Flavonoids and Cardiovascular Disease

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Flavonoids and Cardiovascular Disease Julie Lovegrove Hugh Sinclair Professor of Human Nutrition University of Reading Micronutrients and Health APPG University of Reading 2014 www.reading.ac.uk

Global ageing population

Heart Disease is the Biggest Killer

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

PHE Change 4 life campaigns

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

What is a portion? ½ 1 2 3 80g fresh / tinned / frozen or 40g dried fruit / pulses / nuts Source: Food Standards Agency. http://www.eatwell.gov.uk

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. 2003. 78 (suppl) 544S-551S

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

Dietary Flavonoid classes

Dietary Flavonoids Dietary sources Red wine & grape juice (>1g/l) Green (210 mg/g) & Black teas (70 mg/g) Fruits and vegetables Fruits (30-700 mg/100g)

Flavanoids intake (mg/day) in adult Europeans Vogialzoglou et al. PLOSone. 2015;10:e0128132

Potential Health Benefits of Flavonoids

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;135:459-463

Difficult to measure dietary intake Kuhnle G Molecuar Aspets of Medicine. 2017 Nov 16 [EPUB]

Metabolism of flavonoids Jaegar et al., Molecular Aspects of Medicine. 2017 [Epub]

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

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

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

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;344-351

Flavanols and cardiovascular function

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;1024-29

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;1246-55

Possible mechanisms of flavonoids and vascular protection

Platelet function

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.

Are we what we eat?

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

Should there be a dietary recommendation for flavanols?

Eatwell guide

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

University of Reading 2014 www.reading.ac.uk

Thank you

Possible mechanism of action Stoclet et al., Eur. J. Pharmo. 2004:299-313