Ginkgo Biloba - Research:
Clinical pharmacology: Cerebral insufficiency
Cerebral insufficiency is an inexact term to describe a collection of symptoms associated with dementia (21, 22). In dementia owing to degeneration with neuronal loss and impaired neurotransmission, decline of intellectual function is associated with disturbances in the supply of oxygen and glucose. In clinical studies G. biloba effectively managed symptoms of cerebral insufficiency including difficulty in concentration and memory, absent-mindedness, confusion, lack of energy, tiredness, decreased physical performance, depressive mood, anxiety, dizziness, tinnitus, and headache (20–22). Several mechanisms of action of G. biloba have been described: effects on blood circulation such as the vasoregulating activity of arteries, capillaries, veins (increased blood flow); rheological effects (decreased viscosity, by PAF-receptor antagonism); metabolic changes such as increased tolerance to anoxia; beneficial influence on neurotransmitter disturbances; and prevention of damage to membranes by free radicals (22). Treatment of humans with G. biloba extract has been shown to improve global and local cerebral blood flow and microcirculation (74–76), to protect against hypoxia (77), to improve blood rheology, including inhibition of platelet aggregation (74, 78–81), to improve tissue metabolism (82), and to reduce capillary permeability (83).
A critical review of 40 published clinical trials (up to the end of 1990) using an orally administered G. biloba extract in the treatment of cerebral insufficiency concluded that only eight of the studies were well performed (21, 22). Almost all trials reported at least a partially positive response at dosages of 120–160mg a day (standardized extract) and treatment for at least 4–6 weeks (21, 22). In a comparison of G. biloba with published trials using co-dergocrine (dihydroergotoxine), a mixture of ergoloid mesilates used for the same purpose, both G. biloba extract and co-dergocrine showed similar efficacy. A direct comparison of 120mg of G. biloba standardized extract and 4.5mg codergocrine showed similar improvements in both groups after 6 weeks (84).
A meta-analysis of 11 placebo-controlled, randomized double-blind studies in elderly patients given G. biloba extract (150 mg orally per day) for cerebral insufficiency concluded that eight studies were well performed (85). Significant differences were found for all analysed single symptoms, indicating the superiority of the drug in comparison with the placebo. Analysis of the total score of clinical symptoms indicated that seven studies confirmed the effectiveness of G. biloba extract, while one study was inconclusive (85).
Peripheral arterial occlusive disease
The effectiveness of G. biloba extract in the treatment of intermittent claudication (peripheral arterial occlusive disease Fontaine stage II), as compared with a placebo, was demonstrated in placebo-controlled, double-blind clinical trials by a statistically significant increase in walking distance (1, 23, 24). Sixty patients with peripheral arterial occlusive disease in Fontaine stage IIb who were treated with the drug (120–160mg for 24 weeks) and underwent physical training also clearly increased their walking distance (25).
Out of 15 controlled trials (up to the end of 1990) only two (23, 24) were of acceptable quality (22–24). The results of both studies were positive and showed an increase in walking distance in patients with intermittent claudication after 6 months (23), and an improvement of pain at rest in patients treated with 200 mg of G. biloba extract for 8 weeks (24).
After meta-analysis of five placebo-controlled clinical trials (up to the end of 1991) of G. biloba extract in patients with peripheral arterial disease, investigators concluded that the extract exerted a highly significant therapeutic effect (26).
Vertigo and tinnitus
Ginkgo biloba extracts have been used clinically in the treatment of inner ear disorders such as hearing loss, vertigo, and tinnitus. In a placebo-controlled, double-blind study of 68 patients with vertiginous syndrome of recent onset, treatment with G. biloba extract (120–160mg daily, for 4–12 weeks) produced a statistically significant improvement as compared with the placebo group (27).
The results of clinical studies on the treatment of tinnitus have been contradictory. At least six clinical studies have assessed the effectiveness of G. biloba extract for the treatment of tinnitus. Three studies reported positive results (86, 87, 88). One multicentre, randomized, double-blind, 13-month study of 103 patients with tinnitus showed that all patients improved, irrespective of the prognostic factor, when treated with G. biloba extract (160mg/day for 3 months) (86). Three other clinical trials reported negative outcomes (89–91). Statistical analysis of an open study (80 patients) without placebo, coupled with a double-blind, placebo-controlled part (21 patients), demonstrated that a concentrated G. biloba extract (29.2 mg/day for 2 weeks) had no effect on tinnitus (91).
References:
20. German Commission E monograph, Trockenextrakt (35–67: 1) aus Ginkgo-biloba- Blättern Extrakt mit Aceton-Wasser. Bundesanzeiger, 1994, 46:7361–7362.
21. Kleijnen J, Knipschild P. Ginkgo biloba. Lancet, 1992, 340:1136–1139.
22. Kleijnen J, Knipschild P. Ginkgo biloba for cerebral insufficiency. British journal of clinical pharmacology, 1992, 34:352–358.
23. Bauer U. Six month double-blind randomized clinical trial of Ginkgo biloba extract versus placebo in two parallel groups in patients suffering from peripheral arterial insufficiency. Arzneimittel-Forschung, 1984, 34:716–720.
24. Saudreau F, Serise JM, Pillet J. Efficacité de l'extrait de Ginkgo biloba dans le traitement des artériopathies obliterantes chroniques des membres inferieurs au stade III de la classification de Fontaine. Journal malade vasculare, 1989, 14:177– 182.
25. Blume J et al. Placebokontrollierte Doppelblindstudie zur Wirksamkeit von Ginkgo biloba-Spezialextrakt EGb 761 bei austrainierten Patienten mit Claudicatio intermittens. VASA, 1996, 2:1–11.
26. Schneider B. Ginkgo biloba Extrakt bei peripheren arteriellen Verschlußkrankheiten. Arzneimittel-Forschung, 1992, 42:428–436.
27. Haguenauer JP et al. Traitement des troubles de l'equilibre par l'extrait de Ginkgo biloba. Presse medicale, 1986, 15:1569–1572.
74. Költringer P et al. Die Mikrozirkulation und Viskoelastizität des Vollblutes unter Ginkgo biloba extrakt. Eine plazebokontrollierte, randomisierte Doppelblind-Studie. Perfusion, 1989, 1:28–30.
75. Költringer P et al. Mikrozirkulation unter parenteraler Ginkgo biloba Extrakt- Therapie. Wiener Medizinische Wochenschrift, 1989, 101:198–200.
76. Jung F et al. Effect of Ginkgo biloba on fluidity of blood and peripheral microcirculation in volunteers. Arzneimittel-Forschung, 1990, 40:589–593.
77. Schaffler K, Reeh PW. Doppelblindstudie zur hypoxieprotektiven Wirkung eines standardisierten Ginkgo-biloba-Präparates nach Mehrfachverabreichung an gesunden Probanden. Arzneimittel-Forschung, 1985, 35:1283–1286.
78. Hofferberth B. Simultanerfassung elektrophysiologischer, psychometrischer und rheologischer Parameter bei Patienten mit hirnorganischem Psychosyndrom und erhöhtem Gefässrisiko-Eine Placebo-kontrollierte Doppelblindstudie mit Ginkgo biloba-Extrakt EGB 761. In: Stodtmeister R, Pillunat LE, eds. Mikrozirkulation in Gehirn und Sinnesorganen. Stuttgart, Ferdinand Enke, 1991:64–74.
79. Witte S. Therapeutical aspects of Ginkgo biloba flavone glucosides in the context of increased blood viscosity. Clinical hemorheology, 1989, 9:323–326.
80. Artmann GM, Schikarski C. Ginkgo biloba extract (EGb 761) protects red blood cells from oxidative damage. Clinical hemorheology, 1993, 13:529–539.
81. Ernst E, Marshall M. Der Effekt von Ginkgo-biloba-Spezialextrakt EGb 761 auf die Leukozytenfilterabilität-Eine Pilotstudie. Perfusion, 1992, 8:241–244.
82. Rudofsky G. Wirkung von Ginkgo-biloba-extrakt bei arterieller Verschlusskrankheit. Fortschritte der Medizin, 1987, 105:397–400.
83. Lagrue G, et al. Oedèmes cycliques idiopathiques. Rôle de l'hyperperméabilité capillaire et correction par l'extrait de Ginkgo biloba. Presse médicale, 1986, 15:1550– 1553.
84. Gerhardt G, Rogalla K, Jaeger J. Medikamentöse Therapie von Hirnleistungsstörungen. Randomisierte Vergleichsstudie mit Dihydroergotoxin und Ginkgo biloba- Extrakt. Fortschritte der Medizin, 1990, 108:384–388.
85. Hopfenmüller W. Nachweis der therapeutischen Wirksamkeit eines Ginkgo biloba Spezialextraktes. Arzneimittel-Forschung, 1994, 44:1005–1013.
86. Meyer B. Etude multicentrique randomisée a double insu face au placebo du traitement des acouphènes par l'extrait de Ginkgo biloba. Presse medicale, 1986, 15:1562–1564.
87. Sprenger FH. Gute Therapieergebnisse mit Ginkgo biloba. Ärztliche Praxis,1986, 12:938–940.
88. Witt U. Low power laser und Ginkgo-Extrakte als Kombinationstherapie. Hamburg, Germany (unpublished document; available through NAPRALERT.
89. Coles RRA. Trial of an extract of Ginkgo biloba (EGB) for tinnitus and hearing loss. Clinical otolaryngology, 1988, 13:501–504.
90. Fucci JM et al. Effects of Ginkgo biloba extract on tinnitus: a double blind study. St. Petersberg, FL, Association for Research in Otolaryngology, 1991.
91. Holgers KM, Axelson A, Pringle I. Ginkgo biloba extract for the treatment of tinnitus. Audiology, 1994, 33:85–92.
Source: WHO Monographs 1999- 2010
