Numerous epidemiology studies support the concept that diets rich in plant foods are associated with a reduced risk for vascular disease.

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2 Numerous epidemiology studies support the concept that diets rich in plant foods are associated with a reduced risk for vascular disease. Fruits/Vegetables - Multivariate adjusted RR for >=3 times/day vs. <1 time/day - Ischemic heart disease mortality RR=.76 (95% CI:.56, 1.3) - CVD mortality RR=.73 (95% CI:.58,.92) - All cause mortality RR=.85 (95% CI:.72, 1.) adjusted for age, sex, race, energy, physical activity, alcohol consumption, smoking, plus others 14

3 Numerous epidemiology studies support the concept that diets rich in plant foods are associated with a reduced risk for vascular disease. 35 Age-Adjusted CHD Mortality, % Mean Flavonoid Intake (mg/day) Hertog et al., Arch Intern Med, 1995;155: C 15 (C 6 -C 3 -C 6 ) basic skeleton Flavonoids O B A C 3 most common classes R 1 R 1 R 1 HO O + HO O R 2 R 2 HO O R 2 O Anthocyanins Flavonols Flavan-3-ols 15

4 Flavanol Profiles Cocoa and Chocolate B-type procyanidins Cranberries A- and B-type B procyanidins few monomers Peanuts A- and B-type B procyanidins few monomers Tea Procyanidins and Prodelphinidins few oligomers Apple B-type procyanidins Blueberries B-type procyanidins Almond B-type procyanidins Wine B-type procyanidins Grape Seeds B-type procyanidins Galloylated Lazarus et al., J. Ag. Food Chem., 47, Can common foods provide significant amounts of flavonoids? Healthy volunteers, y. Asked to refrain from taking vitamin supplements, and food rich in flavonoids for 24 h, and fasted overnight. Subjects ingested a flavonoid-rich chocolate food (, 35, 7, and 15 g) and bread. Blood was drawn at h, 2 h and 6 h. The chocolate contained 1.3 mg/g of epicatechin and 5.3 mg/g of total procyanidins. 16

5 Plasma Concentrations of Cocoa Flavanols and Dimeric Procyanidins After Consuming.375 g/kg of Cocoa [nmol/l] Dimer B CAT EPI Antioxidant Capacity (s) TRAP TBARS TBARS [µmol [ MDA/L] Time (h) Epicatechin [nm] Holt et al. AJCN 22; 76: 798 Platelet Activation Resting GPIIb-IIIa IIIa P-Selectin ADP Epinephrine Fibrinogen Receptor PAC1-FITC binding GPIIb-IIIa IIIa Activated GPIb-IX IX complex CD42a-PerCP binding GPIb-IX IX Surface P-Selectin CD62-PE binding 17

6 Flavonoids: Platelet Reactivity Consumption of cocoa beverage increases closure time (time to clot) Closure Time (sec) Baseline 2 hour 6 hour Caffeine Cocoa Rein et al. AJCN 72: 3-35, 2 Wine, Grape Products, and Cocoa Reduce Platelet Function Pelligrini et al., 1996 Pace-Asciak et al., 1996 Rein et al., 2 Osman et al., 1998 Keevil et al., 2 Freedman et al., 21 Rein et al., 2 Pearson et al., 22 Holt et al., 22 Murphy et al., 23 Innes et al., 23 18

7 Endothelium Dependent Vasorelaxing Activity of Flavanols Changes in RNO and FMD after Flavanol-Rich Cocoa Consumption nmol/l Flow-Mediated Dilation (%) Before After Flavanol-Low Before After Flavanol-Rich Time (h) Heiss et al. JAMA 23; 29: 13 19

8 Peripheral Arterial Tone (PAT) Itamar Medical Foundation; Caesarea, Israel) Day 1 Day 5 Baseline Post Cocoa Baseline Post Cocoa Fisher et al., J Hypertens 21: , 2286, 23 2

9 Wine, Grape Products, and Cocoa and Chocolate Enhances Endothelial Function in vitro and in vivo Fitzpatrick et al., 1993, 2 Cishek et al., 1997 Adriambelosan et al., 1997 Agewall et al., 2 Hashimoto et al., 21 Stein et al., 1999 Karim et al., 2 Engler et al., 22, 24 Rein et al., 2 Heiss et al., 23 21

10 Pathogenesis of Atherothrombotic Disease Diabetes Smoking Risk Factors Hypertension Oxidative Stress Endothelial Dysfunction [ NO] Dyslipidemia Estrogen Withdrawal Homocysteine Vasoconstriction Local mediators: Endothelin, AngII, TXA 2, Superoxide anion, Catecholamines Smooth muscle cell proliferation Thrombosis t - PA PAI - 1 Platelet adhesion & aggregation Vascular Lesion Progression Plaque Rupture Thrombosis and Vasospasm Inflammation Adhesion molecules Cytokines Growth factors Coronary Events Changes in food processing and food storage Changes in agricultural practices Improved nutrient profiles in plants and animals Conventional genetics GMO 22

11 Improved nutrient profiles in plants and animals Improved food products Food safety Acceptability Palatability Economic viability Health Optimization Health Agencies Identification of new targets for improved quality of life Identification of new targets for disease prevention Risk-Benefit Analysis 23

12 Potential Health Impacts of Excessive Flavonoid Intake.the fetus may be exposed to high circulating levels of flavonoids,, which may elicit toxic responses that may otherwise be innocuous to the mother. Skibola & Smith, Free Radic Biol Med, 29: , 2 Perhaps pregnant women should restrict their intake of fruits Paul Harvey, 23 Who do we protect? Will future legislation require food industries to educate susceptible populations on the putative risks, as well as the putative benefits, of modified foods? Will the expectation be that foods are optimized for the general population (eg( non-smokers; non- pregnant women), or that they be optimized for susceptible populations (eg( smokers; pregnant women)? 24

13 Adversity presents danger, as well as opportunity. The omics omics revolution provides a path through which food can be tailored to significantly enhance health. The above requires the teams with diverse backgrounds, and a education program that targets the public, as well as regulatory and government officials. Nutrition education programs that ignore the concept of risk- benefit set the stage for public confusion and anger at the food industry. However, education programs that include this concept will result in more realistic expectations of what food can provide to the individual, the family and the general population. 25

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