Enhancement of learning and memory by flavonoids

Lead Research Organisation: University of Reading
Department Name: Food and Nutritional Sciences

Abstract

Representing one of the most important lifestyle factors, diet can strongly influence the incidence of cardiovascular disease and neurodegenerative diseases and thus a healthy diet is crucial for healthy ageing. Various bioactive constituents of certain foods and beverages, in particular a class of compounds called flavonoids, have generated interest over the last few years. Recent dietary intervention studies, in particular those using wine, tea, cocoa or blueberries, have begun to demonstrate beneficial effects on the function of blood vessels and on mental performance. While such foods and beverages differ greatly in chemical composition, nutrient content and calories per serving, they have in common that they are amongst the major dietary sources of two groups of flavonoids known as anthocyanins and flavanols. Dietary supplementation studies in humans and animal models using foods or extracts rich in these flavonoids have indicated that they possess an ability to enhance memory and learning. It is thought that they may do this by 1) protecting vulnerable brain cells, 2) enhancing existing brain cell function, 3) stimulating brain cell regeneration, or 4) triggering the growth of new brain cells and/or new blood vessels. Building on existing human and animal work conducted in our laboratory, this multidisciplinary study is designed to determine how specific flavonoids may enhance memory and learning by focussing on their potential to stimulate the growth of new neurons and blood vessels, and the molecular events which determine these changes. The study will also provide crucial information on the ability of flavonoid-rich foods to produce improvements in memory and learning in human older adults using both behavioural and state-of-the-art, brain imaging (fMRI) techniques. The outcomes of this proposal have implications for exploiting the potential beneficial health effects of flavonoid components of the diet, particularly with relation to counteracting the decline in human learning and memory which is associated with normal and abnormal ageing. If we are able to determine which flavonoids are the most beneficial, and how and where they work in the brain, this will help us develop future strategies to maximise these dietary agents in our foods, for example, by developing plants or novel functional food products with high levels of specific flavonoids. In addition, specific dietary advice on food consumption will be improved, as will guidelines to prevent the indiscriminate marketing of food supplements on the basis of putative protective effects. The proposal will broaden understanding of the role that diet plays in the prevention of human brain ageing and the enhancement of a range of cognitive abilities (e.g., spatial memory, long-term memory). The study will also provide the background for new and promising preventive treatments for tackling cognitive decline. The results of this study therefore have important implications for an ageing population where an increase in healthy ageing is greatly desired. Moreover, the potential benefits in terms of quality of life are relevant to the population as a whole, as are the potential savings in health care costs.

Technical Summary

Dietary derived flavonoids have been shown to protect against age-related cognitive decline in animals and humans. These beneficial effects have been attributed to their potential to act selectively within neuronal signalling pathways that regulate neuronal viability, morphology, neurogenesis and angiogenesis. This proposal is designed to unravel the mechanisms by which flavonoids and flavonoid-rich foods influence learning and memory in animals and humans. In animal investigations, we will underpin changes in our behavioural measures of learning and memory with state-of-the-art measurements of neuronal morphology, angiogenesis and neurogenesis. This will be achieved via the reconstruction of whole neuron and vessel structure from z-stacks of confocal microscope-captured images (Leica TCS SP2 AOBS) using neuroanatomical analysis (Neurolecida; MBF Bioscience). The cellular and molecular basis of morphological changes will be addressed using: 1) targeted gene arrays for neurogenesis, neurotrophins and receptors; 2) Western immunoblotting of relevant signalling pathways, notably mitogen-activated protein kinase (MAPK), cAMP response element-binding protein (CREB), brain-derived neurotrophic factor (BDNF) and downstream pathways involved to de novo protein synthesis (mTOR, Arc.Arg3.1 etc); 3) Immunohistochemical analysis of NMDA and AMPA- receptor density and neurogenesis. We will also perform a randomised, double blind, cross-over human intervention study using a group of healthy older adults. The study will employ an analytically well characterised food containing a defined and standardised amount of flavanols (495mg) and a macro- and micronutrient-matched control that contains a low amount of flavanols (23 mg). The success of this intervention will be assessed through changes in neural activity (BOLD) using a state-of-the-art fMRI scanning technique, as well as by performance on a broad range of cognitive tests and measurements of serum BDNF.

Publications

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Cifuentes-Gomez T (2015) Factors Affecting the Absorption, Metabolism, and Excretion of Cocoa Flavanols in Humans. in Journal of agricultural and food chemistry

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Lamport DJ (2014) Fruits, vegetables, 100% juices, and cognitive function. in Nutrition reviews

 
Description Dietary intake of flavanols improves human cognitive performance both acutely and chronically
Exploitation Route Public health messages to increase flavanol intake at population level
Sectors Agriculture, Food and Drink,Education,Healthcare,Pharmaceuticals and Medical Biotechnology

 
Description BBSRC Bioscience for Health Strategy Committee
Geographic Reach National 
Policy Influence Type Membership of a guidance committee
 
Description Diet and Brain Health
Geographic Reach Asia 
Policy Influence Type Influenced training of practitioners or researchers
Impact Greater underdtanding of the influence of flavonoids and brain health and fruit and vegetable intake and prevention of brain disease.
 
Description Alpro Foundation Grant
Amount £150,000 (GBP)
Organisation Alpro Foundation 
Sector Charity/Non Profit
Country Belgium
Start 02/2010 
End 01/2012
 
Description BBSRC DRINC research grant 2013
Amount £717,105 (GBP)
Funding ID BB/L02540X/1 
Organisation Biotechnology and Biological Sciences Research Council (BBSRC) 
Sector Public
Country United Kingdom
Start 12/2014 
End 10/2017
 
Description European Union 7th Framework research grant
Amount £366,000 (GBP)
Organisation European Commission 
Department Seventh Framework Programme (FP7)
Sector Public
Country European Union (EU)
Start 07/2009 
End 06/2012
 
Description Mars Symboscience 
Organisation Mars Incorporated UK
Department Mars Symboscience
Country United States 
Sector Academic/University 
PI Contribution R&D of new products based on the research
Collaborator Contribution Help with the synthesis of physiologically relevant metabolites of flavanols, through the use of their facilities.
Impact Manuscript and addtional funding
 
Description The effects of Champagne wine consumption on brain health 
Organisation Comité Interprofessionnel du Vin de Champagne (CIVIC)
Country France 
Sector Charity/Non Profit 
PI Contribution Wrote proposals and hosted PhD students
Collaborator Contribution Two Partly funded PhD studentships. Further expands the flavonoid/brain and vascular research programme.
Impact Partly funded PhD studentship. Further expands the flavonoid/brain research programme.
Start Year 2006
 
Description The effects of flavanols on brain and vascular health 
Organisation Mars Incorporated UK
Country United Kingdom 
Sector Private 
PI Contribution Wrote successful grant application and hosted PhD student
Collaborator Contribution Supply of research intervention diets for human clinical trial (£60,000). Fully funded PhD studenship (stipend + fees + runing costs). Enhances my groups work in the flavonoid vascular area.
Impact Greatly expands the flavonoid brain and vascular research programme.
Start Year 2007
 
Description 3rd International Conference on Polyphenols and Health 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Health professionals
Results and Impact International conference; 40 min oral presentation

Press release and round table discussions.
Year(s) Of Engagement Activity 2009
 
Description 3rd International Congress on Wine and Health 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Participants in your research and patient groups
Results and Impact International conference; 30 min oral presentation

Press release
Year(s) Of Engagement Activity 2008
 
Description 3rd International Congress on Wine and Health 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact International conference; 20 min oral presentation

Conference press release and individual interviews. French media interest
Year(s) Of Engagement Activity 2008
 
Description 4th Internation Conference on Polyphenols and Health 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact 45 min Plenary lecture with questions and discussion afterwards, around 20 min

Requests for publications and further work with Industry stimulated.
Year(s) Of Engagement Activity 2011
 
Description 5th Internation Conference on Polyphenols and Health 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact 1h Plenary session with round table discussion (1h). Discussion was wide ranging and set targets for research over the next 2-5 years

requests for Industry projects and manuscript requests
Year(s) Of Engagement Activity 2013
 
Description Annual Congress Oxidants and Antioxidants in Biology 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Health professionals
Results and Impact International conference; 15 min oral presentation

Collaboration
Year(s) Of Engagement Activity 2007
 
Description Diet and Brain Health Film 
Form Of Engagement Activity A magazine, newsletter or online publication
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact Recorded and film for the University of Reading regarding the research area. ~15 min and published on the Universities website

Increased recruitment. Increased Industrial funding.
Year(s) Of Engagement Activity 2010
 
Description Fourth European Nutrigenomics Conference 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Participants in your research and patient groups
Results and Impact European Conference; 20 min oral presentation

Press release for conference and media interest
Year(s) Of Engagement Activity 2008
 
Description Mars Nutrition Research Council 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact Industrial Conferenece; 40 min oral presentation

Funding directed towards this research in 2007, 2008 and 2009.
Year(s) Of Engagement Activity 2007
 
Description Oxygen Club California 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Health professionals
Results and Impact International conference; 45 min oral presentation

Press conference and discussion regarding future research focus in the area.
Year(s) Of Engagement Activity 2009
 
Description Oxygen Club of California 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Participants in your research and patient groups
Results and Impact International conference; 30 min oral presentation.

media interest in the USA
Year(s) Of Engagement Activity 2007
 
Description Royal Pharmaceutical Society 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Health professionals
Results and Impact International conference; 45 min oral presentation

Press release and media interviews
Year(s) Of Engagement Activity 2009
 
Description Science Museum's Dana Centre 
Form Of Engagement Activity Participation in an open day or visit at my research institution
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact public event venue for contemporary science debate.

Press conference leading to interviews with The Times, The Observer, The Daily Mail and The Wine Spectator about some of the MRC research outputs. 1h show on Superfoods which aired on BBC2 in August 2007. Interviews with Channel 4 News and BBC radio. The MRC was referred to as funder where possible.
Year(s) Of Engagement Activity 2007
 
Description Scirus Topic Pages 
Form Of Engagement Activity A magazine, newsletter or online publication
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Health professionals
Results and Impact Design of website

more public awareness of the research area
Year(s) Of Engagement Activity 2012
 
Description Sixth Form Summer School 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Schools
Results and Impact organisation and running of the laboratory sessions as part of the School of Food Biosciences 'Sixth Form Open Day'. This course gives A-level students a chance to experience the academic research environment. Experiments related to this MRC grant were used in order to show how certain nutrients may be beneficial to human brain health. June 2005, 2006, 2007 and 2008

Increased recruitment of students.
Year(s) Of Engagement Activity
 
Description Society for Free Radical Research-International 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Health professionals
Results and Impact International conference; 30 min oral presentation

Media interest
Year(s) Of Engagement Activity 2007
 
Description TV Programme 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Media (as a channel to the public)
Results and Impact Part of TV programme "Britain's Favourite Supermarket Foods". Filmed a section for this programme on the MRC funded research.

Further media interest and school presentations
Year(s) Of Engagement Activity 2012
 
Description TV Programme 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Media (as a channel to the public)
Results and Impact Part of a TV programme 'The Food Hospital". Filmed a piece relating to the MRC funded research.

A number of schools have requested lay talks to pupils.
Year(s) Of Engagement Activity 2014
 
Description The Nutrition Society 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Health professionals
Results and Impact International conference; 30 min oral presentation

Press release and significant media interest. Collaborations made and grants applied for.
Year(s) Of Engagement Activity 2008
 
Description The Times, The Observer, The Daily Mail and The Wine Spectator 
Form Of Engagement Activity A magazine, newsletter or online publication
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Media (as a channel to the public)
Results and Impact Edited Interviews for publication, mainly 2007 and 2008

Interest from the general public and NHS
Year(s) Of Engagement Activity 2009
 
Description Third European Nutrigenomics Conference 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Health professionals
Results and Impact European conference; 20 min oral presentation

Conference press release and media interest
Year(s) Of Engagement Activity 2007
 
Description Website articles - Various 
Form Of Engagement Activity A magazine, newsletter or online publication
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact Usually telephone interviews followed by publication of edited interview on public websites.

Interest from the general public usually by email
Year(s) Of Engagement Activity