Crystal F. Haskell

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.

Consumption of cocoa flavanols results in acute improvements in mood and cognitive performance during sustained mental effort

Cocoa flavanols (CF) positively influence physiological processes in ways that suggest their consumption may improve aspects of cognitive function. This study investigated the acute cognitive and subjective effects of CF consumption during sustained mental demand. In this randomized, controlled, double-blinded, balanced, three period crossover trial 30 healthy adults consumed drinks containing 520 mg, 994 mg CF and a matched control, with a three-day washout between drinks. Assessments included the state anxiety inventory and repeated 10-min cycles of a Cognitive Demand Battery comprising of two serial subtraction tasks (Serial Threes and Serial Sevens), a Rapid Visual Information Processing (RVIP) task and a ‘mental fatigue’ scale, over the course of 1 h. Consumption of both 520 mg and 994 mg CF significantly improved Serial Threes performance. The 994 mg CF beverage significantly speeded RVIP responses but also resulted in more errors during Serial Sevens. Increases in self-reported ‘mental fatigue’ were significantly attenuated by the consumption of the 520 mg CF beverage only. This is the first report of acute cognitive improvements following CF consumption in healthy adults. While the mechanisms underlying the effects are unknown they may be related to known effects of CF on endothelial function and blood flow.

DHA supplementation improved both memory and reaction time in healthy young adults: a randomized controlled trial

BACKGROUND Docosahexaenoic acid (DHA) is important for brain function, and its status is dependent on dietary intakes. Therefore, individuals who consume diets low in omega-3 (n-3) polyunsaturated fatty acids may cognitively benefit from DHA supplementation. Sex and apolipoprotein E genotype (APOE) affect cognition and may modulate the response to DHA supplementation. OBJECTIVES We investigated whether a DHA supplement improves cognitive performance in healthy young adults and whether sex and APOE modulate the response. DESIGN Healthy adults (n = 176; age range: 18-45 y; nonsmoking and with a low intake of DHA) completed a 6-mo randomized, placebo-controlled, double-blind intervention in which they consumed 1.16 g DHA/d or a placebo. Cognitive performance was assessed by using a computerized cognitive test battery. For all tests, z scores were calculated and clustered into cognitive domains as follows: episodic and working memory, attention, reaction time (RT) of episodic and working memory, and attention and processing speed. ANCOVA was conducted with sex and APOE as independent variables. RESULTS RTs of episodic and working memory improved with DHA compared with placebo [mean difference (95% CI): -0.18 SD (-0.33, -0.03 SD) (P = 0.02) and -0.36 SD (-0.58, -0.14 SD) (P = 0.002), respectively]. Sex × treatment interactions occurred for episodic memory (P = 0.006) and the RT of working memory (P = 0.03). Compared with the placebo, DHA improved episodic memory in women [0.28 SD (0.08, 0.48 SD); P = 0.006] and RTs of working memory in men [-0.60 SD (-0.95, -0.25 SD); P = 0.001]. APOE did not affect cognitive function, but there were some indications of APOE × sex × treatment interactions. CONCLUSIONS DHA supplementation improved memory and the RT of memory in healthy, young adults whose habitual diets were low in DHA. The response was modulated by sex. This trial was registered at the New Zealand Clinical Trials Registry (http://www.anzctr.org.au/default.aspx) as ACTRN12610000212055.

Chewing gum alleviates negative mood and reduces cortisol during acute laboratory psychological stress.

The notion that chewing gum may relieve stress was investigated in a controlled setting. A multi-tasking framework which reliably evokes stress and also includes performance measures was used to induce acute stress in the laboratory. Using a randomised crossover design forty participants (mean age 21.98 years) performed on the multi-tasking framework at two intensities (on separate days) both while chewing and not chewing. Order of workload intensity and chewing conditions were counterbalanced. Before and after undergoing the platform participants completed the state portion of the State-Trait Anxiety Inventory, Bond-Lader visual analogue mood scales, a single Stress Visual Analogue Scale and provided saliva samples for cortisol measurement. Baseline measures showed that both levels of the multi-tasking framework were effective in significantly reducing self-rated alertness, calmness and contentment while increasing self-rated stress and state anxiety. Cortisol levels fell during both levels of the stressor during the morning, reflecting the predominance of a.m. diurnal changes, but this effect was reversed in the afternoon which may reflect a measurable stress response. Pre-post stressor changes (Delta) for each measure at baseline were subtracted from Delta scores under chewing and no chewing conditions. During both levels of stress the chewing gum condition was associated with significantly better alertness and reduced state anxiety, stress and salivary cortisol. Overall performance on the framework was also significantly better in the chewing condition. The mechanisms underlying these effects are unknown but may involve improved cerebral blood flow and/or effects secondary to performance improvement during gum chewing.

Effects of Cholinesterase Inhibiting Sage ( Salvia officinalis ) on Mood, Anxiety and Performance on a Psychological Stressor Battery

Salvia officinalis (sage) has previously been shown both to possess in vitro cholinesterase inhibiting properties, and to enhance mnemonic performance and improve mood in healthy young participants. In this double-blind, placebo-controlled, crossover study, 30 healthy participants attended the laboratory on three separate days, 7 days apart, receiving a different treatment in counterbalanced order on each occasion (placebo, 300, 600 mg dried sage leaf). On each day mood was assessed predose and at 1 and 4 h postdose. Each mood assessment comprised completion of Bond–Lader mood scales and the State Trait Anxiety Inventory (STAI) before and after 20 min performance of the Defined Intensity Stress Simulator (DISS) computerized multitasking battery. In a concomitant investigation, an extract of the sage leaf exhibited dose-dependent, in vitro inhibition of acetylcholinesterase and, to a greater extent, butyrylcholinesterase. Both doses of sage led to improved ratings of mood in the absence of the stressor (that is, in pre-DISS mood scores) postdose, with the lower dose reducing anxiety and the higher dose increasing ‘alertness’, ‘calmness’ and ‘contentedness’ on the Bond–Lader mood scales. The reduced anxiety effect following the lower dose was, however, abolished by performing the DISS, with the same dose also being associated with a reduction of alertness during performance. Task performance on the DISS battery was improved for the higher dose at both postdose sessions, but reduced for the lower dose at the later testing session. The results confirm previous observations of the cholinesterase inhibiting properties of S. officinalis, and improved mood and cognitive performance following the administration of single doses to healthy young participants.

A double-blind, placebo-controlled, multi-dose evaluation of the acute behavioural effects of guarana in humans

The present study aimed to systematically assess acute, dose-related behavioural effects of an extract of guaraná plant for the first time in humans. This double-blind, counterbalanced, placebo-controlled study (n = 26) assessed the acute mood and cognitive effects throughout the day of four different doses (37.5mg, 75mg, 150mg and 300mg) of a standardised guaraná extract (PC-102). Assessment included the Cognitive Drug Research computerized test battery and Bond-Lader mood scales. Guaraná improved secondary memory performance and increased alert and content mood ratings. The two lower doses produced more positive cognitive effects than the higher doses. This research supports previous findings of cognitive improvements following 75mg guaraná and provides the first exploration of different dose effects of guaraná in humans. The findings suggest that the effects cannot be attributed to caffeine alone.

Cognitive and mood effects of 8 weeks' supplementation with 400 mg or 1000 mg of the omega-3 essential fatty acid docosahexaenoic acid (DHA) in healthy children aged 10-12 years.

Abstract Introduction: Despite media and public expectation of efficacy, no study to date has investigated the cognitive and mood effects of omega 3 supplementation in healthy children. Subjects and methods: This randomised, double-blind, placebo-controlled, parallel groups pilot study assessed the cognitive and mood effects of either 400 mg or 1000 mg of docosahexaenoic acid (DHA) in 90 healthy children aged 10–12 years. Cognitive performance and mood was assessed prior to, and 8 weeks following, commencement of treatment. Results: There was a significant treatment effect on one cognitive measure (speed of word recognition), with the lower dose speeding, and the higher dose slowing, performance. Overall, the pattern of results strongly suggests that this effect was due to chance fluctuations in performance and that the treatments had no consistent or interpretable effect on performance. Conclusions: The results here do not suggest that supplementation with these doses of DHA for 8 weeks has any beneficial effect on brain function in cognitively intact children.

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.

Effects of a multi-vitamin/mineral supplement on cognitive function and fatigue during extended multi-tasking

A significant minority of the population consume multi‐vitamins/minerals for their putative health benefits, including potentially beneficial effects on cognitive performance, fatigue and mood. The current study investigated the effect of supplementation with a multi‐vitamin/mineral on fatigue and cognitive function in healthy females.

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.