Ginkgo Biloba

A tree with a long evolutionary history

The National Center for Complementary and Integrative Health (NCCIH) describes ginkgo as a deciduous tree so ancient that it is commonly called a living fossil, the last remaining species of a primitive family of plants. It says ginkgo has a long history of use in Chinese medicine for cough, diarrhea and other conditions, and that the leaf, usually as an extract, is now the most commonly used form.

Records in Chinese materia medica

A 2022 review of ginkgo leaves, seeds and outer seed coat reports that the Ming dynasty Compendium of Materia Medica and the Qing dynasty Bencao Fengyuan recorded the plant as able to reduce phlegm, clear poison, and treat diarrhea and frequent urination. As summarized by the review, classical Chinese herbal books and the Chinese Pharmacopoeia give its main effects as relieving cough, reducing phlegm, clearing poison and relieving diarrhea.

Only the abstract of that review was available for this page, and it does not separate records about the leaf from records about the seed. It does not state that the classical texts described memory or circulation uses, so the modern indications covered below should not be read back into those records. A 2009 Cochrane review says only that leaf extracts have long been used in China as a traditional medicine for various disorders.

Standardized extracts developed in Europe

A 2019 analytical paper describes herbal medicinal products based on ginkgo leaf refined dry extract as a European development from a species traditionally used in East Asia. The extract most often tested in trials, EGb 761, is made by Schwabe in Karlsruhe, Germany, according to the Ginkgo Evaluation of Memory (GEM) report, which says the formulation is used in many branded ginkgo products sold in the United States.

The sources reviewed for this page do not give dates for the development of these extracts or describe how they were first licensed or marketed in Germany or elsewhere, so those details are not covered here.

Names for the plant and its products

The plant is Ginkgo biloba, also called the maidenhair tree. The literature also uses the spelling gingko, and the Cochrane dementia review searched for the terms ginkgo, gingko, tanakan and EGb 761. Products are described as ginkgo leaf extract, Ginkgo biloba extract (GBE) or, for the defined extract used in many trials, EGb 761.

Leaf extract, seed and crude plant

The sources separate three kinds of material. Standardized leaf extracts are the subject of nearly all the trials discussed here. NCCIH describes fresh ginkgo seeds as toxic when eaten, and says serious effects have also followed roasted seeds or the crude plant. Research on one extract, mainly EGb 761, should not be assumed to apply to other leaf products or to the seeds.

Place within Machipedia

This page is a member of the Machipedia family page Herbal Medicine, which covers herbal practice in general and should be read alongside it. Related pages include Traditional Chinese Medicine, in which ginkgo was recorded, Ginseng, a separate herbal page, Dietary Supplements, the category under which NCCIH says ginkgo is promoted, and Nutritional Psychiatry.

What the products are

NCCIH reports that ginkgo is promoted as a dietary supplement, and that the leaf is usually taken as an extract. The trial literature mostly concerns standardized extracts, in which the content of ginkgo flavone glycosides and terpene lactones (the ginkgolides and bilobalide) is adjusted to defined amounts. In the claudication trials the extracts were supplied as film-coated tablets.

How the research uses it

Trials in older adults gave a standardized extract or placebo for periods ranging from about 24 weeks in symptom studies to a median of 6.1 years in the GEM prevention trial and 5 years in GuidAge. One trial tested a once-daily formulation of EGb 761. This page reports no amounts, and product labels and clinicians, not an encyclopedia, are the proper source on how a given product is used.

Memory, cognition and dementia

NCCIH lists cognitive impairment and dementia among the conditions for which ginkgo is promoted, and says it has also been promoted for enhancing cognitive performance in healthy people. The Cochrane dementia review says a standardized extract is widely prescribed for memory and concentration problems, confusion, depression, anxiety, dizziness, tinnitus and headache.

The same review says proposed mechanisms include increasing blood supply by dilating blood vessels, reducing blood viscosity, modifying neurotransmitter systems and reducing free radicals. These are stated as proposals, and the review does not present them as established.

Circulation, tinnitus and other claims

The claudication review describes ginkgo as a vasoactive agent used to treat intermittent claudication, which is leg muscle pain during walking that eases with rest. The 2013 tinnitus review notes reports suggesting ginkgo may help tinnitus, alongside a strong placebo effect in tinnitus management. NCCIH also lists anxiety, heart disease, diabetes, premenstrual syndrome and schizophrenia among promoted uses.

Prevention of dementia

The GEM study, sponsored by NIH institutes, randomized 3,069 volunteers aged 75 or older (2,587 with normal cognition, 482 with mild cognitive impairment) to EGb 761 or placebo for a median of 6.1 years. Dementia occurred in 277 people taking ginkgo and 246 taking placebo (hazard ratio 1.12, 95% CI 0.94 to 1.33), and the authors concluded ginkgo did not reduce dementia incidence.

GuidAge enrolled 2,854 adults aged 70 or older in France with memory complaints for 5 years. Probable Alzheimer disease was diagnosed in 61 ginkgo and 73 placebo participants (hazard ratio 0.84, 95% CI 0.60 to 1.18), and the authors reported no reduction in progression. NCCIH counts three large studies with no reduction in dementia risk.

Symptoms in people with cognitive impairment

A 2009 Cochrane review included 36 trials, most small and under three months, with nine of six months (2,016 participants). Results for cognition, daily living, mood and caregiver burden were inconsistent, nine trials in Alzheimer disease (925 people) showed no consistent benefit, and the reviewers called the evidence inconsistent and unreliable.

A 24-week trial in about 400 outpatients with mild to moderate dementia and neuropsychiatric symptoms found greater improvement on cognitive and neuropsychiatric scales with a once-daily EGb 761 formulation than with placebo, with similar adverse event rates. A second report gives separate Alzheimer disease and vascular dementia results.

Tinnitus and claudication

The 2022 Cochrane tinnitus review included 12 trials (1,915 participants) at high or unclear risk of bias. Pooling two studies (85 participants), ginkgo may have little to no effect on tinnitus severity, with very low certainty evidence. The 2013 version found no evidence of effect when tinnitus was the primary complaint.

The claudication review of 14 trials (739 participants) found a change in walking distance of about 65 meters (95% CI -1.8 to 131) on a flat treadmill, with publication bias likely to have inflated it, and concluded there is no evidence of a clinically significant benefit.

Conflicting syntheses

Syntheses reach different conclusions. A 2014 meta-analysis of seven of 15 placebo-controlled trials of EGb 761 in dementia (2,684 people) reported results significantly favoring EGb 761 for cognition, daily living and global rating, and concluded efficacy. A 2020 expert review states EGb 761 is the only pharmacological treatment recommended in existing guidelines for symptomatic treatment of mild cognitive impairment.

The Cochrane review called evidence for dementia inconsistent and unreliable, and NCCIH says ginkgo may have a modest benefit for dementia symptoms but that the evidence is inconsistent and it is unclear whether it helps milder impairment. These differing positions are reported as stated.

Trial quality and sponsorship

The Cochrane dementia review said many early trials used unsatisfactory methods, were small, and could not exclude publication bias. The claudication review notes that authors of some included trials were employed by a manufacturer or relied on its internal reports, and the 2014 meta-analysis lists a manufacturer employee as an author.

GEM was funded by NIH institutes, with tablets donated by Schwabe, which the report says had no role in design, analysis or approval; GuidAge was funded by Ipsen. Funding of the other trials and of the 2020 review was not verified for this page.

Bleeding and drug interactions

NCCIH says ginkgo may increase bleeding risk in people taking anticoagulants such as warfarin and may interact with other drugs. A review of dietary supplements found ginkgo associated with bleeding in patients on anticoagulants, with conflicting evidence for overall risk, and a warfarin interaction review lists ginkgo among items with increased bleeding risk.

A meta-analysis of 18 trials found no laboratory signal of higher bleeding risk, and GEM found no difference in major bleeding (hazard ratio 0.97), though hemorrhagic strokes were 16 with ginkgo and 8 with placebo, a nonsignificant difference. GEM excluded people taking warfarin or with bleeding disorders.

Seizures and seeds

NCCIH says fresh ginkgo seeds are toxic when eaten. A review describes seed toxins that cause convulsions, allergy and other effects, and a case report describes generalized convulsions in a woman without epilepsy after eating a large amount of nuts.

A report of two people with controlled epilepsy describes recurrent seizures within two weeks of starting a leaf extract, which resolved on stopping; as a case report it cannot establish cause. The 2022 tinnitus review found no serious adverse effects, including seizures, in four studies of 1,154 participants.

Common effects, product quality and who should ask a clinician

The claudication review lists gastrointestinal complaints, headache and allergic skin reactions as common effects. Analytical papers describe ginkgo products adulterated with rutin, quercetin or other plant extracts. One laboratory analysis found one or more adulterants in 48 of 59 supplements, and another method flagged adulterated or ginkgo-free products among 20 tested.

NCCIH advises talking with a health care provider before using ginkgo, notes it may be unsafe in pregnancy, and says it might cause early labor or extra bleeding near delivery. Ginkgo has not been shown to prevent dementia and should not delay or replace assessment of memory problems, tinnitus or leg pain on walking.