Ginkgo

In Chinese medicine the seed, bai guo, is decocted for cough and wheezing and to reduce vaginal discharge. Raw seed, or seed eaten in large amounts, is recognised in the tradition as toxic.

The leaf entered European medicine through pharmaceutical research. An extract was developed in Germany from 1965, and the first registered extract, EGb 761, was launched in France in 1974 ^{45Reference 45Isah · 2015ReviewRethinking Ginkgo biloba L.: medicinal uses and conservation — reviewView study →}. Western herbalists now use the leaf in circulatory and memory-support formulas.

Several double-blind RCTs of EGb 761 at 240 mg/day in Alzheimer’s, vascular and mixed dementia report small improvements in cognition and, more consistently, in neuropsychiatric symptoms and caregiver-rated function ^{4,5,6Reference 4Ihl R et al. · 2011RCTEfficacy and safety of a once-daily formulation of Ginkgo biloba extract EGb 761 in dementia with neuropsychiatric features: a randomized controlled trial — randomised controlled trialView study →Reference 5Napryeyenko O et al. · 2007RCTGinkgo biloba special extract in dementia with neuropsychiatric featuresView study →Reference 6Napryeyenko O et al. · 2009RCTEfficacy and tolerability of Ginkgo biloba extract EGb 761 by type of dementia: analyses of a randomised controlled trial — randomised controlled trialView study →}. A large multicentre US RCT was closer to null ^{7Reference 7Schneider LS et al. · 2005RCTA randomized, double-blind, placebo-controlled trial of two doses of Ginkgo biloba extract in dementia of the Alzheimer’s type — randomised controlled trialView study →}.

The 2009 Cochrane review pooled the trials and concluded the evidence of benefit is “inconsistent and unreliable,” largely because of heterogeneity and older positive trials of uncertain quality ^{1Reference 1Birks J et al. · 2009Meta-analysisGinkgo biloba for cognitive impairment and dementia — systematic review and meta-analysisView study →}.

Later meta-analyses restricted to 240 mg for 22–24 weeks are more favourable, finding statistically significant gains in cognition and activities of daily living, especially where neuropsychiatric symptoms are present ^{2,3Reference 2Tan MS et al. · 2015Meta-analysisEfficacy and adverse effects of ginkgo biloba for cognitive impairment and dementia: a systematic review and meta-analysis — systematic review and meta-analysisView study →Reference 3Yang G et al. · 2016Meta-analysisGinkgo Biloba for Mild Cognitive Impairment and Alzheimer’s Disease: A Systematic Review and Meta-Analysis of Randomized Controlled Trials — systematic review and meta-analysisView study →}.

Gap: effect sizes are small and clinically borderline; trial quality is heterogeneous and much of the positive data is industry-sponsored on one extract.

The flavonol glycosides of EGb 761 — glycosides of quercetin, kaempferol and isorhamnetin — are direct peroxyl- and hydroxyl-radical scavengers in vitro ^{8Reference 8Maitra I et al. · 1995In vitroPeroxyl radical scavenging activity of Ginkgo biloba extract EGb 761 — in vitro studyView study →}. The whole extract protects hippocampal neurons against beta-amyloid- and oxidative-stress-induced death in cell and animal models ^{9Reference 9Bastianetto S et al. · 2000In vitroThe Ginkgo biloba extract (EGb 761) protects hippocampal neurons against cell death induced by beta-amyloid — in vitro studyView study →} and reduces oxidative damage in the retina ^{10Reference 10Droy-Lefaix MT et al. · 1995AnimalAntioxidant effect of a Ginkgo biloba extract (EGb 761) on the retina — animal model studyView study →}.

Gap: no trial has measured an antioxidant outcome, such as oxidative-stress biomarkers tied to a clinical endpoint, in people taking ginkgo.

A randomised double-blind trial in idiopathic sudden hearing loss with vertigo found benefit ^{12Reference 12Burschka MA et al. · 2001RCTEffect of treatment with Ginkgo biloba extract EGb 761 (oral) on unilateral idiopathic sudden hearing loss in a prospective randomized double-blind study of 106 outpatients — randomised controlled trialView study →}. A later randomised double-blind trial reported EGb 761 240 mg to be at least as effective as betahistine, the standard antivertigo drug, with better tolerability ^{13Reference 13Sokolova L et al. · 2014RCTTreatment of Vertigo: A Randomized, Double-Blind Trial Comparing Efficacy and Safety of Ginkgo biloba Extract EGb 761 and Betahistine — randomised controlled trialView study →}.

The effects are attributed to improved microcirculation and central vestibular compensation.

Gap: the trials are small, several are manufacturer-linked, and the vertigo populations are heterogeneous. There is no large independent replication against an active comparator.

The terpene trilactones give ginkgo a mechanism no flavonoid herb shares. Ginkgolide B is a potent antagonist of platelet-activating factor (PAF), the phospholipid mediator that drives platelet aggregation and inflammatory signalling ^{11Reference 11DeFeudis FV et al. · 2000ReviewGinkgo biloba extract (EGb 761) and CNS functions: basic studies and clinical applications — reviewView study →}.

In thrombin-stimulated human platelets it blocks Syk and p38 MAPK phosphorylation and suppresses granule release ^{14Reference 14Liu X et al. · 2014In vitroGinkgolide B inhibits platelet release by blocking Syk and p38 MAPK phosphorylation in thrombin-stimulated platelets — in vitro studyView study →}.

This is the pharmacological basis for ginkgo’s circulatory effects and for its bleeding risk.

Gap: the PAF antagonism is well shown in vitro and in animals, but no human trial has tested a therapeutic antiplatelet benefit. Clinically, the same action shows up mainly as bleeding risk.

A meta-analysis of randomised controlled trials found that EGb 761 240 mg/day added to antipsychotics significantly reduced tardive dyskinesia symptoms versus placebo in patients with schizophrenia ^{15Reference 15Zheng W et al. · 2016Meta-analysisExtract of Ginkgo biloba for Tardive Dyskinesia: Meta-analysis of Randomized Controlled Trials — meta-analysisView study →}. The proposed mechanism is protection against neuroleptic-induced oxidative damage in the basal ganglia.

Gap: the pooled trials come largely from one research setting and population, and need independent replication.

A randomised, double-blind, placebo-controlled trial of EGb 761 (240 or 480 mg/day) in generalised anxiety disorder and adjustment disorder reported a dose-dependent reduction in anxiety scores over four weeks ^{16Reference 16Woelk H et al. · 2007RCTGinkgo biloba special extract EGb 761 in generalized anxiety disorder and adjustment disorder with anxious mood: a randomized, double-blind, placebo-controlled trial — randomised controlled trialView study →}.

Gap: one trial only, and the mechanism in anxiety is not well defined.

Meta-analyses of ginkgo (oral and injectable diterpene-lactone preparations) as an add-on in acute ischaemic stroke report improved neurological function and activities of daily living ^{17Reference 17Chong PZ et al. · 2020Meta-analysisEfficacy and Safety of Ginkgo biloba in Patients with Acute Ischemic Stroke: A Systematic Review and Meta-Analysis — systematic review and meta-analysisView study →}.

Most contributing RCTs are small, single-region and at high risk of bias, and the earlier Cochrane review found no reliable evidence to support routine use ^{18Reference 18Zeng X et al. · 2005Meta-analysisGinkgo biloba for acute ischaemic stroke — systematic review and meta-analysisView study →}.

Injectable Chinese preparations differ substantially from the oral EGb 761 leaf extract.

Gap: the meta-analytic benefit rests on low-quality trials of preparations, often injectable, unlike the standardised oral leaf extract.

An early meta-analysis found EGb 761 modestly increased pain-free walking distance versus placebo in peripheral arterial disease ^{20Reference 20Pittler MH et al. · 2000Meta-analysisGinkgo biloba extract for the treatment of intermittent claudication: a meta-analysis of randomized trials — meta-analysisView study →}, supported by a multicentre EGb 761 RCT ^{21Reference 21Peters H et al. · 1998RCTDemonstration of the efficacy of ginkgo biloba special extract EGb 761 on intermittent claudication—a placebo-controlled, double-blind multicenter trial — randomised controlled trialView study →}.

The 2009 Cochrane review, with more and larger trials, concluded the effect on walking distance was small and of uncertain clinical significance ^{19Reference 19Nicolaï SP et al. · 2009Meta-analysisGinkgo biloba for intermittent claudication — systematic review and meta-analysisView study →}.

Gap: the direction is positive, but the size of the effect is small.

Two small placebo-controlled trials of EGb 761 report improvement in premenstrual symptoms, particularly congestive and breast symptoms (mastalgia) rather than mood ^{22,23Reference 22Ozgoli G et al. · 2009RCTA randomized, placebo-controlled trial of Ginkgo biloba L. in treatment of premenstrual syndrome — randomised controlled trialView study →Reference 23Tamborini A et al. · 1993RCTTamborini A, & Taurelle R (1993). [Value of standardized Ginkgo biloba extract (EGb 761) in the management of congestive symptoms of premenstrual syndrome] — randomised controlled trial. Revue francaise de gynecologie et d’obstetrique. https://pubmed.ncbi.nlm.nih.gov/8235261/View study →}.

Gap: two small trials, with no large or recent confirmation.

The Cochrane review of ginkgo for tinnitus as a primary complaint found no convincing evidence of benefit ^{24,25Reference 24Sereda M et al. · 2022Systematic reviewGinkgo biloba for tinnitus — systematic reviewView study →Reference 25Hilton MP et al. · 2013Meta-analysisGinkgo biloba for tinnitus — systematic review and meta-analysisView study →}. A signal appears only when tinnitus is a secondary symptom in people with cognitive impairment taking ginkgo for dementia.

Gap: Cochrane-level evidence is negative for primary tinnitus; any signal is confined to tinnitus secondary to cognitive decline.

The proposed ocular mechanism is improved retinal blood flow and antioxidant protection ^{10Reference 10Droy-Lefaix MT et al. · 1995AnimalAntioxidant effect of a Ginkgo biloba extract (EGb 761) on the retina — animal model studyView study →}. The Cochrane review identified only two small trials and concluded there is insufficient evidence to determine whether ginkgo benefits AMD ^{26Reference 26Evans JR · 2013Systematic reviewGinkgo biloba extract for age-related macular degeneration — systematic reviewView study →}.

Gap: only two small trials exist.

A systematic review of RCTs in healthy people found no robust, durable effect on memory, attention or executive function ^{28Reference 28Canter PH et al. · 2007Systematic reviewGinkgo biloba is not a smart drug: an updated systematic review of randomised clinical trials testing the nootropic effects of G. biloba extracts in healthy people — systematic reviewView study →}, and a large JAMA trial in older adults without dementia was null for memory enhancement ^{27Reference 27Solomon PR et al. · 2002RCTGinkgo for memory enhancement: a randomized controlled trial — randomised controlled trialView study →}. Acute single doses can shift performance on some speed and attention tasks in a dose-dependent way ^{29Reference 29Kennedy DO et al. · 2000RCTThe dose-dependent cognitive effects of acute administration of Ginkgo biloba to healthy young volunteers — randomised controlled trialView study →}, but this does not carry through to sustained cognitive improvement.

Gap: chronic dosing in healthy adults is consistently null; only transient, task-specific acute effects have been seen.

The Ginkgo Evaluation of Memory (GEM) study randomised roughly 3,000 older adults with normal cognition or mild cognitive impairment to EGb 761 240 mg/day or placebo for a median of about six years. It found no reduction in the incidence of dementia or Alzheimer’s disease ^{30Reference 30DeKosky ST et al. · 2008RCTGinkgo biloba for prevention of dementia: a randomized controlled trial — randomised controlled trialView study →}, and a companion analysis found no slowing of cognitive decline ^{31,32Reference 31Snitz BE et al. · 2009RCTGinkgo biloba for preventing cognitive decline in older adults: a randomized trial — randomised controlled trialView study →Reference 32DeKosky ST et al. · 2006RCTThe Ginkgo Evaluation of Memory (GEM) study: design and baseline data of a randomized trial of Ginkgo biloba extract in prevention of dementia — randomised controlled trialView study →}.

Bleeding. Ginkgolides antagonise platelet-activating factor, and observational and case data associate ginkgo, especially alongside antiplatelet or anticoagulant drugs (warfarin, aspirin, clopidogrel), with an increased risk of haemorrhage ^{33,36Reference 33Chan AL et al. · 2011ObservationalRisk of hemorrhage associated with co-prescriptions for Ginkgo biloba and antiplatelet or anticoagulant drugs — observational cohort studyView study →Reference 36Mai NTQ et al. · 2025ObservationalImpact of Ginkgo biloba drug interactions on bleeding risk and coagulation profiles: A comprehensive analysis — observational studyView study →}. A large Veterans Administration cohort found no significant warfarin interaction ^{34Reference 34Stoddard GJ et al. · 2015ObservationalGinkgo and Warfarin Interaction in a Large Veterans Administration Population — observational cohort studyView study →}, and a careful review judged the interaction evidence weaker than commonly stated ^{35Reference 35Bone KM · 2008ReviewPotential interaction of Ginkgo biloba leaf with antiplatelet or anticoagulant drugs: what is the evidence? — reviewView study →}. The prudent course is to avoid combining ginkgo with blood-thinning drugs and to stop it about two weeks before surgery.

Seeds. Ginkgo seeds contain ginkgotoxin (4-O-methylpyridoxine), which can cause vitamin-B6-responsive seizures in poisoning cases ^{37,38Reference 37Kosaki Y et al. · 2020Case reportEpileptic Seizure from Ginkgo Nut Intoxication in an Adult — case reportView study →Reference 38Fujisawa M et al. · 2002Case reportGas chromatography-mass spectrometry analysis of 4-O-methylpyridoxine (MPN) in the serum of patients with ginkgo seed poisoning — case reportView study →}. The leaf extract is not implicated.

Ginkgolic acids. Crude leaf and homemade preparations carry high levels of these allergenic compounds, which the standardised extract limits to under 5 ppm ^{42,43Reference 42van Beek et al. · 2009ReviewChemical analysis and quality control of Ginkgo biloba leaves, extracts, and phytopharmaceuticals — reviewView study →Reference 43European Medicines AgencyAssessment report on Ginkgo biloba L., folium}.

Rodent carcinogenicity. Chronic high-dose ginkgo extract caused liver and thyroid tumours in a two-year US National Toxicology Program study in rats and mice ^{39,40Reference 39National Toxicology Program · 2013AnimalToxicology and carcinogenesis studies of Ginkgo biloba extract (CAS NoView study →Reference 40Rider CV et al. · 2014AnimalToxicity and carcinogenicity studies of Ginkgo biloba extract in rat and mouse: liver, thyroid, and nose are targets — animal (rat and mouse) carcinogenicity studyView study →}. The human relevance at supplement doses is uncertain and debated ^{41Reference 41Mei N et al. · 2017Case reportReview of Ginkgo biloba-induced toxicity, from experimental studies to human case reports — reviewView study →}, but the finding places ginkgo on some regulatory watch-lists.

Drug metabolism. In a probe-drug study in healthy volunteers, the standardised extract EGb 761 had no relevant effect on CYP1A2, CYP2C9, CYP2C19, CYP2D6 or CYP3A4 ^{47Reference 47Zadoyan et al. · 2012Clinical trialEffect of Ginkgo biloba special extract EGb 761® on human cytochrome P450 activity: a cocktail interaction study in healthy volunteers — clinical studyView study →}. Two smaller studies saw modest changes after repeated dosing: lower omeprazole levels, suggesting faster clearance through CYP2C19 ^{48Reference 48Yin et al. · 2004Clinical trialPharmacogenetics and herb-drug interactions: experience with Ginkgo biloba and omeprazole — clinical studyView study →}, and higher levels of talinolol, a drug carried by P-glycoprotein ^{49Reference 49Fan et al. · 2009Clinical trialEffect of Schisandra chinensis extract and Ginkgo biloba extract on the pharmacokinetics of talinolol in healthy volunteers — clinical studyView study →}.