Food For Thought: Berry Flavonoids and brain function

1. Food For Thought: Berry Flavonoids and brain function Caroline Saunders www.reading.ac.uk

2. 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)

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

4. 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

5. The Actions of Flavonoids in our Body Cell studies Animal Studies Human studies Berry Flavonoids - Improving brain health

6. Age (years) Prevalence of AD (%) Prevalence of PD (%) 35-59 0.2 0.07 60-69 0.3 0.18 70-79 3.2 1.72 Life Expectancy is increasing 80-89 6.2 10.8 • Increased health care costs and general demand on the NHS. • Reduced quality of life for the elderly population.

7. 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

8. Neurotransmitter Receptor Activate Inhibit Tyrosine kinase PI 3-kinase PKC MAP kinase cascades ERK1/2 Akt/PKB JNK p38 c-jun CREB Neuronal survival and Function Neuronal Apoptosis Increases in cognition performance and memory Brain Ageing

9. Quercetin Similarity between flavonoids and pharmacological drugs PI3 Kinase Inhibitor MEK Inhibitor PD98059 LY294002 Epicatechin

10. 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

11. How do we measure these effects?

12. * * * * Blueberry Effects of a Blueberry-rich diet on Spatial Working Memory Correct Choices (All trials) 8 6 4 Number correct (out of 8) 2 0 Baseline 3 weeks 6 weeks 9 weeks 12 weeks Young Old Williams et al: FRBM, 2008

13. Go-Nogo Radial Maze

14. Improvements in Human AttentionGo-NoGo Task after acute blueberry supplementation Subjects : 18-30 yrs Subjects: 60-75 yrs 60 60 Flavonoid * 56 56 Placebo 52 52 * Mean no. of correctly detected targets Mean no. of correctly detected targets 48 48 Flavonoid 44 44 Placebo 40 40 36 36 Pre-drink Pre-drink 1h post 5h post 1h post 5h post Sustained ability to correctly detect target stimuli following flavonoid supplementation compared to the placebo (* p < 0.05; n=14).

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

16. Brain Imaging using fMRI scanning

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

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

19. A human intervention study – randomised double blind cross over • Suitable placebo • Ethical approval • Recruitment (n=60) & screening visit • 2 Intervention Visits • Approximate cost £200,000 (acute study), £400,000 (Chronic)

20. Acknowledgements Dr Jeremy Spencer Dr David Jukes Setareh Tabatabaee For further information contact Caroline Saunders (c.j.saunders@reading.ac.uk)