Antioxidant NutrientsSection AAntioxidant NutrientsOxidants and AntioxidantsWhat Is a Free Radical?Examples of Free Radicals and their Half-LivesFree Radical FormationAntioxidant Systems of Physiological Relevance in HumansAntioxidant Systems of Physiological Relevance in HumansAntioxidant Systems in CellsAntioxidant Defense ProcessesAntioxidant Defense ProcessesRole of Nutrients in Antioxidant SystemsRole of Nutrients in Antioxidant SystemsRole of Nutrients in Antioxidant SystemsAntioxidant Mechanism of Vitamin E“Protective” Intake Levels of Antioxidant NutrientsSection BEvolution of the Human DietNutrition Transition Fat Consumption Patterns—JapanDiet Constituents Implicated on Disease RiskCriteria for Diet-Disease RelationshipsDietary Fat Intake and Breast Cancer-Related DeathsFish Consumption and Risk of CVDDiet and Blood PressureThe DASH StudyDietary Patterns and Blood Pressure: The DASH DietSection CSerum Cholesterol and Coronary Heart DiseaseCholesterol and CVDSerum LDL and CHD RiskSerum HDL and CHDDiet and AtherosclerosisDiet and AtherosclerosisDietary Factors Affecting Blood CholesterolNon-Dietary Factors Affecting Blood CholesterolOther Nutrients Associated with Risk of CHDFolate and Vitamin B: InterrelationshipsThis work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike License. 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User is responsible for obtaining permissions for use from third parties as needed.Antioxidant NutrientsBenjamin Caballero, MD, PhDJohns Hopkins UniversitySection AAntioxidant Nutrients4Antioxidant Nutrients Ascorbic acid Alpha-tocopherol Beta-carotene Selenium Manganese5Oxidants and AntioxidantsAntioxidants Free radical scavengers:−Extracellular/circulating−CellularX CytosolicX Membrane-boundPro-Oxidants Substrate oxidation Antimicrobial defense Radiation Sunlight Ionized compounds Aging Oxygen6What Is a Free Radical? An unbound compound (i.e., free) having one or more unpaired electronsR O H O HHydroxyl group Hydroxyl radical(good guy) (bad guy)7Examples of Free Radicals and their Half-LivesHydroxyl radical HO•1 x 10-9sec.Singlet oxygen11 x 10-6Alkoxyl radical RO•1 x 10-6Peroxyl radical ROO•7Semiquinone radical Q•- daysO28Free Radical Formation Oxidation of substrates with high oxygen affinity (for example, fatty acids) Microbial lysis Environmental exposure (sunlight, radiation, high-oxygen levels)9Antioxidant Systems of Physiological Relevance in Humans Water-Soluble− Ascorbate− Glutathione− Urate− Bilirubin10Antioxidant Systems of Physiological Relevance in Humans Lipid-soluble− Alpha-tocopherol− Beta-carotene− Lycopene− Lutein− Zeaxanthin− Ubiquinol-1011Antioxidant Systems in Cells12Antioxidant Defense Processes Prevention—Balance between oxidative load and antioxidant function Interception—Local antioxidant levels Repair—Mostly enzymatic13Antioxidant Defense Processes Prevention—Vitamin E, ascorbic acid, beta-carotene Interception—Vitamin E, glutathione, superoxide dismutase Repair—DNA repair system, reductases14Role 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 radicalsO215Role of Nutrients in Antioxidant Systems Carotenoids− Beta-carotene quenches 1 ; may also inhibit free-radical-generating reactions− Autoregenerate with release of thermal energyO216Role of Nutrients in Antioxidant Systems Selenium− Constituent of glutathione peroxidase Manganese− Constituent of superoxide dismutase (MnSOD) Copper, zinc− Constituents of superoxide dismutase (CuZnSOD)17Antioxidant Mechanism of Vitamin ELOO•LOOHk ~ 102Chainreaction!•Vitamin C18“Protective” Intake Levels of Antioxidant NutrientsProtectivelevel*RDAVitamin C >600 mg 60Vitamin E >200 IU 10Selenium 70–120 µg 70* Daily intakes associated with a risk reduction of 25% or moreSection BDiet and Chronic Diseases20Evolution of the Human Diet15–2050–7015–2010–1560–7510–1551225–3040+20FatSugarStarchProteinHunter-GatherersPeasantAgriculturistsModern Affluent Societies1405–1560–1201020Salt (g/day)Fiber (g/day)21Nutrition Transition Fat Consumption Patterns—Japan05101520253035404550% Fat Energy 1946 1950 1955 1960 1965 1970 1975 1980 1990Notes Available22Diet Constituents Implicated on Disease Risk Fats  Cholesterol Fiber Antioxidant vitamins and minerals Sugar Protein Calcium and vitamin D Folic acid Iron23Criteria for Diet-Disease Relationships Strength of association Dose-response relationship Temporally correct association Consistency of association Specificity of association Biological plausibility185-01Notes Available24Dietary Fat Intake and Breast Cancer-Related DeathsNotes Available25Fish Consumption and Risk of CVDFish Consumption, g/day0 <18 18–34 >35MI 1.0 0.88 0.76 0.56 CHD 1.0 0.88 0.84 0.62CVD 1.0 0.94 0.89 0.74All causes 1.0 1.02 0.98 0.85Notes Available26Diet and Blood Pressure Sodium Calcium Potassium Magnesium Alcohol27The DASH Study120122124126128130132BL1234567WeeksSystolic BPControlFruits and Veg.DASH dietNotes Available28Dietary Patterns and Blood Pressure: The DASH DietControl F & V DASHFat (% cal) 36 36 26Cholesterol (mg) 233 184 150Fiber (g) 9 31 31Potassium (mg) 1752 4101 4415Magnesium (mg) 176 423 480Calcium (mg) 443 534 1265Sodium (mg) 3028 2816 2859Section CFats and Cardiovascular Disease30Serum Cholesterol and Coronary Heart Disease0255075100125<204 205-234 235-264 265-294 >295Serum Cholesterol (mg/100mL)CHD IncidenceNotes Available31Cholesterol and CVD The cholesterol hypothesis of coronary heart disease Dietary cholesterol, blood cholesterol, and atherosclerosis Dietary factors affecting blood cholesterol levels Non-dietary