittent claudication, vertigo, and tinnitus (Blumenthal et al., 1998; WHO, 1999).

Duration of Administration

German Commission E made the following recommendations: for chronic cognitive disorders, a minimum of eight weeks with administration for more than three months subject to medical review; for intermittent claudication, not less than six weeks; for vertigo and tinnitus (vascular origin), use for more than six to eight weeks has no therapeutic benefit (Blumenthal et al., 1998).

Clinical studies suggest the following duration: for cerebral insufficiency, four weeks to one year as observed in clinical trials (Kanowski et al., 1997; Grässel, 1992; Le Bars et al., 1997; Taillandier et al., 1986; Hofferberth, 1994; Vesper and Hansgen, 1994; Brautigam et al., 1998; Halama et al., 1988; Hofferberth, 1989; Wesnes et al., 1987; Arrigo, 1986; Rigney et al., 1999). Improvements are typically seen after eight to twelve weeks of treatment; 24 weeks for peripheral vascular disease (Bauer, 1984; Peters et al., 1998; Schweizer and Hautmann, 1999; Pittler and Ernst, 2000).

Chemistry

Standardized Preparations

The active constituents in ginkgo extract are unique diterpene lactones, ginkgolides A, B, C, and J, and the sesquiterpene lactone bilobalide (WHO, 1999). Standardized dry ginkgo extract contains 22–27% ginkgo flavonol glycosides (based on flavones like quercetin, kaempferol, and isorhamnetin) and 5–7% terpene lactones of which 2.9% is bilobalide and 3.1% the ginkgolides A, B, and C (Kleijnen and Knipshild, 1992). The relative amounts of the various flavonoids or the ginkgolide and bilobalide components of the terpenoids may vary across different commercial preparations (Sticher, 1993). Ginkgo extract contains trace amounts of ginkgolic acid, a potential allergen, which is limited to a maximum of 5 ppm by German authorities (Blumenthal et al., 1998). Extensive reviews of ginkgo chemistry have been written (Van Beek, 1998; Tang and Eisenbrandt, 1992; Braquet, 1988,1989).

Pharmacological Actions

Humans

Improves cognition (Rigney et al., 1999; Le Bars et al., 1997); improves working memory (Rigney et al., 1999); improves short-term visual memory in people with dementia (Brautigam et al., 1998); improves short-term memory in people with cerebral insufficiency (Grässel, 1992); improves social functioning in people with dementia (Le Bars et al., 1997); improves concentration in people with dementia (Vesper and Hansgen, 1994); improves attention in people with dementia (Hofferberth, 1989); improves tinnitus in people with dementia (Halama et al., 1988; Arrigo, 1986); improves intermittent claudication (Pittler and Ernst 2000; Schweizer and Hautmann, 1999; Peters et al., 1998; Bauer, 1984); increases alpha wave brain activity and decreases theta wave activity (Brown, 1997); improves activities of daily living (ADL) scores in people under 60 years old, and improves mood and sleep in older individuals (Cock1e et al., 2000). Inhibits binding of platelet activating factor (PAF) to platelets, which inhibits platelet aggregation and increases blood fluidity (Jung et al., 1990; Guinot et al., 1989); reduces thrombosis, inflammation, allergy, and bronchoconstriction (Smith et al., 1996), increases pancreatic b-cell function with increased insulin and C-peptide levels (Kudolo, 2000).

Animal          

Protects against cerebral ischemia (WHO, 1999; Larssen et al., 1978; Rapin et al., 1986; Le Poncin-Lafitte et al., 1980); decreases cerebral edema induced by trauma or toxins (Chatterjee and Gabard, 1984; Otani et al., 1986; Borzeix, 1985; Blumenthal et al., 1998); improves memory and learning (WHO, 1999; Winter, 1991); increases arteriolar diameter in the pia mater and increases cerebral blood flow by intravenous infusion (WHO, 1999; Krieglstein et al., 1986).

In vitro         

Inhibits lipid peroxidation (Cott, 1995); flavonoids and terpenoid constituents are antioxidant and free radical scavenging (Pincemail et al., 1989; WHO, 1999); attacks oxygen free radicals (Sastre et al., 1998); inhibits monoamine oxidase A and B (White et al., 1996) but more recent research has shown that ginkgo does not inhibit MAO in vivo (Fowler et al., 2000; Porsolt, 2000); inhibits platelet aggregation (Van Beek et al., 1998); protects against apoptosis (Ahlemeyer and Krieglstein, 1998); protects against cerebral hypoxia (Oberpichler et al., 1988; Krieglstein, 1995; Blumenthal et al., 1998).

Mechanism of Action

Ginkgolides (primarily ginkgolide B)   

Inhibit platelet activating factor (PAF) (WHO, 1999; Bracquet, 1988, 1989; Oberpichler, 1990).

Inhibit 3’5’-cyclic GMP phosphodiesterase, leading to endothelium relaxation (WHO, 1999; DeFeudis, 1991).

Flavonoid fraction (especially quercetin)

Increases serotonin release and uptake (Ahlemeyer and Krieglstein, 1998).

Inhibits age-related reduction of muscarinergic cholinoceptors and alpha-adrenoceptors, and stimulates choline uptake in the hippocampus (DeFeudis, 1998; Blumenthal et al., 1998).

Acts as a free-radical scavenger (Smith et al, 1996).

Inhibits nitric oxide formation, which may cause its neuroprotective effects. Pre-treatment (15 days) with ginkgo reduced significantly, in a dose-dependent manner, post-ischemic brain MDA levels and post-ischemic brain edema (Calapai et al., 2000).

Antagonism of PAF, antioxidant and metabolic actions, and effects on neurotransmitters may be due to the flavonoids and terpenoids, acting together or separately (Logani et al., 2000).

Contraindications

Ginkgo should not be used by persons who have a history of allergy to the herb (this is considered rare) (Blumenthal et al., 1998; Brinker, 2001). It is also contraindicated in bleeding disorders due to increased bleeding potential associated with chronic use (6–12 months) or before elective surgery (Brinker, 2001). The product sheet of the leading ginkgo preparation (EGb 761) notes that the 120 mg dosage should not be used in children under 12. In addition, it recommends to use all necessary precautionary measures in administering ginkgo extracts for treatment of depressive mood and headache not associated with demential syndromes since these conditions have not been sufficiently investigated (Schwabe, 2001).

Pregnancy and Lactation: According to Commission E, no known restrictions (Blumenthal et al., 1998) although no long-term studies have been conducted on pregnant or lactating woman.

Adverse Effects

In general, ginkgo extract has produced few adverse effects in clinical trials, with effects for ginkgo being the same as for placebo. Rare cases of stomach or intestinal upsets, headaches, or allergic skin reaction have been documented (Blumenthal et al., 1998). Ginkgo has also been reported to cause dizziness and palpitations. Several case reports of bleeding associated with ginkgo use have been reported, including two reports of subdural hematoma (Rowin and Lewis, 1996; Gilbert, 1997), one report of subarachnoid hemorrhage (Vale, 1998), one report of intracerebral hemorrhage (Matthews, 1998), and one report of anterior chamber bleeding in the eye (hyphema) (Rosenblatt and Mindel, 1997). However, animal experiments have suggested a protective effect of ginkgo extract on subarachnoid hemorrhage-induced vasospasm and vasculopathy (Kurtsoy et al., 2000).

Drug Interactions

MAO-Inhibition

A safety review suggested that ginkgo extract may potentiate MAO-inhibiting drugs (McGuffin et al., 1997), but the evidence is questionable. Recent studies have concluded that ginkgo does not inhibit MAO in vivo, and that a different mechanism may be responsible for some of ginkgo’s effects on the central nervous system (Fowler et al., 2000; Porsolt et al., 2000).

Anticoagulants and antiplatelet drugs

Interaction with drugs inhibiting blood coagulation cannot be excluded. A single case of a spontaneous hyphema after combined intake of a ginkgo-containing pharmaceutical preparation and aspirin has been documented (Rosenblatt and Mindel, 1997). However, in a placebo-controlled double-blind study carried out in 50 subjects over a period of 7 days, interactions of ginkgo special extract EGb 761 (daily dose 240 mg) with acetyl salicylic acid (aspirin, daily dose 500 mg) could not be demonstrated (Schwabe, 2001). There is a single case of an intracerebral hemorrhage after concomitant intake of warfarin and ginkgo described in the literature (Matthews, 1998). However, further investigation revealed that the patient received two other drugs (amiodarone and lovastatin) with known interactions with warfarin (Schwabe, 1998). A recent randomized, double-blind, placebo-controlled crossover study has concluded that ginkgo does not interact with warfarin (Engelsen et al., 2002).

Diuretics      

One old case report of intravenous use of ginkgo (300 mg/day) speculated the possibility that ginkgo may potentiate the effect of thiazide diuretics by increasing capillary permeability, but the clinical relevance, if any, is not clear (Lagrue et al., 1986). A review of this case suggests that ginkgo did not increase capillary permeability but decreased the shock-induced hyperpermeability (Busse, 2001).

Anticonvulsants

One paper reported the presence of a potential neurotoxin (4’-O-methylpyroxidine) in both the ginkgo leaf and seed; the author suggests that ginkgo should thus be used with caution by epileptic patients being treated with anticonvulsants (Arenz et al., 1996). However, an analysis of this case report shows that the toxic concentration of this compound after oral administration of ginkgo is 11 mg/kg of body weight (BW). Thus, the toxic dose is an estimated 11,000 times higher than the maximum daily dose of commercial ginkgo extract (60 mcg) corresponding to 1 mcg/kg BW (Leistner, 1997). Further, the bilobalide in ginkgo has anticonvulsant effects (Sasaki et al., 1995). Thus, there is no clinical evidence to support cautions regarding use of ginkgo extract with anticonvulsants.

Antidepressant

Ginkgo can offset sexual dysfunction symptoms in patients taking antidepressants (SSRIs, MAOIs, and tricyclics) (Brinker, 2001).

Other

Use of ginkgo for 12–18 months potentiated papaverine intracavernosal injections in men where papaverine alone was previously ineffective (Sikora et al., 1989). Use of ginkgo before and after kidney transplant helped prevent PAF-induced organ rejection when used with cyclosporine (Brinker, 2001). In one case report, ginkgo used with trazodone resulted in coma that was immediately resolved by injection of 1 mg flumazenil (Brinker, 2001).

American Herbal Products Association (AHPA) Safety Rating

Class 1: Herbs that can be safely consumed when used appropriately.

Regulatory Status

Argentina: Standardized extracts (Ginkgo NF) are approved for peripheral and cerebrovascular disorders.

Austria: A standardized extract (EGb 761) is approved for cerebral and nutritional insufficiencies, dementia, intermittent claudication, and supportive treatment of hearing deficits.

Brazil: Standardized extracts (Ginkgo NF) are approved for cerebrovascular deficits; peripheral vascular disorders; neurosensorial disorders of vascular origin in the ears, eyes, and nose, and migraine headaches.

Canada: New Drug if claims made. Extract form is unacceptable as food ingredient (HPB, 1993). Permitted as a homeopathic drug requiring premarket authorization and assignment of a Drug Identification Number (DIN). Thirty-two ginkgo homeopathic preparations are listed in the Drug Product Database (DPD) (Health Canada, 2001).

Denmark: Standardized ginkgo extracts (most of which comply with Ginkgo NF) are approved for memory and concentration deficits, tiredness, continuing dizziness, and tinnitus in the elderly, tendency to cold extremities, and intermittent claudication.

France: Marketed under the brand name Tanakan^® (EGb 761) is a prescription medication (Itil et al., 1996). The standardized extract (EGb 761) is approved for treating symptoms of cerebral insufficiencies, intermittent claudication, Raynaud’s disease, certain dizziness and/or tinnitus syndromes, and retinal conditions due to probable ischemia.

Germany: Only semi-purified normalized (standardized) dry extracts (35–67:1) with less than 5 ppm ginkolic acids are approved drugs of the German Commission E; Active Ingredient Classification ASK No. 05939 (Blumenthal et al., 1998). Dry extract, (35–67:1) is official in the German Pharmacopoeia,
standardized to contain no less than 22.0% and no more than 27.0% flavone glycosides, as well as no less than 5.0% and no more than 7.0% terpene lactones, of which 2.8–3.4% are ginkgolides A, B, and C and 2.5–3.2% are bilobalide (DAB, 2000). Licensed for the treatment of cerebral dysfunction with attendant memory loss, dementia, poor concentration, etc., plus vertigo and tinnitus of vascular origin, and for intermittent claudication (Blumenthal et al., 1998). Marketed both as a prescription and a nonprescription drug.

Mexico: Standardized extracts (Ginkgo NF) are approved for treating diminished mental capacities, demential syndromes, dizziness, and tinnitus.

Spain: A standardized extract (Ginkgo NF) is approved for cerebral insufficiencies (such as dizziness, headache, and memory deficits), and peripheral vascular disorders.

Sweden: Classified as Natural Remedy, requiring premarket authorization. As of January, 2001, six ginkgo products are listed in the Medical Products Agency (MPA) “Authorised Natural Remedies,” and a monograph is published with the approved indication: “Herbal remedy for the treatment of long-standing symptoms in elderly people such as difficulties of memory and concentration, vertigo, tinnitus and feeling of tiredness. Prior to treatment other serious conditions should have been ruled out by doctor” (MPA, 1998, 2001; Tunón, 1999).

Switzerland: Herbal medicine with positive classification (List D) by the Interkantonale Konstrollstellefar Heilmittel (IKS) and corresponding sales Category D with sale limited to pharmacies and drugstores, without prescription (Morant and Ruppanner, 2001; Ruppanner and Schaefer, 2000). There are nine ginkgo monopreparation phytomedicines, nine polypreparations and three ginkgo homeopathic preparations listed in the Swiss Codex 2000/01 (Ruppanner and Schaefer, 2000). Standardized ginkgo extracts, most of which comply with Ginkgo NF, are approved for concentration difficulties, forgetfulness, and dizziness (due to arteriosclerotic complaints).

U.K.: Not entered in the General Sale List (GSL). Standardized extracts, are available.

U.S.: Dietary supplement (USC, 1994). Dried leaf containing no less than 0.8% flavonol glycosides is official in the National Formulary 19th edition (USP 25-NF 20, 2002). Standardized extracts are commonly sold.

Clinical Review

More than 120 clinical studies have been published on standardized ginkgo extract. The table “Clinical Studies on Ginkgo” outlines 35 studies including 3,541 participants. Two trials found negative results: one on dementia (Van Dongen et al., 2000) and one on tinnitus (Drew and Davies, 2001). The remaining 33 studies found positive effects for indications including Alzheimer’s disease and dementia, peripheral vascular disease (intermittent claudication), asthma, acute mountain (altitude) sickness, deafness, adjunct therapy in colorectal cancer, sexual dysfunction, and depression.

Eighteen studies involving a total of 1,672 participants supported the use of ginkgo in treating dementia due to cardiovascular insufficiency, Alzheimer’s disease, or multi-infarct dementia, or to slow the clinical deterioration of patients with dementia or to improve cognitive symptoms. Of these 18 studies, five were randomized, double-blind, placebo controlled, multi-center (R, DB, PC, MC) studies involving a total of 663 participants (Le Bars et al., 1997; Kanowski et al., 1997; Grässel, 1992; Vesper and Hansgen, 1994; Taillandier et al., 1986); 11 were R, DB, PC with a total of 898 participants (Brautigam et al., 1998; Hofferberth, 1994, 1989; Halama, 1991; Rai et al., 1991; Schmidt et al., 1991; Brüchert et al., 1991; Eckmann, 1990; Vorberg et al., 1989; Halama et al., 1988; Wesnes et al., 1987); and two were R, DB, PC, crossover (CO) studies involving a total of 111 participants (Rigney et al., 1999; Arrigo, 1986).

Three R, DB, PC studies (Bauer, 1984; Peters et al., 1998; Schweizer and Hautmann, 1999), with a total of 264 participants, focused on ginkgo for treatment of peripheral arterial insufficiency/intermittent claudication, with positive results.

Of the remaining studies investigating the use of ginkgo for various disorders, one R, DB, PC study (20 participants) found inconclusive results for the use of ginkgo for moderately severe depression (Halama, 1990); one R, DB, PC, CO study (8 participants) found positive effects for hypoxia (Schaffler and Reeh 1985); two R, DB, PC studies and one DB, PC study on altitude sickness (total 110 participants) had positive results (Gertsch et al., 2002; Roncin et al., 1996; Leadbetter et al., 2001); one R, DB, PC, MC study (Meyer, 1986) on 103 patients found ginkgo improved the evolution of tinnitus; one R, DB, C study (20 participants) (Dubreuil, 1986) found ginkgo superior to nicergoline for acute cochlear deafness; one PC study of 61 patients with asthma reported positive effects (Li et al., 1997); one open-labeled study (63 participants) investigating sexual dysfunction secondary to antidepressant use found positive effects (Cohen and Bartlik, 1998); one Phase II study (32 participants) suggests a good benefit-risk ratio of ginkgo combined with 5-FU therapy as second line treatment for advance colorectal cancer (Hauns et al., 2001); and one DB study (12 participants) investigating the effect of ginkgo extract on brain electrophysiology found that pharmacological effects on the central nervous system are statistically significant when compared to placebo (Itil et al., 1996). One R, DB, PC, CO study (21 participants) concluded that warfarin and ginkgo do not interact (Engelsen et al., 2002).

Note: the reviews and meta-analyses discussed below are not listed in the table “Clinical Studies on Ginkgo.” In a review of 40 clinical studies conducted through 1991 on the use of ginkgo for symptoms associated with cerebral insufficiency, eight R, DB, PC trials of the 40 studies met inclusion criteria for a well-designed study (Kleijnen and Knipschild, 1992). All but one (Hartmann and Frick, 1991) of these eight studies concluded that ginkgo extract was as effective as co-dergocrine and superior to placebo. Symptoms most often reported improved were concentration and memory, anxiety, dizziness, tinnitus, and headache. Ginkgo was well-tolerated and side effects compared favorably to five studies assessing Hydergine^®, another widely-used product for cerebral insufficiency. Ginkgo and Hydergine^® were deemed equally effective for treatment of cerebral insufficiency.

A recent Cochrane review of 33 trials on ginkgo extract found that the trials showed “promising evidence of improvement in cognition and function” (Birks et al., 2002).

In a review and meta-analysis of the scientific literature, researchers evaluated the effects of treatment with ginkgo extract on objective measures of cognitive function in elderly patients with vascular dementia, cognitive impairment, or both (Oken et al., 1998). Of more than 50 articles, only four met reasonable inclusion criteria for adequate clinical trial design, with a total of 212 subjects in each of the placebo and ginkgo treatment groups (Le Bars et al., 1997; Hofferberth, 1994; Kanowski et al., 1997; Wesnes et al., 1987). Standardized ginkgo extract produced a significant effect size of 0.40 on cognitive function in Alzheimer’s (p<0.0001) comparable with the findings of a trial on donepezil (Rogers et al., 1998). The clinical trials reviewed did not determine whether there is improvement in noncognitive behavior or daily function. A comparison review of PC efficacy studies evaluated the clinical relevance of acetylcholinesterase inhibitors and ginkgo special extract EGb 761 for Alzheimer’s dementia. The study concluded that EGb 761 and second generation cholinesterase inhibitors are equally effective in treating mild to moderate Alzheimer’s dementia (Wettstein, 2000). A meta-analysis of nine DB, PC trials found ginkgo extract more effective for dementia than placebo, with few adverse side effects (Ernst and Pittler, 1999). A review of trials on ginkgo use for clinical improvement of memory and other cognitive functions found that ginkgo produces a significant therapeutic benefit; however, long-term studies have not evaluated its sustained benefits in cognitive function, especially if drug therapy is subsequently interrupted. The author cites the need for further studies to test the relative efficacy of different doses of ginkgo (Soholm, 1998).

The Cochrane Review selected R, controlled trials (C) that studied ginkgo and age-related macular degeneration. The review concluded that in the one identified trial on that condition, a beneficial effect was observed on 20 patients. However, the author encourages additional research due to the small number of patients included in the trial (Evans, 2000).

One meta-analysis of eight R, DB, PC studies (Pittler and Ernst, 2000) concluded that ginkgo is effective for intermittent claudication but questioned the clinical relevance based on the modest size of the overall treatment effect; patients in the ginkgo groups had a longer distance of pain-free walking than those in the placebo groups (average increase of 34 meters).

Shortly after completion of this monograph, a new study on ginkgo extract for cognitive abilities in healthy older adults (over 60) was published finding no significant improvement in various measured parameters at a dose of 120 mg/day for four weeks (Solomon et al., 2002). Previously, at least four trials of various sizes and designs had suggested that ginkgo extract did contribute to increased mental performance in asymptomatic subjects (Mix and Crews, 2002; Stough et al., 2001; Mix and Crews, 2000).

The most comprehensive review of research and clinical information on ginkgo is compiled by DeFeudis (1998).

Branded Products*

Bio-Biloba^®: Pharma Nord ApS / Sadelmagervej 30-32, DK-7100 / Vejle / Denmark / Tel: +43-75-85-7400 / Fax: +43-75-85-7474 / www.pharmanord.com.

Concentrated Ginkgo leaf liquid: Quindao Fengyi Biotechnology Limited. Contact information not available. Each milliliter contains 14.5 mg flavone glycosides and 2.8 mg terpene lactones.

EGb-761: Dr. Willmar Schwabe Pharmaceuticals / International Division / Willmar Schwabe Str. 4, D-76227 / Karlsruhe / Germany / Tel: +49-721-4005 ext. 294 / www.schwabepharma.com / Email: melville-eaves@schwabe.de. The standardized mono-extract of dried leaves from ginkgo (50:1) consists of 24% ginkgo flavonol glycosides and 6% terpene lactones, of which 2.9% is bilobalide and 3.1% is the ginkgolides A, B, and C. Contains less than 5 ppm ginkgolic acids and conforms to the German Commission E requirements for GBE.

Geriaforce^®: CH-9325 Roggwil TG / Switzerland / Tel: +41 71 454 61 61 / Fax: +41 71 454 61 62 / www.bioforce.com / Email: info@bioforce.ch. Each tablet contains an ethanolic extract of fresh leaves 1:4, with a content of flavonol glycosides of 0.20 mg/ml and ginkgolides 0.34 mg/ml.

Ginkgold^®: Nature’s Way Products, Inc. / 10 Mountain Spring Parkway / Springville, Utah 84663 / U.S.A. / Tel: (801) 489-1500 / www.naturesway.com. The standardized mono-extract (EGb-761) of dried leaves from ginkgo (50:1) consists of 24% ginkgo flavonol glycosides and 6% terpene lactones, of which 2.9% is bilobalide and 3.1% is the ginkgolides A, B, and C. Contains less than 5 ppm ginkgolic acids and conforms to the German Commission E requirements for GBE.

Kaveri^®: Lichtwer Pharma AG / Wallenroder Strasse 8-14 / 13435 / Berlin / Germany / Tel: +49-30-40-3700 / Fax: +49-30-40-3704-49 / www.lichtwer.de. Prepared from the standardized mono-extract (LI-1370) of dried leaves from ginkgo (50:1) containing at least 25% flavonol glycosides and 6% terpene lactones. Contains less than 5 ppm ginkgolic acids and conforms to the German Commission E requirements for GBE.

LI-1370: Lichtwer Pharma AG, Berlin, Germany. The standardized mono-extract of dried leaves from ginkgo (50:1) contains at least 25% flavonol glycosides and 6% terpene lactones (Vesper and Hansgen, 1994) and conforms to the German Commission E specifications. Contains less than 5 ppm ginkgolic acids and conforms to the German Commission E requirements for GBE.

Rökan^®: Spitzner GmbH / Postfach 763, 76261 Ettlingen, Germany / Tel. +49 72 43 – 106 01 / Fax +49 72 43 – 106 333 / www.spitzner.de / Email: info@spitzner.de. The standardized mono-extract (EGb-761) of dried leaves from ginkgo (50:1) consists of 24% ginkgo flavonol glycosides and 6% terpene lactones, of which 2.9% is bilobalide and 3.1% is the ginkgolides A, B, and C. Contains less than 5 ppm ginkgolic acids and conforms to the German Commission E requirements for GBE.

Tanakan^®: 4. Beaufor-Ipsen / Paris, France / Tel.: +33 (0) 1 44 30 42 15 / Fax: +33 (0) 1 44 30 42 04 / www.beaufour-ipsen.com/ / Email: contact.web@beaufour-ipsen.com. The standardized mono-extract (EGb-761) of dried leaves from ginkgo (50:1) consists of 24% ginkgo flavonol glycosides and 6% terpene lactones, of which 2.9% is bilobalide and 3.1% is the ginkgolides A, B, and C. Contains less than 5 ppm ginkgolic acids and conforms to the German Commission E requirements for GBE.

Tebonin^® forte: Dr. Willmar Schwabe Pharmaceuticals. The standardized mono-extract (EGb-761) of dried leaves from ginkgo (50:1) consists of 24% ginkgo flavonol glycosides and 6% terpene lactones, of which 2.9% is bilobalide and 3.1% is the ginkgolides A, B, and C. Contains less than 5 ppm ginkgolic acids and conforms to the German Commission E requirements for GBE.

*American equivalents, if any, are found in the Product Table beginning on page 398.

References

Ahlemeyer B, Kriegelstein J. Neuroprotective effects of Ginkgo biloba extract. In: Lawson L, Bauer R, editors. Phytomedicines of Europe chemistry and biological activity. Washington D.C.: American Chemical Society; 1998. p. 210–220.

Arenz A, Klein M, Fiehe K, Groß J, Drewke C, Hemscheidt T, Leistner E. Occurrence of neurotoxic 4’-o-methylpyridoxine in Ginkgo biloba leaves, ginkgo medications and Japanese ginkgo food. Planta Med 1996;62:548–51.

Arrigo A. Treatment of chronic cerebrovascular insufficiency with Ginkgo biloba extract. Therapiewoche 1986;36:5208–18.

Bauer U. 6-Month double-blind randomised clinical trial of Ginkgo biloba extract versus placebo in two parallel groups in patients suffering from peripheral arterial insufficiency. Arzneimittelforschung 1984;34(6):716–20.

Birks J, Grimley EJ, Van Dongen M. Ginkgo biloba for cognitive impairment and dementia [Cochrane Review]. In: The Cochrane Library, Issue 4, 2002. Oxford. Update Software.

Blume J, Kieser M, Hölscher U. Placebo-controlled double blind study on the efficacy of Ginkgo biloba special extract EGb 761 in maximum-level trained patients with intermittent claudication. VASA 1996;25(3):265–74.

Blume J, Kieser M, Hölscher U. Efficacy of Ginkgo biloba special extract EGb 761 in peripheral arterial occlusive disease. Fortschr Med(Originalien) 1998;116:137–43.

Blumenthal M. Herb Sales Down 15% in Mainstream Market. HerbalGram 2001;51:69.

Blumenthal M, Busse WR, Goldberg A, Gruenwald J, Hall T, Riggins CW, Rister RS, editors. Klein S, Rister RS (trans.). The Complete German Commission E Monographs—Therapeutic Guide to Herbal Medicines. Austin (TX): American Botanical Council; Boston (MA): Integrative Medicine Communication; 1998. p. 136–8.

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