Sceletium tortuosum (Zembrin® ) ameliorates experimentally induced anxiety in healthy volunteers.

OBJECTIVE: To investigate the anxiolytic properties of a standardized extract of Sceletium tortuosum (trademarked-Zembrin® ). METHODS: Two studies utilized a placebo-controlled, double-blind, between-subject experimental design to investigate the effects of a single dose of Sceletium tortuosum (25 mg, Zembrin® ) on laboratory stress/anxiety responding in 20 young healthy volunteers. To elicit feelings of stress/anxiety, participants completed 20 min of the multitasking framework in study 1 and a 5-min simulated public speaking task in study 2. Study 1 measured subjective experiences of mood at baseline, prestress induction, and poststress induction. Study 2 measured subjective experiences of anxiety and physiological indicators of stress (heart rate [HR] and galvanic skin response) at baseline, prestress induction, during stress induction, and poststress induction. RESULTS: A series of analysis of covariances (baseline entered as the covariate) revealed no treatment effect in study 1; however, study 2 revealed subjective anxiety levels to be significantly lower in the Zembrin® group at the prestress induction point and a significant interaction between treatment and time on HR. Taken together, results indicate that a single dose of Zembrin® can ameliorate laboratory stress/anxiety responding in healthy volunteers. CONCLUSION: We provide the first tentative behavioral evidence to support the anxiolytic properties of Sceletium tortuosum (25 mg Zembrin® ).

A systematic review of research investigating the physiological and psychological effects of combining Ginkgo biloba and Panax ginseng into a single treatment in humans: Implications for research design and analysis.

BACKGROUND AND PURPOSE: The traditional herbal supplements Panax ginseng and Ginkgo biloba are self-medicated by members of the general public and prescribed by healthcare professionals in some EU countries for numerous health complaints. Clinical evidence is mixed and mechanisms of action are not fully understood. There is clinical interest into the synergistic effects of combining both herbs. METHODS: We systematically review the literature investigating the effects of combination treatments on physiological and psychological outcomes in humans. We identified all studies meeting inclusion criteria: (a) written in English; (b) peer-reviewed; (c) conducted in humans; (d) including either a proprietary Panax ginseng/Ginkgo biloba treatment or a study preparation containing both; (e) placebo-controlled; (f) utilizing standardized extracts. We critically discuss each trial; calculate standardized effect sizes where possible and provide recommendations for research design and analysis. RESULTS: Eight studies were identified and all investigated a proprietary combination treatment, Gincosan® . Studies are of high quality and robust; however, practice effects, choice of statistical model, and reliance upon null-hypothesis significance testing hinder generalized estimates of effect. The most consistent results are benefits to aspects of the circulatory/cardiovascular system in patient populations and "secondary memory" performance in patient and healthy populations. Two studies demonstrate synergy in healthy populations following a single dose; however, synergy in patient populations and following repeated dosing has not yet been directly tested. CONCLUSIONS: A Panax ginseng and Ginkgo biloba combination treatment can improve aspects of physiological and cognitive function in humans; however, evidence for synergy requires further investigation and future research should directly investigate synergy following repeated dosing.

The effects of chronic trans-resveratrol supplementation on aspects of cognitive function, mood, sleep, health and cerebral blood flow in healthy, young humans.

Single doses of resveratrol have previously been shown to increase cerebral blood flow (CBF) with no clear effect on cognitive function or mood in healthy adults. Chronic resveratrol consumption may increase the poor bioavailability of resveratrol or otherwise potentiate its psychological effects. In this randomised, double-blind, placebo-controlled, parallel-groups study, a total of sixty adults aged between 18 and 30 years received either placebo or resveratrol for 28 d. On the 1st and 28th day of treatment, the performance of cognitively demanding tasks (serial subtractions, rapid visual information processing and 3-Back) (n 41 complete data sets) was assessed, alongside blood pressure (n 26) and acute (near-IR spectroscopy (NIRS)) and chronic (transcranial Doppler) measures of CBF (n 46). Subjective mood, sleep quality and health questionnaires were completed at weekly intervals (n 53/54). The results showed that the cognitive effects of resveratrol on day 1 were restricted to more accurate but slower serial subtraction task performance. The only cognitive finding on day 28 was a beneficial effect of resveratrol on the accuracy of the 3-Back task before treatment consumption. Subjective ratings of 'fatigue' were significantly lower across the entire 28 d in the resveratrol condition. Resveratrol also resulted in modulation of CBF parameters on day 1, as assessed by NIRS, and significantly increased diastolic blood pressure on day 28. Levels of resveratrol metabolites were significantly higher both before and after the day's treatment on day 28, in comparison with day 1. These results confirm the acute CBF effects of resveratrol and the lack of interpretable cognitive effects.

Effects of resveratrol alone or in combination with piperine on cerebral blood flow parameters and cognitive performance in human subjects: a randomised, double-blind, placebo-controlled, cross-over investigation.

Previous research has shown that resveratrol can increase cerebral blood flow (CBF) in the absence of improved cognitive performance in healthy, young human subjects during the performance of cognitively demanding tasks. This lack of cognitive effects may be due to low bioavailability and, in turn, reduced bioefficacy of resveratrol in vivo. Piperine can alter polyphenol pharmacokinetics, but previous studies have not investigated whether this affects the efficacy of the target compound. Therefore, the objective of the present study was to ascertain whether co-supplementation of piperine with resveratrol affects the bioavailability and efficacy of resveratrol with regard to cognition and CBF. The present study utilised a randomised, double-blind, placebo-controlled, within-subjects design, where twenty-three adults were given placebo, trans-resveratrol (250 mg) and trans-resveratrol with 20 mg piperine on separate days at least a week apart. After a 40 min rest/absorption period, the participants performed a selection of cognitive tasks and CBF was assessed throughout the period, in the frontal cortex, using near-IR spectroscopy. The presence of resveratrol and its conjugates in the plasma was confirmed by liquid chromatography-MS analysis carried out following the administration of the same doses in a separate cohort (n 6). The results indicated that when co-supplemented, piperine and resveratrol significantly augmented CBF during task performance in comparison with placebo and resveratrol alone. Cognitive function, mood and blood pressure were not affected. The plasma concentrations of resveratrol and its metabolites were not significantly different between the treatments, which indicates that co-supplementation of piperine with resveratrol enhances the bioefficacy of resveratrol with regard to CBF effects, but not cognitive performance, and does this without altering bioavailability.

Cognitive effects of two nutraceuticals Ginseng and Bacopa benchmarked against modafinil: a review and comparison of effect sizes.

Over recent years there has been increasing research into both pharmaceutical and nutraceutical cognition enhancers. Here we aimed to calculate the effect sizes of positive cognitive effect of the pharmaceutical modafinil in order to benchmark the effect of two widely used nutraceuticals Ginseng and Bacopa (which have consistent acute and chronic cognitive effects, respectively). A search strategy was implemented to capture clinical studies into the neurocognitive effects of modafinil, Ginseng and Bacopa. Studies undertaken on healthy human subjects using a double-blind, placebo-controlled design were included. For each study where appropriate data were included, effect sizes (Cohen's d) were calculated for measures showing significant positive and negative effects of treatment over placebo. The highest effect sizes for cognitive outcomes were 0.77 for modafinil (visuospatial memory accuracy), 0.86 for Ginseng (simple reaction time) and 0.95 for Bacopa (delayed word recall). These data confirm that neurocognitive enhancement from well characterized nutraceuticals can produce cognition enhancing effects of similar magnitude to those from pharmaceutical interventions. Future research should compare these effects directly in clinical trials.

Docosahexaenoic acid-rich fish oil modulates the cerebral hemodynamic response to cognitive tasks in healthy young adults.

A number of recent studies have assessed the impact of dietary omega-3 polyunsaturated fatty acids (n-3 PUFAs) on behavioral outcomes; however, very little attention has been given to their impact upon brain function in physiological terms. Sixty-five healthy adults aged 18-29yrs took part in this double-blind, placebo-controlled study assessing the effects of 12 weeks daily dietary supplementation with docosahexaenoic acid-rich fish oil (1g, 2g) or placebo (olive oil). Relative changes in the concentration of oxyhemoglobin and deoxyhemoglobin were assessed in the prefrontal cortex using near-infrared spectroscopy during performance of nine computerized cognitive tasks. Supplementation with both doses of fish oil, in comparison with placebo, resulted in significantly increased concentrations of oxyhemoglobin and total levels of hemoglobin, indicative of increased cerebral blood flow, during the cognitive tasks. Changes in hemodynamic response to tasks were not accompanied by consistent changes in cognitive performance.

DHA-rich oil modulates the cerebral haemodynamic response to cognitive tasks in healthy young adults: a near IR spectroscopy pilot study.

The impact of dietary n-3 PUFA on behavioural outcomes has been widely researched; however, very little attention has been given to their impact on brain functioning in physiological terms. A total of twenty-two healthy adults took part in this double-blind, placebo-controlled study, wherein the cerebral haemodynamic effects of 12 weeks of daily dietary supplementation with either 1 g DHA-rich or 1 g EPA-rich fish oil (FO) or placebo (1 g olive oil) were assessed. Relative changes in the concentration of oxygenated Hb (oxy-Hb) and deoxygenated Hb were assessed in the prefrontal cortex using near IR spectroscopy (NIRS) during the performance of four computerised cognitive tasks. Supplementation with DHA-rich FO, in comparison with placebo, resulted in a significant increase in the concentrations of oxy-Hb and total levels of Hb, indicative of increased cerebral blood flow (CBF), during the cognitive tasks. In comparison, no effect on CBF was observed following supplementation with EPA-rich FO, where concentration changes in the chromophores followed the same pattern as placebo. These encouraging pilot data warrant further application of NIRS in this area.

No effect of 12 weeks' supplementation with 1 g DHA-rich or EPA-rich fish oil on cognitive function or mood in healthy young adults aged 18-35 years.

The n-3 PUFA are a unique class of fatty acids that cannot be manufactured by the body, and must be acquired via dietary sources. In the UK, as well as in other Western nations, these 'essential' fatty acids are consumed in quantities that fall below government guidelines. The present study explored the effects of 12 weeks' dietary supplementation with 1 g/d of two types of fish oil (FO; DHA-rich and EPA-rich) in 159 healthy young adults aged 18-35 years. An assessment of performance on a battery of computerised cognitive tasks and mood measures took place before and following the 12-week treatment regimen. Venous blood samples were also supplied by participants at both time points which were later analysed for serum fatty acid concentrations. Despite good adherence to the study protocol - as reflected in increased concentrations of n-3 serum fatty acids - compared with placebo, the observed effects of both active treatments were minimal. The only finding of note revealed that supplementation with EPA-rich FO may reduce subjective mental fatigue at times of high cognitive demand, although further investigation is required. These findings, taken together with other recent reports of null effects, suggest that dietary supplementation with n-3 PUFA in healthy, normally developing and impairment-free populations is unlikely to result in cognitive enhancement.

Monoterpenoid extract of sage (Salvia lavandulaefolia) with cholinesterase inhibiting properties improves cognitive performance and mood in healthy adults.

Extracts of sage (Salvia officinalis/lavandulaefolia) with terpenoid constituents have previously been shown to inhibit cholinesterase and improve cognitive function. The current study combined an in vitro investigation of the cholinesterase inhibitory properties and phytochemical constituents of a S. lavandulaefolia essential oil, with a double-blind, placebo-controlled, balanced crossover study assessing the effects of a single dose on cognitive performance and mood. In this latter investigation 36 healthy participants received capsules containing either 50 µL of the essential oil or placebo on separate occasions, 7 days apart. Cognitive function was assessed using a selection of computerized memory and attention tasks and the Cognitive Demand Battery before the treatment and 1-h and 4-h post-dose. The essential oil was a potent inhibitor of human acetylcholinesterase (AChE) and consisted almost exclusively of monoterpenoids. Oral consumption lead to improved performance of secondary memory and attention tasks, most notably at the 1-h post-dose testing session, and reduced mental fatigue and increased alertness which were more pronounced 4-h post-dose. These results extend previous observations of improved cognitive performance and mood following AChE inhibitory sage extracts and suggest that the ability of well-tolerated terpenoid-containing extracts to beneficially modulate cholinergic function and cognitive performance deserves further attention.

Panax ginseng (G115) improves aspects of working memory performance and subjective ratings of calmness in healthy young adults.

OBJECTIVE: There is a lack of research into the cognitive and mood effects of repeated ginseng ingestion. The present study assessed the effects of Panax ginseng (G115) on subjective mood and aspects of 'working' memory processes, following a single dose and following sub-chronic (7 days) ingestion, in healthy volunteers. METHODS: A placebo-controlled, double-blind, randomised, crossover was utilised. Thirty volunteers (mean age 22.87 years; SD 4.01) received each treatment (200 mg; 400 mg; placebo) for 8 days, in a counter balanced order, with a 6-day wash-out period. Testing was on days 1 and 8 of each treatment period, at pre-dose, 1, 2.5 and 4 h post-dose. RESULTS: Results revealed dose-related treatment effects (p < 0.05). Two hundred milligrams slowed a fall in mood at 2.5 and 4 h on day 1 and at 1 and 4 h on day 8, but slowed responding on a mental arithmetic task across day 1 and at 1 and 2.5 h on day 8. The 400 mg dose also improved calmness (restricted 2.5 and 4 h on day 1) and improved mental arithmetic across days 1 and 8. CONCLUSIONS: We found no evidence of additional benefits, nor attenuation of acute effects following repeated ingestion of Panax ginseng (G115).

Effects of resveratrol on cerebral blood flow variables and cognitive performance in humans: a double-blind, placebo-controlled, crossover investigation.

BACKGROUND: The many putative beneficial effects of the polyphenol resveratrol include an ability to bolster endogenous antioxidant defenses, modulate nitric oxide synthesis, and promote vasodilation, which thereby improves blood flow. Resveratrol may therefore modulate aspects of brain function in humans. OBJECTIVE: The current study assessed the effects of oral resveratrol on cognitive performance and localized cerebral blood flow variables in healthy human adults. DESIGN: In this randomized, double-blind, placebo-controlled, crossover study, 22 healthy adults received placebo and 2 doses (250 and 500 mg) of trans-resveratrol in counterbalanced order on separate days. After a 45-min resting absorption period, the participants performed a selection of cognitive tasks that activate the frontal cortex for an additional 36 min. Cerebral blood flow and hemodynamics, as indexed by concentration changes in oxygenated and deoxygenated hemoglobin, were assessed in the frontal cortex throughout the posttreatment period with the use of near-infrared spectroscopy. The presence of resveratrol and its conjugates in plasma was confirmed by HPLC after the same doses in a separate cohort (n = 9). RESULTS: Resveratrol administration resulted in dose-dependent increases in cerebral blood flow during task performance, as indexed by total concentrations of hemoglobin. There was also an increase in deoxyhemoglobin after both doses of resveratrol, which suggested enhanced oxygen extraction, that became apparent toward the end of the 45-min absorption phase and was sustained throughout task performance. Cognitive function was not affected. Resveratrol metabolites were present in plasma throughout the cognitive task period. CONCLUSION: These results showed that single doses of orally administered resveratrol can modulate cerebral blood flow variables.

Supplementing cognitive aging: a selective review of the effects of ginkgo biloba and a number of everyday nutritional substances.

This review concerns a number of substances that have been receiving much attention, particularly in the media, for their potential to protect against age-related cognitive decline, and a focus is placed upon recent findings. Omega-3 fatty acids appear to play important roles in preserving neuronal structure and function and minimizing cognitive decline, whereas the antioxidant vitamins C and E appear to be particularly beneficial for combating age-related oxidative stress when administered in combination. Fruit and vegetable polyphenols also offer great potential, although most research thus far has involved rodents. Finally, there is mixed evidence regarding the cognitive enhancing properties of Ginkgo biloba, and the B vitamins folate and cobalamin, with all of these requiring further investigation.

Panax ginseng has no effect on indices of glucose regulation following acute or chronic ingestion in healthy volunteers.

In the absence of effective pharmacotherapy for diabetes there has been an increase in the use of, and research into, alternative treatment strategies. These include exercise, dietary interventions and the use of supplements including extracts of ginseng. Two separate, placebo-controlled, double-blind, cross-over studies investigating the effects of chronic ingestion of Panax ginseng (study 1 used G115, study 2 used Cheong Kwan Jang) on glycated Hb (HbA1c; study 1, n 18; study 2, n 11), fasting plasma insulin (study 1, n 17; study 2, n 12), fasting plasma glucose and postprandial response (following breakfast) (study 1, n 23; study 2, n 14) in healthy volunteers are reported. In both studies it was found that Panax ginseng had no effect on any gluco-regulatory parameter investigated. These results are not consistent with those reported for a diabetic sample (albeit using slightly different outcomes). These results would suggest that chronic use of Panax ginseng by non-diabetic individuals will have little long-term effect on glucose regulation. The benefits to glucose regulation associated with long-term ginseng use may only be present in populations with compromised glucose control; however, further research is needed to confirm such a speculation.

Differential sensitivity to rotations of facial features in the Thatcher illusion.

A developmental study is presented in which participants must detect the Thatcher illusion in order to match unfamiliar faces on identity. 114 participants between 6 and 67 years of age completed a matching task whereby face pairs were presented upright or under inversion. At all ages, participants were more accurate matching upright than inverted faces. In an altered version of the Thatcher task, where only the eyes or mouth were inverted, all participants were more accurate and faster to detect eye manipulations than mouth manipulations. The results are discussed in terms of the developmental significance of face inversion, the Thatcher illusion, and the salience for protection from the Thatcher illusion.

Effects of Panax ginseng, consumed with and without glucose, on blood glucose levels and cognitive performance during sustained 'mentally demanding' tasks.

Single doses of the traditional herbal treatment Panax ginseng have recently been shown to lower blood glucose levels and elicit cognitive improvements in healthy, overnight-fasted volunteers. The specific mechanisms responsible for these effects are not known. However, cognitive improvements may be related to the glycaemic properties of Panax ginseng. Using a double-blind, placebo-controlled, balanced-crossover design, 27 healthy young adults completed a 10 minute "cognitive demand" test battery at baseline. They then consumed capsules containing either ginseng (extract G115) or a placebo and 30 minutes later a drink containing glucose or placebo. A further 30 minutes later (i.e. 60 minutes post-baseline/capsules) they completed the "cognitive demand" battery six times in immediate succession. Depending on the condition to which the participant was allocated on that particular day, the combination of capsules/drink treatments corresponded to a dose of: 0mg G115/0 mg glucose (placebo); 200mg G115/0 mg glucose (ginseng); 0 mg G115/25 g glucose (glucose) or 200 mg G115/25 g glucose (ginseng/glucose combination). The 10 minute "cognitive demand" battery comprised a Serial Threes subtraction task (2 min); a Serial Sevens subtraction task (2 min); a Rapid Visual Information Processing task (5 min); and a "mental fatigue" visual analogue scale. Blood glucose levels were measured prior to the day's treatment, and before and after the post-dose completions of the battery. The results showed that both Panax ginseng and glucose enhanced performance of a mental arithmetic task and ameliorated the increase in subjective feelings of mental fatigue experienced by participants during the later stages of the sustained, cognitively demanding task performance. Accuracy of performing the Rapid Visual Information Processing task (RVIP) was also improved following the glucose load. There was no evidence of a synergistic relationship between Panax ginseng and exogenous glucose ingestion on any cognitive outcome measure. Panax ginseng caused a reduction in blood glucose levels 1 hour following consumption when ingested without glucose. These results confirm that Panax ginseng may possess glucoregulatory properties and can enhance cognitive performance.

Single doses of Panax ginseng (G115) reduce blood glucose levels and improve cognitive performance during sustained mental activity.

Single doses of the traditional herbal treatment Panax ginseng have recently been shown to elicit cognitive improvements in healthy young volunteers. The mechanisms by which ginseng improves cognitive performance are not known. However, they may be related to the glycaemic properties of some Panax species. Using a double-blind, placebo-controlled, balanced crossover design, 30 healthy young adults completed a 10 min test battery at baseline, and then six times in immediate succession commencing 60 min after the day's treatment (placebo, 200mg G115 or 400mg G115). The 10 min battery comprised a Serial Threes subtraction task (2 min); a Serial Sevens task (2 min); a Rapid Visual Information Processing task (5 min); then a 'mental fatigue' visual analogue scale. Blood glucose was measured prior to each day's treatment, and before, during and after the post-dose completions of the battery. Both the 200mg and 400mg treatments led to significant reductions in blood glucose levels at all three post-treatment measurements (p 0.005 in all cases). The most notable behavioural effects were associated with 200mg of ginseng and included significantly improved Serial Sevens subtraction task performance and significantly reduced subjective mental fatigue throughout all (with the exception of one time point in each case) of the post-dose completions of the 10 min battery (p 0.05). Overall these data suggest that Panax ginseng can improve performance and subjective feelings of mental fatigue during sustained mental activity. This effect may be related to the acute gluco-regulatory properties of the extract.