Food For Thought: Berry Flavonoids and brain function Caroline Saunders

Overview What are berry flavonoids and what are their postulated health benefits? How do berry flavonoids work? How do we measure their effect? Current research (Department of Food and Nutritional Sciences, University of Reading)

A wide array of Fruits and vegetables Red wine: (Flavanol, Flavonols) Cocoa: (Flavanols and procyanidins) Green & Black Tea: (Flavanols) Berries: (Anthocyanins) Citrus: (Flavanone) Dietary Flavonoids

Epidemiology Fruit & Vegetables may delay the onset of Alzheimer’s disease (AD)(The Kame project) A flavonoid rich diet reduces the risk of AD (Commenges et al., 2000) Hypertension, heart disease & dementia are rare in island-dwelling Kuna Amerinds Hollenberg and coworkers

The Actions of Flavonoids in our Body Antioxidants Inhibit Cancer Cell growth Inhibit inflammation Reduce cardiovascular disease Lower blood pressure Protect neurons Enhance neuronal function Stimulate neuronal regeneration Induce neurogenesis Berry Flavonoids - Improving brain health Cell studies Animal Studies Human studies

Prevalence of AD (%) Age (years) Prevalence of PD (%) Increased health care costs and general demand on the NHS. Reduced quality of life for the elderly population. Life Expectancy is increasing

Cells communicate by a complex network of proteins within the cell A messenger molecule activates cell receptors which induces a complex signalling cascade resulting in a change in the cells behaviour – Gene expression – Cell death (apoptosis) – Cell survival and enhanced function

Activate Inhibit Neurotransmitter Receptor PKC PI 3-kinase Tyrosine kinase MAP kinase cascades JNKp38 ERK1/2 Akt/PKB Neuronal survival and Function Neuronal Apoptosis CREB c-jun Brain Ageing Increases in cognition performance and memory

LY PD98059 Epicatechin PI3 Kinase Inhibitor MEK Inhibitor Quercetin Similarity between flavonoids and pharmacological drugs

Neurogenesis Flavonoids improve blood flow (Fisher et al., 2006; Dinges et al., 2006 Stimulates new blood vessel growth which occurs in parallel with neurogenesis (Zhao et al., 2008) Learning and Memory

How do we measure these effects?

Correct Choices (All trials) Baseline3 weeks6 weeks9 weeks12 weeks Number correct (out of 8) YoungOld Effects of a Blueberry-rich diet on Spatial Working Memory Blueberry * * * * Williams et al: FRBM, 2008

Go-Nogo Radial Maze

Improvements in Human Attention Go-NoGo Task after acute blueberry supplementation Mean no. of correctly detected targets Sustained ability to correctly detect target stimuli following flavonoid supplementation compared to the placebo (* p < 0.05; n=14). Subjects : yrsSubjects: yrs Flavonoid Placebo * Pre-drink 1h post 5h post Flavonoid Placebo * Pre-drink 1h post 5h post Mean no. of correctly detected targets

Biochemical analysis After Flavonoid supplementation ↑ CREB (Neuronal survival & plasticity) ↑ BDNF (Encourages growth of new neurons) ↑ Nitric Oxide (Vasodilator)

Brain Imaging using fMRI scanning

Current Research (Department of Food & Nutritional Sciences), University of Reading

Identification & quantification of anthocyanins in blueberry by HPLC Delphilidin Anthocyanin content of different blueberry varieties Cyanidin Petunidin Malvidin

A human intervention study – randomised double blind cross over Suitable placebo Ethical approval Recruitment (n=60) & screening visit 2 Intervention Visits Blood BP & SI 8.00 Test Battery mg FL or Control Blood BP & SI Test Battery 1.00 Approximate cost £200,000 (acute study), £400,000 (Chronic)

Acknowledgements Dr Jeremy Spencer Dr David Jukes Setareh Tabatabaee For further information contact Caroline Saunders