Mental Performance and Sport: Caffeine and Co-consumed Bioactive Ingredients.

The plant defence compound caffeine is widely consumed as a performance enhancer in a sporting context, with potential benefits expected in both physiological and psychological terms. However, although caffeine modestly but consistently improves alertness and fatigue, its effects on mental performance are largely restricted to improved attention or concentration. It has no consistent effect within other cognitive domains that are important to sporting performance, including working memory, executive function and long-term memory. Although caffeine's central nervous system effects are often attributed to blockade of the receptors for the inhibitory neuromodulator adenosine, it also inhibits a number of enzymes involved both in neurotransmission and in cellular homeostasis and signal propagation. Furthermore, it modulates the pharmacokinetics of other endogenous and exogenous bioactive molecules, in part via interactions with shared cytochrome P450 enzymes. Caffeine therefore enjoys interactive relationships with a wide range of bioactive medicinal and dietary compounds, potentially broadening, increasing, decreasing, or modulating the time course of their functional effects, or vice versa. This narrative review explores the mechanisms of action and efficacy of caffeine and the potential for combinations of caffeine and other dietary compounds to exert psychological effects in excess of those expected following caffeine alone. The review focusses on, and indeed restricted its untargeted search to, the most commonly consumed sources of caffeine: products derived from caffeine-synthesising plants that give us tea (Camellia sinensis), coffee (Coffea genus), cocoa (Theabroma cacao) and guaraná (Paullinia cupana), plus multi-component energy drinks and shots. This literature suggests relevant benefits to mental performance that exceed those associated with caffeine for multi-ingredient energy drinks/shots and several low-caffeine extracts, including high-flavanol cocoa and guarana. However, there is a general lack of research conducted in such a way as to disentangle the relative contributions of the component parts of these products.

Acute cognitive performance and mood effects of coffee berry and apple extracts: A randomised, double blind, placebo controlled crossover study in healthy humans.

Background: Polyphenols from coffee berry (chlorogenic acid) and apple (flavanol) have been shown to improve mood and increase cerebral blood flow in healthy humans. These effects may underpin the cognitive effects of polyphenols seen previously.Objective: The aim of the present paper was to extend previous research by investigating the effects of coffee berry at high and low doses when combined with apple extract on cognitive performance and mood.Design: This randomised, double-blind, placebo controlled, crossover trial included 46 healthy males and females,18-49 years of age (mean age 23 years),consuming: 1100 mg coffee berry extract, 1100 mg coffee berry extract plus 275 mg apple extract, 100 mg coffee berry extract plus 275 mg apple extract or placebo on 4 separate occasions, completing cognitive and mood assessments pre-dose and then again at 1-, 3- and 6 hrs post-dose.Results: Analysis revealed a consistent pattern of alerting effects following 1100 mg coffee berry extract. Limited effects on cognitive function were observed. Specifically, faster peg and ball performance (executive function) was observed following 1100 mg coffee berry plus apple extract and accuracy on the Rapid Visual Information Processing (RVIP) task increased on the third of four repetitions following 1100 mg coffee berry alone. Interestingly, more false alarms on RVIP were observed following the same intervention.Conclusions: In line with previous findings, 1100 mg coffee berry engendered increased arousal. The absence of effects on mood when an apple extract was added, and the potential for the low dose of caffeine within the coffee berry to act synergistically with polyphenols, raise interesting future avenues of research.Abbreviations: Cognitive demand battery (CDB), Profile Of Mood States (POMS), Visual Analogue Scale (VAS), Rapid Visual Information Processing (RVIP).

The Acute and Chronic Cognitive Effects of a Sage Extract: A Randomized, Placebo Controlled Study in Healthy Humans.

The sage (Salvia) plant contains a host of terpenes and phenolics which interact with mechanisms pertinent to brain function and improve aspects of cognitive performance. However, previous studies in humans have looked at these phytochemicals in isolation and following acute consumption only. A preclinical in vivo study in rodents, however, has demonstrated improved cognitive outcomes following 2-week consumption of CogniviaTM, a proprietary extract of both Salvia officinalis polyphenols and Salvia lavandulaefolia terpenoids, suggesting that a combination of phytochemicals from sage might be more efficacious over a longer period of time. The current study investigated the impact of this sage combination on cognitive functions in humans with acute and chronic outcomes. Participants (n = 94, 25 M, 69 F, 30-60 years old) took part in this randomised, double-blind, placebo-controlled, parallel groups design where a comprehensive array of cognitions were assessed 120- and 240-min post-dose acutely and following 29-day supplementation with either 600 mg of the sage combination or placebo. A consistent, significant benefit of the sage combination was observed throughout working memory and accuracy task outcome measures (specifically on the Corsi Blocks, Numeric Working Memory, and Name to Face Recall tasks) both acutely (i.e., changes within day 1 and day 29) and chronically (i.e., changes between day 1 to day 29). These results fall slightly outside of those reported previously with single Salvia administration, and therefore, a follow-up study with the single and combined extracts is required to confirm how these effects differ within the same cohort.

A Randomized, Crossover Study of the Acute Cognitive and Cerebral Blood Flow Effects of Phenolic, Nitrate and Botanical Beverages in Young, Healthy Humans.

BACKGROUND: In whole foods, polyphenols exist alongside a wide array of other potentially bioactive phytochemicals. Yet, investigations of the effects of combinations of polyphenols with other phytochemicals are limited. OBJECTIVE: The current study investigated the effects of combining extracts of beetroot, ginseng and sage with phenolic-rich apple, blueberry and coffee berry extracts. DESIGN: This randomized, double-blind, placebo-controlled crossover design investigated three active beverages in 32 healthy adults aged 18-49 years. Each investigational beverage comprised extracts of beetroot, ginseng and sage. Each also contained a phenolic-rich extract derived from apple (containing 234 mg flavanols), blueberry (300 mg anthocyanins) or coffee berry (440 mg chlorogenic acid). Cognition, mood and CBF parameters were assessed at baseline and then again at 60, 180 and 360 min post-drink. RESULTS: Robust effects on mood and CBF were seen for the apple and coffee berry beverages, with increased subjective energetic arousal and hemodynamic responses being observed. Fewer effects were seen with the blueberry extract beverage. CONCLUSIONS: Either the combination of beetroot, ginseng and sage was enhanced by the synergistic addition of the apple and coffee berry extract (and to a lesser extent the blueberry extract) or the former two phenolic-rich extracts were capable of evincing the robust mood and CBF effects alone.

Acute Effects of a Polyphenol-Rich Leaf Extract of Mangifera indica L. (Zynamite) on Cognitive Function in Healthy Adults: A Double-Blind, Placebo-Controlled Crossover Study.

Extracts made from the leaves of the mango food plant (Mangifera indica L., Anacardiaceae) have a long history of medicinal usage, most likely due to particularly high levels of the polyphenol mangiferin. In rodent models, oral mangiferin protects cognitive function and brain tissue from a number of challenges and modulates cerebro-electrical activity. Recent evidence has confirmed the latter effect in healthy humans following a mangiferin-rich mango leaf extract using quantitative electroencephalography (EEG). The current study therefore investigated the effects of a single dose of mango leaf extract, standardised to contain >60% mangiferin (Zynamite®), on cognitive function and mood. This study adopted a double-blind, placebo-controlled cross-over design in which 70 healthy young adults (18 to 45 years) received 300 mg mango leaf extract and a matched placebo, on separate occasions, separated by at least 7 days. On each occasion, cognitive/mood assessments were undertaken pre-dose and at 30 min, 3 h and 5 h post-dose using the Computerised Mental Performance Assessment System (COMPASS) assessment battery and the Profile of Mood States (POMS). The results showed that a single dose of 300 mg mango leaf extract significantly improved performance accuracy across the tasks in the battery, with domain-specific effects seen in terms of enhanced performance on an 'Accuracy of Attention' factor and an 'Episodic Memory' factor. Performance was also improved across all three tasks (Rapid Visual Information Processing, Serial 3s and Serial 7s subtraction tasks) that make up the Cognitive Demand Battery sub-section of the assessment. All of these cognitive benefits were seen across the post-dose assessments (30 min, 3 h, 5 h). There were no interpretable treatment related effects on mood. These results provide the first demonstration of cognition enhancement following consumption of mango leaf extract and add to previous research showing that polyphenols and polyphenol rich extracts can improve brain function.

Acute and Chronic Effects of Green Oat (Avena sativa) Extract on Cognitive Function and Mood during a Laboratory Stressor in Healthy Adults: A Randomised, Double-Blind, Placebo-Controlled Study in Healthy Humans.

Green oat (Avena sativa) extracts contain several groups of potentially psychoactive phytochemicals. Previous research has demonstrated improvements in cognitive function following a single dose of these extracts, but not following chronic supplementation. Additionally, whilst green oat extracts contain phytochemicals that may improve mood or protect against stress, for instance species-specific triterpene saponins, to date this possibility has not been examined. The current study investigated the effects of a single dose and four weeks of administration of a novel, Avena sativa herbal extract (cognitaven®) on cognitive function and mood, and changes in psychological state during a laboratory stressor. The study adopted a dose-ranging, double-blind, randomised, parallel groups design in which 132 healthy males and females (35 to 65 years) received either 430 mg, 860 mg, 1290 mg green oat extract or placebo for 29 days. Assessments of cognitive function, mood and changes in psychological state during a laboratory stressor (Observed Multitasking Stressor) were undertaken pre-dose and at 2 h and 4 h post-dose on the first (Day 1) and last days (Day 29) of supplementation. The results showed that both a single dose of 1290 mg and, to a greater extent, supplementation for four weeks with both 430 mg and 1290 mg green oat extract resulted in significantly improved performance on a computerised version of the Corsi Blocks working memory task and a multitasking task (verbal serial subtractions and computerised tracking) in comparison to placebo. After four weeks, the highest dose also decreased the physiological response to the stressor in terms of electrodermal activity. There were no treatment-related effects on mood. These results confirm the acute cognitive effects of Avena sativa extracts and are the first to demonstrate that chronic supplementation can benefit cognitive function and modulate the physiological response to a stressor.

The Acute and Chronic Cognitive and Cerebral Blood Flow Effects of a Sideritis scardica (Greek Mountain Tea) Extract: A Double Blind, Randomized, Placebo Controlled, Parallel Groups Study in Healthy Humans.

BACKGROUND: The presence of polyphenols such as hydroxy-cinnamic acids and flavonoids in Sideritis scardica (Greek mountain tea) are likely responsible for the cognitive and mood effects of its consumption and this could be underpinned by the ability of such polyphenols to prevent monoamine neurotransmitter reuptake and to increase cerebral blood flow (CBF). OBJECTIVE: The current study extends the small amount of Sideritis scardica literature in humans by assessing both cognitive and mood outcomes in a sample of older adults, as well as blood pressure (BP) and CBF, in a subsample, utilizing near-infrared spectroscopy (NIRS). DESIGN: This randomized, double-blind, placebo-controlled, parallel groups trial randomized N = 155, 50⁻70-year-old male and female participants who were assessed for the cognitive (N = 140), mood (N = 142), BP (N = 133) and CBF (N = 57) effects of two doses of Greek mountain tea (475 and 950 mg) as well as an active control of 240 mg Ginkgo biloba, and a placebo control, following acute consumption (Day 1) and following a month-long consumption period (Day 28). RESULTS: Relative to the placebo control, 950 mg Greek mountain tea evinced significantly fewer false alarms on the Rapid Visual Information Processing (RVIP) task on Day 28 and significantly reduced state anxiety following 28 days consumption (relative also to the active, Ginkgo control). This higher dose of Greek mountain tea also attenuated a reduction in accuracy on the picture recognition task, on Day 1 and Day 28, relative to Ginkgo and both doses of Greek mountain tea trended towards significantly faster speed of attention on both days, relative to Ginkgo. Both doses of Greek mountain tea, relative to placebo, increased oxygenated haemoglobin (HbO) and oxygen saturation (Ox%) in the prefrontal cortex during completion of cognitively demanding tasks on Day 1. The higher dose also evinced greater levels of total (THb) and deoxygenated (Hb) haemoglobin on Day 1 but no additional effects were seen on CBF on Day 28 following either dose of Greek mountain tea. Ginkgo biloba led to lower levels of Ox% and higher levels of Hb on Day 1 and lower levels of both HbO and THb on Day 28. CONCLUSIONS: The significantly improved cognitive performance following Greek mountain tea on Day 1 could be due to significant modulation of the CBF response. However, these improvements on Day 28 are more likely to be due to the reductions in state anxiety and, taken together, suggests that the former mechanism is more likely to facilitate acute cognitive effects and the latter more likely to underpin more prolonged cognitive improvements.

Cognitive and Mood Effects of a Nutrient Enriched Breakfast Bar in Healthy Adults: A Randomised, Double-Blind, Placebo-Controlled, Parallel Groups Study.

OBJECTIVES: Few previous studies have assessed the effects of concomitant administration of multiple potentially psychoactive nutrients. METHODS: 95 healthy adult participants consumed either a nutrient enriched breakfast bar (containing α-Linolenic acid, l-tyrosine, l-theanine, vitamins, minerals and 21.5 mg of caffeine) or an isocaloric, macronutrient matched control bar for 56 days. Cognitive function and mood were assessed pre-dose and at 40- and 160-min post-dose on the 1st and 56th day of the intervention period. RESULTS: The results demonstrated acute effects of treatment across post-dose assessments on both assessment days in terms of alertness, and on tasks assessing attention, working and episodic memory and executive function, including cognitively demanding Serial subtraction and Rapid Visual Information Processing tasks. There were no evident chronic effects independent of the breakfast bars' acute effects. DISCUSSION: These results demonstrate that a nutrient enriched breakfast bar with low caffeine content can exert striking beneficial effects on acute cognitive function and alertness.

Potential benefits of phytochemicals against Alzheimer's disease.

Our current therapeutic drugs for Alzheimer's disease are predominantly derived from the alkaloid class of plant phytochemicals. These drugs, such as galantamine and rivastigmine, attenuate the decline in the cholinergic system but, as the alkaloids occupy the most dangerous end of the phytochemical spectrum (indeed they function as feeding deterrents and poisons to other organisms within the plant itself), they are often associated with unpleasant side effects. In addition, these cholinesterase inhibiting alkaloids target only one system in a disorder, which is typified by multifactorial deficits. The present paper will look at the more benign terpene (such as Ginkgo biloba, Ginseng, Melissa officinalis (lemon balm) and Salvia lavandulaefolia (sage)) and phenolic (such as resveratrol) phytochemicals; arguing that they offer a safer alternative and that, as well as demonstrating efficacy in cholinesterase inhibition, these phytochemicals are able to target other salient systems such as cerebral blood flow, free radical scavenging, anti-inflammation, inhibition of amyloid-ß neurotoxicity, glucoregulation and interaction with other neurotransmitters (such as γ-aminobutyric acid) and signalling pathways (e.g. via kinase enzymes).

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.

Dietary nitrate modulates cerebral blood flow parameters and cognitive performance in humans: A double-blind, placebo-controlled, crossover investigation.

Nitrate derived from vegetables is consumed as part of a normal diet and is reduced endogenously via nitrite to nitric oxide. It has been shown to improve endothelial function, reduce blood pressure and the oxygen cost of sub-maximal exercise, and increase regional perfusion in the brain. The current study assessed the effects of dietary nitrate on cognitive performance and prefrontal cortex cerebral blood-flow (CBF) parameters in healthy adults. In this randomised, double-blind, placebo-controlled, parallel-groups study, 40 healthy adults received either placebo or 450 ml beetroot juice (~5.5 mmol nitrate). Following a 90 minute drink/absorption period, participants performed a selection of cognitive tasks that activate the frontal cortex for 54 min. Near-Infrared Spectroscopy (NIRS) was used to monitor CBF and hemodynamics, as indexed by concentration changes in oxygenated and deoxygenated-haemoglobin, in the frontal cortex throughout. The bioconversion of nitrate to nitrite was confirmed in plasma by ozone-based chemi-luminescence. Dietary nitrate modulated the hemodynamic response to task performance, with an initial increase in CBF at the start of the task period, followed by consistent reductions during the least demanding of the three tasks utilised. Cognitive performance was improved on the serial 3s subtraction task. These results show that single doses of dietary nitrate can modulate the CBF response to task performance and potentially improve cognitive performance, and suggest one possible mechanism by which vegetable consumption may have beneficial effects on brain function.

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.

Epigallocatechin gallate, cerebral blood flow parameters, cognitive performance and mood in healthy humans: a double-blind, placebo-controlled, crossover investigation.

OBJECTIVE: The aim of the study was to assess the effects of oral ingestion of the 'green tea' polyphenol epigallocatechin gallate (EGCG) on cognitive performance, mood and localised cerebral blood flow (CBF) parameters in healthy human adults. METHOD: In this double-blind, placebo-controlled, crossover study, 27 healthy adults received placebo and two doses (135 and 270 mg) of EGCG in counterbalanced order on separate days. Following a 45-min resting absorption period, participants performed a selection of computerised cognitive tasks that activate the frontal cortex for a further 42 min. CBF and haemodynamics, as indexed by concentration changes in oxygenated and deoxygenated haemoglobin, were assessed in the frontal cortex throughout the post-treatment period using Near-infrared spectroscopy (NIRS). RESULTS: During the post-dose task performance period, the administration of 135 mg EGCG resulted in reduced CBF in the frontal cortex, as indexed by significantly lower concentrations of both oxygenated and total haemoglobin, in comparison with placebo. Heart rate was significantly reduced from pre dose to post dose across all treatments. No significant differences were observed for the level of deoxygenated haemoglobin or on any of the cognitive performance/mood measures. CONCLUSIONS: These results demonstrate that a single dose of orally administered EGCG can modulate CBF parameters in healthy humans but that this is not associated with changes in cognitive performance or mood.

Herbal extracts and phytochemicals: plant secondary metabolites and the enhancement of human brain function.

Humans consume a wide range of foods, drugs, and dietary supplements that are derived from plants and which modify the functioning of the central nervous sytem (CNS). The psychoactive properties of these substances are attributable to the presence of plant secondary metabolites, chemicals that are not required for the immediate survival of the plant but which are synthesized to increase the fitness of the plant to survive by allowing it to interact with its environment, including pathogens and herbivorous and symbiotic insects. In many cases, the effects of these phytochemicals on the human CNS might be linked either to their ecological roles in the life of the plant or to molecular and biochemical similarities in the biology of plants and higher animals. This review assesses the current evidence for the efficacy of a range of readily available plant-based extracts and chemicals that may improve brain function and which have attracted sufficient research in this regard to reach a conclusion as to their potential effectiveness as nootropics. Many of these candidate phytochemicals/extracts can be grouped by the chemical nature of their potentially active secondary metabolite constituents into alkaloids (caffeine, nicotine), terpenes (ginkgo, ginseng, valerian, Melissa officinalis, sage), and phenolic compounds (curcumin, resveratrol, epigallocatechin-3-gallate, Hypericum perforatum, soy isoflavones). They are discussed in terms of how an increased understanding of the relationship between their ecological roles and CNS effects might further the field of natural, phytochemical drug discovery.

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.