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Ginkgo Fails to Enhance Memory in Short-Term Trial

November 2002

Mitochondrial antioxidant

According to the free radical theory of aging, oxygen-derived free radicals are responsible for the age-associated decline in cellular function. Mitochondria have recently been shown to play a key role in cellular aging since these "energy factories" of the cell are major targets for free radical attack. Mitochondrial DNA (mtDNA) is particularly vulnerable and accumulates genetic damage over time. There is abundant experimental evidence that oxidative damage to mtDNA accumulates within both liver and brain mitochondria.

Ginkgo biloba extract is a potent antioxidant and scavenger of most free radical species, such as hydroxyl and peroxyl radicals and superoxide anions, which is likely to enhance its wide-ranging therapeutic benefits. It is known to protect the energy-producing mitochondria within the cells,24 thus enhancing oxygen utilization and cellular respiration.

The aim of an experimental study by Sastre et al.25 was to test whether ginkgo extract could prevent age-associated changes in mitochondria and, if so, to determine whether this effect was due to protection against oxidative stress. In this study, the brain and liver mitochondria of old mice fed ginkgo extract in their drinking water was compared to those of young and old control mice.

The results confirmed that ginkgo prevents age-related changes in mitochondria. Mitochondria from the rats given ginkgo exhibited significantly less genetic damage, peroxide generation and oxidation of the crucial antioxidant glutathione than the untreated old rats. In addition, mitochondria from the old rats given the ginkgo extract resembled those of the young rats much more closely, being similar in size and morphology. The study concluded that standardized ginkgo extract prevents age-related decline in mitochondrial structure and function by protecting mitochondria from oxidative damage.

Membrane-stabilizing activities are also important in the prevention of cell damage and aging, as the health and stability of cell membranes are crucial to the function of the cell. The membranes are vulnerable to lipid peroxidation induced by free radicals.

Oxygen deprivation produces free radicals that can overwhelm the body's own free radical scavengers, such as superoxide dismutase (SOD) and glutathione peroxidase. This leads to peroxidation and damage of membrane lipids. PAF (platelet-activating factor), which also accumulates in the brain during ischemia, stimulates production of additional free radicals. The reperfusion stage, when blood comes back to the oxygen-deprived area, has been shown to cause even more cell damage due to increased lipid peroxidation.

Medicinal Use

Since the 1960s, standardized ginkgo leaf extract has been used in research and clinical studies throughout the world. Laboratory research and clinical studies over the past three decades have validated the ancient use of the ginkgo tree as a medicinal remedy. Ginkgo biloba extract has demonstrated effectiveness in improving circulation, particularly in the brain. It is a registered drug in Germany where its major therapeutic applications are "cerebral insufficiency," degenerative dementia, such as Alzheimer's disease, neurosensory problems (e.g. ringing ears, dizziness and impaired vision) and peripheral circulatory disturbances (e.g. leg cramps). It has also been found to be useful in a variety of other conditions, such as impotence due to impaired blood circulation, and fluid retention and breast tenderness in premenstrual syndrome (PMS). Ginkgo is also known to prevent damage from radiation exposure (tested in Chernobyl) and has demonstrated exceptional effectiveness in preventing acute mountain sickness and vascular reactivity to cold exposure and high altitudes.* Besides being used as a prescription drug in Europe, ginkgo is also sold over the counter in lower dosages and used in the prevention of various symptoms of aging, such as decline of hearing, vision and memory.

Roncin JP, Schwartz F, D'Arbigny P. EGb 761 in control of acute mountain sickness and vascular reactivity to cold exposure. Aviat Space Environ Med 1996;May;67(5):445-52.

Preventing brain damage from lack of oxygen

Brain cells are more susceptible to free radical damage than other cells because their membranes have a higher content of unsaturated fatty acids (phospholipids) and are particularly vulnerable to peroxidation.

Brain cells are also more susceptible to hypoxia (cerebral ischemia) than any other cells. They require large amounts of energy to function, and when blood supply is restricted there is not enough oxygen and glucose for membrane function and energy production. The result is usually a variety of metabolic changes, such as acidosis, electrolyte shifts, free radical production and increased release of free fatty acids, prostaglandins and neurotransmitters.

Ginkgo extract has shown a remarkable ability to prevent such metabolic disturbances in experimental studies of insufficient oxygen supply to the brain.26

An interesting study on the biochemical events in the rat brain after ischemia27 suggests that lack of oxygen alone cannot initiate peroxidation. This process requires restoration of oxygen supply. It is therefore concluded that the more severe brain damage happens during the reperfusion phase (restoration of circulation) after ischemia. It was shown that administration of ginkgo extract before the ischemic injury prevented reduction of SOD activity and reduced lipid peroxide contents of the mitochondria in the rat brain. This was a clear indicator of the extract's protective effect against post-ischemic injury due to free radical production.

Ginkgo Is A Multi-Component Extract

Ginkgo leaf extract is a complex mixture containing substances with several active components: flavone glycosides (flavonoids with attached sugar molecules unique to ginkgo), terpenes (Ginkgolides and bilobalides), and organic acids. Flavonoids are a group of substances common in the plant kingdom, occurring as pigments in flowers and fruits. They have a wide range of biochemical functions as antioxidants, free radical scavengers, enzyme inhibitors, enzyme inducers and more. Flavonoids are known to make vitamin C more effective, to increase the strength of capillary walls, and to improve microcirculation. The three major flavonoids in ginkgo are quercitin, kaempferol and isorhamnetine. In addition there are some proanthocyanidins, which can also be found in grape seed, pine bark and bilberry extract. The bilobalides and Ginkgolides have not been found in any other plants. Their unique molecular structure was discovered by the Japanese chemist Nakanishi in 1966, and it has so far been impossible to synthesize them in the lab. The range of their biochemical actions include anti-aggregatory blood platelet activity and reduction of blood viscosity.

Additional neuroprotective actions

A condition common to many chronic and acute neurological disorders is excitotoxicity-oversensitivity of neurons to the excitatory neurotransmitter glutamate. A series of laboratory experiments28-30 suggests that ginkgo extract can protect neurons from excitotoxicity, preventing glutamate-induced calcium influx leading to cell death.

A study31 showed the protective effect of ginkgo extract on mice injected with a neurotoxin known as MPTP. This neurotoxin brings about a close approximation of Parkinson's disease in humans, monkeys and mice. When the mice were pretreated with ginkgo, the neurotoxicity of MPTP was prevented in a dose-dependent manner.

MPTP selectively damages the dopamine system in the nigrostriatal region affected by Parkinson's disease. When the mice were treated with ginkgo extract after exposure to the toxin, dopamine levels recovered more rapidly. Other studies have shown that ginkgo improves dopamine uptake under conditions of oxidative stress.

Brain metabolism generates hydrogen peroxide, a cytotoxic agent that generates oxidative stress in the brain, contributes to cerebral injury and edema following ischemia, and causes programmed cell death (apoptosis) in cortical neurons (nerve cells). Hydrogen peroxide damages DNA and oxidizes lipids and proteins through reactions that have not been entirely clarified but are thought to involve iron and copper ions.

Interesting studies by Oyama et al.32 and Ni et al.33 demonstrated that ginkgo extract is able to protect neurons from oxidative stress induced by hydrogen peroxide. When neurons were treated with ginkgo extract for one hour before adding hydrogen peroxide, it was highly effective in protecting nerve cells from damage and death.

One study suggests that hydrogen peroxide activates nuclear factor kappa beta in bovine endothelial cells, thus contributing to atherosclerosis, and demonstrates that ginkgo extract blocks this activation.34

Preventing abnormal blood clotting

Another interesting action of ginkgo extract is its inhibition of platelet aggregation and adhesion, which may reduce the risk of thrombus formation. This effect is at least partly exerted by the Ginkgolide terpenes in the extract, which have been shown to be potent inhibitors of platelet-activating factor (PAF). Platelet-activating factor is known to be involved in many inflammatory and allergic processes including bronchial constriction, besides being an activator of platelet aggregation and release of inflammatory components.

A stress antidote

Imagine the potential in our modern world for a compound that reduces the negative effects of stress on the body with no side effects. Ginkgo biloba shows great promise in this direction.

Stress give rise to stress hormones that are both good and bad for us. They are essential for adaptation to acute physical stressors-as in fight or flight situations.35,36 In our mental and emotional stress situations today, however, we usually do not have much use for these hormones. They therefore accumulate in the body and give rise to disease through their immunosuppressive and neurotoxic effects. One of the detrimental effects of glucocorticoid excess is its ability to damage the hippocampus area of the brain. This area is a structure in the limbic system that is critical to cognitive functions such as learning and memory.

Behavioral studies in rats and mice (whose response patterns are very similar to humans) demonstrated that repeated oral administration of ginkgo extract had significant anti-stress effects, determined in several kinds of stress tests.37-39

One study demonstrated that treatment with ginkgo extract decreased serum corticosteroid levels by 50%.40 The remaining 50% may be the normal level in conditions without stress. This theory is supported by the fact that no detrimental effects on either animal or human health were observed. The results indicate that ginkgo does not affect basal adrenal function but controls the stress-induced excess of corticosteroid levels.

In vivo findings that ginkgo extract can enhance adaptation under stressful conditions supports its extensive use in the elderly to improve their capacity to cope with the demands of everyday living.41 An interesting "side effect" of chronic ginkgo treatment in rats42 was the observation that these animals lived significantly longer than the animals that received placebo.

Prevention. . . ginkgo's most important benefit!

Hundreds of scientific studies have confirmed ginkgo's beneficial effects in the human body. Due to its multiple mechanisms of action, ginkgo provides enormous potential protection against our most feared diseases. Aging humans have much to gain from using ginkgo biloba extract as a preventative measure to help maintain neurological and circulatory health.

The fact that one study failed to show improved memory in healthy people who received 40 mg of ginkgo (three times a day) for only six weeks is not relevant to those seeking long-term anti-aging effects. The authors of the JAMA study acknowledge that higher doses of ginkgo for longer periods of exposure might produce the desired effects.


  1. Solomon PR, Adams F, Silver A, Zimmer J, Deveaux R. Ginkgo for memory enhancement: a randomized controlled trial. Journal of the American Medical Association 2002;288(7):835-40.
  2. Mix, JA., Crew WD. A double-blind, placebo controlled randomized trial of Ginkgo Biloba extract EGb761 in a sample of cognitively intact older adults: neuropsycological findings. Human Psychopharmacology Clin Exp 2002; 17:267-77.
  3. Lebars PL, et. al. Ginkgo biloba for dementia. Journal of the American Medical Association 1997;278:1327-1332.
  4. Kleijnen J, Knipschild P. Ginkgo biloba for cerebral insufficiency. Br J Clin Pharmacol 1992;Oct;34(4):352-8.
  5. DeFeudis FV. Coronary atherosclerosis: current therapeutic approaches and future trends. Life Sci 1991;49(10):689-705 .
  6. Blass, Metabolic alterations common to neural and non-neural cells in Alzheimer's disease. Hippocampus 1993;3;Spec No:45-53.
  7. LeBars PL, Katz MM, Berman N, et al. A placebo-controlled, double-blind, randomized trial of an extract of ginkgo biloba for dementia. JAMA 1997;278:1327-1332.
  8. Maurer K, Ihl R, Dierks T, Frolich L. Clinical efficacy of ginkgo biloba special extract EGb 761 in dementia of the Alzheimer type. J Psychiatr Res 1997;Nov-Dec;31(6):645-55.
  9. Subhan, Hindmarch. The psychopharmacological effects of ginkgo biloba extract in normal healthy volunteers. Int J Clin Pharmacol Res 1984;4(2):89-93.
  10. Rigney U, Kimber S, Hindmarch I. The effects of acute doses of standardized ginkgo biloba extract on memory and psychomotor performance in volunteers. Phytother Res 1999;Aug;13(5):408-15.
  11. Schubert et al. Depressive episode primarily unresponsive to therapy in elderly patients: efficacy of ginkgo biloba extract (EGB 761) in combination with antidepressants. Geriatr Forsch 1993;3:45-53.
  12. Schneider B. Ginkgo biloba extract in peripheral arterial diseases. Meta-analysis of controlled clinical studies. Arzneimittelforschung 1992;Apr; 42(4): 428-36.
  13. Koltai M, Tosaki A, Hosford D, Braquet P. . Ginkgolide B protects isolated hearts against arrhythmias induced by ischemia but not reperfusion. Eur J Pharmacol 1989;May 19;164(2):293-302.
  14. Shen J-G, Zhou D-Y. Efficiency of Ginkgo biloba extract (EGb 761) in antioxidant protection against myocardial ischemia and reperfusion injury. Biochem Mol Biol Int 1995;35:125-134.
  15. Haramaki N, Aggarwal S, Kawabata T, Droy-Lefaix MT, Packer L. Effects of natural antioxidant ginkgo biloba extract (EGB 761) on myocardial ischemia-reperfusion injury. Free Radic Biol Med 1994; Jun;16(6):789-94.
  16. Akiba S, Kawauchi T, Oka T, Hashizume T, Sato T. Inhibitory effect of the leaf extract of ginkgo biloba L. on oxidative stress-induced platelet aggregation. Biochem Mol Biol Int 1998;Dec;46(6):1243-8.
  17. Sikora R, et al. Ginkgo biloba extract in the therapy of erectile dysfunction. J Urol 1989;141:188A.
  18. Doly M, Droy-Lefaix MT, Bonhomme B, Braquet P. Effect of ginkgo biloba extract on the electrophysiology of the isolated retina from a diabetic rat. Presse Med 1986;Sep 25;15(31):1480-3.
  19. Baudouin C, Pisella PJ, Ettaiche M, Goldschild M, Becquet F, Gastaud P, Droy-Lefaix MT. Effects of EGb761 and superoxide dismutase in an experimental model of retinopathy generated by intravitreal production of superoxide anion radical. Graefes Arch Clin Exp Ophthalmol 1999;Jan;237(1):58-66.
  20. Chung HS, Harris A, Kristinsson JK, Ciulla TA, Kagemann C, Ritch R. Ginkgo biloba extract increases ocular blood flow velocity. J Ocul Pharmacol Ther 1999;Jun;15(3):233-40.
  21. Bascher V and Steinert W: Differential diagnosis of sudden deafness and therapy with high dose infusions of ginkgo biloba extract. In: Vertigo, Nausea, Tinnitus and Hypoacusia in Metabolic Disorders, Amsterdam, 1988, pp. 575-582.
  22. Jung HW, Chang SO, Kim CS, Rhee CS, Lim DH. Effects of ginkgo biloba extract on the cochlear damage induced by local gentamicin installation in guinea pigs. J Korean Med Sci 1998;Oct;13(5):525-8.
  23. Meyer B. A multicenter, double-blind, drug versus placebo study of ginkgo biloba extract in the treatment of tinnitus. Presse Med 1986;5:1562-4.
  24. Du G, Willet K, Mouithys-Mickalad A, Sluse-Goffart CM, Droy-Lefaix MT, Sluse FE. EGb 761 protects liver mitochondria against injury induced by in vitro anoxia/reoxygenation. Free Radic Biol Med 1999;Sep;27(5-6):596-604.
  25. Sastre J, Pallardo FV, Garcia de la Asuncion J, Vina J. Mitochondria, oxidative stress and aging. Free Radic Res 2000;Mar;32(3):189-98.
  26. Schaffler K, Reeh PW. Double blind study of the hypoxia protective effect of a standardized ginkgo biloba preparation after repeated administration in healthy subjects. Arzneimittelforschung 1985;35(8):1283-6.
  27. Seif El Nasr M; El Fattah AA. Lipid peroxide, phospholipids, glutathione levels and superoxide dismutase activity in rat brain after ischaemia: effect of ginkgo biloba extract. Pharmacol Res 1995;Nov;32:5, 273-8.
  28. Kobayashi MS, Han D, Packer L. Antioxidants and herbal extracts protect HT-4 neuronal cells against glutamate-induced cytotoxicity. Free Radic Res 2000;Feb;32(2):115-24.
  29. Zhu L, Wu J, Liao H, Gao J, Zhao XN, Zhang ZX. Antagonistic effects of extract from leaves of ginkgo biloba on glutamate neurotoxicity. Zhongguo Yao Li Xue Bao 1997;Jul;18(4):344-7.
  30. Oyama Y, Hayashi A, Ueha T. Ca(2+)-induced increase in oxidative metabolism of dissociated mammalian brain neurons: effect of extract of ginkgo biloba leaves. Jpn J Pharmacol 1993;Apr;61(4):367-70.
  31. Wu WR, Zhu XZ. Involvement of monoamine oxidase inhibition in neuroprotective and neurorestorative effects of ginkgo biloba extract against MPTP-induced nigrostriatal dopaminergic toxicity in C57 mice. Life Sci 1999;65(2):157-64.
  32. Oyama Y, Chikahisa L, Ueha T, Kanemaru K, Noda K. Ginkgo biloba extract protects brain neurons against oxidative stress induced by hydrogen peroxide. Brain Res 1996;Mar 18;712(2):349-52.
  33. Ni, Y., Yzhao, B., Hou, J., and Xin, W. Preventive effect of ginkgo biloba on apoptosis in rat cerebellar neuronal cells induced by hydroxyl radicals. Neurosci Lett 1996;214: 115-118,.
  34. Wei Z, Peng Q, Lau BH, Shah V. Ginkgo biloba inhibits hydrogen peroxide-induced activation of nuclear factor kappa B in vascular endothelial cells. Gen Pharmacol 1999;Nov;33(5):369-75.
  35. Johnson EO, Kamilaris TC, Chrousos GP, Gold PW. Mechanisms of stress: a dynamic overview of hormonal and behavioral homeostasis. Neurosci Biobehav Rev 1992;Summer;16(2):115-30.
  36. Munck A, Naray-Fejes-Toth A. Glucocorticoids and stress: permissive and suppressive actions. Ann N Y Acad Sci 1994;Nov 30;746:115-30; discussion 131-3.
  37. Porsolt RD, Martin P, Lenegre A, Fromage S, Drieu K. Effects of an extract of ginkgo biloba (EGB 761) on "learned helplessness" and other models of stress in rodents. Pharmacol Biochem Behav 1990;Aug;36(4):963-71.
  38. Rodriguez de Turco EB, Droy-Lefaix MT, Bazan NG. EGb 761 inhibits stress-induced polydipsia in rats. Physiology and Behavior 1993;May;53(5):1001-2.
  39. Rapin JR, Lamproglou I, Drieu K, DeFeudis FV. Demonstration of the "anti-stress" activity of an extract of ginkgo biloba (Egb 761) using a discrimination learning task. Gen Pharmacol 1994;Sep;25(5):1009-16.
  40. Amri H, Drieu K, Papadopoulos V. Ex vivo regulation of adrenal cortical cell steroid and protein synthesis, in response to adrenocorticotropic hormone stimulation, by the ginkgo biloba extract EGb 761 and isolated ginkgolide B. Endocrinology 1997;Dec;138(12):5415-26.
  41. Rai, G.S., Shovlin, C. and Wesnes, K.A. A double-blind, placebo-controlled study of ginkgo biloba extract in elderly out-patients with mild to moderate memory impairment. Current Medical Research and Opinion 1991;12: 350-355.
  42. Winter JC. The effects of an extract of ginkgo biloba, EGb 761, on cognitive behavior and longevity in the rat. Physiol Behav 1998;Feb 1;63(3):425-33.