PhytoScience - Article

Ginkgo beloba

 

Ginkgo is considered the oldest tree species to survive on earth, with a history dating back over 200 million years. Ginkgo species were once common in North America and Europe. Ginkgo biloba is the only surviving member of the ginkgo family. While its relatives became extinct in other parts of the world Ginkgo biloba survived in China, where it became known to Europeans in the eighteenth century, and subsequently was introduced as an ornamental tree throughout the Western world.

Now ginkgo trees are found in virtually every city in the United States. It was first introduced to the U.S. in 1784. The common name Ginkgo is a phonetic pronunciation of a Japanese name for the tree. The species name "biloba" refers to the two distinct lobes, typical of the tree's leaves.

Ginkgos have survived over millions of years because of their genetic tenacity. They are long-lived trees, remarkably resistance to disease, pests, and fires. They also are extremely tolerant of air pollution, and are often planted in harsh city environments where most trees will not survive.

The most common tree along Manhattan sidewalks is ginkgo. The trees will get to be over 100 feet tall. In Japan and China trees over a thousand years old are found at ancient temples. Its unique fan-shaped leaves with two lobes make it one of the easiest trees to identify once you become familiar with the unusual leaf shape.

Ginkgo leaf is first mentioned in Lan Mao's Dian Nan Ben Cao (Pharmaceutical Natural History of Southern Yunnan), published in 1436 during the Ming dynasty. Lan Mao notes external use to treat skin and head sores as well as freckles. Internal use of the leaves is first noted in Liu Wen-Tai's Ben Cao Pin Hui Jing Yao (Essentials of the Pharmacopoeia Ranked According to Nature and Efficacy), an imperial commissioned work recorded in 1505. Liu Wen Tai notes use of the leaves in the treatment of diarrhea. The leaves of ginkgo are known in Chinese medicine as bai-guo-ye. Recent clinical reports in modern China suggest that the leaves lower serum cholesterol levels and have some clinical value in angina pectoris.

Over three hundred scientific studies on the chemistry, pharmacology and clinical effects of gingko leaf have been conducted by European researchers over the last 20 to 30 years. Unlike most herbs, ginkgo leaf extracts, rather than crude leaf material, are used for clinical purposes.

The majority of studies on ginkgo leaf extract have involved a product produced by a German/French consortium, referred to in the scientific literature as EGb761. Ginkgo products are standardized to contain 24% of the bioflavonoids which occur in the leaf, as well as ginkgolides and bilobilides, a complex group of compounds found only in the ginkgo tree. Since virtually all research on ginkgo has involved high standardized extracts calibrated to specific quantities of chemical components, it is not possible to apply information from studies on the standardized extracts to ginkgo leaf itself.

Proported Uses

  • Asthma
  • Bronchitis
  • Cardiovascular disease
  • Circulatory disorders
  • Hearing loss
  • Memory loss
  • Raynaud's disease
  • Sexual dysfunction
  • Stress
  • Tinnitus

Mechanism of Action

The active constituents, bilobalide and ginkgolides, improve the tolerance of brain tissue to hypoxia by increasing cerebral blood flow. Ginkgo can increase blood flow to the brain through arterial vasodilatation by stimulating prostaglandin biosynthesis or indirectly stimulating norepinephrine release. Ginkgo has slight anti-inflammatory and spasmolytic activities that are similar to papaverine. It has free-radical scavenging activity for hydroxyl, nitric oxide, peroxyl, and superoxide radicals; it is as effective as uric acid. Ginkgo increases tolerance to ischemic conditions and seems to inhibit the platelet-activating factor.

Animal studies have shown that ginkgo has a beneficial effect on neurotransmitter disturbance that can restore vascular tone of the smooth muscle cells by maintaining alpha-adrenergic constrictive and beta-adrenergic relaxation vaso-regulation. Ginkgo can also suppress cell proliferation, decrease levels of proliferating cell nuclear antigen, and increase expression of p53, a tumor suppressor gene, in human hepatocellular carcinoma cells.

Adverse Reactions

Common: Headache, dizziness, GI upset, flatulence, diarrhea, contact dermatitis, and palpitations.
Case reports: Seizures were reported in patients predisposed to seizures or on medications that lower the seizure threshold (e.g. prochlorperazine, chlorpromazine, perphenazine, etc.). Spontaneous bleeding, including hematomas and hyphema, was also reported.

Product that contains ginkgolic acid may increase the risk of allergic reaction.

Interactions

Monoamine oxidase inhibitors (MAO-I): Ginkgo may potentiate the effects of MAO-Is.
Anticoagulants / Antiplatelets: Ginkgo may induce spontaneous bleeding possibly associated with reduced platelet aggregation resulting from inhibition of platelet activating factor by ginkgolide components.
Antipsychotics / Prochlorperazine: Ginkgo may cause seizures when combined with medications that lower the seizure threshold.
Insulin: Ginkgo can alter insulin secretion and affect blood glucose levels.
Drugs metabolized by Cytochrome P450: Preliminary evidence suggests that ginkgo can affect the CYP450 1A2, 2D6, and 3A4 enzymes. But because of conflicting data, it is not clear whether it induces or inhibits the individual enzymes.
Trazodone: Ginkgo extract was associated with coma in a patient with Alzheimer's disease who was also taking trazodone.

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 the leaves have been used in traditional medicine to treat respiratory diseases, circulatory disorders, sexual dysfunction, and loss of hearing. Ginkgo biloba extract exhibits anti-infective, chemopreventive, anticancer, and cytotoxic effects in vitro.

Supplementation with Ginkgo improved cognitive performance in healthy adults, and demented patients but data are conflicting. Ginkgo biloba may also reduce the severity of acute mountain sickness, but the evidence is mixed. More studies are warranted.

Ginkgo has also been implicated in reducing the risk of ovarian cancer but this is based only on epidemiological and biological data. Orally administered capsules of Ginkgo biloba exocarp polysaccharides reduced tumor area in patients with gastric cancer. In another study, an injectable form of Ginkgo extract and 5-flurouracil were administered to patients with advanced colorectal cancer. Data suggests benefits of the combination therapy. Further studies are needed to determine the anticancer potential of oral Ginkgo supplements.

Ginkgo use is associated with adverse effects and it can also interact with prescription medications. Ginkgo supplementation for dementia may increase risk of stroke. Patients should use caution before taking Ginkgo supplements.

Product Warnings

Ginkgo biloba extracts should not contain ginkgolic acid. Discontinue use of Ginkgo at least 36 hours before surgery. 

References

  1. Chavez M, et al. Ginkgo: History, Use and Pharmacologic Properties. Hospital Pharmacy 1998;33:658-72.
  2. 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. 2004;210(2):159-169.
  3. 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. 2006;26(1A):9-22.
  4. Xu AH, Chen HS, Sun BC, Xiang XR, Chu YF, Zhai F, Jia LC. Therapeutic mechanism of ginkgo biloba exocarp polysaccharides on gastric cancer. World J Gastroenterol. 2003;9(11):2424-7.
  5. Kennedy DO, Scholey AB, Wesnes KA. Modulation of cognition and mood following administration of single doses of Ginkgo biloba, ginseng, and a ginkgo/ginseng combination to healthy young adults. Physiol Behav 2002;75:739-51.
  6. LeBars, PL, et al. A placebo-controlled, double-blind, randomized trial of an extract of ginkgo biloba for dementia. JAMA 1997;278:1327-32.
  7. Solomon PR, et al. Ginkgo for memory enhancement: a randomized controlled trial. JAMA 2002;288:835-40.
  8. Le Bars PL, et al. A 26-week analysis of a double-blind, placebo controlled trial of the ginkgo biloba extract Egb 761 in dementia. Dement Geriatr Cogn Disorder 2000;11:230-7.
  9. 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. 2007;13(3):376-385.
  10. Dos Santos-Neto LL, de Vilhena Toledo MA, Medeiros-Souza P, de Souza GA. The use of herbal medicine in Alzheimer's disease-a systematic review. Evid Based Complement Alternat Med. 2006;3(4):441-445.
  11. 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. 2007;22(5):265-278.
  12. Ye B, Aponte M, Dai Y, et al. Ginkgo biloba and ovarian cancer prevention: epidemiological and biological evidence. Cancer Lett. 2007;251(1):43-52.
  13. Hauns B, Haring B, Kohler S, et al. Phase II study of combined 5-fluorouracial/Ginkgo biloba extract (GBE 761 ONC) therapy in 5-fluorouracil pretreated patients with advanced colorectal cancer. Phytother Res 2001;15(1):34-8.
  14. Newall C, et al. Herbal Medicines: A Guide for Health Care Professionals. London: Pharmaceutical Press; 1996.
  15. Rowin J, Lewis SL. Spontaneous bilateral subdural hematomas associated with chronic ginkgo biloba ingestion. Neurology 1996;46:1775-6.
  16. Kleijnen J, Knipschild P. Ginkgo biloba. Lancet 1992;340:1136-9.
  17. Gregory PJ. Seizure associated with ginkgo biloba? Ann Int Med 2001;134:344.
  18. Matthews MK. Association of Ginkgo biloba with intracerebral hemorrhage. Neurology 1998;50:1934.
  19. Gilbert GJ. Ginkgo biloba. Neurology 1997;48:1137.
  20. Rosenblatt M, Mindel J. Spontaneous hyphema associated with ingestion of ginkgo biloba extract. N Eng J Med 1997;336:1108.
  21. Brinker F. Herb Contraindications and Drug Interactions, 2nd ed. Sandy (OR): Eclectic Med Pub; 1998.
  22. 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 2000;40:647.
  23. Budzinski JW, et al. An in vitro evaluation of human cytochrome P450 3A4 inhibition by selected commercial extracts and tinctures. Phytomedicine 2000;7:273-82.
  24. Scott GN, Elmer GW. Update on natural product-drug interactions. Am J Health-Syst Pharm 2002;59:339-47.
  25. Gertsch JH, Seto TB, Mor J, Onopa J. Ginkgo biloba for the prevention of severe acute mountain sickness (AMS) starting one day before rapid ascent. High Alt Med Biol. 2002;3(1):29-37.
  26. Moraga FA, Flores A, Serra J, et al. Ginkgo biloba decreases acute mountain sickness in people ascending to high altitude at Ollagüe (3696 m) in northern Chile. Wilderness Environ Med 2007;18(4):251-7.
  27. 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. 2005;165(3):296-301.
  28. 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 2004;328(7443):797.
  29. Dodge HH, Zitzelberger T, Oken BS, et al. A randomized placebo-controlled trial of ginkgo biloba for the prevention of cognitive decline. Neurology 2008.

Disclaimer:
These statements have not been evaluated by the FDA. Any product mentioned is not intended to diagnose, treat, cure or prevent any disease.