Flavonoids and Cardiovascular Disease

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1 Flavonoids and Cardiovascular Disease Julie Lovegrove Hugh Sinclair Professor of Human Nutrition University of Reading Micronutrients and Health APPG University of Reading

2 Global ageing population

3 Heart Disease is the Biggest Killer

4 Global Disability-Adjusted Life Years (DALYs) Dietary risks Diabetes Cardiovascular diseases Neoplasms Forouzanfar MH et al, The Lancet 11 Sept 2015

5 PHE Change 4 life campaigns

6 Fruit & Vegetable Recommendations Portions of fruit & vegetables / day 9 Greece WHO >400 g per person per day 5 Country

7 What is a portion? ½ g fresh / tinned / frozen or 40g dried fruit / pulses / nuts Source: Food Standards Agency.

8 Fruits & vegetables and heart disease Reduced risk Increased risk 4% disease burden due to low fruit & vegetable consumption ~30% coronary heart disease & ~20% stroke due to < 600 g / day Hu F.B. Am J Clin Nutr (suppl) 544S-551S

9 Fibre eg soluble, insoluble Minerals eg Mg, Ca, Fe, K Mn, Se Vitamins eg vitamin C, E, B, folate Nitrates Phytochemicals eg Carotenoids, Isoflavones, Flavonoids

10 Dietary Flavonoid classes

11 Dietary Flavonoids Dietary sources Red wine & grape juice (>1g/l) Green (210 mg/g) & Black teas (70 mg/g) Fruits and vegetables Fruits ( mg/100g)

12 Flavanoids intake (mg/day) in adult Europeans Vogialzoglou et al. PLOSone. 2015;10:e

13 Potential Health Benefits of Flavonoids

14 Dietary flavonoids and CHD risk Meta-A of prospective cohort studies (n=452,564) 15% reduction in CHD risk Reduced risk Increased risk Jiang et al., Thrombosis Research. 2015;135:

15 Difficult to measure dietary intake Kuhnle G Molecuar Aspets of Medicine Nov 16 [EPUB]

16 Metabolism of flavonoids Jaegar et al., Molecular Aspects of Medicine [Epub]

17 Impact of increasing flavonoid-rich F&V on circulating flavonoids n=152 men and women increased CVD risk. Increased dose (+2,+4,+6) high flavonoid (HF); low flavonoid (LF) F&V vs control (P=0.0001) +2 (6wk) +4 (6wk) +6 (6wk) Additional F&V portions Chong et al, Eur. J. Nutr. 2013;52:361-58

18 CVD Risk Factors Obesity Gender Raised cholesterol Genotype Raised blood pressure Ethnicity Raised triacylglycerol Age Vascular dysfunction Menopausal status Diabetes Inflammation DIET Smoking Alcohol Physical activity Non-modifiable Stress Modifiable Lifestyle

19 CVD Risk Factors & the Endothelium Hypertension Dyslipidaemia Physical Inactivity Aging Smoking Diabetes Infection / Inflammation Homocysteine Menopause Endothelial Dysfunction Atherosclerotic lesion formation and progression Cardiovascular Disease Events

20 FMD predicts CVD events Reduced risk Increased risk Every 1% higher FMD associated with 10% lower RR for CVD Ras et al., Int J Cardiol. 2013:168;

21 Flavanols and cardiovascular function

22 High flavanol intake (917mg) and vascular function (FMD) High flavanols (917mg) Low flavanols (37mg) High flavanol intake beneficially effected postprandial vascular function Schroeter et al. PNAS:2006;103;

23 High flavonol intake (900mg/d) and vascular function (FMD) Significant increase in FMD acutely after 900mg cocoa flavanols (day 0 and 14) Significant increase in FMD chronically after 900mg/day cocoa flavanols Acute on chronic differences not significant after 14 days Sansone et al., Brit J Nutr. 2015:114;

24 Possible mechanisms of flavonoids and vascular protection

25 Platelet function

26 Ingestion of quercetin-rich onion soup inhibits platelet aggregation 500 ml of quercetin-rich soup (69mg) or quercetin-poor (5mg) Hubbard, et al. Br. J. Nutr. 2006:96(3);482-8.

27 Are we what we eat?

28 Fruit and Vegetable intake in UK 5 a day campaign Less than 27% of adults are meeting 5 a day recommendations

29 Should there be a dietary recommendation for flavanols?

30 Eatwell guide

31 Conclusions Fruit and vegetable consumption is associated with a reduction in CVD risk UK has a 5-a-day recommendation, but has no guidance on specific types of fruits or vegetables Dietary flavonoids from various dietary sources can improve vascular function and reduce platelet function High flavonoid intake are associated with lower CVD risk

32 University of Reading

33

34 Thank you

35 Possible mechanism of action Stoclet et al., Eur. J. Pharmo. 2004: