Ginkgo biloba is our oldest species of tree. It is estimated to have lived some 200 million years ago. Fossils have been found that date as far back as the Permian period of the Paleozoic era. It is the only surviving species of the family Ginkgoaceae. It is a native of the Far East where the tree was brought back from near extinction through its cultivation for medicinal uses. It was brought to America in the late 1700''s and has primarily been used here as an ornamental.

This is a very hardy, dioecious tree with light green fan shaped leaves. It can reach heights up to 125 feet and is extremely hardy, as it is resistant to many insects, diseases and pollution. Individual trees have been known to live as long as 1000 years. Female trees produce fruit in the autumn months. This fruit is plum shaped and orangish/tan in color.

The leaves and inner seed of the fruit have been reported as having medicinal qualities, however the fruit''s pulp is considered toxic (see Averse Effects) and should be handled with care.

The seed has been used for approximately 3000 years in China for it''s curative powers. It was traditionally used for the treatment of asthma and other respiratory ailments. More recently, extensive research on the herb has been conducted on the healing properties of the leaf extract. Germany and France have run literally hundreds of studies on the leaf extract. These studies along with similar studies in America, have shown significant results. The extract of Ginkgo biloba has been studied for its effectiveness in the treatment of Acrocyanosis, Alzheimer's disease, Cerebral atherosclerosis, Cerebral insufficiencies, Cochlear deafness, Dementia, Depression, Menopause, Peripheral and cerebral circulatory stimulation, Peripheral vascular disease, Raynaud's syndrome, Retinopathy, Senility, Short-term memory loss, Tinnitus, Vascular Diseases, and Vertigo (see Clinical Studies).

It is a commonly prescribed herb in Europe and is often used as one source of phytomedicines.

Due to different cultivation and harvesting methods it is generally thought that the best quality of leaves are obtained from plantations located in Europe and America. It is not considered an herb to grow yourself for medicinal usage, as the quantities to obtain the potency levels needed are quite large. It should also be noted, that there are seasonal variations in active constituent content of the leaves. Autumn is thought by some to be the best time for harvesting in this regard.

It is said to be effective in improving the blood flow to the hands and the feet as well as stimulating the brain and reducing short-term memory loss. It increases blood flow to the brain, the uptake of glucose by brain cells, and has been said to improve the transmission of nerve signals. In studies, Ginkgo biloba has been reported as demonstrating anti-oxidant abilities with improvements of the platelet and nerve cell functions and blood flow to the nervous system and brain. It has also been reported as reducing blood viscosity. It''s ability to increase vascular dilation, may help reduce retinal damage due to macular degradation and may reverse deafness caused by reduced blood flow (see Clinical Studies).

Medicinal parts: Fresh or dried-leaf and seed.

The average Ginkgo biloba preparation is a 50:1 extract standardized to 24% of the Ginkgo flavone glycosides. This is made from the leaves and usually extracted with acetone and water.

The World wide sales of Ginkgo biloba (extract taken from the leaves) was reported as reaching an estimated U.S. $500 million in 1991. In Europe, commercially available preparations based on the commercial product EGb 761 had a turnover of about $500 million a year estimated in 1993. ¹ It has been reported that the sales in the United States reached approximately $240 million in 1997. ²

Biochemical Constituents - Flavonoid glycosides (such as quercetin and kaempferol) and diterpenes - including the terpene structures called ginkgolides (A, B, and C) and bilobalide. Pro-anthocyanidins, hetrerosides, bioflavones (such as sciaopitysin, ginkgetin, isoginkgentin, bilobetin, and ginkgolic acid), essential oil, and tannins.

Biochemical Constituents - Detailed - Acacetin, acenapthene, acetic-acid, afzelin, alanine, amentoflavone, g-aminobutyric-acid, anacardic-acid, apigenin, arabinose, arginine, ascorbic-acid, ash, asparagine, aspartic-acid, betulaprenols, bilobalide, bilobanone, bilobetin, bilobol, butyric-acid, calcium, calcium-oxalate, caproic-acid, caprylic-acid, carbohydrates, cardanol, cardol, beta-carotene, d-catechin, ceryl-alcohol tw, citric-acid, copper, p-coumaric-acid, p-cymene, cysteine, cystine, -(e)-dihydroatlantone jsg, -(z)-dihydroatlantone jsg, -dimethyl--diiso-propylbenzene, dna - fl(male), docosanol, elemol, l-epicatechin, l-epigallocatechin, alpha-ethyllathosterol, beta-eudesmol, gamma-eudesmol, fat, fiber, formic-acid, fructose, gadoleic-acid, galactose, d-gallocatechin, ginkgetin, ginkgol, ginkgolic-acid, ginkgolide-a, ginkgolide-acid, ginkgolide-b, ginkgolide-c, ginkgolide-m, ginnol, ginnon, d-glucaric-acid, glucomannan, glucose, glutamic-acid, glycine, -heptacosanol, hexacosanol, alpha-hexenal, histidine, homoserine, hydroginkgolic-acid, -hydroxyanacardic-acid, -hydroxyginkgolic-acid, -hydroxykynurenic-acid, alpha-ionone, beta-ionone, ipuranol, iron, isoginkgetin, isoleucine, -isopropylphenol, isorhamnetin, kaempferol, kaempferol--o-alpha('-p-coumaroyl-glucosyl-beta--rhamnoside), kaempferol--rhamno-glucoside, kaempferol-rutinoside, leucine, trans-linalool-oxide, linoleic-acid, alpha-linolenic-acid, luteolin, lysine, magnesium, manganese, mannan, mannose, methionine, ''-methoxybilobetin ''-methoxypyridoxine, ''-o-methylmyricetin-rutinoside, myristic-acid, niacin, nonacosane, -nonacosanol, nonacosanol, octacosanol, oleic-acid, -(e)--oxo-dihydroatlantone, palmitic-acid, palmitoleic-acid, pantothenic-acid -(pentadec--enyl)--di-hydroxybenzoic-acid, zz''-(-pentadien--diyl)diphenol, pentosans, pentosans, phenylalanine, phosphorus, pinitol, pulnin, tassium, procyanidin, prodelphinidin, proline, propionic-acid, protein, quercetin, quercetin--o-alpha('-p-coumaroyl-glucosyl-beta--rhamnoside), quercetin-rhamnoglucoside, quercetin--rutinoside quinic-acid, raffinose, riboflavin, sciadopitysin, sequoyitol, serine, alpha-sesamin, shikimic-acid, sitosterol, sodium, spinasterol, starch, stearic-acid, stigmasterol, succinic-acid, sucrose, tannin, thiamin, threonine, thymol, p-tolyl-propylene, tricetin, -trimethyl-dihydronaphthalene, tryptophan, tyrosine, uroshiols valerianic-acid, valine, wax, xylose, zinc ^{3/ 4}

Dosages are usually based on the severity of the symptoms and the type of problem. On average administration should last not less than 6 weeks. In very severe cases, at least 8 weeks. However, in cases of tinnitus and vertigo 6-8 weeks is usually considered sufficient. ¹⁰

 

TABLE 1 - Usual Dosage for Teas

Adults:	Pour 1 pt. boiling water over ½ ounce leaves. Steep 15 minutes. Take cup 1-2 x day
Children:	No known Studies conducted to date - Do not use with children under 2 y.s. Use with Extreme Care for children 2 years and older. Always consult with a physician.

 

TABLE 2 - Usual Herbal Dosages (unless otherwise specified in Tables 3)

i.e. Alzheimer''s disease; multi-infarct dementia; mental deterioration due to aging; menopausal depression; vascular insufficiency

Adults:	Ginkgo biloba extract standardized at 24% ginkgoflavonglycosides @ 80mg 3 x a day
Children:	No known Studies conducted to date - Do not use with children under 2 y.s. Use with Extreme Care for children 2 years and older. Always consult with a physician.

 

TABLE 3 - Usual Dosage for Peripheral Arterial Occlusive/Vertigo/Tinnitus

Adults:	Ginkgo biloba extract standardized at 24% ginkgoflavonglycosides @ 60- 80mg 3 x a day
Children:	No known Studies conducted to date - Do not use with children under 2 y.s. Use with Extreme Care for children 2 years and older. Always consult with a physician.

Note: GBE needs to be taken for 12 to 24 weeks before the effects can be determined. It will only be effective if the usage is constantly maintained.

HOW SUPPLIED

It is usually orally taken in a solid or liquid form.

REFERENCES

1. Sticher-O: Ginkgo biloba: A Modern Phytomedicine, Vierteljahrsschrift der Naturforschenden Gesellschaft in Zuerich (1993)138(3): 125-168
2. Dana Canedy: Real Medicine or Medicine Show? Growth of Herbal Sales Raises Issues About Value. New York Times. July 23, 1998:C1.
3. Duke, James A.: Handbook of Phytochemical Constituents of GRAS Herbs and Other Economic Plants. Boca Raton, FL. CRC Press, 1992. ISBN 0849371929
4. Sticher O: Quality of Ginkgo Preparation, Planta Med (1993 Feb) 59(1):2-11, Zuerich (1993)138(3): 125-168
5. Pincemail J, Thirion A, Dupuis M, Braquet P, Drieu K, Deby C: Ginkgo biloba Extract Inhibits Oxygen Species Production Generated by Phorbolmyristate Acetate Stimulated Human Leukocytes, Experientia (1987 Feb 15)
6. Ramassamy C Naudin B Christen Y Clostre F Costentin J: Prevention by Ginkgo biloba extract (EGb 761) and trolox C of the decrease in synaptosomal dopamine or serotonin uptake following incubation, Biochem Pharmacol (1992 Dec 15) 44(12):2395-401
7. Ramassamy C Christen Y Clostre F Costentin J: The Ginkgo biloba extract, EGb761, increases synaptosomal uptake of 5- hydroxytryptamine: in-vitro and ex-vivo studies, J Pharm Pharmacol (1992 Nov) 44(11):943-5
8. Ramassamy C Girbe F Christen Y Costentin J: Ginkgo biloba extract EGb 761 or trolox C prevent the ascorbi acid/Fe2+ induced decrease in synaptosomal membrane fluidity, Free Radic Res Commun (1993) 19(5):341-50
9. Moreau JP, Eck CR, McCabe J, Skinner S: Absorption, Distribution and Elimination of a Labeled Extract of Ginkgo biloba Leaves in the Rat, (Absorption, distribution et elimination de l''extrait marque de feuilles deGinkgo biloba chez le rat), Presse Med (1986 Sep 25) 15(31):1458-61 (Published in French)
10. Mark Blumenthal: The Complete Commission E Monographs, American Botanical Council, 1998, ISBN 096555550X
11. Fourtillan JB, Brisson AM, Girault J, Ingrand I, Decourt JP, Drieu K, Jouenne P, Biber A: Pharmacokinetic Properties of Bilobalide and Ginkgolides A and B in Healthy Subjects after Intravenous and Oral Administration of Ginkgo biloba Extract (EGb761) (Proprietes pharmacocinetiques du Bilobalide et des Ginkgolides A et B chez lesujet sain apres administrations intraveineuses et orales d''extrait de Ginkgobiloba (EGb 761), Therapie (1995 Mar-Apr) 50(2):137-44 (Published in French)
12. Oken BS, Storzbach DM, Kaye JA: The Efficacy of Ginkgo biloba on Cognitive Function in Alzheimer Disease, Arch Neurol 1998 Nov;55(11):1409-15
13. Hopfenmuller W: Evidence for a Therapeutic Effect of Ginkgo biloba Special Extract: Meta-Analysis of 11 Clinical Trials in Patients with Cerebrovascular Insufficiency in Old Age. Arzneim Forsch. 1994;44:1005-1013
14. Kleijnen J, Knipschild P: Ginkgo biloba for Cerebral Insufficiency, Br J Clin Pharmacol . 1992:34:352-358
15. The Journal of the American Botanical Council and the Herb Research Foundation, Ginkgo biloba Extract--Efficacy in Early Stage Alzheimer''s Disease, # 34 - Summer 1995
16. Allard M:Treatment of the Disorders of Aging with Ginkgo biloba Extract. From pharmacology to Clinical Medicine, PRESSE MED 1986 Sep 25; 15(31):1540-5 (Published in FRENCH)
17. Itil T, Martorano D: Natural Substances in Psychiatry (Ginkgo biloba in Dementia), Psychopharmacol Bull 31:147-158; 1995
18. Le Bars PL, Katz MM, Berman N, Itil TM, Freedman AM, Schatzberg AF: A Placebo-controlled, Double-Blind, Randomized Trial of an Extract of Ginkgo biloba for Dementia. North American EGb Study Group. York Institute for Medical Research
19. Allain H Raoul P Lieury A LeCoz F Gandon JM d''Arbigny P: Effect of two doses of Ginkgo biloba extract (EGb 761) on the dual- coding test in elderly subjects, Clin Ther (1993 May-Jun) 15(3):549-58
20. Grassel E: Effect of Ginkgo-Biloba extract on Mental Performance, Fortschr Med (1992 Feb 20) 110(5):73-6 (Published in German)
21. Rai GS, Shovlin C, Wesnes KA: A Double-blind, Placebo Controlled Study of Ginkgo biloba Extract In Elderly Out-patients with Mild to Moderate Memory Impairment, Curr Med Res Opin 12:350-355; 1991
22. Stoll S, Scheuer K, Pohl O, Muller WE: Ginkgo biloba Extract (EGb 761) Independently Improves Changes in Passive Avoidance Learning and Brain Membrane Fluidity in the Aging Mouse., Pharmacopsychiatry 1996 Jul;29(4):144-9
23. Hofferberth B: The effect of Ginkgo biloba Extract on Neurophysiological and Psychometric measurement Results in Patients with Psychotic Organic Brain Syndrome, A Double-blind Study Against Placebo (Einfluss von Ginkgo biloba-Extrakt auf neurophysiologische und psychometrischeMessergebnisse bei Patienten mit hirnorganischem Psychosyndrom. EineDoppelblindstudie gegen Plazebo), Arzneimittelforschung (1989 Aug) 39(8):918-22 (Published in German)
24. Lebuisson DA, Leroy L, Rigal G: Treatment of Senile Macular Degeneration with Ginkgo biloba Extract. A Preliminary Double-blind Drug vs. Placebo Study (Traitement des degenerescences "maculaires seniles" par l''extrait de Ginkgobiloba. Etude preliminaire a double insu face au placebo). Presse Med (1986 Sep 25) 15(31):1556-8 (Published in French)
25. Raabe A, Raabe M, Ihm P: Therapeutic follow-up using automatic perimetry in chronic cerebroretinalischemia in elderly patients. Prospective Double-blind Study with Graduated Dose Ginkgo biloba Treatment (EGb 761)] (Therapieverlaufskontrolle mittels automatisierter Perimetrie bei chronischer zerebroretinaler Mangelversorgung alterer Patienten. Prospektive randomisierte Doppelblinduntersuchung mit dosisgestaffelter Ginkgo biloba-Behandlung (EGb761), Klin Monatsbl Augenheilkd (1991 Dec) 199(6):432-8 (Published in German)
26. Schaffler K, Reeh PW: Double blind study of the hypoxia protective effect of a standardized Ginkgobiloba preparation after repeated administration in healthy subjects (Doppelblindstudie zur hypoxieprotektiven Wirkung eines standardisierten Ginkgo-Biloba-Praparates nach Mehrfachverabreichung an gesunden Probanden), Arzneimittelforschung (1985) 35(8):1283-6 (Published in German)
27. P Eber O: Collagen-induced Thrombocyte Aggregation in Parenteral Therapy Using Ginkgobiloba (Die kollageninduzierte Thrombozytenaggregation unter parenteraler Ginkgo-biloba-Therapie)., Wien Med Wochenschr (1989 Mar 15) 139(5):92-4 (Published in German)
28. Touvay C, Etienne A, Braquet P: Inhibition of Antigen-induced Lung Anaphylaxis in theGuinea-pig by BN 52021 a New specific Paf-acether Receptor Antagonist Isolated from Ginkgo biloba, Agents Actions (1986 Jan) 17(3-4):371-2
29. Chung Kuo, Chung Hsi I, Chieh Ho, Tsa Chih: Effects of Ginkgo Leave Concentrated Oral Liquor in Treating Asthma [Article in Chinese], 1997 Apr;17(4):216-8
30. Haguenauer JP, et al.: Treatment of Disturbances of Equilibrium with Ginkgo biloba Extract. A Multicentre, Double-Blind, Drug versus Placebo Study, Presse Med 15:1569-1572; 1986
31. Cano Cuenca B, Marco Algarra J, Perez del Valle B, Pellicer Pascual FJ: (The Effect of Ginkgo biloba on Cochleovestibulary Pathology of Vascular origin.)[Article in Spanish], Bergne An Otorrinolaringol Ibero Am 1995;22(6):619-29
32. Warburton DM: Clinical Psychopharmacology of Ginkgo biloba Extract (Psycho-pharmacologie clinique de l''extrait de Ginkgo biloba), Presse Med (1986 Sep 25) 15(31):1595-604 (Published in French)
33. Loas G, Rose D, Nowaczkowski P, Lernout P, Duron B: Exploratory Study of Amitriptyline Resistance in Depressed Patients: results of WHO French collaborating center on depressions resistant to treatments].[Article in French] Ann Med Psychol (Paris) 1996 Jun;154(3):202-3, Hopital Pinel, Amiens, France
34. Kleijnen J Knipschild P: Ginkgo biloba for Cerebral Insufficiency, Br J Clin Pharmacol (1992 Oct) 34(4):352-8
35. Clostre F: From the Body to the Cell Membrane: The Different Levels of Pharmacological Action of Ginkgo biloba Extract, PRESSE MED 1986 Sep 25; 15(31):1529-38 (Published in FRENCH)
36. Hitzenberger G: The Effect of Ginkgo biloba Special Extract (EGb 761, Tebofortan), Wien Med Wochenschr (1992) 142(17):371-9 (Published in German)
37. Koltringer P Langsteger W Klima G Reisecker F Eber O: Hemorheologic Effects of Ginkgo biloba Extract EGb 761. Dose-dependent effect of EGb 761 on microcirculation and viscoelasticity of blood, Fortschr Med (1993 Apr 10) 111(10):170-2 (Published in German)
38. Hopfenmuller W: Proof of the Therapeutical Effectiveness of a Ginko Biloba Special Extract - meta-analysis of 11 clinical trials in aged patients with cerebral insufficiency, Arzneim-Forsch (GERMANY) 44:1005-1013; 1994
39. Etienne A Hecquet F Clostre F: Mechanism of Action of Ginkgo biloba Extract in Experimental Cerebral Edema, (Mecanismes d''action de l''extrait de Ginkgo biloba sur l''oedeme cerebral experimental), Presse Med (1986 Sep 25) 15(31):1506-10
40. Otani M Chatterjee SS Gabard B Kreutzberg GW: Effect of an Extract of Ginkgo biloba on Triethyltin-Induced Cerebral Edema, ACTA NEUROPATHOL (BERL) (1986) 69(1-2):54-65
41. Apaydin C Oguz Y Agar A Yargicoglu P Demir N Aksu G: Visual evoked potentials and optic nerve histopathology in normal and diabetic rats and effect of Ginkgo biloba extract, In: Acta Ophthalmol (Copenh) (1993 Oct) 71(5):623-8
42. Doly M, Droy-Lefaix MT, Braquet P: Oxidative Stress in DiabeticRetina. EXS 62:299-307; 1992.
43. Lanthony P, Cosson JP: The Course of Color Vision in Early Diabetic Retinopathy Treated with Ginkgo biloba Extract. A Preliminary Double-blind Versus Placebo Study (Evolution de la vision des couleurs dans la retinopathie diabetique debutantetraitee par extrait de Ginkgo biloba. Etude preliminaire a double insu contreplacebo), J Fr Ophtalmol (1988) 11(10):671-4 (Published in French)
44. Hoffmann F Beck C Schutz A Offermann P: Ginkgo extract EGb 761 (tenobin)/HAES versus naftidrofuryl (Dusodril)/HAES. A Randomized Study of Therapy of Sudden Deafness: Laryngorhinootologie (1994 Mar) 73(3):149-52 (Published in German)
45. Olivier-J; Plath-P: Combined Low Power Laser Therapy and Extracts of Ginkgo biloba in a Blind Trial of Treatment for Tinnitus, Laser Therapy (1993) 5(3): 137-139
46. Holgers KM Axelsson A Pringle I: Ginkgo biloba Extract for the Treatment of Tinnitus, Audiology (1994 Mar-Apr) 33(2):85-92
47. Dubreuil C: Therapeutic Trial in Acute Cochlear Deafness. A Comparative Study of Ginkgo biloba Extract and Nicergoline (Essai therapeutique dans les surdites cochleaires aigues. Etude comparative del''extrait de Ginkgo biloba et de la nicergoline), Presse Med (1986 Sep 25) 15(31):1559-61 (Published in French)
48. Gonda R Takeda K Shimizu N Tomoda M: Characterization of a Neutral Polysaccharide Having Activity on the Reticuloendothelial System from the Rhizome of Curcuma Longa, Chem PharmBull (Tokyo)(1992 Jan)40(1):185-8
49. Atzori C Bruno A Chichino G Bombardelli E Scaglia M Ghione M: Activity of Bilobalide, a Sesquiterpene from Ginkgo bilobavon Pneumocystis Carinii, In: Antimicrob Agents Chemother (1993 Jul) 37(7):1492-6
50. 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 Jul-Sep) 88(7-9):447-57 (Published in French)
51. Ernst E.: Ginkgo biloba Extract in Peripheral Arterial Diseases: A Systematic Research Based on Controlled Studies in the Literature. Fortsch Med. 1996;114:85-87
52. Roncin J, Schwartz F, D''Arbigny P: EGb 761 in Control of Acute Mountain sickness and Vascular reactivity to Cold Exposure. Aviat Space Environ Med. 1996;67:445-452
53. Schneider B: Ginkgo biloba Extract in Peripheral Arterial Diseases. Meta-analysis of Controlled Clinical Studies. Arzneim Forschung 42:428-436; 1992
54. Jung F, Mrowietz C, Kiesewetter H, Wenzel E: Effect of Ginkgo biloba on Fluidity of Blood and Peripheral Microcirculation in Volunteers, Arzneimittelforschung (1990 May) 40(5):589-93
55. Bauer U: 6-Month Double-blind Randomised Clinical Trial of Ginkgo biloba Extract Versus placebo in Two Parallel Groups in Patients Suffering from Peripheral Arterial insufficiency, Arzneimittelforschung (1984) 34(6):716-2079
56. Peters H, Kieser M, Holscher U: Demonstration of the Efficacy of Special Extract EGb 761 on Intermittent Claudication--a Placebo-Controlled, Double-blind Multicenter trial. Vasa 1998 May;27(2):106-10
57. Itokawa H, Totsuka N, Nakahara K, Maezuru M, Takeya K, Kondo M, Inamatsu M, Morita H: A Quantitative Structure-activity Relationship for antitumor Activity of Long-chain Phenols from Ginkgo biloba L., Chem Pharm Bull (Tokyo) (1989 Jun) 37(6):1619-21
58. Bolanos-Jimenez F, Manhaes de Castro R, Sarhan H, Prudhomme N, Drieu K, FillionG: Stress-induced 5-HT1A Receptor Desensitization: Protective Effects of Ginkgo biloba Extract (EGb 761), Fundam Clin Pharmacol (1995) 9(2):169-74
59. Emerit I, Arutyunyan R, Oganesian N, Levy A, Cernjavsky L, Sarkisian T, Pogossian A, Asrian K: Radiation-induced Clastogenic Factors: Anticlastogenic Effect of Ginkgo biloba Extract, Free Radic Biol Med (1995 Jun) 18(6):985-91
60. Kose K, Dogan P: Lipoperoxidation Induced by Hydrogen Peroxide in Human Erythrocyte Membranes. 2. Comparison of the Antioxidant Effect of Ginkgo biloba Extract (EGb 761)With Those of Water-soluble and Lipid-soluble Antioxidants, J Int Med Res (1995 Jan-Feb) 23(1):9-18
61. Pietri S, Seguin JR, d''Arbigny P, Drieu K, Culcasi M: Ginkgo biloba Extract (EGb 761) Pretreatment Limits free Radical-induced Oxidative Stress in Patients Undergoing Coronary Bypass Surgery. Cardiovasc Drugs Ther 1997 Apr;11(2):121-31
62. Castelli D, Colin L, Camel E, Ries G: Pretreatment of Skin with a Ginkgo biloba Extract/Sodium Carboxymethyl-beta-1,3-glucan Formulation Appears to Inhibit the Elicitation of Allergic Contact Dermatitis in Man, Contact Dermatitis 1998 Mar;38(3):123-6
63. Rowin J, Lewis SL: Spontaneous Bilateral Subdural Hematomas Associated with Chronic Ginkgo biloba Ingestion. Neurology 1996;46:1775-6
64. Rosenblatt M, and Mindel J: Spontaneous Hyphema Associated with Ingestion of Ginkgo biloba Extract NEJM (1997)336;15:1108
65. Bergner, P: Drug-herb Interactions, Medical Herbalism 1997;9(2):1
66. Lepoittevin JP Benezra C Asakawa Y: Allergic contact dermatitis to Ginkgo biloba L.: Relationship with Urushiol., Arch Dermatol Res (1989) 281(4):227-30
67. Tomb RR, Foussereau J, Sell Y: Mini-epidemic of Contact Dermatitis from Ginkgo Tree Fruit (Ginkgo biloba L.).In: Contact Dermatitis (1988 Oct) 19(4):281-33
68. American Herbal Products Asociation: Handbook of Botanical Safety, Edited by McCuffin M, Hobbs C, Upton R, Goldberg A: CRC Press 1997

 

 

Additional References:

• Duke, James A.: Handbook of Biologically Active Phytochemicals and Their Activities, Boca Raton, FL., CRC Press, 1992

• Duke, James A.: Handbook of Phytochemical Constituents of GRAS Herbs and Other Economic Plants. Boca Raton, FL. CRC Press, 1992. ISBN 0849371929
• Mark Blumenthal: The Complete Commision E Monographs, American Botanical Council, 1997, ISBN 096555550X
• Edited by Timothy R. Tomlinson and Olayiwola Akerele: Medicinal Plants, Their Role in Health and Biodiversity, University of Pennsylvania Press, 1998
• Reader Digest: The Family Guide to Natural Medicine, 1993, the Reader''s Digest Association, Inc., ISBN 0-89577-433-X
• Michael Murray, N.D. and Joseph Pizzorno, N.D: Encyclopedia of Natural Medicine, 2 ^nd ed, Prima Publishing, 1998, ISBN 0-7615-1157-1
• Time Life: The Drug and Natural Medicine Advisor, 1997, Time-Life Books, ISBN 0-7835-4938-5/ 0-7835-5300-5
• Michael A Weiner, Ph.D & Janet A. Weiner: Herbs that Heal, 1994, Quantum Books, ISBN 0-912845-11
• Ara Der Marderosian, Ph.D and Lawrence E. Liberti, MS: Natural Products Medicine, 1988, George F.
• Michael A Weiner, Ph.D & Janet A. Weiner: Herbs that Heal, 1994, Quantum Books, ISBN 0-912845-11
• Michael Tierra, C.A., N.D.: The Way of Herbs, Pocket Books, 1990, ISBN, 0-671-72403-7
• Michael Castleman: The Healing Herbs ,Bantam Books, 1991, ISBN 0-553-56988-0
• Edited by Timothy R. Tomlinson and Olayiwola Akerele: Medicinal Plants, Their Role in Health and Biodiversity, University of Pennsylvania Press, 1998
• Edited by C.K. Atal and M. Kapur: Cultivation and Utilization of Medicinal Plants, Regional Research Laboratory, Council of Scientific and Industrial Research Jammu-Tawi, 1982
• Clinical and Psychometric Aspects of the Therapeutic Effects of GBE: Effects of GBE and Organic Cerebral Impairment, Paris, London, John Lilley, 1985
• Letzel H, Schoop W: Ginkgo biloba extract EGb 761 and pentoxifylline in intermittent claudication. Secondary analysis of the clinical effectiveness. [Article in German] Vasa 1992;21(4):403-10
• Drug-herb Interactions, Medical Herbalism 1997
• Chinn E, Silverthorne J, Hohtola A: Light-regulated and Organ-specific Expression of types 1, 2, and 3 Light-Harvesting Complex b mRNAs in Ginkgo biloba, Plant Physiol (1995 Feb) 107(2):593-602
• Chinn E, Silverthorne J: Light-dependent Chloroplast Development and Expression of a Light- harvesting Chlorophyll a/b-binding Protein Gene in the Gymnosperm Ginkgo biloba, Plant Physiol (1993 Nov) 103(3):727-
• Michel PF: The Doyen of Trees: The Ginkgo biloba (Le doyen des arbres: le Ginkgo biloba), Presse Med (1986 Sep 25) 15(31):1450-4 (Published in French)
• Stucker O, Pons C, Duverger JP, Drieu K, D''Arbigny P: Effect of Ginkgo biloba Extract (EGb 761) on the Vasospastic Response of Mouse Ccutaneous Arterioles to Platelet Activation, Int J Microcirc Clin Exp 1997 Mar-Apr;17(2):61-6
• Taillandier J, Ammar A, Rabourdin JP, Ribeyre JP, Pichon J, Niddam S, Pierart H: Treatment of Cerebral Aging Disorders with Ginkgo biloba Extract. A Longitudinal Multicenter Double-blind Drug vs. Placebo study (Traitement des troubles du vieillissement cerebral par l''extrait de Ginkgobiloba. Etude longitudinale multicentrique a double insu face au placebo), Presse Med (1986 Sep 25) 15(31):1583-7 (Published in French)
• Long R Yin R Zhen Y: Partial Purification and Analysis of Allergenicity, Immunogenicity of Ginkgo biloba L. Pollen, Hua Hsi I Ko Ta Hsueh Hsueh Pao (1992 Sep) 23(4):429-32 (Published in Chinese)
• Joyeux M, Lobstein A, Anton R, Mortier F: Comparative antilipoperoxidant, antinecrotic and scavenging Properties of Terpenes and Biflavones from Ginkgo and Some Flavonoids, Planta Med (1995 Apr) 61(2):126-9

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The following adverse reactions have been reported as associated with the use of Ginkgo biloba but are considered rare in their occurrence:

• Diarrhea
• Edema
• Erythema
• Headaches
• Irritability
• Nausea
• Restlessness
• Vomiting

The following adverse reactions have been reported as associated with the use of Ginkgo biloba when taken in conjunction with a blood thinner:

• Spontaneous hyphema
• Spontaneous bilateral subdural hematomas
• Retinal hemorrhage
• Clotting problems

Fruit:

The following adverse reactions have been reported as associated with contact of the Ginkgo biloba Tree itself and especially the fruit. ^66/67/68

• Contact Dermatitis

The following adverse reactions have been reported as associated with ingestion of the Ginkgo biloba fruit:

• Contact Dermatitis
• Tenesmus
• Perioral erythema
• Rectal burning

Seed:

Care should be taken if the seed is to be used. There have been reports of high toxicity from ingested raw seeds. Cooked seeds are considered safe. ⁶⁸

 

Leaf/leaf Extract:

Body as a Whole - The possibility of an allergic reaction to the herb should be kept in mind during therapy; Headaches

Cardiovascular System -

Digestive System - Nausea, Vomiting, Diarrhea

Metabolic and Nutritional - Clotting Problems

Nervous System - Restlessness, Irritability

Skin and Appendages - Edema, Erythema

The following adverse reactions have been reported as associated with the use of Ginkgo biloba when taken in conjunction with a blood thinner:

• Spontaneous Hyphema
• Spontaneous bilateral subdural hematomas
• Retinal hemorrhage

As with all Herbs and Drugs, the potential for interaction by a variety of mechanisms

(e.g. pharmacodynamic, pharmacokinetic drug inhibition or enhancement, etc.) is a possibility.

• According to recent studies on drug and herb interactions, Ginkgo biloba extracts should not be used while taking blood thinning medications such as heparin, warfarin or coumarin derivative. ^63/65
• Caution should also be taken with aspirin as anecdotes have been recorded of unfavorable interactions.

Copyright 1999 Rxlist - All rights reserved

• Some people have intolerance for the intake of Ginkgo in any amount - stop taking immediately if any adverse effects manifest (see Adverse Reactions)

• Do not use if pregnant or nursing (no clinical data available)
• Should not be used for children under the age of 2 years (no clinical data available)
• Use only with physician approval if utilizing with children over the age of 2 years
• Do not use without approval and monitoring by a physician if you have hemophilia or have any other clotting disorder
• Do not use without approval and monitoring by a physician if taking any blood thinning medicine including aspirin

 

CONTRAINDICATIONS

• Do not use if you have hemophilia or have any other clotting disorder without approval and monitoring by a physician as Ginkgo biloba has been reported as having anticoagulant activity.

• According to recent studies on drug and herb interactions, Ginkgo biloba extracts should not be used while taking blood thinning medications such as heparin, warfarin or coumarin derivative. ^63/65 Caution should also be taken with aspirin as anecdotes of unfavorable interactions have been recorded.

• Do not handle the fruit if you are allergic to poison ivy, mango rind, and cashew nut shell oil, as they are structurally similar to the allergens of Ginkgo biloba. ^66/67/68

 

USAGE IN PREGNANCY

Do not use if pregnant - Safety for use in pregnancy has not been established.

General

The possibility of an allergic reaction to the herb should be kept in mind during therapy.

 

Laboratory Tests

You should always notify your physician when undertaking any herbal therapy for a prolonged period.  It is always recommended that periodic assessments, some of which may include laboratory testing, occur during any therapy.

 

Carcinogenesis, Mutagenesis, and Impairment of Fertility

Studies in animals have not been performed with this herb.

 

Pregnancy

Do not use if pregnant - Safety for use in pregnancy has not been established. Some contraindications are thought to exist.

Nursing Mothers

This herb is not recommended for nursing mothers - Safety for use in pregnancy has not been established as many ingested substances are excreted in human milk.

 

Pediatric Use

This herb is not recommended for children under the age of 2 years.

Studies have not been conducted on the effect of this herb on children, therefore Extreme Caution should be taken and a physician consulted before usage with children over the age of 2 years.

Copyright 1999 Rxlist - All rights reserved

No available data.

• Do not use if you have hemophilia or have any other clotting disorder without approval and monitoring by a physician as Ginkgo biloba has been reported as having anticoagulant activity.

• According to recent studies on drug and herb interactions, Ginkgo biloba extracts should not be used while taking blood thinning medications such as heparin, warfarin or coumarin derivative. ^63/65 Caution should also be taken with aspirin as anecdotes of unfavorable interactions have been recorded.

• Do not handle the fruit if you are allergic to poison ivy, mango rind, and cashew nut shell oil, as they are structurally similar to the allergens of Ginkgo biloba. ^66/67/68

 

Copyright 1999 Rxlist - All rights reserved

CLINICAL PHARMACOLOGY

Pharmacodynamics:

The extract of Ginkgo biloba characterized @ 24% Ginkgo flavone glycosides has been shown to inhibit platelet aggregation ²⁷, and demonstrates a "scavenging" effect on free radicals. ⁵ It also appears to inhibit histamines, and leukotriene production. ⁶ It has demonstrated the ability to inhibit the reduction of muscarinergic cholinoceptors and 2-adrenoceptors. It has the ability to alter the rheological properties of blood (see Clinical Studies).

The European Ginkgo product sold as EGb 761 has demonstrated an excitatory effect on the lateral vestibular nuclei (LVN) neurons and in-vivo and in-vitro studies shown to increase synaptosomal uptake of 5- hydroxytryptamine. ⁷

It has also been shown to prevent the ascorbic acid/Fe2+ induced decrease in synaptosomal membrane fluidity. "Preoccupation of neuronal membrane lipids induced by ascorbic acid/Fe2+ is associated with a decrease in membrane fluidity which, in turn, reduces the ability of the dopamine transporter to take up dopamine." ⁸

"The extract (Ginkgo biloba) slows down O2 consumption (respiratory burst) of stimulated cells by its inhibitory action on NADPH-oxides, the enzyme responsible for the reduction of O2 to O-2. Consequently, superoxide anion (O-.2) and hydrogen peroxide (H2O2) production is significantly decreased when the PMNs stimulation is done in the presence of the extract at concentrations of 500, 250 and 125 micrograms/ml. Moreover, the hydroxyl radical generation (OH) is very much decreased at concentrations as low as 15.6 micrograms Gbe/ml, which indicates that the extract also has free radical scavenging activity. Gbe is able at least to reduce very severely the activity of myeloperoxidase contained in neutrophils" ⁵.

Systemic Bioavailability-

Absorption rate was found to be 60% in tests with rats. ^9/10

Kinetic model	Two-compartment
T1/2	4.5 Hr
Peak absorption	1.5 hours
Distribution	High affinity for glandular, neuronal tissues and eyes 9

 

Bioavailabity of ginkgolides A for humans has been reported at 98-100%, Ginkgolide B was 79-93% and over 70% or greater for bilobalide. ¹⁰

A study of 12 volunteers showed after single dose administration of Ginkgo biloba Extract @.90 mg to 3.36 mg "when given (ginkgo) orally, while fasting, the extents of bioavailability are high, as shown by bioavailability coefficients (FAUC) mean (+/- SD) values equal to 0.80 (+/- 0.09), 0.88 (+/- 0.21) and 0.79 (+/- 0.30) for Ginkgolide A, Ginkgolide B and Bilobalide respectively. Food intake does not change AUC quantitatively but increases Tmax. ¹¹

LD ^50___

LD ⁵⁰ was 7725-mg/kg b.d. weight after oral application in the mouse. Therefore, toxicity can be considered very low. ¹⁰

 

PUBLISHED STUDIES

Alzheimer''s Disease/ Dementia /Aging/Memory/Mental Capability-

also see Cerebral Vascular Insufficiency)

Studies using Ginkgo biloba extract standardized to contain 24% ginkgo flavone glycosides have demonstrated the ability to normalize the acetylcholine receptors in the hippocampus and to increase cholinergic transmission in aged animals. These mechanisms are considered some of the major factors in Alzheimer''s disease. Ginkgo performance on these as well as several other elements of the disease supports its usage in the treatment of this and other geriatric illnesses labeled "senility". Unfortunately, to date, the studies have reported only reversals or delays in the progression of Alzheimer''s disease and its activity is still not fully understood.

 

A meta-analysis of more than 50 English and non-English-language articles in which G. biloba extract was

used to study the effects on dementia or cognitive-impairment concluded that the majority did not meet inclusion criteria for dementia or Alzheimer''s Disease." Further research in the area will need to determine if there are functional improvements and to determine the best dosage. Additional research will be needed to define which ingredients in the ginkgo extract are producing its effect in individuals with AD." ¹²

 

Two double blind studies were conducted which demonstrated Ginkgo''s value medicinally for Alzheimer''s Disease. One study was conducted with 216 patients who had been diagnosed with either Alzheimer''s disease or multi-infarct dementia. These patients were given either a placebo or 240 mg of Ginkgo biloba standardized extract for a period of 24 weeks. Of the 156 patients who completed the study and using the Standard Clinical Global Impression Rating scale, there was a significant improvement over the placebo effect on the patients. ^{13/ 14}

 

A randomized, double-blind study of 40 patients diagnosed with senile dementia of the Alzheimer type assessed cognitive function, memory and attention using Ginkgo biloba extract (EGb 761) versus placebo. While improvement was noted in psychopathology, psychomotor performance, functional dynamics and neurophysiology, significant improvement was found in memory and attention as measured by SKT. "Improvement continued to be noted in the ginkgo group over the three-month course of the study. The ginkgo extract was well tolerated and no side effects were recorded during the trial" ¹⁵.

 

"Concerning Alzheimer''s disease and dementia, no firm conclusion can be drawn for the time being due to the lack of animal model. However, experimental data suggest that the product may act on a number of major elements of these diseases. From what is already known about Ginkgo biloba extract, it appears that it fulfills the conditions laid down by the W.H.O. concerning the development of drugs effective against cerebral aging." ¹⁶

 

"In a pilot bioequivalency study, the effects of three different commercially available EGb (Ginkgo biloba) products were examined. Findings indicated significant quantitative central nervous system (CNS) effects in, at least, one of the three. Furthermore, the CNS effects of Ginkgo were similar to other psychoactive compounds classified as cognitive activators. Recent studies in which EGb 761 demonstrated therapeutic effects in the treatment of dementia have earned EGb the approval of the German BGA (Bundesgesundheit Amt) for use in the treatment of dementia." ¹⁷

 

In a 52-week, randomized double-blind, placebo-controlled, parallel-group, multicenter study, EGb 761, a Ginkgo biloba extract, was studied in patients with Alzheimer disease and multi-infarct dementia. Of 309 patients included, 202 provided evaluable data for the full study period. It was concluded that EGb was safe and " in a substantial number of cases, improving the cognitive performance and the social functioning of demented patients for 6 months to 1 year." ¹⁸

 

In a double-blind study of 18 elderly men and women (mean age, 69.3 years) with slight age-related memory impairment, Ginkgo biloba (EGb 761) extract (320 mg or 600 mg) was compared to placebo using a crossover-study design. Ginkgo treated patients showed an improvement in the speed of information processing over placebo. ¹⁹

 

In a 24 week randomized-placebo-controlled study, Ginkgo biloba extract EGb 761 was studied in 72 outpatients diagnosed with cerebral insufficiency. Statistically significant improvements in short-term memory and basic learning rate were reported for the Ginkgo treated patients. ²⁰ Similar results were reported with 31 patients over the age of 50 who received "a standardized Ginkgo biloba extract (containing 24% flavonoid glycosides and 6% terpenes)" in a 6 month double-blind, placebo controlled, parallel group design study. ²¹

 

Studies in mice using Ginkgo extract (EGb 761) showed significant improvement in short-term memory and of membrane fluidity in the aged animals but no improvement in long-term memory. There was no significant correlation between short term memory performance and membrane fluidity. ²²

 

A placebo-controlled double-blind trial involving 36 patients with classical symptoms of organic syndrome studied the therapeutic effect of Ginkgo biloba extract EGb 761 (rokan) measured by quantified EEG, saccadic eye movements and psychometric tests. After 4 weeks of therapy and also after 8 weeks a significant difference was observed in both saccadic test and psychometric tests compared to the placebo control group. "In parallel, the number of correct answers given in the Wiener Determination Test and Number Connection Test increased significantly compared to the control group." ²³

 

"Senile macular degeneration is a frequent cause of blindness for which there is no satisfactory medical treatment. A double-blind trial comparing Ginkgo biloba extract with a placebo was conducted in 10 out-patients at the Hospital Foch. Drug effectiveness was assessed on the results of fundoscopy and of measurements of visual acuity and visual field. In spite of the small population sample, a statistically significant improvement in long distance visual acuity was observed after treatment with Ginkgo biloba extract. The assumed pathogenesis of senile macular degeneration is discussed with emphasis on free oxygenated radicals." ²⁴

 

Ginkgo biloba (EGb761) extract was studied in 24 elderly patients with visual field disturbances in a randomized double blind trial. "The relative sensitivity of damaged retinal areas was more strongly influenced than ''healthy'' areas. The assessment by both doctors and patients of the general condition of the patients showed a significant improvement after the course of therapy. The results presented here show that damage to the visual field by chronic lack of blood flow are significantly reversible". ²⁵

 

"A randomized, placebo-controlled, double-blind, crossover study was run in 8 healthy, male subjects (mean age 27.3 +/- 2.6 years, mean BW 75.3 +/- 9.7 kg) to demonstrate a possible hypoxia-protective effect of standardized Ginkgo flavonglycosides after subchronical administration. …..Under cumulative exposure to hypoxic hypoxia fixation time of saccadic eye movements and complex choice reaction time were significantly improved by Ginkgo flavonglycosides vs placebo. These results could be explained as a hypoxia-protective phenomenon--supporting the therapy of cerebral insufficiency." ²⁶

 

Arteriosclerotic Disorders-

(see also Cerebral Vascular Insufficiency)

"24 patients suffering from arteriosclerotic disorders were divided into 2groups. One half received 250 ml NaCl with 25 ml Ginkgo-Biloba- extract the other 12 were treated with 250 ml NaCl without this substance. The collagen-induced platelet aggregation was determined before, immediately after infusion and on the next day. The platelet aggregation increased in both collectives after infusion. In the group treated with Ginkgo-Biloba-extract after 1 day values returned into normal range while the aggregation remained increased in the NaCl-group." ²⁷ (see also Alzheimer''s/Dementia/ Aging…..)

 

Asthma-

Ginkgo is being studied for possible usage in the treatment of asthma. Antioxidant flavonoids seem to inhibit histamine release and leukotriene production. ²⁸

 

" To determine the effects of Ginkgo leave concentrated oral liquor (GLC) on airway inflammation. Airway hyperreactivity and clinical symptoms and pulmonary functions of asthma patients were determined. In contrast to placebo group, GLC significantly reduced airway hyperreactivity (P < 0.05) and improved clinical symptoms (P < 0.05), pulmonary functions (P < 0.05) of the asthmatic patients." ²⁹

 

Equilibrium/Vertigo -

(see also Cerebral Vascular Insufficiency )

"This study, conducted in 3 centers, included 70 patients with vertiginous syndrome of recent onset and undetermined origin. In a double-blind trial extending over a 3-month period they were given either Ginkgo biloba extract or a placebo. The effectiveness of Ginkgo biloba extract on the intensity, frequency and duration of the disorder was statistically significant. At the end of the trial, 47 % of the patients treated were rid of their symptoms as against 18% of those who received the placebo". ³⁰

 

"Clinical and functional results of this therapy in a group of 70 patients complaining of vertigo. The Ginkgo biloba extract (4 ml/12 h per mouth) has been continued during 6 months. Neck and vertebrobasilar insufficiency were predominant causes. Six months later statistically significant changes regarding the decrease of intensity of tinnitus and vertigo crises were confirmed. Besides favorable alterations in the peripherical symptomatology as a relative hearing improvement turned up." ³¹

 

Depression -

Studies with animals have demonstrated that this herb may be effective the treatment of depression and aging. It has been demonstrated that Ginkgo biloba extract effects the reduction of serotonin receptors. In studies with older rats, serotonin receptor sites have shown up to a 33% increase. Studies with human patients have noted an increase in the patients outlook (see Clinical Studies - Alzheimer''s and Cerebral Vascular Insufficiency).

 

"From this general review of the pharmacological, psychopharmacological and clinical studies performed with Ginkgo biloba extract, the following conclusions can be drawn: The drug seems to be effective in patients with vascular disorders, in all types of dementia and even in patients suffering from cognitive disorders secondary to depression, because of its beneficial effects on mood. Of special concern are people who are just beginning to experience deterioration in their cognitive function. Ginkgo biloba extract might delay deterioration and enable these subjects to maintain a normal life and escape institutionalization. In addition, Ginkgo biloba extract appears to be a safe drug, being well tolerated, even in doses many times higher than those usually recommended." ³²

 

Impotence -

Due to it''s ability to increase micro-circulation (increase of blood flow through all arteries, veins, and capillaries but especially the peripherals), it has been suggested by that there is potential use of Ginkgo in the treatment of impotence. However, there are no clinical studies to date which supports this hypothesis.

 

Cerebral Vascular Insufficiency/Cerebral Edema/Cerebral Ischaemia -

Many studies have been conducted using Ginkgo biloba Standardized Extract for the treatment of cerebral vascular insufficiency. In most all of the studies conducted, Ginkgo was reported as having significantly reduced effects of cerebral vascular insufficiency s.c. as depression, vertigo, headaches, dizziness, short term memory-loss, and Tinnitus. In eight of these studies patients were given dosages from 120 to 160 mg for the duration of 4 through 12 months. Almost all the patients showed improvements in the areas of concern. ^33/34/38/39

 

To evaluate the effects and determine the mechanisms of action of Ginkgo biloba, numerous pharmacological studies have involved experiments using different pathologies of ischaemia at both cellular and molecular levels. It was found that Ginkgo extract reduced vascular, tissular, metabolic, neurological and behavioral disturbances. "The pharmacological effects of Ginkgo biloba extract concern vascular, rheological and metabolic processes. Several membrane mechanisms seem to be involved: protection of the membrane ultrastructure against free radicals, modulation of some enzymatic systems and ionic pumps." ³⁵

 

Ginkgo has been found to be a free radical scavenger and the special extract has positive effects on hemorheology and platelet aggregation, in addition to protection against hypoxia and ischaemia. It also possesses PAD antagonistic properties, "hampers an experimentally induced cerebral edema, has favorable properties on neurotransmitters and enhances cerebral bloodflow." ³⁶

 

Visco-elasticity of whole blood has been investigated and significant dose-dependent increases in microcirculation were found in a randomized open clinical trial involving 42 patients which "confirms the positive effect of EGb 761 on the microcirculation and whole-blood visco-elasticity in patients with pathological visco-elasticity values, already found in earlier studies, and shows it to be dependent on the dose employed." ³⁷ Dose-dependence, important in microcirculation was less marked in the case of visco-elasticity.

 

One study to determine the effect of Ginkgo biloba extract on the cerebral edema in rats intoxicated with triethyltin chloride (TET) found that the brains of TET-treated rats showed elevated water and sodium levels as well as a significant increase in the sodium/potassium ratio. These animals did not show water and electrolyte changes. "Thus, we conclude that this extract has a protective effect on the development of a cytotoxic edema in the white matter of the brain." ⁴⁰

 

Diabetes/Retinopathy-

Ginkgo biloba extract may be valuable in the treatment of visual impairment and pathological histology of the optic nerve in diabetics. A study evaluating its therapeutic role in the optic nerve in rats found that Ginkgo biloba extract entraps oxygenated free radicals, and is also a strong inhibitor of the platelet activation factor (PAF). "It was concluded that this extract could be encouraging for human clinical trials of diabetes." ⁴¹

 

Alterations usually associated with diabetic retinopathy are classical thickening of the basal membrane of retinal capillaries and associated modification of retinal vessel permeability. Several experimental studies establishing the participation of oxygenated free radicals have resulted in the conclusion that Ginkgo biloba extract (EGb 761) had free radical scavenging properties. "In conclusion, the authors discuss the possible utilization of a free radical scavenger, s.c. as EGb 761, in the prevention of the retinal impairment in diabetes." ⁴²

 

In another 6-month double-blind study involving 29 diabetic subjects with early diabetic retinopathy, an improvement tendency was evidenced in subjects treated with Ginkgo biloba extract, while those treated with placebo showed aggravation. The functional criterion was the color vision evolution, studied by the Desaturated Panel D-15 and the 100-Hue Farnsworth test at the beginning of the trial and 6 months later. Clinical results "on visual function corroborate the pharmacological actions of Ginkgo biloba extract on diabetic retina." ⁴³

 

"A neutral polysaccharide, named ukonan D, was isolated from the rhizome of Curcuma longa L. It produced a single band on electrophoresis and a single peak on gel chromatography, and its molecular mass was estimated to be 28, 000. It showed remarkable reticuloendothelial system-potentiating activity in a carbon clearance test". ⁴⁸

 

 

Hearing Loss/Cochlear Deafness/Tinnitus-

In a group of 80 patients having idiopathic sudden hearing loss for no more than 10-days a random reference-controlled study compared Ginkgo EGb 761 (Tebonin)+HAES to Naftidrofuryl (Dusodril)+HAES. It was found that while some patients developed side effects s.c. as orthostatic dysregulation or headache or sleep disturbances, 40% showed complete remission of hearing loss after one week. "Minimizing side effects should be one of the most important goals in therapy of sudden hearing loss until the efficiency of infusion therapy is proved." ⁴⁴

 

Although many treatments have been tried for the annoying and often debilitating condition of tinnitus, none has been consistently successful. A study was carried out involving a blind trial of laser therapy combined with doses of an extract of Ginkgo biloba (50 mg) in 2 groups of 20 patients, one experimental and one control. Only 20 of the 40 patients received real laser irradiation, whereas all 40 received the Ginkgo extract. It was found that 50% of the experimental group had a reduction in Tinnitus of more than10 dB, compared with 5% in the control group. The authors suggest that this combined photochemotherapy is a "promising treatment for Tinnitus." ⁴⁵

 

A 2-part Swedish study examined previous contradictory results of treatment of Tinnitus using Ginkgo biloba extract (GBE). Patients reporting a positive effect on Tinnitus in the open study (part 1) were included in the double-blind placebo-controlled study (part 2). Of 20 patients who had persistent severe Tinnitus, 7 preferred GBE to placebo, 7 placebo to GBE and 6 patients had no preference. This study concluded that "Statistical group analysis gives no support to the hypothesis that GBE has any effect on Tinnitus" and "Since there is no objective method to measure the symptom, the search for an effective drug can only be made on an individual basis." ⁴⁶

 

A double-blind therapeutic trial comparing Ginkgo biloba extract and a standard alpha blocker (nicergoline) in the treatment of cochlear deafness found that "a significant recovery was observed in both therapeutic groups, but improvement was distinctly better in the Ginkgo biloba group." ⁴⁷

 

Pneumocystis carinii-

"The sesquiterpene bilobalide, extracted from Ginkgo biloba leaves, was tested in vitro and in vivo for the ability to inhibit Pneumocystis carinii growth." ⁴⁸ Daily intraperitoneal administration of bilobalide lowered the number of organisms by 99% in pharmacologically immunosuppressed rats. "These studies suggest that the sesquiterpene bilobalide might be useful for therapy of and prophylaxis against P. carinii infections in humans." ⁴⁹

 

PMS-

From 165 patients having congestive symptoms of premenstrual syndrome (PMS), 143 observations were available in a controlled multicentric double blind study versus placebo to evaluate the effect of standardized Ginkgo biloba extract (EGb 761). "With a good acceptability, EGb 761 was effective against the congestive symptoms of PMS, particularly breast symptoms with a statistical significance between EGb 761 and placebo. Neuropsychological symptoms were also improved. EGb 761 is an alternative of interest to therapeutics already used in treating PMS or can be associated without any inconvenience." ⁵⁰

Peripheral Arterial Disease/Claudication-

EGb 761 improves perfusion peripherally as well as centrally. More than 15 European studies suggest a reduction of claudication symptoms in patients treated with EGb 761, including a 50% increase in pain-free walking distance. Simultaneous benefits on central and peripheral perfusion are demonstrated in a randomized, placebo-controlled trial among 44 Himalayan climbers. The 22 subjects treated with 160 mg/d of EGb 761 developed significantly fewer cerebral and respiratory symptoms of mountain sickness than climbers taking the placebo. EGb 761 also decreased vasomotor disorders of the extremities, measured by plethysmography and symptom scores. ^51/52

 

"Meta-analysis is considered as a statistical tool for quantitatively summarizing the results of clinical trials with comparable aims (treatments) and designs." ⁵³ It gives an estimate (and confidence interval) for the global effect of the treatment of interest, if homogeneity of the effects between the trials can be assumed. A treadmill exercise was quantified in 5 placebo-controlled clinical trials which showed that there was a mean increase in walking distance when taking Ginkgo biloba extract EGb 761 versus placebo. The conclusion was that "the meta-analysis revealed a highly significant therapeutic effect of EGb 761 for the treatment of peripheral arterial disease." ⁵³

 

A study involving (n=10) apparently healthy subjects showed that no significant changes in blood pressure or heart rate occurred when Ginkgo biloba was administered. Neither Ginkgo nor placebo influenced haematocrit, plasma viscosity, erythrocyte rigidity, thrombocyte and leukocyte count as well as thrombocyte aggregation and the number of circulating thrombocyte aggregates. However, a remarkable influence on erythrocyte aggregation was observed. The blood flow in the nail fold capillaries also increased significantly by about 57% after administration. ⁵⁴

 

GBE was shown to be active and significantly superior to placebo in a 6-month double-blind randomized clinical trial of Ginkgo biloba extract (GBE) as coated tablets versus placebo in two parallel groups suffering peripheral arteriopathy (Fontaine''s stage IIb). The results of the study showed improved pain-free walking distance, maximum walking distance and plethysmography recordings which "correlated with the physician''s and patients'' overall assessment of response to treatment." ⁵⁵

 

Visco-elasticity of whole blood has been investigated and significant dose-dependent increases in microcirculation were found in a randomized open clinical trial involving 42 patients which "confirms the positive effect of EGb 761 on the microcirculation and whole-blood visco-elasticity in patients with pathological visco-elasticity values, already found in earlier studies, and shows it to be dependent on the dose employed." ³⁷ Dose-dependence, important in microcirculation was less marked in the case of visco-elasticity.

 

In a group of 111 patients with peripheral occlusive arterial disease (POAD) in Fontaine stage IIb and intermittent claudication, prolongation of patients'' pain-free walking distance resulted from treatment with Ginkgo biloba special extract EGb 761 (Tebonin forte). This multicentric, randomized, placebo-controlled double-blind study confirmed the results of former clinical studies with EGb 761. "Tolerability was very good with no adverse events under EGb 761 and one case of heartburn and gastric pain in the placebo group. It can be concluded from the results of this study that treatment with EGb 761 in P.A. patients with Fontaine stage IIb is very safe and causes a significant and therapeutically relevant prolongation of the patients'' walking distance." ⁵⁶

 

Anti-Tumor Activity--

A study was done on the anti-tumor phenolic compounds (long-chain phenols) from Ginkgo biloba L. A quantitative structure-activity relationship was derived using the Hansch-Fujita equation with the aim of obtaining compounds with strong anti-tumor activity. "It was found that the activities mainly depended on log P (an optimum log P of 8.3) and a low-lying ELUMO value. 4- Undecylcatechol, selected on the basis of the above results, exhibited strong anti-tumor activity against Sarcoma 180 ascites and P- 388 lymphocytic leukemia." ⁵⁷

 

Anti-Oxidant/Radiation/Stress--

Ginkgo biloba extract "(EGb 761) appears to restore the age-related decreased capacity to adapt to a chronic stressor. ⁵⁸" Possible protective effects of EGb 761 on sub-chronic cold stress was studied in hippocampal 5-HTlA receptors in old isolated rats. It was found that "stress-induced desensitization of 5-HT1A receptors was prevented by the administration of EGb 761 (50 mg/kg per os/14 days). These results clearly indicate that 5-HT1A receptors are desensitized by stress and point out the reduced capacity of old rats to cope with the adverse effects of a chronic stressor." ⁵⁸

 

It has been shown that clastogenic factors occur in persons irradiated accidentally, and those under oxidative stress, and that CF-induced chromosome damage is prevented by superoxidase dismutase (SOD) which is not appropriate for long-term prophylactic treatment. This study evaluated the anticlastogenic effect of the Ginkgo biloba extract EGb 761, known for its superoxide scavenging properties. "Preliminary results obtained in a small series of liquidators showed regression or complete disappearance of CFs in the plasma after 2 months of treatment with EGb 761 (3 x 40 mg/d) ." ⁵⁹

 

An in-vitro study was done to compare the antioxidant potency of EGb 761 with a number of well-known antioxidants. Water-soluble ascorbic acid, glutathione and uric acid were studied as well as the lipid-soluble alpha-tocopherol and retinol acetate. It was found that all except ascorbic acid have antioxidant potential in a concentration-dependent manner. The antioxidant potency of EGb 761 appears to be comparable with that of alpha-tocopherol and retinol acetate, more effective than water-soluble antioxidants, and as effective as lipid-soluble antioxidants. ⁶⁰

 

A "clinical study was designed to evaluate, in 15 patients undergoing aortic valve replacement, whether the extent of CPB- and reperfusion-induced lipid peroxidation, ascorbate depletion, tissue necrosis, and cardiac dysfunction is reduced by orally administered EGb 761, a Ginkgo biloba extract with potent in vitro antiradical properties." Patients received either EGb 761 (Tanakan, 320 mg/day,n=8) or placebo for 5 days before surgical intervention. EGb 761 was found to decrease free radical levels. "Our results demonstrate the usefulness of adjuvant EGb 761 therapy in limiting oxidative stress in cardiovascular surgery and suggest the possible role of highly bioavailable terpene constituents of the drug." ⁶¹

 

Contact Dermatitis--

A double-blind versus placebo study using 22 subjects (Caucasian women aged 22-55 years) with allergic contact dermatitis from various substances used selected contact allergens from various substances in the European standard series. Following patch removal 68.2% showed significantly reduced skin reactivity on the treated site versus untreated and/or placebo sites. The findings indicate that "Ginkgo biloba/carboxymethyl-beta-1,3-glucan formulation can mitigate against allergic contact dermatitis." ⁶²

 

Copyright 1999 Rxlist - All rights reserved

Patients should be advised to inform their physician if they are taking or plan to take any prescription or over-the-counter blood thinning drug with this herb.

Patients should be advised to notify their physician if they become pregnant or intend to become pregnant during therapy.

Patients should be advised to notify their physician if they are breast feeding an infant and are using or intend to use this herb.

Patients should be advised to immediately stop usage if they develop a rash, hives, or edema.

Patients should be advised to stop usage if they experience nausea, vomiting, diarrhea.

Copyright 1999 Rxlist - All rights reserved