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| Date: 04-30-2016 | HC# 041651-543 |
Ong Lai Teik D, Lee XS, Lim CH, Low CM, Muslima M, Aquili L. Ginseng and Ginkgo biloba effects on cognition as modulated by cardiovascular reactivity: A randomised trial. PLoS One. March 3, 2016;11(3):e0150447. doi: 10.1371/journal.pone.0150447.
Ginkgo (Ginkgo biloba, Ginkgoaceae) leaf extract and Asian ginseng (Panax ginseng, Araliaceae) root are used as cognitive enhancers. However, the clinical trial evidence of cognitive benefits is equivocal, the mechanism is unknown, and few studies evaluate the physiological correlates between ginkgo or Asian ginseng and cognition. There is a link between stress and cognition; namely, stress impairs learning, memory, and cognitive flexibility. In vivo studies show that ginkgo and Asian ginseng can improve stress markers. The purpose of this double-blind, placebo-controlled, crossover study was to understand whether cardiovascular (CV) reactivity (a physiological measure of stress) may modulate the beneficial effects of Asian ginseng and ginkgo on cognition.
Undergraduate students (n = 48; mean age, 20.2 years) were recruited at Sunway University; Bandar Sunway, Selangor, Malaysia. Excluded subjects regularly consumed caffeine, Asian ginseng, or ginkgo; were diabetic; had hormone-sensitive conditions, autoimmune diseases, bleeding conditions, or heart conditions; or took medications known to interact with either Asian ginseng or ginkgo.
Cognition was measured using the Psychology Experiment Building Language (PEBL) test battery, which included visual search (VS) task, PEBL psychomotor vigilance task (PPVT), Stroop task, Bechara's Iowa gambling task, Berg's card sorting test, and the Tower of London task. The cognitive tests were completed in 3 sets of 2 tasks (Berg+Tower of London, Stroop+Iowa, and VS+PPVT). To ensure that changes in cognitive scores were due to the treatment and not learning, all subjects first completed a practice day where they performed the cognitive tests until they could no longer improve on their previous attempt by > 5%. Blood pressure (BP) and heart rate (HR) were used as measures of CV reactivity. On the 3 test days, BP and HR were recorded at baseline, 60 min after consuming the treatment, and after the completion of each set of cognitive tasks.
A power calculation was performed to determine the sample size required (n = 24 per group) to establish a power level of 80% based on repeated measures analysis of variance (ANOVA). Subjects were randomly assigned to either the ginkgo group (12 males and 12 females) or the Asian ginseng group (16 females and 8 males). On the 3 test days, the ginkgo group received an acute dose of either placebo, 120 mg, or 240 mg ginkgo in a crossover fashion, and the ginseng group received an acute dose of either placebo, 500 mg, or 1000 mg Asian ginseng in a crossover fashion. The ginkgo extract (GBE24/6; MediPharm Industries; Ipoh, Perak, Malaysia) was standardized to contain 24% ginkgo flavone glycosides and 6% ginkgo terpenes. The Asian ginseng extract (GNC, Inc.; Pittsburgh, Pennsylvania) was standardized to contain 3% ginsenosides. There was a 48-hour washout period between each test day. To control for order effects, a Latin Square design was used to block-randomize both treatment order and the order of the cognitive tests.
Cognitive, BP, and HR data for the ginseng group were analyzed using one-way repeated measures ANOVA for placebo, medium dose, and high dose. Gender differences within the ginseng group could not be evaluated because there was an unequal number of males and females. As there were equal numbers of males and females in the ginkgo group, a mixed-design ANOVA (2x3) was used to evaluate the ginkgo data, with gender as the between-subject factor and dose as the within-subject factor (gender*dose).
For the ginkgo group, there was a significant gender*dose effect observed for the Berg and Stroop tasks. In women, both doses of ginkgo reduced the number of errors on the Berg task significantly more than placebo (P = 0.039 for the 120-mg dose and P = 0.013 for the 240-mg dose). In men taking ginkgo, the number of errors significantly increased on the Berg task compared with baseline and placebo (P < 0.05 for all). Similar results were observed on the Stroop task. In women, both doses of ginkgo reduced the number of errors significantly more than placebo (P = 0.027 for the 120-mg dose and P = 0.047 for the 240-mg dose), while for men, there was an increase in errors with both doses of ginkgo. Although a similar trend was observed with the VS+PPVT, the effect was not significant. Overall, ginkgo generally improved cognitive performance in women and worsened performance in men. Ginseng had no significant effects on any of the cognitive tasks.
In regard to CV reactivity, systolic and diastolic BP were significantly increased 60 min after 240 mg ginkgo compared with placebo (P = 0.037). Diastolic BP was significantly decreased 60 min after 1000 mg Asian ginseng compared with placebo (P = 0.047). Therefore, normalized scores (percentage change from baseline) were used to evaluate the CV response to cognitive tasks. During placebo, the greatest CV response was observed with the Stroop+Iowa tasks, while the VS+PPVT elicited the lowest response; i.e., the CV changes were task-specific and analysis showed that they were also time independent. Analysis of the ginkgo data by gender showed that during placebo, the CV response to the cognitive tasks was significantly increased above baseline in females, while males displayed a blunted CV response to the tasks. CV reactivity in the ginseng group during placebo was similar to the males in the ginkgo group, as they also had a blunted CV response to the cognitive tasks. It is noted that, arguably, the blunted CV response may be due to reduced engagement or interest in the tasks; blunted CV response is also related to poor cognitive performance.
Treatment with 240 mg ginkgo significantly reduced systolic and diastolic BP compared to placebo following the Stroop+Iowa tasks (P = 0.002 and P = 0.003, respectively). A significant gender*dose effect was observed following the Berg+Tower of London tasks; only the women taking 240 mg ginkgo had a significant decrease in diastolic BP compared to placebo (P = 0.005). After the VS+PPVT, the 1000-mg dose of Asian ginseng significantly increased diastolic BP and increased HR compared with placebo (P = 0.007 and P = 0.011, respectively). Asian ginseng had no effect on BP and HR following the Stroop+Iowa and Berg+Tower of London tasks.
In summary, ginkgo improved executive function as measured with Stroop and Berg tasks in women but not in men, and Asian ginseng had no effect on cognition. The authors conclude that CV reactivity may be a mechanism by which ginkgo, but not ginseng, improves some measures of cognitive performance, and that this effect is gender-specific. Further, ginkgo improved performance only on those tasks which elicited a strong CV response during placebo. It is recommended that future studies evaluate additional markers of stress to confirm these preliminary findings and investigate how physiological correlates of task engagement relate to CV reactivity, ginkgo treatment, and cognitive performance.
This trial was well designed. A power calculation was performed to determine the required number of subjects. The inclusion of a training day provided evidence that the improvement in cognitive performance was due to the treatment. The use of block randomization and normalized scores controlled for potentially confounding variables. The statistical analyses tested main effects, order effects, gender*dose effects, time effects, and the impact of cognitive testing on CV response. The reporting of the trial was good; a Consolidated Standards of Reporting Trials (CONSORT) checklist was included in the supplemental information. The trial was registered with ClinicalTrials.gov (identifier: NCT02386852). No conflicts of interest were reported.
—Heather S. Oliff, PhD