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This work is licensed under a Creative Commons Attribution -NonCommercial-ShareAlikeLice nse. Your use of this material constitutes acceptance of that license and the conditions of use of materials on this 2006, The Johns Hopkins University and Benjamin Caballero. All rights reserved. Use of these materials permitted only in accordance with license rights granted. Materials provided AS IS ; no representations or warranties provided. User assumes all responsibility for use, and all liability related thereto, and must independently review all materials for accuracy and efficacy. May contain materials owned by others. User is responsible for obtaining permissions for use from third parties as NutrientsBenjamin Caballero, MD, PhDJohns Hopkins UniversitySection AAntioxidant Nutrients4 Antioxidant Nutrients Ascorbic acid Alpha-tocopherol Beta-carotene Selenium Manganese5 Oxidants and AntioxidantsAntioxidants Free radical scavengers: Extracellular/circulating CellularXCytosolicXMembrane-boundPro-Oxi dants Substrate oxidation Antimicrobial defense Radiation Sunlight Ionized compounds Aging Oxygen6 What Is a Free Radical?

5 Oxidants and Antioxidants Antioxidants Free radical scavengers: −Extracellular/ circulating −Cellular XCytosolic XMembrane-bound Pro-Oxidants Substrate oxidation Antimicrobial defense Radiation Sunlight Ionized compounds Aging Oxygen

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1 This work is licensed under a Creative Commons Attribution -NonCommercial-ShareAlikeLice nse. Your use of this material constitutes acceptance of that license and the conditions of use of materials on this 2006, The Johns Hopkins University and Benjamin Caballero. All rights reserved. Use of these materials permitted only in accordance with license rights granted. Materials provided AS IS ; no representations or warranties provided. User assumes all responsibility for use, and all liability related thereto, and must independently review all materials for accuracy and efficacy. May contain materials owned by others. User is responsible for obtaining permissions for use from third parties as NutrientsBenjamin Caballero, MD, PhDJohns Hopkins UniversitySection AAntioxidant Nutrients4 Antioxidant Nutrients Ascorbic acid Alpha-tocopherol Beta-carotene Selenium Manganese5 Oxidants and AntioxidantsAntioxidants Free radical scavengers: Extracellular/circulating CellularXCytosolicXMembrane-boundPro-Oxi dants Substrate oxidation Antimicrobial defense Radiation Sunlight Ionized compounds Aging Oxygen6 What Is a Free Radical?

2 An unbound compound ( , free) having one or more unpaired electronsR O HO HHydroxyl groupHydroxyl radical(good guy)(bad guy)7 Examples of Free Radicals and their Half-LivesHydroxyl radicalHO 1 x oxygen11 x 10-6 Alkoxyl radicalRO 1 x 10-6 Peroxyl radicalROO 7 Semiquinone radicalQ -daysO28 Free Radical Formation Oxidation of substrates with high oxygen affinity (for example, fatty acids) Microbial lysis Environmental exposure (sunlight, radiation, high-oxygen levels)9 Antioxidant Systems of Physiological Relevance in Humans Water-Soluble Ascorbate Glutathione Urate Bilirubin10 Antioxidant Systems of Physiological Relevance in Humans Lipid-soluble Alpha-tocopherol Beta-carotene Lycopene Lutein Zeaxanthin Ubiquinol-1011 Antioxidant Systems in Cells12 Antioxidant Defense Processes Prevention Balance between oxidative load and antioxidant function Interception Local antioxidant levels Repair Mostly enzymatic13 Antioxidant Defense Processes Prevention Vitamin E, ascorbic acid, beta-carotene Interception Vitamin E, glutathione, superoxide dismutase Repair DNA repair system, reductases14 Role of Nutrients in Antioxidant Systems Vitamin E Protects lipids from the cell membrane bilayer from attack by free radicals Vitamin C Quenches 1 in cytosol Recycles vitamin E after it captures free radicalsO215 Role of Nutrients in Antioxidant Systems Carotenoids Beta-carotene quenches 1.

3 May also inhibit free-radical-generating reactions Autoregenerate with release of thermal energyO216 Role of Nutrients in Antioxidant Systems Selenium Constituent of glutathione peroxidase Manganese Constituent of superoxide dismutase (MnSOD) Copper, zinc Constituents of superoxide dismutase (CuZnSOD)17 Antioxidant Mechanism of Vitamin ELOO LOOHk ~ 102 Chainreaction! Vitamin C18 Protective Intake Levels of Antioxidant NutrientsProtectivelevel*RDAV itamin C>600 mg60 Vitamin E>200 IU10 Selenium70 120 g70* Daily intakes associated with a risk reduction of 25% or moreSection BDiet and Chronic Diseases20 Evolution of the Human Diet15 2050 7015 2010 1560 7510 1551225 3040+20 FatSugarStarchProteinHunter-GatherersPea santAgriculturistsModern Affluent Societies1405 1560 1201020 Salt (g/day)Fiber (g/day)21 Nutrition Transition Fat Consumption Patterns Japan05101520253035404550% Fat Energy 194619501955196019651970197519801990 Notes Available22 Diet Constituents Implicated on Disease Risk Fats Cholesterol Fiber Antioxidant vitamins and minerals Sugar Protein Calcium and vitamin D Folic acid Iron23 Criteria for Diet-Disease Relationships Strength of association Dose-response relationship Temporally correct association Consistency of association Specificity of association Biological plausibility185-01 Notes Available24 Dietary Fat Intake and Breast Cancer-Related DeathsNotes Available25 Fish Consumption and Risk of CVDFish Consumption, g/day0<1818 34> Available26 Diet and Blood Pressure Sodium Calcium Potassium Magnesium Alcohol27 The DASH Study120122124126128130132BL1234567 WeeksS ysto lic BPControlFruits and dietNotes Available28 Dietary Patterns and Blood Pressure.

4 The DASH DietControlF & VDASHFat (% cal)363626 Cholesterol (mg)233184150 Fiber (g)93131 Potassium (mg)175241014415 Magnesium (mg)176423480 Calcium (mg)4435341265 Sodium (mg)302828162859 Section CFats and Cardiovascular Disease30 Serum Cholesterol and Coronary Heart Disease0255075100125<204205-234235-264265-294>295 Serum Cholesterol (mg/100mL)CHD IncidenceNotes Available31 Cholesterol and CVD The cholesterol hypothesis of coronary heart disease Dietary cholesterol, blood cholesterol, and atherosclerosis Dietary factors affecting blood cholesterol levels Non-dietary factors affecting blood cholesterol levels32 Serum LDL and CHD LDL (mg/dL)Coronary Heart Disease Relative Riskmenwomen200300400500600 Notes Available33 Serum HDL and CHD05010015020020304050607075+Serum HDL Concentration (mg/dL)Morbidity RatiomenwomenNotes Available34 Diet and Atherosclerosis Low-fat diets Lower blood cholesterol but also tend to lower LDL and HDL Low-saturated, high-monounsaturated diets Lower blood cholesterol and LDL, tend to increase HDL35 Diet and Atherosclerosis High-carbohydrate diets Modest lowering effect on all lipid fractions, but rise in TG Fish oils Strong lowering effect on blood TG, but minor effect of lipoprotein fractions36 Dietary Factors Affecting Blood Cholesterol Increase Saturated fat Cholesterol Trans fatty acids Decrease Monounsaturated fat PUFA (fish oil) Fiber37 Non-Dietary Factors Affecting Blood Cholesterol Increase Smoking Excess body fat Alcohol Decrease Exercise Estrogens38 Other Nutrients Associated with Risk of CHD Folic acid Vitamins and IronB6 B1239 Folate and Vitamin B: InterrelationshipsHomocysteineMethionine Methyl-THFTHF5,10-methylene-THFB6B12 Copyright 2005, Benjamin Caballero and The Johns Hopkins University.

5 All rights reserved. Use of these materials permitted only in accordance with license rights granted. Materials provided AS IS ; no representations or warranties provided. User assumes all responsibility for use, and all liability related thereto, and must independently review all materials for accuracy and efficacy. May contain materials owned by others. User is responsible for obtaining permissions for use from third parties as needed.


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