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Ginkgo

Traceable back 300 million years, the ginkgo is the oldest surviving species of tree. Although it died out in Europe during the Ice Age, ginkgo survived in China, Japan, and other parts of East Asia. It has been cultivated extensively for both ceremonial and medical purposes, and some particularly revered trees have been lovingly tended for more than 1,000 years.
In traditional Chinese herbology, tea made from ginkgo seeds has been used for numerous problems, most particularly asthma and other respiratory illnesses. The leaf was not used. But in the 1950s, German researchers started to investigate the medical possibilities of ginkgo leaf extracts rather than remedies using the seeds. Thus, modern ginkgo preparations are not the same as the traditional Chinese herb, and the comparisons often drawn are incorrect.

What Is Ginkgo Used for Today?

Fairly good evidence indicates that ginkgo is effective for Alzheimer's disease and other severe forms of memory and mental function decline; when used for this purpose, it appears to be as effective as standard drugs. 1,2-7,48,50,109,149,163,171
Inconsistent evidence hints that ginkgo might be helpful for enhancing memory and mental function in seniors without severe memory loss as well. 8-14,73,103,110,111,112 Weak evidence hints that ginkgo (alone or in combination with ginseng or vinpocetine ) may be helpful for enhancing memory or alertness in younger people. 15-18,90,113 Combining phosphatidylserine (another substance used to enhance mental function) along with ginkgo might increase its efficacy. 153
In addition, ginkgo may be effective for the treatment of restricted circulation in the legs due to hardening of the arteries known as intermittent claudication . 19-22,114
One substantial, well-designed double-blind, placebo-controlled study found evidence that ginkgo extract taken at a dose of 480 mg or 240 mg daily may be helpful for anxiety . 148
Weak and, in some cases inconsistent, evidence from preliminary double-blind trials hints that ginkgo might be helpful for glaucoma , 72macular degeneration , 68,71conjunctivitis , 168PMS , 29Raynaud’s disease , 69sudden hearing loss , 32,33vertigo , 31 and vitiligo . 115
Although study results conflict, on balance the evidence suggests that ginkgo is not helpful for tinnitus (ringing in the ear). 34-39,96,116
Three small, double-blind trials enrolling a total of about 100 people found preliminary evidence that use of the herb Ginkgo biloba can help prevent altitude sickness . 30,102,159 However, a large scale, double-blind study enrolling 614 people, failed to find benefit. 117 (The drug acetazolamide, however, did provide significant benefits compared to placebo.) A similarly designed smaller study enrolling 57 people also failed to find ginkgo effective. 160 Overall, the balance of evidence suggests that ginkgo is not effective for this purpose.
Numerous case reports and uncontrolled studies raised hopes that ginkgo might be an effective treatment for sexual dysfunction in men or women , particularly in those cases related to certain antidepressant medications. 23-27 However, the results of a number of double-blind studies (see Why Does this Database Rely on Double-blind Studies? ) indicate that ginkgo is no more effective than placebo, whether or not subjects are taking antidepressants. 70,129,161
One small study failed to find ginkgo helpful for the treatment of cocaine dependence . 118 Two studies failed to find ginkgo helpful in multiple sclerosis . 128,154 In addition, another study found ginkgo biloba did not improve cognitive function on neuropsychological test scores compared to placebo in a randomized trial of 121 patients with multiple sclerosis. 172 This was also supported in a review of 4 studies. However, ginkgo was associated with improving fatigue symptoms after 4 weeks when compared to placebo. 174
Chinese research suggests that ginkgo might enhance the effects of drugs used for schizophrenia (both phenothiazines as well as atypical antipsychotic drugs). 28,93 Antipsychotic drugs can cause a neurological condition called tardive dyskinesia , which involves troubling, uncontrollable body movements. 170 One randomized study found that ginkgo (240 mg/day for 12 weeks) was more helpful than placebo in reducing tardive dyskinesia symptoms in people with schizophrenia.
An open study evaluated combination therapy with ginkgo extract and the chemotherapy drug 5FU for the treatment of pancreatic cancer, on the theory that ginkgo might enhance blood flow to the tumor and thereby help 5FU penetrate better. 40 The results were promising, but much better research must be performed before ginkgo can be recommended for this use. Similarly inadequate evidence hints at benefits in dyslexia. 156
Ginkgo has also been proposed as a treatment for depression and diabetic retinopathy , but there is little evidence that it is effective for these conditions.
Note : There are some theoretical safety concerns regarding ginkgo and diabetes . See Safety Issues for more information.

What Is the Scientific Evidence for Ginkgo?

Alzheimer’s Disease and Non-Alzheimer’s Dementia

In the past, European physicians believed that the cause of mental deterioration with age (senile dementia) was reduced circulation in the brain due to atherosclerosis. Since ginkgo is thought to improve circulation, 42-44 they assumed that ginkgo was simply getting more blood to brain cells and thereby making them work better.
However, the contemporary understanding of age-related memory loss and mental impairment no longer considers chronically restricted circulation the primary issue. Ginkgo (and other drugs used for dementia) may instead function by directly stimulating nerve-cell activity and protecting nerve cells from further injury, 45 although improvement in circulatory capacity may also play a role.
Numerous double-blind, placebo-controlled studies have found ginkgo extract effective for dementia; among these, studies rated as “high quality” by accepted scientific norms included a total of more than 2,000 people. 46-48,50,109,152 For example, one major US trial published in 1997 enrolled more than 300 people with Alzheimer’s disease or non-Alzheimer’s dementia. 6 Participants were given either 40 mg of Ginkgo biloba extract or placebo 3 times daily for a period of 52 weeks. The results showed significant but not entirely consistent improvements in the treated group.
Another study, published in 2007, followed 400 people for 22 weeks, and used twice the dose of ginkgo. 157 The results of this trial indicated that ginkgo was significantly superior to placebo. (Technically, it was superior in the primary outcome measure, the SKT cognitive test battery, as well as on all secondary outcome measures.) The areas in which ginkgo showed the most marked superiority as compared to placebo included “apathy/indifference, anxiety, irritability/lability, depression/dysphoria and sleep/nighttime behaviour.” In addition, a 6-month study found ginkgo equally effective as the drug donepezil (taken at a dose of 5 mg daily). 149
On the other hand, one fairly large study drew headlines for finding ginkgo extract ineffective. 51 This 24-week, double-blind, placebo-controlled study of 214 people with either mild to moderate dementia or ordinary age-associated memory loss found no effect with ginkgo extract at a dose of 240 mg or 160 mg daily. However, this study has been sharply criticized for a number of serious flaws in its design. 94 But in another community-based study among 176 elderly subjects with early-stage dementia, researchers found no beneficial effect for 120 mg of ginkgo extract given daily for six months. 164
But, a 2011 systematic review of 9 placebo-controlled, randomized trials found more promising evidence for ginkgo. 171 The trials, which involved 2,372 people with Alzheimer's disease or another form of dementia, ranged from 12-52 weeks. Those in the ginkgo group did have improvements in their cognition scores. And, a subgroup of people with Alzheimer's disease also showed improvements in their activities of daily living.
The ability of ginkgo to prevent or delay a decline in cognitive function is less clear. In a placebo-controlled trial of 118 cognitively-intact adults 85 years or older, ginkgo extract seemed to effectively slow the decline in memory function over 42 months. The researchers also reported a higher incidence of stroke in the group that took ginkgo, a finding that requires more investigation (see Safety Issues below). 162
In a 2009 review of 36 randomized trials involving 4,423 patients with declining mental function (including dementia), researchers concluded ginkgo appears safe. But, there is inconsistent evidence regarding whether it works. 166

Enhancing Mental Function in Healthy People

Ginkgo has shown less consistent promise for enhancing mental function in people who experience the relatively slight decline in cognitive function that typically accompanies increased age.
For example, in a double-blind, placebo-controlled trial, 241 seniors complaining of mildly impaired memory were given either placebo or ginkgo for 24 weeks. 52 The results showed that ginkgo produced modest improvements in certain types of memory.
Another double-blind, placebo-controlled trial examined the effects of ginkgo extract in 40 men and women (ages 55 to 86) who did not suffer from any mental impairment. 53 Over a 6-week period, the results showed improvements in measurements of mental function.
Possible benefits were seen in six other trials as well, involving a total of about 250 people. 54-57,110,119,112
Set against these positive findings is the 24-week study mentioned above, which found no benefit in ordinary age-related memory loss. 58 The reason for this negative outcome may be flaws in this trial’s design, as noted above. 94 However, three other studies enrolling a total of about 400 seniors also failed to find significant benefit with daily use of ginkgo. 103,130-131 Another double-blind, placebo-controlled study used a one-time dose of ginkgo, and again found no benefits. 73
Besides these negative trials, there is another weakness in the evidence: inconsistency even among positive trials. There are numerous measurable aspects of memory and mental function, and studies of ginkgo have examined a great many of these. Unfortunately the exact areas of benefits seen vary widely.
For example, in one positive study, ginkgo may speed the ability to memorize letters but not expand the number of letters that can be retained; while in another positive study, the reverse may be true. This type of inconsistency tends to decrease the confidence one can place in these apparently positive studies, because if ginkgo were really working, one would expect its effects to be more reproducible.
A total of about 15 controlled trials have examined the effects of ginkgo on memory and mental function in younger people. 59,60,90,104,113,134-136,155,158 However, again, results are inconsistent, with many negative results, and the positive ones failing to indicate a consistent pattern of benefit. 155,158
Several small double-blind, placebo-controlled studies have evaluated combined treatment with ginseng or vinpocetine for enhancing mental function in young people. 104-106,108,139 The results, overall, are unconvincing. Weak evidence suggests that combining phosphatidylserine with ginkgo might increase its efficacy. 153 In two studies, ginkgo combined with the Ayurvedic herb brahmi failed to improve mental function. 62,120
The bottom line: It is not clear whether ginkgo actually enhances memory and mental function in healthy seniors or healthy younger people. Benefits, if they do exist, are probably slight.

Intermittent Claudication

In intermittent claudication , impaired circulation can cause a severe, cramp-like pain in one's legs after walking only a short distance. According to 9 double-blind, placebo-controlled trials, ginkgo can significantly increase pain-free walking distance. 63,114 However, a second review of 11 randomized trials with 477 patients found that although gingko had greater pain-free walking distance than placebo, the improvemed distance was not considered clinically relevant. 173
One double-blind study enrolled 111 people for 24 weeks. 64 Subjects were measured for pain-free walking distance by walking up a 12% slope on a treadmill at 3 kilometers per hour (about 2 miles per hour). At the beginning of treatment, both the placebo and ginkgo (120 mg daily) groups were able to walk about 350 feet without pain. By the end of the trial, both groups had improved, although the ginkgo group improved significantly more. Participants taking ginkgo showed about a 40% increase in pain-free walking distance as compared to only a 20% improvement in the placebo group.
Similar improvements were also seen in a double-blind, placebo-controlled trial of 60 people who had achieved maximum benefit from physical therapy. 65
A 24-week, double-blind, placebo-controlled study of 74 people with intermittent claudication found that ginkgo at a dose of 240 mg per day was more effective than at 120 mg per day. 66 A 2009 review of 11 trials with 477 subjects suggested that those who took ginkgo biloba were able to walk further than control patients, although the results were limited by differences among the trials. 167 However, not all studies have been positive. In a randomized trail involving 62 individuals (averaging 70 years of age), 300 mg of ginkgo per day was no better than placebo at improving pain-free walking distance over 4 months of treatment. 165

PMS Symptoms

One double-blind, placebo-controlled study evaluated the benefits of ginkgo extract for women with PMS symptoms. 67 This trial enrolled 143 women, 18 to 45 years of age, and followed them for two menstrual cycles. Each woman received either the ginkgo extract (80 mg twice daily) or placebo beginning on day 16 of the first cycle. Treatment was continued until day 5 of the next cycle, and resumed again on day 16 of that cycle. As compared to placebo, ginkgo significantly relieved major symptoms of PMS, especially breast pain and emotional disturbance. In another similarly designed trial involving 85 university students, Ginkgo biloba L. significantly reduced PMS symptom severity compared to placebo. 169

Anxiety

In a double-blind, placebo-controlled study of 107 people with various forms of anxiety (specifically, generalized anxiety disorder or adjustment disorder with anxious mood), ginkgo extract taken at a dose of 240 mg or 480 mg daily proved significantly more effective than placebo. 148

Macular Degeneration

Macular degeneration , one of the most common causes of vision loss in seniors, may respond to ginkgo.
In a 6-month, double-blind, placebo-controlled study of 20 people with macular degeneration, use of ginkgo at a dose of 160 mg daily resulted in improved visual acuity. 68
A 24-week, double-blind study of 99 people with macular degeneration compared ginkgo extract at a dose of 240 mg per day with ginkgo at a dose of 60 mg daily. 71 The results showed that vision improved in both groups, but to a greater extent with the higher dose.

Vertigo

A 3-month, double-blind trial of 70 people with a variety of vertigo conditions found that ginkgo extract given at a dose of 160 mg twice daily produced results superior to placebo 75 By the end of the trial, 47% of the people given ginkgo had significantly recovered versus only 18% in the placebo group.

Glaucoma

A small double-blind, placebo-controlled trial found that use of ginkgo extract at a dose of 120 mg daily for 8 weeks significantly improved the visual field in people with glaucoma . 72

Tinnitus

Studies of Ginkgo biloba extract for treating tinnitus have yielded conflicting results. 76-81,96 While some small studies found benefit, the largest and best-designed of these trials failed to find ginkgo effective. In a 12-week, double-blind trial, 1,121 people with tinnitus were given either placebo or standardized ginkgo at a dose of 50 mg 3 times daily. 82 The results showed no difference between the treated and the placebo groups.

Dosage

The standard dosage of ginkgo is 40 mg to 80 mg 3 times daily of a 50:1 extract standardized to contain 24% ginkgo-flavone glycosides. Levels of toxic ginkgolic acid and related alkylphenol constituents should be kept under 5 parts per million.
In an analysis performed in 2006 by the respected testing organization ConsumerLab.com , some tested ginkgo products were found to be contaminated with lead. 132

Safety Issues

Ginkgo appears to be relatively safe. Extremely high doses have been given to animals for long periods of time without serious consequences, and results from human trials are also generally reassuring. 83,121 Safety in young children, pregnant or nursing women, or those with severe liver or kidney disease, however, has not been established.
In all the clinical trials of ginkgo up through 1991 combined, involving a total of almost 10,000 participants, the incidence of side effects produced by ginkgo extract was extremely small. There were 21 cases of gastrointestinal discomfort, and even fewer cases of headaches, dizziness, and allergic skin reactions. 84
However, there are few potential problems. Perhaps the most serious have been the numerous case reports of internal bleeding associated with use of ginkgo (spontaneous as well as following surgery). 85,86,97-99,107,122-123,133 Based on these reports, as well as previous evidence that ginkgo inhibits platelet function, 124 studies have been performed to determine whether ginkgo significantly affects bleeding time or other measures of blood coagulation, with somewhat inconsistent results. 125,126,127,140 Prudence suggests that ginkgo should not be used by anyone during the periods before or after surgery or labor and delivery, or by those with bleeding problems such as hemophilia.
It also seems reasonable to hypothesize that ginkgo might interact with blood-thinning drugs, amplifying their effects on coagulation. However, two studies found no interaction between ginkgo and warfarin (Coumadin), 100,141-142 and another found no interaction with clopidogrel. (Although, it did find a slight interaction with the related drug cilostazol.) 150 While these findings are reassuring, prudence indicates physician supervision before combining ginkgo with blood-thinning drugs.
One study found that when high concentrations of ginkgo were placed in a test tube with hamster sperm and ova, the sperm were less able to penetrate the ova. 87 However, since we have no idea whether this much ginkgo can actually come into contact with sperm and ova when they are in the body rather than a test tube, these results may not be meaningful in real life.
The ginkgo extracts approved for use in Germany are processed to remove alkylphenols, including ginkgolic acids, which have been found to be toxic. 88 The same ginkgo extracts are available in the United States. However, other ginkgo extracts and whole ginkgo leaf might contain appreciable levels of these dangerous constituents.
Seizures have also been reported with the use of ginkgo leaf extract in people with previously well-controlled epilepsy; in one case, the seizures were fatal. 89,143 It has been suggested that ginkgo might interfere with the effectiveness of some antiseizure medications, specifically phenytoin and valproic acid . 144 Another possible explanation is contamination of ginkgo leaf products with ginkgo seeds, the seeds of the ginkgo plant contain a neurotoxic substance called 4-methoxypyridoxine (MPN). 101 Finally, the drug tacrine (also used to improve memory) has been associated with seizures, and ginkgo may affect the brain in ways similar to tacrine. 92 Regardless of the explanation, prudence suggests that people with epilepsy should avoid ginkgo.
According to a study in rats, ginkgo extract may cause the body to metabolize the drug nicardipine (a calcium channel blocker ) more rapidly, thereby decreasing its effects. 49 In addition, this finding also suggests potential interactions with numerous other drugs, although more research is needed to know for sure which ones might be affected.
Antibiotics in the aminoglycoside family can cause hearing loss by damaging the nerve carrying hearing sensation from the ear. One animal study evaluated the potential benefits of ginkgo for preventing hearing loss, and found instead that the herb increased damage to the nerve. 41 Based on this finding, individuals using aminoglycosides should avoid ginkgo.
It has been suggested that ginkgo might cause problems for people with type 2 diabetes both by altering blood levels of medications as well as by directly affecting the blood-sugar regulating system of the body. 95,145 However, the most recent and best designed studies have failed to find any such actions. 146-147 Nonetheless, until this situation is clarified, people with diabetes should use ginkgo only under physician supervision.

Interactions You Should Know About

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References

1 Schulz V, Hansel R, Tyler VE. Rational Phytotherapy: A Physicians' Guide to Herbal Medicine .3rd ed. Berlin, Germany: Springer-Verlag; 1998:288-292.

2 Kleijnen J, Knipschild P. Ginkgo biloba.Lancet. 1992;340:1136-1139.

3 Kanowski S, Herrmann WM, Stephan K, et al. Proof of efficacy of the Ginkgo biloba special extract EGb 761 in outpatients suffering from mild to moderate primary degenerative dementia of the Alzheimer type or multi-infarct dementia. Pharmacopsychiatry. 1996;29:47-56.

4 Hofferberth B. The efficacy of EGb 761 in patients with senile dementia of the Alzheimer type, a double-blind, placebo-controlled study on different levels of investigation. Hum Psychopharmacol. 1994;9:215-222.

5 Schulz V, Hansel R, Tyler VE. Rational Phytotherapy: A Physicians' Guide to Herbal Medicine. 3rd ed. Berlin, Germany: Springer-Verlag; 1998:46.

6 Le Bars PL, Katz MM, Berman N, et al. A placebo-controlled, double-blind, randomized trial of an extract of Ginkgo biloba for dementia. North American EGb Study Group. JAMA. 1997;278:1327-1332.

7 van Dongen MC, van Rossum E, Kessels AG, et al. The efficacy of ginkgo for elderly people with dementia and age-associated memory impairment: new results of a randomized clinical trial. J Am Geriatr Soc. 2000;48:1183-1194.

8 Brautigam MR, Blommaert FA, Verleye G, et al. Treatment of age-related memory complaints with Ginkgo biloba extract: a randomized double blind placebo-controlled study. Phytomedicine. 1998;5:425-434.

9 Mix JA, Crews WD Jr. An examination of the efficacy of Ginkgo biloba extract EGb 761 on the neuropsychologic functioning of cognitively intact older adults. J Altern Complement Med. 2000;6:219-229.

10 Winther K, Randlov C, Rein E, et al. Effects of Ginkgo biloba extract on cognitive function and blood pressure in elderly subjects. Curr Ther Res. 1998;59:881-888.

11 Rai GS, Shovlin C, Wesnes KA. A double-blind, placebo controlled study of Ginkgo biloba extract ('Tanakan™') in elderly outpatients with mild to moderate memory impairment. Curr Med Res Opin. 1991;12:350-355.

12 Rigney U, Kimber S, Hindmarch I. The effects of acute doses of standardized Ginkgobiloba extract on memory and psychomotor performance in volunteers. Phytotherapy Res. 1999;13:408-415.

13 Allain H, Raoul P, Lieury A, et al.Effect of two doses of Ginkgo biloba extract (EGb 761) on the dual-coding test in elderly subjects. Clin Ther. 1993;15:549-558.

14 van Dongen MC, van Rossum E, Kessels AG, et al. The efficacy of ginkgo for elderly people with dementia and age-associated memory impairment: new results of a randomized clinical trial. J Am Geriatr Soc. 2000;48:1183-1194.

15 Kennedy DO, Scholey AB, Wesnes KA. The dose-dependent cognitive effects of acute administration of Ginkgo biloba to healthy young volunteers. Psychopharmacology (Berl). 2000;151:416-423.

16 Hindmarch I. Activity of Ginkgo biloba extract on short term memory [in French]. Presse Med. 1986;15:1592-1594.

17 Warot D, Lacomblez L, Danjou P, et al. Comparative effects of Ginkgo biloba extracts on psychomotor performances and memory in healthy subjects [in French]. Therapie. 1991;46:33-36.

18 Wesnes KA, Faleni RA, Hefting NR, et al. The cognitive, subjective, and physical effects of a ginkgo biloba/panax ginseng combination in healthy volunteers with neurasthenic complaints. Psychopharmacol Bull. 1997;33:677-683.

19 Pittler MH, Ernst E. Ginkgo biloba extract for the treatment of intermittent claudication: a meta-analysis of randomized trials. Am J Med. 2000;108:276-281.

20 Peters H, Kieser M, Holscher U. Demonstration of the efficacy of Ginkgo biloba special extract EGb 761 on intermittent claudication—A placebo-controlled, double-blind multicenter trial. Vasa. 1998;27:106-110.

21 Blume J, Kieser M, Holscher U. Placebo-controlled, double-blind study on the effectiveness of Ginkgo biloba special extract EGb 761 in trained patients with intermittent claudication [translated from German]. Vasa. 1996;25:265-274.

22 Schweizer J, Hautmann C. Comparison of two dosages of Ginkgo biloba extract EGb 761 in patients with peripheral arterial occlusive disease Fontaine's Stage IIb. A randomized, double-blind, multicentric clinical trial. Arzneimittelforschung. 1999,49:900-904.

23 Cohen AJ, Bartlik B. Ginkgo biloba for antidepressant-induced sexual dysfunction. J Sex Marital Ther. 1998;24:139-143.

24 Cohen A, Bartlik B. Treatment of sexual dysfunction with Ginkgo biloba extract [scientific reports]. Presented at: 150th Annual Meeting of the American Psychiatric Association; May 18-21, 1997; San Diego, CA.

25 Cohen A. Treatment of antidepressant-induced sexual dysfunction with Ginkgo biloba extract [abstract #176]. Presented at: 149th Annual Meeting of the American Psychiatric Association; May 5-8, 1996; New York, NY.

26 Cohen A. Long-term safety and efficacy of Ginkgo biloba extract in the treatment of antidepressant-induced sexual dysfunction. Available at: http://www.priory.com/pharmol/gingko . Accessed June 15, 1997.

27 McCann B. Botanical could improve sex lives of patients on SSRIs. Drug Topics. 1997;141:33.

28 Liu P, Luo H, Shen Y, et al. Combined use of Ginkgo biloba extracts on the efficacy and adverse reactions of various antipsychotics [translated from Chinese]. Chin J Clin Pharmacol. 1997;13:193-198.

29 Tamborini A, Taurelle R. Value of standardized Ginkgo biloba extract (EGb 761) in the management of congestive symptoms of premenstrual syndrome [translated from French]. Rev Fr Gynecol Obstet. .1993;88:447-457.

30 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;67:445-452.

31 Haguenauer JP, Cantenot F, Koskas H, et al. Treatment of balance disorders using Ginkgo biloba extract. A multicenter, double blind, drug versus placebo study [translated from French]. Presse Med. 1986;15:1569-1572.

32 Burschka MA, Hassan HA, Reineke T, et al. Effect of treatment with Ginkgo biloba extract EGb 761 (oral) on unilateral idiopathic sudden hearing loss in a prospective randomized double-blind study of 106 outpatients. Eur Arch Otorhinolaryngol. 2001;258:213-219.

33 Reisser CH, Weidauer H. Ginkgo biloba extract EGb 761Ŵ or pentoxifylline for the treatment of sudden deafness: a randomized, reference-controlled, double-blind study. Acta Otolaryngol. 2001;121:579-584.

34 Morgenstern C, Biermann E. Long-term tinnitus therapy with ginkgo special extract EGb 761 [translated from German]. Fortschr Med. 1997;115:57-58.

35 Holgers KM, Axelsson A, Pringle I. Ginkgo biloba extract for the treatment of tinnitus. Audiology. 1994;33:85-92.

36 Ernst E, Stevinson C. Ginkgo biloba for tinnitus: a review. Clin Otolaryngol. 1999;24:164-167.

37 Coles R. Trial of an extract of Ginkgo biloba (EGB) for tinnitus and hearing loss [letter. Clin Otolaryngol. 1988;13:501-502.

38 Drew S, Davies E. Effectiveness of Ginkgo biloba in treating tinnitus: double blind, placebo controlled trial. BMJ. 2001;322:1-6.

39 Meyer B. Multicenter randomized double-blind drug vs. placebo study of the treatment of tinnitus with Ginkgo biloba extract [translated from French]. Presse Med. 1986;15:1562-1564.

40 Hauns B, Haring B, Kohler S, et al. Phase II study with 5-fluorouracil and Ginkgo biloba extract (GBE 761 ONC) in patients with pancreatic cancer. Arzneimittelforschung. 1999;49:1030-1034.

41 Miman MC, Ozturan O, Iraz M, et al. Amikacin ototoxicity enhanced by Ginkgo biloba extract (EGb 761). Hear Res. 2002;169:121-129.

42 Jung F, Mrowietz C, Kiesewetter H, et al. Effect of Ginkgo biloba on fluidity of blood and peripheral microcirculation in volunteers. Arzneimittelforschung. 1990;40:589-593.

43 DeFeudis FV. Ginkgo biloba Extract (EGb 761): Pharmacological Activities and Clinical Applications. Paris, France: Elsevier Science; 1991:143-146.

44 Kleijnen J, Knipschild P. Ginkgo biloba.Lancet. 1992;340:1136-1139.

45 Schulz V, Hansel R, Tyler VE. Rational Phytotherapy: A Physicians' Guide to Herbal Medicine. 3rd ed. Berlin, Germany: Springer-Verlag; 1998:41.

46 Kleijnen J, Knipschild P. Ginkgo biloba.Lancet. 1992;340:1136-1139.

47 Kanowski S, Herrmann WM, Stephan K, et al. Proof of efficacy of the Ginkgo biloba special extract EGb 761 in outpatients suffering from mild to moderate primary degenerative dementia of the Alzheimer type or multi-infarct dementia. Pharmacopsychiatry. 1996;29:47-56.

48 Hofferberth B. The efficacy of EGb 761 in patients with senile dementia of the Alzheimer type, a double-blind, placebo-controlled study on different levels of investigation. Hum Psychopharmacol. 1994;9:215-222.

49 Shinozuka K, Umegaki K, Kubota Y, et al. Feeding of Ginkgo biloba extract (GBE) enhances gene expression of hepatic cytochrome P-450 and attenuates the hypotensive effect of nicardipine in rats. Life Sci. 2002;70:2783-2792.

50 Le Bars PL, Katz MM, Berman N, et al. A placebo-controlled, double-blind, randomized trial of an extract of Ginkgo biloba for dementia. North American EGb Study Group. JAMA. 1997;278:1327-1332.

51 van Dongen MC, van Rossum E, Kessels AG, et al. The efficacy of ginkgo for elderly people with dementia and age-associated memory impairment: new results of a randomized clinical trial. J Am Geriatr Soc. 2000;48:1183-1194.

52 Brautigam MR, Blommaert FA, Verleye G, et al. Treatment of age-related memory complaints with Ginkgo biloba extract: a randomized double blind placebo-controlled study. Phytomedicine. 1998;5:425-434.

53 Mix JA, Crews WD Jr. An examination of the efficacy of Ginkgo biloba extract EGb 761 on the neuropsychologic functioning of cognitively intact older adults. J Altern Complement Med. 2000;6:219-229.

54 Winther K, Randlov C, Rein E, et al. Effects of Ginkgo biloba extract on cognitive function and blood pressure in elderly subjects. Curr Ther Res. 1998;59:881-888.

55 Rai GS, Shovlin C, Wesnes KA. A double-blind, placebo controlled study of Ginkgo biloba extract ('Tanakan™') in elderly outpatients with mild to moderate memory impairment. Curr Med Res Opin. 1991;12:350-355.

56 Rigney U, Kimber S, Hindmarch I. The effects of acute doses of standardized Ginkgobiloba extract on memory and psychomotor performance in volunteers. Phytotherapy Res. 1999;13:408-415.

57 Allain H, Raoul P, Lieury A, et al.Effect of two doses of Ginkgo biloba extract (EGb 761) on the dual-coding test in elderly subjects. Clin Ther. 1993;15:549-558.

58 van Dongen MC, van Rossum E, Kessels AG, et al. The efficacy of ginkgo for elderly people with dementia and age-associated memory impairment: new results of a randomized clinical trial. J Am Geriatr Soc. 2000;48:1183-1194.

59 Kennedy DO, Scholey AB, Wesnes KA. The dose-dependent cognitive effects of acute administration of Ginkgo biloba to healthy young volunteers. Psychopharmacology (Berl). 2000;151:416-423.

60 Hindmarch I. Activity of Ginkgo biloba extract on short term memory [in French]. Presse Med. 1986;15:1592-1594.

61 Warot D, Lacomblez L, Danjou P, et al. Comparative effects of Ginkgo biloba extracts on psychomotor performances and memory in healthy subjects [in French]. Therapie. 1991;46:33-36.

62 Maher BF, Stough C, Shelmerdine A, et al. The acute effects of combined administration of Ginkgo biloba and Bacopa monniera on cognitive function in humans. Hum Psychopharmacol. 2002;17:163-164.

63 Pittler MH, Ernst E. Ginkgo biloba extract for the treatment of intermittent claudication: a meta-analysis of randomized trials. Am J Med. 2000;108:276-281.

64 Peters H, Kieser M, Holscher U. Demonstration of the efficacy of Ginkgo biloba special extract EGb 761 on intermittent claudication—A placebo-controlled, double-blind multicenter trial. Vasa. 1998;27:106-110.

65 Blume J, Kieser M, Holscher U. Placebo-controlled, double-blind study on the effectiveness of Ginkgo biloba special extract EGb 761 in trained patients with intermittent claudication [translated from German]. Vasa. 1996;25:265-274.

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