Ginkgo biloba in Alzheimer's disease: evidence from studies is mixed

Patients with Alzheimer's disease may profit from Ginkgo compounds, as long as high doses are used. With regard to the therapy goal "activities of daily living”, this has been demonstrated by studies. Concerning the therapy goals "cognitive function”, "general accompanying psychopathological symptoms”, and "quality of life of caregiving relatives”, the studies at least indicate a benefit of Ginkgo. However, studies are also available that do not show a benefit, so that ultimately it remains unclear how great the effect of this treatment is. This is the result of the final report by the Institute for Quality and Efficiency in Health Care (IQWiG) published on 21 November 2008.

Study populations vary greatly

IQWiG searched for studies that investigated therapy goals relevant for patients with Alzheimer's disease and their relatives. These outcomes included cognitive function (e.g., memory) and competence in daily activities (e.g., personal hygiene), as well as accompanying psychopathological symptoms (e.g., depression, agitation) or quality of life. The minimum study duration (period in which patients were treated with Ginkgo compounds) was 16 weeks.

A total of 7 studies including nearly 1800 participants were considered in the benefit assessment. Different patient populations participated in the studies: age and gender, as well as disease severity and accompanying psychopathological symptoms of patients varied greatly between studies.

The 2 most recent and largest studies (about 630 participants) had been conducted in the Ukraine. They therefore originated from a health care setting that differs greatly from the German setting. However, one can assume that German patients may also profit from Ginkgo biloba, but the positive effect may be smaller than in the 2 Ukrainian studies.

Size of the potential effect unclear

IQWiG found evidence, in particular in the 2 Ukrainian studies, that patients with Alzheimer's disease cope better with daily activities if they use high-dose Ginkgo biloba (240 mg per day). This treatment may also have a positive effect on memory and mental health. In addition, relatives seem to be less exposed to emotional stress. However, no evidence, but merely indications exist for this outcome. It remains unclear how large all of these potential effects are. This is mainly due to the fact that the results of the individual studies varied greatly.

The conclusions on the benefit of Ginkgo biloba only apply to a dose of 240 mg daily. No benefit has been shown for lower doses. Moreover, due to the lack of reliable comparative studies, it remains unclear how Ginkgo biloba compares to other drugs used in Alzheimer's disease.
The results on adverse drug effects were also inconsistent. The studies did not indicate an increase in certain adverse effects; however, patients in the Ginkgo biloba groups generally discontinued the study more often than those in the placebo groups.

Additional studies required for the German health care setting

As the results of the different studies varied greatly (and it is unclear why), in IQWiG's opinion further clinical comparisons are necessary. IQWiG suspects that the heterogeneity of results is caused by the differences in study populations.

During the course of the report production, IQWiG initially came to definitely less positive conclusions (see preliminary reports 1.0 and 2.0). This is due to the fact that the 2 Eastern European studies, which showed particularly positive effects in patients with Alzheimer's disease, became available only during the course of the assessment. Nevertheless, further studies clarifying any open questions remaining would be desirable in future. Among other things, this includes studies that compare Ginkgo biloba with other treatment alternatives or identify subgroups of patients who essentially profit from it. However, such studies should preferably be conducted in a health care setting comparable to that of Western countries.

IQWiG report draws no conclusions on a preventive effect

A frequently cited study recently published in JAMA (2008;300:2253-2262) cannot answer these questions either. This study investigated a Ginkgo compound in the prevention of dementia (including Alzheimer's disease) in about 3000 men and women aged 75 years and older. The study included patients who did not show symptoms of manifest dementia at the start of the study. The results do not provide evidence that Ginkgo can prevent or at least delay dementia.

When comparing the JAMA study with the IQWiG final report, one needs to consider that the benefit described by IQWiG only refers to people already suffering from Alzheimer's disease. Moreover, the patients in the 2 Eastern European studies, which strongly influenced the results of the IQWiG report, were comparatively young, disease severity was advanced, and accompanying symptoms, such as depression and agitation, were common. It therefore cannot be excluded that only patients with such accompanying psychopathological symptoms profit from Ginkgo compounds.

Procedure of report production

The preliminary results (preliminary report) were published by IQWiG at the end of February 2008 and interested parties were invited to submit comments. Unclear aspects from the comments on the preliminary report were discussed with the authors of the comments in an oral debate in April 2008. The preliminary report was subsequently revised and the final report sent to the contracting agency, the Federal Joint Committee, at the end of September 2008. The meeting minutes of the debate and the written comments will be published in a separate document simultaneously with the final report.

This IQWiG report is part of a comprehensive commission awarded by the Federal Joint Committee concerning the assessment of treatment options for patients with Alzheimer's disease. A final report on the drug class of cholinesterase inhibitors was already published in April 2007. A further part of the IQWiG commission investigates the drug memantine. Finally, the Institute is also assessing non-drug interventions . The preliminary reports on the 2 last-mentioned commissions are already available.

The executive summary provides an overview of the background, methods, and further results of the final report on Ginkgo compounds.

Contact: Tel. +49 (0221)-35685-0, info@iqwig.de