Effects of daily consumption of wild blueberry on cognition and urinary metabolites in school-aged children: a pilot study.

PURPOSE: Acute intervention with wild blueberry (WBB) has previously revealed positive cognitive and mood effects in typically developing children; however, it is unclear whether effects persist after daily supplementation. In addition, no data have been published exploring the metabolite profiles of children following berry consumption, to our knowledge. A study of this kind could provide insight into a mechanism of action for the cognitive and mood improvements observed previously in children. The aim of this pilot study was to assess cognitive performance and urinary metabolite concentrations in healthy 7-10-year-old children across a 4 week daily WBB drink intervention. METHODS: This pilot study examined the effects of daily WBB consumption for 4 weeks (766 mg total polyphenols; 253 mg anthocyanins; equivalent to 240 g fresh blueberries per day) on cognition and mood in 15 healthy 7-10-year-old children. Polyphenol metabolites were measured in 24 h urine before and after the 4 week intervention. RESULTS: Chronic WBB-related benefits were seen on cognitively demanding trials on the modified attention network task, a task measuring executive functioning. Specifically, the WBB group maintained significantly higher accuracy on incongruent trials (96%; SE 0.03) compared with placebo participants (85%; SE 0.03; p = 0.038) after the 4 week intervention, suggesting WBB was of most benefit on the more difficult aspects of the task. No significant WBB-related effects were observed on the auditory verbal learning task or the child's version of the positive and negative affect schedule. Urinary metabolite analyses indicated significant increases in different metabolites in WBB and placebo groups after 4 week consumption. CONCLUSION: The research demonstrates 24 h WBB bioavailability in a child cohort for the first time with increases in urinary hippuric acid excretion during 2 week daily WBB consumption. This study highlights the importance of conducting a larger study in children investigating the mechanism of action behind cognitive effects using bioavailability data.

Polyphenols and Cognition In Humans: An Overview of Current Evidence from Recent Systematic Reviews and Meta-Analyses.

BACKGROUND: There is increasing interest in the impact of dietary influences on the brain throughout the lifespan, ranging from improving cognitive development in children through to attenuating ageing related cognitive decline and reducing risk of neurodegenerative diseases. Polyphenols, phytochemicals naturally present in a host of fruits, vegetables, tea, cocoa and other foods, have received particular attention in this regard, and there is now a substantial body of evidence from experimental and epidemiological studies examining whether their consumption is associated with cognitive benefits. OBJECTIVE: The purpose of this overview is to synthesise and evaluate the best available evidence from two sources, namely meta-analyses and systematic reviews, in order to give an accurate reflection of the current evidence base for an association between polyphenols and cognitive benefits. METHOD: Four meta-analyses and thirteen systematic reviews published between 2017-2020 were included, and were categorised according to whether they reviewed specific polyphenol-rich foods and classes or all polyphenols. A requirement for inclusion was assessment of a behavioural cognitive outcome in humans. RESULTS: A clear and consistent theme emerged that whilst there is support for an association between polyphenol consumption and cognitive benefits, this conclusion is tentative, and by no means definitive. Considerable methodological heterogeneity was repeatedly highlighted as problematic such that the current evidence base does not support reliable conclusions relating to efficacy of specific doses, duration of treatment, or sensitivity in specific populations or certain cognitive domains. The complexity of multiple interactions between a range of direct and indirect mechanisms of action is discussed. CONCLUSIONS: Further research is required to strengthen the reliability of the evidence base.

Cannabidiol improves survival and behavioural co-morbidities of Dravet syndrome in mice.

BACKGROUND AND PURPOSE: Dravet syndrome is a severe, genetic form of paediatric epilepsy associated with premature mortality and co-morbidities such as anxiety, depression, autism, motor dysfunction and memory deficits. Cannabidiol is an approved anticonvulsive drug in the United States and Europe for seizures associated with Dravet syndrome in patients 2 years of age and older. We investigated its potential to prevent premature mortality and improve associated co-morbidities. EXPERIMENTAL APPROACH: The efficacy of sub-chronic cannabidiol administration in two mouse models of Dravet syndrome was investigated. The effect of cannabidiol on neonatal welfare and survival was studied using Scn1a-/- mice. We then used a hybrid, heterozygote Scn1a+/- mouse model to study the effect of cannabidiol on survival and behavioural co-morbidities: motor deficits (rotarod and static-beam test), gait abnormality (gait test), social anxiety (social interaction test), anxiety-like (elevated plus maze) and depressive-like behaviours (sucrose preference test) and cognitive impairment (radial arm maze test). KEY RESULTS: In Scn1a-/- mice, cannabidiol increased survival and delayed worsening of neonatal welfare. In Scn1a+/- mice, chronic cannabidiol administration did not show any adverse effect on motor function and gait, reduced premature mortality, improved social behaviour and memory function, and reduced anxiety-like and depressive-like behaviours. CONCLUSION AND IMPLICATIONS: We are the first to demonstrate a potential disease-modifying effect of cannabidiol in animal models of Dravet syndrome. Cannabidiol treatment reduced premature mortality and improved several behavioural co-morbidities in Dravet syndrome mice. These crucial findings may be translated into human therapy to address behavioural co-morbidities associated with Dravet syndrome.

Systematic Review of the Effects of Blueberry on Cognitive Performance as We Age.

The effect of flavonoid-rich food, such as blueberries, on cognitive function has been subject to a growing amount of research interest in recent years. Epidemiological, prospective, preclinical, and clinical trials have revealed positive cognitive benefits from flavonoid interventions, particularly in relation to the amelioration of cognitive decline in older adults. This review will specifically consider the existing clinical research from both acute and chronic blueberry interventions on cognition in human subjects. The results of 11 studies are reported with 4 studies considering blueberry intervention with children aged 7-10 years, 4 considering adults aged 60 years and older, and 3 considering adults suffering from mild cognitive impairment (MCI). Findings from these studies indicate that cognitive benefits may be found for delayed memory and executive function in children and for delayed memory, executive function, and psychomotor function in older healthy and MCI adults. There is less evidence to suggest positive benefits of blueberry intervention on working memory. Recommendations for future research, including dose used, cognitive tasks, and age groups considered, are proposed.