Ginkgo biloba - Ginkgo

Description

Considered the oldest surviving tree species (200 million years), ginkgo is termed a living fossil. An individual tree can live 1,000 years, growing to a height of 30 - 40 m and 1 - 1.5 m in diameter. Its unique leaves are prominent features, fan-like with two lobes (biloba = two-lobed). This medium-sized tree is dioecious, having distinct male and female trees. The leaves are long-petioled (stems), two lobed, with forked veins radiating from the petiole end. The leaves turn yellow and shed in the fall. In Chinese philosophy the unique leaf was considered by the Taoists to represent unity within duality. The fruit, or nut, is yellow with a woody stone. It is no longer found in the wild but is prominent in temples throughout Asia. It was imported to Europe in 1730 as it grows well in temperate climates. It is seen along gardens, street and city parks in Europe as it can handle city pollution quite well. It is believed to be able to clean up pollution where it lives.

Constituents

The most active ingredients are terpenoid flavonglycosides (ginkgolide A,B,C,J,M), the ginkgolides differ in number and position of -OH group present on C1, C3 and/or C7 of a spirononame framework. Ginkgo also contains other flavonoids such as quercetin, luteolin, kaempferols, catechins ( catechin, epicatechin and others), proanthocyanidins ( procyanidin and prodelphinidin). We also find lactones, ligins, steroids (sitosterol, ipuranol), starches, alkanes, alcohol and organic acids.(1-5) This herb it often standardized to 24% flavonglycoside (10% of which should be quercetin) and 6% terpene ginkgolides.(6) This extract is often called Ginkgo biloba extract or Gbx.

Mode of Action

During the last three decades of research on the plant, oral administration of the extract (Gbx) has been shown to have many physiological effects. Because of the high flavonoid content, the first focus of scientific study was the human vascular system. In several studies Gbx protected the body from arterial blockage, while increasing levels of glucose and ATP at the cellular level to maintain the energy level of individual cells that might be affected.(7-10) By stabilizing the blood brain barrier (BBB) Gbx lowers swelling (edema) in the brain, one of the most significant causes of aging. This stabilization is direct, through action on the ionic potential across the membranes, and indirectly, through action on intracellular (mitochondrial) respiration.(11) The reduction of the edema also decreases complications, toxic buildup, ionic exchange problems and the neurological consequences.(12) It can also modulate cerebral energy metabolism.(13)

Ginkgo has been shown to have an inhibitory effect on platelet aggregation(14) and neutralizes free radicals, inhibiting lipid peroxidation of membranes, thus helping to maintain integrity and permeability of cell walls.(15) Quercitin and ginkgolide B seems to be the most likely constituent candidates for causing these effects. It has been shown to have a great ability to protect the heart, blood vessels and brain against the destructive influence of free radicals.(16) The free radical inhibition of Gbx not only destroys the free radicals but stops their formation and membrane pre-oxidation. In this process, Gbx has been shown to increase beneficial prostaglandins. In these studies, cellular damage caused by free radical destruction of the retina in diabetic individuals was inhibited by Gbx.(17) It was also found to oxygenate senile macular degeneration.(18) Gbx has also afforded protection against laser-induced lesions of the retinal cells.(19) On the neurological level, Gbx produces a significant increase in dopamine synthesis (a critical neurotransmitter)(20) and inhibits histamine by influencing the muscular receptor sites.(21) Gbx stimulates the release of the catecholamine neurotransmitters (epinephrine and norepinephrine).(22) Thus it has a profound effect on the glandular, cardiovascular and nervous systems. Further studies in this area have enriched scientific knowledge of the feedback and regulatory role of Gbx.(23-25)

Gbx has been found to ``reactivate`` norepinephrine and the beta-receptors, producing among other things, dilation of airways in the lungs, dilation of peripheral blood vessels (muscular circulation). We thus find Ginkgo a beneficial antiasthmatic and bronchodialtor. This whole physiological system is said to lose vigor during aging, triggering symptoms of memory loss, speech defects and decreased alertness. Gbx has been shown to aid in regulating and invigorating these areas.(26) By increasing peripheral circulation it has been shown successful in treating intermittent claudication.(27)

Oral use of Gbx has been shown to significantly increase the number of cholinergic receptor sites in the brain.(28) This makes the major neural transmission system in the brain work better. The following activities have been discovered from this research.(29,30)
- A direct action on both arteries and veins to increase blood supply to the brain.
- Stimulation of neurotransmitter release into the synapse.
- Inhibition of enzymatic breakdown of neurotransmitters.
- Stimulation of the release of endogenous relaxing factors in the arterial endothelium (such as prostacyclin EDRF).
- reduced depression

Animal and in vitro models are not only validated by clinical studies on humans, but the results give great hope for Ginkgo`s long term clinical use. In persons recovering from blood clots in the arteries of the heart, Gbx was found to lower blood pressure and dilate peripheral blood vessels, including the capillaries.(31) Reliability was great.(32)

In clinical studies on the elderly, Gingko has been shown to increase capillary and venous blood flow to the head with a resulting decreased resistance to flow. This flow was not accompanied by hypotension or any appreciable variation in blood pressure — all too commonly found with many pharmaceutical drugs.(33,34) Gbx regulatory action combated disturbances resulting from vascular spasm and restored tone to circulatory areas subject to vascular paralysis.(35) These effects were gained by increasing peripheral circulation while not reducing cerebral circulation. Even in elderly patients 62-86 years old, with inadequate blood flow to their brain due to age and arteriosclerosis, 15 out of 20 patients showed improvement over a period as short as two weeks.(36) In longer statistically-significant studies, (described by the authors as clinical remarkable) the results were confirmed with the use of Gbx.(37) There have been many clinical studies related to Gbx`s effect on vascularity. Results of several (primarily double blind placebo control trials) are as follows:

- 65% successful treatment of 30 patients with focal or diffuse cerebral vascular disease.(38)
- 80% success in 47 patients with cerebral insufficiency as measured by mental improvement, EEG, cerebral angiograms.(39)
- 80-92% success with chronic cerebral insufficiency.(40,41)
- 80% success in headache treatment with long term use.(42)
- 23 of 30 cases of dystrophy from venous insufficiency complication of varicose disease improved.(43)
- 40% success in treating 49 elderly patients with insufficiency in arterial flow to the lower limbs with complication of senile diabetes mellitus.(44)
- 72-82% success in toning the arterioles to produce vasodilation in chronic vasculopathies.(45,46)

Ginkgo biloba extract has seen success in treatment of disturbances of the inner ear. In several studies 40-74% improvement was reported for patients with persistent ringing in the ears, vertigo and hearing loss.(47,48,49) Another study reported a 88% success rate with 49 patients suffering from various problems including hearing loss, ringing, vertigo and labyrinthinitis.(50) Studies done strictly on vertigo have had an approximately 50% success rate.(51,52) Hemorrhoids have been successfully treated by the oral use of Gbx. Up to 86% of patients reported halted bleeding and pain. Less effectiveness was noted for anal fissures.(53,54) Improvement in erection has been shown in men with previous dysfunction of erectile impotence.(55,56) At doses of 120 mg daily, mental behavior has been significantly improved in elderly patients who originally had problems with alertness.(57) Even in young healthy girls, benefits were found at a 600 mg dose of Gbx daily.(58) The girls improved results on a test when consuming Gbx one hour before the test.(59) Alertness was shown to increase, and corresponding EEG readings improved in elderly people with dementia disorders.(60)

Gbx has undergone one long term study showing that not only does improvement continue but patients that show little improvement in short term studies showed improvement.(61) It is obvious that studies of Gbx on Alzheimer patients was essential. There have been several successful studies in this area including one release in a JAMA issue dedicated to the theme of aging. In this study it showed that twice as many Alzheimer patients showed improvements in ADAS Cog. score of 4 points, while taking Gbx, as compared to control group.(62) Although it is hard to really even define Alzheimer`s disease for research purposes, preliminary and ongoing studies in this area have had some exciting results.(63,64) Improvements (sometime only modest), in walking ability, visual acuity, hearing, equilibrium, mood, EEG readings and other subjective measures have all shown improvement.(65,66)

Therapeutic Action

Stimulant, astringent, nervine.

Energetics

Traditional Chinese,

The nut of ginkgo is sweet, bitter, astringent and neutral but slightly poisonous. It enters the Lung and Kidney meridians. It expels phlegm, stops discharges, stabilizes the lower burners and stops wheezing.(67-69)

Folklore

History and folklore are almost inseparable with this plant. It is often called ``the doyenne of trees``, because of its antiquity.(70) Ginkgo is extremely resistant to all kinds of pollution, virus and fungi, and was therefore extensively planted throughout Asia and later Europe. The nuts (kernels) of ginkgo have been used medicinally since the Household Materia Medica of China (1350 A.D.) with a substantial folklore.

Modern Western use is limited to the leaf only, usually in an extract form. The extract is somewhat different than most herbs. It really has no folklore. Modern usage started in the 1970`s with a large body of scientific literature assembled in a short period of time. Ginkgo`s main use can be said to be extending the functional life of many people. A herb of longevity from a living fossil tree.

Dosage

There seems to be no standard dosage as yet. Studies have been conducted from 40 - 600 mg daily of the 24% flavoglycosides and 6% terpenes. A common dosage is 120 mg, twice a day of Gbx. There seems to be little effect of straight tinctures.

Toxicity and Contraindications

There have been extensive toxicity studies on this herb. Virtually none was found. Even large doses during long term use showed no toxicity and no change in hormonal or blood assays.(71) There have been a very low incidence of stomach or intestinal upset, headaches or allergic skin reaction.(72)

Official Recognition and Medical References

Germany Commission E, p. 136 - 38
PDR p. 871-873
France Approved as an non-prescription drug
USA Dietary Supplement
China Pharmacopeia, non-prescription drug

References

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6. Mowrey, D.,Ibid.
7. Larsen R.G. Dupeyron et al; Modele d`eschemie cerbrale experimentale par microspheres chez le rat. Etude l`effect de deux extraits de ginkgo biloba et du
naftidrofuril; Therapie,, 1978, p. 33, 651.
8. Rapin, J.R., Le poncin-Lafitte, M; Modele experimental d`ischemie cerebrale. Action preventive de l`extrait de ginkgo; Sem. Hop Paris, p. 55, 2047, 1979.
9. Le Ponin-Lafitte, M, et al; Effects of ginkgo biloba on changes induced by quantitative cerebral microembolization in rats; Arch. Int. Pharmacodyn. p. 243,236, 1980.
10. Rapin, J.R. et al; Consonsommation cerebrale du glucose. Effect de l`extrait de ginkgo biloba; Press Med 15(31), p. 1494-7, 1986.
11. Spinnewyn B, Blavet, N. et al; Effects de l`extrait de ginkgo biloba sure un modele d`ischemie cerebrale chez la gerbille; Press Med., 15(31, p. 1511, 1986.
12. Etienne, A, Hecquet, F et al; Mecanismes d`action de l`extrait de ginkgo biloba sure l`oedeme cerebral experimental; Press Med., 15 (31, p. 1506-10, 1986.
13. Chatterjee, S.S., Agnoli, A., et al ed.; Effect of Ginkgo Biloba Extract on Organic Cerebral Impairment, John Libbery Eurotext; London, 1985.
14. Brorzeix, M.G. et al; Researches sure l`action antiagregant de l`extract de
ginkgo biloba. Activite au niveau des arteres et de veines de la pie-mere chez le lapin; Arch. Int Pharmacodyn., p. 243,236, 1980.
15. Pincemail,J., Deby C.; Proprietes antiradicalaires de l`extract de ginkgo biloba; Press Med 15(31), p. 1475-9, 1986.
16. Brunello, N., Ralagni, G., et al, Effect of an extract of Ginkgo biloba on noradrenergic systems of rat cerebral cortex, Pharm. Res. com 17, 1985, p.1063-1072.
17. Doly, M, Droy-Lefaix M.T. et al; Effect de l`extrait de ginkgo biloba sur l`electrophysiologies de la retine isolee de rat diabetique; Press Med., 15(31) 1480-31986.
18. Lebuissen D.A., et al; Traitemaent des degenerescences maculaires senile par l`extrait de ginkgo biloba. Etude preliminaire a double insuface au placebo; Press Med 15(31), 1556-8, 1986.
19. Clairambault P., et al; Effect de l`extrait de ginkgo biloba sur les lesions induites par une photocoagulation au laser a l`argon sur la retine de lapin; Sem Hop. Paris
62, 57, 1986.
20. Le Poncin-Lafitte, M., et al; Ischemie cerebrale apres ligature non stimultanee de arteres carotide chez le rat: effect de l`extrait de ginkgo biloba; Sem. Hop Paris, 58, 403, 1982.
21. Vilain, B., et al; Effecr of an extract of ginkgo biloba on the illeum of guinea-pigs; Gen Pharmac. 13, 225, 1982.
22. Auguet, M., et al; Effect of an extract of ginkgo biloba on rabbit isolated aorta, Gen Pharmac, 13, 225, 1982.
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24. Auguet, M., et al; Effect on an extract of ginkgo biloba and diverse substances on the phasic and tonic components of the contraction of an isolated rabbit aorta; Gen Pharmarc, 14, 277, 1983.
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26. Mowrey, D., Ibid.
27. Blumenthal, M., (ed.) et al., The Complete German Commission E Monographs: Therapeutic Guide to Herbal Medicines, American Botanical Council, Austin, TX, 1998, p. 137
28. Taylor, J.E.; Liasions des neuromediateur a leur recepteurs dans le cerveau de rats. Effect de l`administration chronique de l`extrait de ginkgo biloba; Press Med., 15(31), 1491-3, 1986.
29. Auguet, M., et al; Bases pharmacologuques de l`impact vasculaire de l`extrait de ginkgo biloba; Press Med., 15(31), 1524-8, 1986.
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31. Trounier, H.; Klinish-pharmakologische untersuchungen ueber den effect eines extraktes aus ginkgo biloba beim post thrombotischen syndrom; Arzneimittel Forschung, 18, 551, 1968.
32. Gautherie, M. et al; Effect vasodilateur de l`extrait de ginkgo biloba mesure part thermometrie et thermographie cutanees; Therapie, 27, 881, 1972.
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35. Auguet, M., et al, Ibid. 1986.
36. Galley, et al; Tanakan et cerveau se-nile. Etude radiocirculagraphique; Bordeaux Med, 10, 171, 1977.
37. 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; Arzeimittal Forschung, 34, 716, 1984.
38. Montanni, R., et al; Impiego di un estratto di ginkgo biloba (TEBONIN) nella terrapia delle vasculopatie cerebraili; Min Card., 17, 1096, 1969.
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40. Moreau; Un nouveau stimulant circulatoiere cerebral; Nouv. Press Med., 4, 2401,1975.
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44. Locatelli, G.R., et al; Effetto del tebonin (estrtto delle foglei di ginkgo biloba) nel trattamentto dell`arteriopatia periferica senile; Min. Card, 17, 1103, 1969.
45. Sorbini, E.; La gikgo biloba nella terapia vascolare; Minerva Med., 64, 4201, 1973.
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47. Moreau,Ibid, 1975.
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49. Natalie, R., et al; Le tanakan dans les syndromes cochleovestibulaierea relevant d`une etiologie vasculaiere. Traitement de long cours; Gaz. Med. France, 86, 1381,1979.
50. Montanini, R., Ibid., 1969.
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52. Metyer, B.; Etude multicentrique randomisee a double insuface au placeba du traitement des acouphenes par l`extrait de ginkgo bilobal; Press Med, 15(31),1562-4, 1986.
53. Parnaud, E.; Ginkor en protologie courant. A propos de 36 observations; theraroidaires, Med. Chir. Dig., 3, 437, 1974.
54. Soullard, J., et al; Experimentation du ginkor en protogie; Sem Hop Paris, 54, 1177, 1978.
55. Sikora, R., et al, Ginkgo biloba extract in therapy of erectile dysfunction; J. of Urology 141:188A 1989.
56. Sohn, M. and Sikora, R.; Ginkgo biloba extract in therapy of erectile dysfunction; J. Sex Edu. Ther. 17;53-61, 1991.
57. Gesser, B., et al; Study of the long-term action of a ginkgo biloba extract on vigilance and mental performance as determined by means of quantitaive pharmaco- EEG and psychometric. measurements; Arzneimittel-Forschung, 35(9), 1459, 1985
58. Hindmarch, I., et al; Activite de l`extract de ginkgo biloba sur la memoire a court terme; Press-Med. 15(31), 1592-4, 1986.
59. Mowrey, D., Ibid
60. Pidoux, B.; Effect sure l`activite fonctionnelle cerebrale de l`extrait de ginkgo biloba. Bilan d`etudes clinques et experimentales; Press Med., 15(13), 1588-91,1986.
61. Taillandier, J., et al; Traitment des trouble du vieillisswment cerebral par l`extrait de ginkgo biloba; Press Med., 15(31), 1540-5, 1986.
62. LeBar, P.L., et al; Gingko Extract Improves Cognitive and Social Function in Subset of Demented Patient; JAMA 278:1327-32 1997.
63. Clostre, F.; De l`organisme aux membranes cellulaire; les differents niveax
pharmacologiques de l`extract de ginkgo biloba; Press Med., 15(31), 1526-38, 1986.
64. Allard, M.; Traitment des troubles du vieillissemebnt par extrait de ginkgo biloba;Press Med, 15(31, 1540-5, 1986.
65. Kaye, J.A., et al; Gikgo worth investigating further for Alzheimer`s diseas; Arch Neurol; 55:1409-1415.
66. Kanowski, W.M., Herrmann, K.S., Wierich, W., et al; Proof of Efficacy of Ginkgo biloba Extract in Outpatient Suffering from Mild to Moderate Primary Degenerative Dementia of the Alzheimer Type or Multi-infarct Dementia; Phytomedicine, Vol. 4(1), p. 3-13, 1997.
67. Hsu Hong-yen, Chen Yuh-Pan, et al; Oriental Materia Medica: A Concise Guide; Oriental Healing Arts Institute; Long Beach, CA.; p. 610-11, 1986.
68. Bensky, D., Gamble, A.; Chinese Herbal Medicine:Materia Medica; Eastland Press Seattle; p. 560-61, 1986.
69. Tierra, M.; Planetary Herbology; Lotus Press; Santa Fe; p. 345. 1988,
70. Michek, P.F.; Le doyen des arbres: le ginkgo biloba; Press Med., 15(31) 1450-4, 1986.
71. Felber, J.P.; Effect de l`extract de ginkgo biloba sure les parametres biologiques endocrine; Press Med., 15(13), 1573-4, 1986.
72. Blumenthal, M. (ed.) et al., The Complete German Commission E Monographs: Therapeutic Guide to Herbal Medicines, Ibid.