Health Benefits of Fruit Polyphenols. 40% fat meal induces:

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Health Benefits of Fruit olyphenols Clinical evidence of fruit-derived polyphenol action in the postprandial

Britt Burton-Freeman, hd Institute for Food Safety and Health Center for Nutrition Research Illinois Institute

edu 7 9 7 ostprandial State after meal Modern / Western meal induces glucose spikes and prolonged elevation of

March Glucose drink increases ROS and NF-kappa B activity ROS NF-kB activity % fat meal induces: Marked

1 Health Benefits of Fruit olyphenols Clinical evidence of fruit-derived polyphenol action in the postprandial state and effects on blood pressure. Britt Burton-Freeman, hd Institute for Food Safety and Health Center for Nutrition Research Illinois Institute of Technology ostprandial State after meal Modern / Western meal induces glucose spikes and prolonged elevation of lipids 7 meal Glucose lipids OXIDATIVE STRESS and INFLAMMATION 8am am pm pm pm ILSI Australia-Asia Conference March Glucose drink increases ROS and NF-kappa B activity ROS NF-kB activity % fat meal induces: Marked increases in inflammatory markers Marked increases in platelet aggregation % Monocytes with Intracellular TNFa TNF α 8 IL-ß. Dhindsa et al % Monocytes with Adherent CDa latelets Hyson et al.. Time (hours after test meal) % Monocytes with Intracellular IL-b. Time (hours after test meal)

Western diet, ostprandial challenges Everyday and Disease Risk Hyperglycemia / Hyperlipidemia Inflammation Common problem in multiple diseases coaguability ox glycated products NO Endothelial

S ulmonary diseases Cancer Neurological diseases INFLAMMATION Autoimmune diseases Arthritis Cardio- and Cerebro- Vascular diseases Alzheimer's Diabetes Burton-Freeman BJN Disease and Disease

2 Western diet, ostprandial challenges Everyday and Disease Risk Hyperglycemia / Hyperlipidemia Inflammation Common problem in multiple diseases coaguability ox glycated products NO Endothelial Dysfunction OXIDATIVE STRESS and INFLAMMATION insulin glucose NO Insulin Insulin Resistance Resistant IRS- B-cell deterioration TG, FFA RL, sd ox Endothelial Dysfunction coaguability O L Y H E N O L S ulmonary diseases Cancer Neurological diseases INFLAMMATION Autoimmune diseases Arthritis Cardio- and Cerebro- Vascular diseases Alzheimer's Diabetes Burton-Freeman BJN Disease and Disease Complications Metabolic Syndrome, Atherosclerosis, Diabetes, Hypertension, Stroke Atheromas contain multiple cell types that critically influence atherogenesis In vitro work supporting Anti-inflammatory effects of polyphenols olyphenols Vascular cells --Endothelium --Smooth muscle cells free fatty acids cytokines AGE RR Cytokines IL- IL-b TNFa Chemokines MC- MIF Gs LTs Etc Inflammatory cells --Macrophages --T lymphocytes --Mast cells olyphenols ox Libby, Copyright. et American al. Circulation Heart Association ;:8-88 Adapted from Jungbauer and Medjakovic, Maturitas

Modified / Oxidized Readily Enter the Artery Wall Where They May Be Modified and Inflammation Vessel Lumen Adhesion Molecules Monocyte Vessel Lumen Oxidation of Lipids and Apo B Endothelium

3 Modified / Oxidized Readily Enter the Artery Wall Where They May Be Modified and Inflammation Vessel Lumen Adhesion Molecules Monocyte Vessel Lumen Oxidation of Lipids and Apo B Endothelium Hydrolysis of hosphatidylcholine to Lysophosphatidylcholine MC- Endothelium Aggregation Modified (oxidized ) ro-inflammatory Other Chemical Modifications Intima Cytokines NF-kB Macrophage Modified (ox) Intima Steinberg D, et al. N Engl J Med. 989;:9-9. Slide Source: Lipids Online Nathan CF. J Clin Invest. 987;79:9-. Studying olyphenols Whole food Raw rocessed juice, concentrate, formulation Extracts Grape seed Tomato Spices Essential oils urified compounds Resveratrol Anthocyanins Curcumin Lycopene Cell culture Animal models Human Epidemiology Clinical Safety/tolerability Bioavailability Efficacy EVIDENCE..

Strawberry prevents meal-induced increase in oxidized (ox) in overweight men and women Strawberry attenuates postprandial inflammatory response in Overweight men and women U/L Bagel Bagel Cream n

rotection SMBL IL- IL-b 8.. MBL SMBL lacebo % fat Meal lacebo beverage % Strawberry fat Meal Strawberry beverage - Burton-Freeman et al. JACN Treatment, p<.8 8 Edirisinghe et al.

4 Strawberry prevents meal-induced increase in oxidized (ox) in overweight men and women Strawberry attenuates postprandial inflammatory response in Overweight men and women U/L Bagel Bagel Cream n cream cheese cheese Egg Whole with margarine milk cantaloupe Whole milk Canteloupe 7 Calories % fat Breakfast lacebo beverage Breakfast Strawberry beverage Oxidized minutes Oxidation MBL rotection SMBL IL- IL-b 8.. MBL SMBL lacebo % fat Meal lacebo beverage % Strawberry fat Meal Strawberry beverage - Burton-Freeman et al. JACN Treatment, p<.8 8 Edirisinghe et al. BJN in press time IL-, Treatment, p<. IL-b, Treatment, p=. Strawberry reduces the postprandial insulin requirement for glucose control in overweight men and women Strawberry and IL- after weeks feeding: Response to high fat meal challenge in OW men and women µu/ml 8 7 Insulin p=.8 MBL StrBL lacebo MBL % fat Meal Strawberry StrBL % fat Meal pg/ml - IL- 8 Minutes after high fat challenge meal wk lacebo Beverage wk Strawberry Beverage Edirisinghe et al. BJN Ellis et al. JAT

Strawberry and fibrinolysis (AI-) after weeks feeding: Response to high fat meal challenge in OW men and

Strawberry 8 Minutes after high fat challenge meal Ellis et al.

supplementation (vs placebo) weeks on MC- after LS challenge Oxidized is decreased with GSE after weeks

5 Strawberry and fibrinolysis (AI-) after weeks feeding: Response to high fat meal challenge in OW men and women Wine blocks meal-induced activation of proinflammatory transcription factor, NF-kB AI- 8 7 lacebo Strawberry 8 Minutes after high fat challenge meal Ellis et al. J Athero Thrombosis Blanco-Colio et al Circulation No Wine Vodka Full Wine Low Wine F-extract supplementation (vs placebo) weeks on MC- after LS challenge Oxidized is decreased with GSE after weeks supplementation in MS patients Dose of GSE (mg/day) lacebo F-extract Reduction in Oxidized Broekhuizen LN et al BJN Sivaprakasapilla, B et al 9 Metab Clin Exp

d ts. CAD Effect of purple grape juice on flowmediated vasodilation GSE and change in blood pressure GSE Dose mg/day mg/day lacebo - - - mmhg -8 - - Systolic Diastolic Stein, J. H. et al.

6 d ts. CAD Effect of purple grape juice on flowmediated vasodilation GSE and change in blood pressure GSE Dose mg/day mg/day lacebo mmhg Systolic Diastolic Stein, J. H. et al. Circulation 999;:- - - <., n=8 Copyright 999 American Heart Association Sivaprakasapilla, B et al 9 Metab Clin Exp Mechanism of activation of e-nos by polyphenolics elucidated using GSE Acetylcholine olyphenols Effect of removing antioxidant capacity of polyphenolics OCH OCH Endothelial cell Muscarinic receptor Ca IK/Akt ROS 7 8 Methylation H CO OCH Ca /CaM enos OCH Smooth muscle cell Vasodilation cgm Nitric oxide (NO) sgc % Relaxation 8 Ca /CaM: Calcium calmodulin complex, cgm: cyclic GM, sgc: soluble guanyl cyclase Edirisinghe et al. (8) Clin. Sci. and (9) J Ag Food Chem Ac GSE Ac Met. GSE GSE ( µ mol/l) ( µ mol/l) ( µ mol/l) ( µ mol/l) ( µ mol/l) Edirisinghe et al.,(8) Clin. Sci. Ring Ring n=, <.

Summary Studying olyphenols We spend most of our life in a postprandial state

polyphenol-rich foods have clinical evidence for attenuating postprandial

in lowering blood pressure Where do we go from here?

Tomato Spices Essential oils urified compounds Resveratrol Anthocyanins Curcumin

Safety/tolerability Bioavailability Efficacy Combating inflammation through diet

Jody Randolph Rose Giordano Julie Talbot Eunyoung ark Sarah Thomas Katie

7 Summary Studying olyphenols We spend most of our life in a postprandial state Exaggerated postprandial responses are linked with disease risk Certain polyphenol-rich foods have clinical evidence for attenuating postprandial responses and maintaining system balance GSE polyphenols appear to have a role in lowering blood pressure Where do we go from here? Whole food Raw rocessed juice, concentrate, formulation Extracts Grape seed Tomato Spices Essential oils urified compounds Resveratrol Anthocyanins Curcumin Lycopene Cell culture Animal models Human Epidemiology Clinical Safety/tolerability Bioavailability Efficacy Combating inflammation through diet ACKNOWLEDGEMENTS Indika Edirisinghe Tissa Kappagoda Amanda Linares Collin Ellis Jody Randolph Rose Giordano Julie Talbot Eunyoung ark Sarah Thomas Katie Banaszewski Jack Cappozzo Nursing Staff Illinois Institute of Technology Institute for Food Safety and Health University of California Davis bburton@iit.edu

Berries and Cardiovascular Health

Berries and Cardiovascular Health Britt Burton-Freeman, PhD Institute for Food Safety and Health Illinois Institute of Technology bburton@iit.edu Berry Health Benefits Symposium Westlake Village CA, 2011