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Background

Cardiovascular disease (CVD) was a preplanned secondary outcome of the Ginkgo Evaluation of Memory (GEM) Study. The trial previously reported that Ginkgo biloba (G. biloba) had no effect on the primary outcome, incident dementia.

Methods and Results

The double-blind trial randomized 3069 participants over 75 years of age to 120 mg of G. biloba EGb 761 twice daily or placebo. Mean follow up was 6.1 years. The identification and classification of CVD was based on methods used in the Cardiovascular Health Study. Differences in time to event between G. biloba and placebo were evaluated using Cox proportional hazards regression adjusted for age and gender. There were 355 deaths in the study, 87 due to coronary heart disease with no differences between G. biloba and placebo. There were no differences in incident myocardial infarction (n=164), angina pectoris (n=207) or stroke (151) between G. biloba and placebo. There were 24 hemorrhagic strokes, 16 on G. biloba and 8 on placebo (not significant). There were only 35 peripheral vascular disease (PVD) events, 12 (0.8%) on G. biloba and 23 (1.5%) on placebo (p=0.04 exact test). Most of the PVD cases had either vascular surgery or amputation.

Conclusion

There was no evidence that G. biloba reduced total or CVD mortality or CVD events. There were more PVD events in the placebo arm. G. biloba cannot be recommended for preventing CVD. Further clinical trials of PVD outcomes might be indicated.

Purpose

Evidence from in vitro and in vivo studies suggests that Ginkgo biloba has cancer chemopreventive properties, but epidemiological evidence is sparse. We analyzed cancer as a secondary endpoint in the Ginkgo Evaluation of Memory (GEM) Study, the largest randomized, double-blind, placebo-controlled clinical trial of Ginkgo supplementation to date.

Methods

A total of 3,069 GEM participants 75+ years of age were randomized to twice-daily doses of either 120mg Ginkgo extract (EGb 761) or placebo and followed for a median 6.1 years. We identified hospitalizations for invasive cancer by reviewing hospital admission and discharge records for all reported hospitalizations over follow-up. Using an intention-to-treat approach, we compared the risk of cancer hospitalization between participants assigned to treatment and those assigned to placebo.

Results

During the intervention, there were 148 cancer hospitalizations in the placebo group and 162 in the EGb 761 group (Hazard ratio [HR], 1.09; 95% confidence interval [CI], 0.87–1.36; p=0.46). Among the site-specific cancers analyzed, we observed an increased risk of breast (HR, 2.15; 95% CI, 0.97–4.80; p=0.06) and colorectal (HR, 1.62; 95% CI, 0.92–2.87; p=0.10) cancer, and a reduced risk of prostate cancer (HR, 0.71; 95% CI, 0.43–1.17; p=0.18).

Conclusions

Overall, these results do not support the hypothesis that regular use of Ginkgo biloba reduces the risk of cancer.

Context

Ginkgo biloba is widely used for its potential effects on memory and cognition. To date, adequately powered clinical trials testing the effect of G biloba on dementia incidence are lacking.

Objective

To determine effectiveness of G biloba vs placebo in reducing the incidence of all-cause dementia and Alzheimer disease (AD) in elderly individuals with normal cognition and those with mild cognitive impairment (MCI).

Design, Setting, and Participants

Randomized, double-blind, placebo-controlled clinical trial conducted in 5 academic medical centers in the United States between 2000 and 2008 with a median follow-up of 6.1 years. Three thousand sixty-nine community volunteers aged 75 years or older with normal cognition (n=2587) or MCI (n=482) at study entry were assessed every 6 months for incident dementia.

Intervention

Twice-daily dose of 120-mg extract of G biloba (n=1545) or placebo (n=1524).

Main Outcome Measures

Incident dementia and AD determined by expert panel consensus.

Results

Five hundred twenty-three individuals developed dementia (246 receiving placebo and 277 receiving G biloba) with 92% of the dementia cases classified as possible or probable AD, or AD with evidence of vascular disease of the brain. Rates of dropout and loss to follow-up were low (6.3%), and the adverse effect profiles were similar for both groups. The overall dementia rate was 3.3 per 100 person-years in participants assigned to G biloba and 2.9 per 100 person-years in the placebo group. The hazard ratio (HR) for G biloba compared with placebo for all-cause dementia was 1.12 (95% confidence interval [CI], 0.94–1.33; P=.21) and for AD, 1.16 (95% CI, 0.97–1.39; P=.11). G biloba also had no effect on the rate of progression to dementia in participants with MCI (HR, 1.13; 95% CI, 0.85–1.50; P=.39).

Conclusions

In this study, G biloba at 120 mg twice a day was not effective in reducing either the overall incidence rate of dementia or AD incidence in elderly individuals with normal cognition or those with MCI.

Context

The herbal product Ginkgo biloba is taken frequently with the intention of improving cognitive health in aging. However, evidence from adequately powered clinical trials is lacking regarding its effect on long-term cognitive functioning.

Objective

To determine whether G biloba slows the rates of global or domain-specific cognitive decline in older adults.

Design, Setting, and Participants

The Ginkgo Evaluation of Memory (GEM) study, a randomized, double-blind, placebo-controlled clinical trial of 3069 community-dwelling participants aged 72 to 96 years, conducted in 6 academic medical centers in the United States between 2000 and 2008, with a median follow-up of 6.1 years.

Intervention

Twice-daily dose of 120-mg extract of G biloba (n=1545) or identical-appearing placebo (n=1524).

Main Outcome Measures

Rates of change over time in the Modified Mini-Mental State Examination (3MSE), in the cognitive subscale of the Alzheimer Disease Assessment Scale (ADAS-Cog), and in neuropsychological domains of memory, attention, visual-spatial construction, language, and executive functions, based on sums of z scores of individual tests.

Results

Annual rates of decline in z scores did not differ between G biloba and placebo groups in any domains, including memory (0.043; 95% confidence interval [CI], 0.034-0.051 vs 0.041; 95% CI, 0.032-0.050), attention (0.043; 95% CI, 0.037-0.050 vs 0.048; 95% CI, 0.041-0.054), visuospatial abilities (0.107; 95% CI, 0.097-0.117 vs 0.118; 95% CI, 0.108-0.128), language (0.045; 95% CI, 0.037-0.054 vs 0.041; 95% CI, 0.033-0.048), and executive functions (0.092; 95% CI, 0.086-0.099 vs 0.089; 95% CI, 0.082-0.096). For the 3MSE and ADAS-Cog, rates of change varied by baseline cognitive status (mild cognitive impairment), but there were no differences in rates of change between treatment groups (for 3MSE, P=.71; for ADAS-Cog, P=.97). There was no significant effect modification of treatment on rate of decline by age, sex, race, education, APOE*E4 allele, or baseline mild cognitive impairment (P>.05).

Conclusion

Compared with placebo, the use of G biloba, 120 mg twice daily, did not result in less cognitive decline in older adults with normal cognition or with mild cognitive impairment.

Trial Registration

clinicaltrials.gov Identifier: NCT00010803

Background

European Regulation 1924/2006 states that all health claims made on foods need to be substantiated scientifically.

Objective

To apply the PASSCLAIM criteria for the scientific substantiation of health claims on foods to herbal supplements containing Ginkgo biloba. Evaluation of three selected claimed health effects for G. biloba (improvement of blood circulation, improvement of symptoms of old age, and improvement of memory) was achieved through review of publicly available scientific data. A total of 35 human intervention studies were evaluated. Commercially available products claimed to contain mainly G. biloba (N=29) were randomly sampled in the Netherlands and analyzed for their content on ginkgo extract. Also, a toxicological risk assessment was performed.

Results

The three selected health claims investigated could not be substantiated. This was mainly because of a lack of data from studies in healthy volunteers. In most studies results performed with a 24% standardized G. biloba extract were described. However, our chemical analysis showed that 25 of the 29 sampled products did not contain the required minimum 24% standardized extract. Moreover, in most preparations the content of substances typical for G. biloba did not conform to what was declared on the label. Since toxicity data for G. biloba are very limited, a safety limit could not be established.

Conclusions

Evidence is lacking for three health claims of herbal products with G. biloba. Neither safety nor efficacy can be guaranteed at the recommended daily dose. The multidisciplinary approach described in this paper provides good insight into issues that are relevant for the evaluation of health claims for herbal food supplements.

Objectives

Personality factors parsimoniously capture the variation in dispositional characteristics that affect behaviours, but their value in predicting medication non-adherence is unclear. We investigated the relationship between five-factor model personality factors (Conscientiousness, Neuroticism, Agreeableness, Extraversion, and Openness) and medication non-adherence among older participants during a six-year randomized placebo-controlled trial (RCT).

Design

Observational cohort data from 771 subjects aged ≥72 years enrolled in the Ginkgo Evaluation of Memory study, a RCT of Ginkgo biloba for prevention of dementia.

Methods

Random effects logistic regression analyses examined effects of NEO Five-Factor Inventory scores on medication non-adherence, determined via pill counts every 6 months (median follow-up 6.1 years) and defined as taking <80% of prescribed pills. Analyses adjusted for covariates linked with non-adherence in prior studies.

Results

Each 5 year increment in participant age was associated with a 6.7% greater probability of non-adherence (95% confidence interval, CI [2.4, 11.0]). Neuroticism was the only personality factor associated with non-adherence: a 1 SD increase was associated with a 3.8% increase in the probability of non-adherence (95% CI [0.4, 7.2]). Lower cognitive function was also associated with non-adherence: a 1 SD decrease in mental status exam score was associated with a 3.0% increase in the probability of non-adherence (95% CI [0.2, 5.9]).

Conclusions

Neuroticism was associated with medication non-adherence over 6 years of follow-up in a large sample of older RCT participants. Personality measurement in clinical and research settings might help to identify and guide interventions for older adults at risk for medication non-adherence.

Objective To evaluate the efficacy of ginkgo biloba, acetazolamide, and their combination as prophylaxis against acute mountain sickness.

Design Prospective, double blind, randomised, placebo controlled trial.

Setting Approach to Mount Everest base camp in the Nepal Himalayas at 4280 m or 4358 m and study end point at 4928 m during October and November 2002.

Participants 614 healthy western trekkers (487 completed the trial) assigned to receive ginkgo, acetazolamide, combined acetazolamide and ginkgo, or placebo, initially taking at least three or four doses before continued ascent.

Main outcome measures Incidence measured by Lake Louise acute mountain sickness score ≥ 3 with headache and one other symptom. Secondary outcome measures included blood oxygen content, severity of syndrome (Lake Louise scores ≥ 5), incidence of headache, and severity of headache.

Results Ginkgo was not significantly different from placebo for any outcome; however participants in the acetazolamide group showed significant levels of protection. The incidence of acute mountain sickness was 34% for placebo, 12% for acetazolamide (odds ratio 3.76, 95% confidence interval 1.91 to 7.39, number needed to treat 4), 35% for ginkgo (0.95, 0.56 to 1.62), and 14% for combined ginkgo and acetazolamide (3.04, 1.62 to 5.69). The proportion of patients with increased severity of acute mountain sickness was 18% for placebo, 3% for acetazoalmide (6.46, 2.15 to 19.40, number needed to treat 7), 18% for ginkgo (1, 0.52 to 1.90), and 7% for combined ginkgo and acetazolamide (2.95, 1.30 to 6.70).

Conclusions When compared with placebo, ginkgo is not effective at preventing acute mountain sickness. Acetazolamide 250 mg twice daily afforded robust protection against symptoms of acute mountain sickness.

Objective

To determine whether Ginkgo biloba is effective in treating tinnitus.

Design

Double blind, placebo controlled trial using postal questionnaires.

Participants

1121 healthy people aged between 18 and 70 years with tinnitus that was comparatively stable; 978 participants were matched (489 pairs).

Intervention

12 weeks' treatment with either 50 mg Ginkgo biloba extract LI 1370 three times daily or placebo.

Main outcome measures

Participants' assessment of tinnitus before, during, and after treatment. Questionnaires included items assessing perception of how loud and how troublesome tinnitus was. Changes in loudness were rated on a six point scale. Changes in how troublesome were rated on a five point scale.

Results

There were no significant differences in primary or secondary outcome measures between the groups. 34 of 360 participants receiving active treatment reported that their tinnitus was less troublesome after 12 weeks of treatment compared with 35 of 360 participants who took placebo.

Conclusions

50 mg Ginkgo biloba extract LI 1370 given 3 times daily for 12 weeks is no more effective than placebo in treating tinnitus.

Background

The benefit of Ginkgo biloba has been discussed controversially. The aim of this review was to assess the effects of Ginkgo biloba in Alzheimer's disease as well as vascular and mixed dementia covering a variety of outcome domains.

Methods

We searched MEDLINE, EMBASE, the Cochrane databases, CINAHL and PsycINFO for controlled trials of ginkgo for Alzheimer's, vascular or mixed dementia. Studies had to be of a minimum of 12 weeks duration with at least ten participants per group. Clinical characteristics and outcomes were extracted. Meta-analysis results were expressed as risk ratios or standardized mean differences (SMD) in scores.

Results

Nine trials using the standardized extract EGb761® met our inclusion criteria. Trials were of 12 to 52 weeks duration and included 2372 patients in total. In the meta-analysis, the SMDs in change scores for cognition were in favor of ginkgo compared to placebo (-0.58, 95% confidence interval [CI] -1.14; -0.01, p = 0.04), but did not show a statistically significant difference from placebo for activities in daily living (ADLs) (SMD = -0.32, 95% CI -0.66; 0.03, p = 0.08). Heterogeneity among studies was high. For the Alzheimer subgroup, the SMDs for ADLs and cognition outcomes were larger than for the whole group of dementias with statistical superiority for ginkgo also for ADL outcomes (SMD = -0.44, 95% CI -0.77; -0.12, p = 0.008). Drop-out rates and side effects did not differ between ginkgo and placebo. No consistent results were available for quality of life and neuropsychiatric symptoms, possibly due to the heterogeneity of the study populations.

Conclusions

Ginkgo biloba appears more effective than placebo. Effect sizes were moderate, while clinical relevance is, similar to other dementia drugs, difficult to determine.

Abstract

Ginkgo biloba

extract (GBE) and anthocyanins are considered beneficial for various vascular diseases. This study was performed to evaluate the effect of GBE and anthocyanins on visual function in patients with normal tension glaucoma (NTG) based on the vascular theory of mechanisms of glaucomatous optic nerve damage. Retrospective analysis was carried out by a chart review of 332 subjects (209 men and 123 women) who were treated with anthocyanins (n=132), GBE (n=103), or no medication (control, n=97). Humphrey Visual Field (HVF) test, logarithm of the minimal angle of resolution best-corrected visual acuity (logMAR BCVA), intraocular pressure, blood pressure, and fasting blood glucose were determined before and after treatment. Complete ocular and systemic examinations were performed. The mean follow-up duration was 23.82±9.84 (range, 12–59) months; the mean anthocyanin treatment duration was 24.32±10.43 (range, 6–53) months, and the mean GBE treatment duration was 23.81±10.36 months (range, 6–59) months. After anthocyanin treatment, the mean BCVA for all eyes improved from 0.16 (±0.34) to 0.11 (±0.18) logMAR units (P=.008), and HVF mean deviation improved from −6.44 (±7.05) to −5.34 (±6.42) (P=.001). After GBE treatment, HVF mean deviation improved from −5.25 (±6.13) to −4.31 (±5.60) (P=.002). A generalized linear model demonstrated that the final BCVA was not affected by demographic differences among the groups. These results suggest that anthocyanins and GBE may be helpful in improving visual function in some individuals with NTG.

Background

The 'Hawthorne Effect' may be an important factor affecting the generalisability of clinical research to routine practice, but has been little studied. Hawthorne Effects have been reported in previous clinical trials in dementia but to our knowledge, no attempt has been made to quantify them. Our aim was to compare minimal follow-up to intensive follow-up in participants in a placebo controlled trial of Ginkgo biloba for treating mild-moderate dementia.

Methods

Participants in a dementia trial were randomised to intensive follow-up (with comprehensive assessment visits at baseline and two, four and six months post randomisation) or minimal follow-up (with an abbreviated assessment at baseline and a full assessment at six months). Our primary outcomes were cognitive functioning (ADAS-Cog) and participant and carer-rated quality of life (QOL-AD).

Results

We recruited 176 participants, mainly through general practices. The main analysis was based on Intention to treat (ITT), with available data. In the ANCOVA model with baseline score as a co-variate, follow-up group had a significant effect on outcome at six months on the ADAS-Cog score (n = 140; mean difference = -2.018; 95%CI -3.914, -0.121; p = 0.037 favouring the intensive follow-up group), and on participant-rated quality of life score (n = 142; mean difference = -1.382; 95%CI -2.642, -0.122; p = 0.032 favouring minimal follow-up group). There was no significant difference on carer quality of life.

Conclusion

We found that more intensive follow-up of individuals in a placebo-controlled clinical trial of Ginkgo biloba for treating mild-moderate dementia resulted in a better outcome than minimal follow-up, as measured by their cognitive functioning.

Trial registration

Current controlled trials: ISRCTN45577048

Purpose:

To examine the effects of Ginkgo biloba extract EGb 761® on neuropsychiatric symptoms of dementia.

Patients and methods:

Randomized, controlled, double-blind, multicenter clinical trial involving 410 outpatients with mild to moderate dementia (Alzheimer’s disease with or without cerebrovascular disease, vascular dementia), scoring at least 5 on the Neuropsychiatric Inventory (NPI), with at least one item score of 3 or more. Total scores on the SKT cognitive test battery (Erzigkeit’s short syndrome test) were between 9 and 23. After random allocation, the patients took 240 mg of EGb 761® or placebo once daily for a period of 24 weeks. Changes from baseline to week 24 in the NPI composite and in the SKT total score were the primary outcomes. The NPI distress score was chosen as a secondary outcome measure to evaluate caregivers’ distress.

Results:

The NPI composite score improved by −3.2 (95% confidence interval −4.0 to −2.3) in patients taking EGb 761® (n = 202), but did not change (−0.9; 0.9) in those receiving placebo (n = 202), which resulted in a statistically significant difference in favor of EGb 761® (P < 0.001). Treatment with EGb 761® was significantly superior to placebo for the symptoms apathy/indifference, sleep/night-time behavior, irritability/lability, depression/dysphoria, and aberrant motor behavior. Caregivers’ distress evaluation revealed similar baseline pattern and improvements.

Conclusion:

Treatment with EGb 761®, at a once-daily dose of 240 mg, was safe, effectively alleviated behavioral and neuropsychiatric symptoms in patients with mild to moderate dementia, and improved the wellbeing of their caregivers.

Objective

To assess the feasibility, safety, and efficacy of Ginkgo biloba extract (GBE) on delaying the progression to cognitive impairment in normal elderly aged 85 and older.

Methods

Randomized, placebo-controlled, double-blind, 42-month pilot study with 118 cognitively intact subjects randomized to standardized GBE or placebo. Kaplan-Meier estimation, Cox proportional hazard, and random-effects models were used to compare the risk of progression from Clinical Dementia Rating (CDR) = 0 to CDR = 0.5 and decline in episodic memory function between GBE and placebo groups.

Results

In the intention-to-treat analysis, there was no reduced risk of progression to CDR = 0.5 (log-rank test, p = 0.06) among the GBE group. There was no less of a decline in memory function among the GBE group (p = 0.05). In the secondary analysis, where we controlled the medication adherence level, the GBE group had a lower risk of progression from CDR = 0 to CDR = 0.5 (HR = 0.33, p = 0.02), and a smaller decline in memory scores (p = 0.04). There were more ischemic strokes and TIAs in the GBE group (p = 0.01).

Conclusions

In unadjusted analyses, Ginkgo biloba extract (GBE) neither altered the risk of progression from normal to Clinical Dementia Rating (CDR) = 0.5, nor protected against a decline in memory function. Secondary analysis taking into account medication adherence showed a protective effect of GBE on the progression to CDR = 0.5 and memory decline. Results of larger prevention trials taking into account medication adherence may clarify the effectiveness of GBE. More stroke and TIA cases observed among the GBE group requires further study to confirm.

Ginkgo Biloba extract (GBE) is increasingly used to alleviate symptoms of age related cognitive impairment, with preclinical evidence pointing to a pro-cholinergic effect. While a number of behavioral studies have reported improvements to working memory (WM) associated with GBE, electrophysiological studies of GBE have typically been limited to recordings during a resting state. The current study investigated the chronic effects of GBE on steady state visually evoked potential (SSVEP) topography in nineteen healthy middle-aged (50-61 year old) male participants whilst completing an object WM task. A randomized double-blind crossover design was employed in which participants were allocated to receive 14 days GBE and 14 days placebo in random order. For both groups, SSVEP was recorded from 64 scalp electrode sites during the completion of an object WM task both pre- and 14 days post-treatment. GBE was found to improve behavioural performance on the WM task. GBE was also found to increase the SSVEP amplitude at occipital and frontal sites and increase SSVEP latency at left temporal and left frontal sites during the hold component of the WM task. These SSVEP changes associated with GBE may represent more efficient processing during WM task completion.

A multitude of factors are involved in regulating the blood coagulation homeostatic processes in the body, which may ultimately lead to thromboemboli and thrombosis. The resolution of blood clots after healing is as important as clot formation at the site of a vascular lesion. This is accomplished by fibrinolytic drugs such as streptokinase (SK) and urokinase.

It must be noted that administration of SK may be accompanied by the lysis of blood clots in unwanted sites, and complications such as general lytic conditions, severe hemorrhaging, reduced serum fibrinogen and allergies can occur. Anti-SK antibodies neutralize the effects of SK. Studies on natural compounds and medicinal herbs with fewer side effects have been ongoing. In the present study, the fibrinolytic effect of Ginkgo biloba, an herb grown in Iran, was investigated.

A polyphenolic method was used to obtain Ginkgo extract from its leaves. The fibrinolytic effects of SK (positive control) were compared with those of Ginkgo extract using a fluorometry method.

In producing a labelled clot, fibrinogen was labelled with the fluorescent agent fluorescein isothiocyanate and precipitated in the presence of Ca2+. SK (100 U/mL to 1000 U/mL) and Ginkgo extract were added to labelled fibrin in a plasma environment at dilutions of 1, 1:10, 1:100 and 1:1000 (volume/volume). The fluorescence of the solution was measured between 15 min and 60 min later.

A linear relationship was observed between the fluorescence measured and SK concentrations ranging from 300 U/mL to 700 U/mL. Ginkgo extract displayed a remarkable effect in resolving the clot. As Ginkgo extract remained in the environment, fluorescence increased notably, showing a time-dependent relationship.

Overall, the results indicate that the effects of Ginkgo extract on the fibrinolytic system are similar to those of SK; hence, this herbal extract can be used as a complement to or a substitute for SK. Additionally, it is proposed that the effects of the active ingredients of Ginkgo extract should be studied in animals. Further studies are warranted for evaluating the possible side effects and toxicity of Ginkgo extract in human subjects.

PURPOSE

Medical therapies for treatment of peripheral artery disease (PAD) are limited. Ginkgo biloba has been reported to increase maximal and pain-free walking distance among patients with (PAD); however, the evidence is inconsistent. The objective of this study was to compare the effects of 300 mg/d of Ginkgo biloba (EGb 761) vs. placebo on treadmill walking time and related cardiovascular measures among subjects with PAD.

METHODS

A double-blind, placebo-controlled, parallel design trial with a 4 month duration was employed. Subjects were 62 adults, age 70 ± 8 years (mean, SD), with claudication symptoms of PAD. The primary study outcomes were maximal and pain free walking time on a treadmill. Secondary outcomes included flow mediated vasodilation (FMVD), a measure of antioxidant status as assessed by determining antibody levels to epitopes of oxidized LDL, and questionnaires addressing walking impairment and quality of life.

RESULTS

Maximal treadmill walking time increased by 20±80s and 91±242s in the placebo and EGb 761 groups, respectively (P=0.12). Pain-free walking time increased by 15±31s and 21±43s, respectively (P=0.28). No significant differences were detected between groups for any of the secondary outcomes.

CONCLUSIONS

In older adults with PAD, Ginkgo biloba produced a modest but insignificant increase in maximal treadmill walking time and flow-mediated vasodilation. These data do not support the use of Ginkgo biloba as an effective therapy for PAD, although a longer duration of use should be considered in any future trials.

Purpose

Based on the vascular theory of glaucoma pathogenesis, we wanted to evaluate the effect of Ginkgo biloba extract (GBE) on peripapillary blood flow in patients with normal tension glaucoma (NTG).

Methods

Thirty patients with NTG were randomly placed in the GBE-treated or control groups. The GBE-treated group received 80 mg GBE orally, twice a day for four weeks, and the control group received a placebo twice a day for four weeks. Complete ocular examinations including visual field, Heidelberg retina flowmeter, and systemic examinations were performed on the first study day and on the day treatment was completed.

Results

After GBE treatment, the mean blood flow, volume, and velocity increased at almost all points, and there was a statistically significant increase in blood flow at almost all points, in comparison to the placebo. Blood volume significantly increased only in the superior nasal and superior temporal neuroretinal rim areas. GBE also significantly increased blood velocity in areas of the inferior temporal neuroretinal rim and superior temporal peripapillary area.

Conclusions

GBE administration appears to have desirable effect on ocular blood flow in NTG patients.

Purpose

We assessed the human in vivo metabolic drug interaction profile of Ginkgo biloba extract EGb 761® with respect to the activities of major cytochrome P450 (CYP) enzymes.

Methods

A single-center, open-label, randomized, three-fold crossover, cocktail phenotyping design was applied. In random order, the following treatments were administered to 18 healthy men and women for 8 days each: placebo twice daily, EGb 761® 120 mg twice daily, and EGb 761® 240 mg in the morning and placebo in the evening. In the morning of day 8, administration was performed together with the orally administered phenotyping cocktail (enzyme, metric): 150 mg caffeine (CYP1A2, paraxanthine/caffeine plasma ratio 6-h postdose), 125 mg tolbutamide (CYP2C9, plasma concentration 24-h postdose), 20 mg omeprazole (CYP2C19, omeprazole/5-hydroxy omeprazole plasma ratio 3-h postdose), 30 mg dextromethorphan (CYP2D6, dextromethorphan/dextrorphan plasma ratio 3-h postdose), and 2 mg of midazolam (CYP3A, plasma concentration 6-h postdose). Formally, absence of a relevant interaction was assumed if the 90% confidence intervals (CIs) for EGb 761®/placebo ratios of the metrics were within the 0.70–1.43 range.

Results

EGb 761®/placebo ratios for phenotyping metrics were close to unity for all CYPs. Furthermore, respective CIs were within the specified margins for all ratios except CYP2C19 for EGb 761® 120 mg twice daily (90% CI 0.681–1.122) and for CYP2D6 for EGb 761® 240 mg once daily (90% CI 0.667–1.281). These findings were attributed to the intraindividual variability of the metrics used. All treatments were well tolerated.

Conclusion

EGb 761® has no relevant effect on the in vivo activity of the major CYP enzymes in humans and therefore has no relevant potential to cause respective metabolic drug–drug interactions.

Background

Numerous studies have looked at the potential benefits of various nootropic drugs such as Ginkgo biloba extract (EGb761®; Tanakan®) and piracetam (Nootropyl®) on age-related cognitive decline often leading to inconclusive results due to small sample sizes or insufficient follow-up duration. The present study assesses the association between intake of EGb761® and cognitive function of elderly adults over a 20-year period.

Methods and Findings

The data were gathered from the prospective community-based cohort study ‘Paquid’. Within the study sample of 3612 non-demented participants aged 65 and over at baseline, three groups were compared: 589 subjects reporting use of EGb761® at at least one of the ten assessment visits, 149 subjects reporting use of piracetam at one of the assessment visits and 2874 subjects not reporting use of either EGb761® or piracetam. Decline on MMSE, verbal fluency and visual memory over the 20-year follow-up was analysed with a multivariate mixed linear effects model. A significant difference in MMSE decline over the 20-year follow-up was observed in the EGb761® and piracetam treatment groups compared to the ‘neither treatment’ group. These effects were in opposite directions: the EGb761® group declined less rapidly than the ‘neither treatment’ group, whereas the piracetam group declined more rapidly (β = −0.6). Regarding verbal fluency and visual memory, no difference was observed between the EGb761® group and the ‘neither treatment’ group (respectively, β = 0.21 and β = −0.03), whereas the piracetam group declined more rapidly (respectively, β = −1.40 and β = −0.44). When comparing the EGb761® and piracetam groups directly, a different decline was observed for the three tests (respectively β = −1.07, β = −1.61 and β = −0.41).

Conclusion

Cognitive decline in a non-demented elderly population was lower in subjects who reported using EGb761® than in those who did not. This effect may be a specific medication effect of EGb761®, since it was not observed for another nootropic medication, piracetam.

Ginkgo biloba extract (GBE) facilitates blood flow, influences nitric oxide systems, and has a relaxant effect on smooth muscle tissue. These processes are important to the sexual response in women and, hence, it is feasible that GBE may have a therapeutic effect. The present study was the first to provide an empirical examination of the effects of both short- and long-term GBE administration on subjective and physiological (vaginal photoplethysmography) measures of sexual function in women with Sexual Arousal Disorder. A single dose of 300 mg GBE had a small but significant facilitatory effect on physiological, but not subjective, sexual arousal compared to placebo in 99 sexually dysfunctional women. The long-term effects of GBE on sexual function were assessed in 68 sexually dysfunctional women who were randomly assigned to 8 weeks treatment of either (1) GBE (300 mg/daily), (2) placebo, (3) sex therapy which focused on training women to attend to genital sensations, or (4) sex therapy plus GBE. When combined with sex therapy, but not alone, long-term GBE treatment significantly increased sexual desire and contentment beyond placebo. Sex therapy alone significantly enhanced orgasm function compared with placebo. Long-term GBE administration did not significantly enhance arousal responses beyond placebo. It was concluded that (1) neither short- or long-term administration of GBE alone substantially impacts sexual function in women, (2) a substantial placebo effect on sexual function exists in women with sexual concerns, and (3) teaching women to focus on genital sensations during sex enhances certain aspects of women’s sexual functioning.

Aged dogs demonstrate cognitive decline that is linked to brain aging. The purpose of the present study was to examine if a commercially available nutraceutical supplement that may be neuroprotective and contains phosphatidylserine, Ginkgo biloba, vitamin E, and pyridoxine could improve cognitive function in aged beagles. Nine aged beagles were tested on performance on a delayed-non-matching-to-position task, which is a neuropsychological test of short-term visuospatial memory. All subjects were tested on 5 baseline sessions; then, to assess the supplement, a crossover design was used in which 1 group received the supplement and the other a control substance in the 1st phase, with treatment conditions being reversed in the 2nd phase. Performance accuracy was significantly improved in supplemented dogs compared with control dogs and the effect was long lasting. These findings suggest that the nutraceutical supplement can improve memory in aged dogs.

Tinnitus is a symptom frequently encountered by ear, nose, and throat practitioners. A causal treatment is rarely possible, and drug and nondrug treatment options are limited. One of the frequently prescribed treatments is Ginkgo biloba extract. Therefore, randomized, placebo-controlled clinical trials of Ginkgo biloba extract preparations were searched for and reviewed systematically. There is evidence of efficacy for the standardized extract, EGb 761® (Dr Willmar Schwabe GmbH & Co KG Pharmaceuticals, Karlsruhe, Germany), in the treatment of tinnitus from three trials in patients in whom tinnitus was the primary complaint. Supportive evidence comes from a further five trials in patients with age-associated cognitive impairment or dementia in whom tinnitus was present as a concomitant symptom. As yet, the efficacy of other ginkgo preparations has not been proven, which does not necessarily indicate ineffectiveness, but may be due to flawed clinical trials. In conclusion, EGb 761®, a standardized Ginkgo biloba extract, is an evidence-based treatment option in tinnitus.

Introduction

Extract of Ginkgo biloba (EGb), a dietary supplement used for a number of conditions including dementia, has been suggested to increase cerebral blood flow (CBF). The purpose of this study was to determine if changes in CBF could be detected by dynamic susceptibility contrast-enhanced magnetic resonance imaging (DSC-MRI) in elderly human subjects taking EGb.

Methods

DSC-MRI was performed in nine healthy men (mean age 61±10 years) before and after 4 weeks of 60 mg EGb taken twice daily. One subject underwent six consecutive scans to evaluate intrasubject reproducibility. CBF values were computed before and after EGb, and analyzed at three different levels of spatial resolution, using voxel-based statistical parametric mapping (SPM), and regions of interest in different lobes, and all regions combined.

Results

Normalized intrasubject CBF (nCBF) measurements had a standard deviation of 7% and 4% in gray and white matter (WM) regions, respectively. SPM using an uncorrected, voxel-level threshold of P≤0.001 showed a small CBF increase in the left parietal–occipital region. CBF in individual lobar regions did not show any significant change post-EGb, but all regions combined showed a significant increase of non-normalized CBF after EGb (15% in white and 13% in gray matter, respectively, P≤0.0001).

Conclusion

nCBF measured by DSC-MRI has good intra-subject reproducibility. In this small cohort of normal elderly individuals, a mild increase in CBF is found in the left parietal–occipital WM after EGb, as well as a small but statistically significant increase in global CBF.

The prevalence of hypertension is higher among African-Americans than whites. However, inconsistent findings have been reported on the incidence of hypertension among middle-aged and older African-Americans and whites and limited data are available on the incidence of hypertension among Hispanics and Asians in the US. Therefore, this study investigated the age-specific incidence of hypertension by ethnicity for 3,146 participants from the Multi-Ethnic Study of Atherosclerosis. Participants, age 45–84 years at baseline, were followed for a median of 4.8 years for incident hypertension, defined as systolic blood pressure ≥ 140 mmHg, diastolic blood pressure ≥ 90 mmHg, or the initiation of antihypertensive medications. The crude incidence rate of hypertension, per 1,000 person-years, was 56.8 for whites, 84.9 for African-Americans, 65.7 for Hispanics, and 52.2 for Chinese. After adjustment for age, gender, and study site, the incidence rate ratio (IRR) for hypertension was increased for African-Americans age 45–54 (IRR=2.05, 95% CI=1.47, 2.85), 55–64 (IRR=1.63, 95% CI=1.20, 2.23), and 65–74 years (IRR=1.67, 95% CI=1.21, 2.30) compared with whites, but not for those 75–84 years of age (IRR=0.97, 95% CI=0.56, 1.66). Additional adjustment for health characteristics attenuated these associations. Hispanic participants also had a higher incidence of hypertension compared with whites; however, hypertension incidence did not differ for Chinese and white participants. In summary, hypertension incidence was higher for African-Americans compared with whites between 45 and 74 years of age but not after age 75 years. Public health prevention programs tailored to middle-age and older adults are needed to eliminate ethnic disparities in incident hypertension.

The regular extract of Ginkgo biloba has been shown to possess neuroprotective properties in disorders like hypoxia, ischemia, seizure activity and peripheral nerve damage. Also, G. biloba has received attention as a potential cognitive enhancer for the treatment of Alzheimer's disease, but there is not any documentation about the effect of an extract of G. biloba on astrocytes. Therefore, the aim of this study was examined the effects of G. biloba extract on the rat's hippocampal astrocytes after scopolamine based amnesia. In this study, 36 adult male Wistar rats were used. Rats were randomly distributed into control, sham, protective and treatment groups. The rats in the sham group only received scopolamine hydrobromide (3 mg/kg) intraperitoneally. The rats in the protective and treatment groups received G. biloba extract (40, 80 mg/kg) for 7 days intraperitoneally before and after scopolamine injection. Forty eight hours after the last injection, the brains of the rats were withdrawn and fixed with paraformaldehide, and then after histological processing, the slices were stained with phosphotungstic acid-haematoxylin for astrocytes. Data were analyzed by the analysis of variance (ANOVA) post hoc Tukey test; P<0.05 was considered significant. Results showed that scopolamine can reduce the number of astrocytes in all areas of hippocampal formation compared with the control. However, G. biloba extract can compensate for the reduction in the number of astrocytes in the hippocampus before or after the encounter with scopolamine. We concluded that a pretreatment and treatment injection of G. biloba extract can have a protective effect for astrocytes in all areas of hippocampal formation.