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- Ginkgo (Ginkgo biloba, Ginkgoaceae)
- EGb 761®
- Dementia
- Systematic Review/Meta-analysis
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Date:
03-13-2015 | HC# 021561-516
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Re: Meta-analysis Demonstrates Safety and Efficacy of Defined Ginkgo Extract EGb 761® for Treating Dementia in the Elderly
Gauthier
S, Schlaefke S. Efficacy and
tolerability of Ginkgo biloba extract
EGb 761® in dementia: a systematic review and meta-analysis of
randomized placebo-controlled trials. Clin
Interv Aging. November 28, 2014;9:2065-2077.
Many
older adults suffer from Alzheimer's disease (AD) and cerebrovascular disease.
The leading clinically-tested proprietary ginkgo (Ginkgo biloba, Ginkgoaceae) leaf extract EGb 761® has
shown a variety of mechanisms related to treating AD in vivo, including
repairing mitochondrial function, modulating neuroplasticity, and increasing
dopamine concentrations in only frontal brain areas.
EGb
761 is an acetonic (60% per weight) dry extract of ginkgo leaves standardized
to contain 22-27% ginkgo flavonglycosides, 5-7% terpene lactones (2.8-3.4%
ginkgolides A, B, and C, and 2.6-3.2% bilobalide), and less than 5 ppm
ginkgolic acids. It is produced by Dr. Willmar Schwabe GmbH & Co. KG,
Karlsruhe, Germany.
Processing
methods and bioactive compound content are integral to establishing efficacy
and safety in botanicals and may greatly differ among products. This systematic
review and meta-analysis investigates clinical trials using the standardized
product EGb 761 for the treatment of AD and/or vascular dementia (VaD). The
statistical analysis used in this study was funded by Schwabe; one of the authors
(Schlaefke) is an employee of the
company.
This
study searched the databases PubMed (to December 2012), EMBASE (2006-2011), and
PASCAL (to December 2011) using the search terms "gingk*,"
"ginkg*," "clinical trial," "clinical*,"
"trial," "randomized," "gingko,"
"ginkgo," "human/ct," "homme/ctfr,"
"clinical study," "double blind procedure," and
"py>2005." Included clinical trials were randomized,
placebo-controlled, and double-blind, with a duration of 20 weeks or more. The
included trials used EGb 761 for the treatment of AD, VaD, or a combination of
the two conditions, according to diagnostic requirements from a variety of
internationally recognized sources of criteria. Also, trials must have used two
of the three following outcome measures: cognition, activities of daily living
(ADL), and clinical global impression. Trials with patients having other mental
deficiencies or that incorporated EGb 761 in conjunction with cholinesterase
inhibiting drugs (e.g., donepezil [Aricept®] and tacrine [Cognex®])
were excluded.
This
study located 15 randomized, placebo-controlled, clinical trials of EGb 761; of
these, eight were excluded due to failure to meet inclusion criteria listed
above. Patients from the seven included trials took 120 mg (two trials) or 240
mg (six trials) of EGb 761 for 22-26 weeks (one trial tested both dosages). The
Jadad Scale, used to evaluate the trial quality (1 to 5, with 5 indicating the
highest trial robustness), indicated "appropriate" quality with
scores of 3 for two trials and of 5 for five trials. From the trials, 2,625
patients were evaluated, with 1,396 taking EGb 761 and 1,229 taking placebo.
Females within studies made up between 50-86% of patients, and the age range of
patients was from 63-79 years. Physical metrics such as height, weight, body
mass index, and cognitive metrics were not different at baseline between
treatment and placebo groups.
The
seven included trials used two different but overlapping validated cognitive
assessment tools. Five of the trials reported significant beneficial effects on
cognition of those taking EGb 761 as compared to those in the placebo group
(P=0.03). This was found to be dose dependent, and those taking 240 mg of EGb
761 had significantly better cognitive performance than those in the placebo
group (P=0.04). ADL was measured by four different scales. Those taking EGb 761
scored significantly better as compared to those in the placebo group
(P<0.001), and those taking 240 mg had a significantly higher ADL
"improvement" than those in the placebo group (P=0.001).
Also,
in clinical global impression assessments using three different rating scales,
those taking EGb 761 rated significantly better than those taking the placebo
(P=0.01); this was also observed in those taking 240 mg of EGb 761 as compared
to those in the placebo group (P=0.007). In general, the odds ratio for
cognitive improvement in those taking EGb 761 as compared to placebo was 2.48
(95% confidence intervals [CI], 1.17, 5.28, P=0.02). The odds ratio for
improvement in clinical global impression for EGb 761 treatment as compared to
placebo was 3.18 (95% CI, 1.78, 5.67, P<0.0001).
In
two of the studies, patients with adverse events (AEs) were
"slightly" more numerous in those taking EGb 761 than those taking
the placebo; however, in the other five trials, those with AEs were equally
distributed between groups. The relative risk (RR) ratio for AEs with EGb 761
was 0.96 (95% CI, 0.90, 1.01). Likewise, serious AEs were comparable in all
trials across the treatment groups. In both treatment and placebo groups, AEs
included headache, dizziness, hypertension, tinnitus, angina pectoris, and
respiratory tract infection. The AEs causing early termination of patient
participation in either group were symptoms typical of dementia, including
agitation, anxiety, insomnia, or unspecific symptoms such as constipation,
nausea, headache, and dizziness.
Overall, the results of this meta-analysis suggest
that 240 mg daily intake of EGb 761 is effective in improving cognition, ADL,
and clinical global impression in those suffering from AD and/or VaD, with
minimal adverse side effects. This phytomedicinal formulation may be a useful
adjuvant therapy in those suffering from cognitive decline.
—Amy C. Keller,
PhD
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