Kim, H. S., G. Y. Kim, C. W. Yeo, M. Oh, J. L. Ghim, J. H. Shon, E. Y. Kim, D. H. Kim and J. G. Shin. 2013. The effect of ginkgo biloba extracts on the pharmacokinetics and pharmacodynamics of cilostazol and its active metabolites in healthy Korean subjects. Br J Clin Pharmacol. [Epub ahead of print]
AIM: The primary objective of this study was to evaluate the effects of Ginkgo biloba extracts (GBE) on the pharmacokinetics of cilostazol and its metabolites. Secondary objective was to assess the effect of GBE on pharmacodynamics of cilostazol.
METHODS: A randomized, double-blind, two-way crossover study was conducted with 34 healthy Korean subjects. All subjects were given an oral dose of cilostazol (100 mg) plus GBE (80 mg) or cilostazol (100 mg) plus placebo twice daily for 7 days. Plasma concentrations of cilostazol and its active metabolites (3,4-dehydrocilostazol and 4'-trans-hydroxycilostazol) were measured using liquid chromatography tandem mass spectroscopy (LC-MS/MS) on day 7 for pharmacokinetic assessment. ADP-induced platelet aggregation and bleeding time were measured at baseline and on day 7 for pharmacodynamic assessment.
RESULTS: The geometric mean ratios of AUCτ for cilostazol plus GBE versus cilostazol plus placebo were 0.96 (90% CI, 0.89-1.03; p=0.20) for cilostazol; 0.96 (90% CI, 0.90-1.02; p=0.30) for 3,4-dehydrocilostazol; and 0.98 (90% CI, 0.93-1.03; p=0.47) for 4'-trans-hydroxycilostazol, respectively. The change of aggregation after administration of cilostazol plus GBE seemed to be 1.31 times higher compared with cilostazol plus placebo without statistical significance (p=0.20). There were no significant changes in bleeding time and adverse drug reaction between the treatments.
CONCLUSIONS: Co-administration of GBE showed no statistically significant effects on the pharmacokinetics of cilostazol in healthy subjects. The long-term large cohort clinical study seems to be remained to evaluate the possible pharmacodynamic interaction between cilostazol and GBE, since there was remarkable, but no statistically significant, increase of platelet aggregation inhibition.
Ihl, R. 2013. Effects of Ginkgo biloba extract EGb 761® in dementia with neuropsychiatric features: review of recently completed randomised, controlled trials Int J Psychiatry Clin Pract. 17, 1: 8-14.
Abstract: Objective. We review four randomised, controlled trials investigating the efficacy of Ginkgo biloba extract EGb 761(®) in elderly patients with Alzheimer or vascular dementia with neuropsychiatric features. Methods. Patients with a total score of 9-23 in the Syndrom-Kurz test (SKT) cognitive test battery (cognitive domain) and with a composite score 6 and greater in the Neuropsychiatric Inventory (NPI; behavioural domain) were included. Three trials compared 2 × 120 mg/day or 1 × 240 mg/day EGb 761(®) to placebo while one used donepezil as an active control. The duration of randomised treatment was 22 or 24 weeks. Results. One thousand, two hundred and ninety-four patients were analysed for efficacy. Patients treated with EGb 761(®) showed improvements of cognitive performance and behavioural symptoms that were associated with advances in activities of daily living and a reduced burden to caregivers. Placebo-treated patients, on the other hand, showed only minimal improvements or signs of progression. In each placebo-controlled trial, EGb 761(®) was significantly superior in all mentioned domains (p < 0.01). In the actively controlled trial, EGb 761(®) and donezepil as well as a combination of both drugs had similar effects. Conclusions. The review supports the efficacy of EGb 761(®) in age-related dementia with neuropsychiatric features. The drug was safe and well-tolerated.
Diamond, B. J. and M. R. Bailey. 2013. Ginkgo biloba: Indications, Mechanisms, and Safety. Psychiatr Clin North Am. 36, 1: 73-83.
Abstract: Ginkgo biloba special extract (EGb761) is used in most randomized control trials. Indications include cognition and memory in Alzheimer disease, age-associated dementia, cerebral insufficiency, intermittent claudication, schizophrenia, and multi-infarct dementia. Dosages range from 80 to 720 mg/d for durations of 2 weeks to 2 years. Mechanisms of action include increasing cerebral blood flow, antioxidant and antiinflammatory effects, with antiplatelet effects attributed to flavone and terpene lactones. Possible interactions with monoamine oxidase inhibitors, alprazolam, haloperidol, warfarin, and nifedipine have been reported. Optimal dosage/duration, dose-response characteristics, drug interactions, bioavailability, long-term effects, and optimal intervention timing should be the focus of future work.
Hong, J. M., D. H. Shin, Y. A. Lim, J. S. Lee and I. S. Joo. 2013. Ticlopidine with Ginkgo Biloba extract: A Feasible Combination for Patients with Acute Cerebral Ischemia. Thromb Res. pii: S0049-3848 (13) 00031-5.
BACKGROUND: Even though clopidogrel is the most used drug for cardiovascular prevention, resistance occurs in significant numbers. Therefore, we evaluated platelet aggregation ability of thienopyridines in relation with various genotypes.
METHOD: The study population was randomly assigned with clopidogrel (n=43), ticlopidine (n=41), or ticlopidine plus Gingko Biloba extract (EGb) (n=43). Dosage was maintained as 75mg clopidogrel daily, 250mg ticlopidine twice daily, and 250mg ticlopidine plus 80mg Gingko Biloba extract twice daily. Using multiple electrodes aggregometry, platelet aggregation was measured by activators of adenosine diphosphate (ADP), arachidonic acid (ASP), and thrombin (TRAP) at baseline (T0), 7days (T1), and 90days (T2). Side-effects were analyzed in the 3 groups. Inhibition of platelet aggregation (IPA) was defined as percent decrease at T0 and T1. Non-responsiveness (
RESULTS: There was no difference of general demographics and platelet aggregation at baseline in all groups. A significant difference of platelet aggregation showed on ADP test in the groups at T1 (28.9±17.2 vs.22.7±11.1 vs. 14.6±10.3%, p<0.001) and T2 (27.5±24.5 vs.18.3±16.6 vs. 14.4±9.8%, p=0.007), whereas ASP (p=0.064) and TRAP tests (p=0.143) had no differences at T1. Serious adverse events had no differences among the groups (p=0.902). CYP2C19 *2 alleles had poor responsiveness of clopidogrel (p=0.038), and not in ticlopidine (p=0.780).
CONCLUSIONS: This finding suggests that ticlopidine plus Gingko Biloba extract has sufficient anti-platelet abilities with an acceptable profile of adverse events and CYP2C19 *2 alleles are associated with clopidogrel responsiveness.
Barton, D. L., K. Burger, P. J. Novotny, T. R. Fitch, S. Kohli, G. Soori, M. B. Wilwerding, J. A. Sloan, L. A. Kottschade, K. M. Rowland Jr., S. R. Dakhil, D. A. Nikcevich and C. L. Loprinzi. The use of Ginkgo biloba for the prevention of chemotherapy-related cognitive dysfunction in women receiving adjuvant treatment for breast cancer, N00C9. Support Care Cancer. 21, 4: 1185-1192.
PURPOSE: Patients undergoing treatment for cancer often report problems with their cognitive function, which is an essential component of health-related quality of life. Pursuant to this, a two-arm randomized, placebo-controlled, double-blind, phase III clinical trial was conducted to evaluate Ginkgo biloba (EGB 761) for the prevention of chemotherapy-related cognitive dysfunction in patients with breast cancer.
METHODS: Previously chemotherapy naïve women about to receive adjuvant chemotherapy for breast cancer were randomized to receive 60 mg of EGB 761 or a matching placebo twice daily. The study agent was to begin before their second cycle of chemotherapy and to be taken throughout chemotherapy and 1 month beyond completion. The primary measure for cognitive function was the High Sensitivity Cognitive Screen (HSCS), with a secondary measure being the Trail Making Tests (TMT) A and B. Subjective assessment of cognitive function was evaluated by the cognitive subscale of the Perceived Health Scale (PHS) and the Profile of Mood States (POMS). Data were collected at baseline and at intervals throughout and after chemotherapy, up to 24 months after completion of adjuvant treatment. The primary statistical analysis included normalized area under the curve (AUC) comparisons of the HSCS, between the arms. Secondary analyses included evaluation of the other measures of cognition as well as correlational analyses between self-report and cognitive testing.
RESULTS: One hundred and sixty-six women provided evaluable data. There were no significant differences in AUC up to 12 months on the HSCS between arms at the end of chemotherapy or at any other time point after adjuvant treatment. There were also no significant differences in TMT A or B at any data point. Perceived cognitive functions, as measured by the PHS and confusion/bewilderment subscale of the POMS, were not different between arms at the end of chemotherapy. There was also little correlation between self-reported cognition and cognitive testing. No differences were observed in toxicities per Common Terminology Criteria for Adverse Events (CTCAE) assessment between Ginkgo biloba and placebo throughout the study; however, after chemotherapy, the placebo group reported worse nausea (p = .05).
CONCLUSION: This study did not provide any support for the notion that Ginkgo biloba, at a dose of 60 mg twice a day, can help prevent cognitive changes from chemotherapy. These analyses do provide data to further support the low associations between patients' self-report of cognition and cognitive performance, based on more formal testing.
Polanski, J. F. and O. L. Cruz. 2013. Evaluation of antioxidant treatment in presbyacusis: prospective,
placebo-controlled, double-blind, randomised trial.J Laryngol Otol. 15: 1-8.
Objective: There are many well-known aetiological mechanisms of presbyacusis,
and free radicals have been shown to play an important role. This study aimed to
evaluate the effect of antioxidant agents on the hearing threshold of patients
with presbyacusis. Methods: One hundred and twenty individuals were divided into
four groups and received one of the following treatment schemes: ginkgo biloba dry extract, α-lipoic acid plus vitamin C,
papaverine chlorhydrate plus vitamin E, or placebo. All participants were
evaluated at recruitment and after six months, using pure tone audiometry (at
isolated and average frequencies), speech recognition threshold and percentage
index of speech recognition. Results: The various treatments had no effect on
any of the evaluated measures of hearing, either between groups or over time.
Conclusion: There was no statistically significant change in the hearing
threshold after treatment with any of the tested drugs, during the study
Blonk, M., A. Colbers, A. Poirters, B. Schouwenberg and D. Burger. 2012. Effect of Ginkgo biloba on the
pharmacokinetics of raltegravir in healthy volunteers. Antimicrob Agents
Chemother. 56, 10: 5070-5075.
Abstract: Medicinal herbs may cause clinically relevant drug interactions with
antiretroviral agents. Ginkgo biloba
extract is a popular herbal product among HIV-infected patients because of its
positive effects on cognitive function. Raltegravir, an HIV integrase inhibitor,
is increasingly being used as part of combined antiretroviral therapy. Clinical
data on the potential inhibitory or inductive effect of ginkgo biloba on the pharmacokinetics of raltegravir were
lacking, and concomitant use was not recommended. We studied the effect of ginkgo biloba extract on the pharmacokinetics of
raltegravir in an open-label, randomized, two-period, crossover phase I trial in
18 healthy volunteers. Subjects were randomly assigned to a regimen of 120 mg of
ginkgo biloba twice daily for 15 days plus
a single dose of raltegravir (400 mg) on day 15, a washout period, and 400 mg of
raltegravir on day 36 or the test and reference treatments in reverse order.
Pharmacokinetic sampling of raltegravir was performed up to 12 h after intake on
an empty stomach. All subjects (9 male) completed the trial, and no serious
adverse events were reported. Geometric mean ratios (90% confidence intervals)
of the area under the plasma concentration-time curve from dosing to infinity
(AUC(0-∞)) and the maximum plasma concentration (C(max)) of raltegravir with
ginkgo biloba versus raltegravir alone
were 1.21 (0.93 to 1.58) and 1.44 (1.03 to 2.02). Ginkgo biloba did not reduce raltegravir exposure. The
potential increase in the C(max) of raltegravir is probably of minor importance,
given the large intersubject variability of raltegravir pharmacokinetics and its
reported safety profile.
Yasuno, F., S. Tanimukai, M. Sasaki, C. Ikejima, F. Yamashita, C. Kodama,
K. Mizukami and T. Asada. 2012. Combination of Antioxidant Supplements Improved Cognitive Function in the
Alzheimers Dis. 32, 4: 895-903.
Abstract: Although nutrients or agents with antioxidant properties were reported to
show a preventive effect on cognitive decline in animal studies, epidemiologic
data on select antioxidants have shown conflicting results. We investigated
whether a combination of antioxidants from supplements is effective for the
improvement of cognitive function of elderly. Forty-one subjects from a
community dwelling aged 65 years and older took supplements containing n-3
polyunsaturated fatty acids (n-3 PUFA), lycopene, and Ginkgo biloba extracts (GE) daily for 3 years. The data
of 622 subjects without supplement intake were used as control. We investigated
the changes in cognitive function during a 3-year follow-up. We also
investigated the influence of apolipoprotein E (APOE) genotype on the effect of
antioxidants. We found that a combination of antioxidants improved cognitive
function of aged persons after 3 years. Our present study also indicated this
improvement in cognitive function with supplement intake in both APOE4
non-carrier (E4-) and APOE4 carrier (E4+) groups. Especially, in E4+, we found a
large effect size of the improvement of cognition. When multiple antioxidants
are used in combination, they protect against vulnerability to other agents and
synergistically potentiate their antioxidant properties. These synergistically
potentiated antioxidant effects of agents contribute to the improvement of
Attia, A., S. R. Rapp, L. D. Case, R. D'Agostino, G. Lesser, M. Naughton,
K. McMullen, R. Rosdhal and E. G. Shaw. 2012. Phase II study of Ginkgo biloba in
irradiated brain tumor patients: effect on cognitive function, quality of life,
and mood. J Neurooncol. 109, 2: 357-363.
Abstract: Ginkgo biloba has been reported to
improve cognitive function in older adults and patients with Alzheimer's disease
and multi-infarct dementia. We conducted an open-label phase II study of this
botanical product in symptomatic irradiated brain tumor survivors. Eligibility
criteria included: life expectancy ≥30 weeks, partial or whole brain radiation
≥6 months before enrollment, no imaging evidence of tumor progression in
previous 3 months, or stable or decreasing steroid dose, and no brain tumor
treatment planned while on study. The Ginkgo
biloba dose was 120 mg/day (40 mg t.i.d.) for 24 weeks followed by a
6-week washout period. Assessments performed at baseline, 12, 24 (end of
treatment), and 30 weeks (end of washout) included KPS, Functional Assessment of
Cancer Therapy-Brain (FACT-Br), Profile of Mood States, Mini-Mental Status Exam,
Trail Making Test Parts A (TMT-A) and B (TMT-B), Digit Span Test, Modified Rey
Osterrieth Complex Figure (ROCF), California Verbal Learning Test Part II, and
the F-A-S Test. Results: Of the 34 patients enrolled on study, 23 (68 %)
completed 12 weeks of treatment and 19 (56 %) completed 24 weeks of treatment.
There were significant improvements at 24 weeks in: executive function (TMT-B)
(p = 0.007), attention/concentration (TMT-A) (p = 0.002), and non-verbal memory
(ROCF-immediate/delayed recall) (p = 0.001/0.002), mood (p = 0.002), FACT-Br
subscale (p = 0.001), and the FACT physical subscale (p = 0.003). Conclusions:
Some improvement in quality of life and cognitive function were noted with Ginkgo biloba. However, treatment with Ginkgo biloba was associated with a high dropout
Hasanzadeh, E., M. R. Mohammadi, A. Ghanizadeh, S. A. Rezazadeh, M. Tabrizi, F. Rezaei and
S. Akhondzadeh. 2012. A Double-Blind Placebo Controlled Trial of Ginkgo biloba Added to Risperidone in Patients with
Autistic Disorders. Child Psychiatry Hum Dev. 43, 5: 674-682.
Abstract: Ginkgo biloba has been reported to
affect the neurotransmitter system and to have antioxidant properties that could
impact the pathogenesis of Autism Spectrum Disorder. Based on these studies, we
decided to assess the effectiveness of Ginkgo
biloba extract (Ginko T.D., Tolidaru, Iran) as an adjunctive agent to
risperidone in the treatment of autism. Forty-seven outpatients with a DSM-IV-TR
diagnosis of autism ages between 4 and 12 years were assigned to this double
blinded clinical trial and were randomly divided into two groups. One group
received risperidone plus Ginko T.D and the other received risperidone plus
placebo. The dose of risperidone was 1-3 mg/day and the dose of Ginko T.D. was
80 mg/day for patients under 30 kg and 120 mg/day for patients above 30 kg.
Patients were assessed using Aberrant Behavior Checklist-Community (ABC-C)
rating scale and the side effect check list every 2 weeks until the endpoint.
None of the 5 subscales of ABC-C rating scale showed significant differences
between the two groups. Incidents of side effects were not significantly
different between the two groups. Adding Ginkgo
biloba to risperidone did not affect the treatment outcome of ADs.
Nevertheless, further observations are needed to confirm this result.
Herrschaft, H., A. Nacu, S. Likhachev, I. Sholomov, R. Hoerr and S. Schlaefke. 2012. Ginkgo biloba extract EGb 761(®) in
dementia with neuropsychiatric features: A randomised, placebo-controlled trial
to confirm the efficacy and safety of a daily dose of 240 mg. J
Psychiatr Res. 46, 6: 716-723.
Abstract: A multi-centre, double-blind, randomised, placebo-controlled, 24-week trial
with 410 outpatients was conducted to demonstrate efficacy and safety of a
240 mg once-daily formulation of Ginkgo
biloba extract EGb 761(®) in patients with mild to moderate dementia
(Alzheimer's disease or vascular dementia) associated with neuropsychiatric
symptoms. Patients scored 9 to 23 on the SKT cognitive battery, at least 6 on
the Neuropsychiatric Inventory (NPI), with at least one of four key items rated
at least 4. Primary outcomes were the changes from baseline to week 24 in the
SKT and NPI total scores. The ADCS Clinical Global Impression of Change
(ADCS-CGIC), Verbal Fluency Test, Activities of Daily Living International Scale
(ADL-IS), DEMQOL-Proxy quality-of-life scale and 11-point box scales for
tinnitus and dizziness were secondary outcome measures. Patients treated with
EGb 761(®) (n = 200) improved by 2.2 ± 3.5 points (mean ± sd) on the SKT total
score, whereas those receiving placebo (n = 202) changed only slightly by
0.3 ± 3.7 points. The NPI composite score improved by 4.6 ± 7.1 in the EGb
761(®)-treated group and by 2.1 ± 6.5 in the placebo group. Both drug-placebo
comparisons were significant at p < 0.001. Patients treated with EGb 761(®)
also showed a more favourable course in most of the secondary efficacy
variables. In conclusion, treatment with EGb 761(®) at a once-daily dose of
240 mg was safe and resulted in a significant and clinically relevant
improvement in cognition, psychopathology, functional measures and quality of
life of patients and caregivers.
Mancuso, C., R. Siciliano, E. Barone and P. Preziosi. 2012. Natural substances and Alzheimer's disease: From preclinical studies to
evidence based medicine. Biochim Biophys
Acta. 1822, 5:616-624.
Abstract: Over the last 10years, the potential therapeutic effects of nutraceuticals to
prevent or delay Alzheimer's disease were proposed. Among dietary antioxidants
curcumin, Ginkgo biloba and carnitines
were extensively studied for their neuroprotective effects. The rationale for
this alternative therapeutic approach was based on several preclinical studies
which suggested the neuroprotective effects for curcumin, Ginkgo biloba and acetyl-l-carnitine due to either a free
radical scavenging activity or the inhibition of pro-inflammatory pathways or
the potentiation of the cell stress response. However, although these are
interesting premises, clinical studies were not able to demonstrate significant
beneficial effects of curcumin, Ginkgo
biloba and acetyl-l-carnitine in improving cognitive functions in
Alzheimer's disease patients. The aim of this review is to summarize the main
pharmacologic features of curcumin, Ginkgo
biloba and carnitines as well as to underlie the main outcomes reached by
clinical studies designed to demonstrate the efficacy of these natural
substances in Alzheimer's disease patients. This article is part of a Special
Issue entitled: Antioxidants and Antioxidant Treatment in Disease.
Perry, E. and M. J. Howes. 2011. Medicinal plants and dementia therapy: herbal hopes for brain aging?. CNS Neurosci
Ther. 17, 6: 683-698.
Abstract: An escalating "epidemic" of diseases like Alzheimer's has not yet been met by
effective symptomatic treatments or preventative strategies. Among a few current
prescription drugs are cholinesterase inhibitors including galantamine,
originating from the snowdrop. Research into ethnobotanicals for memory or
cognition has burgeoned in recent years. Based on a multi-faceted review of
medicinal plants or phytochemicals, including traditional uses, relevant
bioactivities, psychological and clinical evidence on efficacy and safety, this
overview focuses on those for which there is promising clinical trial evidence
in people with dementia, together with at least one other of these lines of
supporting evidence. With respect to cognitive function, such plants reviewed
include sage, Ginkgo biloba, and complex
mixtures of other traditional remedies. Behavioral and psychological symptoms of
dementia (BPSD) challenge carers and lead to institutionalization. Symptoms can
be alleviated by some plant species (e.g., lemon balm and lavender alleviate
agitation in people with dementia; St John's wort treats depression in the
normal population). The ultimate goal of disease prevention is considered from
the perspective of limited epidemiological and clinical trial evidence to date.
The potential value of numerous plant extracts or chemicals (e.g., curcumin)
with neuroprotective but as yet no clinical data are reviewed. Given intense
clinical need and carer concerns, which lead to exploration of such alternatives
as herbal medicines, the following research priorities are indicated:
investigating botanical agents which enhance cognition in populations with mild
memory impairment or at earliest disease stages, and those for BPSD in people
with dementia at more advanced stages; establishing an ongoing authoritative
database on herbal medicine for dementia; and further epidemiological and follow
up studies of promising phytopharmaceuticals or related nutraceuticals for
Zhao, Y and B. Zhao. 2012. Natural antioxidants in prevention and management of Alzheimer's
disease. Front Biosci (Elite Ed).
Abstract: Alzheimer's disease (AD) is the most common neurodegenerative disease that
causes dementia in the elderly. As the aging population increases, the
prevalence of AD has increased remarkably worldwide and AD has become one of the
leading causes of disability and death among the elderly. A number of drugs have
been approved for the treatment of AD; however, they produce only modest
benefits and have a wide range of side effects. Therefore, extensive studies are
underway to identify effective drugs that are free of undesirable side effects.
As accumulating evidences have implicated oxidative stress in the initiation and
progression of AD, the potential of using nature antioxidants for prevention and
treatment of AD has attracted considerable attention. The present review
discusses the involvement of oxidative stress in the pathogenesis of AD and the
neuroprotective effects of natural antioxidants, such as Ginkgo biloba flavonoids, soybean isoflavones, theanine
and nicotine in cell culture and AD transgenic animal models, specifically,
their inhibition on Abeta-induced neurotoxicity and the underlined molecular
Ihl, R., M. Tribanek and N. Bachinskaya. 2011. Efficacy and Tolerability of a Once Daily Formulation of Ginkgo biloba Extract EGb 761® in Alzheimer's Disease and Vascular Dementia: Results from a Randomised Controlled Trial. Pharmacopsychiatry. 45, 2: 41-46.
Abstract: A 24-week randomised controlled trial was conducted to assess the efficacy of a 240 mg once-daily preparation of Ginkgo biloba extract EGb 761® in 404 outpatients≥50 years diagnosed with mild to moderate dementia (SKT 9-23), Alzheimer's disease (AD) or vascular dementia (VaD), with neuropsychiatric features (NPI total score≥5).Separate analyses were performed for diagnostic subgroups (probable or possible AD; VaD).333 patients were diagnosed with AD and 71 with VaD. EGb 761® treatment was superior to placebo with respect to the SKT total score (drug-placebo differences: 1.7 for AD, p<0.001, and 1.4 for VaD, p<0.05) and the NPI total score (drug-placebo differences: 3.1 for AD, p<0.001 and 3.2 for VaD, p<0.05). Significant drug-placebo differences were found for most secondary outcome variables with no major differences between AD and VaD subgroups. Rates of adverse events in EGb 761® and placebo groups were essentially similar.EGb 761® improved cognitive functioning, neuropsychiatric symptoms and functional abilities in both types of dementia.
Rocher, M. N., D. Carré, B. Spinnewyn, J. Schulz, S. Delaflotte, B. Pignol, P. E. Chabrier, and M. Auguet. 2011.Long-term treatment with standardized Ginkgo biloba Extract (EGb 761) attenuates cognitive deficits and hippocampal neuron loss in a gerbil model of vascular dementia. Fitoterapia 82, 7: 1075-1080.
Abstract: The standardized extract of Ginkgo biloba EGb 761 has been used to reduce cognitive dysfunction. The present study was designed to evaluate the effect of postischemic oral treatment with EGb 761 in a model of vascular dementia in gerbils. Daily oral posttreatment with EGb 761 led to a significant recovery of spatial memory assessed by the object location test, inhibited the decrease in plasma SOD activity and protected the hippocampal CA1 neurons, even when administered after the insult. These data provide further evidence for the therapeutic potential of EGb 761 in the treatment of vascular dementia.
R. Kaschel. 2011. Specific memory effects of Ginkgo biloba extract EGb 761 in middle-aged healthy volunteers. Phytomedicine 18, 14: 1202-7.
Introduction Recent reviews showed that Ginkgo biloba extract EGb 761(1) is effective to enhance performance in patients with cognitive impairment (e.g., dementia). The aim of this study was to investigate the effects of EGb 761 on memory and the specificity of such effects on distinct memory functions in middle-aged healthy volunteers.
Methods: A total of 188 healthy subjects aged 45-56 years were randomised to receive EGb 761 (240mg once daily) or placebo for 6 weeks. Outcome measures were the change in memory performance in a demanding standardised free recall paradigm (list of appointments) and a less demanding standardised recognition test (driving-route). Based on previous findings we predicted superiority of EGb 761 in recall testing. Specificity in effects was assessed by separating immediate vs. delayed and quantitative vs. qualitative free recall measures.
Results: After 6 weeks, EGb 761-treated subjects improved significantly in quantity of recall, i.e., the number of correctly recalled appointments (drug-placebo differences: p=0.038 for immediate and p=0.008 for delayed recall). Effects on qualitative recall performance (ratio of false to correct items) were similar (drug-placebo differences: p=0.092 for immediate and p=0.010 for delayed recall). No superiority of Ginkgo was evident in another everyday memory test which asked for recognition of a driving route (drug-placebo differences: p>0.10). The incidence of adverse events was low and not significantly different between treatment groups.
Discussion: EGb 761 (240mg once daily) improves free recall of appointments in middle-aged healthy volunteers, which requires high demands on self-initiated retrieval of learned material. This function is known to be sensitive to normal aging, i.e., reduced in healthy middle-aged subjects. No effects are seen in a less demanding everyday memory task which does not tap this critical function. This ties in with previous studies which found specific patterns of benefit from EGb 761 in demanding cognitive tasks
Howes, M. J. and E. Perry. 2011. The role of phytochemicals in the treatment and prevention of dementia. Drugs Aging 28, 6: 439-468.
Abstract: Dementia pathologies such as Alzheimer's disease (AD) are reaching epidemic proportions, yet they are not successfully managed by effective symptomatic treatments. Only five drugs have been developed to alleviate cognitive symptoms, and more effective and safe treatments are needed for both the cognitive symptoms and behavioural and psychological symptoms of dementia (BPSD). As two of these licensed drugs (cholinesterase inhibitors [ChEIs]) are naturally derived (galantamine and rivastigmine), the potential for plants to yield new therapeutic agents has stimulated extensive research to discover new ChEIs together with plant extracts, phytochemicals and their derivatives with other mechanistic effects relevant to dementia treatment. This review presents the potential and actual therapeutic strategies for dementia in relation to the known mechanisms of dementia pathology. Phytochemicals that have shown mechanistic effects relevant to the pathological targets in dementia are discussed, with an emphasis on those showing positive clinical trial evidence. Those phytochemicals discussed include the alkaloid physostigmine, a ChEI from the calabar bean (Physostigma venenosum), which has been used as a template for the development of synthetic derivatives that inhibit acetylcholinesterase, including the drug rivastigmine. Also discussed are other ChEI alkaloids including huperzine A, from Huperzia serrata, and galantamine, originally from the snowdrop (Galanthus woronowii); both alkaloids improve cognitive functions in AD patients. Other phytochemicals discussed include cannabinoids (e.g. cannabidiol) from Cannabis sativa, which are emerging as potential therapeutic agents for BPSD, and resveratrol (occurs in various plants) and curcumin (from turmeric [Curcuma longa]), which have been investigated for their pharmacological activities relevant to dementia and their potential effects on delaying dementia progression. The review also discusses plant extracts, and their known constituents, that have shown relevant mechanistic effects for dementia and promising clinical data, but require more evidence for their clinical efficacy and safety. Such plants include Ginkgo biloba, which has been extensively studied in numerous clinical trials, with most outcomes showing positive effects on cognitive functions in dementia patients; however, more reliable and consistent clinical data are needed to confirm efficacy. Other plants and their extracts that have produced promising clinical data in dementia patients, with respect to cognition, include saffron (Crocus sativus), ginseng (Panax species), sage (Salvia species) and lemon balm (Melissa officinalis), although more extensive and reliable clinical data are required. Other plants that are used in traditional practices of medicine have been suggested to improve cognitive functions (e.g. Polygala tenuifolia) or have been associated with alleviation of BPSD (e.g. the traditional prescription yokukansan); such remedies are often prescribed as complex mixtures of different plants, which complicates interpretation of pharmacological and clinical data and introduces additional challenges for quality control. Evidence for the role of natural products in disease prevention, the primary but considerably challenging aim with respect to dementia, is limited, but the available epidemiological and clinical evidence is discussed, with most studies focused on ChEIs, nicotine (from Nicotiana species), curcumin, wine polyphenols such as resveratrol and G. biloba. Challenges for the development of phytochemicals as drugs and for quality control of standardized plant extracts are also considered.
Keheyan, G., L. A. Dunn and W. L. Hall. 2011. Acute Effects of Ginkgo Biloba Extract on Vascular Function and Blood Pressure. Plant Foods Hum Nutr. 66, 3 :209-211.
Abstract: We investigated whether a single dose of standardized Ginkgo biloba extract (GBE) can improve vascular function. A randomised controlled crossover trial was conducted on 14 young healthy men, who received GBE or placebo. The digital volume pulse was monitored to measure reflection index (DVP-RI) and stiffness index (DVP-SI) and peripheral augmentation index (pAIx) was assessed using radial pulse wave analysis at baseline and 2, 4 and 6 h after treatment. DVP-SI was slightly higher 2 h following GBE compared to placebo (P < 0.05); other outcome variables were unaffected by treatment.
Szczurko, O., N. Shear, A. Taddio and H. Boon. 2011. Ginkgo biloba for the treatment of vitilgo vulgaris: an open label pilot clinical trial. BMC Complement Altern Med. 15, 11: 21.
BACKGROUND: Vitiligo is a common hypopigmentation disorder with significant psychological impact if occurring before adulthood. A pilot clinical trial to determine the feasibility of an RCT was conducted and is reported here.
METHODS: 12 participants 12 to 35 years old were recruited to a prospective open-label pilot trial and treated with 60 mg of standardized G. biloba two times per day for 12 weeks. The criteria for feasibility included successful recruitment, 75% or greater retention, effectiveness and lack of serious adverse reactions. Effectiveness was assessed using the Vitiligo Area Scoring Index (VASI) and the Vitiligo European Task Force (VETF), which are validated outcome measures evaluating the area and intensity of depigmentation of vitiligo lesions. Other outcomes included photographs and adverse reactions. Safety was assessed by serum coagulation factors (platelets, PTT, INR) at baseline and week 12.
RESULTS: After 2 months of recruitment, the eligible upper age limit was raised from 18 to 35 years of age in order to facilitate recruitment of the required sample size. Eleven participants completed the trial with 85% or greater adherence to the protocol. The total VASI score improved by 0.5 (P = 0.021) from 5.0 to 4.5, range of scale 0 (no depigmentation) to 100 (completely depigmented). The progression of vitiligo stopped in all participants; the total VASI indicated an average repigmentation of vitiligo lesions of 15%. VETF total vitiligo lesion area decreased 0.4% (P = 0.102) from 5.9 to 5.6 from baseline to week 12. VETF staging score improved by 0.7 (P = 0.101) from 6.6 to 5.8, and the VETF spreading score improved by 3.9 (P < 0.001)) from 2.7 to -1.2. There were no statistically significant changes in platelet count, PTT, or INR.
CONCLUSIONS: The criteria for feasibility were met after increasing the maximum age limit of the successful recruitment criterion; participant retention, safety and effectiveness criteria were also met. Ingestion of 60 mg of Ginkgo biloba BID was associated with a significant improvement in total VASI vitiligo measures and VETF spread, and a trend towards improvement on VETF measures of vitiligo lesion area and staging. Larger, randomized double-blind clinical studies are warranted and appear feasible.
Gorby, H. E., A. M. Brownawell and M. C. Falk. 2010. Do specific dietary constituents and supplements affect mental energy? Review of the evidence. Nutr Rev. 68, 12: 697-718.
Abstract: The numbers of marketing claims and food, beverage, and drug products claiming to increase mental energy have risen rapidly, thus increasing the need for scientific specificity in marketing and food label claims. Mental energy is a three-dimensional construct consisting of mood (transient feelings about the presence of fatigue or energy), motivation (determination and enthusiasm), and cognition (sustained attention and vigilance). The present review focuses on four dietary constituents/supplements (Ginkgo biloba, ginseng, glucose, and omega-3 polyunsaturated fatty acids) to illustrate the current state of the literature on dietary constituents and mental energy. The strongest evidence suggests effects of Ginkgo biloba on certain aspects of mood and on attention in healthy subjects, as well as associations between omega-3 polyunsaturated fatty acids and reduced risk of age-related cognitive decline. Limitations of the current data and challenges for future research are discussed.
Esposito, M. and M. Carotenuto. 2010. Ginkgolide B complex efficacy for brief prophylaxis of migraine in school-aged children: an open-label study. Neurol Sci. 32, 1: 79-81.
Abstract: Primary headaches (migraines and tension-types headaches) are very common in school-aged children. Ginkgolide B, a herbal constituent extract from Ginkgo biloba tree leaves, was considered as a promising pharmacological aid for the treatment of migraine in adult patients because of its modulation of the glutamatergic transmission in the CNS and on antiplatelet activating factor (PAF). The aim of study is to verify the effectiveness and safety of association of Ginkgolide B/Coenzyme Q10/Riboflavin/Magnesium complex for brief prophylaxis in a population of school-aged children with migraine. In our sample after 3 months of treatment with association of Ginkgolide B/CoenzymeQ10/Riboflavin/Magnesium complex, the mean frequency per month of migraine was significantly decreased (9.71 ± 4.33 vs. 4.53 ± 3.96 attacks; p < 0.001). Our findings suggest that in childhood headache management, the use of alternative treatments must be considered not to evoke a placebo effect, but as soft therapy without adverse reactions.
Campos, H. C., M. D. da Rocha, F. P. Viegas, P. C. Nicastro, P. C. Fossaluzza, C. A. Fraga, E. J. Barreiro and Viegas C Jr. 2010. The Role of Natural Products in the Discovery of New Drug Candidates for the Treatment of Neurodegenative Disorders II: Alzheimer's Disease. CNS Neurol Disord Drug Targets. 10, 2: 251-270.
Abstract: The present review is part II in a series (part I focuses on Parkinson's Disease) that addresses the value of natural product chemistry in the discovery of medicines for the treatment of neurodegenerative disorders. Data reviewed document that a host of products from plant species and derivatives have neuroprotectant effects in vitro and in vivo. In addition, besides neuroprotection, natural products also demonstrate biological effects that target biochemical pathways underlying associated symptoms of neurdegnerative disorders that include cognitive impairments, energy/fatigue, mood, and anxiety. This part of the review series focuses specifically upon Alzheimer's Disease (AD). AD is postulated to result from extracellular formation of amyloid plaques and intracellular deposits of neurofibrilary tangles in the hippocampus, cerebral cortex and other areas of the brain essential for cognitive function. Plaques are formed mostly from the deposition -amyloid (A ), a peptide derived from the amyloid precursor protein (APP). Filamentous tangles are formed from paired helical filaments composed of neurofilament and hyperphosphorilated tau protein, a microtubule-associated protein. In addition, environmental factors can engender the production of cytokines that are closely related to the installation of an inflammatory process that contributes to neuronal death and the development and the progression of AD. In this review we focus on the recent main contribuitions of natural products chemistry to the discovery of new chemical entities usefull to the control and prevention of AD installation and progression. More than sixteen plant species, including Ginseng, Celastrus paniculatus, Centella asiatica, Curcuma longa, Ginkgo biloba, Huperzia serrata, Lycoris radiate, Galanthus nivalis, Magnolia officinalis, Polygala tenuifolia, Salvia lavandulaefolia, Salvia miltiorrhiza, Coptis chinensis, Crocus sativus, Evodia rutaecarpa, Sanguisorba officinalis, Veratrum grandiflorum and Picrorhiza kurvoa, are discussed as potential sources of active extracts. In addition, more than sixty secondary metabolites are under evaluation for their efficacy on controlling symptoms and to impede the development and progression of AD.
Fransen, H. P., S. M. Pelgrom, B. Stewart-Knox, D. de Kaste and H. Verhagen. 2010. Assessment of health claims, content, and safety of herbal supplements containing Ginkgo biloba. Food Nutr Res. 54.
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.
Haines, D. D., B. Varga, I. Bak, B. Juhasz, F. F. Mahmoud, H. Kalantari, R. Gesztelyi, I. Lekli, A. Czompa and A. Tosaki. 2010. Summative interaction between astaxanthin, Ginkgo biloba extract (EGb761) and vitamin C in Suppression of respiratory inflammation: a comparison with ibuprofen Phytother Res. 25, 1: 128-136.
Abstract: In this study, combinations of Ginkgo biloba leaf extract (EGb761) plus the carotenoid antioxidant astaxanthin (ASX) and vitamin C were evaluated for a summative dose effect in the inhibition of asthma-associated inflammation in asthmatic guinea-pigs. Ovalbumin-sensitized Hartley guinea-pigs challenged with ovalbumin aerosol to induce asthma, were administered EGb761, ASX, vitamin C or ibuprofen. Following killing, bronchoalveolar lavage (BAL) fluid was evaluated for inflammatory cell infiltrates and lung tissue cyclic nucleotide content. Each parameter measured was significantly altered to a greater degree by drug combinations, than by each component acting independently. An optimal combination was identified that included astaxanthin (10 mg/kg), vitamin C (200 mg/kg) and EGb761 (10 mg/kg), resulting in counts of eosinophils and neutrophils each 1.6-fold lower; macrophages 1.8-fold lower, cAMP 1.4-fold higher; and cGMP 2.04-fold higher than levels in untreated, asthmatic animals (p < 0.05). In conclusion, EGb761, ASX and vitamin C are shown here to interact summatively to suppress inflammation with efficacy equal to or better than ibuprofen, a widely used non-steroidal antiinflammatory drug (NSAID). Such combinations of non-toxic phytochemicals constitute powerful tools for the prevention of onset of acute and chronic inflammatory disease if consumed regularly by healthy individuals; and may also augment the effectiveness of therapy for those with established illness.
Canis, M., B. Olzowy, C. Welz, M. Suckfüll and K. Stelter. 2010. Simvastatin and Ginkgo biloba in the treatment of subacute tinnitus: a retrospective study of 94 patients. Am J Otolaryngol. 32, 1: 19-23.
OBJECTIVES: Studies suggest that hypercholesterolemia promotes the development of inner ear disorders such as tinnitus. However, the underlying pathomechanisms are still not clearly defined.
METHODS: A retrospective study was performed to assess whether a reduction of serum cholesterol by 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors may result in a relief of subacute tinnitus. Remission rates of 58 patients were investigated after 4 months of treatment with simvastatin (40 mg). Results were compared to treatment with Ginkgo biloba (120 mg; n = 36) as control group. Differences between tinnitus score at the day of first treatment and after 4 months were used as main outcome measure.
RESULTS: After treatment with simvastatin or G biloba, tinnitus score decreased from 41.3 ± 10.4 to 37.4 ± 17.3 and from 44.7 ± 11.2 to 41.2 ± 8.7, respectively. However, independently of the treatment regimen, differences of tinnitus scores were considered not significant.
CONCLUSIONS: After administration of simvastatin over 4 months, this retrospective study has shown no significant efficacy in treatment of subacute tinnitus. For a more conclusive answer, further prospective, double-blind, and placebo-controlled studies with a larger number of patients are needed.