Ginkgo Biloba

Introduction Overview

Generic Name

Ginkgo Biloba

Brand Name

N/A (commonly available as an herbal supplement without standardized brand names)

Dosage Form

Tablet, Capsule, Extract, Liquid, Powder (herbal supplement forms; standardized extracts are common)

Drug Class

Herbal products

Pharmacokinetics

Absorption:
Ginkgo Biloba extracts contain a variety of pharmacologically active constituents, including flavonoid glycosides and terpenoids. Upon oral administration, the herbal constituents are absorbed variably and incompletely in the gastrointestinal tract. Flavonoids are relatively well absorbed, subject to metabolic modification by intestinal enzymes and gut microbiota. The complex composition leads to interindividual variability in absorption. Peak plasma concentrations of standardized Ginkgo extracts typically occur within 1 to 2 hours after ingestion. Food can delay but generally does not significantly reduce bioavailability.

Distribution:
Once absorbed, flavonoid glycosides and terpenoids circulate predominantly bound to plasma proteins, facilitating widespread distribution to various tissues, including cerebral and peripheral tissues. Limited studies indicate that constituents can cross the blood-brain barrier, which is believed to mediate potential neuroprotective effects. The volume of distribution is not well characterized due to the complex mixture of bioactive compounds. The binding to plasma proteins is moderate but significant, influencing free drug concentrations and pharmacodynamic profile.

Metabolism:
Ginkgo Biloba components are extensively metabolized primarily via phase II conjugation reactions, including glucuronidation, sulfation, and methylation, mostly in the liver and intestinal mucosa. The flavonoid aglycones are formed after hydrolysis of glycosides and then further modified. Gut microbiota also play a role in metabolizing certain constituents, producing various metabolites that may contribute to the overall pharmacological effect. There is limited involvement of cytochrome P450 enzymes, suggesting relatively low risk of metabolic drug interactions. However, some studies observed minor modulation of CYP enzymes by Ginkgo extracts.

Elimination:
The elimination of Ginkgo constituents and their metabolites occurs primarily via renal excretion, with some biliary/fecal elimination. The elimination half-life varies depending on the constituent but generally ranges from 4 to 24 hours. The complex mixture complicates precise kinetic profiling. Repeated dosing may achieve steady state concentrations after several days. No accumulation is typically seen with standard dosing regimens. The clearance is influenced by standard renal and hepatic functions, but detailed pharmacokinetic parameters in special populations remain poorly defined.

Dosage Forms

Available Dosage Forms:
Ginkgo Biloba is available widely as an herbal supplement in various dosage forms. These include:
- Oral tablets (standardized leaf extract) typically containing 40 mg, 60 mg, 80 mg, or 120 mg per tablet
- Oral capsules (standardized extract), common doses are 60 mg and 120 mg
- Oral liquid extracts and tinctures, often standardized equivalent to certain mg of dry extract per mL
- Powders or teas derived from Ginkgo biloba leaves, though less commonly used in standardized form
- Other specialty formulations blended with additional herbal products

Dosages for Adults and Adolescents:
The commonly recommended dose of standardized Ginkgo Biloba extract for adults is 120 mg to 240 mg daily, divided into two or three doses. Doses are typically standardized to contain 24% flavone glycosides and 6% terpenoids. For cognitive impairment or peripheral artery disease, clinical trials often use 120-240 mg daily. There is limited evidence supporting pediatric use, and safety has not been established in children and adolescents; thus, it is generally not recommended under 18 years without medical supervision.

Specific Patient Populations:
Data regarding dosing in elderly patients suggest similar dose ranges, but with close monitoring due to increased risk of bleeding and comorbidities. No formal dosage adjustments have been established for hepatic or renal impairment, but caution is advised given limited pharmacokinetic data in these groups. Pregnant and breastfeeding women are advised to avoid Ginkgo Biloba due to safety concerns. Patients undergoing surgery should discontinue use at least two weeks prior due to increased bleeding risk.

Mechanism Of Action

Ginkgo Biloba exerts its pharmacological effects primarily through its complex mixture of bioactive compounds, mainly flavonoid glycosides and terpenoids such as ginkgolides and bilobalide. These constituents act synergistically to produce antioxidant, anti-inflammatory, and vasoregulatory effects.

At the molecular level, the flavonoid components function as potent free radical scavengers, neutralizing reactive oxygen species and reducing oxidative stress within neuronal and vascular tissues. This antioxidant action is believed to protect cells against lipid peroxidation and DNA damage, potentially slowing neurodegenerative processes and vascular endothelial dysfunction.

Terpenoid lactones, especially ginkgolides, have been shown to antagonize platelet-activating factor (PAF) receptors, thereby inhibiting platelet aggregation and improving microcirculation. This antiplatelet activity underlies the proposed benefit in peripheral vascular disease and reduces the risk of microthrombi. Additionally, bilobalide contributes neuroprotective effects through modulation of neurotransmitter systems and mitochondrial stabilization.

Ginkgo Biloba extract enhances cerebral blood flow by vasodilation, mediated partly by nitric oxide pathways and inhibition of vasoconstrictive mechanisms. It also modulates neurotransmitter systems including cholinergic, glutamatergic, and serotonergic pathways, which may translate into improved cognitive function and mood regulation. Comparative studies indicate that while its mechanisms overlap with cholinesterase inhibitors and vasodilators, Ginkgo offers a multi-targeted approach due to its diverse constituent profile.

Clinical studies support these mechanisms, showing improvements in symptomatology linked to oxidative stress, thrombosis, and cerebral hypoperfusion. However, variability in extract standardization and study designs have produced inconsistent efficacy results, emphasizing the need for further detailed pharmacodynamic research.

Pharmacological Actions

Antioxidant activity through scavenging of free radicals, reducing oxidative cellular damage.
Platelet-activating factor (PAF) receptor antagonist action, resulting in antiplatelet and anti-thrombotic effects.
Vasodilatory effects improving microcirculation and cerebral blood flow.
Neuroprotective actions mediated by mitochondrial stabilization and modulation of neurotransmitter systems.
Anti-inflammatory effects by inhibiting pro-inflammatory mediators and pathways.
Modulation of cholinergic and glutamatergic neurotransmission potentially enhancing cognitive function.
Improvement of blood rheology and reduction of blood viscosity.
Potential anxiolytic and mood-stabilizing effects via serotonergic pathway interactions.
Inhibition of monoamine oxidase activity contributing to neuropsychiatric effects.
Improvement of endothelial function through nitric oxide synthesis enhancement.
Mild diuretic activity reported in some studies.
Regulation of cerebral metabolism and energy utilization.
Possible modulation of neuronal apoptosis pathways supporting neuroprotection.
Inhibition of PAF-mediated inflammatory and immune responses.
Modest antihypertensive effects through vascular smooth muscle relaxation.

Therapeutic Or Clinical Uses

Adjunctive treatment for cognitive impairment and dementia, including Alzheimer's disease and vascular dementia.
Management of intermittent claudication and peripheral arterial disease by improving blood flow.
Relief of symptoms associated with vertigo and tinnitus.
Supportive therapy for anxiety and mood disorders as an alternative or complement.
Potential adjunct in schizophrenia for movement disorders like tardive dyskinesia caused by antipsychotic therapy.
Symptomatic treatment of premenstrual syndrome.
Used in some patients to alleviate symptoms following ischemic stroke.
Off-label use in sexual dysfunction related to antidepressant therapy.
Investigational use for altitude sickness prevention.
Explored in adjunctive treatment for multiple sclerosis symptoms.
Investigated in treatment of macular degeneration, though lacking conclusive evidence.
Used in various conditions like migraine prophylaxis and chronic fatigue syndrome, though efficacy is uncertain.
Sometimes employed for tinnitus caused by noise trauma or vascular insufficiency.
Herbal supplementation intended to improve memory and concentration in healthy individuals.
Used to support peripheral circulation disorders and Raynaud's phenomenon.

Side Or Adverse Effects

Allergic reactions including rash, hives, pruritus, and potentially anaphylaxis.
Gastrointestinal disturbances such as nausea, vomiting, stomach pain, diarrhea, and constipation.
Headache and dizziness reported frequently.
Dry mouth sensation.
Palpitations, arrhythmias or irregular heart rate in rare cases.
Bleeding complications including increased risk of bruising, nosebleeds, bleeding gums, and prolonged bleeding time.
Potential seizures particularly in patients with seizure disorders or predispositions.
Hypersensitivity reactions resembling poison ivy or other plant allergies.
Sleep disturbances including insomnia and restlessness.
Rare neurological adverse events including tremor and paresthesia.
Rare reports of stroke or transient ischemic attacks possibly linked to bleeding risk.
Unusual fatigue or weakness.
Potential exacerbation of bleeding in patients on anticoagulants or antiplatelet agents.
Possible hematologic abnormalities in sensitive individuals.
Mild hypotension or orthostatic dizziness in some adults.

Precautions

Use with caution in patients with bleeding or clotting disorders due to antiplatelet effects.
Discontinue use at least two weeks prior to surgery or invasive procedures to reduce bleeding risk.
Avoid use in patients with epilepsy or seizure disorders due to potential seizure risk.
Monitor carefully when used concurrently with anticoagulants, antiplatelets, or NSAIDs.
Avoid use in individuals with known allergies to Ginkgo or related plants such as poison ivy or sumac.
Careful consideration before use in patients with diabetes mellitus as glucose metabolism may be affected.
Probably unsafe during pregnancy due to bleeding and premature labor risk; avoid use unless absolutely necessary.
Likely unsafe during breastfeeding; consult healthcare provider before use.
Not recommended for children without medical supervision.
Use cautiously in patients with glucose-6-phosphate dehydrogenase deficiency.
Avoid concomitant use with other herbal supplements that affect coagulation or seizure threshold.
Store supplements in proper conditions to avoid degradation and contamination.
Consult healthcare provider before starting if taking any prescription medications due to potential interactions.
Regularly review use in elderly patients who may be more susceptible to bleeding and side effects.
Educate patients about signs of unusual bleeding and allergic reactions.

Warnings

Not approved by the FDA for treatment of any medical conditions; use is as a dietary supplement.
Risk of serious bleeding events, including intracranial hemorrhage and gastrointestinal bleeding.
Risk of seizures especially in predisposed individuals.
Avoid use with blood-thinning medications without medical supervision.
Potential contamination of herbal supplements with toxic metals or adulterants from unregulated sources.
May interact with multiple medications leading to clinically significant interactions.
Use in pregnancy and breastfeeding is contraindicated due to insufficient safety data and potential risks.
Discontinue use and seek medical attention if signs of allergic reactions or severe skin reactions occur.
Not to be used as substitute for prescribed medications without consulting a healthcare provider.
Risk of overdose if using multiple forms or supplements simultaneously.
Potential for variable potency and composition between different Ginkgo products.
Avoid use if history of bleeding disorders or recent hemorrhagic stroke.
Careful monitoring necessary if used in elderly or patients with comorbidities.
Avoid in patients undergoing elective surgery unless discontinued timely.
Inconsistent evidence on efficacy necessitates cautious interpretation of therapeutic claims.

Contraindication

Known hypersensitivity or allergy to Ginkgo Biloba or related plants (e.g., poison ivy, poison oak, sumac).
Active bleeding disorders or coagulopathy.
Concurrent use with anticoagulants (e.g., warfarin, Coumadin) unless closely monitored.
History of seizures or epilepsy without medical supervision.
Pregnancy and breastfeeding due to likely unsafe profile.
Use of NSAIDs and other drugs that increase bleeding risk without healthcare provider advice.
Use in children without medical supervision due to safety concerns.
Use with other herbal supplements that affect coagulation or nervous system excitability without caution.
Patients scheduled for surgery unless stopped at least two weeks prior.
Severe hepatic or renal impairment where pharmacokinetics might be altered significantly.
Patients with glucose-6-phosphate dehydrogenase deficiency without monitoring.
Individuals with unstable cardiovascular conditions without physician guidance.
Use in patients with active or recent hemorrhagic stroke.
Use concurrently with HIV medications or chemotherapy without consulting provider due to unknown interactions.
Use in patients with psychiatric disorders treated with antipsychotics without supervision.

Drug Interactions

Increased bleeding risk when combined with anticoagulants such as warfarin, heparin, and direct oral anticoagulants.
Enhanced bleeding risk with antiplatelet drugs including aspirin, clopidogrel, and NSAIDs like ibuprofen and naproxen.
Possible interactions with anticonvulsants, altering seizure threshold and efficacy.
Potential interactions with insulin and oral hypoglycemics requiring glucose monitoring.
Interactions with antidepressants and antipsychotics potentially affecting drug levels and side effects.
Modulation of cytochrome P450 enzymes is minimal but may alter metabolism of some drugs.
Avoid combining with other herbal supplements that affect coagulation (e.g., garlic, ginseng, saw palmetto, turmeric).
Concomitant use with drugs affecting the central nervous system may potentiate effects or side effects.
Use with HIV, malaria, tuberculosis, or hepatitis C medications requires medical advice due to unknown interactions.
Possible interactions with medications for asthma, allergies, cancer, and autoimmune diseases.
Potential to decrease effectiveness or increase side effects of heartburn or GERD medications.
May interfere with erectile dysfunction medications, impacting efficacy or safety.
Interactions with migraine treatments and immune modulating drugs have been reported.
Combination with NSAIDs may increase the risk of gastrointestinal bleeding or ulceration.
Polypharmacy increases risk for complex interactions; comprehensive medication review advised.

Preparations Of The Drug

Standardized Ginkgo Biloba leaf extract, commonly standardized to 24% flavone glycosides and 6% terpene lactones.
Oral tablets containing 40 mg, 60 mg, 80 mg, or 120 mg of standardized extract.
Capsules available in doses from 60 mg to 120 mg standardized extract.
Liquid extracts and tinctures standardized for flavonoid and terpenoid content.
Powdered leaf preparations used for herbal teas or encapsulated dose forms.
Blended formulations combining Ginkgo with other herbal constituents targeting cognitive or vascular health.
Multi-ingredient dietary supplements including Ginkgo Biloba marketed for memory and circulatory support.
Non-standardized raw leaf or seed products (generally discouraged and considered unsafe).
Roasted and processed seeds available in some traditional medicine preparations (note: raw seeds are toxic).
Ginkgo extracts supplied by various dietary supplement manufacturers with variable purity and potency.
Some preparations may include additional antioxidants or vitamins to enhance efficacy.
Sustained-release tablet and capsule forms available in certain markets.
Standardized extracts produced using water, alcohol, or acetone extraction methods to optimize bioactive content.
Preparations intended for oral administration only; no approved parenteral forms.
Use of purified fractions (e.g., isolated ginkgolides) remains investigational.