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Anthocyanins and cognitive function

Anthocyanins and cognitive function

Exploring the physiological factors cogbitive to energy balance Dark chocolate addiction women with polycystic ovary syndrome: a scoping review. Watson, A. It is conceivable that heterogeneity in flavonoid absorption and metabolism may diminish beneficial associations between intakes and cognitive outcomes reported in studies.

Anthocyanins and cognitive function -

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Effects of anthocyanin-rich supplementation on cognition of the cognitively healthy middle-aged and older adults: a systematic review and meta-analysis of randomized controlled trials. Ruo Chen Feng , Ruo Chen Feng. is with the High-Dependency Unit, Tan Tock Seng Hospital, National Health Group.

Oxford Academic. Google Scholar. Yan Hong Dong. are with the Alice Lee Centre for Nursing Studies, Yong Loo Lin School of Medicine, National University of Singapore. is with the Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore.

Xian Li Hong. is with the Medical Intensive Care Unit, Tan Tock Seng Hospital, National Health Group. Ya Su. is with the Shanghai Jiao Tong University, School of Nursing. is with the Faculty of Health Sciences, Hokkaido University. Xi Vivien Wu. is with the NUSMED Healthy Longevity Translational Research Programme, National University of Singapore.

Xi Vivien Wu , Alice Lee Centre for Nursing Studies, Yong Loo Lin School of Medicine, National University of Singapore, Level 2, Clinical Research Centre, Block MD 11, 10 Medical Dr, Singapore E-mail: nurwux nus. Select Format Select format.

Notably, the intervention duration was half that of Mastroiacovo et al. Additionally, participants in the current study were considerably younger with mean age A study investigating the effect of cocoa flavanol intake combined with exercise on executive function found that, whilst flavanol intake increased cerebral oxygenation during the executive function task, there was no impact on cognitive performance.

Furthermore, exercise alone improved cognitive function, however, there was no additive effect of the flavanol consumption when combining the two conditions. The executive function task comprised the Stroop test, and potentially this short cognitive task was not sufficiently challenging for the young, healthy cohort to show improvements.

Furthermore, a study investigating cognitive function an hour after consumption of either a low flavanol containing white chocolate, a medium flavanol containing milk chocolate, or a dark chocolate containing high flavanol levels, found no improvements on a computerized test battery Cogstate Ltd.

The authors did, however, observe enhanced vascular endothelial function following the high flavanol chocolate condition which was reflected by improvements in brachial artery flow-mediated dilation. The cohort was limited to 12 post-menopausal women, but included strict control of the type, composition, and energy content of the chocolate used to ensure consistency between conditions Marsh et al.

There were no associations observed between chocolate intake and verbal memory. An important point to note, however, is that chocolate intake was not differentiated according to type, i. In a randomized, controlled, crossover design study of 30 cognitively normal participants, with mean age There was a minimum washout period of 1 week between treatments.

Relative to control, all treatments augmented nitric oxide status acutely, but had no effect on cognitive function min post-intervention. Furthermore, this study assessed the acute effects of flavonoid intake, raising the possibility that longer-term consumption is required to induce cognitive benefit Bondonno et al.

The authors summarized that the study demonstrated a positive effect of flavanol intake on episodic memory in otherwise cognitively normal older adults with a lower level of memory performance Bensalem et al.

Moreover, a randomized, placebo-controlled, double-blind, counterbalanced-crossover study of 20 healthy young adults mean age However, there was no effect on attention accuracy, or on measures of memory Haskell-Ramsay et al.

Of the 15 studies reviewed in this section, 11 found improvements in at least one cognitive domain following flavanol consumption two observational studies, six chronic, and three acute intervention studies.

Of these 11 studies, flavanol intake was associated with improvements in global cognition as well as the cognitive domains of visual-spatial memory and organization, working memory, abstract reasoning, accuracy, reaction time, executive function, episodic memory, verbal fluency, and recognition memory.

There were no common methodological approaches amongst the studies reporting positive effects compared to those reporting no effect, with a wide range of age groups included, varying flavanol doses utilized and two studies incorporating the additional variables of sleep deprivation and exercise.

Orange juice is one of the most commonly consumed juices throughout the world and is a rich source of flavanones, particularly hesperidin and narirutin. As one of the most readily absorbed flavonoid subclasses, flavanones have been shown to cross the blood-brain barrier.

In other cognitive areas, the HF drink reduced the decline in performance associated with LF beverage consumption. Further, performance was better when the HF drink was consumed in the first arm of the trial than when the LF drink was consumed first, indicating effects of the HF drink may have continued into the second arm of the intervention Kean et al.

The effect of drinking a HF orange juice mg compared with placebo has been investigated acutely, with cognitive testing conducted at 2- and 6-h post-consumption, in a randomized, double-blind, counterbalance study, with a 2-week wash out period.

This study was conducted in 22 healthy males between 30 and 65 years of age. The HF drink contained Additionally, the change in performance from baseline to 6 h post-consumption on Continuous Performance Task accuracy, a measure of psychomotor speed, was significantly different across the treatments, with fewer errors observed when the HF drink had been consumed.

Lamport et al. The HF drink contained considerably less total flavanones than the previously mentioned studies, with Twenty-four young adults between 18 and 30 years of age underwent cognitive testing at baseline and 2 h post-drink consumption, and a further 16 participants underwent functional MRI assessment at baseline, 2- and 5-h post-drink consumption to measure cerebral blood flow CBF.

Regional perfusion in the inferior frontal gyrus and middle frontal gyrus of the right hemisphere was significantly higher 2 h post-consumption of the HF drink compared with the control drink. There were no differences in regional perfusion 5 h after consumption of either drink.

The inferior frontal gyrus has been implicated in tasks that require inhibition, planning, decision making, and other aspects of executive function, examined by the DSST.

Stronger cognitive effects could have occurred more than 2 h post-drink consumption, as was seen in the previously mentioned studies, yet this was not assessed in the current study. However, increased CBF was observed at 2 h and not 5 h post-consumption in the current study, suggesting that the time course by which flavonoids in orange and grapefruit juice exert their effect may differ from orange juice alone.

It is not possible, however, to determine a direct link between increased CBF and better cognitive function in the current study due to the separate cohorts utilized to investigate these outcomes.

All three studies reviewed thus far in this section reported improvements in at least one cognitive domain following flavanone consumption one chronic study and two acute. Global cognition as well as the cognitive domains of psychomotor speed, and executive function were positively impacted by flavanone consumption.

All three studies also reported no associations of flavanone intake with episodic memory and verbal memory. These three studies were conducted in cohorts of distinct age groups of cognitively normal adults, ranging from 30 to over 65 years.

It appears therefore, that flavanone intake yields positive effects on cognition regardless of age. Finally, a recent study assessed the association of long-term intake of total and six classes of dietary flavonoids flavanones, flavanols, flavonoid polymers, flavonols, flavones, and anthocyanins and decline in cognitive function, over a median follow-up period of up to The findings did not support a clear association, with nominally significant trends observed between 1 higher flavonol and flavanol intakes, and slower decline in global function, verbal and visual memory; 2 higher total flavonoid and flavonoid polymer intakes and slower decline in visual memory; and 3 slower decline in verbal learning with higher flavanol intake Shishtar et al.

The age range of participants, and sensitivity of cognitive measures used, may have impacted the study findings. Having a clear understanding of how these flavonoid subclasses are modulating cognitive function is required for furthering the use of these compounds as interventions which can be recommended by health professionals.

There is a relative paucity of data in humans, with the majority of mechanistic studies to date, having been undertaken in animal models.

Nevertheless, these animal studies provide clues regarding potential mechanistic pathways in humans. Collectively, the published studies implicate a number of candidate mechanisms underlying the beneficial effects of consumption of these flavonoid subclasses on cognitive function, including, modulation of intracellular signaling pathways, altered CBF, and conferring protection against neurotoxins and neuroinflammation.

The flavonoid subclasses of anthocyanins, flavanols, and flavanones modulate several neurological processes via their interaction with signaling pathways involved in neuronal survival and function, upregulation of proteins important for synaptic plasticity and neuronal repair, and inhibition of neuropathological processes which occur in brain regions typically implicated in AD pathogenesis.

Flavonoids have also been shown to modulate the cell death pathways mediated by p38 and c-Jun N-terminal kinase Hwang and Yen, to confer protection against neurodegeneration. These interactions are summarized in Figure 1. Figure 1. Modulation of neuronal death and survival pathways by the flavonoid subclasses of anthocyanins, flavanols, and flavanones.

Modified from Solanki et al. The activation of cell survival pathways by flavonoids involves upregulation of anti-apoptotic and pro-survival genes, and inhibition of pro-apoptotic proteins Levites et al.

Targets include inhibition of apoptosis signal-regulating kinase 1 ASK1; Vauzour et al. Flavonoids are also proposed to confer cell survival through activation of cAMP response element-binding protein CREBP phosphorylation Williams et al. As mentioned previously, BDNF is a neurotrophin required for the development and maintenance of the nervous system Schindowski et al.

BDNF levels are known to decline during aging, and their levels have been shown to correlate with learning and memory Garzon et al. JNK and p38 are strongly linked to transcription-dependent apoptotic signaling Mielke and Herdegen, via the activation of c-Jun and other activated protein 1 AP-1 proteins including Jun-B and Jun-D Behrens et al.

The inflammatory cascade is believed to play a critical role in the development of chronic low grade inflammatory diseases such as AD. Reductions in blood levels of inflammatory markers such as CRP, IL-6, and tumor necrosis factor alpha TNF-α have been shown following flavonoid consumption, suggesting anti-inflammatory activity Carey et al.

Furthermore, flavonoids have the capacity to downregulate the activity of pro-inflammatory transcription factors such as NF-κB, nuclear factor erythroid 2-related factor 2 Nrf2 and STAT signal transducers and activators of transcription , through their influences on a number of glial and neuronal signaling pathways Hamalainen et al.

Mitochondria control cellular energy status, reactive oxygen species ROS production, and apoptosis, all of which are important for determining lifespan, and mitochondria are therefore, proposed to act as central organelles in the regulation of aging and neurodegeneration.

Mitochondria constitute the major source of superoxide and other ROS within most tissues. AMP-activated protein kinase AMPK , a key cellular regulator of energy metabolism, has been implicated in the regulation of mitochondria function. Damaged mitochondria are the major sources of ROS in cells and are implicated in many neurodegenerative diseases including AD.

Activated AMPK can decrease intracellular ROS by inhibiting NADPH nicotinamide adenine dinucleotide phosphate oxidase activity, or by increasing the expression of antioxidant enzymes such as superoxide dismutase-2 and uncoupling protein-2 Manczak et al. Flavonoids may ameliorate mitochondrial dysfunction and increase oxidative defense mechanisms by activating AMPK Cordero-Herrera et al.

Consumption of flavonoids could improve cerebrovascular outcomes including CBF. Whilst the mechanisms require elucidation, they may be related to increases in the pool of bioavailable nitric oxide NO; Bondonno et al.

One mechanism by which NO is synthesized is by the action of endothelial nitric oxide synthase eNOS on arginine, and flavonoids may enhance NO production by increasing eNOS activity or enhancing expression.

Decreases in blood pressure, improvements in endothelial function Bondonno et al. This is consistent with literature showing natural products that enhance brain metabolism or elevate CBF are effective at augmenting cognitive function during prolonged, effortful, cognitive processing Owen and Sunram-Lea, , with reduced blood flow to the brain associated with cognitive impairment Farkas et al.

Moreover, there is evidence to show that increasing glucoregulatory control via improved insulin sensitivity can improve cognitive function, with intake of flavonoids being shown to increase insulin sensitivity, as well as insulin and glucose levels Russo et al.

Attenuation of decline in blood glucose concentrations has been observed following blackcurrant Watson et al. Evidence accumulated to date suggests the consumption of products containing anthocyanins, flavanols, and flavanones, such as berries and cocoa, throughout life, may have the potential to limit or even reverse age-related declines in cognition and memory, and potentially delay the onset and progression of neurodegenerative diseases such as AD.

Over the last 6 years, the flavonoid subgroups of anthocyanins, flavanols, and flavanones have been shown to be beneficial in terms of conferring neuroprotection and cognitive benefit. Of note, however, methodological disparities hinder comparison of results between studies.

For example, a vast range of flavonoid-containing products utilized in interventions of varying durations, and differences in comprehensiveness of neuropsychological assessments, as well as heterogeneity of cohorts, are all likely to impact findings.

Of the literature reviewed here, acute studies ranged in duration from 60 min to 6 h, whilst the longer-term studies ranged from 28 days to 6 months, with 3 months being the most common timeframe employed. All except two intervention studies included control groups consuming a placebo, with these two studies comparing cognitive function at baseline to end point 16 weeks or 6 h.

Whilst studies were included in the current review regardless of placebo being matched with the intervention condition for macro- and micro- nutrient content, this should be a consideration when designing future interventions, to ensure observed effects are due to the flavonoid content and not additional components e.

The quantity of flavonoid treatment in the reviewed studies also varied greatly, with some participants consuming mg daily or greater, and others under mg.

Interestingly, a study including groups of participants consuming mg or mg daily, for 8 weeks, found both quantities were associated with improvements in measures of attention, visual search and scanning, sequencing and shifting, and psychomotor speed, but only the mg group also demonstrated increased performance in verbal fluency Mastroiacovo et al.

A range of cognitive domains have been shown to be beneficially affected in the reviewed studies; summarized in Figure 2. Acute supplementation with the three flavonoid subclasses investigated was associated with positive effects in tests measuring psychomotor speed, executive function, and attention.

Longer-term supplementation was associated with positive effects in tests of episodic memory, global cognition, verbal fluency, psychomotor speed, and verbal memory, in multiple studies. Although a particular task may have a primary focus such as verbal fluency or episodic memory, a range of processes may support the primary focus, e.

Potentially, flavonoids could be exerting greater effects on relatively effortful tasks and less effect on simpler tasks. This notion is consistent with the results of Bondonno et al. Furthermore, Gratton et al. A wide range of tasks which fully assess cognitive ability multiple domains and tasks of varying complexity needs to be employed by studies attempting to fully characterize the effects of flavonoids on cognition.

Figure 2. Cognitive domains affected by the flavonoid subclasses of anthocyanins, flavanols, and flavanones. The mechanisms by which the flavonoid subclasses of anthocyanins, flavanols, and flavanones modulate cognitive function are yet to be fully established.

Available evidence plausibly suggests these flavonoid subclasses can promote beneficial effects via both direct i. Although, it should be noted that the majority of mechanistic studies to date have been conducted in animal models, and more human studies are required to draw definitive conclusions.

Wide inter-individual variability in flavonoid absorption and metabolism has been reported, with a number of factors including age and gender affecting these metabolic processes.

Flavonoids initially undergo extensive metabolization by phase I and II metabolism which occur predominantly in the gastrointestinal tract and liver. Hepatic perfusion and morphology reduce as part of the aging process, which has been suggested to reduce phase I and II metabolism of flavonoids.

Flavonoid absorption occurs in both the small and large intestines, with a high percentage reaching the colon where there is exposure to colonic microbiota Williamson and Clifford, The microbiome plays a key role in catabolizing unabsorbed flavonoids into smaller molecules which may become bioavailable.

It is conceivable that heterogeneity in flavonoid absorption and metabolism may diminish beneficial associations between intakes and cognitive outcomes reported in studies. Ideally, urinary flavonoid excretion results would be taken into account in analyses, and to inform personalized health goals.

Overall, additional prospective studies conducted in diverse populations, and adequately powered intervention studies with long durations, are required to thoroughly examine the effect of consumption of the flavonoid subclasses of anthocyanins, flavanols, and flavanones on clinically relevant cognitive outcomes.

Moreover, the characterization of appropriate dosage, timeframes for intake, and form of flavonoids, remains to be fully determined. Whilst animal models have shown promising results with interventions of timeframes such as 2 months, this represents a considerably larger percentage of total lifespan for animals than it does for humans, and a longer time-frame could be needed to show enhanced outcomes in human trials.

Both acute and chronic effects of these flavonoid subclasses also need to be investigated using neuroimaging techniques in conjunction with cognitive and physiological measures to further elucidate the underlying biological mechanisms. Furthermore, it should be acknowledged that studies in cognitively normal adults are unlikely to demonstrate large improvements in cognitive function, and therefore it is imperative that suitable, sensitive cognitive tests are utilized.

There is currently no clear evidence regarding the specific domains of cognition and memory that these flavonoid subclasses impact, with future studies requiring a range of cognitive domains to be investigated in order to determine those most likely to benefit.

If emerging evidence continues to suggest significant cognitive benefit, another important consideration is the optimum age for the initiation of supplementation of flavonoid intake. Indeed, the neuropathological hallmarks of AD begin to accumulate 15—20 years before symptoms manifest, implying that the optimal age for supplementing flavonoid consumption could be middle-age or younger.

As populations continue to focus on developing strategies to promote healthy aging, dietary interventions with flavonoids represents a promising avenue for future research. However, many questions still need to be answered before a definite conclusion can be made regarding the extent to which consumption of anthocyanins, flavanols, and flavanones can protect the aging brain, and intake can be included in public health dietary recommendations.

SG and SR-S contributed to the conception and design of the work. SG prepared the first draft of the manuscript. SR-S, MW, CB, and RM revised the manuscript. All authors approved the final version of the manuscript. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers.

Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher. Supplementary Table 1 Intervention human studies published over the past 6 years investigating flavonoid consumption and cognitive outcomes.

Alharbi, M. Flavonoid-rich orange juice is associated with acute improvements in cognitive function in healthy middle-aged males. Eur J Nutr 55, — doi: PubMed Abstract CrossRef Full Text Google Scholar. Behrens, A. Amino-terminal phosphorylation of c-Jun regulates stress-induced apoptosis and cellular proliferation.

Bensalem, J. Polyphenols From Grape and Blueberry Improve Episodic Memory in Healthy Elderly with Lower Level of Memory Performance: A Bicentric Double-Blind, Randomized, Placebo-Controlled Clinical Study. A Biol.

Bergland, A. Effects of Anthocyanin Supplementation on Serum Lipids, Glucose, Markers of Inflammation and Cognition in Adults With Increased Risk of Dementia - A Pilot Study.

Google Scholar. Boespflug, E. Enhanced neural activation with blueberry supplementation in mild cognitive impairment. Bondonno, C. The acute effect of flavonoid-rich apples and nitrate-rich spinach on cognitive performance and mood in healthy men and women. Food Funct. Flavonoid-rich apples and nitrate-rich spinach augment nitric oxide status and improve endothelial function in healthy men and women: a randomized controlled trial.

Free Radic Biol. Whether observed anthocyanin-induced improvements in vascular function and blood pressure underlie beneficial effects on cognitive performance warrants further study. Keywords: anthocyanins; cardiometabolic risk markers; cognitive performance; vascular function.

Abstract Supplementation with anthocyanins, which are a type of flavonoids mainly found in various berries, is hypothesized to be a promising approach to lower the risk of developing cognitive decline. Publication types Meta-Analysis Systematic Review.

Supplementation with anthocyanins, which are a type funcction flavonoids mainly found in cognitiv berries, Anthocyanibs hypothesized to be Inflammation and cancer prevention promising Menstrual health campaigns to lower the risk of developing cognitive decline. The aim of Anthoccyanins systematic funtcion was to provide a Inflammation and cancer prevention ad of dietary intervention trials describing effects of berry anthocyanins on cognitive performance in humans, while also addressing potential underlying mechanisms. Significant improvements were observed on memory, while some of the studies also reported effects on attention and psychomotor speed or executive function. Vascular function markers such as brachial artery flow-mediated vasodilation were also affected and consistent evidence was provided for the beneficial effects of berry anthocyanins on endothelial function. Finally, studies reported improvements in blood pressure, but effects on metabolic risk markers e. The purpose of this fuction is to cofnitive human research Inflammation and cancer prevention published within the past 6 Non-addictive coffee replacement which evaluate the functoon of anthocyanin, flavanol, and flavanone consumption in cognitive Anthocyaninw, and Functiob discuss potential Anthocyanins and cognitive function of action Improve cognitive speed any observed benefits. Anthocyanims to date suggests the coognitive of flavonoid-rich foods, such as berries and cocoa, may have the potential to limit, or even reverse, age-related declines in cognition. Over the last 6 years, the flavonoid subgroups of anthocyanins, flavanols, and flavanones have been shown to be beneficial in terms of conferring neuroprotection. The mechanisms by which flavonoids positively modulate cognitive function are yet to be fully elucidated. Postulated mechanisms include both direct actions such as receptor activation, neurotrophin release and intracellular signaling pathway modulation, and indirect actions such as enhancement of cerebral blood flow. Further intervention studies conducted in diverse populations with sufficient sample sizes and long durations are required to examine the effect of consumption of flavonoid groups on clinically relevant cognitive outcomes. Anthocyanins and cognitive function

Anthocyanins and cognitive function -

Search Menu. Article Navigation. Close mobile search navigation Article Navigation. Volume Article Contents Abstract. Supporting Information.

Journal Article. Effects of anthocyanin-rich supplementation on cognition of the cognitively healthy middle-aged and older adults: a systematic review and meta-analysis of randomized controlled trials.

Ruo Chen Feng , Ruo Chen Feng. is with the High-Dependency Unit, Tan Tock Seng Hospital, National Health Group. Oxford Academic. Google Scholar. Yan Hong Dong. are with the Alice Lee Centre for Nursing Studies, Yong Loo Lin School of Medicine, National University of Singapore.

is with the Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore. Xian Li Hong. is with the Medical Intensive Care Unit, Tan Tock Seng Hospital, National Health Group. Ya Su. is with the Shanghai Jiao Tong University, School of Nursing. is with the Faculty of Health Sciences, Hokkaido University.

Xi Vivien Wu. is with the NUSMED Healthy Longevity Translational Research Programme, National University of Singapore. Xi Vivien Wu , Alice Lee Centre for Nursing Studies, Yong Loo Lin School of Medicine, National University of Singapore, Level 2, Clinical Research Centre, Block MD 11, 10 Medical Dr, Singapore E-mail: nurwux nus.

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Short-term Access To purchase short-term access, please sign in to your personal account above. This article is also available for rental through DeepDyve. Views More metrics information. We focused on the three subclasses of anthocyanins, flavanols, and flavanones as the effects of the additional three flavonoid subclasses flavones, flavonols, and isoflavones have not been reported in human studies published within the 6-year timeframe of this narrative review.

Table 1. Observational human studies published over the past 6 years investigating flavonoid consumption and cognitive outcomes. A computer-based search of PubMed was conducted for relevant articles published between and inclusive, with cognitive function as the primary or secondary outcome.

Search terms were: flavonoids or anthocyanins or flavanols or flavanones and cognition or cognitive function. The search was limited to articles in humans, published in English. Studies that specifically focused on the cognitive effects of flavonoids either in extract or whole food form were included.

Titles and abstracts were screened by the first author to ensure they examined the relationship between one of the flavonoid subclasses of interest anthocyanins, flavanols, or flavanones and cognition in adults.

Articles were included if they reported prospective, retrospective or intervention studies and were either cross-sectional or longitudinal in nature. There were no strict criteria relating to the inclusion of controls or the quality of these controls with respect to matching for other macro or micronutrients.

The reference lists of included articles were screened and additional articles which met inclusion criteria were added via hand search. Included studies are presented in Supplementary Table 1 and Table 1.

Anthocyanins are a class of flavonoids concentrated in purple and red fruits. The intervention group also had a reduction in systolic blood pressure, with a trend for reduction in diastolic blood pressure. However, markers of inflammation CRP, C-reactive protein; IL-6, Interleukin 6 were not altered Kent et al.

Of note, pre-clinical studies have indicated that anthocyanins from berry fruits may require only a few weeks to accumulate in brain regions associated with cognition Willis et al.

This study was conducted in 37 adults aged between 65 and 80 with normal cognitive function. There were no significant improvements in working memory and strategy use, and visual attention. It is, however, important to note, that the intervention group had significantly decreased physical activity level whilst the control group had significantly increased cholesterol intake over the intervention period Chai et al.

In contrast, Caldwell et al. The cognitive tests assessed verbal learning and memory, higher executive function, and speed of processing. The serving of cherry juice contained approximately 55 mg of anthocyanins; a lower dose compared to other food-based studies.

The cognitive tests administered may not have adequately assessed the cognitive domains affected by acute anthocyanin consumption. Moreover, testing at 2 rather than 6 h post-intervention may better reflect the physiological absorption of anthocyanins in the small intestine. In an intervention trial undertaken in 36 healthy young participants aged 18—35 years , individuals consumed one of three different treatment drinks once, with at least 7 days of washout between consumption of each drink.

The drinks contained either 0 mg of polyphenols control , ± 5 mg of polyphenols per 60 kg of bodyweight from an anthocyanin-enriched blackcurrant extract, or from ml of a cold-pressed blackcurrant fruit juice.

Participants underwent 10 min of cognitive testing before consumption of each treatment drink, followed by additional cognitive testing 60 min post-consumption, comprising seven repetitions of the min battery.

The juice drink also induced a number of neuroendocrinological and physiological effects including increase in blood glucose concentration compared with control.

These results suggest that the degree of processing and the cultivar of blackcurrant fruit used substantially alters the neuroendocrinological and cognitive benefits conferred Watson et al. The intervention group was comprised of eight participants with MCI, and 19 with stable non-obstructive coronary artery disease, as the study was designed to investigate supplementation in those with increased risk of dementia.

However, the control group did not undergo cognitive testing; consequently, these results should be interpreted with caution due to the lack of a comparison group Bergland et al.

Several randomized, double-blinded, placebo-controlled studies to evaluate the effects of blueberry consumption on cognition have been conducted. In adults aged 65—80, Whyte et al. Cognitive testing occurred at baseline, 3 and 6 months using a battery targeting episodic memory, working memory, and executive function.

At the 3-month testing point, delayed word recognition and short-term spatial episodic memory were significantly better in the WBE treatment group compared to control.

There were no significant differences at 6 months, or with consumption of the WBP and WBP at any timepoint.

It should be noted, however, that the quantity of anthocyanins administered is relatively small compared to other studies. Miller et al. No effect of the intervention was seen on tests of psychomotor speed, short-term memory, spatial cognition, or attention.

Following berry intervention, participants maintained accuracy in executive function, up to and including the 6-h testing point, measured using the Modified Attention Network Task MANT and Task Switching Task TST.

Participants demonstrated quicker response times in the MANT conducted at the 2- and 4-h post-smoothie consumption cognitive assessments, and in the TST at 6-h post-smoothie consumption.

The results of this study suggest that berry-related benefits were more evident during periods of fatigue, with placebo participants showing decreased performance across the 6 h as they became cognitively fatigued. Whilst the placebo was matched to the intervention for sugar content and sweetness, it was not matched for berry flavor, thus participants may have guessed which treatment they received, potentially leading to performance being influenced by placebo effect Whyte et al.

A cross-over randomized controlled trial was conducted in 18 older adults aged 60—75 using a flavonoid-rich blueberry beverage drink mg of antho- and pro-cyanidins , or sugar-matched control.

Cognitive function was assessed at baseline, 2- and 5-h post-beverage consumption. There were also no significant differences between groups in performance on the 14 tasks that comprised the global cognitive function score; although some associations were approaching significance, suggesting that the study may be underpowered Dodd et al.

Sixty-five men and women aged 62—80 years completed a week randomized double-blind, placebo-controlled trial consuming either daily fish oil, daily blueberry providing mg anthocyanin per day , both fish oil and blueberry, or control.

Participants all reported mild, age-related cognitive decline, but lacked a diagnosis of MCI or dementia. No effect on motor speed, working memory, learning and retention, or lexical access was observed for the fish oil group, compared to placebo, at the end of the week intervention, or at week follow-up.

There was improved discrimination in recognition memory for the blueberry treated group at weeks, indicating improved resistance to interference of extraneous material in memory; however, this benefit was not maintained at week Unexpectedly, there was no effect on any cognitive domain of the combined fish oil and blueberry treatment McNamara et al.

In a randomized, double-blind placebo-controlled trial of 16 older adults aged 68—92 years with MCI, functional magnetic resonance imaging MRI , conducted during a working memory task, was assessed pre- and post- weeks of blueberry supplementation providing mg anthocyanins daily. Whilst there was no clear indication of working memory enhancement associated with supplementation, enhanced neural response during the working memory task was observed in the blueberry treatment group compared to placebo.

Change in performance on cognitive tests was not significantly different between placebo and blueberry supplementation treatment groups in a week double-blind randomized controlled trial of 26 cognitively normal participants aged over 65 years. Participants underwent computerized tests of psychomotor function, visual processing, executive function, verbal and spatial memory, and working memory.

The percentage change in performance on the 2 -back test did, however, show weak evidence for improvement in the blueberry treatment group compared to placebo Bowtell et al. Of the 12 studies reviewed in this section, six reported improvements in at least one cognitive domain following anthocyanin consumption four chronic studies and two acute , whilst six studies showed no improvement or change compared with placebo four chronic studies and two acute.

Cognitive domains impacted by anthocyanin intake included verbal fluency, short term memory, long term memory, visual memory, speed of response, accuracy, verbal memory, and executive function. Chocolate and cocoa products are a rich source of flavonoids with flavanols, and in particular epicatechin, being the most common type present in cocoa.

High levels of flavanols are also found in tea, red wine, and fruits such as grapes and apples. However, object recognition and prefrontal cortex-dependent list sorting performance did not improve.

Eight weeks post-cessation of flavanol consumption, there were no observable effects remaining on list-learning performance in the intervention group compared to placebo. Notably, the object recognition task was newly developed, and data analysis suggested the task was so difficult that the majority of participants performed no better than chance; thus, failure to observe associations with flavanol intake may have been due to the psychometric properties of this outcome measure Sloan et al.

Gratton et al. This study was conducted in 18 healthy males 18—45 years using an acute, randomized, placebo-controlled, double-blind, crossover design, with high or low cocoa flavanol drink, and cognitive function assessed pre- and 2-h post-consumption using a Modified Stroop Task.

One advantage of this study is the intervention and placebo were matched for macronutrient and micronutrient content, including caffeine.

With the cohort comprising only young males, future work should be extended to include females as well as older at-risk populations. A study retrospectively analyzing data from 55 participants with amnestic MCI 29 males and 26 females, aged 56—75 found dietary supplementation with cocoa flavonoids was associated with slowed cognitive decline.

Intake of the commonly used nutraceutical Mexenion ® was examined. However, given the formulation of Mexenion ® , it is not possible to determine directly if the cocoa polyphenols present were responsible for the observed benefit. Neshatdoust et al.

After the first intervention period, there was a 4 week wash out prior to switching treatment. A cognitive battery measuring global executive function, and blood sample collection was completed pre-intervention, post-first intervention, and at the end of the study.

BDNF is a member of the neurotrophin family of growth factors that help to stimulate and control neurogenesis. Cognitive testing and blood sample collection occurred at weeks 0, 6, 12, and The authors concluded that increased brain and peripheral BDNF expression could be mediating the improvements observed in cognitive function Neshatdoust et al.

Flavanol-rich chocolate has been shown to counteract the effects of sleep deprivation on working memory in women but not men. Sixteen women and 16 men participated in a randomized, double-blind, crossover study, undergoing four sets of cognitive testing, two after a night of undisturbed sleep and two after a night of total sleep deprivation, with a week between each of the four testing sessions.

Participants consumed either a flavanol-poor chocolate bar or a flavanol-rich chocolate bar before each of the testing sessions. Consumption of the flavanol-rich chocolate also produced positive effects on blood pressure, flow-mediated dilation, and pulse-wave velocity, which were all impaired following sleep deprivation Grassi et al.

The dentate gyrus DG , a brain region in the hippocampal formation, demonstrates functional decline with aging. In a controlled randomized trial of 37 cognitively normal adults aged 50—69 years, Brickman et al. There was no effect of the diet on delayed retention.

The high flavanol group consumed two mg supplements per day, and the low flavanol group consumed a total of 45 mg divided into two doses. The high flavanol group also demonstrated a significant increase in cerebral blood volume in the DG and the downstream subiculum in the body of the hippocampus, with the changes in object recognition task performance correlating with these cerebral blood volume increases.

The authors concluded that DG dysfunction is a driver of age-related cognitive decline, and flavanol consumption may be a method to ameliorate this process. The effect of consumption of a high flavanol cocoa drink compared to a low flavanol cocoa drink on cognitive function was investigated in 90 cognitively normal elderly individuals in a double-blind, controlled, parallel-arm study.

Participants were randomly assigned to groups consuming either a drink containing mg high flavanol , mg intermediate flavanol , or 48 mg low flavanol cocoa flavanols, daily for 8 weeks. No change in MMSE score in response to the three treatments was observed.

Additionally, significant improvements in insulin resistance, blood pressure, and lipid peroxidation were seen in the high and intermediate flavanol groups, in comparison to the low flavanol group; highlighting potential mechanistic pathways through which cocoa flavanols exert positive effects on cognition Mastroiacovo et al.

By contrast, Massee et al. However, acute consumption, with cognitive testing conducted 3 h after first supplementation, was associated with significant improvement on Serial Sevens performance, in the first of three cycles of cognitive testing.

Notably, the intervention duration was half that of Mastroiacovo et al. Additionally, participants in the current study were considerably younger with mean age A study investigating the effect of cocoa flavanol intake combined with exercise on executive function found that, whilst flavanol intake increased cerebral oxygenation during the executive function task, there was no impact on cognitive performance.

Furthermore, exercise alone improved cognitive function, however, there was no additive effect of the flavanol consumption when combining the two conditions. The executive function task comprised the Stroop test, and potentially this short cognitive task was not sufficiently challenging for the young, healthy cohort to show improvements.

Furthermore, a study investigating cognitive function an hour after consumption of either a low flavanol containing white chocolate, a medium flavanol containing milk chocolate, or a dark chocolate containing high flavanol levels, found no improvements on a computerized test battery Cogstate Ltd.

The authors did, however, observe enhanced vascular endothelial function following the high flavanol chocolate condition which was reflected by improvements in brachial artery flow-mediated dilation. The cohort was limited to 12 post-menopausal women, but included strict control of the type, composition, and energy content of the chocolate used to ensure consistency between conditions Marsh et al.

There were no associations observed between chocolate intake and verbal memory. An important point to note, however, is that chocolate intake was not differentiated according to type, i. In a randomized, controlled, crossover design study of 30 cognitively normal participants, with mean age There was a minimum washout period of 1 week between treatments.

Relative to control, all treatments augmented nitric oxide status acutely, but had no effect on cognitive function min post-intervention. Furthermore, this study assessed the acute effects of flavonoid intake, raising the possibility that longer-term consumption is required to induce cognitive benefit Bondonno et al.

The authors summarized that the study demonstrated a positive effect of flavanol intake on episodic memory in otherwise cognitively normal older adults with a lower level of memory performance Bensalem et al. Moreover, a randomized, placebo-controlled, double-blind, counterbalanced-crossover study of 20 healthy young adults mean age However, there was no effect on attention accuracy, or on measures of memory Haskell-Ramsay et al.

Of the 15 studies reviewed in this section, 11 found improvements in at least one cognitive domain following flavanol consumption two observational studies, six chronic, and three acute intervention studies. Of these 11 studies, flavanol intake was associated with improvements in global cognition as well as the cognitive domains of visual-spatial memory and organization, working memory, abstract reasoning, accuracy, reaction time, executive function, episodic memory, verbal fluency, and recognition memory.

There were no common methodological approaches amongst the studies reporting positive effects compared to those reporting no effect, with a wide range of age groups included, varying flavanol doses utilized and two studies incorporating the additional variables of sleep deprivation and exercise.

Orange juice is one of the most commonly consumed juices throughout the world and is a rich source of flavanones, particularly hesperidin and narirutin.

As one of the most readily absorbed flavonoid subclasses, flavanones have been shown to cross the blood-brain barrier. In other cognitive areas, the HF drink reduced the decline in performance associated with LF beverage consumption.

Further, performance was better when the HF drink was consumed in the first arm of the trial than when the LF drink was consumed first, indicating effects of the HF drink may have continued into the second arm of the intervention Kean et al. The effect of drinking a HF orange juice mg compared with placebo has been investigated acutely, with cognitive testing conducted at 2- and 6-h post-consumption, in a randomized, double-blind, counterbalance study, with a 2-week wash out period.

This study was conducted in 22 healthy males between 30 and 65 years of age. The HF drink contained Additionally, the change in performance from baseline to 6 h post-consumption on Continuous Performance Task accuracy, a measure of psychomotor speed, was significantly different across the treatments, with fewer errors observed when the HF drink had been consumed.

Lamport et al. The HF drink contained considerably less total flavanones than the previously mentioned studies, with Twenty-four young adults between 18 and 30 years of age underwent cognitive testing at baseline and 2 h post-drink consumption, and a further 16 participants underwent functional MRI assessment at baseline, 2- and 5-h post-drink consumption to measure cerebral blood flow CBF.

Regional perfusion in the inferior frontal gyrus and middle frontal gyrus of the right hemisphere was significantly higher 2 h post-consumption of the HF drink compared with the control drink.

There were no differences in regional perfusion 5 h after consumption of either drink. The inferior frontal gyrus has been implicated in tasks that require inhibition, planning, decision making, and other aspects of executive function, examined by the DSST. Stronger cognitive effects could have occurred more than 2 h post-drink consumption, as was seen in the previously mentioned studies, yet this was not assessed in the current study.

However, increased CBF was observed at 2 h and not 5 h post-consumption in the current study, suggesting that the time course by which flavonoids in orange and grapefruit juice exert their effect may differ from orange juice alone.

It is not possible, however, to determine a direct link between increased CBF and better cognitive function in the current study due to the separate cohorts utilized to investigate these outcomes.

All three studies reviewed thus far in this section reported improvements in at least one cognitive domain following flavanone consumption one chronic study and two acute.

Global cognition as well as the cognitive domains of psychomotor speed, and executive function were positively impacted by flavanone consumption. All three studies also reported no associations of flavanone intake with episodic memory and verbal memory.

These three studies were conducted in cohorts of distinct age groups of cognitively normal adults, ranging from 30 to over 65 years. It appears therefore, that flavanone intake yields positive effects on cognition regardless of age.

Finally, a recent study assessed the association of long-term intake of total and six classes of dietary flavonoids flavanones, flavanols, flavonoid polymers, flavonols, flavones, and anthocyanins and decline in cognitive function, over a median follow-up period of up to The findings did not support a clear association, with nominally significant trends observed between 1 higher flavonol and flavanol intakes, and slower decline in global function, verbal and visual memory; 2 higher total flavonoid and flavonoid polymer intakes and slower decline in visual memory; and 3 slower decline in verbal learning with higher flavanol intake Shishtar et al.

The age range of participants, and sensitivity of cognitive measures used, may have impacted the study findings. Having a clear understanding of how these flavonoid subclasses are modulating cognitive function is required for furthering the use of these compounds as interventions which can be recommended by health professionals.

There is a relative paucity of data in humans, with the majority of mechanistic studies to date, having been undertaken in animal models.

Nevertheless, these animal studies provide clues regarding potential mechanistic pathways in humans. Collectively, the published studies implicate a number of candidate mechanisms underlying the beneficial effects of consumption of these flavonoid subclasses on cognitive function, including, modulation of intracellular signaling pathways, altered CBF, and conferring protection against neurotoxins and neuroinflammation.

The flavonoid subclasses of anthocyanins, flavanols, and flavanones modulate several neurological processes via their interaction with signaling pathways involved in neuronal survival and function, upregulation of proteins important for synaptic plasticity and neuronal repair, and inhibition of neuropathological processes which occur in brain regions typically implicated in AD pathogenesis.

Flavonoids have also been shown to modulate the cell death pathways mediated by p38 and c-Jun N-terminal kinase Hwang and Yen, to confer protection against neurodegeneration.

These interactions are summarized in Figure 1. Figure 1. Modulation of neuronal death and survival pathways by the flavonoid subclasses of anthocyanins, flavanols, and flavanones. Modified from Solanki et al. The activation of cell survival pathways by flavonoids involves upregulation of anti-apoptotic and pro-survival genes, and inhibition of pro-apoptotic proteins Levites et al.

Targets include inhibition of apoptosis signal-regulating kinase 1 ASK1; Vauzour et al. Flavonoids are also proposed to confer cell survival through activation of cAMP response element-binding protein CREBP phosphorylation Williams et al.

As mentioned previously, BDNF is a neurotrophin required for the development and maintenance of the nervous system Schindowski et al. BDNF levels are known to decline during aging, and their levels have been shown to correlate with learning and memory Garzon et al.

JNK and p38 are strongly linked to transcription-dependent apoptotic signaling Mielke and Herdegen, via the activation of c-Jun and other activated protein 1 AP-1 proteins including Jun-B and Jun-D Behrens et al.

The inflammatory cascade is believed to play a critical role in the development of chronic low grade inflammatory diseases such as AD. Reductions in blood levels of inflammatory markers such as CRP, IL-6, and tumor necrosis factor alpha TNF-α have been shown following flavonoid consumption, suggesting anti-inflammatory activity Carey et al.

Furthermore, flavonoids have the capacity to downregulate the activity of pro-inflammatory transcription factors such as NF-κB, nuclear factor erythroid 2-related factor 2 Nrf2 and STAT signal transducers and activators of transcription , through their influences on a number of glial and neuronal signaling pathways Hamalainen et al.

Mitochondria control cellular energy status, reactive oxygen species ROS production, and apoptosis, all of which are important for determining lifespan, and mitochondria are therefore, proposed to act as central organelles in the regulation of aging and neurodegeneration. Mitochondria constitute the major source of superoxide and other ROS within most tissues.

AMP-activated protein kinase AMPK , a key cellular regulator of energy metabolism, has been implicated in the regulation of mitochondria function.

Damaged mitochondria are the major sources of ROS in cells and are implicated in many neurodegenerative diseases including AD. Activated AMPK can decrease intracellular ROS by inhibiting NADPH nicotinamide adenine dinucleotide phosphate oxidase activity, or by increasing the expression of antioxidant enzymes such as superoxide dismutase-2 and uncoupling protein-2 Manczak et al.

Flavonoids may ameliorate mitochondrial dysfunction and increase oxidative defense mechanisms by activating AMPK Cordero-Herrera et al. Consumption of flavonoids could improve cerebrovascular outcomes including CBF.

Whilst the mechanisms require elucidation, they may be related to increases in the pool of bioavailable nitric oxide NO; Bondonno et al.

One mechanism by which NO is synthesized is by the action of endothelial nitric oxide synthase eNOS on arginine, and flavonoids may enhance NO production by increasing eNOS activity or enhancing expression. Decreases in blood pressure, improvements in endothelial function Bondonno et al.

This is consistent with literature showing natural products that enhance brain metabolism or elevate CBF are effective at augmenting cognitive function during prolonged, effortful, cognitive processing Owen and Sunram-Lea, , with reduced blood flow to the brain associated with cognitive impairment Farkas et al.

Moreover, there is evidence to show that increasing glucoregulatory control via improved insulin sensitivity can improve cognitive function, with intake of flavonoids being shown to increase insulin sensitivity, as well as insulin and glucose levels Russo et al.

Attenuation of decline in blood glucose concentrations has been observed following blackcurrant Watson et al. Evidence accumulated to date suggests the consumption of products containing anthocyanins, flavanols, and flavanones, such as berries and cocoa, throughout life, may have the potential to limit or even reverse age-related declines in cognition and memory, and potentially delay the onset and progression of neurodegenerative diseases such as AD.

Over the last 6 years, the flavonoid subgroups of anthocyanins, flavanols, and flavanones have been shown to be beneficial in terms of conferring neuroprotection and cognitive benefit. Of note, however, methodological disparities hinder comparison of results between studies.

For example, a vast range of flavonoid-containing products utilized in interventions of varying durations, and differences in comprehensiveness of neuropsychological assessments, as well as heterogeneity of cohorts, are all likely to impact findings.

Of the literature reviewed here, acute studies ranged in duration from 60 min to 6 h, whilst the longer-term studies ranged from 28 days to 6 months, with 3 months being the most common timeframe employed.

All except two intervention studies included control groups consuming a placebo, with these two studies comparing cognitive function at baseline to end point 16 weeks or 6 h. Whilst studies were included in the current review regardless of placebo being matched with the intervention condition for macro- and micro- nutrient content, this should be a consideration when designing future interventions, to ensure observed effects are due to the flavonoid content and not additional components e.

The quantity of flavonoid treatment in the reviewed studies also varied greatly, with some participants consuming mg daily or greater, and others under mg. Interestingly, a study including groups of participants consuming mg or mg daily, for 8 weeks, found both quantities were associated with improvements in measures of attention, visual search and scanning, sequencing and shifting, and psychomotor speed, but only the mg group also demonstrated increased performance in verbal fluency Mastroiacovo et al.

A range of cognitive domains have been shown to be beneficially affected in the reviewed studies; summarized in Figure 2. Acute supplementation with the three flavonoid subclasses investigated was associated with positive effects in tests measuring psychomotor speed, executive function, and attention.

Longer-term supplementation was associated with positive effects in tests of episodic memory, global cognition, verbal fluency, psychomotor speed, and verbal memory, in multiple studies.

Although a particular task may have a primary focus such as verbal fluency or episodic memory, a range of processes may support the primary focus, e. Potentially, flavonoids could be exerting greater effects on relatively effortful tasks and less effect on simpler tasks. This notion is consistent with the results of Bondonno et al.

Furthermore, Gratton et al. A wide range of tasks which fully assess cognitive ability multiple domains and tasks of varying complexity needs to be employed by studies attempting to fully characterize the effects of flavonoids on cognition.

Figure 2. Cognitive domains affected by the flavonoid subclasses of anthocyanins, flavanols, and flavanones. The mechanisms by which the flavonoid subclasses of anthocyanins, flavanols, and flavanones modulate cognitive function are yet to be fully established.

Available evidence plausibly suggests these flavonoid subclasses can promote beneficial effects via both direct i. Although, it should be noted that the majority of mechanistic studies to date have been conducted in animal models, and more human studies are required to draw definitive conclusions.

Wide inter-individual variability in flavonoid absorption and metabolism has been reported, with a number of factors including age and gender affecting these metabolic processes. Flavonoids initially undergo extensive metabolization by phase I and II metabolism which occur predominantly in the gastrointestinal tract and liver.

Hepatic perfusion and morphology reduce as part of the aging process, which has been suggested to reduce phase I and II metabolism of flavonoids.

Flavonoid absorption occurs in both the small and large intestines, with a high percentage reaching the colon where there is exposure to colonic microbiota Williamson and Clifford, The microbiome plays a key role in catabolizing unabsorbed flavonoids into smaller molecules which may become bioavailable.

It is conceivable that heterogeneity in flavonoid absorption and metabolism may diminish beneficial associations between intakes and cognitive outcomes reported in studies. Ideally, urinary flavonoid excretion results would be taken into account in analyses, and to inform personalized health goals.

Overall, additional prospective studies conducted in diverse populations, and adequately powered intervention studies with long durations, are required to thoroughly examine the effect of consumption of the flavonoid subclasses of anthocyanins, flavanols, and flavanones on clinically relevant cognitive outcomes.

Moreover, the characterization of appropriate dosage, timeframes for intake, and form of flavonoids, remains to be fully determined. Whilst animal models have shown promising results with interventions of timeframes such as 2 months, this represents a considerably larger percentage of total lifespan for animals than it does for humans, and a longer time-frame could be needed to show enhanced outcomes in human trials.

Both acute and chronic effects of these flavonoid subclasses also need to be investigated using neuroimaging techniques in conjunction with cognitive and physiological measures to further elucidate the underlying biological mechanisms.

Furthermore, it should be acknowledged that studies in cognitively normal adults are unlikely to demonstrate large improvements in cognitive function, and therefore it is imperative that suitable, sensitive cognitive tests are utilized.

There is currently no clear evidence regarding the specific domains of cognition and memory that these flavonoid subclasses impact, with future studies requiring a range of cognitive domains to be investigated in order to determine those most likely to benefit.

If emerging evidence continues to suggest significant cognitive benefit, another important consideration is the optimum age for the initiation of supplementation of flavonoid intake. Indeed, the neuropathological hallmarks of AD begin to accumulate 15—20 years before symptoms manifest, implying that the optimal age for supplementing flavonoid consumption could be middle-age or younger.

As populations continue to focus on developing strategies to promote healthy aging, dietary interventions with flavonoids represents a promising avenue for future research.

However, many questions still need to be answered before a definite conclusion can be made regarding the extent to which consumption of anthocyanins, flavanols, and flavanones can protect the aging brain, and intake can be included in public health dietary recommendations.

SG and SR-S contributed to the conception and design of the work. SG prepared the first draft of the manuscript. SR-S, MW, CB, and RM revised the manuscript. All authors approved the final version of the manuscript. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers.

Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher. Supplementary Table 1 Intervention human studies published over the past 6 years investigating flavonoid consumption and cognitive outcomes.

Press Anghocyanins The systematic review Anthocyanihs published in Weightlifting techniques International Journal of Molecular Sciences was conducted by BioActor fhnction collaboration with Maastricht University and Anthocyanins and cognitive function functioj Inflammation and cancer prevention of berry anthocyanins dognitive cognitive performance. The research was Anthoocyanins by S. This systematic review of randomized Placebo-Controlled Studies in Humans provides further evidence into the beneficial effects of berry anthocyanins on cognitive performance such as attention and psychomotor speed, executive function, and memory. Moreover, effects on vascular function and cardiometabolic risk markers were investigated. Anthocyanins are a specific type of flavonoids abundantly found in various berries such as blueberry, black raspberry, and Aronia berry, to which these molecules confer the specific colours.

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