Ginkgo

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Ginkgo

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Ginkgo

Common Names

  • Fossil tree
  • Maidenhair tree
  • Kew tree
  • Bai guo ye
  • Yinhsing

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For Patients & Caregivers

How It Works

Ginkgo does not improve memory or brain function, and does not prevent or decrease the occurrence of dementia or Alzheimer’s disease.

Ginkgo biloba, one of the oldest living tree species, is used in traditional Chinese medicine and is also a popular supplement marketed to improve memory and circulation. Although some studies have observed these effects, large clinical trials do not support the use of ginkgo to improve memory or prevent memory loss. In addition, one study noted that ginkgo supplementation in older adults may increase stroke risk. Therefore, more studies are needed to determine risks and any benefits with ginkgo supplementation.

Ginkgo inhibits platelet-activating factor, which is important for blood clotting, and therefore has blood-thinning qualities.

Purported Uses
  • To prevent memory loss or decline
    In several large studies among elderly patients, ginkgo did not improve memory. It also did not prevent Alzheimer’s disease or dementia, and did not prevent what is commonly known as “brain fog” among cancer patients.
  • To manage cardiovascular disease
    A large analysis did not find any benefit with ginkgo for heart disease.
  • To treat tinnitus
    Studies are mixed on whether ginkgo can help tinnitus.
Do Not Take If
  • You have a blood clotting disorder.
  • You have a history of seizures.
  • You are at risk for stroke: Ginkgo may increase this risk.
  • You are taking warfarin or other blood thinners: Ginkgo may have additive effects, increasing the risk of spontaneous bleeding.
  • You are taking antipsychotic medications or prochlorperazine: Case reports suggest ginkgo may cause seizures when combined with these medications.
  • You are taking insulin: Ginkgo can alter insulin secretion and affect blood glucose levels.
  • You are taking trazodone: In one case, ginkgo extract was associated with coma in a woman with Alzheimer’s disease who was also taking trazodone. Use with caution and ask your doctor.
  • You are taking an antiretroviral such as efavirenz: Case reports suggest ginkgo may reduce the effectiveness of this drug.
  • You are taking nonsteroidal anti-inflammatory drugs (NSAIDs): Ginkgo can increase adverse effects.
  • You are taking amlodipine: Animal studies suggest ginkgo may increase the risk of side effects of this drug. Clinical relevance has yet to be determined.
  • You are taking a CYP 3A4 substrate drug: Ginkgo may increase the risk of side effects of these drugs.
  • You are taking a P-glycoprotein substrate drug: Ginkgo may increase the risk of side effects of these drugs.
  • You are taking a UGT substrate drug: Lab studies suggest ginkgo may increase the risk of side effects of these drugs. Clinical relevance has yet to be determined.
Side Effects

Case reports

Low blood levels of sodium: Several cases which caused confused state, malaise, headaches, and fatigue. This condition improved after ginkgo supplements were stopped.

Spontaneous bleeding: In a few cases, including in the eye and brain, related to ginkgo supplementation.

Prolonged bleeding: Among some healthy volunteers in a study that evaluated the interaction of ginkgo with antiplatelet drugs.

Seizures: In a few patients who were prone to seizures or on medications that lower the seizure threshold (e.g. prochlorperazine, chlorpromazine, perphenazine, etc.), ginkgo may have induced seizures.

Rash and itching: In a man after repeatedly ingesting a natural product containing ginkgo and vinpocetine.

Acute hemolytic anemia: In a patient after receiving a ginkgo injection for dementia. Symptoms resolved after IV fluids and discontinuation of product.

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For Healthcare Professionals

Scientific Name
Ginkgo biloba
Clinical Summary

Ginkgo biloba is one of the oldest living tree species. It is cultivated around the world for its medicinal properties and aesthetic value. The seeds and leaves have been used in traditional Chinese medicine to treat respiratory diseases, circulatory disorders, sexual dysfunction, and hearing loss. It is also marketed as a supplement to support memory and circulation.

Clinical studies including the large Ginkgo Evaluation of Memory (GEM) study generally show supplementation with ginkgo does not improve cognitive performance or prevent Alzheimer’s disease or dementia (4) (5) (6) (7) (8). In addition, positive effects from earlier studies were not confirmed in more recent trials and some systematic reviews determined there was insufficient evidence on any benefits in adults with either normal cognition or mild cognitive impairment (9) (10).

Although two trials suggest potential benefit with ginkgo in acute ischemic stroke (11) (12), a study in older adults noted increased stroke incidence (4), and a meta-analysis suggests evidence is generally weak with a high risk of bias (54). In addition, the large GEM study did not find benefit with ginkgo for cardiovascular disease incidence or mortality (13). Studies on whether ginkgo can help tinnitus are mixed (14) (15) (55) (56), as are studies for other conditions such as ADHD (16) (17).

Studies on ginkgo in cancer patients are quite limited (3) (21), and secondary outcome data from the aforementioned GEM study does not support the use of ginkgo to reduce cancer risk (22). It is also ineffective in preventing chemotherapy-associated cognitive dysfunction in breast cancer patients (23).

Although some preliminary data suggested ginkgo may reduce ovarian cancer risk (20), animal models suggest that high doses may have hepatocarcinogenic effects (24) (25). More studies are needed to determine the significance of these findings.

Purported Uses
  • Cardiovascular disease
  • Memory loss
  • Tinnitus
Mechanism of Action

Ginkgo interacts with several cytochrome P450 enzymes. Pretreatment with G. biloba extract induces expression of CYP3A proteins and mRNA and increases CYP3A activity (26). It also inhibits CYP2B6 catalytic activity and bupropion hydroxylation (27). Ginkgo may play a role in decreasing high-glucose-induced endothelial inflammation via inhibition of interleukin-6 activation (28), and repeated intake of ginkgo enhanced cell proliferation and neuroblast differentiation (29). Flavonoids present in ginkgo extracts inhibited estrogen biosynthesis via aromatase inhibition, decreased CYP19 mRNA, and induced transcriptional suppression (30).

Chemopreventive properties of bilobalide, a terpene trilactone, may occur via alterations in cryptal cell proliferation and drug-metabolizing enzyme activities (1). Exocarp polysaccharides from ginkgo affected expression of c-myc, bcl-2 and c-fos genes, which can inhibit proliferation and induce apoptosis and differentiation of human gastric tumor cells (3).

Adverse Reactions

Case reports

Hyponatremia: Several cases, which included symptoms of confused state, malaise, headaches, and fatigue. Plasma sodium normalized following cessation of ginkgo supplements (57).
Spontaneous bleeding: Including hematomas (31) (32), hyphema (33), and cerebral and intracerebral bleeding (34) (35).
Prolonged bleeding time: Among some healthy volunteers in a pharmacodynamic study that evaluated the interaction of ginkgo with antiplatelet drugs (36).
Seizures: In predisposed patients or those on medications that lowered the seizure threshold (37).
Cutaneous reaction: Pruritus and macular erythema in a man after repeatedly ingesting a natural product containing ginkgo and vinpocetine (38).
Acute hemolytic anemia (with injected ginkgo): In a patient with glucose-6-phosphate dehydrogenase (G6PD) deficiency receiving a G. biloba injection for dementia prophylaxis. Symptoms resolved following intravenous fluid infusion and discontinuation of G. biloba  (39).

Herb-Drug Interactions
  • Cytochrome P450 substrates: Laboratory studies and a few case reports suggest ginkgo can inhibit and induce the CYP450 1A2, 2D6, and 3A4 enzymes, but data are conflicting (26) (27) (40) (41) (42) (43). Clinical relevance has yet to be determined.
  • P-glycoprotein substrates: In healthy volunteers, ginkgo inhibits P-glycoprotein and may interfere with drugs that are transported by P-glycoprotein (44).
  • UGT (Uridine 5’-diphospho-glucuronosyltransferase) substrates: In vitro, ginkgo modulates UGT enzymes and may increase the side effects of drugs metabolized by them (45). Clinical relevance has yet to be determined.
  • MATE1 substrates: Laboratory studies indicate that isorhamnetin, a compound present in ginkgo is a strong inhibitor of the human multidrug and toxic compounds extrusion transporter 1 (hMATE1), responsible for the excretion of various drugs in the kidney and liver (46). Clinical relevance has yet to be determined.
  • Anticoagulants / Antiplatelets: Human studies and case reports indicate that ginkgo may induce or prolong bleeding time (36) (47).
  • Nonsteroidal anti-inflammatory drugs (NSAIDS): Adverse event reports indicate that ginkgo can have additive anticoagulant/antiplatelet effects (48).
  • Antipsychotics / Prochlorperazine: Case reports suggest ginkgo may cause seizures when combined with medications that lower the seizure threshold (37).
  • Insulin: Laboratory and human studies suggest ginkgo can alter insulin secretion and affect blood glucose levels (49) (50).
  • Trazodone: Ginkgo extract was associated with coma in a patient with Alzheimer’s disease who was also taking trazodone (47).
  • Efavirenz: Case reports suggest ginkgo may inhibit the effects of this drug (43) (51).
  • Midazolam: A study in healthy subjects suggests ginkgo may decrease serum concentrations (52).
  • Amlodipine: Animal studies suggest that a multiherbal formula containing ginkgo could inhibit the metabolism of amlodipine (53). Clinical relevance has yet to be determined.
Dosage (OneMSK Only)
References
  1. Suzuki R, Kohno H, Sugie S, et al. Preventive effects of extract of leaves of ginkgo (Ginkgo biloba) and its component bilobalide on azoxymethane-induced colonic aberrant crypt foci in rats. Cancer Lett. Jul 16 2004;210(2):159-169.
  2. Pretner E, Amri H, Li W, et al. Cancer-related overexpression of the peripheral-type benzodiazepine receptor and cytostatic anticancer effects of Ginkgo biloba extract (EGb 761). Anticancer Res. Jan-Feb 2006;26(1a):9-22.
  3. Xu AH, Chen HS, Sun BC, et al. Therapeutic mechanism of Ginkgo biloba exocarp polysaccharides on gastric cancer. World J Gastroenterol. Nov 2003;9(11):2424-2427.
  4. Dodge HH, Zitzelberger T, Oken BS, et al. A randomized placebo-controlled trial of Ginkgo biloba for the prevention of cognitive decline. Neurology. May 6 2008;70(19 Pt 2):1809-1817.
  5. DeKosky ST, Williamson JD, Fitzpatrick AL, et al. Ginkgo biloba for prevention of dementia: a randomized controlled trial. JAMA. Nov 19 2008;300(19):2253-2262.
  6. Snitz BE, O’Meara ES, Carlson MC, et al. Ginkgo biloba for preventing cognitive decline in older adults: a randomized trial. JAMA. Dec 23 2009;302(24):2663-2670.
  7. Vellas B, Coley N, Ousset PJ, et al. Long-term use of standardised Ginkgo biloba extract for the prevention of Alzheimer’s disease (GuidAge): a randomised placebo-controlled trial. Lancet Neurol. Oct 2012;11(10):851-859.
  8. Solomon PR, Adams F, Silver A, et al. Ginkgo for memory enhancement: a randomized controlled trial. JAMA. Aug 21 2002;288(7):835-840.
  9. Birks J, Grimley Evans J. Ginkgo biloba for cognitive impairment and dementia. Cochrane Database Syst Rev. Jan 21 2009(1):Cd003120.
  10. Butler M, Nelson VA, Davila H, et al. Over-the-Counter Supplement Interventions to Prevent Cognitive Decline, Mild Cognitive Impairment, and Clinical Alzheimer-Type Dementia: A Systematic Review. Ann Intern Med. Jan 2 2018;168(1):52-62.
  11. Li S, Zhang X, Fang Q, et al. Ginkgo biloba extract improved cognitive and neurological functions of acute ischaemic stroke: a randomised controlled trial. Stroke Vasc Neurol. Dec 2017;2(4):189-197.
  12. 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. Nov 2013;22(8):e557-563.
  13. Kuller LH, Ives DG, Fitzpatrick AL, et al. Does Ginkgo biloba reduce the risk of cardiovascular events? Circ Cardiovasc Qual Outcomes. Jan 2010;3(1):41-47.
  14. Han SS, Nam EC, Won JY, et al. Clonazepam quiets tinnitus: a randomised crossover study with Ginkgo biloba. J Neurol Neurosurg Psychiatry. Aug 2012;83(8):821-827.
  15. Rejali D, Sivakumar A, Balaji N. Ginkgo biloba does not benefit patients with tinnitus: a randomized placebo-controlled double-blind trial and meta-analysis of randomized trials. Clin Otolaryngol Allied Sci. Jun 2004;29(3):226-231.
  16. Shakibaei F, Radmanesh M, Salari E, et al. Ginkgo biloba in the treatment of attention-deficit/hyperactivity disorder in children and adolescents. A randomized, placebo-controlled, trial. Complement Ther Clin Pract. May 2015;21(2):61-67.
  17. 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. Feb 1 2010;34(1):76-80.
  18. Gertsch JH, Basnyat B, Johnson EW, et al. Randomised, double blind, placebo controlled comparison of Ginkgo biloba and acetazolamide for prevention of acute mountain sickness among Himalayan trekkers: the prevention of high altitude illness trial (PHAIT). BMJ. Apr 3 2004;328(7443):797.
  19. Moraga FA, Flores A, Serra J, et al. Ginkgo biloba decreases acute mountain sickness in people ascending to high altitude at Ollague (3696 m) in northern Chile. Wilderness Environ Med. Winter 2007;18(4):251-257.
  20. Ye B, Aponte M, Dai Y, et al. Ginkgo biloba and ovarian cancer prevention: epidemiological and biological evidence. Cancer Lett. Jun 18 2007;251(1):43-52.
  21. Hauns B, Haring B, Kohler S, et al. Phase II study of combined 5-fluorouracil/Ginkgo biloba extract (GBE 761 ONC) therapy in 5-fluorouracil pretreated patients with advanced colorectal cancer. Phytother Res. Feb 2001;15(1):34-38.
  22. Biggs ML, Sorkin BC, Nahin RL, et al. Ginkgo biloba and risk of cancer: secondary analysis of the Ginkgo Evaluation of Memory (GEM) Study. Pharmacoepidemiol Drug Saf. Jul 2010;19(7):694-698.
  23. Barton DL, Burger K, Novotny PJ, et al. The use of Ginkgo biloba for the prevention of chemotherapy-related cognitive dysfunction in women receiving adjuvant treatment for breast cancer, N00C9. Support Care Cancer. Apr 2013;21(4):1185-1192.
  24. Hoenerhoff MJ, Pandiri AR, Snyder SA, et al. Hepatocellular carcinomas in B6C3F1 mice treated with Ginkgo biloba extract for two years differ from spontaneous liver tumors in cancer gene mutations and genomic pathways. Toxicol Pathol. Aug 2013;41(6):826-841.
  25. Mei N, Guo X, Ren Z, et al. Review of Ginkgo biloba-induced toxicity, from experimental studies to human case reports. J Environ Sci Health C Environ Carcinog Ecotoxicol Rev. Jan 2 2017;35(1):1-28.
  26. Deng Y, Bi HC, Zhao LZ, et al. Induction of cytochrome P450 3A by the Ginkgo biloba extract and bilobalides in human and rat primary hepatocytes. Drug Metab Lett. Jan 2008;2(1):60-66.
  27. Lau AJ, Chang TK. Inhibition of human CYP2B6-catalyzed bupropion hydroxylation by Ginkgo biloba extract: effect of terpene trilactones and flavonols. Drug Metab Dispos. Sep 2009;37(9):1931-1937.
  28. Chen JS, Chen YH, Huang PH, et al. Ginkgo biloba extract reduces high-glucose-induced endothelial adhesion by inhibiting the redox-dependent interleukin-6 pathways. Cardiovasc Diabetol. May 3 2012;11:49.
  29. Yoo DY, Nam Y, Kim W, et al. Effects of Ginkgo biloba extract on promotion of neurogenesis in the hippocampal dentate gyrus in C57BL/6 mice. J Vet Med Sci. Jan 2011;73(1):71-76.
  30. Park YJ, Choo WH, Kim HR, et al. Inhibitory Aromatase Effects of Flavonoids from Ginkgo biloba Extracts on Estrogen Biosynthesis. Asian Pac J Cancer Prev. 2015;16(15):6317-6325.
  31. Rowin J, Lewis SL. Spontaneous bilateral subdural hematomas associated with chronic Ginkgo biloba ingestion. Neurology. Jun 1996;46(6):1775-1776.
  32. Gilbert GJ. Ginkgo biloba. Neurology. Apr 1997;48(4):1137.
  33. Rosenblatt M, Mindel J. Spontaneous hyphema associated with ingestion of Ginkgo biloba extract. N Engl J Med. Apr 10 1997;336(15):1108.
  34. Matthews MK, Jr. Association of Ginkgo biloba with intracerebral hemorrhage. Neurology. Jun 1998;50(6):1933-1934.
  35. Pedroso JL, Henriques Aquino CC, Escorcio Bezerra ML, et al. Ginkgo biloba and cerebral bleeding: a case report and critical review. Neurologist. Mar 2011;17(2):89-90.
  36. Aruna D, Naidu MU. Pharmacodynamic interaction studies of Ginkgo biloba with cilostazol and clopidogrel in healthy human subjects. Br J Clin Pharmacol. Mar 2007;63(3):333-338.
  37. Gregory PJ. Seizure associated with Ginkgo biloba? Ann Intern Med. Feb 20 2001;134(4):344.
  38. Cohen PR. Fixed Drug Eruption to Supplement Containing Ginkgo biloba and Vinpocetine: A Case Report and Review of Related Cutaneous Side Effects. J Clin Aesthet Dermatol. Oct 2017;10(10):44-47.
  39. Lai SW, Chen JH, Kao WY. Acute hemolytic anemia in glucose-6-phosphate dehydrogenase deficiency complicated by Ginkgo biloba. Acta Haematol. 2013;130(4):288-290.
  40. Scott GN, Elmer GW. Update on natural product—drug interactions. Am J Health Syst Pharm. Feb 15 2002;59(4):339-347.
  41. Hellum BH, Hu Z, Nilsen OG. Trade herbal products and induction of CYP2C19 and CYP2E1 in cultured human hepatocytes. Basic Clin Pharmacol Toxicol. Jul 2009;105(1):58-63.
  42. Lin YY, Chu SJ, Tsai SH. Association between priapism and concurrent use of risperidone and Ginkgo biloba. Mayo Clin Proc. Oct 2007;82(10):1289-1290.
  43. Wiegman DJ, Brinkman K, Franssen EJ. Interaction of Ginkgo biloba with efavirenz. AIDS Jun 1 2009;23(9):1184-1185.
  44. Fan L, Mao XQ, Tao GY, et al. Effect of Schisandra chinensis extract and Ginkgo biloba extract on the pharmacokinetics of talinolol in healthy volunteers. Xenobiotica. Mar 2009;39(3):249-254.
  45. Mohamed ME, Frye RF. Effects of herbal supplements on drug glucuronidation. Review of clinical, animal, and in vitro studies. Planta Med. Mar 2011;77(4):311-321.
  46. Kawasaki T, Ito H, Omote H. Components of foods inhibit a drug exporter, human multidrug and toxin extrusion transporter 1. Biol Pharm Bull. 2014;37(2):292-297.
  47. Chen XW, Serag ES, Sneed KB, et al. Clinical herbal interactions with conventional drugs: from molecules to maladies. Curr Med Chem. 2011;18(31):4836-4850.
  48. Haller C, Kearney T, Bent S, et al. Dietary supplement adverse events: report of a one-year poison center surveillance project. J Med Toxicol. Jun 2008;4(2):84-92.
  49. Kudolo GB. The effect of 3-month ingestion of Ginkgo biloba extract on pancreatic beta-cell function in response to glucose loading in normal glucose tolerant individuals. J Clin Pharmacol. Jun 2000;40(6):647-654.
  50. Budzinski JW, Foster BC, Vandenhoek S, et al. An in vitro evaluation of human cytochrome P450 3A4 inhibition by selected commercial herbal extracts and tinctures. Phytomedicine. Jul 2000;7(4):273-282.
  51. Naccarato M, Yoong D, Gough K. A potential drug-herbal interaction between Ginkgo biloba and efavirenz. J Int Assoc Physicians AIDS Care (Chic). Mar-Apr 2012;11(2):98-100.
  52. Robertson SM, Davey RT, Voell J, et al. Effect of Ginkgo biloba extract on lopinavir, midazolam and fexofenadine pharmacokinetics in healthy subjects. Curr Med Res Opin. Feb 2008;24(2):591-599.
  53. Wang R, Zhang H, Sun S, et al. Effect of Ginkgo Leaf Tablets on the Pharmacokinetics of Amlodipine in Rats. Eur J Drug Metab Pharmacokinet. Dec 2016;41(6):825-833.
  54. Ji H, Zhou X, Wei W, et al. Ginkgol biloba extract as an adjunctive treatment for ischemic stroke: A systematic review and meta-analysis of randomized clinical trials. Medicine (Baltimore). Jan 2020;99(2):e18568.
  55. Procházková K, Šejna I, Skutil J, et al. Ginkgo biloba extract EGb 761(®) versus pentoxifylline in chronic tinnitus: a randomized, double-blind clinical trial. Int J Clin Pharm. Oct 2018;40(5):1335-1341.
  56. Spiegel R, Kalla R, Mantokoudis G, et al. Ginkgo biloba extract EGb 761(®) alleviates neurosensory symptoms in patients with dementia: a meta-analysis of treatment effects on tinnitus and dizziness in randomized, placebo-controlled trials. Clin Interv Aging. 2018;13:1121-1127.
  57. Hamilton N, Alamri Y, Allan C, et al. Ginkgo biloba-related hyponatraemia: a reminder that herbal supplements are not benign. Intern Med J. Nov 2019;49(11):1458-1460.
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