J Agric Food Chem — Rechner, A. Flavonois Mol. Cancer80, 95—

Flavonoids and mood regulation -

Brain Res Bull. Kravitz BA, Corrada MM, Kawas CH. Elevated C-reactive protein levels are associated with prevalent dementia in the oldest-old. Duong T, Nikolaeva M, Acton PJ.

Wood JA, Wood PL, Ryan R, Graff-Radford NR, Pilapil C, Robitaille Y, et al. Roberts RO, Geda YE, Knopman DS, Boeve BF, Christianson TJ, Pankratz VS, et al. Association of C-reactive protein with mild cognitive impairment. Zaciragic A, Lepara O, Valjevac A, Arslanagic S, Fajkic A, Hadzovic-Dzuvo A, et al.

Williams P, Sorribas A, Howes MJ. Nat Prod Rep. Szekely CA, Thorne JE, Zandi PP, Ek M, Messias E, Breitner JC, et al. Spencer JP, Vafeiadou K, Williams RJ, Vauzour D. Neuroinflammation: modulation by flavonoids and mechanisms of action. Mol Asp Med.

Spilsbury A, Vauzour D, Spencer JP, Rattray M. Regulation of NF-kappaB activity in astrocytes: effects of flavonoids at dietary-relevant concentrations. Biochem Biophys Res Commun. Vafeiadou K, Vauzour D, Lee HY, Rodriguez-Mateos A, Williams RJ, Spencer JP. The citrus flavanone naringenin inhibits inflammatory signalling in glial cells and protects against neuroinflammatory injury.

Arch Biochem Biophys. Nanri A, Yoshida D, Yamaji T, Mizoue T, Takayanagi R, Kono S. Dietary patterns and C-reactive protein in Japanese men and women. Am J Clin Nutr. Chun OK, Chung SJ, Claycombe KJ, Song WO. Serum C-reactive protein concentrations are inversely associated with dietary flavonoid intake in U.

Karlsen A, Retterstol L, Laake P, Paur I, Bohn SK, Sandvik L, et al. Anthocyanins inhibit nuclear factor-kappaB activation in monocytes and reduce plasma concentrations of pro-inflammatory mediators in healthy adults.

Widlansky ME, Duffy SJ, Hamburg NM, Gokce N, Warden BA, Wiseman S, et al. Effects of black tea consumption on plasma catechins and markers of oxidative stress and inflammation in patients with coronary artery disease. Freese R, Vaarala O, Turpeinen AM, Mutanen M. No difference in platelet activation or inflammation markers after diets rich or poor in vegetables, berries and apple in healthy subjects.

Eur J Nutr. Breteler MM. Grassi D, Desideri G, Necozione S, Lippi C, Casale R, Properzi G, et al. Blood pressure is reduced and insulin sensitivity increased in glucose-intolerant, hypertensive subjects after 15 days of consuming high-polyphenol dark chocolate.

Balzer J, Rassaf T, Heiss C, Kleinbongard P, Lauer T, Merx M, et al. Sustained benefits in vascular function through flavanol-containing cocoa in medicated diabetic patients a double-masked, randomized, controlled trial.

J Am Coll Cardiol. Sorond FA, Lipsitz LA, Hollenberg NK, Fisher ND. Cerebral blood flow response to flavanol-rich cocoa in healthy elderly humans. Neuropsychiatr Dis Treat. PubMed PubMed Central CAS Google Scholar.

Sorond FA, Hurwitz S, Salat DH, Greve DN, Fisher ND. Neurovascular coupling, cerebral white matter integrity, and response to cocoa in older people. Francis ST, Head K, Morris PG, Macdonald IA. The effect of flavanol-rich cocoa on the fMRI response to a cognitive task in healthy young people.

J Cardiovasc Pharmacol. The effects of flavanone-rich citrus juice on cognitive function and cerebral blood flow: an acute, randomised, placebo-controlled cross-over trial in healthy, young adults.

This study by Lamport et al. These findings suggest that a high intake of flavonoids could produce efficient and striking effects on brain vascular function. Gage FH. Mammalian neural stem cells. Zhao C, Deng W, Gage FH. Mechanisms and functional implications of adult neurogenesis.

Hollman PCH. Absorption, bioavailability, and metabolism of flavonoids. Pharm Biol. Xie Y, Yang W, Tang F, Chen X, Ren L. Antibacterial activities of flavonoids: structure-activity relationship and mechanism.

Curr Med Chem. Howell AB, Reed JD, Krueger CG, Winterbottom R, Cunningham DG, Leahy M. A-type cranberry proanthocyanidins and uropathogenic bacterial anti-adhesion activity. Duda-Chodak A. The inhibitory effect of polyphenols on human gut microbiota. J Physiol Pharmacol. PubMed CAS Google Scholar.

Nohynek LJ, Alakomi HL, Kahkonen MP, Heinonen M, Helander IM, Oksman-Caldentey KM, et al. Berry phenolics: antimicrobial properties and mechanisms of action against severe human pathogens. Nutr Cancer. Espley RV, Butts CA, Laing WA, Martell S, Smith H, McGhie TK, et al.

Dietary flavonoids from modified apple reduce inflammation markers and modulate gut microbiota in mice—3. Zhang L, Wang Y, Li D, Ho C-T, Li J, Wan X. The absorption, distribution, metabolism and excretion of procyanidins.

Food Funct. Anthocyanins and their gut metabolites reduce the adhesion of monocyte to TNFα-activated endothelial cells at physiologically relevant concentrations. Krga et al.

These findings suggest that flavonoids metabolised by gut microbiota could directly impact the development of atherosclerosis development in its early stages of development.

Verbeek R, van Tol EA, van Noort JM. Oral flavonoids delay recovery from experimental autoimmune encephalomyelitis in SJL mice. Wang P, Chen H, Zhu Y, McBride J, Fu J, Sang S. Oat avenanthramide-C 2c is biotransformed by mice and the human microbiota into bioactive metabolites—3.

Flavonoid metabolites reduce tumor necrosis factor-α secretion to a greater extent than their precursor compounds in human THP-1 monocytes.

Mol Nutr Food Res. This study by di Gesso et al. These findings suggest that specific combinations of flavonoids could produce optimal anti-inflammatory effects beyond that of their constituents. Wang et al.

These findings suggest that gut microbiota could play a key role in modifying the impact of flavonoids on classical AD neuropathology development. Prince M, Knapp M, Guerchet M, McCrone P, Prina M, Comas-Herrera A, et al.

Dementia UK: update. Download references. Norwich Medical School, Faculty of Medicine and Health Sciences, University of East Anglia, Norwich, NR4 7UQ, UK.

You can also search for this author in PubMed Google Scholar. Correspondence to David Vauzour. Emma Flanagan, Michael Müller, Michael Hornberger and David Vauzour declare they have no conflict of interest. This article does not contain any studies with human or animal subjects performed by any of the authors.

This article is part of the Topical Collection on Neurological Disease and Cognitive Function. Open Access This article is distributed under the terms of the Creative Commons Attribution 4.

Reprints and permissions. Flanagan, E. et al. Impact of Flavonoids on Cellular and Molecular Mechanisms Underlying Age-Related Cognitive Decline and Neurodegeneration.

Curr Nutr Rep 7 , 49—57 Download citation. Published : 27 April Issue Date : June Anyone you share the following link with will be able to read this content:. Sorry, a shareable link is not currently available for this article. Provided by the Springer Nature SharedIt content-sharing initiative.

Download PDF. Abstract Purpose of Review This review summarises the most recent evidence regarding the effects of dietary flavonoids on age-related cognitive decline and neurodegenerative diseases.

Recent Findings Recent evidence indicates that plant-derived flavonoids may exert powerful actions on mammalian cognition and protect against the development of age-related cognitive decline and pathological neurodegeneration.

Summary Mechanisms for the beneficial effects of flavonoids on age-related cognitive decline and dementia are discussed, including modulating signalling pathways critical in controlling synaptic plasticity, reducing neuroinflammation, promoting vascular effects capable of stimulating new nerve cell growth in the hippocampus, bidirectional interactions with gut microbiota and attenuating the extracellular accumulation of pathological proteins.

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Introduction Advances in medical science over the last century have resulted in a considerable increase in human life expectancy. Flavonoids, Age-Related Cognitive Decline and Neurodegeneration Even in the absence of pathological neurodegeneration, age-related cognitive decline has been consistently demonstrated in studies involving both animals and humans.

Mechanisms Underlying the Neuroprotective Effects of Flavonoids Despite the precise causes of cognitive decline remaining unclear, age-related neurodegeneration is considered to be underpinned by several interlinked cellular and molecular mechanisms, including cumulative damage due to chronic neuroinflammation, oxidative stress, impaired mitochondrial function, activation of neuronal apoptosis, deposition of aggregated proteins and excitotoxicity.

Reduction of Neuropathological Protein Accumulation The neuropathological hallmarks of AD are the extracellular deposition of amyloid plaques and the intracellular accumulation of hyperphosphorylated tau proteins—a neuronal microtubule-associated protein regulated by phosphorylation of various protein kinases [ 40 ].

Stimulation of Neuronal Signalling Pathways and Synaptic Plasticity Although the precise sites of the interactions between flavonoids and neuronal signalling pathways remain to be determined, based on existing evidence flavonoids may exert their effects through 1 modulating signalling cascades that control neuronal apoptosis; 2 modulating the expression of specific genes and 3 impacting mitochondrial activity [ 54 ].

Vascular Function and Angiogenesis The integrity of the vascular system becomes increasingly vital with increasing age. Interactions with the Microbiome The gastrointestinal tract plays a key role in protecting and promoting health, including regulating energy metabolism, acting as a barrier to potential toxic compounds present in ingested food and supporting the immune system.

Conclusion With an ageing population, age-related cognitive decline and neurodegeneration pose a significant challenge for the future. Article PubMed CAS Google Scholar Prince M, Bryce R, Albanese E, Wimo A, Ribeiro W, Ferri CP.

Article PubMed Google Scholar Vauzour D, Vafeiadou K, Rodriguez-Mateos A, Rendeiro C, Spencer JP. Article PubMed PubMed Central CAS Google Scholar Gu Y, Nieves JW, Stern Y, Luchsinger JA, Scarmeas N.

Article PubMed PubMed Central Google Scholar Solfrizzi V, Panza F, Frisardi V, Seripa D, Logroscino G, Imbimbo BP, et al. Article PubMed CAS Google Scholar Dixon RA, Wahlin A, Maitland SB, Hultsch DF, Hertzog C, Backman L.

Article Google Scholar Siedlecki KL, Salthouse TA, Berish DE. Article PubMed Google Scholar Barberger-Gateau P, Raffaitin C, Letenneur L, Berr C, Tzourio C, Dartigues JF, et al. Article PubMed CAS Google Scholar Kesse-Guyot E, Fezeu L, Andreeva VA, Touvier M, Scalbert A, Hercberg S, et al.

Article PubMed CAS Google Scholar Letenneur L, Proust-Lima C, Le GA, Dartigues JF, Barberger-Gateau P. Article Google Scholar Williams CM, El Mohsen MA, Vauzour D, Rendeiro C, Butler LT, Ellis JA, et al. Article PubMed CAS Google Scholar Goyarzu P, Malin DH, Lau FC, Taglialatela G, Moon WD, Jennings R, et al.

Article PubMed Google Scholar Barros D, Amaral OB, Izquierdo I, Geracitano L, Do Carmo Bassols Raseira M, Henriques AT, et al. Article PubMed CAS Google Scholar Ramirez MR, Izquierdo I, Do Carmo Bassols Raseira M, Zuanazzi JA, Barros D, Henriques AT. Article PubMed Google Scholar Rendeiro C, Vauzour D, Kean RJ, Butler LT, Rattray M, Spencer JP, et al.

Article PubMed CAS Google Scholar Devore EE, Kang JH, Breteler MM, Grodstein F. Article PubMed CAS PubMed Central Google Scholar Li Q, Zhao HF, Zhang ZF, Liu ZG, Pei XR, Wang JB, et al. Article Google Scholar Walsh DM, Teplow DB. Article PubMed Google Scholar Albert MS, DeKosky ST, Dickson D, Dubois B, Feldman HH, Fox NC, et al.

Article PubMed PubMed Central Google Scholar Mitchell AJ, Shiri-Feshki M. Article PubMed CAS Google Scholar Commenges D, Scotet V, Renaud S, Jacqmin-Gadda H, Barberger-Gateau P, Dartigues JF. Article PubMed CAS Google Scholar Price DL, Tanzi RE, Borchelt DR, Sisodia SS.

Article PubMed CAS Google Scholar Jones L, Harold D, Williams J. Article PubMed CAS Google Scholar Corder EH, Saunders AM, Strittmatter WJ, Schmechel DE, Gaskell PC, Small GW, et al. Article PubMed CAS Google Scholar Packard CJ, Westendorp RG, Stott DJ, Caslake MJ, Murray HM, Shepherd J, et al.

Article PubMed Google Scholar Whitehair DC, Sherzai A, Emond J, Raman R, Aisen PS, Petersen RC, et al. Article PubMed PubMed Central CAS Google Scholar Dai Q, Borenstein AR, Wu Y, Jackson JC, Larson EB.

Article PubMed PubMed Central CAS Google Scholar Field DT, Williams CM, Butler LT. Article PubMed CAS Google Scholar Scholey AB, French SJ, Morris PJ, Kennedy DO, Milne AL, Haskell CF. Article PubMed CAS Google Scholar Lamport DJ, Pal D, Moutsiana C, Field DT, Williams CM, Spencer JP, et al.

Article PubMed PubMed Central CAS Google Scholar Brickman AM, Khan UA, Provenzano FA, Yeung LK, Suzuki W, Schroeter H, et al. Article PubMed PubMed Central CAS Google Scholar Krikorian R, Nash TA, Shidler MD, Shukitt-Hale B, Joseph JA.

Article PubMed CAS Google Scholar Krikorian R, Shidler MD, Nash TA, Kalt W, Vinqvist-Tymchuk MR, Shukitt-Hale B, et al. Article PubMed PubMed Central CAS Google Scholar Desideri G, Kwik-Uribe C, Grassi D, Necozione S, Ghiadoni L, Mastroiacovo D, et al.

Article PubMed CAS Google Scholar Williams RJ, Spencer JP, Rice-Evans C. Article PubMed CAS Google Scholar Savonenko AV, Melnikova T, Hiatt A, Li T, Worley PF, Troncoso JC, et al.

Article PubMed CAS Google Scholar Walsh DM, Selkoe DJ. Article PubMed CAS Google Scholar Mori T, Rezai-Zadeh K, Koyama N, Arendash GW, Yamaguchi H, Kakuda N, et al.

Article PubMed CAS Google Scholar Rezai-Zadeh K, Arendash GW, Hou H, Fernandez F, Jensen M, Runfeldt M, et al. Article PubMed CAS Google Scholar Li Q, Zhao HF, Zhang ZF, Liu ZG, Pei XR, Wang JB, et al. Article PubMed CAS Google Scholar Ono K, Condron MM, Ho L, Wang J, Zhao W, Pasinetti GM, et al.

Article PubMed PubMed Central CAS Google Scholar Onozuka H, Nakajima A, Matsuzaki K, Shin RW, Ogino K, Saigusa D, et al. Article PubMed CAS Google Scholar Amit T, Avramovich-Tirosh Y, Youdim MB, Mandel S.

Article PubMed CAS Google Scholar Ehrnhoefer DE, Bieschke J, Boeddrich A, Herbst M, Masino L, Lurz R, et al. Article PubMed CAS Google Scholar Obregon DF, Rezai-Zadeh K, Bai Y, Sun N, Hou H, Ehrhart J, et al.

Article PubMed CAS Google Scholar Schroeter H, Bahia P, Spencer JPE, Sheppard O, Rattray M, Rice-Evans C, et al. Flowers, chocolates, organ donation — are you in? What is a tongue-tie? What parents need to know. Which migraine medications are most helpful?

How well do you score on brain health? Shining light on night blindness. Can watching sports be bad for your health? Beyond the usual suspects for healthy resolutions. April 14, These plant chemicals, found in most fruits and vegetables, may play an important role in cognitive fitness and dementia prevention.

Class in itself Flavonoids are phytochemicals commonly found in plant foods. Flavonoids and food There are six subclasses of flavonoids, which are abundant in most plant foods. Flavonoid subclass Common food sources Anthocyanidins berries red, blue, and purple , grapes, red wine Flavanols tea black, white, green, oolong , cocoa-based products, grapes, berries, apples, red wine Flavanones citrus fruit oranges, lemons, grapefruit Flavones parsley, thyme, celery, hot peppers Flavonols onions, peppers, broccoli, spinach, apples, berries, tea Polymers berries cranberries, blueberries, strawberries , wine, grapes, black tea Many factors in play Large human studies of flavonoids are still in their early phases, but initial findings show promise.

Color coordination So, to protect your brain from dementia, should you load up your plate with as many flavonoid-rich foods as possible? Share This Page Share this page to Facebook Share this page to Twitter Share this page via Email.

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Plus, get a FREE copy of the Best Diets for Cognitive Fitness. Nutr Hosp — Goyarzu F, Malin DH, Lau FC, Taglialatela G, Moon WD, Jennings R, Moy E, Moy D, Lippold S, Shukitt-Hale B, Joseph JA Blueberry supplemented diet: effects on object recognition memory and nuclear factor-kappa B levels in aged rats.

Harborne JB, Williams CA Advances in flavonoid research since Phytochemistry — Hishikawa K, Nakaki T, Fujita T Oral flavonoid supplementation attenuates atherosclerosis development in apolipoprotein E-deficient mice. Ho SC, Chan ASY, Ho YP, So EKF, Sham A, Zee B, Woo JLF Effects of soy isoflavone supplementation on cognitive function in Chinese postmenopausal women: a double-blind, randomized, controlled trial.

Howes JB, Bray K, Lorenz L, Smerdely P, Howes LG The effects of dietary supplementation with isoflavones from red clover on cognitive function in postmenopausal women. Climacteric — Huang JL, Fu ST, Jiang YY, Cao YB, Guo ML, Wang Y, Xu Z Protective effects of Nicotiflorin on reducing memory dysfunction, energy metabolism failure and oxidative stress in multi-infarct dementia model rats.

Joseph JA, Shukitt-Hale B, Lau FC Fruit polyphenols and their effects on neuronal signaling and behavior in senescence. Joseph JA, Denisova NA, Bielinski D, Fisher DR, Shukitt-Hale B Oxidative stress protection and vulnerability in aging: putative nutritional implications for intervention. Mech Ageing Dev — Joseph JA, Denisova N, Fisher D, Shukitt-Hale B, Bickford P, Prior R, Cao GH Age-related neurodegeneration and oxidative stress: putative nutritional intervention.

Neurol Clin — Joseph JA, Shukitt-Hale B, Denisova NA, Bielinski D, Martin A, McEwen JJ, Bickford PC Reversals of age-related declines in neuronal signal transduction, cognitive, and motor behavioral deficits with blueberry, spinach, or strawberry dietary supplementation.

J Neurosci — Joseph JA, Shukitt-Hale B, Denisova NA, Prior RL, Cao G, Martin A, Taglialatela G, Bickford PC Long-term dietary strawberry, spinach, or vitamin E supplementation retards the onset of age-related neuronal signal-transduction and cognitive behavioral deficits.

Kim DH, Jeon SJ, Son KH, Jung JW, Lee S, Yoon BH, Choi JW, Cheong JH, Ko KH, Ryu JH Effect of the flavonoid, oroxylin A, on transient cerebral hypoperfusion-induced memory impairment in mice.

Koda T, Kuroda Y, Imai H Protective effect of rutin against spatial memory impairment induced by trimethyltin in rats. Nutr Res — Kreijkamp-Kaspers S, Kok L, Grobbee DE, de Haan EHF, Aleman A, Lampe JW, van der Schouw YT Effect of soy protein containing isoflavones on cognitive function, bone mineral density, and plasma lipids in postmenopausal women: a randomized controlled trial.

J Am Med Assoc — Kritz-Silverstein D, Von Muhlen D, Barrett-Connor E, Bressel MAB Isoflavones and cognitive function in older women: the SOy and Postmenopausal Health in Aging SOPHIA Study.

Lau FC, Shukitt-Hale B, Joseph JA The beneficial effects of fruit polyphenols on brain aging. Neurobiol Aging S—S Neuropsychobiology — Lee YB, Lee HJ, Sohn HS Soy isoflavones and cognitive function.

J Nutr Biochem — Letenneur L, Proust-Lima C, Le Gouge A, Dartigues JF, Barberger-Gateau P Flavonoid intake and cognitive decline over a year period.

Am J Epidemiol — Manach C, Scalbert A, Morand C, Remesy C, Jimenez L Polyphenols: food sources and bioavailability. Am J Clin Nutr — Mangels AR, Messina V, Melina V Position of the American Dietetic Association and Dieticians of Canada: vegetarian diets.

J Am Diet Assoc — Article Google Scholar. Manly T, Robinson IH Sustained attention and the frontal lobes. Psychology Press, Hove, pp — Mix JA, Crews WD Jr An examination of the efficacy of Ginkgo biloba extract EGb on the neuropsychologic functioning of cognitively intact older adults.

J Altern Complement Med — Cogn Psychol — Moser DJ, Hoth KF, Robinson RG, Paulsen JS, Sinkey CA, Benjamin ML, Schultz SK, Haynes WG Blood vessel function and cognition in elderly patients with atherosclerosis.

Stroke E—E Arch Neurol Passamonti S, Vrhovsek U, Vanzo A, Mattivi F Fast access of some grape pigments to the brain. J Agric Food Chem — Petersen RC, Smith GE, Waring SC, Ivnik RJ, Tangalos EG, Kokmen E Mild cognitive impairment clinical characterization and outcome.

Am Med Assoc — CAS Google Scholar. Issues of assessment and evidence from fluency tests. Pipingas A, Silberstein RB, Vitetta L, Van Rooy C, Harris EV, Young JM, Frampton CM, Sali A, Nastasi J Improved cognitive performance after dietary supplementation with a pinus radiata bark extract formulation.

Phytother Res — Rabbitt P Methodology of frontal and executive function. Psychology Press, Hove. Rai GS, Shovlin C, Wesnes KA A double-blind, placebo controlled-study of Ginkgo biloba extract tanakan in elderly outpatients with mild to moderate memory impairment.

Curr Med Res Opin — Ramirez MR, Izquierdo I, Raseira MDB, Zuanazzi JA, Barros D, Henriques AT Effect of lyophilised Vaccinium berries on memory, anxiety and locomotion in adult rats. Pharmacol Res — Reed J Cranberry flavonoids, atherosclerosis and cardiovascular health.

Crit Rev Food Sci Nutr — Rohdewald P A review of the French maritime pine bark extract Pycnogenol ® , a herbal medication with a diverse clinical pharmacology. Int J Clin Pharmacol Ther — Clin Neurol Neurosurg — Am J Psychiatry — Rugg MD, Henson RNA Episodic memory retrieval: an event-related functional neuroimaging perspective.

In: Parker AE, Wilding EL, Bussey T eds The cognitive neuroscience of memory encoding and retrieval. Psychology Press, Hove, pp 83— Ryan J, Croft K, Mori T, Wesnes K, Spong J, Downey L, Kure C, Lloyd J, Stough C An examination of the effects of the antioxidant Pycnogenol ® on cognitive performance, serum lipid profile, endocrinological and oxidative stress biomarkers in an elderly population.

J Psychopharmacol Sattar N, Ferns G Endothelial dysfunction. In: Stanner S ed Cardiovascular disease: diet, nutrition and emerging risk factors. Blackwell Publishing, Oxford, pp 63— Shang YZ, Qin BW, Cheng JJ, Miao H Prevention of oxidative injury by flavonoids from stems and leaves of Scutellaria baicalensis Georgi in PC12 cells.

Shukitt-Hale B, Carey A, Simon L, Mark DA, Joseph JA Effects of Concord grape juice on cognitive and motor deficits in aging. Nutrition — Spencer JP The interactions of flavonoids within neuronal signalling pathways. Genes Nutr — Spencer, JPE Flavonoids: modulators of brain function?

Br J Nutr 99 E-Suppl 1 :ES60—ES Spencer JPE, Whiteman M, Jenner P, Halliwell B 5-S-cysteinyl-conjugates of catecholamines induce cell damage, extensive DNA base modification and increases in caspase-3 activity in neurons.

J Neurochem — Exp Neurol — Sun SW, Yu HQ, Zhang H, Zheng YL, Wang JJ, Luo L Quercetin attenuates spontaneous behavior and spatial memory impairment in d-galactose-treated mice by increasing brain antioxidant capacity. Tagawa H, Tomoike H, Nakamura M Putative mechanisms of the impairment of endothelium-dependent relaxation of the aorta with atheromatous plaque in heritable hyperlipidemic rabbits.

Circ Res — Vauzour D, Vafeiadou K, Rodriguez-Mateos A, Rendeiro C, Spencer JPE The neuroprotective potential of flavonoids: a multiplicity of effects. Wechsler D WAIS-R manual: Wechsler adult intelligence scale-revised.

The Psychological Corporation, New York. WHO Medium-term strategic plan — and proposed programme budget — World Health Organization, Geneva.

Williams CM, El Mohsen MA, Vauzour D, Rendeiro C, Butler LT, Ellis JA, Whiteman M, Spencer JPE Blueberry-induced changes in spatial working memory correlate with changes in hippocampal CREB phosphorylation and brain-derived neurotrophic factor BDNF levels. Free Radic Biol Med — Williams RJ, Spencer JPE, Rice-Evans C Flavonoids: antioxidants or signalling molecules?

Wiseman H, JD OReilly, Adlercreutz H, Mallet A, Bowey EA, Rowland IR, Sanders TA Isoflavone phytoestrogens consumed in soy decrease F 2-isoprostane concentrations and increase resistance of low-density lipoprotein to oxidation in humans.

Woo J, Lau E, Ho SC, Cheng F, Chan C, Chan ASY, Haines CJ, Chan TYK, Li MMP, Sham A Comparison of Pueraria lobata with hormone replacement therapy in treating the adverse health consequences of menopause. Download references. Spencer, Dr. Butler and Dr. School of Psychology and Clinical Language Sciences, University of Reading, Earley Gate, Whiteknights, PO Box , Reading, RG6 6AL, UK.

Anna L. Macready, Judi A. Ellis, Claire M. Department of Food and Nutritional Sciences, School of Chemistry, Food and Pharmacy, University of Reading, Reading, UK. Macready, Orla B. You can also search for this author in PubMed Google Scholar. Correspondence to Laurie T. Reprints and permissions.

Macready, A. et al. Flavonoids and cognitive function: a review of human randomized controlled trial studies and recommendations for future studies.

Genes Nutr 4 , — Download citation. Received : 19 July Accepted : 21 July Published : 13 August Issue Date : December Anyone you share the following link with will be able to read this content:. Sorry, a shareable link is not currently available for this article.

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Abstract Evidence in support of the neuroprotective effects of flavonoids has increased significantly in recent years, although to date much of this evidence has emerged from animal rather than human studies. Introduction With the number of people over the age of 60 expected to double between and [ 71 ], the projected incidence of age-related neurodegenerative diseases, and related health care costs, is also set to rise significantly.

Table 1 Characteristics of included human flavonoid RCTs Full size table. Results Across the 15 studies reported here researchers used a total of 55 separate cognitive performance measures comprising two general or global cognitive function tasks, three IQ measures, eight psychomotor speed tasks, 22 executive function and working memory tasks and 20 memory tasks see Table 2.

Table 2 Neuropsychological focus for 55 measures used in 14 human flavonoid RCT studies Full size table.

Barfoot, K. and Lamport, D. Nutrients, 13 7. ISSN It Flaavonoids Flavonoids and mood regulation to refer to the publisher's version if you intend to cite from this work. See Guidance on citing. To link to this item DOI:

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Not really, according to Dr. She says that the standard advice to follow a plant-based diet as much as possible still applies, and eating a variety of colors is a good idea.

How much is enough? Yeh says although there is still no definite recommended daily intake for flavonoids, aiming for the suggested five to nine servings of fruits and vegetables a day is a good goal.

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April 14, These plant chemicals, found in most fruits and vegetables, may play an important role in cognitive fitness and dementia prevention.

Class in itself Flavonoids are phytochemicals commonly found in plant foods. Flavonoids and food There are six subclasses of flavonoids, which are abundant in most plant foods. Flavonoid subclass Common food sources Anthocyanidins berries red, blue, and purplegrapes, red wine Flavanols tea black, white, green, oolongcocoa-based products, grapes, berries, apples, red wine Flavanones citrus fruit oranges, lemons, grapefruit Flavones parsley, thyme, celery, hot peppers Flavonols onions, peppers, broccoli, spinach, apples, berries, tea Polymers berries cranberries, blueberries, strawberrieswine, grapes, black tea Many factors in play Large human studies of flavonoids are still in their early phases, but initial findings show promise.

Color coordination So, to protect your brain from dementia, should you load up your plate with as many flavonoid-rich foods as possible? Share This Page Share this page to Facebook Share this page to Twitter Share this page via Email. Print This Page Click to Print.

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Plus, get a FREE copy of the Best Diets for Cognitive Fitness. Sign me up. Flavonoid subclass. Common food sources. berries red, blue, and purplegrapes, red wine.

citrus fruit oranges, lemons, grapefruit. parsley, thyme, celery, hot peppers. onions, peppers, broccoli, spinach, apples, berries, tea. berries cranberries, blueberries, strawberrieswine, grapes, black tea.

: Flavonoids and mood regulation

Abstract/Summary	The mechanisms of action may include, but are not limited to, promoting the growth of beneficial bacteria while inhibiting the proliferation of pathogens, increasing microbial diversity, and stimulating the production of beneficial metabolites such as SCFAs to maintain overall health. Reprints and permissions. Walsh DM, Teplow DB. Methods , 41, — For instance, studies suggest they reduce cell-damaging free radicals and soothe inflammation. Wang, Y.
Special Issue: Nutrients and Brain Health	Treatment durations vary from 2 weeks [ 14 ] to 13 months [ 7 ], with no obvious relationship between cognitive change and treatment duration. Most of the studies delivered flavonoids via supplements, although one trial also used soy milk [ 13 ] and another used a flavonol-rich chocolate drink [ 14 ]. As outlined earlier, previous animal studies have shown that flavonoids improve visuospatial memory or visuospatial working memory [ 1 , 23 , 31 , 65 , 66 , 72 ]. Of more concern, fewer than half actually investigated aspects of visuospatial memory or visuospatial working memory [ 13 , 21 , 22 , 32 , 48 , 57 ]. Choice of cognitive tasks should also be guided by significant findings in previous, similar flavonoid studies, perhaps in combination with related measures targeting the particular cognitive domain of interest. Most of the same tests were used in these three studies; this continuity of cognitive tasks enables comparisons to be drawn across studies, and helps future studies to determine which factor will is likely to promote treatment success: isoflavone dose, age of target population or an interaction between the two. Most of the studies using healthy populations did not formally screen for cognitive status. Screening is an important consideration, as there is a danger of including participants with MCI within a healthy study sample, which makes interpretation difficult, as results may not be transferable to cognitively healthy populations. Of the three studies using healthy populations that did screen for cognitive impairment, all used the MMSE; one used a cut off score of 27 [ 22 ] for cognitive health, another chose 24 [ 41 ] and a third chose 23 [ 21 ]. If screening tools are to be used as standard, it is important to reach a consensus regarding cut off scores for cognitive health, as samples with lower cut off scores may include individuals with MCI. The traditional MMSE cut off score used in dementia screening is 24, but a recent assessment of diagnostic accuracy suggests that a cut off of 27 is the optimal score for excluding cognitively impaired individuals [ 44 ]. In line with findings from animal studies which show a slowing or even a reversal of age-related decline [ 26 , 27 ], the majority of the studies reviewed looked at flavonoids in the context of older populations, with the exception of the young adult isoflavone study [ 11 ] and the cocoa flavonol study with to year-old female students [ 14 ]. While the ongoing study of flavonoid intake in older populations is important, it is possible that the window of opportunity for slowing or reversal of age-related declines by dietary means occurs much earlier in the life-cycle, so it makes sense to also consider younger populations. Indeed, both studies showed significant differences on tasks of executive function, and the isoflavone trial also found improvements in memory tasks [ 11 ]. Finally, available evidence is limited by a lack of consideration of genetic factors which may influence short- and long-term responses to flavonoid intake, dose-response relationships, absorption, metabolism and excretion factors which influence the bioavailability and efficacy of flavonoids beneficial to cognitive function. Variations in genetic polymorphisms have been largely ignored in human flavonoid epidemiological and intervention studies. Human flavonoid RCT research with respect to cognitive function is at a very early stage, and conclusions are not yet easy to reach. Significant benefits to cognition have been reported in the majority of studies, mainly in executive function, working memory, other memory functions and more general measures such as processing speed. However, there is little consistency across studies in terms of the cognitive domains measured, and the tasks used. While a wide range of tasks has been used, measures of important areas of everyday cognitive functioning are notable by their absence, for instance, prospective and implicit memory. Moreover, although a wide range of tasks have been used within each cognitive domain, measurement of the full range of specific functions within these domains has by no means been covered. Overall, the choice of individual outcome measures has been inconsistent, and there is general confusion as to what the various tasks actually measure. Moreover, the choice of outcome measures does not generally appear to have been guided by results from relevant animal and human flavonoid studies. There is still an over-dependence on general measures of cognitive function that have not been shown to be sensitive to short-term changes over weeks or months in cognitively healthy populations, and which do not inform about specific cognitive functions. The wide range of treatment doses, delivery methods and intervention durations also make interpretation difficult. These findings argue for a more systematic approach to exploring cognitive function, across multiple cognitive domains and across multiple functions within domains, addressing the omissions noted above. Overall, there is a clear and continuing need to explore more fully the relationship between flavonoid intake and cognitive function, and future studies should seek to cover the whole range of functions before a full understanding of flavonoid-mediated cognitive change can be gained. In this potentially fruitful area of human cognitive research, this can be achieved by determining cognitive outcome measures that are sensitive, simple and specific to different cognitive domains. Andres-Lacueva C, Shukitt-Hale B, Galli RL, Jauregui O, Lamuela-Raventos RM, Joseph JA Anthocyanins in aged blueberry-fed rats are found centrally and may enhance memory. Nutr Neurosci — Article CAS PubMed Google Scholar. Baddeley A Testing executive function with a paper-and-pencil test. In: Rabbitt P ed Methodology of executive and frontal lobe function. Psychology Press, Hove, pp 61— Google Scholar. Barros D, Amaral OB, Izquierdo I, Geracitano L, Raseira M, Henriques AT, Ramirez MR Behavioral and genoprotective effects of Vaccinium berries intake in mice. Pharmacol Biochem Behav — Burgess PW Theory and methodology in executive function research. In: Rabbitt P ed Methodology of frontal and executive function. Psychology Press, Hove, pp 81— Carluccio MA, Siculella L, Ancora MA, Massaro M, Scoditti E, Storelli C, Visioli F, Distante A, De Caterina R Olive oil and red wine antioxidant polyphenols inhibit endothelial activation: Antiatherogenic properties of Mediterranean diet phytochemicals. Arterioscler Thromb Vasc Biol — Casadesus G, Shukitt-Hale B, Joseph JA Qualitative versus quantitative caloric intake: are they equivalent paths to successful aging? Neurobiol Aging — Article PubMed Google Scholar. Fertil Steril — Cho J, Kang JS, Long PH, Jing J, Back Y, Chung KS Antioxidant and memory enhancing effects of purple sweet potato anthocyanin and Cordyceps mushroom extract. Arch Pharm Res — Duffy R, Wiseman H, File SE Improved cognitive function in postmenopausal women after 12 weeks of consumption of a soya extract containing isoflavones. File SE, Hartley DE, Elsabagh S, Duffy R, Wiseman H Cognitive improvement after 6 weeks of soy supplements in postmenopausal women is limited to frontal lobe function. Menopause File SE, Jarrett N, Fluck E, Duffy R, Casey K, Wiseman H Eating soya improves human memory. Psychopharmacology — Folstein MF, Folstein SE, McHugh PR Mini-mental state: practical method for grading cognitive state of patients for clinician. J Psychiatr Res — Fournier LR, Ryan BTA, Robison LM, Wiediger M, Park JS, Chew BP, McGuire MK, Sclar DA, Skaer TL, Beerman KA The effects of soy milk and isoflavone supplements on cognitive performance in healthy, postmenopausal women. J Nutr Health Aging CAS PubMed Google Scholar. Francis ST, Head K, Morris PG, Macdonald IA The effect of flavanol-rich cocoa on the fMRI response to a cognitive task in healthy young people. J Cardiovasc Pharmacol S—S Frick M, Weidinger F Endothelial function: a surrogate endpoint in cardiovascular studies? Curr Pharm Design — Article CAS Google Scholar. Galli RL, Shukitt-Hale B, Youdim KA, Joseph JA Fruit polyphenolics and brain aging: nutritional interventions targeting age-related neuronal and behavioral deficits. Ann NY Acad Sci — Gonzalez-Gallego J, Sanchez-Campos S, Tunon MJ Anti-inflammatory properties of dietary flavonoids. Nutr Hosp — Goyarzu F, Malin DH, Lau FC, Taglialatela G, Moon WD, Jennings R, Moy E, Moy D, Lippold S, Shukitt-Hale B, Joseph JA Blueberry supplemented diet: effects on object recognition memory and nuclear factor-kappa B levels in aged rats. Harborne JB, Williams CA Advances in flavonoid research since Phytochemistry — Hishikawa K, Nakaki T, Fujita T Oral flavonoid supplementation attenuates atherosclerosis development in apolipoprotein E-deficient mice. Ho SC, Chan ASY, Ho YP, So EKF, Sham A, Zee B, Woo JLF Effects of soy isoflavone supplementation on cognitive function in Chinese postmenopausal women: a double-blind, randomized, controlled trial. Howes JB, Bray K, Lorenz L, Smerdely P, Howes LG The effects of dietary supplementation with isoflavones from red clover on cognitive function in postmenopausal women. Climacteric — Huang JL, Fu ST, Jiang YY, Cao YB, Guo ML, Wang Y, Xu Z Protective effects of Nicotiflorin on reducing memory dysfunction, energy metabolism failure and oxidative stress in multi-infarct dementia model rats. Joseph JA, Shukitt-Hale B, Lau FC Fruit polyphenols and their effects on neuronal signaling and behavior in senescence. Joseph JA, Denisova NA, Bielinski D, Fisher DR, Shukitt-Hale B Oxidative stress protection and vulnerability in aging: putative nutritional implications for intervention. Mech Ageing Dev — Joseph JA, Denisova N, Fisher D, Shukitt-Hale B, Bickford P, Prior R, Cao GH Age-related neurodegeneration and oxidative stress: putative nutritional intervention. Neurol Clin — Joseph JA, Shukitt-Hale B, Denisova NA, Bielinski D, Martin A, McEwen JJ, Bickford PC Reversals of age-related declines in neuronal signal transduction, cognitive, and motor behavioral deficits with blueberry, spinach, or strawberry dietary supplementation. J Neurosci — Joseph JA, Shukitt-Hale B, Denisova NA, Prior RL, Cao G, Martin A, Taglialatela G, Bickford PC Long-term dietary strawberry, spinach, or vitamin E supplementation retards the onset of age-related neuronal signal-transduction and cognitive behavioral deficits. Kim DH, Jeon SJ, Son KH, Jung JW, Lee S, Yoon BH, Choi JW, Cheong JH, Ko KH, Ryu JH Effect of the flavonoid, oroxylin A, on transient cerebral hypoperfusion-induced memory impairment in mice. Koda T, Kuroda Y, Imai H Protective effect of rutin against spatial memory impairment induced by trimethyltin in rats. Nutr Res — Kreijkamp-Kaspers S, Kok L, Grobbee DE, de Haan EHF, Aleman A, Lampe JW, van der Schouw YT Effect of soy protein containing isoflavones on cognitive function, bone mineral density, and plasma lipids in postmenopausal women: a randomized controlled trial. J Am Med Assoc — Kritz-Silverstein D, Von Muhlen D, Barrett-Connor E, Bressel MAB Isoflavones and cognitive function in older women: the SOy and Postmenopausal Health in Aging SOPHIA Study. Lau FC, Shukitt-Hale B, Joseph JA The beneficial effects of fruit polyphenols on brain aging. Neurobiol Aging S—S Neuropsychobiology — Lee YB, Lee HJ, Sohn HS Soy isoflavones and cognitive function. J Nutr Biochem — Letenneur L, Proust-Lima C, Le Gouge A, Dartigues JF, Barberger-Gateau P Flavonoid intake and cognitive decline over a year period. Am J Epidemiol — Manach C, Scalbert A, Morand C, Remesy C, Jimenez L Polyphenols: food sources and bioavailability. Am J Clin Nutr — Mangels AR, Messina V, Melina V Position of the American Dietetic Association and Dieticians of Canada: vegetarian diets. J Am Diet Assoc — Article Google Scholar. Manly T, Robinson IH Sustained attention and the frontal lobes. Psychology Press, Hove, pp — Mix JA, Crews WD Jr An examination of the efficacy of Ginkgo biloba extract EGb on the neuropsychologic functioning of cognitively intact older adults. J Altern Complement Med — Cogn Psychol — Moser DJ, Hoth KF, Robinson RG, Paulsen JS, Sinkey CA, Benjamin ML, Schultz SK, Haynes WG Blood vessel function and cognition in elderly patients with atherosclerosis. Stroke E—E Arch Neurol Passamonti S, Vrhovsek U, Vanzo A, Mattivi F Fast access of some grape pigments to the brain. J Agric Food Chem — Petersen RC, Smith GE, Waring SC, Ivnik RJ, Tangalos EG, Kokmen E Mild cognitive impairment clinical characterization and outcome. Am Med Assoc — CAS Google Scholar. Issues of assessment and evidence from fluency tests. Pipingas A, Silberstein RB, Vitetta L, Van Rooy C, Harris EV, Young JM, Frampton CM, Sali A, Nastasi J Improved cognitive performance after dietary supplementation with a pinus radiata bark extract formulation. Phytother Res — Rabbitt P Methodology of frontal and executive function. Psychology Press, Hove. Rai GS, Shovlin C, Wesnes KA A double-blind, placebo controlled-study of Ginkgo biloba extract tanakan in elderly outpatients with mild to moderate memory impairment. Curr Med Res Opin — Ramirez MR, Izquierdo I, Raseira MDB, Zuanazzi JA, Barros D, Henriques AT Effect of lyophilised Vaccinium berries on memory, anxiety and locomotion in adult rats. Pharmacol Res — Reed J Cranberry flavonoids, atherosclerosis and cardiovascular health. Crit Rev Food Sci Nutr — Rohdewald P A review of the French maritime pine bark extract Pycnogenol ® , a herbal medication with a diverse clinical pharmacology. Int J Clin Pharmacol Ther — Clin Neurol Neurosurg — Am J Psychiatry — Rugg MD, Henson RNA Episodic memory retrieval: an event-related functional neuroimaging perspective. In: Parker AE, Wilding EL, Bussey T eds The cognitive neuroscience of memory encoding and retrieval. Psychology Press, Hove, pp 83— Ryan J, Croft K, Mori T, Wesnes K, Spong J, Downey L, Kure C, Lloyd J, Stough C An examination of the effects of the antioxidant Pycnogenol ® on cognitive performance, serum lipid profile, endocrinological and oxidative stress biomarkers in an elderly population. J Psychopharmacol Sattar N, Ferns G Endothelial dysfunction. In: Stanner S ed Cardiovascular disease: diet, nutrition and emerging risk factors. Blackwell Publishing, Oxford, pp 63— Shang YZ, Qin BW, Cheng JJ, Miao H Prevention of oxidative injury by flavonoids from stems and leaves of Scutellaria baicalensis Georgi in PC12 cells. Shukitt-Hale B, Carey A, Simon L, Mark DA, Joseph JA Effects of Concord grape juice on cognitive and motor deficits in aging. Nutrition — Spencer JP The interactions of flavonoids within neuronal signalling pathways. Genes Nutr — Spencer, JPE Flavonoids: modulators of brain function? Br J Nutr 99 E-Suppl 1 :ES60—ES Spencer JPE, Whiteman M, Jenner P, Halliwell B 5-S-cysteinyl-conjugates of catecholamines induce cell damage, extensive DNA base modification and increases in caspase-3 activity in neurons. J Neurochem — Exp Neurol — Sun SW, Yu HQ, Zhang H, Zheng YL, Wang JJ, Luo L Quercetin attenuates spontaneous behavior and spatial memory impairment in d-galactose-treated mice by increasing brain antioxidant capacity. Tagawa H, Tomoike H, Nakamura M Putative mechanisms of the impairment of endothelium-dependent relaxation of the aorta with atheromatous plaque in heritable hyperlipidemic rabbits. Circ Res — Vauzour D, Vafeiadou K, Rodriguez-Mateos A, Rendeiro C, Spencer JPE The neuroprotective potential of flavonoids: a multiplicity of effects. Wechsler D WAIS-R manual: Wechsler adult intelligence scale-revised. The Psychological Corporation, New York. WHO Medium-term strategic plan — and proposed programme budget — World Health Organization, Geneva. Williams CM, El Mohsen MA, Vauzour D, Rendeiro C, Butler LT, Ellis JA, Whiteman M, Spencer JPE Blueberry-induced changes in spatial working memory correlate with changes in hippocampal CREB phosphorylation and brain-derived neurotrophic factor BDNF levels. Free Radic Biol Med — Williams RJ, Spencer JPE, Rice-Evans C Flavonoids: antioxidants or signalling molecules? Wiseman H, JD OReilly, Adlercreutz H, Mallet A, Bowey EA, Rowland IR, Sanders TA Isoflavone phytoestrogens consumed in soy decrease F 2-isoprostane concentrations and increase resistance of low-density lipoprotein to oxidation in humans. Woo J, Lau E, Ho SC, Cheng F, Chan C, Chan ASY, Haines CJ, Chan TYK, Li MMP, Sham A Comparison of Pueraria lobata with hormone replacement therapy in treating the adverse health consequences of menopause. Download references. Spencer, Dr. Butler and Dr. School of Psychology and Clinical Language Sciences, University of Reading, Earley Gate, Whiteknights, PO Box , Reading, RG6 6AL, UK. Anna L. Macready, Judi A. Ellis, Claire M. Department of Food and Nutritional Sciences, School of Chemistry, Food and Pharmacy, University of Reading, Reading, UK. Macready, Orla B. You can also search for this author in PubMed Google Scholar. Correspondence to Laurie T. Reprints and permissions. Macready, A. et al. Flavonoids and cognitive function: a review of human randomized controlled trial studies and recommendations for future studies. Genes Nutr 4 , — Download citation. Received : 19 July Accepted : 21 July Published : 13 August Issue Date : December Anyone you share the following link with will be able to read this content:. Sorry, a shareable link is not currently available for this article. Provided by the Springer Nature SharedIt content-sharing initiative. Skip to main content. Search all BMC articles Search. Download PDF. Volume 4 Supplement 4. Abstract Evidence in support of the neuroprotective effects of flavonoids has increased significantly in recent years, although to date much of this evidence has emerged from animal rather than human studies. Introduction With the number of people over the age of 60 expected to double between and [ 71 ], the projected incidence of age-related neurodegenerative diseases, and related health care costs, is also set to rise significantly. Table 1 Characteristics of included human flavonoid RCTs Full size table. Effects of MVPA and flavonoid ingestion may be mediated in part through elevations in circulating gut-derived phenolic metabolites, but this linkage has not yet been conclusively established Nieman et al. MVPA does enhance the release of gut-derived phenolic metabolites following chronic flavonoid ingestion. In a randomized trial with long-distance runners featuring a day intervention with a flavonoid-rich supplement or placebo , serum metabolic signatures from colonic flavonoid metabolites derived from green tea or berries were significantly elevated for at least 14 h coincident with a 3-day intensified exercise period, and these changes persisted through post-exercise recovery Nieman et al. Microbial metabolites were dramatically elevated once the workout commenced — the release of the metabolites into plasma was stimulated by physical exertion. In another study, the combination of 2 weeks of flavonoid supplementation and acute exercise both 45 min brisk walking and 2. These data indicated that acute exercise bouts both brisk walking and intensive running combined with flavonoid supplementation, and an elevated fitness status associated with habitual running, were linked to elevations in plasma levels of gut-derived phenolics. Figure 3. Post-exercise change for 15 selected and grouped plasma gut-derived phenolics. P -values indicate contrasts with the placebo—sit group. Data are represented as means with standard errors of the mean. Several underlying mechanisms could explain these results including flavonoid- and exercise-induced changes in gut permeability and transporter function, increases in gut microbiota richness, and altered gastrointestinal motility and transport rate Nieman et al. Chronic MVPA can modify the composition and functional capacity of the gut microbiota Hughes and Holscher, Cross-sectional human studies have revealed greater α-diversity and an enriched profile of short chain fatty acids SCFAs in athletes compared to sedentary controls Barton et al. One examination of phenotypic features across 3, individuals found a linkage between microbiome diversity and MVPA frequency and duration that was independent of major dietary factors and BMI Manor et al. The interaction between MVPA and the gut microbiota is bidirectional. As already noted, flavonoids are catabolized by and influence composition of the microbiota, and exercise stimulated the bioavailability of flavonoid metabolites Nieman et al. The gut microbiota also has an influence on exercise performance by producing SCFAs that increase muscle blood flow and insulin sensitivity, and can be utilized as fuel Hughes and Holscher, It is therefore reasonable to posit that the connection between physical activity e. Figure 4. Higher flavonoid intake may influence cognitive function by augmenting gut microbial diversity and functionality and increasing circulating levels of gut-derived phenolic metabolites. Moderate-to-vigorous physical activity MVPA adds to this effect by enhancing the release of gut-derived metabolites and improving cognitive function. A complex interaction of factors lifestyle, diet, genetics, and environment all appear to exert influence on cognition in the aging brain. Emerging evidence suggests that there may be potentiating interactions between some of these, including flavonoid intake, microbiome, and physical activity levels exercise. What are the mechanisms responsible for the benefits to cognition, and how can they be fully demonstrated? We hypothesize that it is the phytoactive metabolites from flavonoid ingestion, after catabolism at the gut microbiome level , that interact with cellular and molecular targets signaling pathways to improve neuron connectivity and promote vascular and peripheral flow in the brain. Exercise has demonstrated ability to provoke a surge of these phytoactive flavonoid metabolites into circulation. It follows that the positive cognitive benefits from dietary flavonoids and regular moderate exercise may be a consequence of the enhanced circulation of gut-derived flavonoid metabolites, mediated by the activities of the colonic microbiota. CC: cognition. DN: physical movement. AN: microbiome. All authors contributed to and approved the manuscript. Some of the work described in this review was partially funded through USDA-ARS Project Nos. 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. First and foremost, we thank the generous people who participate in our research. Without them, our research would literally be impossible. Ahles, S. Effects of berry anthocyanins on cognitive performance, vascular function and cardiometabolic risk markers: a systematic review of randomized placebo-controlled intervention studies in humans. doi: PubMed Abstract CrossRef Full Text Google Scholar. Ahmed, M. The protective effects of a polyphenol-enriched protein powder on exercise-induced susceptibility to virus infection. Allen, J. Exercise alters gut microbiota composition and function in lean and obese humans. Sports Exerc. Amin, H. Anthocyanins and their physiologically relevant metabolites alter the expression of IL-6 and VCAM-1 in CD40L and oxidized LDL challenged vascular endothelial cells. Food Res. Anderson, J. A preliminary examination of gut microbiota, sleep, and cognitive flexibility in healthy older adults. Sleep Med. Google Scholar. Angelino, D. Nutrients Anhe, F. A polyphenol-rich cranberry extract protects from diet-induced obesity, insulin resistance and intestinal inflammation in association with increased Akkermansia spp. population in the gut microbiota of mice. Gut 64, — Ayaz, M. Flavonoids as prospective neuroprotectants and their therapeutic propensity in aging associated neurological disorders. Aging Neurosci. Badshah, H. Anthocyanins attenuate body weight gain via modulating neuropeptide Y and GABAB1 receptor in rats hypothalamus. Neuropeptides 47, — Bajaj, J. Elderly patients have an altered gut-brain axis regardless of the presence of cirrhosis. Banfi, D. Impact of microbial metabolites on microbiota-gut-brain axis in inflammatory bowel disease. Barton, W. The microbiome of professional athletes differs from that of more sedentary subjects in composition and particularly at the functional metabolic level. Gut 67, — Bird, R. Aceves-Martins, M. The effect of grape interventions on cognitive and mental performance in healthy participants and those with mild cognitive impairment: a systematic review of randomized controlled trials. Boespflug, E. Enhanced neural activation with blueberry supplementation in mild cognitive impairment. Borsom, E. Do the bugs in your gut eat your memories? Brain Sci. Calabrese, V. Cellular stress responses, hormetic phytochemicals and vitagenes in aging and longevity. Acta , — Canipe, L. Diversity of the gut-microbiome related to cognitive behavioral outcomes in healthy older adults. Cheatham, C. Consumption of wild blueberries for 6 months improves speed of processing in to year-olds experiencing mild cognitive decline. Chen, F. Effects of exercise training interventions on executive function in older adults: a systematic review and meta-analysis. Sports Med. Chu, C. The microbiota regulate neuronal function and fear extinction learning. Nature , — Cremonini, E. Cronin, O. mSystems 3:e Cryan, J. Mind-altering microorganisms: the impact of the gut microbiota on brain and behaviour. Cunha, C. A simple role for BDNF in learning and memory? Deledda, A. Diet-derived antioxidants and their role in inflammation, obesity and gut microbiota modulation. Antioxidants Devenney, K. The effects of an extensive exercise programme on the progression of mild cognitive impairment MCI : study protocol for a randomised controlled trial. BMC Geriatr. Dinan, T. Collective unconscious: how gut microbes shape human behavior. Docampo, M. Glucuronidated flavonoids in neurological protection: structural analysis and approaches for chemical and biological synthesis. Food Chem. Dodd, G. Acute effects of flavonoid-rich blueberry on cognitive and vascular function in healthy older adults. Aging 5, — Duda-Chodak, A. Interaction of dietary compounds, especially polyphenols, with the intestinal microbiota: a review. Duffy, K. A blueberry-enriched diet provides cellular protection against oxidative stress and reduces a kainate-induced learning impairment in rats. Aging 29, — Erickson, K. Physical activity predicts gray matter volume in late adulthood: the cardiovascular health study. Neurology 75, — Espin, J. The gut microbiota: a key factor in the therapeutic effects of poly phenols. Esposito, D. Black currant anthocyanins attenuate weight gain and improve glucose metabolism in diet-induced obese mice with intact, but not disrupted, gut microbiome. Flanagan, E. Impact of flavonoids on cellular and molecular mechanisms underlying age-related cognitive decline and neurodegeneration. Galli, R. Blueberry supplemented diet reverses age-related decline in hippocampal HSP70 neuroprotection. Aging 27, — Gardener, S. Intake of products containing anthocyanins, flavanols, and flavanones, and cognitive function: a narrative review. Gow, A. Activity participation and cognitive aging from age 50 to 80 in the Glostrup cohort. Gratton, G. Dietary flavanols improve cerebral cortical oxygenation and cognition in healthy adults. Gu, Y. Dietary cocoa reduces metabolic endotoxemia and adipose tissue inflammation in high-fat fed mice. Haque, A. Long-term administration of green tea catechins improves spatial cognition learning ability in rats. Hein, S. Systematic review of the effects of blueberry on cognitive performance as we age. A Biol. Hughes, R. Fueling gut microbes: a review of the interaction between diet, exercise, and the gut microbiota in athletes. Hurst, R. Consumption of an anthocyanin-rich extract made from New Zealand blackcurrants prior to exercise may assist recovery from oxidative stress and maintains circulating neutrophil function: a pilot study. Janle, E. Method for evaluating the potential of C 14 labeled plant polyphenols to cross the blood-brain barrier using accelerator mass spectrometry. Methods Phys. B , — Pharmacokinetics and tissue distribution of 14C-labeled grape polyphenols in the periphery and the central nervous system following oral administration. Food 13, — Jennings, A. The role of the gut microbiome in the association between habitual anthocyanin intake and visceral abdominal fat in population-level analysis. Kashiwabara, M. Suppression of neuropeptide production by quercetin in allergic rhinitis model rats. BMC Complement Altern. Kern, T. Structured exercise alters the gut microbiota in humans with overweight and obesity-A randomized controlled trial. Obes 44, — Krikorian, R. Blueberry supplementation improves memory in older adults. Lau, F. Inhibitory effects of blueberry extract on the production of inflammatory mediators in lipopolysaccharide-activated BV2 miroglia. Lee, H. Effect of tea phenolics and their aromatic fecal bacterial metabolites on intestinal microbiota. Letenneur, L. Flavonoid intake and cognitive decline over a year period. Lila, M. Unraveling anthocyanin bioavailability for human health. Food Sci. Macready, A. Flavonoids and cognitive function: a review of human randomized controlled trial studies and recommendations for future studies. Genes Nutr. Mailing, L. Exercise and the gut microbiome: a review of the evidence, potential mechanisms, and implications for human health. Sport Sci. Mancini, E. Green tea effects on cognition, mood and human brain function: a systematic review. Phytomedicine 34, 26— Manderino, L. Preliminary evidence for an association between the composition of the gut microbiome and cognitive function in neurologically healthy older adults. Manor, O. Health and disease markers correlate with gut microbiome composition across thousands of people. Martin, M. Impact of dietary flavanols on microbiota, immunity and inflammation in metabolic diseases. McGuire, S. Dietary supplementation with blueberry extract improves survival of transplanted dopamine neurons. McNamara, R. Cognitive response to fish oil, blueberry, and combined supplementation in older adults with subjective cognitive impairment. Aging 64, — Middleton, L. Changes in cognition and mortality in relation to exercise in late life: a population based study. PLoS One 3:e Miller, M. Dietary blueberry improves cognition among older adults in a randomized, double-blind, placebo-controlled trial. Minghui, R. Risk Reduction of Cognitive Decline and Dementia. Geneva: World Health Organization. WHO guidelines. Moco, S. Metabolomics view on gut microbiome modulation by polyphenol-rich foods. Proteome Res. Morais, C. Anthocyanins as inflammatory modulators and the role of the gut microbiota. Mu, C. Gut microbiota: the brain peacekeeper. Napoli, N. Effect of weight loss, exercise, or both on cognition and quality of life in obese older adults. Nasreddine, Z. The Montreal cognitive assessment, MoCA: a brief screening tool for mild cognitive impairment. Nieman, D. Exercise immunology: future directions. Sport Health Sci. Influence of a polyphenol-enriched protein powder on exercise-induced inflammation and oxidative stress in athletes: a randomized trial using a metabolomics approach. PLoS One 8:e Increased plasma levels of gut-derived phenolics linked to walking and running following two weeks of flavonoid supplementation. Immunometabolism: a multi-omics approach to interpreting the influence of exercise and diet on the immune system. Noble, E. Gut to brain dysbiosis: mechanisms linking Western diet consumption, the microbiome, and cognitive impairment. Novotny, M. Microbiome and cognitive impairment: can any diets influence learning processes in a positive way? Peet, R. The measurement of species diversity. Pereira-Caro, G. Chronic administration of a microencapsulated probiotic enhances the bioavailability of orange juice flavanones in humans. Free Radic. Piercy, K. Physical activity guidelines for Americans From the US department of health and human services. Outcomes e Rajaram, S. Plant-based dietary patterns, plant foods, and age-related cognitive decline.
Introduction	Not really, Flavonoids and mood regulation to Dr. Personal Growth. The effect Flavonoisd glycine administration andd the characteristics Forskolin for men physiological systems in human adults: A systematic review Article Open access 18 October Flavonoids, cognition, and dementia: actions, mechanisms, and potential therapeutic utility for Alzheimer disease. Cui, J.

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Brain Healing vs Flavonoids