Jonathon L. Reay

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.

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 10min test battery at baseline, and then six times in immediate succession commencing 60min after the day’s treatment (placebo, 200mg G115 or 400mg G115). The 10 min battery comprised a Serial Threes subtraction task (2min); a Serial Sevens task (2min); a Rapid Visual Information Processing task (5min); 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 10min 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.

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 G115/0mg glucose (placebo); 200mg G115/0mg glucose (ginseng); 0mg G115/25g glucose (glucose) or 200mg G115/25g 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 days 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.

MDMA polydrug users show process-specific central executive impairments coupled with impaired social and emotional judgement processes

In recent years working memory de.cits have been reported in users of MDMA (3,4-methylenedioxymethamphetamine, ecstasy). The current study aimed to assess the impact of MDMA use on three separate central executive processes (set shifting, inhibition and memory updating) and also on ëprefrontalí mediated social and emotional judgement processes. Fifteen polydrug ecstasy users and 15 polydrug non-ecstasy user controls completed a general drug use questionnaire, the Brixton Spatial Anticipation task (set shifting), Backward Digit Span procedure (memory updating), Inhibition of Return (inhibition), an emotional intelligence scale, the Tromso Social Intelligence Scale and the Dysexecutive Questionnaire (DEX). Compared with MDMA-free polydrug controls, MDMA polydrug users showed impairments in set shifting and memory updating, and also in social and emotional judgement processes. The latter two de.cits remained signi.cant after controlling for other drug use. These data lend further support to the proposal that cognitive processes mediated by the prefrontal cortex may be impaired by recreational ecstasy use.

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.

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.

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.

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

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.

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 (Cohens 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.

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.