Antioxidant Nutrients. Benjamin Caballero, MD, PhD Johns Hopkins University

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1 This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike License. Your use of this material constitutes acceptance of that license and the conditions of use of materials on this site. Copyright 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 needed.

2 Antioxidant Nutrients Benjamin Caballero, MD, PhD Johns Hopkins University

3 Section A Antioxidant Nutrients

4 Antioxidant Nutrients Ascorbic acid Alpha-tocopherol Beta-carotene Selenium Manganese 4

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

6 What Is a Free Radical? An unbound compound (i.e., free) having one or more unpaired electrons R O H O H Hydroxyl group (good guy) Hydroxyl radical (bad guy) 6

7 Examples of Free Radicals and their Half-Lives Hydroxyl radical HO 1 x 10-9 sec. Singlet oxygen 1 1 x 10-6 O2 Alkoxyl radical RO 1 x 10-6 Peroxyl radical ROO 7 Semiquinone radical Q - days 7

8 Free Radical Formation Oxidation of substrates with high oxygen affinity (for example, fatty acids) Microbial lysis Environmental exposure (sunlight, radiation, high-oxygen levels) 8

9 Antioxidant Systems of Physiological Relevance in Humans Water-Soluble Ascorbate Glutathione Urate Bilirubin 9

10 Antioxidant Systems of Physiological Relevance in Humans Lipid-soluble Alpha-tocopherol Beta-carotene Lycopene Lutein Zeaxanthin Ubiquinol-10 10

11 Antioxidant Systems in Cells 11

12 Antioxidant Defense Processes Prevention Balance between oxidative load and antioxidant function Interception Local antioxidant levels Repair Mostly enzymatic 12

13 Antioxidant Defense Processes Prevention Vitamin E, ascorbic acid, beta-carotene Interception Vitamin E, glutathione, superoxide dismutase Repair DNA repair system, reductases 13

14 Role of Nutrients in Antioxidant Systems Vitamin E Protects lipids from the cell membrane bilayer from attack by free radicals Vitamin C Quenches 1 O2 in cytosol Recycles vitamin E after it captures free radicals 14

15 Role of Nutrients in Antioxidant Systems Carotenoids Beta-carotene quenches 1 O2; may also inhibit free-radicalgenerating reactions Autoregenerate with release of thermal energy 15

16 Role of Nutrients in Antioxidant Systems Selenium Constituent of glutathione peroxidase Manganese Constituent of superoxide dismutase (MnSOD) Copper, zinc Constituents of superoxide dismutase (CuZnSOD) 16

17 Antioxidant Mechanism of Vitamin E LOOH k ~ 10 2 LOO Chain reaction! Vitamin C 17

18 Protective Intake Levels of Antioxidant Nutrients Protective level * RDA Vitamin C >600 mg 60 Vitamin E >200 IU 10 Selenium µg 70 * Daily intakes associated with a risk reduction of 25% or more 18

19 Section B Diet and Chronic Diseases

20 Evolution of the Human Diet Hunter- Gatherers Peasant Agriculturists Modern Affluent Societies 40+ Fat Sugar Starch Protein Salt (g/day) Fiber (g/day)

21 Nutrition Transition Fat Consumption Patterns Japan % Fat Energy Notes Available 21

22 Diet Constituents Implicated on Disease Risk Fats Cholesterol Fiber Antioxidant vitamins and minerals Sugar Protein Calcium and vitamin D Folic acid Iron 22

23 Criteria for Diet-Disease Relationships Strength of association Dose-response relationship Temporally correct association Consistency of association Specificity of association Biological plausibility Notes Available

24 Dietary Fat Intake and Breast Cancer-Related Deaths Notes Available 24

25 Fish Consumption and Risk of CVD Fish Consumption, g/day 0 < >35 MI CHD CVD All causes Notes Available 25

26 Diet and Blood Pressure Sodium Calcium Potassium Magnesium Alcohol 26

27 The DASH Study 132 Systolic B P Control Fruits and Veg. DASH diet 120 BL Weeks Notes Available 27

28 Dietary Patterns and Blood Pressure: The DASH Diet Control F & V DASH Fat (% cal) Cholesterol (mg) Fiber (g) Potassium (mg) Magnesium (mg) Calcium (mg) Sodium (mg)

29 Section C Fats and Cardiovascular Disease

30 Serum Cholesterol and Coronary Heart Disease CHD Incidence < >295 Serum Cholesterol (mg/100ml) Notes Available 30

31 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 levels 31

32 Serum LDL and CHD Risk Coronary Heart Disease Relative Risk Serum LDL (mg/dl) men women Notes Available 32

33 Serum HDL and CHD 200 Morbidity Ratio men women Serum HDL Concentration (mg/dl) Notes Available 33

34 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 HDL 34

35 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 fractions 35

36 Dietary Factors Affecting Blood Cholesterol Increase Saturated fat Cholesterol Trans fatty acids Decrease Monounsaturated fat PUFA (fish oil) Fiber 36

37 Non-Dietary Factors Affecting Blood Cholesterol Increase Smoking Excess body fat Alcohol Decrease Exercise Estrogens 37

38 Other Nutrients Associated with Risk of CHD Folic acid Vitamins B6 and Iron B12 38

39 Folate and Vitamin B: Interrelationships Homocysteine Methyl-THF B12 Methionine THF B6 5,10-methylene-THF Copyright 2005, Benjamin Caballero and The Johns Hopkins University. 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. 39

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