Ginkgo biloba: no robust effect on cognitive abilities or mood in healthy young or older adults

Ginkgo biloba extracts are commonly used to prevent or treat memory problems but evidence on the efficacy of ginkgo is equivocal. In any case, the psychological locus of ginkgo's effects is unknown. A 12-week, double-blind, placebo-controlled study assessed effects of ginkgo (120 mg per day) on a wide range of cognitive abilities, executive function, attention and mood in 93 healthy older adults (55-79 years) and in 104 young adults (18-43 years). For the older adult sample, longer-term memory assessed by associational learning tasks showed improvement with ginkgo (d = 0.52, p = 0.04). There was no statistically significant difference on any other measure. For the young adult group no measure showed statistically significant effects of ginkgo enhancement. There were no side effects unequivocally attributable to treatment with ginkgo and those reported by participants in the ginkgo groups were mild and similar to those reported elsewhere.     

Electroencephalograph effects of single doses of Ginkgo biloba and Panax ginseng in healthy young volunteers

Both Ginkgo biloba and Panax ginseng exert a number of physiological effects and have been shown to modulate aspects of cognitive performance. Whilst a number of studies have examined ginkgo's effects on electroencephalograph (EEG) recordings, to date, none have investigated the EEG effects of ginseng. In this double-blind, placebo-controlled, balanced crossover experiment, the effects of single doses of G. biloba (360 mg GK501), P. ginseng (200 mg G115), and an identical placebo, on auditory-evoked potentials, contingent negative variation (CNV), and resting power within the delta, theta, alpha, and beta wavebands, were assessed in 15 healthy volunteers. Each participant was assessed on three separate occasions 4 h after consuming that day's treatment. The order of presentation of the treatments was dictated by a Latin square with 7 days between testing sessions. The results showed that ginseng led to a significant shortening of the latency of the P300 component of the evoked potential. Both ginseng and ginkgo also led to significant reductions in frontal 'eyes closed' theta and beta activity, with additional reduction for ginseng in the alpha waveband. These findings demonstrate for the first time that P. ginseng can directly modulate cerebroelectrical activity, and that these effects are more pronounced than those following G. biloba.     

Acute,dose-dependent cognitive effects of Ginkgo biloba,Panax ginseng and their combination in healthy young volunteers: differential interactions with cognitive demand

The present paper describes three studies examining the acute effects of single doses of Ginkgo biloba (GK501), Ginseng (G115) and their combination (Ginkoba M/E, Pharmaton SA) on the performance of healthy young adults (mean age 21 years) during serial arithmetic tasks with differing cognitive load. In each double-blind, placebo-controlled study three different treatment doses and a placebo were administered, according to a balanced crossover design, with a 7-day washout period between each dose. Participants' scores on two computerised serial subtraction tasks (Serial Threes and Serial Sevens) were assessed pre-dosing and at 1, 2.5, 4 and 6 h thereafter. A number of significant time, dose and task-specific effects were associated with each treatment. There was a dose-dependent improvement in speed of responding during Serial Threes following Ginkgo biloba. Different doses of Ginseng improved accuracy and slowed responses during Serial Sevens. The most striking result, however, was a highly significant and sustained increase in the number of Serial Sevens responses following 320 mg of the Ginkgo-Ginseng combination at all post-treatment testing times. This was accompanied by improved accuracy during Serial Sevens and Serial Threes following the 640 mg and the 960 mg dose, respectively. The paper concludes with speculation into the possible mechanisms underlying these effects.     

The memory enhancing effects of a Ginkgo biloba/Panax ginseng combination in healthy middle-aged volunteers

The effects of capsules containing 60 mg of a standardised extract of Ginkgo biloba (GK501) and 100 mg of a standardised extract of Panax ginseng (G115) on various aspects of cognitive function were assessed in healthy middle-aged volunteers. A double blind, placebo controlled, 14 week, parallel group, repeated assessment, multi-centre trial of two dosing regimens, 160 mg b.i.d. and 320 mg o.d. was conducted. Two hundred and fifty-six healthy middle-aged volunteers successfully completed the study. On various study days (weeks 0, 4, 8, 12 and 14) the volunteers performed a selection of tests of attention and memory from the Cognitive Drug Research computerised cognitive assessment system prior to morning dosing and again, at 1, 3 and 6 h later. The volunteers also completed questionnaires about mood states, quality of life and sleep quality. The Ginkgo/ginseng combination was found significantly to improve an Index of Memory Quality, supporting a previous finding with the compound. This effect represented an average improvement of 7.5% and reflected improvements to a number of different aspects of memory, including working and long-term memory. This enhancement to memory was seen throughout the 12-week dosing period and also after a 2-week washout. This represents the first substantial demonstration of improvements to the memory of healthy middle-aged volunteers produced by a phytopharmaceutical.     

Effects of Ginkgo biloba on alertness and chemosensory function in healthy adults

Ginkgo biloba is reported to enhance cognitive function in patients with selected neural disorders. Its effects in healthy, young adults are less well characterized. This work explored whether Ginkgo biloba could ameliorate decrements in alertness post-prandially and/or enhance chemosensory function. Both are functions that could be influenced by enhanced cerebral blood flow and neuronal metabolism, reported properties of the compound. A double-blind placebo-controlled study was conducted with 19 males and 20 females with a mean age of 23.6 +/- 5.4 years and mean weight of 70.0 +/- 1.9 kg. Participants were supplemented for 13 weeks with either Ginkgo biloba (mean dose 184.5 mg/d (range 130-234 mg/d)) or placebo and administered various alertness, performance, affective state and chemosensory tests at weeks 1, 5, 9 and 13. Participants did experience the post-prandial affective state decrement (i.e. post-lunch dip), but not the performance decrement. Performance on the chemosensory tests improved over the 13-week study. However, Ginkgo biloba was ineffective at alleviating the symptoms of the post-lunch dip or at enhancing taste and smell function.     

Anti-stress effects of Ginkgo biloba and Panax ginseng: a comparative study

Stress is a global menace fortified by the advancement of industrialization. Failure of stress management is due to lack of proper evaluation of anti-stress products. We explored the anti-stress potential of the Ginkgo biloba (G. biloba, 30 mg/kg, p.o.) and compared it with that of Panax ginseng (P. ginseng, 100 mg/kg, p.o.) against acute stress (AS) and chronic stress (CS) models in rats. Immediately after AS and CS, the rats were sacrificed, and adrenal glands and stomach were dissected out for weight determination and scoring of the ulcer index (UI), respectively, as well as changes in biochemical parameters like plasma glucose (GL), triglycerides (TG), cholesterol (CL), creatine kinase (CK), and serum corticosterone (CORT) were also estimated. AS significantly increased UI, adrenal gland weight (AGW), GL, CK activity, and CORT, whereas G. biloba significantly reduced them. P. ginseng significantly reverted GL and CK activity. In CS, a significant increase was found in the UI, AGW, CK activity, and CORT with a decrease in the level of CL and TG. G. biloba did not produce any significant effect on CS-induced alterations. P. ginseng reduced the UI, AGW, plasma GL, TG, CK activity, and CORT level significantly. From the above study, G. biloba is more effective in AS, whereas for CS, P. ginseng will be a better option. Hence these extracts possess significant anti-stress properties and can be used for the treatment of stress-induced disorders.     

Modulation of cognitive performance following single doses of 120 mg Ginkgo biloba extract administered to healthy young volunteers

Previous research from our laboratory demonstrated that administration of single doses (120, 240, 360 mg) of standardised Ginkgo biloba extract (GBE) had linear, dose-dependent, positive effects on the speed of performing attention tasks in comparison to placebo. However, whilst the lowest dose, which is typical of a recommended daily dose, had no effect on the speed of attention task performance it did engender mild improvements in secondary memory performance. The current study presents a reanalysis of data from three methodologically identical studies that each included a treatment of 120 mg GBE and matched placebo.All three studies were of a multiple dose, placebo-controlled, double-blind, balanced-crossover design, employing four or five treatment arms in total. Across the studies 78 healthy young participants received 120 mg GBE and placebo in randomly counterbalanced order, separated by a wash-out period of at least 7 days. On each study day participants' performance on the Cognitive Drug Research (CDR) computerised cognitive assessment battery was measured immediately prior to dosing and at 1, 2.5, 4 and 6 hr following treatment, with scores collapsed into the six measures (speed of attention, accuracy of attention, secondary memory, working memory, speed of memory, quality of memory) which have previously been derived by factor analysis of the data from CDR subtests.The results showed that 120 mg of Ginkgo engendered a significant improvement on the 'quality of memory' factor that was most evident at 1 and 4 hr post-dose, but had a negative effect on performance on the 'speed of attention' factor that was most evident at 1 and 6 hr post-dose.The current study confirmed the previous observation of modestly improved memory performance following 120 mg of GBE, but suggests that acute administration of this typical daily dose may have a detrimental effect on the speed of attention task performance which is opposite to that seen previously following higher doses.     

The dose-dependent cognitive effects of acute administration of Ginkgo biloba to healthy young volunteers

RATIONALE: Chronic administration of extracts from the leaves of the tree Ginkgo biloba is known to improve aspects of cognitive performance. However, little is known about the effects of acute doses of Ginkgo on coherent cognitive domains. Recent factor analysis of test measures from subtasks of the Cognitive Drug Research (CDR) computerised assessment battery has revealed that four primary cognitive 'factors' corresponding to speed of attention, accuracy of attention, speed of memory and quality of memory can be useful to describe cognitive function changes. OBJECTIVE: The present study aimed at assessing whether acute administration of Ginkgo biloba had any consistent effect on the four CDR factors. METHODS: The study utilised a placebo-controlled, multi-dose, double-blind, balanced, crossover design. Twenty participants received 120 mg, 240 mg and 360 mg of a standardised extract of Ginkgo (GK501, Pharmaton, SA) or a matching placebo. Cognitive performance was assessed using the CDR computerised test battery immediately prior to dosing and at 1, 2.5, 4 and 6 h thereafter. The primary outcome measures were the four aspects of cognitive performance, which have previously been derived by factor analysis of CDR subtests. RESULTS: Compared with the placebo, administration of Ginkgo produced a number of significant changes on the performance measures. The most striking of these was a dose-dependent improvement of the 'speed of attention' factor following both 240 mg and 360 mg of the extract, which was evident at 2.5 h and was still present at 6 h. Additionally, there were a number of time- and dose-specific changes (both positive and negative) in performance of the other factors. CONCLUSIONS: We conclude that acute administration of Ginkgo biloba is capable of producing a sustained improvement in attention in healthy young volunteers.     

Effects of alcohol and flunitrazepam on mood and performance in healthy young men

Alcohol and flunitrazepam did not have any pharmacokinetic interactions when ingested 30 minutes apart at night. Flunitrazepam, 2.0 mg, but not 0.8 Gm/kg alcohol had a strong deleterious effect on performance shortly after ingestion. The combination of flunitrazepam and alcohol impaired tracking in a divided attention task the following morning.     

Effects of a combined extract of Ginkgo biloba and Bacopa monniera on cognitive function in healthy humans

Extracts of Ginkgo biloba and Bacopa monniera have been shown to produce positive effects on cognitive function in healthy subjects. While the exact mechanisms are not known, it has been suggested that antioxidant properties and cholinergic modulation may play a role. In the current study the sub-chronic (2 weeks) and chronic (4 weeks) effects of an extract containing Ginkgo biloba (120 mg) and Bacopa monniera (300 mg) (Blackmores Ginkgo Brahmi) on cognitive function were examined. The study was a randomized, double-blind, placebo-controlled, independent group design in which 85 healthy subjects were allocated to one of two treatment conditions (placebo or combined Ginkgo biloba and Bacopa monniera extract). Testing was conducted at baseline and 2 and 4 weeks post treatment. The results showed that the combined extract relative to placebo did not demonstrate any significant effects on tests investigating a range of cognitive processes including attention, short-term and working memory, verbal learning, memory consolidation, executive processes, planning and problem solving, information processing speed, motor responsiveness and decision making. These findings suggest that at least within the current treatment duration and doses, an extract containing Ginkgo biloba and Bacopa monniera had no cognitive enhancing effects in healthy subjects.     

Effects on cognition and mood in postmenopausal women of 1-week treatment with Ginkgo biloba

In a double-blind, placebo-controlled study, postmenopausal women (53-65 years old) were randomly assigned to 7-day treatment with Ginkgo (120 mg/day, n=15) or matched placebo (n=16). They were given a battery of cognitive tests and measurements of mood and menopausal symptoms at baseline (before treatment began) and at the end of 7 days. The group treated with Ginkgo was significantly better than the placebo group in a matching-to-sample test of nonverbal memory, but the groups did not differ in immediate or delayed paragraph recall or in delayed recall of pictures. In a test of frontal lobe function (rule shifting) and in the Paced Auditory Serial Addition Test (PASAT) (which measures sustained attention but also involves frontal lobe function), the group treated with Ginkgo performed significantly better than the placebo group. However, the groups did not differ in a test of planning. The treatments did not differ in their effects on the volunteers' ratings of menopausal symptoms, sleepiness, bodily symptoms or aggression. The benefits of Ginkgo on memory and frontal lobe function found in this study are modest but are unlikely to be secondary to major mood changes.     

Effects of Ginkgo biloba extract on the pharmacokinetics of bupropion in healthy volunteers

AIMS

To assess the effects of Ginkgo biloba extract on the pharmacokinetics of bupropion in healthy volunteers.

METHODS

Fourteen healthy male volunteers (age range 19–25 years) received orally administered bupropion (150 mg) alone and during treatment with G. biloba 240 mg day⁻¹ (two 60-mg capsules taken twice daily) for 14 days. Serial blood samples were obtained over 72 h after each bupropion dose, and used to derive pharmacokinetic parameters of bupropion and its CYP2B6-catalysed metabolite, hydroxybupropion.

RESULTS

Ginkgo biloba extract administration resulted in no significant effects on the AUC_0–∞ of bupropion and hydroxybupropion. Bupropion mean AUC_0–∞ value was 1.4 µg·h ml⁻¹[95% confidence interval (CI) 1.2, 1.6] prior to G. biloba treatment and 1.2 µg·h ml⁻¹ (95% CI 1.1, 1.4) after 14 days of treatment. Hydroxybupropion mean AUC_0–∞ value was 8.2 µg·h ml⁻¹ (95% CI 6.5, 10.4) before G. biloba administration and 8.7 µg·h ml⁻¹ (95% CI 7.1, 10.6) after treatment. The C_max of hydroxybupropion increased from 221.8 ng ml⁻¹ (95% CI 176.6, 278.6) to 272.7 ng ml⁻¹ (95% CI 215.0, 345.8) (P = 0.038) and the t_1/2 of hydroxybupropion fell from 25.0 h (95% CI 22.7, 27.5) to 21.9 h (95% CI 19.9, 24.1) (P = 0.000).

CONCLUSIONS

Ginkgo biloba extract administration for 14 days does not significantly alter the basic pharmacokinetic parameters of bupropion in healthy volunteers. Although G. biloba extract treatment appears to reduce significantly the t_1/2 and increase the C_max of hydroxybupropion, no bupropion dose adjustments appear warranted when the drug is administered orally with G. biloba extract, due to the lack of significant change observed in AUC for either bupropion or hydroxybupropion.     

Effects of Ginkgo biloba administered after spatial learning on water maze and radial arm maze performance in young adult rats

Ginkgo biloba is reported to improve learning and memory in animals. However, many studies do not directly test the effects of Ginkgo on memory because the drug is administered during the learning phase of the experiments. In this study, we examined the effect of 10 mg/kg, 20 mg/kg, or 40 mg/kg G. biloba extract on spatial memory by administering the drug in the interval between training and testing. Rats were tested for long-term reference memory retention in the radial arm maze and in the Morris water maze during daily probe trials in which the hidden platform was removed. G. biloba had no effect on reference memory in either the water maze or radial arm maze. To test short-term working spatial memory using the radial arm maze, animals were removed after receiving the reward from 4 of the 8 arms and were returned to complete the maze 2 h later. While Ginkgo had no effect on working memory, over time animals exposed to Ginkgo learned task better than control animals. Thus, Ginkgo appears to enhance neither short-term working memory nor long-term reference memory, but it may promote learning of spatial information.