Crystal F. Haskell-Ramsay

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.

Multivitamins and minerals modulate whole-body energy metabolism and cerebral blood-flow during cognitive task performance: a double-blind, randomised, placebo-controlled trial

BackgroundThe brain is by far the most metabolically active organ in the body, with overall energy expenditure and local blood-supply closely related to neural activity. Both energy metabolism and cerebral vaso-dilation are dependent on adequate micronutrient status. This study investigated whether supplementation with ascending doses of multi-vitamin/minerals could modulate the metabolic and cerebral blood-flow consequences of performing cognitive tasks that varied in difficulty.MethodsIn this randomised, double-blind, placebo-controlled, parallel-groups study 97 healthy females (25–49 y), who were not selected on the basis of any nutritional parameters, received either placebo or one of two doses of multivitamins/minerals. Cerebral blood-flow (CBF) parameters in the frontal cortex, and total energy expenditure (TotalEnergy), carbohydrate and fat oxidation (CarbOxi/FatOxi), were measured during 5 tasks of graded cognitive difficulty and a control task (5 min per task) using Near-infrared spectroscopy (NIRS) and Indirect calorimetry of exhaled pulmonary gas (ICa) respectively. Assessments took place 60 min after the first dose and following eight weeks supplementation.ResultsDuring task performance supplementation with the first dose of micronutrients led to a dose-dependent increase in TotalEnergy and FatOxi throughout the post-dose assessment period following the higher dose, and increases in the total concentration of haemoglobin, a proxy measure for CBF, during task performance following the lower dose of vitamins/minerals (also containing coenzyme-Q10). Chronic supplementation over 8 weeks led to a dose-dependent increase in TotalEnergy during the task period. There were no interpretable effects on mood or cognitive performance.ConclusionsThese results show that acute supplementation with micronutrients in healthy adults can modulate metabolic parameters and cerebral blood flow during cognitive task performance, and that the metabolic consequences are sustained during chronic supplementation. These findings suggest that both brain function and metabolism are amenable to micronutrient supplementation, even in adults who are assumed to have nutritional status typical of the population.Trial registrationClinicalTrials.gov - NCT02381964.

Montmorency Tart cherries (Prunus cerasus L.) modulate vascular function acutely, in the absence of improvement in cognitive performance.

Cerebral blood volume and metabolism of oxygen decline as part of human ageing, and this has been previously shown to be related to cognitive decline. There is some evidence to suggest that polyphenol-rich foods can play an important role in delaying the onset or halting the progression of age-related health disorders such as CVD and Alzheimers disease and to improve cognitive function. In the present study, an acute, placebo-controlled, double-blinded, cross-over, randomised Latin-square design study with a washout period of at least 14 d was conducted on twenty-seven, middle-aged (defined as 45-60 years) volunteers. Participants received either a 60 ml dose of Montmorency tart cherry concentrate (MC), which contained 68·0 (sd 0·26) mg cyanidin-3-glucoside/l, 160·75 (sd 0·55) mean gallic acid equivalent/l and 0·59 (sd 0·02) mean Trolox equivalent/l, respectively, or a placebo. Cerebrovascular responses, cognitive performance and blood pressure were assessed at baseline and 1, 2, 3 and 5 h following consumption. There were significant differences in concentrations of total Hb and oxygenated Hb during the task period 1 h after MC consumption (P≤0·05). Furthermore, MC consumption significantly lowered systolic blood pressure (P≤0·05) over a period of 3 h, with peak reductions of 6±2 mmHg at 1 h after MC consumption relative to the placebo. Cognitive function and mood were not affected. These results show that a single dose of MC concentrate can modulate certain variables of vascular function; however, this does not translate to improvements in cognition or mood.

The Effects of Supplementation with a Vitamin and Mineral Complex with Guaraná Prior to Fasted Exercise on Affect, Exertion, Cognitive Performance, and Substrate Metabolism: A Randomized Controlled Trial

Exercise undertaken in a fasted state can lead to higher post-exercise mental fatigue. The administration of a vitamin and mineral complex with guaraná (MVM + G) has been shown to attenuate mental fatigue and improve performance during cognitively demanding tasks. This placebo-controlled, double-blind, randomized, balanced cross-over study examined the effect of MVM + G consumed prior to morning exercise on cognitive performance, affect, exertion, and substrate metabolism. Forty active males (age 21.4 ± 3.0 year; body mass index (BMI) 24.0 ± 2.4 kg/m2; maximal oxygen consumption (V̇O2max) 57.6 ± 7.3 mL/min/kg) completed two main trials, consuming either MVM + G or placebo prior to a 30-min run at 60% V̇O2max. Supplementation prior to exercise led to a small but significant reduction in Rating of Perceived Exertion (RPE) during exercise compared to the placebo. The MVM + G combination also led to significantly increased accuracy of numeric working memory and increased speed of picture recognition, compared to the placebo. There were no significant effects of supplementation on any other cognitive or mood measures or on substrate metabolism during exercise. These findings demonstrate that consuming a vitamin and mineral complex containing guaraná, prior to exercise, can positively impact subsequent memory performance and reduce perceived exertion during a moderate-intensity run in active males.

Acute effects of a wild green-oat (Avena sativa) extract on cognitive function in middle-aged adults: A double-blind, placebo-controlled, within-subjects trial

Objectives: A wild green-oats extract (Neuravena®) containing a range of potentially bioactive components, including flavonoids and triterpene saponins, has previously been shown to enhance animal stress responses and memory, and improve cognitive performance in humans at a dose of 1600 mg. Methods This double-blind, placebo-controlled, counterbalanced cross-over study assessed the effects of single doses of the green-oat extract (GOE) across a broad range of cognitive domains in healthy adults aged 40–65 years who self-reported that they felt that their memory had declined with age. Participants attended on six occasions, receiving a single dose of either placebo, 800, or 1600 mg GOE on each occasion, with the counterbalanced order of treatments repeated twice for each participant. Cognitive function was assessed with a range of computerized tasks measuring attention, spatial/working/episodic memory, and executive function pre-dose and at 1, 2.5, 4, and 6 hours post-dose. Results The results showed that 800mg GOE increased the speed of performance across post-dose assessments on a global measure including data from all of the timed tasks. It also improved performance of a delayed word recall task in terms of errors and an executive function task (Peg and Ball) in terms of decreased thinking time and overall completion time. Working memory span (Corsi blocks) was also increased, but only on the second occasion that this dose was taken. Discussion These results confirm the acute cognitive effects of GOE seen in previous research, and suggest that the optimal dose lies at or below 800 mg.

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.

The Effect of Breakfast Prior to Morning Exercise on Cognitive Performance, Mood and Appetite Later in the Day in Habitually Active Women.

Pre-exercise nutritional practices for active females exercising for mood, cognitive and appetite benefits are not well established. Results from an initial field pilot study showed that higher energy intake at breakfast was associated with lower fatigue and higher overall mood and alertness post-exercise (all p < 0.05). In a follow-up, randomised, controlled trial, 24 active women completed three trials in a balanced, cross-over design. At 0815 h participants completed baseline cognitive tasks, mood and appetite visual analogue scales (VAS) and were administered a cereal breakfast (providing 118 or 236 kcal) or no breakfast. After 45 min, they completed a 30 min run at 65% heart rate reserve (HRR). Parameters were re-assessed immediately after exercise, then hourly until lunch (~1240 h), immediately post-lunch and at 1500 and 1900 h via a mobile phone. Breakfast enhanced feelings of relaxation before lunch (p < 0.05, d > 0.40), though breakfast was detrimental for working memory mid-afternoon (p = 0.019, d = 0.37) and mental fatigue and tension later in the day (all p < 0.05, d > 0.038). Breakfast was also beneficial for appetite control before lunch irrespective of size (all p < 0.05, d > 0.43). These data provide information on pre-exercise nutritional practices for active females and suggest that a small breakfast eaten prior to exercise can benefit post-exercise mood and subjective appetite ratings.

The Impact of Epicatechin on Human Cognition: The Role of Cerebral Blood Flow

Epicatechin is a monomeric flavanol found in food sources such as tea, apples, berries and cocoa. A number of large-scale epidemiological studies have demonstrated an association between the consumption of these foods and cognitive function, as well as improved blood flow. The aim of this review is to summarise the evidence from intervention studies to clarify the effect of epicatechin on cognition and to consider the role of increased cerebral blood flow as a mechanism for any effects. The effects of epicatechin as consumed in cocoa are, therefore, reviewed here as this represents the only dietary source where it is purported to be the major active component. Our main findings are that a) the positive modulation of tasks that involve memory, executive function and processing speed in older adults; b) the cognitive benefits are more often shown in studies containing more than 50 mg epicatechin/day; and c) all studies with a duration of 28 days or longer in populations >50 years old demonstrate a cognitive improvement. However, as highlighted by this review, it is not currently possible to attribute effects solely to epicatechin without consideration of synergies. In order to overcome this issue, further studies examining the cognitive effects of epicatechin in isolation are required. The role of cerebral blood flow also requires further investigation through simultaneous measurement alongside cognitive function.

The Acute Effects of Caffeinated Black Coffee on Cognition and Mood in Healthy Young and Older Adults

Cognitive and mood benefits of coffee are often attributed to caffeine. However, emerging evidence indicates behavioural effects of non-caffeine components within coffee, suggesting the potential for direct or synergistic effects of these compounds when consumed with caffeine in regular brewed coffee. The current randomised, placebo-controlled, double-blind, counterbalanced-crossover study compared the effects of regular coffee, decaffeinated coffee, and placebo on measures of cognition and mood. Age and sex effects were explored by comparing responses of older (61–80 years, N = 30) and young (20–34 years, N = 29) males and females. Computerised measures of episodic memory, working memory, attention, and subjective state were completed at baseline and 30 min post-drink. Regular coffee produced the expected effects of decreased reaction time and increased alertness when compared to placebo. When compared to decaffeinated coffee, increased digit vigilance accuracy and decreased tiredness and headache ratings were observed. Decaffeinated coffee also increased alertness when compared to placebo. Higher jittery ratings following regular coffee in young females and older males represented the only interaction of sex and age with treatment. These findings suggest behavioural activity of coffee beyond its caffeine content, raising issues with the use of decaffeinated coffee as a placebo and highlighting the need for further research into its psychoactive effects.

Volatile terpenes and brain function : investigation of the cognitive and mood effects of Mentha × Piperita l. essential oil with in vitro properties relevant to central nervous system function.

Background: Extracts of several members of the monoterpene-rich Lamiaceae sub-family Nepetoideae, including those from the Salvia (sage), Melissa (Lemon balm) and Rosmarinus (rosemary) genera, evince cognitive and mood effects in humans that are potentially related to their effects on cholinergic and GABAergic neurotransmission. To date, despite promising in vitro properties, the cognitive and mood effects of the closely related Mentha spicata (spearmint) and Mentha piperita (peppermint) remain unexplored. This study therefore assessed the human cognitive/mood effects of the M. spicata/piperita essential oil with the most promising, brain-relevant in vitro properties according to pre-trial in vitro screening. Design: Organic spearmint and peppermint (Mentha spicata/piperita) essential oils were pre-screened for neurotransmitter receptor binding and acetylcholinesterase (AChE) inhibition. In a double-blind, placebo-controlled, balanced cross-over study, 24 participants (mean age 25.2 years) consumed single doses of encapsulated placebo and 50 µL and 100 µL of the most promising essential oil (peppermint with nicotinic/GABAA receptor binding and AChE inhibitory properties, that increased calcium influx in a CAD cell neuronal model). Psychological functioning was assessed with mood scales and a range of standardised, cognitively demanding tasks pre-dose and at 1, 3 and 6 h post-dose. Results: The highest (100 µL) dose of essential oil improved performance on the cognitively demanding Rapid Visual Information Processing task (RVIP) at 1 h and 3 h post-dose and both doses attenuated fatigue and improved performance of the Serial 3 s subtraction task at 3 h post-dose. Conclusion: Peppermint (Mentha piperita) essential oil with high levels of menthol/menthone and characteristic in vitro cholinergic inhibitory, calcium regulatory and GABAA/nicotinic receptor binding properties, beneficially modulated performance on demanding cognitive tasks and attenuated the increase in mental fatigue associated with extended cognitive task performance in healthy adults. Future investigations should consider investigating higher doses.