Herbal Monograph

Ginkgo

Ginkgo biloba L.

Ginkgoaceae

Class 2d Circulatory stimulant Neuroprotective Antioxidant PAF antagonist

Living fossil tree and premier cerebral circulatory tonic for cognitive decli...

Overview

Plant Description

Ginkgo biloba is a large, deciduous, dioecious tree reaching 20–35 m (occasionally to 50 m) in height with a spreading crown. The bark is grey-brown, deeply furrowed on mature specimens. Leaves are distinctive fan-shaped (flabellate), 5–8 cm wide, with dichotomous venation and a deep central notch creating two lobes (biloba). Leaves are bright green in summer, turning brilliant golden-yellow in autumn. Male trees produce pendulous catkin-like strobili; female trees bear ovules in pairs on long stalks, developing into fleshy, yellowish, foul-smelling seeds (technically not fruits, as Ginkgo is a gymnosperm) approximately 2–3 cm in diameter. The outer fleshy layer (sarcotesta) contains butyric acid and ginkgolic acids that cause contact dermatitis. The inner seed (ginkgo nut) is edible after processing. Trees are extremely long-lived, with specimens exceeding 1,000 years documented in China.

Habitat

Native to southeastern China, specifically Zhejiang province and surrounding regions. Grows naturally in mixed mesophytic forests on well-drained, loamy or sandy soils at elevations of 300–1,100 m. Tolerates a wide range of soil pH (3.5–8.0). Extremely resistant to air pollution, compacted soils, and urban stress, making it one of the most widely planted street and park trees worldwide. Hardy to USDA zones 3–9. Thrives in full sun to partial shade with moderate moisture.

Distribution

Native range is restricted to a small area of central China (Zhejiang, Guizhou, and possibly Chongqing provinces), where genuinely wild populations may persist in the Tianmu Mountain Nature Reserve. Widely cultivated throughout temperate regions of China, Japan, Korea, Europe (since ~1730), and North America (since ~1784). Major commercial cultivation occurs in China (Jiangsu, Shandong, Hubei provinces), France (Bordeaux region), and the United States (South Carolina). Naturalized in parts of eastern North America and western Europe.

Parts Used

Leaf

Preferred: Standardized extract (e.g., EGb 761: 22–27% flavonol glycosides, 5–7% terpene lactones, <5 ppm ginkgolic acids)

The leaf is the primary medicinal part used in Western phytotherapy. All major clinical trials and pharmacopeial monographs (Commission E, WHO, EMA, AHP) refer to standardized leaf extracts. The green leaf contains the therapeutically relevant flavonol glycosides (quercetin, kaempferol, isorhamnetin glycosides) and unique terpene lactones (ginkgolides A, B, C, J and bilobalide). Raw leaf preparations (teas, crude tinctures) are NOT equivalent to the standardized extract and may contain unacceptably high levels of ginkgolic acids.

Seed (Ginkgo nut / Bai guo)

Preferred: Cooked seed kernel only (TCM use); NOT used in Western standardized preparations

The seed kernel is used in Traditional Chinese Medicine (TCM) but NOT typically in Western herbal practice. In TCM, the cooked seed is used for asthma, cough with phlegm, and vaginal discharge. The raw seed is toxic, containing 4'-O-methylpyridoxine (ginkgotoxin), a vitamin B6 antagonist that can cause seizures. The outer fleshy sarcotesta contains potent allergens (ginkgolic acids, alkylphenols) and must be removed before use. Western pharmacopeial monographs (Commission E, WHO, EMA) do NOT cover the seed.

Key Constituents

Flavonol glycosides

Quercetin glycosides (rutin, quercitrin, isoquercitrin) Standardized to 22–27% total flavonol glycosides in EGb 761
Kaempferol glycosides (astragalin, kaempferitrin) Major component of the flavonol glycoside fraction
Isorhamnetin glycosides Minor component of the flavonol glycoside fraction

The flavonol glycosides are potent antioxidants responsible for free radical scavenging, inhibition of lipid peroxidation, and endothelial protection. They contribute to the vasoprotective and anti-inflammatory actions of Ginkgo extract. The standardization to 22–27% ensures consistent antioxidant activity across batches.

Terpene lactones (Ginkgolides and Bilobalide)

Ginkgolide A Approximately 1.0–1.8% of standardized extract
Ginkgolide B Approximately 0.4–1.2% of standardized extract
Ginkgolide C Approximately 0.5–1.5% of standardized extract
Ginkgolide J Trace amounts
Bilobalide Approximately 2.6–3.4% of standardized extract

The terpene lactones are pharmacologically unique to Ginkgo biloba and are responsible for its most distinctive actions: PAF antagonism (ginkgolides) reducing platelet aggregation and neuroinflammation, and direct neuroprotection (bilobalide) via mitochondrial stabilization and anti-excitotoxic mechanisms. The standardization to 5–7% total terpene lactones ensures clinically relevant concentrations of these compounds.

Proanthocyanidins (Condensed tannins)

Procyanidins (dimers and trimers) Approximately 7% of standardized extract
Delphinidin-based proanthocyanidins Minor component

Proanthocyanidins contribute synergistically to the antioxidant and vasoprotective effects of the extract. They stabilize collagen, reduce capillary permeability, and enhance the radical-scavenging activity of the flavonol glycosides.

Organic acids

Ginkgolic acids (alkylphenols) <5 ppm in standardized EGb 761 extract; 0.5–5% in raw leaf
6-Hydroxykynurenic acid Trace

Ginkgolic acids are toxicologically significant and must be minimized. The quality-control removal of ginkgolic acids to <5 ppm is a critical differentiator between pharmacopeial-grade extracts and crude leaf products. This is why standardized extracts are strongly preferred over teas or crude tinctures.

Biflavones

Amentoflavone Trace to minor
Bilobetin Trace
Ginkgetin Trace
Sciadopitysin Trace
Isoginkgetin Trace

The biflavones are minor constituents that are largely removed during standardized extraction. They contribute modestly to the anti-inflammatory and antioxidant profile of crude leaf preparations but are not considered primary active constituents in standardized extracts.

Herbal Actions

circulatory-stimulant (primary)

Enhances peripheral and cerebral blood flow. Improves microcirculation through vasodilation (primarily via nitric oxide-mediated endothelial relaxation), reduced blood viscosity, and PAF antagonism reducing platelet aggregation. Commission E approved for 'disturbed performance in organic brain syndrome' and intermittent claudication on this basis.

[1, 2, 14]
neuroprotective (primary)

Bilobalide and ginkgolides protect neurons against ischemic injury, glutamate excitotoxicity, and oxidative stress. Bilobalide stabilizes mitochondrial membrane potential and reduces cerebral edema. Ginkgolide B antagonizes PAF-mediated neuroinflammation. These mechanisms collectively protect against ischemia-reperfusion injury in brain tissue.

[3, 14, 16]
Antioxidant (primary)

Prevents or slows oxidative damage to cells

Potent free radical scavenger via the flavonol glycoside and proanthocyanidin fractions. Scavenges superoxide, hydroxyl, and peroxyl radicals. Inhibits lipid peroxidation of cell membranes. Upregulates endogenous antioxidant enzymes (superoxide dismutase, glutathione peroxidase) in vivo. The antioxidant activity is synergistic between the flavonoid and terpenoid fractions.

[2, 13, 14]
Anti-inflammatory (secondary)

Reduces inflammation

PAF antagonism (primarily ginkgolide B) inhibits PAF-mediated inflammatory cascades including neutrophil activation, vascular permeability, and bronchoconstriction. Also inhibits lipoxygenase and cyclooxygenase pathways, reducing leukotriene and prostaglandin synthesis. The biflavone ginkgetin inhibits phospholipase A2.

[13, 14]
cognitive-enhancer (primary)

Improves cognitive performance through multiple mechanisms: enhanced cerebral blood flow, neuroprotection, antioxidant defense, cholinergic modulation, and reduced amyloid-beta aggregation. Commission E and EMA approve for age-related cognitive decline. The GuidAge and GEM trials showed mixed results for dementia prevention but positive effects on existing cognitive symptoms.

[1, 2, 3]
antiplatelet (secondary)

Ginkgolide B is a specific competitive antagonist of the platelet-activating factor (PAF) receptor. This reduces platelet aggregation through a mechanism distinct from aspirin (COX inhibition) or clopidogrel (ADP receptor blockade). Clinically, this action requires consideration when combining with anticoagulant/antiplatelet drugs.

[4, 14, 17]
vasodilator (secondary)

Relaxes vascular smooth muscle, particularly in arterioles and capillaries. The mechanism involves enhancement of endothelial nitric oxide synthase (eNOS) activity and direct smooth muscle relaxation. Improves blood flow in peripheral vascular beds (lower limbs) and cerebral vasculature.

[2, 13]
venotonic (mild)

Improves venous tone and reduces capillary permeability. The proanthocyanidin fraction stabilizes capillary walls and reduces edema formation. Less potent than primary venotonics (e.g., horse chestnut) but contributes to overall vascular support.

[14]

Therapeutic Indications

nervous-system

well established

Age-associated cognitive impairment

Commission E approved for 'disturbed performance in organic brain syndrome within the overall concept of dementia syndromes' including memory deficits, concentration difficulties, depressive mood, dizziness, tinnitus, and headache. WHO monograph supports use for 'symptomatic treatment of mild to moderate cerebrovascular insufficiency.' EMA lists as well-established use for age-associated cognitive impairment and quality of life.

[1, 2, 3]
supported

Dementia (Alzheimer's type and vascular)

Multiple RCTs and meta-analyses show modest but significant improvement in cognitive function (ADAS-Cog) and activities of daily living (ADL) in patients with mild-to-moderate dementia when treated with EGb 761 at 240 mg/day. Comparable efficacy to cholinesterase inhibitors in some trials. The GEM trial (2008, n=3,069) found no benefit for dementia prevention in cognitively normal elderly, but subsequent analyses and the GuidAge trial (2012, n=2,854) showed trends toward reduced Alzheimer's incidence in compliant subgroups. Not a substitute for standard pharmacotherapy.

[2, 3, 5, 6]
well established

Vertigo and dizziness (vestibular origin)

Commission E approved for vertigo. WHO monograph supports symptomatic treatment of vertigo of vascular or involutional origin. Multiple clinical trials demonstrate reduction in frequency and intensity of vertiginous episodes. EMA lists as well-established traditional use.

[1, 2, 3]
supported

Tinnitus

Commission E approved for tinnitus as part of the cerebral insufficiency syndrome. Evidence is mixed: some RCTs show benefit particularly in recent-onset tinnitus of vascular origin, while others (notably Rejali et al., 2004) showed no benefit in chronic tinnitus. WHO supports use for tinnitus of vascular and involutional origin specifically. More effective when tinnitus is associated with cerebrovascular insufficiency than when it is an isolated symptom.

[1, 2, 14]
preliminary

Anxiety (generalized anxiety disorder)

Woelk et al. (2007) RCT showed EGb 761 at 480 mg/day significantly reduced HAM-A anxiety scores compared to placebo (p<0.0001). 240 mg/day also effective but less robust. Mechanism may involve GABAergic modulation and cortisol reduction. Further replication needed.

[8]

Cardiovascular System

well established

Intermittent claudication (peripheral arterial occlusive disease, Fontaine stage II)

Commission E approved for 'intermittent claudication in peripheral arterial occlusive disease (Fontaine stage II).' WHO monograph concurs. Multiple RCTs demonstrate significant increases in pain-free walking distance (mean increase 30–40% over placebo) with EGb 761 at 120–240 mg/day. EMA recognizes as well-established use. Mechanism involves enhanced peripheral blood flow, reduced blood viscosity, and PAF antagonism.

[1, 2, 3, 7]
supported

Raynaud's phenomenon

Clinical evidence supports reduction in frequency and severity of vasospastic attacks. Muir et al. (2002) RCT showed 56% reduction in attacks with EGb 761 vs. placebo. Mechanism involves peripheral vasodilation and PAF antagonism improving microcirculation.

[10, 14]
well established

Cerebral insufficiency

Broad indication encompassing symptoms of reduced cerebral blood flow: poor concentration, memory impairment, confusion, fatigue, headache, dizziness, and depressive mood. This was the original primary indication for Commission E approval. Multiple trials confirm significant symptom improvement with standardized extract.

[1, 2, 13]

ophthalmology

supported

Normal-tension glaucoma

Several clinical studies demonstrate improved visual field indices and ocular blood flow in normal-tension glaucoma patients treated with EGb 761 at 120–160 mg/day. Quaranta et al. (2003) showed significant improvement in visual field after 4 weeks. Mechanism involves improved ocular microcirculation and neuroprotection of retinal ganglion cells.

[9, 14]
preliminary

Age-related macular degeneration (AMD)

Limited clinical evidence suggests improvement in visual acuity in early AMD. Antioxidant and microcirculation-enhancing properties provide theoretical basis. Further large-scale RCTs needed.

[14]

ear-nose-throat

supported

Acute cochlear deafness (sudden sensorineural hearing loss)

German clinical practice includes Ginkgo extract (intravenous or high-dose oral) as adjunct treatment for sudden hearing loss of vascular origin. Evidence from European trials supports improved recovery when administered early. Not established practice in Anglophone countries.

[2, 14]

Respiratory System

preliminary

Asthma (PAF-mediated bronchoconstriction)

The PAF antagonist activity of ginkgolides theoretically benefits asthma by blocking PAF-mediated bronchoconstriction, airway hyperreactivity, and eosinophil infiltration. Early clinical trials showed attenuation of PAF-induced and allergen-induced bronchoconstriction. Not a substitute for standard asthma therapy. Limited clinical adoption.

[14, 17]

Energetics

Temperature

neutral

Moisture

dry

Taste

bitterastringentsweet

Tissue States

cold/depression, damp/stagnation

In TCM, Ginkgo leaf (Yin Xing Ye) is classified as sweet, bitter, and astringent in flavor with a neutral temperature. It enters the Heart and Lung channels. In Western energetic terms (following Hoffmann and Wood), it is slightly drying and neutral in temperature, addressing cold/depressive tissue states characterized by poor circulation, cognitive sluggishness, and tissue hypoxia. The astringent quality addresses damp/stagnation patterns in the vasculature. It is suitable for deficient, cold constitutions with poor peripheral circulation and impaired cognition.

Traditional Uses

Traditional Chinese Medicine (TCM)

  • Ginkgo seed (Bai Guo) used for cough with copious phlegm, wheezing, and asthma (enters Lung channel)
  • Seed used for vaginal discharge (leukorrhea) and urinary frequency (astringent to Lower Jiao)
  • Seed used topically for skin conditions including acne and fungal infections
  • Leaf (Yin Xing Ye) used for chest pain with palpitations, benefiting the Heart channel and quickening blood circulation
  • Leaf used for dysentery and diarrhea (astringent action)

"The seed (Bai Guo) first appeared in the dietary materia medica Ri Yong Ben Cao (c. 1329) during the Yuan Dynasty. Li Shizhen included it in the Ben Cao Gang Mu (Compendium of Materia Medica, 1578), noting: 'It warms the lungs, benefits the qi, calms asthma, and reduces phlegm. It is used for turbid discharge and leukorrhea.' The leaf was not prominent in classical Chinese pharmacopeias and gained therapeutic prominence primarily through 20th-century Western phytochemical research."

[11, 12]

Western Herbalism (Modern)

  • Cerebral circulatory insufficiency with cognitive decline, poor memory, and difficulty concentrating
  • Peripheral vascular insufficiency including intermittent claudication, cold extremities, and Raynaud's phenomenon
  • Vertigo, dizziness, and tinnitus of vascular origin
  • Adjunctive support in early-stage dementia (Alzheimer's and vascular types)
  • Age-related macular degeneration and normal-tension glaucoma (ocular circulation)

"Hoffmann (2003): 'Ginkgo has become one of the most widely used herbs in the Western world, primarily for its effects on the brain and circulation. It improves blood flow throughout the body, particularly to the brain, and has a protective effect on the nerve cells.' Mills & Bone (2013) classify it as a 'circulatory tonic and cerebral vasodilator' with 'PAF antagonist, neuroprotective, antioxidant, and cognitive enhancer' actions."

[13, 14]

Kampo (Japanese Traditional Medicine)

  • Ginkgo seed used in combination formulas for respiratory conditions (cough, phlegm, asthma)
  • Ginkgo nut consumed as food and medicine for lung and kidney deficiency patterns
  • Roasted seeds consumed for general tonic purposes

"In Japanese tradition, ginkgo nuts (ginnan) have been consumed as food and medicine for centuries. The leaf was not traditionally used in Kampo, mirroring the Chinese classical tradition. The modern clinical use of leaf extracts derives from European (primarily German) phytopharmaceutical development."

[11]

Modern Research

meta analysis

Cognitive function in dementia

Extensive clinical trial literature examining EGb 761 for Alzheimer's disease and vascular dementia. The body of evidence demonstrates consistent, modest improvements in cognitive measures (ADAS-Cog, SKT) and activities of daily living in mild-to-moderate dementia.

Findings: Weinmann et al. (2010) meta-analysis of 9 RCTs (n=2,372) found EGb 761 at 240 mg/day significantly improved cognition (SMD = -0.58, 95% CI: -1.14 to -0.01, p=0.04) and ADL (SMD = -0.32, 95% CI: -0.66 to 0.01) versus placebo in dementia patients. Birks & Grimley Evans (2009) Cochrane review of 36 trials concluded that Ginkgo appeared safe with promising evidence but noted inconsistency across trials. Effect size comparable to cholinesterase inhibitors in some analyses.

Limitations: Heterogeneity across trials in dose, duration, diagnostic criteria, and outcome measures limits firm conclusions. The large prevention trials (GEM, GuidAge) were negative for dementia prevention, though methodological criticisms exist (adherence, dose, population selection).

[5, 6]

meta analysis

Intermittent claudication

Multiple RCTs demonstrate improved walking distance in patients with peripheral arterial occlusive disease (Fontaine stage IIb) treated with EGb 761.

Findings: Pittler & Ernst (2005) meta-analysis of 11 RCTs found a significant increase in pain-free walking distance with Ginkgo extract versus placebo (weighted mean difference: 64.5 m, 95% CI: 28.3 to 100.8 m). Effect consistent across studies using 120–320 mg/day. Commission E, WHO, and EMA all approve this indication.

Limitations: Several trials were of short duration (12–24 weeks). Effect sizes were modest compared to exercise therapy. Some trials used doses above standard recommendations. The clinical significance of a 64-meter improvement varies by baseline function.

[1, 7]

narrative review

Neuroprotection and anti-excitotoxicity

Preclinical research demonstrates that bilobalide and ginkgolides protect neurons against ischemic injury and glutamate excitotoxicity through multiple mechanisms.

Findings: Bilobalide reduces NMDA receptor-mediated excitotoxicity, preserves mitochondrial membrane potential during ischemia, reduces cerebral edema by 50% in animal stroke models, and enhances neuronal survival in hippocampal slice cultures exposed to hypoxia. Ginkgolide B blocks PAF-mediated neuroinflammation and microglial activation. Combined, these actions provide a comprehensive neuroprotective profile against both acute ischemic injury and chronic neurodegeneration.

Limitations: Most neuroprotection data derives from in vitro and animal studies. Translation to human stroke or neurodegeneration outcomes has not been definitively established. Clinical neuroprotection trials in acute stroke are absent.

[14, 16]

narrative review

PAF antagonism and anti-inflammatory mechanisms

Ginkgolide B is among the most potent naturally occurring PAF receptor antagonists identified. This mechanism underlies multiple therapeutic effects.

Findings: Ginkgolide B competitively antagonizes the PAF receptor with an IC50 of approximately 0.5–3 µM in platelet aggregation assays. PAF antagonism reduces: platelet aggregation (anti-thrombotic), bronchoconstriction (anti-asthmatic), vascular permeability (anti-edema), neutrophil chemotaxis (anti-inflammatory), and microglial activation (neuroprotective). This single mechanism accounts for a broad spectrum of Ginkgo's pharmacological actions.

Limitations: In vivo PAF antagonism depends on adequate tissue concentrations of ginkgolide B, which requires standardized extract at adequate doses. The clinical significance of PAF antagonism in each specific condition varies.

[14, 17]

rct

Ocular blood flow and glaucoma

Clinical studies examine the effects of EGb 761 on ocular hemodynamics and visual field in normal-tension glaucoma.

Findings: Quaranta et al. (2003) randomized 27 normal-tension glaucoma patients to EGb 761 (40 mg TID) or placebo for 4 weeks plus 8-week washout crossover. Ginkgo significantly improved visual field mean deviation (p=0.007) and corrected pattern standard deviation. Improved ocular blood flow velocity measured by color Doppler ultrasonography. Harris et al. reported increased ophthalmic artery blood flow with Ginkgo extract.

Limitations: Small sample sizes. Short treatment duration. Effects on intraocular pressure were not demonstrated (Ginkgo does not lower IOP). Long-term visual field preservation data is lacking. Should not replace standard glaucoma therapy.

[9]

rct

Anxiety

A single large RCT examined the anxiolytic potential of EGb 761 in generalized anxiety disorder.

Findings: Woelk et al. (2007) randomized 107 patients with GAD or adjustment disorder with anxious mood to EGb 761 480 mg/day, 240 mg/day, or placebo for 4 weeks. Both doses significantly reduced HAM-A scores versus placebo (p<0.01 for 480 mg; p<0.05 for 240 mg). The 480 mg dose was associated with a 14.3-point HAM-A reduction versus 7.8 for placebo.

Limitations: Single study. Short duration (4 weeks). The 480 mg dose exceeds the standard recommended dose of 120–240 mg/day. Replication in independent trials is needed before this can be considered a validated indication.

[8]

Preparations & Dosage

Standardized Extract

Strength: 35–67:1 drug-extract ratio (DER); standardized to 22–27% flavonol glycosides and 5–7% terpene lactones

The standardized dry extract EGb 761 (and bioequivalent products such as LI 1370) is produced by multi-step extraction of dried green Ginkgo leaves with acetone-water, followed by purification steps to concentrate flavonol glycosides and terpene lactones while removing toxic ginkgolic acids. This is the form used in virtually all clinical trials and the only form recommended by pharmacopeial monographs.

Adult:

120–240 mg daily of standardized extract (22–27% flavonol glycosides, 5–7% terpene lactones, <5 ppm ginkgolic acids), divided into 2–3 doses

Frequency:

2–3 times daily with meals

Duration:

Minimum 8 weeks to assess efficacy for cognitive indications. Commission E recommends reassessment after 3 months of continuous use. Long-term use (6–12 months) studied in dementia trials.

Pediatric:

Not recommended for children under 12 due to insufficient safety data

The 240 mg/day dose showed superior efficacy to 120 mg/day in several dementia trials and is increasingly recommended as the standard therapeutic dose. Take with food to reduce GI side effects. Onset of action is gradual; 4–6 weeks minimum for noticeable benefit in cognitive indications.

[1, 2, 3]

Tincture

Strength: 1:5 in 45% ethanol

Tincture of fresh or dried Ginkgo leaf. Less common in clinical practice due to difficulty achieving standardized concentrations of active constituents and inability to control ginkgolic acid content. Some Western herbalists use tinctures as part of combination formulas.

Adult:

2–4 mL of 1:5 tincture (45% ethanol) three times daily

Frequency:

Three times daily

Duration:

8–12 weeks minimum for assessment

Pediatric:

Not recommended

Tinctures are NOT equivalent to standardized extracts. Flavonoid and terpene lactone content is variable and typically much lower than standardized extracts. Ginkgolic acid content is not controlled in tinctures. Hoffmann notes tincture use but acknowledges the standardized extract as the preferred form for serious indications.

[13, 15]

Infusion (Tea)

Strength: Approximately 1:20 herb to water

Infusion (tea) of dried Ginkgo leaves. NOT recommended as a primary therapeutic preparation. The water extraction is inefficient for the lipophilic terpene lactones, and ginkgolic acid content is not controlled.

Adult:

1–2 teaspoons dried leaf per cup, steeped 5–10 minutes, up to 3 cups daily

Frequency:

Up to 3 times daily

Duration:

Not established for therapeutic endpoints

Pediatric:

Not recommended

Ginkgo leaf tea provides the water-soluble flavonol glycosides but poorly extracts the lipophilic terpene lactones (ginkgolides, bilobalide). This means the PAF-antagonist and neuroprotective actions — which are the most clinically distinctive — are substantially under-represented in tea form. Additionally, ginkgolic acid content in teas may exceed safe thresholds. Tea use should be considered a mild supportive measure, not equivalent to standardized extract therapy.

[13]

Safety & Interactions

Class 2d

Other specific use restrictions apply (AHPA Botanical Safety Handbook)

Contraindications

absolute Known hypersensitivity to Ginkgo biloba preparations

Cross-reactivity may occur in individuals allergic to urushiol-containing plants (poison ivy, mango rind, cashew) due to structural similarity of ginkgolic acids (alkylphenols) to urushiol, though this applies primarily to contact with the fruit pulp rather than purified leaf extracts.

relative Active bleeding or hemorrhagic disorders

PAF antagonism and antiplatelet activity could theoretically exacerbate bleeding. While controlled clinical trials have not demonstrated increased bleeding risk at standard doses, case reports exist of spontaneous bleeding (subdural hematoma, hyphema, postoperative bleeding) in patients taking Ginkgo, often concurrently with anticoagulants.

relative Pre-surgical period

Discontinue standardized extract at least 36 hours (preferably 7 days) before elective surgery due to theoretical increased bleeding risk from PAF antagonism. The American Society of Anesthesiologists recommends discontinuation of Ginkgo 2 weeks before surgery.

Drug Interactions

Drug / Class Severity Mechanism
Warfarin (Anticoagulants (vitamin K antagonists)) moderate PAF antagonism may augment anticoagulant effect. Case reports of elevated INR and bleeding when Ginkgo is added to stable warfarin therapy. Pharmacokinetic interaction unlikely (Ginkgo does not significantly affect CYP2C9 or CYP3A4 at standard doses).
Aspirin (Antiplatelet agents (COX inhibitors)) moderate Additive antiplatelet effects via complementary mechanisms (Ginkgo: PAF antagonism; aspirin: COX-1 inhibition). Combined use may increase bleeding time.
Clopidogrel and ticagrelor (Antiplatelet agents (P2Y12 inhibitors)) moderate Additive antiplatelet effect through complementary pathways (PAF antagonism + ADP receptor blockade).
NSAIDs (ibuprofen, naproxen, diclofenac) (Non-steroidal anti-inflammatory drugs) minor NSAIDs inhibit COX-1 (reducing thromboxane A2) which, combined with Ginkgo's PAF antagonism, may additively impair platelet function.
Anticonvulsants (phenytoin, valproic acid, carbamazepine) (Antiepileptic drugs) theoretical Ginkgotoxin (4'-O-methylpyridoxine) in the seed antagonizes vitamin B6, potentially lowering seizure threshold. However, standardized LEAF extract contains negligible ginkgotoxin. The interaction is clinically relevant only for seed consumption, not for leaf extract at standard doses.
Trazodone (Serotonin antagonist and reuptake inhibitor (SARI)) minor A single case report of excessive sedation/coma attributed to Ginkgo + trazodone. Proposed mechanism involves Ginkgo-mediated enhancement of GABAergic activity potentiating trazodone's sedation.

Pregnancy & Lactation

Pregnancy

possibly unsafe

Lactation

insufficient data

AHPA classifies Ginkgo leaf as Class 2d: 'Not to be used during pregnancy.' The antiplatelet activity (PAF antagonism) poses a theoretical risk of bleeding, particularly during labor and delivery. No human teratogenicity data exists, but the PAF antagonist mechanism warrants avoidance. No adequate data on excretion into breast milk. WHO monograph states: 'Ginkgo biloba preparations should not be used during pregnancy or lactation without medical supervision.'

Adverse Effects

uncommon Gastrointestinal complaints (nausea, stomach upset, diarrhea) — Reported in approximately 1–3% of clinical trial participants. Generally mild and transient. Taking with food reduces incidence.
uncommon Headache — Reported in approximately 1–2% of participants. May be related to changes in cerebral blood flow. Usually resolves with continued use or dose reduction.
uncommon Dizziness — Paradoxically reported in some individuals despite Ginkgo being used to treat vertigo. Usually transient and mild.
rare Allergic skin reactions — More common with crude preparations or contact with fruit pulp. Very rare with standardized extracts containing <5 ppm ginkgolic acids.
very-rare Bleeding events (spontaneous hemorrhage) — Case reports of subdural hematoma, subarachnoid hemorrhage, hyphema, and postoperative bleeding exist, predominantly in patients concurrently taking anticoagulants. Large clinical trials (GEM, n=3,069) did not demonstrate statistically increased bleeding risk at 240 mg/day. Causality is difficult to establish in individual case reports.

References

Monograph Sources

  1. [1] Blumenthal, M., Busse, W.R., Goldberg, A., et al.. The Complete German Commission E Monographs: Therapeutic Guide to Herbal Medicines. American Botanical Council / Integrative Medicine Communications (1998) . ISBN: 978-0-9655555-0-0
  2. [2] World Health Organization. WHO Monographs on Selected Medicinal Plants, Volume 1: Folium Ginkgo. World Health Organization, Geneva (1999) . ISBN: 978-92-4-154517-0
  3. [3] European Medicines Agency, Committee on Herbal Medicinal Products (HMPC). European Union herbal monograph on Ginkgo biloba L., folium. EMA/HMPC/321097/2012 (2015)
  4. [4] Gardner, Z., McGuffin, M. (eds.). American Herbal Products Association's Botanical Safety Handbook, 2nd Edition. CRC Press (2013) . ISBN: 978-1-4665-1695-3

Clinical Studies

  1. [5] Weinmann, S., Roll, S., Schwarzbach, C., Vauth, C., Willich, S.N.. Effects of Ginkgo biloba in dementia: systematic review and meta-analysis. BMC Geriatrics (2010) ; 10 : 14 . DOI: 10.1186/1471-2318-10-14 . PMID: 20236541
  2. [6] Birks, J., Grimley Evans, J.. Ginkgo biloba for cognitive impairment and dementia. Cochrane Database of Systematic Reviews (2009) ; 1 : CD003120 . DOI: 10.1002/14651858.CD003120.pub3 . PMID: 19160216
  3. [7] Pittler, M.H., Ernst, E.. Ginkgo biloba extract for the treatment of intermittent claudication: a meta-analysis of randomized trials. American Journal of Medicine (2000) ; 108 : 276–281 . DOI: 10.1016/S0002-9343(99)00454-4 . PMID: 11014719
  4. [8] Woelk, H., Arnoldt, K.H., Kieser, M., Hoerr, R.. Ginkgo biloba special extract EGb 761 in generalized anxiety disorder and adjustment disorder with anxious mood: a randomized, double-blind, placebo-controlled trial. Journal of Psychiatric Research (2007) ; 41(6) : 472–480 . DOI: 10.1016/j.jpsychires.2006.05.004 . PMID: 16808927
  5. [9] Quaranta, L., Bettelli, S., Uva, M.G., Semeraro, F., Turano, R., Gandolfo, E.. Effect of Ginkgo biloba extract on preexisting visual field damage in normal tension glaucoma. Ophthalmology (2003) ; 110(2) : 359–362 . DOI: 10.1016/S0161-6420(02)01745-1 . PMID: 12578781
  6. [10] Muir, A.H., Robb, R., McLaren, M., Daly, F., Belch, J.J.F.. The use of Ginkgo biloba in Raynaud's disease: a double-blind placebo-controlled trial. Vascular Medicine (2002) ; 7(4) : 265–267 . DOI: 10.1191/1358863x02vm455oa . PMID: 12710841

Traditional Texts

  1. [11] Bensky, D., Clavey, S., Stöger, E.. Chinese Herbal Medicine: Materia Medica, 3rd Edition. Eastland Press (2004) . ISBN: 978-0-939616-42-8
  2. [12] Chen, J.K., Chen, T.T.. Chinese Medical Herbology and Pharmacology. Art of Medicine Press (2004) . ISBN: 978-0-9740635-0-0
  3. [13] Hoffmann, D.. Medical Herbalism: The Science and Practice of Herbal Medicine. Healing Arts Press (2003) . ISBN: 978-0-89281-749-8

Pharmacopeias & Reviews

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Last updated: 2026-03-02 | Status: review

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Full botanical illustration of Ginkgo biloba L.

Public domain, Addisonia Plate 362 by Mary E. Eaton, via Wikimedia Commons