A double-blind, placebo controlled study of Ginkgo biloba extract ('tanakan') in elderly outpatients with mild to moderate memory impairment.

Curr Med Res Opin, 12(6):350-5 1991

Thirty-one patients over the age of 50 years and showing a mild to moderate degree of memory impairment entered a 6-month double-blind, placebo controlled, parallel group design study to assess the effects of a standardized Ginkgo biloba extract (containing 24% flavonoid glycosides and 6% terpenes) on cognitive function. Patients were allocated at random to receive oral doses of 40 mg Ginkgo biloba extract or identical placebo 3-times daily. Assessments were made at baseline and after 12 and 24 weeks of treatment using a range of psychometric tests. Efficacy data were available for 27 patients (15 in the placebo group and 12 in the active treatment group). Statistical analysis of the data as compared to baseline suggests that Ginkgo biloba extract had a beneficial effect on cognitive function in this group of patients. Performance on the Digit Copying sub-test of the Kendrick battery was significantly improved at both 12 and 24 weeks, while the median speed of response on a computerized version of a classification task also showed a significant superiority over placebo at 24 weeks.




Ginkgo biloba for antidepressant-induced sexual dysfunction.

J Sex Marital Ther, 24(2):139-43 1998 Apr-Jun

In an open trial ginkgo biloba, an extract derived from the leaf of the Chinese ginkgo tree and noted for its cerebral enhancing effects, was found to be 84% effective in treating antidepressant-induced sexual dysfunction predominately caused by selective serotonin reuptake inhibitors (SSRIs, N = 63). Women (n = 33) were more responsive to the sexually enhancing effects of ginkgo biloba than men (N = 30), with relative success rates of 91% versus 76%. Ginkgo biloba generally had a positive effect on all 4 phases of the sexual response cycle: desire, excitement (erection and lubrication), orgasm, and resolution (afterglow). This study originated from the observation that a geriatric patient on ginkgo biloba for memory enhancement noted improved erections. Patients exhibited sexual dysfunction secondary to a variety of antidepressant medications including selective serotonin reuptake inhibitor (SSRIs), serotonin and nonrepinephrine reuptake inhibitor (SNRIs) monoamine oxidase inhibitor (MAOIs), and tricyclics. Dosages of ginkgo biloba extract ranged from 60 mg qd to 120 mg bid (average = 209mg/d). The common side effects were gastrointestinal disturbances, headache, and general central nervous system activation. The article includes a discussion of presumed pharmacologic mechanisms, including effects on platelet activating factor, prostaglandins, peripheral vasodilatation, and central serotonin and norepinephrine receptor factor modulation.




A natural and broad spectrum nootropic substance for treatment of SDAT--the Ginkgo biloba extract.

Prog Clin Biol Res, 40(5):1247-60 1989

The efficacy of the Ginkgo biloba extract was not only found clinically or in standardised ratings but also documented by objective data, obtained by a computerized EEG method, the DYNAMIC BRAIN MAPPING and BRAIN FUNCTION MONITORING SYSTEM (Dr. T. Itil, New York). A one year open trial comprise 25 parkinson patients with additional signs of SDAT. Data from 3 selected cases were given: The short time efficacy of the substance after the infusion and the long-term result after the oral medication. The maps showed less slower and more faster waves. Without any side effects the Ginkgo biloba extract seems to be a substance with a broad spectrum of influence. Our therapeutic findings in parkinsonian patients with SDAT and the data taken from healthy elderly volunteers revealed that the computerized EEG method may have another big advantage: It seems that the so-called anteriorisation of the Theta waves can be taken as a preclinical sign of an incipient change in brain metabolism. As a consequence--it might be that these changes are reversible by an adequate nootropic treatment. Further studies and treatment experiences must confirm these preliminary findings.




Effect of Ginkgo biloba on fluidity of blood and peripheral microcirculation in volunteers.

Arzneimittelforschung, 40(5):589-93 1990 May

In a randomized placebo controlled single-blind cross-over study of n = 10 apparently healthy subjects the influence of Ginkgo biloba (Kaveri) on blood fluidity and cutaneous microcirculation was studied. Microcirculation was measured before and every 30 min for 4 h after administration of Ginkgo biloba; fluidity of blood was determined before and after 1, 2 and 4 h. Significant changes in blood pressure or heart rate were found neither during Ginkgo phase nor placebo phase. Haematocrit, plasma viscosity, erythrocyte rigidity, thrombocyte and leukocyte count as well as thrombocyte aggregation and the number of circulating thrombocyte aggregates were also not influenced by the Ginkgo nor the placebo solution. In contrast a remarkable influence on the erythrocyte aggregation was observed: comparing two samples a significant decrease by 15.6% (p less than 0.001) with regard to the initial value was observed after 2 h. The blood flow in the nail fold capillaries also increased significantly by about 57% (p less than 0.004) 1 h after administration.




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, 29(2):47-56 1996 Mar

The efficacy of the ginkgo biloba special extract EGb 761 in outpatients with presenile and senile primary degenerative dementia of the Alzheimer type (DAT) and multi-infarct dementia (MID) according to DSM-III-R was investigated in a prospective, randomized, double-blind, placebo-controlled, multi-center study. After a 4-week run-in period, 216 patients were included in the randomized 24-week treatment period. These received either a daily oral dose of 240 mg EGb 761 or placebo. In accordance with the recommended multi-dimensional evaluation approach, three primary variables were chosen: the Clinical Global Impressions (CGI Item 2) for psychopathological assessment, the Syndrom-Kurztest (SKT) for the assessment of the patient's attention and memory, and the N¨urnberger Alters-Beobachtungsskala (NAB) for behavioral assessment of activities of daily life. Clinical efficacy was assessed by means of a responder analysis, with therapy response being defined as response in at least two of the three primary variables. The data from the 156 patients who completed the study in accordance with the study protocol were taken into account in the confirmatory analysis of valid cases. The frequency of therapy responders in the two treatment groups differed significantly in favor of EGb 761, with p <0.005 in Fisher's Exact Test. The intent-to-treat analysis of 205 patients led to similar efficacy results. Thus, the clinical efficacy of the ginkgo biloba special extract EGb 761 in dementia of the Alzheimer type and multi-infarct dementia was confirmed. The investigational drug was found to be well tolerated.




A placebo-controlled, double-blind, randomized trial of an extract of Ginkgo biloba for dementia. North American EGb Study Group.

JAMA, 278(16):1327-32 1997 Oct 22-29

CONTEXT: EGb 761 is a particular extract of Ginkgo biloba used in Europe to alleviate symptoms associated with numerous cognitive disorders. Its use in dementias is based on positive results from only a few controlled clinical trials, most of which did not include standard assessments of cognition and behavior. OBJECTIVE: To assess the efficacy and safety of EGb in Alzheimer disease and multi-infarct dementia. DESIGN: A 52-week, randomized double-blind, placebo-controlled, parallel-group, multicenter study. PATIENTS: Mildly to severely demented outpatients with Alzheimer disease or multi-infarct dementia, without other significant medical conditions. INTERVENTION: Patients assigned randomly to treatment with EGb (120 mg/d) or placebo. Safety, compliance, and drug dispensation were monitored every 3 months with complete outcome evaluation at 12, 26, and 52 weeks. PRIMARY OUTCOME MEASURES: Alzheimer's Disease Assessment Scale-Cognitive subscale (ADAS-Cog), Geriatric Evaluation by Relative's Rating Instrument (GERRI), and Clinical Global Impression of Change (CGIC). RESULTS: From 309 patients included in an intent-to-treat analysis, 202 provided evaluable data for the 52-week end point analysis. In the intent-to-treat analysis, the EGbgroup had an ADAS-Cog score 1.4 points better than the placebo group (P=.04) and a GERRI score 0.14 points better than the placebo group (P=.004). The same patterns were observed with the evaluable data set in which 27% of patients treated with EGb achieved at least a 4-point improvement on the ADAS-Cog, compared with 14% taking placebo (P=.005); on the GERRI, 37% were considered improved with EGb, compared with 23% taking placebo (P=.003). No difference was seen in the CGIC. Regarding the safety profile of EGb, no significant differences compared with placebo were observed in the number of patients reporting adverse events or in the incidence and severity of these events. CONCLUSIONS: EGb was safe and appears capable of stabilizing and, in a substantial number of cases, improving the cognitive performance and the social functioning of demented patients for 6 months to 1 year. Although modest, the changes induced by EGb were objectively measured by the ADAS-Cog and were of sufficient magnitude to be recognized by the caregivers in the GERRI.




Demonstration of the efficacy of ginkgo biloba special extract EGb 761 on intermittent claudication--a placebo-controlled, double-blind multicenter trial.

Vasa, 11(2):106-10 1998 May

BACKGROUND: A multicentric, randomized, placebo-controlled double-blind study on ginkgo biloba special extract EGb 761 (Tebonin forte) in patients suffering from peripheral occlusive arterial disease (POAD) in Fontaine stage II b was carried out in order to prove its clinical efficacy in this indication according to guidelines of European Community authorities and the German Angiological Society and to confirm the results of former clinical studies with EGb 761. PATIENTS AND METHODS: In total, 111 patients with angiographically proven POAD in Fontaine stage II b and intermittent claudication (pain-free walking distance <150 m on the treadmill) were recruited in 5 centers and treated with either EGb 761 or placebo at a daily dose of 3 times 1 film-coated tablet over a duration of 24 weeks following a 2-week placebo run-in period. The primary response variable was the difference of the pain-free walking distance between the start of treatment and after 8, 16 and 24 weeks as measured on the treadmill (walking speed 3 km/h and slope of 12%) under standardized conditions. RESULTS: At the start of the treatment period, the mean pain-free walking distances were very similar with 108.5 m in the EGb 761 group and 105.2 m in the placebo group. At the end of the treatment period these values increased to 153.2 m and 126.6 m, respectively. The group differences were statistically significant at all three control visits with p = 0.017, p = 0.007, and p = 0.016. The differences for the maximum walking distance and the relative increases of the pain-free walking distance and the maximum distance were also significantly higher in the EGb 761 group with p-values <0.05 each. In both groups Doppler indices remained nearly unchanged during therapy. The subjective assessment of the patients demonstrated an amelioration of complaints in both groups. Tolerability was very good with no adverse events under EGb 761 and one case of heartburn and gastric pain in the placebo group. CONCLUSIONS: It can be concluded from the results of this study that treatment with EGb 761 in POAD patients with Fontaine stage II b is very safe and causes a significant and therapeutically relevant prolongation of of the patients' walking distance.




Ginkgo biloba extract (EGb 761) pretreatment limits free radical-induced oxidative stress in patients undergoing coronary bypass surgery.

Cardiovasc Drugs Ther, 11(2):121-31 1997 Apr

A growing body of evidence supports the trigger role of free radicals in the delayed functional and metabolic myocardial recovery following cardiopulmonary bypass (CPB) in humans, thus opening the field to specific therapies. This 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 a matching placebo (n = 7) for 5 days before surgical intervention. Plasma samples were obtained from the peripheral circulation and the coronary sinus at crucial stages of the operation (i.e., before incision, during ischemia, and within the first 30 minutes post-unclamping), and up to 8 days postoperatively. Upon aortic unclamping, EGb 761 inhibited the transcardiac release of thiobarbituric acid-reactive species (p <0.05), as assessed by high-performance liquid chromatography, and attenuated the early (5-10 minute) decrease in dimethylsulfoxide/ascorbyl free radical levels, an electron spin resonance index of the plasma ascorbate pool (p <0.05). EGb 761 also significantly reduced the more delayed leakage of myoglobin (p = 0.007) and had an almost significant effect on ventricular myosin leakage (p = 0.053, 6 days postoperatively). The clinical outcome of recovery of treated patients was improved, but not significantly, compared with untreated patients. 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.




Dietary supplement users: demographics, product use, and medical system interaction.

J Am Board Fam Pract, 278(16):265-71 1997 Jul-Aug

BACKGROUND: Dietary supplements-defined as vitamins and minerals, herbal products, tissue extracts, proteins and amino acids, and other products-are purchased to improve health and prevent disease. Little has been published, however, about the characteristics of either the products or the people who use them. METHODS: Consecutive customers visiting two health food stores during a 15-day period were interviewed by telephone. They were asked about their use of dietary supplements, demographics, and their use of the established health care system. RESULTS: Of the 194 customers contacted, 136 (70.1 percent) completed the survey. Respondents took a total of 805 supplements, most often to prevent a health problem (84.3 percent). Herbal products were most commonly used. Garlic, ginseng, and Ginkgo biloba were the herbs most frequently used. Fifty products were found to have previously reported toxicities, including vitamin A, which 9 customers were taking in megadoses. Most customers were white (94.1 percent), female (75.7 percent), had at least 1 year of college education (70.6 percent), had health insurance (95.6 percent), and had a regular physician (85.3 percent). CONCLUSION: Most of the dietary supplements consumed appear to be safe, but 50 of 805 had previously reported toxicities including megadoses of vitamin A. Garlic, ginseng, and Ginkgo biloba were the most commonly ingested herbs, and the medical literature supports their effectiveness for some conditions in humans. Customers of two health food stores had average to above-average education and took dietary supplements to stay healthy. They used the conventional health care system but did not typically consult their physician about dietary supplements. The pattern of use suggests that physicians might not be adequately addressing preventive and wellness issues in discussions with their patients. Furthermore, physicians might need to learn about dietary supplements so they can communicate with patients about them.




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, 278(16):716-20 1984

79 patients suffering from peripheral arteriopathy (Fontaine's stage IIb) completed a 6-month double-blind randomised clinical trial of Ginkgo biloba extract (GBE) (as coated tablets containing 40 mg GBE; r¨okan) versus placebo in two parallel groups. From the results of measurements of pain-free walking distance, maximum walking distance and plethysmography recordings, GBE was shown to be active and significantly superior to placebo. These results correlated with the physician's and patients' overall assessment of response to treatment.




Oxidative stress in diabetic retina.

EXS, 4(5):299-307 1992

Electron paramagnetic resonance (EPR) spectroscopy was used to directly measure free radical generation in ischemic/reperfused diabetic rat retina. Tissue was frozen at 77 degrees K after 90 min ischemia, and 90 min ischemia followed by 1 min, 3 min, 5 min, and 24 hours reperfusion, respectively. After 90 min of ischemia followed by 1 min, 3 min, 5 min, and 24 hours of reperfusion (n = 10 in each group), free radical signal intensity was increased from its diabetic nonischemic control value of 12 +/- 3 arbitrary units to 58 +/- 6 (P <0.05), 62 +/- 7 (P <0.05), 32 +/- 5 (P <0.05), and 14 +/- 4 arbitrary units, respectively. The peak intensity of free radical production was observed after 90 min ischemia followed by 3 min of reperfusion; therefore, this time point was selected to study the retinal free radical production in superoxide dismutase (conjugated with polyethylene glycol, PEG-SOD) and EGb 761 (Ginkgo biloba extract)-treated groups. With 7,500, 15,000, and 30,000 U/liter of SOD, and 25, 50, and 100 mg/kg of EGb 761, a dose-dependent reduction in oxygen free radical production was detected, respectively, which may be responsible for the attenuation of abnormal postischemic function in ischemic and reperfused diabetic retina.




Direct measurement of free radicals in ischemic/reperfused diabetic rat retina.

Clin Neurosci, 4(5):240-5 1997

Electron paramagnetic resonance (EPR) spectroscopy was used to directly measure free radical generation in ischemic/reperfused diabetic rat retina. Tissue was frozen at 77 degrees K after 90 min ischemia, and 90 min ischemia followed by 1 min, 3 min, 5 min, and 24 hours reperfusion, respectively. After 90 min of ischemia followed by 1 min, 3 min, 5 min, and 24 hours of reperfusion (n = 10 in each group), free radical signal intensity was increased from its diabetic nonischemic control value of 12 +/- 3 arbitrary units to 58 +/- 6 (P <0.05), 62 +/- 7 (P <0.05), 32 +/- 5 (P <0.05), and 14 +/- 4 arbitrary units, respectively. The peak intensity of free radical production was observed after 90 min ischemia followed by 3 min of reperfusion; therefore, this time point was selected to study the retinal free radical production in superoxide dismutase (conjugated with polyethylene glycol, PEG-SOD) and EGb 761 (Ginkgo biloba extract)-treated groups. With 7,500, 15,000, and 30,000 U/liter of SOD, and 25, 50, and 100 mg/kg of EGb 761, a dose-dependent reduction in oxygen free radical production was detected, respectively, which may be responsible for the attenuation of abnormal postischemic function in ischemic and reperfused diabetic retina.




Peroxyl radical scavenging activity of Ginkgo biloba extract EGb 761.

Biochem Pharmacol, 49(11):1649-55 1995 May 26

Antioxidant mechanisms have been proposed to underlie the beneficial pharmacological effects of EGb 761, an extract from Ginkgo biloba leaves used for treating peripheral vascular diseases and cerebrovascular insufficiency in the elderly. In vitro evidence has been reported that EGb 761 scavenges various reactive oxygen species, i.e. nitric oxide, and the superoxide, hydroxyl, and oxoferryl radicals. However, the ability of EGb 761 to scavenge peroxyl radicals (reactive species mainly involved in the propagation step of lipid peroxidation) has not been investigated. To characterize further the antioxidant action of EGb 761, we measured the protective effects of EGb 761 during: (1) the oxidation of B-phycoerythrin by peroxyl radicals generated in aqueous solution by 2,2'-azobis (2-amidinopropane) hydrochloride (AAPH); and (2) the reaction of luminol or cis-parinaric acid with peroxyl radicals generated from 2,2'-azobis (2,4-dimethylvaleronitrile) (AMVN) in liposomes or in human low density lipoprotein (LDL), respectively. To evaluate the peroxyl radical scavenging activity of EGb 761 in a more physiologically relevant model of damage to lipid-containing systems, we also analyzed the effect of the extract on the oxidation of human LDL exposed to the azo-initiators in terms of: (1) accumulation of cholesterol linoleate ester hydroperoxides, (2) depletion of alpha-tocopherol and beta-carotene, and (3) changes in intrinsic tryptophan fluorescence. EGb 761 afforded protection against oxidative damage in all the systems we analyzed; thus, it is an efficient scavenger of peroxyl radicals. This result extends the oxygen radical scavenging properties of the extract and supports the hypothesis of an antioxidant therapeutic action of EGb 761.




Effects of flavonoids of Ginkgo biloba on proliferation of human skin fibroblast.

Skin Pharmacol, 10(4):200-5 1997

Ginkgo biloba studies have focused on the anti-inflammatory effects of the major components, ginkgolide and bilobalide, whereas little is known about their effect on fibroblasts. This study demonstrated the enhancing effects of Ginkgo L. extracts, especially the flavonoid fractions: quercetin, kaempferol, sciadopitysin, ginkgetin, isoginkgetin, on the proliferation of normal human skin fibroblast in vitro measured by MTT (3-[4,5-dimethylthiazole-2-yl]-2,5-diphenyl-tetrazolium bromide) assay and direct hemocytometer cell count. Furthermore, increased production of collagen and extracellular fibronectin were documented by radioisotope (2,3-3H-proline) incorporated collagen assay, procollagen type I C-peptide assay and by immunoturbidimetric assay. These proliferative effects suggest another useful pharmacologic application of Ginkgo L. extracts in addition to their well-known anti-inflammatory effect.




Ginkgo biloba extract (EGb 761) protects human low density lipoproteins against oxidative modification mediated by copper.

Biochem Biophys Res Commun, 11(2):360-6 1995 Jul 17

The antioxidant effects of Ginkgo biloba extract (EGb 761) on copper-mediated human low density lipoprotein (LDL) oxidative modification were evaluated by several techniques. Human LDL (0.5 mg/ml) in phosphate buffered saline, pH 7.4, was incubated with 10 microM cupric sulfate at 37 degrees C under air for 8 hours and 24 hours in the presence of varying concentrations of EGb 761. Increases in LDL apoB carbonylation, lipid peroxidation, apoB electrophoretic mobility and LDL fluorescence were all inhibited when the incubation mixture contained EGb 761 at concentrations less than 100 micrograms/ml. This inhibition was EGb 761-concentration-dependent. Thus, EGb 761 has powerful antioxidant effects on copper-mediated LDL oxidative modification.




Radiation-induced clastogenic factors: anticlastogenic effect of Ginkgo biloba

Free Radic Biol Med, 11(2):985-91 1995 Jun

Clastogenic factors (CFs) were first described in the blood of persons irradiated accidentally or for therapeutic reasons. Work of our laboratory has shown that they occur also under other circumstances, which are characterized by oxidative stress, and that CF-induced chromosome damage is regularly prevented by superoxide dismutase (SOD). Recently we found CFs in a high percentage of salvage personnel of the Chernobyl reactor accident. These liquidators represent a high-risk population and might benefit from cancer chemoprevention by antioxidants. SOD would have to be injected and is not appropriate for long-term prophylactic treatment. In the present study, we therefore evaluated the anticlastogenic effect of the Ginkgo biloba extract EGb 761, which is known for its superoxide scavenging properties. EGb 761 was tested on CF-treated blood cultures of healthy donors. After establishing the optimal protective EGb concentration, using CFs produced by irradiation of whole blood from healthy volunteers, the extract was tested on cultures exposed to CFs from plasma of persons irradiated as liquidators. The anticlastogenic effect could be confirmed for a final concentration of 100 micrograms/ml. In 12 consecutive experiments, CFs induced an average of 18.00 +/- 4.41 aberrations/100 cells. This was reduced to 7.33 +/- 3.08 in the parallel cultures receiving 100 micrograms/ml EGb 761 (p <.001). SOD was anticlastogenic in the same system at concentrations of 30 cytochrome C units/ml (approximately 10 micrograms/ml). 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).> < .001). SOD was anticlastogenic in the same system at concentrations of 30 cytochrome C units/ml (approximately 10 micrograms/ml). 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).




A double-blind, placebo controlled study of Ginkgo biloba extract ('tanakan') in elderly outpatients with mild to moderate memory impairment.

Curr Med Res Opin, 12(6):350-5 1991

Thirty-one patients over the age of 50 years and showing a mild to moderate degree of memory impairment entered a 6-month double-blind, placebo controlled, parallel group design study to assess the effects of a standardized Ginkgo biloba extract (containing 24% flavonoid glycosides and 6% terpenes) on cognitive function. Patients were allocated at random to receive oral doses of 40 mg Ginkgo biloba extract or identical placebo 3-times daily. Assessments were made at baseline and after 12 and 24 weeks of treatment using a range of psychometric tests. Efficacy data were available for 27 patients (15 in the placebo group and 12 in the active treatment group). Statistical analysis of the data as compared to baseline suggests that Ginkgo biloba extract had a beneficial effect on cognitive function in this group of patients. Performance on the Digit Copying sub-test of the Kendrick battery was significantly improved at both 12 and 24 weeks, while the median speed of response on a computerized version of a classification task also showed a significant superiority over placebo at 24 weeks.




Ginkgo biloba for antidepressant-induced sexual dysfunction.

J Sex Marital Ther, 24(2):139-43 1998 Apr-Jun

In an open trial ginkgo biloba, an extract derived from the leaf of the Chinese ginkgo tree and noted for its cerebral enhancing effects, was found to be 84% effective in treating antidepressant-induced sexual dysfunction predominately caused by selective serotonin reuptake inhibitors (SSRIs, N = 63). Women (n = 33) were more responsive to the sexually enhancing effects of ginkgo biloba than men (N = 30), with relative success rates of 91% versus 76%. Ginkgo biloba generally had a positive effect on all 4 phases of the sexual response cycle: desire, excitement (erection and lubrication), orgasm, and resolution (afterglow). This study originated from the observation that a geriatric patient on ginkgo biloba for memory enhancement noted improved erections. Patients exhibited sexual dysfunction secondary to a variety of antidepressant medications including selective serotonin reuptake inhibitor (SSRIs), serotonin and nonrepinephrine reuptake inhibitor (SNRIs) monoamine oxidase inhibitor (MAOIs), and tricyclics. Dosages of ginkgo biloba extract ranged from 60 mg qd to 120 mg bid (average = 209mg/d). The common side effects were gastrointestinal disturbances, headache, and general central nervous system activation. The article includes a discussion of presumed pharmacologic mechanisms, including effects on platelet activating factor, prostaglandins, peripheral vasodilatation, and central serotonin and norepinephrine receptor factor modulation.




A natural and broad spectrum nootropic substance for treatment of SDAT--the Ginkgo biloba extract.

Prog Clin Biol Res, 40(5):1247-60 1989

The efficacy of the Ginkgo biloba extract was not only found clinically or in standardised ratings but also documented by objective data, obtained by a computerized EEG method, the DYNAMIC BRAIN MAPPING and BRAIN FUNCTION MONITORING SYSTEM (Dr. T. Itil, New York). A one year open trial comprise 25 parkinson patients with additional signs of SDAT. Data from 3 selected cases were given: The short time efficacy of the substance after the infusion and the long-term result after the oral medication. The maps showed less slower and more faster waves. Without any side effects the Ginkgo biloba extract seems to be a substance with a broad spectrum of influence. Our therapeutic findings in parkinsonian patients with SDAT and the data taken from healthy elderly volunteers revealed that the computerized EEG method may have another big advantage: It seems that the so-called anteriorisation of the Theta waves can be taken as a preclinical sign of an incipient change in brain metabolism. As a consequence--it might be that these changes are reversible by an adequate nootropic treatment. Further studies and treatment experiences must confirm these preliminary findings.




Effect of Ginkgo biloba on fluidity of blood and peripheral microcirculation in volunteers.

Arzneimittelforschung, 40(5):589-93 1990 May

In a randomized placebo controlled single-blind cross-over study of n = 10 apparently healthy subjects the influence of Ginkgo biloba (Kaveri) on blood fluidity and cutaneous microcirculation was studied. Microcirculation was measured before and every 30 min for 4 h after administration of Ginkgo biloba; fluidity of blood was determined before and after 1, 2 and 4 h. Significant changes in blood pressure or heart rate were found neither during Ginkgo phase nor placebo phase. Haematocrit, plasma viscosity, erythrocyte rigidity, thrombocyte and leukocyte count as well as thrombocyte aggregation and the number of circulating thrombocyte aggregates were also not influenced by the Ginkgo nor the placebo solution. In contrast a remarkable influence on the erythrocyte aggregation was observed: comparing two samples a significant decrease by 15.6% (p less than 0.001) with regard to the initial value was observed after 2 h. The blood flow in the nail fold capillaries also increased significantly by about 57% (p less than 0.004) 1 h after administration.




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, 29(2):47-56 1996 Mar

The efficacy of the ginkgo biloba special extract EGb 761 in outpatients with presenile and senile primary degenerative dementia of the Alzheimer type (DAT) and multi-infarct dementia (MID) according to DSM-III-R was investigated in a prospective, randomized, double-blind, placebo-controlled, multi-center study. After a 4-week run-in period, 216 patients were included in the randomized 24-week treatment period. These received either a daily oral dose of 240 mg EGb 761 or placebo. In accordance with the recommended multi-dimensional evaluation approach, three primary variables were chosen: the Clinical Global Impressions (CGI Item 2) for psychopathological assessment, the Syndrom-Kurztest (SKT) for the assessment of the patient's attention and memory, and the N¨urnberger Alters-Beobachtungsskala (NAB) for behavioral assessment of activities of daily life. Clinical efficacy was assessed by means of a responder analysis, with therapy response being defined as response in at least two of the three primary variables. The data from the 156 patients who completed the study in accordance with the study protocol were taken into account in the confirmatory analysis of valid cases. The frequency of therapy responders in the two treatment groups differed significantly in favor of EGb 761, with p <0.005 in Fisher's Exact Test. The intent-to-treat analysis of 205 patients led to similar efficacy results. Thus, the clinical efficacy of the ginkgo biloba special extract EGb 761 in dementia of the Alzheimer type and multi-infarct dementia was confirmed. The investigational drug was found to be well tolerated.




A placebo-controlled, double-blind, randomized trial of an extract of Ginkgo biloba for dementia. North American EGb Study Group.

JAMA, 278(16):1327-32 1997 Oct 22-29

CONTEXT: EGb 761 is a particular extract of Ginkgo biloba used in Europe to alleviate symptoms associated with numerous cognitive disorders. Its use in dementias is based on positive results from only a few controlled clinical trials, most of which did not include standard assessments of cognition and behavior. OBJECTIVE: To assess the efficacy and safety of EGb in Alzheimer disease and multi-infarct dementia. DESIGN: A 52-week, randomized double-blind, placebo-controlled, parallel-group, multicenter study. PATIENTS: Mildly to severely demented outpatients with Alzheimer disease or multi-infarct dementia, without other significant medical conditions. INTERVENTION: Patients assigned randomly to treatment with EGb (120 mg/d) or placebo. Safety, compliance, and drug dispensation were monitored every 3 months with complete outcome evaluation at 12, 26, and 52 weeks. PRIMARY OUTCOME MEASURES: Alzheimer's Disease Assessment Scale-Cognitive subscale (ADAS-Cog), Geriatric Evaluation by Relative's Rating Instrument (GERRI), and Clinical Global Impression of Change (CGIC). RESULTS: From 309 patients included in an intent-to-treat analysis, 202 provided evaluable data for the 52-week end point analysis. In the intent-to-treat analysis, the EGbgroup had an ADAS-Cog score 1.4 points better than the placebo group (P=.04) and a GERRI score 0.14 points better than the placebo group (P=.004). The same patterns were observed with the evaluable data set in which 27% of patients treated with EGb achieved at least a 4-point improvement on the ADAS-Cog, compared with 14% taking placebo (P=.005); on the GERRI, 37% were considered improved with EGb, compared with 23% taking placebo (P=.003). No difference was seen in the CGIC. Regarding the safety profile of EGb, no significant differences compared with placebo were observed in the number of patients reporting adverse events or in the incidence and severity of these events. CONCLUSIONS: EGb was safe and appears capable of stabilizing and, in a substantial number of cases, improving the cognitive performance and the social functioning of demented patients for 6 months to 1 year. Although modest, the changes induced by EGb were objectively measured by the ADAS-Cog and were of sufficient magnitude to be recognized by the caregivers in the GERRI.




Demonstration of the efficacy of ginkgo biloba special extract EGb 761 on intermittent claudication--a placebo-controlled, double-blind multicenter trial.

Vasa, 11(2):106-10 1998 May

BACKGROUND: A multicentric, randomized, placebo-controlled double-blind study on ginkgo biloba special extract EGb 761 (Tebonin forte) in patients suffering from peripheral occlusive arterial disease (POAD) in Fontaine stage II b was carried out in order to prove its clinical efficacy in this indication according to guidelines of European Community authorities and the German Angiological Society and to confirm the results of former clinical studies with EGb 761. PATIENTS AND METHODS: In total, 111 patients with angiographically proven POAD in Fontaine stage II b and intermittent claudication (pain-free walking distance <150 m on the treadmill) were recruited in 5 centers and treated with either EGb 761 or placebo at a daily dose of 3 times 1 film-coated tablet over a duration of 24 weeks following a 2-week placebo run-in period. The primary response variable was the difference of the pain-free walking distance between the start of treatment and after 8, 16 and 24 weeks as measured on the treadmill (walking speed 3 km/h and slope of 12%) under standardized conditions. RESULTS: At the start of the treatment period, the mean pain-free walking distances were very similar with 108.5 m in the EGb 761 group and 105.2 m in the placebo group. At the end of the treatment period these values increased to 153.2 m and 126.6 m, respectively. The group differences were statistically significant at all three control visits with p = 0.017, p = 0.007, and p = 0.016. The differences for the maximum walking distance and the relative increases of the pain-free walking distance and the maximum distance were also significantly higher in the EGb 761 group with p-values <0.05 each. In both groups Doppler indices remained nearly unchanged during therapy. The subjective assessment of the patients demonstrated an amelioration of complaints in both groups. Tolerability was very good with no adverse events under EGb 761 and one case of heartburn and gastric pain in the placebo group. CONCLUSIONS: It can be concluded from the results of this study that treatment with EGb 761 in POAD patients with Fontaine stage II b is very safe and causes a significant and therapeutically relevant prolongation of of the patients' walking distance.




Ginkgo biloba extract (EGb 761) pretreatment limits free radical-induced oxidative stress in patients undergoing coronary bypass surgery.

Cardiovasc Drugs Ther, 11(2):121-31 1997 Apr

A growing body of evidence supports the trigger role of free radicals in the delayed functional and metabolic myocardial recovery following cardiopulmonary bypass (CPB) in humans, thus opening the field to specific therapies. This 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 a matching placebo (n = 7) for 5 days before surgical intervention. Plasma samples were obtained from the peripheral circulation and the coronary sinus at crucial stages of the operation (i.e., before incision, during ischemia, and within the first 30 minutes post-unclamping), and up to 8 days postoperatively. Upon aortic unclamping, EGb 761 inhibited the transcardiac release of thiobarbituric acid-reactive species (p <0.05), as assessed by high-performance liquid chromatography, and attenuated the early (5-10 minute) decrease in dimethylsulfoxide/ascorbyl free radical levels, an electron spin resonance index of the plasma ascorbate pool (p <0.05). EGb 761 also significantly reduced the more delayed leakage of myoglobin (p = 0.007) and had an almost significant effect on ventricular myosin leakage (p = 0.053, 6 days postoperatively). The clinical outcome of recovery of treated patients was improved, but not significantly, compared with untreated patients. 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.




Dietary supplement users: demographics, product use, and medical system interaction.

J Am Board Fam Pract, 278(16):265-71 1997 Jul-Aug

BACKGROUND: Dietary supplements-defined as vitamins and minerals, herbal products, tissue extracts, proteins and amino acids, and other products-are purchased to improve health and prevent disease. Little has been published, however, about the characteristics of either the products or the people who use them. METHODS: Consecutive customers visiting two health food stores during a 15-day period were interviewed by telephone. They were asked about their use of dietary supplements, demographics, and their use of the established health care system. RESULTS: Of the 194 customers contacted, 136 (70.1 percent) completed the survey. Respondents took a total of 805 supplements, most often to prevent a health problem (84.3 percent). Herbal products were most commonly used. Garlic, ginseng, and Ginkgo biloba were the herbs most frequently used. Fifty products were found to have previously reported toxicities, including vitamin A, which 9 customers were taking in megadoses. Most customers were white (94.1 percent), female (75.7 percent), had at least 1 year of college education (70.6 percent), had health insurance (95.6 percent), and had a regular physician (85.3 percent). CONCLUSION: Most of the dietary supplements consumed appear to be safe, but 50 of 805 had previously reported toxicities including megadoses of vitamin A. Garlic, ginseng, and Ginkgo biloba were the most commonly ingested herbs, and the medical literature supports their effectiveness for some conditions in humans. Customers of two health food stores had average to above-average education and took dietary supplements to stay healthy. They used the conventional health care system but did not typically consult their physician about dietary supplements. The pattern of use suggests that physicians might not be adequately addressing preventive and wellness issues in discussions with their patients. Furthermore, physicians might need to learn about dietary supplements so they can communicate with patients about them.




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, 278(16):716-20 1984

79 patients suffering from peripheral arteriopathy (Fontaine's stage IIb) completed a 6-month double-blind randomised clinical trial of Ginkgo biloba extract (GBE) (as coated tablets containing 40 mg GBE; r¨okan) versus placebo in two parallel groups. From the results of measurements of pain-free walking distance, maximum walking distance and plethysmography recordings, GBE was shown to be active and significantly superior to placebo. These results correlated with the physician's and patients' overall assessment of response to treatment.




Oxidative stress in diabetic retina.

EXS, 4(5):299-307 1992

Electron paramagnetic resonance (EPR) spectroscopy was used to directly measure free radical generation in ischemic/reperfused diabetic rat retina. Tissue was frozen at 77 degrees K after 90 min ischemia, and 90 min ischemia followed by 1 min, 3 min, 5 min, and 24 hours reperfusion, respectively. After 90 min of ischemia followed by 1 min, 3 min, 5 min, and 24 hours of reperfusion (n = 10 in each group), free radical signal intensity was increased from its diabetic nonischemic control value of 12 +/- 3 arbitrary units to 58 +/- 6 (P <0.05), 62 +/- 7 (P <0.05), 32 +/- 5 (P <0.05), and 14 +/- 4 arbitrary units, respectively. The peak intensity of free radical production was observed after 90 min ischemia followed by 3 min of reperfusion; therefore, this time point was selected to study the retinal free radical production in superoxide dismutase (conjugated with polyethylene glycol, PEG-SOD) and EGb 761 (Ginkgo biloba extract)-treated groups. With 7,500, 15,000, and 30,000 U/liter of SOD, and 25, 50, and 100 mg/kg of EGb 761, a dose-dependent reduction in oxygen free radical production was detected, respectively, which may be responsible for the attenuation of abnormal postischemic function in ischemic and reperfused diabetic retina.




Direct measurement of free radicals in ischemic/reperfused diabetic rat retina.

Clin Neurosci, 4(5):240-5 1997

Electron paramagnetic resonance (EPR) spectroscopy was used to directly measure free radical generation in ischemic/reperfused diabetic rat retina. Tissue was frozen at 77 degrees K after 90 min ischemia, and 90 min ischemia followed by 1 min, 3 min, 5 min, and 24 hours reperfusion, respectively. After 90 min of ischemia followed by 1 min, 3 min, 5 min, and 24 hours of reperfusion (n = 10 in each group), free radical signal intensity was increased from its diabetic nonischemic control value of 12 +/- 3 arbitrary units to 58 +/- 6 (P <0.05), 62 +/- 7 (P <0.05), 32 +/- 5 (P <0.05), and 14 +/- 4 arbitrary units, respectively. The peak intensity of free radical production was observed after 90 min ischemia followed by 3 min of reperfusion; therefore, this time point was selected to study the retinal free radical production in superoxide dismutase (conjugated with polyethylene glycol, PEG-SOD) and EGb 761 (Ginkgo biloba extract)-treated groups. With 7,500, 15,000, and 30,000 U/liter of SOD, and 25, 50, and 100 mg/kg of EGb 761, a dose-dependent reduction in oxygen free radical production was detected, respectively, which may be responsible for the attenuation of abnormal postischemic function in ischemic and reperfused diabetic retina.




Peroxyl radical scavenging activity of Ginkgo biloba extract EGb 761.

Biochem Pharmacol, 49(11):1649-55 1995 May 26

Antioxidant mechanisms have been proposed to underlie the beneficial pharmacological effects of EGb 761, an extract from Ginkgo biloba leaves used for treating peripheral vascular diseases and cerebrovascular insufficiency in the elderly. In vitro evidence has been reported that EGb 761 scavenges various reactive oxygen species, i.e. nitric oxide, and the superoxide, hydroxyl, and oxoferryl radicals. However, the ability of EGb 761 to scavenge peroxyl radicals (reactive species mainly involved in the propagation step of lipid peroxidation) has not been investigated. To characterize further the antioxidant action of EGb 761, we measured the protective effects of EGb 761 during: (1) the oxidation of B-phycoerythrin by peroxyl radicals generated in aqueous solution by 2,2'-azobis (2-amidinopropane) hydrochloride (AAPH); and (2) the reaction of luminol or cis-parinaric acid with peroxyl radicals generated from 2,2'-azobis (2,4-dimethylvaleronitrile) (AMVN) in liposomes or in human low density lipoprotein (LDL), respectively. To evaluate the peroxyl radical scavenging activity of EGb 761 in a more physiologically relevant model of damage to lipid-containing systems, we also analyzed the effect of the extract on the oxidation of human LDL exposed to the azo-initiators in terms of: (1) accumulation of cholesterol linoleate ester hydroperoxides, (2) depletion of alpha-tocopherol and beta-carotene, and (3) changes in intrinsic tryptophan fluorescence. EGb 761 afforded protection against oxidative damage in all the systems we analyzed; thus, it is an efficient scavenger of peroxyl radicals. This result extends the oxygen radical scavenging properties of the extract and supports the hypothesis of an antioxidant therapeutic action of EGb 761.




Effects of flavonoids of Ginkgo biloba on proliferation of human skin fibroblast.

Skin Pharmacol, 10(4):200-5 1997

Ginkgo biloba studies have focused on the anti-inflammatory effects of the major components, ginkgolide and bilobalide, whereas little is known about their effect on fibroblasts. This study demonstrated the enhancing effects of Ginkgo L. extracts, especially the flavonoid fractions: quercetin, kaempferol, sciadopitysin, ginkgetin, isoginkgetin, on the proliferation of normal human skin fibroblast in vitro measured by MTT (3-[4,5-dimethylthiazole-2-yl]-2,5-diphenyl-tetrazolium bromide) assay and direct hemocytometer cell count. Furthermore, increased production of collagen and extracellular fibronectin were documented by radioisotope (2,3-3H-proline) incorporated collagen assay, procollagen type I C-peptide assay and by immunoturbidimetric assay. These proliferative effects suggest another useful pharmacologic application of Ginkgo L. extracts in addition to their well-known anti-inflammatory effect.




Ginkgo biloba extract (EGb 761) protects human low density lipoproteins against oxidative modification mediated by copper.

Biochem Biophys Res Commun, 11(2):360-6 1995 Jul 17

The antioxidant effects of Ginkgo biloba extract (EGb 761) on copper-mediated human low density lipoprotein (LDL) oxidative modification were evaluated by several techniques. Human LDL (0.5 mg/ml) in phosphate buffered saline, pH 7.4, was incubated with 10 microM cupric sulfate at 37 degrees C under air for 8 hours and 24 hours in the presence of varying concentrations of EGb 761. Increases in LDL apoB carbonylation, lipid peroxidation, apoB electrophoretic mobility and LDL fluorescence were all inhibited when the incubation mixture contained EGb 761 at concentrations less than 100 micrograms/ml. This inhibition was EGb 761-concentration-dependent. Thus, EGb 761 has powerful antioxidant effects on copper-mediated LDL oxidative modification.




Radiation-induced clastogenic factors: anticlastogenic effect of Ginkgo biloba

Free Radic Biol Med, 11(2):985-91 1995 Jun

Clastogenic factors (CFs) were first described in the blood of persons irradiated accidentally or for therapeutic reasons. Work of our laboratory has shown that they occur also under other circumstances, which are characterized by oxidative stress, and that CF-induced chromosome damage is regularly prevented by superoxide dismutase (SOD). Recently we found CFs in a high percentage of salvage personnel of the Chernobyl reactor accident. These liquidators represent a high-risk population and might benefit from cancer chemoprevention by antioxidants. SOD would have to be injected and is not appropriate for long-term prophylactic treatment. In the present study, we therefore evaluated the anticlastogenic effect of the Ginkgo biloba extract EGb 761, which is known for its superoxide scavenging properties. EGb 761 was tested on CF-treated blood cultures of healthy donors. After establishing the optimal protective EGb concentration, using CFs produced by irradiation of whole blood from healthy volunteers, the extract was tested on cultures exposed to CFs from plasma of persons irradiated as liquidators. The anticlastogenic effect could be confirmed for a final concentration of 100 micrograms/ml. In 12 consecutive experiments, CFs induced an average of 18.00 +/- 4.41 aberrations/100 cells. This was reduced to 7.33 +/- 3.08 in the parallel cultures receiving 100 micrograms/ml EGb 761 (p <.001). SOD was anticlastogenic in the same system at concentrations of 30 cytochrome C units/ml (approximately 10 micrograms/ml). 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).> < .001). SOD was anticlastogenic in the same system at concentrations of 30 cytochrome C units/ml (approximately 10 micrograms/ml). 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).