Reviewed: Kaschel R. Specific memory effects of Ginkgo biloba extract EGb 761 in middle-aged healthy volunteers. Phytomed. November 15, 2011;18(14):1202-1207.

Extracts of ginkgo (Ginkgo biloba, Ginkgoaceae) leaves are used to enhance mental performance in people with age-related cognitive impairment. Randomized controlled trials have demonstrated effectiveness of ginkgo extracts in reducing cognitive symptoms in people with dementia. Fewer trials have studied ginkgo in healthy people, and the effects of ginkgo on cognitive function in younger people is not clear, although a previous review of the use of ginkgo extract in controlled clinical trials on healthy subjects indicated that a majority of the trials (13 of 16) resulted in positive outcomes for various cognitive effects, including short-term memory, speed of processing information, etc.¹

The purpose of this randomized, double-blind, placebo-controlled trial was to investigate the effects of the ginkgo extract EGb 761^® (Dr. Willmar Schwabe Pharmaceuticals; Karlsruhe, Germany) on memory in healthy, middle-aged volunteers. The trial was conducted at a single site in Germany by researchers from the University of Osnabrück; Osnabrück, Germany. Subjects were eligible for the trial if they were mentally healthy, well-educated, and 45-65 years of age. Those with cognitive impairment or a history of major depression, anxiety disorder, or substance abuse and those with impaired liver or kidney function or uncontrolled cardiovascular disease or diabetes were excluded from the trial. Eligible subjects were randomly assigned (1:1) to receive either standardized ginkgo extract (EGb 761) or a matching placebo once daily for 6 weeks. Those in the ginkgo group received 240 mg EGb 761, which contained 22-27% ginkgo flavonoids and 5.0-7.0% terpene lactones consisting of 2.8-3.4% ginkgolides A, B, C, and 2.6-3.2% bilobalide, with a content of ginkgolic acids below 5 ppm.

Four assessments were performed at baseline and after 6 weeks of treatment. Two were objective tests of memory. The first objective test measured recall of a detailed list of appointments, including immediate and delayed recall with both qualitative and quantitative components. The second objective test measured recognition of a driving route after watching a film. The third test was a subjective, self-rated memory questionnaire, and the fourth assessment was a questionnaire evaluating well-being and mood. A total of 188 subjects were randomized, and data from 177 subjects were included in the full analysis set. The average age was 54.2 years in the ginkgo group and 54.8 years in the placebo group. The percentage of females was significantly lower in the ginkgo group than in the placebo group (59.1% versus 76.4%, P=0.014), but no gender differences are detected in these tests.

In the demanding appointment recall test, the ginkgo group had greater quantitative improvement than the placebo group from baseline to 6 weeks (P=0.038 for immediate recall and P=0.008 for delayed recall). The ginkgo group had greater qualitative improvement than the placebo group for delayed recall (P=0.010), but not for immediate recall. (The qualitative measure is the ratio of errors to correct answers.) In the less demanding driving route recognition test, changes were similar in both groups from baseline to 6 weeks. Both groups had small, similar improvements on the subjective memory questionnaire, yet there was a trend in favor of ginkgo extract in the factor score including prospective everyday memory (P=0.58), which ties in well with the results of the appointments test. There were no changes in well-being and mood ratings for either group over the 6-week period. The number of adverse events was similar in both groups and no serious adverse events were reported. Causation could not be ruled out for gastric complaints in 3 subjects from each group, headaches in 4 subjects from the ginkgo group, and conjunctivitis and rash in individuals in the placebo group.

The author points out that subjects in this trial were younger and healthier than subjects in many previous studies showing a benefit of ginkgo extract on cognitive performance. Similar outcomes for healthy, elderly subjects have been shown in several studies, though it is generally difficult to detect significant changes in functions of those who are cognitively intact, especially if using measures intended to detect change in the cognitively impaired. The author states the results of this trial “cast doubt on the [previously held] notion that in individuals younger than 60 years effects of ginkgo are lacking.”²

In this trial, EGb 761 improved memory recall in healthy, middle-aged people performing a complex appointment task. This improvement was not mediated by improvements in mood or in subjective ratings of memory. On the other hand, EGb 761 did not improve performance on a simple test of recognition. According to the author, these results support previous research suggesting that ginkgo extract has very specific patterns of cognitive activity.

—Heather S. Oliff, PhD

References

1. Crews WD, Harrison DW, Griffin ML, Falwell KD, Crist T, et al. The neuropsychological efficacy of ginkgo preparations in healthy and cognitively intact adults: a comprehensive review. HerbalGram. 2005;67:43-62.
2. Canter PH, Ernst E. Ginkgo biloba is not a smart drug: an updated systematic review of randomised clinical trials testing the nootropic effects of G. biloba extracts in healthy people. Hum Psychopharmacol. 2007;22(5):265-278.