Ginkgo biloba


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The use of dietary supplements by patients with cancer has increased significantly over the past 2 decades despite insufficient evidence of safety and effectiveness. Finding reliable sources of information about dietary supplements can be daunting. Patients typically rely on family, friends, and the Internet, often receiving misleading information. 

The ASCO Post’s Integrative Oncology series is intended to facilitate the availability of evidence-based information on integrative and complementary therapies commonly used by patients with cancer. We chose ginkgo biloba for this issue because of their growing use by cancer patients.

Compiled by Barrie R. Cassileth, PhD, and Jyothi Gubili, MS, Memorial Sloan-Kettering Cancer Center. The About Herbs website is managed by K. Simon Yeung, PharmD, MBA, Lac, Memorial Sloan-Kettering Cancer Center.

Ginkgo biloba
Common names: Fossil tree, maidenhair tree, kew tree, bai guo ye, yinhsing, ginkyo.

Overview 

Ginkgo, one of the oldest living trees dating back 250 million years, is prevalent in China, Korea, and Japan. Beginning in 18th century, it began to be cultivated in many parts of the world for its aesthetic value. Known for its sturdiness, ginkgo is believed to be the only flora to have resprouted following the atomic bombing at Hiroshima.

The therapeutic value of ginkgo was first described in the Chinese Materia Medica 5,000 years ago. The seeds were used in traditional Chinese medicine to treat brain, respiratory, and circulatory disorders, as well as sexual dysfunction, loss of hearing, and vertigo. Today, ginkgo leaf extract is used to enhance memory and to treat mild dementia, peripheral vascular disease, tinnitus, and sexual dysfunction. 

Current clinical evidence supports use of ginkgo for peripheral vascular disease. However, data on the herb’s potential to prevent dementia and Alzheimer’s disease are inconclusive. 

Ginkgo is among the top-selling herbal supplements in the United States and Europe. It is available in health food stores and online in the form of tablets, capsules, softgels, liquid extracts, and herbal tea.

The Science

Pharmacologically active constituents of ginkgo include flavonoids, diterpene lactones known as ginkgolides, and bilobalide, a sesquiterpene lactone.

Several clinical trials have been conducted to determine the role of ginkgo in improving cognitive performance in both healthy adults and demented patients, but data are conflicting.1,2

According to data from the Ginkgo Evaluation of Memory (GEM) study, the largest trial of ginkgo for dementia thus far, ginkgo is ineffective in decreasing the incidence of dementia or Alzheimer’s disease in elderly individuals.3 Similar findings were reported by another group.4 Further, ginkgo did not slow down cognitive decline in older adults with normal cognition or with mild cognitive impairment.5

In other studies, ginkgo was less effective compared to the standard treatment for attention deficit hyperactivity disorder (ADHD) in children.6 Current evidence is mixed on ginkgo’s ability to decrease the severity of acute mountain sickness.7,8 More research is warranted.

A few studies have also explored ginkgo’s anticancer potential. Epidemiologic and biologic data show that it reduces the risk of ovarian cancer.9 In patients with gastric cancer, oral administration of capsules containing ginkgo exocarp polysaccharides reduced the tumor area.10 But findings from the GEM study, in which cancer was the secondary outcome, do not support use of ginkgo in reducing the risk of cancer.11 Ginkgo supplementation was also reported ineffective in preventing chemotherapy-associated cognitive dysfunction in a randomized controlled trial of patients with breast cancer.12

Adverse Effects 

Seizures,13 and spontaneous bleeding,14 including hematomas,15,16 hyphema,17 and cerebral bleeding,18 have been reported.

Herb-Drug Interactions

Antipsychotics/prochlorperazine: Ginkgo may cause seizures when taken along with medications that lower the seizure threshold.13

Insulin: Ginkgo can alter insulin secretion and affect blood glucose levels.19

Cytochrome P450 substrates: Ginkgo can both inhibit and induce CYP450 enzymes but data are conflicting.20,21

P-glycoprotein substrates: Ginkgo inhibits P-glycoprotein and may interfere with drugs that are transported by P-glycoprotein.22

Efavirenz (antiretroviral agent): Ginkgo may inhibit its effects.23,24

Nonsteroidal anti-inflammatory drugs: Ginkgo can have additive anticoagulant/antiplatelet effects.25

Uridine 5’-diphospho-glucuronosyltransferase (UGT) substrates: Ginkgo modulates UGT enzymes in vitro and may increase the adverse effects of drugs metabolized by them.26 

Disclosure: Ms. Gubili, Drs. Cassileth, and Yeung  reported no potential conflicts of interest.

References

1. Lovera J, Bagert B, Smoot K, et al: Ginkgo biloba for the improvement of cognitive performance in multiple sclerosis: A randomized, placebo-controlled trial. Mult Scler 13:376-385, 2007.

2. Canter PH, Ernst E: Ginkgo biloba is not a smart drug: An updated systematic review of randomised clinical trials testing the nootropic effects of G. biloba extracts in healthy people. Hum Psychopharmacol 22:265-278, 2007.

3. DeKosky ST, Williamson JD, Fitzpatrick AL, et al: Ginkgo biloba for prevention of Dementia. A randomized controlled trial. JAMA 300:2253-2262, 2008.

4. Vellas B, Coley N, Ousset P-J, 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 11:851-859, 2012.

5. Snitz BE, O’Meara ES, Carlson MC, et al: Ginkgo biloba for preventing cognitive decline in older adults. A randomized trial. JAMA 302:2663-2670, 2009.

6. 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 34:76-80, 2010.

7. Chow T, Browne V, Heileson HL, et al: Ginkgo biloba and acetazolamide prophylaxis for acute mountain sickness: A randomized, placebo-controlled trial. Arch Intern Med 165:296-301, 2005.

8. Gertsch JH, Basnyat B, Johnson WE, 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 328:797, 2004.

9. Ye B, Aponte M, Dai Y, et al: Ginkgo biloba and ovarian cancer prevention: Epidemiological and biological evidence. Cancer Lett 251:43-52, 2007.

10. Xu AH, Chen HS, Sun BC, et al: Therapeutic mechanism of ginkgo biloba exocarp polysaccharides on gastric cancer. World J Gastroenterol 9:2424-2427, 2003.

11. 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 19:694-698, 2010.

12. 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 21:1185-1192, 2013

13. Gregory PJ: Seizure associated with Ginkgo biloba? Ann Intern Med 134:344, 2001

14. Matthews MK: Association of Ginkgo biloba with intracerebral hemorrhage. Neurology 50:1933-1934, 1998.

15. Rowin J, Lewis SL: Spontaneous bilateral subdural hematomas associated with chronic ginkgo biloba ingestion. Neurology 46:1775-1776, 1996.

16. Gilbert GJ: Ginkgo biloba. Neurology 48:1137, 1997

17. Rosenblatt M, Mindel J: Spontaneous hyphema associated with ingestion of Ginkgo biloba extract. N Engl J Med 336:1108, 1997.

18. Pedroso JL, Henriques Aquino CC, Escórcio Bezerra ML, et al: Ginkgo biloba and cerebral bleeding: A case report and critical review. Neurologist 17:89-90, 2011.

19. 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 40:647-654, 2000.

20. Lau AJ, Chang TK: Inhibition of human CYP2B6-catalyzed bupropion hydroxylation by Ginkgo biloba extract: Effect of terpene trilactones and flavonols. Drug Metab Dispos 37:1931-1937, 2009.

21. Hellum BH, Hu Z, Nilsen OG: Trade herbal products and induction of CYP2C19 and CYP2E1 in cultured human hepatocytes. Basic Clin Pharmacol Toxicol 105:58-63, 2009.

22. 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 39:249-254, 2009.

23. Wiegman DJ, Brinkman K, Franssen EJ: Interaction of Ginkgo biloba with efavirenz. AIDS 23:1184-1185, 2009.

24. Naccarato M, Yoong D, Gough K: A potential drug-herbal interaction between Ginkgo biloba and efavirenz. J Int Assoc Physicians AIDS Care (Chic) 11:98-100, 2012

25. Haller C, Kearney T, Bent S, et al: Dietary supplement adverse events: Report of a one-year poison center surveillance project. J Med Toxicol 4:84-92, 2008.

26. Mohamed ME, Frye RF: Effects of herbal supplements on drug glucuronidation. Review of clinical, animal, and in vitro studies. Planta Med 77:311-321, 2011.

Guest Editor

Integrative Oncology is guest edited by Barrie R. Cassileth, MS, PhD, Chief of the Integrative Medicine Service and Laurance S. Rockefeller Chair in Integrative Medicine at Memorial Sloan-Kettering Cancer Center, New York.

The Integrative Medicine Service at Memorial Sloan-Kettering Cancer Center developed and maintains a free website—About Herbs (www.mskcc.org/aboutherbs)—that provides objective and unbiased information about herbs, vitamins, minerals, and other dietary supplements, and unproved anticancer treatments. Each of the 265 and growing number of entries offer health-care professional and patient versions, and entries are regularly updated with the latest research findings.

In addition, the About Herbs app, Memorial Sloan-Kettering Cancer Center’s very first mobile application, was launched last fall. The app is compatible with iPad, iPhone, and iPod Touch devices, and can be downloaded at http://itunes.apple.com/us/app/about-herbs/id554267162?mt=8.



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