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Meta-Analysis Demonstrates Safety and Efficacy of Defined Ginkgo Extract for Treating Dementia in Elderly

Reviewed: 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. 2014;9:2065-2077.

Many older adults suffer from Alzheimer’s disease (AD) or other cerebrovascular diseases. 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 parts per million ginkgolic acids. It is produced by Dr. Willmar Schwabe GmbH & Co. KG of Karlsruhe, Germany.

Processing methods and bioactive compound content are integral to establishing the efficacy and safety of 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 performed 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). 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 inhibitors (e.g., donepezil [Aricept®] and tacrine [Cognex®]) were excluded.

The study authors located 15 randomized, placebo-controlled, clinical trials of EGb 761; of these, eight were excluded due to failure to meet the inclusion criteria listed above. Patients from the seven included trials were prescribed a dosage of 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 (scores range from 1 to 5, with 5 indicating the highest trial robustness), indicated “appropriate” quality, with scores of 3 for two trials and 5 for five trials. From the trials, 2,625 patients were evaluated, with 1,396 taking EGb 761 and 1,229 taking placebo. Females comprised 50% to 86% of the patient population in the studies, and patients ranged from 63 to 79 years old. 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 for those taking EGb 761 as compared to those in the placebo group (P=0.03). These effects were 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 greater improvement in ADL than those in the placebo group (P=0.001).

In clinical global impression assessments using three different rating scales, those taking EGb 761 rated significantly better than those taking 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, slightly more patients taking EGb 761 experienced adverse side effects (ASEs) than those taking the placebo; however, in the other five trials, those with ASEs were equally distributed between groups. The relative risk ratio for ASEs with EGb 761 was 0.96 (95% CI: 0.90, 1.01). Likewise, “serious” ASEs were comparable in all trials across the treatment groups. In both treatment and placebo groups, ASEs included headache, dizziness, hypertension, tinnitus, angina pectoris, and respiratory tract infection. The ASEs 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