Ginkgo biloba drug interactions

Ginkgo

Generic Name: ginkgo (GINK goe)
Brand Name: Ginkgo Biloba, Gingko Biloba

Medically reviewed by Drugs.com on Mar 4, 2019 – Written by Cerner Multum

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What is ginkgo?

Ginkgo is an herb also known as Ginkgo biloba, Abricot Argenté Japonais, Adiantifolia, Arbre aux Écus, Arbre du Ciel, Arbre Fossile, Bai Guo Ye, Baiguo, Extrait de Ginkgo, Fossil Tree, Graine de Ginkgo, Herba Ginkgo Biloba, Japanese Silver Apricot, Kew Tree, Maidenhair Tree, Noyer du Japon, Pei Go Su Ye, Salisburia Adiantifolia, Yen Xing, Yinhsing, and other names.

Ginkgo has been used in alternative medicine as a possibly effective aid in improving mental function or treating anxiety, dementia, leg pain caused by blood circulation problems, premenstrual symptoms, vision problems caused by glaucoma or diabetes, vertigo (dizziness), or a movement disorder (tardive dyskinesia) caused by taking certain antipsychotic drugs.

Ginkgo has also been used to treat seasonal affective disorder, age-related memory loss, asthma, tinnitus (ringing in the ears), high blood pressure, multiple sclerosis, cocaine addiction, or sexual problems caused by taking antidepressants. However, research has shown that ginkgo may not be effective in treating these conditions.

Research has shown that ginkgo is not likely to be effective in treating heart disease.

Other uses not proven with research have included altitude sickness, macular degeneration (age-related vision loss), attention deficit disorder, dyslexia, vitiligo (discolored skin), migraines, bronchitis, digestion problems, urination problems, skin sores, high cholesterol, Raynaud’s syndrome, fibromyalgia, chronic fatigue syndrome, blood clots, stroke, and cancer.

It is not certain whether ginkgo is effective in treating any medical condition. Medicinal use of this product has not been approved by the FDA. Ginkgo should not be used in place of medication prescribed for you by your doctor.

Ginkgo is often sold as an herbal supplement. There are no regulated manufacturing standards in place for many herbal compounds and some marketed supplements have been found to be contaminated with toxic metals or other drugs. Herbal/health supplements should be purchased from a reliable source to minimize the risk of contamination.

Ginkgo may also be used for purposes not listed in this product guide.

Important Information

Follow all directions on the product label and package. Tell each of your healthcare providers about all your medical conditions, allergies, and all medicines you use.

Before taking this medicine

You should not use ginkgo if you also take efavirenz (Sustiva, Atripla).

Ask a doctor, pharmacist, or other healthcare provider if it is safe for you to use this product if you have:

  • diabetes;

  • seizures or epilepsy;

  • a bleeding or blood clotting disorder;

  • an allergy to plants such as poison ivy, poison oak, or poison sumac;

  • any food allergies; or

  • if you are planning a pregnancy (ginkgo may affect your ability to get pregnant).

Ginkgo is considered possibly unsafe to take during pregnancy. This product could cause premature labor, or cause you to bleed heavily during childbirth. Do not use this product if you are pregnant.

Ginkgo may pass into breast milk and may harm a nursing baby. Do not use this product if you are breast-feeding a baby.

Do not give any herbal/health supplement to a child without medical advice.

How should I take ginkgo?

When considering the use of herbal supplements, seek the advice of your doctor. You may also consider consulting a practitioner who is trained in the use of herbal/health supplements.

If you choose to use ginkgo, use it as directed on the package or as directed by your doctor, pharmacist, or other healthcare provider. Do not use more of this product than is recommended on the label.

Ginkgo leaf extract is thought to be likely safe when taken in recommended doses. Ginkgo seeds are possibly unsafe when taken by mouth after roasting them.

Fresh ginkgo seeds in raw form are poisonous and are considered likely unsafe to eat.

Do not use different forms (leaf extract, roasted seeds, tablets, tincture, teas, etc) of ginkgo at the same time without medical advice. Using different formulations together increases the risk of an overdose.

Call your doctor if the condition you are treating with ginkgo does not improve, or if it gets worse while using this product.

Ginkgo can affect blood-clotting and may increase your risk of bleeding. If you need surgery, dental work, or a medical procedure, stop taking ginkgo at least 2 weeks ahead of time.

Store at room temperature away from moisture, heat, and light.

What happens if I miss a dose?

Skip the missed dose if it is almost time for your next scheduled dose. Do not use extra ginkgo to make up the missed dose.

What happens if I overdose?

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

What should I avoid while taking ginkgo?

Avoid using ginkgo together with other herbal/health supplements that can also affect blood-clotting. This includes angelica (dong quai), capsicum, clove, danshen, garlic, ginger, ginkgo, horse chestnut, panax ginseng, poplar, red clover, turmeric, and willow.

Avoid using ginkgo together with other herbal/health supplements that can increase your risk of seizures. This includes EDTA, folic acid, GBL (gamma butyrolactone), GHB (gamma hydroxybutyrate), glutamine, hyssop oil, juniper, L-carnitine (levocarnitine), melatonin, rosemary, sage, wormwood, and others.

Ginkgo side effects

Get emergency medical help if you have signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat.

Stop using ginkgo and call your healthcare provider at once if you have:

  • easy bruising, unusual bleeding (nose, mouth, vagina, or rectum);

  • any bleeding that will not stop;

  • a seizure (convulsions); or

  • weak pulse, weak or shallow breathing, feeling like you might pass out.

Touching or handling ginkgo fruit pulp can cause a severe skin reaction including redness, swelling, blistering, and itching for up to 10 days.

In animal studies, ginkgo leaf extract increased the risk of thyroid cancer and liver cancer. However, very high doses are used in animal studies. It is not known whether these effects would occur in people using doses recommended for human use.

Common side effects may include:

  • upset stomach, constipation;

  • headache, dizziness;

  • fast or pounding heartbeats;

  • mouth irritation; or

  • skin rash.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

What other drugs will affect ginkgo?

Do not take ginkgo without medical advice if you are using a medication to treat any of the following conditions:

  • any type of infection (including HIV, malaria, or tuberculosis);

  • anxiety or depression;

  • asthma or allergies;

  • cancer;

  • erectile dysfunction;

  • heartburn or gastroesophageal reflux disease (GERD);

  • high blood pressure, high cholesterol, or a heart condition;

  • migraine headaches;

  • psoriasis, rheumatoid arthritis, or other autoimmune disorders;

  • a psychiatric disorder; or

  • seizures.

Do not take ginkgo without medical advice if you are using any of the following medications:

This list is not complete. Other drugs may interact with ginkgo, including prescription and over-the-counter medicines, vitamins, and herbal products. Not all possible interactions are listed in this product guide.

Further information

  • Consult with a licensed healthcare professional before using any herbal/health supplement. Whether you are treated by a medical doctor or a practitioner trained in the use of natural medicines/supplements, make sure all your healthcare providers know about all of your medical conditions and treatments.

Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use this medication only for the indication prescribed.

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

Copyright 1996-2018 Cerner Multum, Inc. Version: 5.01.

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Overview

Ginkgo biloba

Also listed as:

Table of Contents > Herbs > Ginkgo biloba

Overview Plant Description What is it Made of? Medicinal Uses and Indications Available Forms How to Take it Precautions Possible Interactions Supporting Research

Ginkgo (Ginkgo biloba) is one of the oldest living tree species. It is also one of the best-selling herbal supplements in the United States and Europe.

Ginkgo has a long history of use in treating blood disorders and memory issues. It is best known today as way to potentially keep your memory sharp. Laboratory studies have shown that ginkgo improves blood circulation by opening up blood vessels and making blood less sticky. It is also an antioxidant.

For those reasons, ginkgo may improve vein and eye health. Although not all studies agree, ginkgo may help treat dementia (including Alzheimer disease) and intermittent claudication, or poor circulation in the legs. It may also protect memory in older adults.

Ginkgo leaves contain flavonoids and terpenoids, which are both antioxidants. In your body, harmful particles called free radicals build up as you age, and may contribute to heart disease, cancer, and Alzheimer disease. Antioxidants like those found in ginkgo fight off free radicals, and stop them from damaging DNA and other cells.

Plant Description

Ginkgo biloba is the oldest living tree species. A single tree can live as long as 1,000 years and grow to a height of 120 feet. It has short branches with fan-shaped leaves and inedible fruits that smell bad. The fruit has an inner seed, which may be poisonous. Ginkgos are tough, hardy trees and are sometimes planted along urban streets in the United States. The leaves turn brilliant colors in the fall.

Although Chinese herbal medicine has used both the ginkgo leaf and seed for thousands of years, modern research has focused on the standardized Ginkgo biloba extract (GBE) made from the dried green leaves. This standardized extract is highly concentrated and seems to treat health problems (particularly circulatory problems) better than the non-standardized leaf alone.

What is it Made of?

Scientists have found more than 40 components in ginkgo. Only two are believed to act as medicine: flavonoids and terpenoids. Flavonoids are plant-based antioxidants. Laboratory and animal studies show that flavonoids protect the nerves, heart muscle, blood vessels, and retina from damage. Terpenoids (such as ginkgolides) improve blood flow by dilating blood vessels and reducing the stickiness of platelets.

Medicinal Uses and Indications

Based on studies conducted in laboratories, animals, and people, ginkgo is used for the following:

Dementia and Alzheimer disease

Ginkgo is widely used in Europe for treating dementia. At first, doctors thought it helped because it improves blood flow to the brain. Now research suggests it may protect nerve cells that are damaged in Alzheimer disease. Several studies show that ginkgo has a positive effect on memory and thinking in people with Alzheimer disease or vascular dementia.

Studies suggest that ginkgo may help people with Alzheimer disease:

  • Improve thinking, learning, and memory (cognitive function)
  • Have an easier time performing daily activities
  • Improve social behavior
  • Have fewer feelings of depression

Several studies have found that ginkgo may work as well as some prescription Alzheimer disease medications to delay the symptoms of dementia. It has not been tested against all of the drugs prescribed to treat Alzheimer disease.

In 2008, a well-designed study with more than 3,000 elderly people found that ginkgo was no better than placebo in preventing dementia or Alzheimer disease.

Intermittent claudication

Because ginkgo improves blood flow, it has been studied in people with intermittent claudication, or pain caused by reduced blood flow to the legs. People with intermittent claudication have a hard time walking without feeling extreme pain. An analysis of 8 studies showed that people taking ginkgo tended to walk about 34 meters farther than those taking placebo. In fact, ginkgo has been shown to work as well as a prescription medication in improving pain-free walking distance. However, regular walking exercises work better than ginkgo in improving walking distance.

Anxiety

One preliminary study found that a special formulation of ginkgo extract called EGB 761 might help relieve anxiety. People with generalized anxiety disorder and adjustment disorder who took this specific extract had fewer anxiety symptoms than those who took placebo.

Glaucoma

One small study found that people with glaucoma who took 120 mg of ginkgo daily for 8 weeks had improvements in their vision.

Memory and thinking

Ginkgo is widely touted as a “brain herb.” Some studies show that it does help improve memory in people with dementia. It is not as clear whether ginkgo helps memory in healthy people who have normal, age-related memory loss. Some studies have found slight benefits, while other studies have found no effect. Some studies have found that ginkgo helps improve memory and thinking in young and middle-aged people who are healthy. And preliminary studies suggest it may be useful in the treatment of Attention Deficit Hyperactivity Disorder (ADHD). The dose that works best seems to be 240 mg per day. Ginkgo is often added to nutrition bars, soft drinks, and fruit smoothies to boost memory and enhance mental performance, although such small amounts probably do not help.

Macular degeneration

The flavonoids found in ginkgo may help stop or reduce some problems with the retina, the back part of the eye. Macular degeneration, often called age-related macular degeneration or AMD, is an eye disease that affects the retina. The number one cause of blindness in the Unites States, AMD is a degenerative eye disease that gets worse as time goes on. Some studies suggest that ginkgo may help preserve vision in those with AMD.

Premenstrual syndrome (PMS)

Two studies with a somewhat complicated dosing schedule found that ginkgo helped reduce PMS symptoms. Women in the studies took a special extract of ginkgo beginning on day 16 of their menstrual cycle and stopped taking it after day 5 of their next cycle, then took it again on day 16.

Raynaud’s phenomenon

One well-designed study found that people with Raynaud’s phenomenon who took ginkgo over a 10-week period had fewer symptoms than those who took placebo. More studies are needed.

Available Forms

  • Standardized extracts containing 24 to 32% flavonoids (also known as flavone glycosides or heterosides) and 6 to 12% terpenoids (triterpene lactones)
  • Capsules
  • Tablets
  • Liquid extracts (tinctures, fluid extracts, and glycerites)
  • Dried leaf for teas

How to Take it

Pediatric

Ginkgo should not be given to children.

Adult

Memory problems and Alzheimer disease: Many studies have used 120 to 240 mg daily in divided doses, standardized to contain 24 to 32% flavone glycosides (flavonoids or heterosides) and 6 to 12% triterpene lactones (terpenoids).

Intermittent claudication: Studies have used 120 to 240 mg per day.

It can take 4 to 6 weeks to see any effects from ginkgo. Ask your doctor to help you find the right dose.

Precautions

The use of herbs is a time-honored approach to strengthening the body and treating disease. However, herbs can trigger side effects and interact with other herbs, supplements, or medications. For these reasons, herbs should be taken with care, under the supervision of a health care provider qualified in the field of botanical medicine.

Ginkgo usually has few side effects. In a few cases, people have reported stomach upset, headaches, skin reactions, and dizziness.

There have been reports of internal bleeding in people who take ginkgo. It is not clear whether the bleeding was due to ginkgo or some other reason, such as a combination of ginkgo and blood-thinning drugs. Ask your doctor before taking ginkgo if you also take blood-thinning drugs.

Stop taking ginkgo 1 to 2 weeks before surgery or dental procedures due to the risk of bleeding. Always alert your doctor or dentist that you take ginkgo.

People who have epilepsy should not take ginkgo, because it might cause seizures.

Pregnant and breastfeeding women should not take ginkgo.

People who have diabetes should ask their doctor before taking ginkgo.

DO NOT eat Ginkgo biloba fruit or seed.

Possible Interactions

Ginkgo may interact with prescription and non-prescription medications. If you are taking any of the following medications, you should not use ginkgo without talking to your doctor first.

Medications broken down by the liver: Ginkgo can interact with medications that are processed through the liver. Because many medications are broken down by the liver, if you take any prescription medications ask your doctor before taking ginkgo.

Seizure medications (anticonvulsants): High doses of ginkgo could interfere with the effectiveness of anti-seizure drugs. These drugs include carbamazepine (Tegretol) and valproic acid (Depakote).

Antidepressants: Taking ginkgo along with a kind of antidepressant called selective serotonin reuptake inhibitors (SSRIs) may increase the risk of serotonin syndrome, a life-threatening condition. Also, ginkgo may strengthen both the good and bad effects of antidepressants known as MAOIs, such as phenelzine (Nardil). SSRIs include:

  • Citalopram (Celexa)
  • Escitalopram (Lexapro)
  • Fluoxetine (Prozac)
  • Fluvoxamine (Luvox)
  • Paroxetine (Paxil)
  • Sertraline (Zoloft)

Medications for high blood pressure: Ginkgo may lower blood pressure, so taking it with blood pressure medications may cause blood pressure to drop too low. There has been a report of an interaction between ginkgo and nifedipine (Procardia), a calcium channel blocker used for blood pressure and heart rhythm problems.

Blood-thinning medications: Ginkgo may raise the risk of bleeding, especially if you take blood-thinners, such as warfarin (Coumadin), clopidogrel (Plavix), and aspirin.

Alprazolam (Xanax): Ginkgo may make Xanax less effective, and interfere with the effectiveness of other drugs taken to treat anxiety.

Ibuprofen (Advil, Motrin): Like ginkgo, the nonsteroidal anti-inflammatory drug (NSAID) ibuprofen also raises the risk of bleeding. Bleeding in the brain has been reported when using a ginkgo product and ibuprofen.

Medications to lower blood sugar: Ginkgo may raise or lower insulin levels and blood sugar levels. If you have diabetes, you should not use ginkgo without first talking to your doctor.

Cylosporine:Ginkgo biloba may help protect the cells of the body during treatment with the drug cyclosporine, which suppresses the immune system.

Thiazide diuretics (water pills): There is one report of a person who took a thiazide diuretic and ginkgo developing high blood pressure. If you take thiazide diuretics, ask your doctor before taking ginkgo.

Trazodone: There is one report of an elderly person with Alzheimer disease going into a coma after taking ginkgo and trazodone (Desyrel), an antidepressant medication.

Supporting Research

Aruna D, Naidu MU.Pharmacodynamic interaction studies of Ginkgo biloba with cilostazol and clopidogrel in healthy human subjects. Br J Clin Pharmacol. 2006 Sep 29; .

Birks J, Grimley Evans J. Ginkgo biloba for cognitive impairment and dementia. Cochrane Database Syst Rev. 2009 Jan 21;(1):CD003120. Review.

Cheuvront, S. N. and Carter, R., III. Ginkgo and memory. JAMA. 2-5-2003;289(5):547-548.

Choi WS, Choi CJ, Kim KS, Lee JH, Song CH, Chung JH, et al. To compare the efficacy and safety of nifedipine sustained release with Ginkgo biloba extract to treat patients with primary Raynaud’s phenomenon in South Korea; Korean Raynaud study (KOARA study). Clin Rheumatol. 2009 Jan 22.

Hilton, M. and Stuart, E. Ginkgo biloba for tinnitus. Cochrane Database Syst Rev. 2004;(2):CD003852.

Ihl R. Effects of Ginkgo biloba extract EGb 761 in dementia with neuropsychiatric features: review of recently completed randomised, controlled trials. Int J Psychiatry Clin Pract. 2013; 17 Suppl 1:8-14.

Ihl R, Tribanek M, Bachinskaya N; GOTADAY Study Group. Efficacy and tolerability of a once daily formulation of Ginkgo biloba extract EGb761 in Alzheimer’s disease and vascular dementia: results from a randomised controlled trial. Pharmacopsychiatry. 2012;45:41-6.

Kenney C, Norman M, Jacobson M, and et al. A double-blind, placebo-controlled, modified crossover pilot study of the effects of Ginkgo biloba on cognitive and functional abilities in multiple sclerosis. American Academy of Neurology 54th Annual Meeting. April 13-20 2002;P06.081.

Le Bars PL, Kieser M, Itil KZ. A 26-week analysis of a double-blind, placebo-controlled trial of the Ginkgo biloba extract EGb761 in dementia. Dement Geriatr Cogn Disord. 2000;11:230-237.

Mantle D, Pickering AT, Perry AK. Medicinal plant extracts for the treatment of dementia: a review of their pharmacology, efficacy and tolerability. CNS Drugs. 2000;13:201-213.

May BH, Yang AW, Zhang AL, Owens MD, Bennett L, Head R, et al. Chinese herbal medicine for Mild Cognitive Impairment and Age Associated Memory Impairment: a review of randomised controlled trials. Biogerontology. 2009 Apr;10(2):109-23. Epub 2008 Aug 21.

Mazza M, Capuano A, Bria P, Mazza S. Ginkgo biloba and donepezil: a comparison in the treatment of Alzheimer’s dementia in a randomized placebo-controlled double-blind study. Eur J Neurol. 2006;13(9):981-5.

Nathan, P. J., Harrison, B. J., and Bartholomeusz, C. Ginkgo and memory. JAMA. 2-5-2003;289(5):546-548.

Oh SM, Chung KH. Antiestrogenic activities of Ginkgo biloba extracts. J Steroid Biochem Mol Biol. 2006;100(4-5):167-76.

Oskouei DS, Rikhtegar R, Hashemilar M, et al. The effect of Ginkgo biloba on functional outcome of patients with acute ischemic stroke: a double-blind, placebo-controlled, randomized clinical trial. J Stroke Cerebrovasc Dis. 2013;22(8):e557-63.

Ozgoli G, Selselei EA, Mojab F, et al. A randomized, placebo-controlled trial of Ginkgo biloba L. in treatment of premenstrual syndrome. J Altern Complement Med. 2009;15:845-51.

Pittler MH, Ernst E. Ginkgo biloba extract for the treatment of intermittent claudication: a meta-analysis of randomized trials. Am J Med. 2000;108(4):276-281.

Salehi B, Imani R, Mohammadi MR, et al. Ginkgo biloba for attention-deficit/hyperactivity disorder in children and adolescents: a double blind, randomized controlled trial. Prog Neuropsychopharmacol Biol Psychiatry. 2010;34:76-80.

Snitz BE, et al; Ginkgo Evaluation of Memory (GEM) Study Investigators. Ginkgo biloba for preventing cognitive decline in older adults: a randomized trial. JAMA. 2009 Dec 23;302(24):2663-70.

Szczurko O, Shear N, Taddio A, Boon H. Ginkgo biloba for the treatment of vitiligo vulgaris: an open label pilot clinical trial. BMC Complement Altern Med. 2011;11:21.

Tamborini A, Taurelle R. Value of standardized Ginkgo biloba extract (EGb 761) in the management of congestive symptoms of premenstrual syndrome . Rev Fr Gynecol Obstet. 1993;88:447-457.

Uebel-von Sandersleben H, Rothenberger A, Albrecht B, Rothenberger LG, Klement S, Bock N. Ginkgo biloba extract EGb 761 in children with ADHD. Z Kinder Jugendpsychiatr Psychother. 2014;42(5):337-47.

Vellas, B., and Grandjean, H. Association of Alzheimer’s disease onset with ginkgo biloba and other symptomatic cognitive treatments in a population of women aged 75 years and older from the EPIDOS study. J Gerontol A Biol.Sci.Med Sci. 2003;58(4):372-377.

Wang BS, Wang H, Song YY, Qi H, Rong ZX, Wang BS, Zhang L, Chen HZ. Effectiveness of standardized ginkgo biloba extract on cognitive symptoms of dementia with a six-month treatment: a bivariate random effect meta-analysis. Pharmacopsychiatry. 2010 May;43(3):86-91.

Weinmann S, Roll S, Schwarzbach C, Vauth C, Willich SN. Effects of Ginkgo biloba in dementia: systematic review and meta-analysis. BMC Geriatr. 2010;10:14.

Woelk H, Arnoldt KH, 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. J Psychiatr Res. 2007;41:472-80.

Review Date: 6/22/2015
Reviewed By: Steven D. Ehrlich, NMD, Solutions Acupuncture, a private practice specializing in complementary and alternative medicine, Phoenix, AZ. Review provided by VeriMed Healthcare Network.

The information provided herein should not be used during any medical emergency or for the diagnosis or treatment of any medical condition. A licensed medical professional should be consulted for diagnosis and treatment of any and all medical conditions. Links to other sites are provided for information only — they do not constitute endorsements of those other sites. © 1997- A.D.A.M., a business unit of Ebix, Inc. Any duplication or distribution of the information contained herein is strictly prohibited.

Complementary and Alternative Medicine

Ginkgo may alter the metabolism and effectiveness of some prescription and non-prescription medications. If you are being treated with any of the following medications, you should not use ginkgo without first talking to your health care provider:

Anticonvulsant medications — High doses of ginkgo could decrease the effectiveness of anticonvulsant therapy, such as carbamazepine (Tegretol) or valproic acid (Depakote), in controlling seizures.

Antidepressant medications — Taking ginkgo along with selective serotonin reuptake inhibitor (SSRIs) antidepressants — including fluoxetin (Prozac), sertraline (Zoloft), paroxetine (Paxil), and escitalopram (Lexapro) — may cause serotonin syndrome. This condition is characterized by rigidity, tachycardia (fast heart rate), hyperthermia (high body temperature), restlessness, and diaphoresis (sweating). Ginkgo may enhance the effects (both good and bad) of antidepressant medications known as MAOIs, such as phenelzine (Nardil).

Antihypertensive medications — Ginkgo may decrease blood pressure, so use of ginkgo along with prescription antihypertensive medications should be monitored by a health care provider. There has been a report of an interaction between ginkgo and nifedipine (Procardia), a calcium channel blocking drug used for blood pressure and arrhythmias.

Blood-thinning medications — Ginkgo has blood-thinning properties and therefore should not be used if you are taking anticoagulant (blood-thinning) medications, such as aspirin, clopidogrel (Plavix), dipyridamole (Persantine), heparin, ticlopidine (Ticlid), or warfarin (Coumadin). There has been bleeding in the brain reported when using a ginkgo product and ibuprofen (Advil), a non-steroidal antiinflammatory drug (NSAID).

Blood sugar lowering medications — Ginkgo was reported to increase insulin levels in healthy subjects and to decrease insulin levels in diabetic patients. Use ginkgo supplements under the supervision of a health care provider if you are diabetic and taking insulin or oral blood sugar lowering drugs.

Cylosporine — Ginkgo biloba may help protect the cells of the body during treatment with the immunosuppressive (decreases immunity) drug cyclosporine.

Thiazide diuretics — Although there has been one literature report of increased blood pressure associated with the use of ginkgo during treatment with thiazide diuretics, this interaction has not been verified by clinical trials. Nevertheless, you should consult with your health care provider before using ginkgo if you are taking thiazide diuretics.

Trazodone — There has been a report of an adverse interaction between ginkgo and trazodone (Desyrel), an antidepressant medication that resulted in an elderly patient going into a coma.

Interactions

Ginkgo Biloba and Memory

Memory Disorders:

Complaints of declining memory are common with advancing age. Memory disorders are associated with difficulty in learning and retaining new information. Dementia is defined as an insidious decline in a number of mental functions resulting in the loss of personal and social independence in a previously competent individual. Even though the most common component of dementia is memory loss, isolated defects in memory or in language do not qualify as dementia, which is usually associated with defective reasoning, decision making and judgment.

Dementia occurs when several of the cerebral systems that support learning, memory, language, emotion and reason are dysfunctional. Dementia can be self-limited (e.g., damage from head trauma or cardiac arrest) or progressive (e.g., dementia associated with Alzheimer’s Disease).

Epidemiological studies indicate that approximately 15% of patients greater than 65 years old suffer from some form of dementia, while the incidence increases to 23% in patients 75 to 84 years old and 48% in patients greater than 85 years old. Objective assessment of memory loss and cognitive impairment is done by using neuropsychological testing (See Table 1).

Interventions to Improve Memory:

For Alzheimer’s Disease associated memory loss cholinesterase inhibitors, such as tacrine (Cognex®), donepezil (Aricept®), rivastigmine (Exelon®) and galantamine (Reminyl®), have been beneficial. Vitamin E, estrogen, non-steroidal anti-inflammatory drugs (NSAIDs) and Ginkgo biloba are also used to slow down the progression of memory loss in these patients. Supportive measures, such as orientation reinforcement to areas where memory loss is observed, and treatment of associated depression, anxiety, sleep disorders or other related conditions is also recommended.

This article will describe the chemical composition, active ingredients, pharmacological properties, adverse reactions, drug interactions, and dosing of Ginkgo biloba leaf extract. Additionally, this article will review some of the trials evaluating the use of Ginkgo biloba specifically for memory impairment or improvement.

Ginkgo Biloba
Background: Ginkgo biloba is obtained from the Ginkgo biloba Linne tree. Threatened with extinction during the ice age, the ginkgo tree survived in China, and it is believed to be the oldest living tree species. The ginkgo tree has been introduced in Europe and North America as an ornamental tree, and it can be found along city streets and in parks. Ginkgo biloba is one of the most widely used and studied herbal products, and in Germany and China, it is the most commonly prescribed herbal medication. Because of the Dietary Supplement Health and Education Act of 1994, the United States Food and Drug Administration (FDA) does not regulate dietary supplements, including herbs, for safety or efficacy. Therefore, unlike prescription and non-prescription drugs approved by the FDA, there is no guarantee of strength, purity or safety of dietary supplements that contain Ginkgo biloba.

Chemical Composition: Ginkgo biloba leaf extract contains flavonol and flavone glycosides, lactone derivatives (ginkgolides), bilobalide, ascorbic acid, catechin, iron-based superoxide, 6-hydroxykinuretic acid, protocatechuic acid, shikimic acid, sterols and vanilic acid. The major classes of active ingredients are the ginkgolides and bilobalides (also known as terpenes) and the flavonoids. The ginkgo seeds contain a potentially toxic substance, ginkgotoxin (4-O-methoxypyridoxine), which has anti-vitamin B6 activity and inhibits GABA formation, which can potentially lead to convulsions and loss of consciousness. The ginkgo tree roots have a greater concentration of the active ingredients. Commercial manufacturers use the Ginkgo biloba leaves to extract the active ingredients. The standardization of Ginkgo biloba leaf extract products is done by the active ingredients: flavones, ginkgolides and bilobalides.

Pharmacology: Even though the chemical components of the ginkgo leaf have distinctive intrinsic pharmacological properties, they work synergistically to produce more potent pharmacological effects (See Table 2). For example, the ginkgo leaf extract protects the neurons from oxidative damage potentially preventing the progression of tissue degeneration in patients with dementia. Additionally, Ginkgo biloba leaf extract improves blood flow throughout the body, and it restores the balance between prostacyclin and thromboxane A2 resulting in improved vasoregulation. Vascular contraction and improvement in the venous tone are thought to be the result of phosphodiesterase inhibition and release of catecholamines. The beneficial effects of Ginkgo biloba leaf extract in Alzheimer’s Disease might also be due to the inhibition of toxicity and cell death induced by beta-amyloid peptides. It has been proposed that Ginkgo biloba leaf extract 1) inhibits monoamine oxidase A and B, 2) inhibits catechol-O-methyl transferase (an enzyme that breaks down adrenergic transmitters), and 3) increases the number of alpha-adrenoreceptors in the brain as there is a decline in alpha-adrenoreceptors with age.

Other proposed mechanisms of action for the Ginkgo biloba leaf extract include possible effects on the benzodiazepine receptors, a possible decrease in glucocorticoid biosynthesis, and a possible increase in pancreatic beta-cell function in response to glucose loading. The pharmacological properties of the Ginkgo biloba seeds are the result of cyanogenic glycosides and ginkgotoxins. The cyanogenic glycosides have antibacterial and antifungal effects, while the ginkgotoxins can cause seizures, loss of consciousness and even death.

Reported Uses: Since ancient times, Ginkgo biloba has been used for medicinal purposes. In the oldest Chinese Materia Medica (2800 B.C.), Ginkgo biloba was recommended for asthma, swelling of the hands and feet, coughs, vascular disorders, aging and for the brain. Since 1965, Gingko biloba has been used in Europe for the treatment of cerebral insufficiency and peripheral vascular disease. See Table 3 for the reported uses of Ginkgo biloba.

Clinical Efficacy: Ginkgo biloba has been clinically studied for the following conditions: peripheral vascular disease, claudication, dementia, cerebral insufficiency, ischemic stroke, tinnitus, memory impairment, asthma, and vertigo.

Ginkgo biloba leaf extract is possibly effective when used for Alzheimer’s vascular or mixed dementia. Studies report that Ginkgo biloba leaf extract can stabilize or improve several measures of cognitive function and social functioning. Outcome studies have not yet verified Ginkgo’s effect on disease progression, and it has not been directly compared to conventional dementia treatment. Clinical improvements in patients treated with Ginkgo biloba leaf extract appear to be similar to clinical improvement in patients treated with donepezil and tacrine. German practitioners consider Ginkgo biloba leaf extract to be the treatment of choice for dementia and for age-related memory dysfunction.

The role of Ginkgo biloba leaf extract in memory impairment will be discussed later in the article.

Ginkgo biloba leaf extract increases pain-free walking in patients with intermittent claudication and in patients with Fontaine’s IIb peripheral arterial occlusive disease. Ginkgo biloba leaf extract was also found to be more effective than placebo when used for vertigo and equilibrium disorders. Some evidence suggests that Ginkgo biloba leaf extract can help breast tenderness and neuropsychological symptoms associated with pre-menstrual syndrome. Limited evidence suggests that treatment with Ginkgo biloba leaf extract can improve color vision in patients with diabetic retinopathy. Finally, clinical studies suggest that Ginkgo biloba leaf extract is possibly ineffective when used for tinnitus and prevention of winter depression in patients with seasonal affective disorder.

Adverse Effects: Orally at typical doses Ginkgo biloba leaf extract can cause mild gastrointestinal upset, headache, dizziness, palpitations, constipation and allergic skin reactions. Larger doses can cause restlessness, diarrhea, nausea, vomiting, and weakness. Other adverse effects are listed in Table 4 Spontaneous bleeding is a serious, potential adverse effect.

Contraindications: Ginkgo biloba is contraindicated in patients with a history of hypersensitivity to Ginkgo preparations. Due to insufficient information, the use of Ginkgo biloba leaf extract in pregnancy and lactation is not recommended. Even though there are not enough data to support that a Ginkgo biloba leaf product was the main cause of seizures in several anecdotal reports, it is recommended to avoid these products in patients with a history of seizures. Ginkgo biloba leaf products should be discontinued at least two weeks prior to elective surgery procedures due to the potential for an increased risk of bleeding.

Drug Interactions: In vitro evidence suggests that Ginkgo biloba leaf extract can inhibit the cytochrome P450 1A2 activity by 13% and 2D6 activity by 9%. Anecdotal evidence suggests that Ginkgo biloba leaf extract might also be an inhibitor and an inducer of 3A4 activity. However, based on current reports, the effects on the cytochrome P450 enzymes are not likely to lead to clinically significant drug interactions. It is important to note that there is the potential for an increased risk of bleeding when Ginkgo biloba is used concurrently with antiplatelet agents , anticoagulants or herbs with coumarin constituents (e.g., angelica, anise, capsicum, celery, chamomile, clove, danshen, garlic, ginger, horseradish, licorice, onion, papain, red clover).

Hypomania has been reported in patients with depression when Ginkgo leaf extract was used in combination with fluoxetine (Prozac®)/buspirone (BuSpar®), St. John’s wort, and melatonin. It is not known whether Ginkgo leaf extract in combination with either fluoxetine alone or buspirone alone can cause hypomania. Ginkgo leaf extract also has the potential to amplify the activity of monoamine oxidase inhibitors, however this effect has not been confirmed in humans.

Due to the fact that Ginkgo leaf extract can alter insulin secretion, patients taking insulin should monitor glucose levels closely. Additionally, due to the anecdotal reports of seizures associated with Ginkgo biloba leaf extract use, patients taking medications known to lower the seizure threshold should avoid the use of Ginkgo leaf products. Some medications known to lower seizure threshold include: propofol (Diprivan®), mexiletine (Mexitil®), amphotericin B (Fungizone®), penicillins, cephalosporins, imipenem/cilastatin (Primaxin®), bupropion (Wellbutrin®), cyclosporine (Neoral®), fentanyl (Sublimaze®), methylphenidate, and theophylline.

Dose and Administration: The Gingko leaf product is produced from green, picked leaves grown on plantaDose and Administration: The Gingko leaf product is produced from green, picked leaves grown on plantations specifically developed for pharmaceutical purposes. Gingko biloba leaf extract is available in various formulations (e.g., capsules, tablets, concentrated liquids, sublingual sprays, bars and cola drinks), as well as many combination products. Standardized products can contain 24% of flavone glycosides and 6% terpenes (ginkgolides and bilobalides). The products most commonly used in clinical trials are Ginkgo biloba standardized leaf extracts EGb 761 (Tanakan) and LI 1370 (Lichewer Pharma) and are available in the United States. Products with similar ingredients include Ginkai® (Lichtwer Pharma), Ginkgo 5®(Pharmline), Ginkgold® and Ginkgo® (Nature’s Way), and Quanterra Mental Sharpness (Warner-Lambert).

The recommended dose of Ginkgo biloba is 40 mg three times a day administered orally, but the daily dose can range from 120 to 600 mg depending on the disorder being treated. The majority of Ginkgo biloba products claim that a minimum of four weeks is required to achieve enhancement of mental focus and improvement of memory and concentration in patients with or without clinically significant cognitive impairments. There are a variety of examples of marketed products specifically for memory enhancement including, Quanterra Mental Status Sharpness®, One-A-Day Memory and Concentration®, AIM GinkgoSense®, and the Ultimate Memory Formula®. The average price of these products is $30.00 for 30 tablets.

Ginkgo biloba for Memory Impairment: In the German Commission E Monograph, Ginkgo biloba is approved for symptomatic treatment of deficits in memory impairment, concentration difficulties and depression from organic brain disease.

Numerous trials have been conducted using standardized Ginkgo biloba extract (GBE) for treatment of dementia syndromes and memory impairment (See Table 5). Several Ginkgo biloba single-dose trials have been conducted to assess its effect on short-term memory. These trials were small, used various doses of Ginkgo biloba, and involved healthy volunteers or elderly patients with mild memory impairment. The studies that reported beneficial effects associated with Ginkgo biloba leaf extract were small uncontrolled studies and have found benefit in one of many cognitive tests administered. The trials that compare Ginkgo biloba to placebo use an array of doses (120 to 240 mg daily), lengths of therapy (6 to 52 weeks), age groups, and disease severity (healthy adults to Alzheimer’s Disease patients). The neuropsychological outcome measured varied between studies, and there was no clear pattern of benefit for Ginkgo biloba-treated patients. Additionally, a recent trial by Solomon and colleagues, assessing the use of Ginkgo biloba for memory impairment in a healthy elderly population failed to show any benefit. Clinical trials evaluating the efficacy of Ginkgo biloba in Alzheimer’s Disease patients report some benefits. A recent trial that assessed the effectiveness of Ginkgo biloba leaf extract in patients with Alzheimer’s Disease or multi-infarct dementia reported a 1.4-point decline on the ADAS-Cog scale (Alzheimer’s Disease Assessment Scale-Cognitive) in the placebo group, compared to a slight improvement in the Ginkgo group. Currently, a multicenter, clinical trial is assessing elderly patients (median age of 80 years) comparing Ginkgo biloba 240 mg administered orally once daily and placebo for six years. The primary endpoint is incidence of dementia and secondary endpoints include incidence of Alzheimer’s Disease, incidence of vascular dementia, changes in cognitive function scores over time, and changes in functional status.

Summary: Despite the lack of well-controlled studies to support the use of Ginkgo biloba leaf extract for prevention and treatment of memory impairment, ginkgo products continue to be heavily marketed and widely used. In 1997, sales of Ginkgo leaf extract products reached $240 million in the United States. In Germany, more than 5 million Ginkgo prescriptions are written for the treatment of dementia, cerebral decline and peripheral arterial insufficiency. A recent summary on the patterns of medication use in the ambulatory adult population in the United States reports that Ginkgo biloba leaf extract was the second most used herbal/dietary supplement. The age group with the highest Ginkgo usage was 45 to 65 year old men and women. The use of Ginkgo biloba leaf extract for memory impairment is marketed and targeted at the healthy adult that experiences forgetfulness. Currently, the claims that Ginkgo biloba has beneficial effects on learning and memory are not supported by the literature. Ginkgo biloba extract was found to stabilize or improve several measures of cognitive function and social functioning in Alzheimer’s Disease, vascular or mixed dementia patients. Ginkgo biloba standardized leaf extract products that have been used in clinical trials varied and not all studies tested the product quality. The use of Ginkgo biloba leaf extract should be monitored for drug interactions, and it should not be used in patients with a history of seizures or during pregnancy and breast-feeding. Spontaneous bleeding is a serious adverse effect, therefore, Ginkgo biloba leaf extract products should not be used in patients with a high risk for bleeding.

References available upon request

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