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Antioxidant Nutrients 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. Antioxidant Nutrients Benjamin Caballero, MD, PhD Johns Hopkins University Section A Antioxidant Nutrients Antioxidant Nutrients Ascorbic acid Alpha-tocopherol Beta-carotene Selenium Manganese 4 Oxidants and Antioxidants Pro-Oxidants Antioxidants Substrate oxidation Free radical scavengers: Antimicrobial defense −Extracellular/ Radiation circulating Sunlight −Cellular Ionized compounds X Cytosolic Aging X Membrane-bound Oxygen 5 What Is a Free Radical? An unbound compound (i.e., free) having one or more unpaired electrons R O H O H Hydroxyl group Hydroxyl radical (good guy) (bad guy) 6 Examples of Free Radicals and their Half-Lives Hydroxyl radical HO• 1 x 10-9 sec. 1 -6 Singlet oxygen O2 1 x 10 Alkoxyl radical RO• 1 x 10-6 Peroxyl radical ROO• 7 Semiquinone radical Q•- days 7 Free Radical Formation Oxidation of substrates with high oxygen affinity (for example, fatty acids) Microbial lysis Environmental exposure (sunlight, radiation, high-oxygen levels) 8 Antioxidant Systems of Physiological Relevance in Humans Water-Soluble − Ascorbate − Glutathione − Urate − Bilirubin 9 Antioxidant Systems of Physiological Relevance in Humans Lipid-soluble − Alpha-tocopherol − Beta-carotene − Lycopene − Lutein − Zeaxanthin − Ubiquinol-10 10 Antioxidant Systems in Cells 11 Antioxidant Defense Processes Prevention—Balance between oxidative load and antioxidant function Interception—Local antioxidant levels Repair—Mostly enzymatic 12 Antioxidant Defense Processes Prevention—Vitamin E, ascorbic acid, beta-carotene Interception—Vitamin E, glutathione, superoxide dismutase Repair—DNA repair system, reductases 13 Role of Nutrients in Antioxidant Systems Vitamin E − Protects lipids from the cell membrane bilayer from attack by free radicals Vitamin C 1 − Quenches O2 in cytosol − Recycles vitamin E after it captures free radicals 14 Role of Nutrients in Antioxidant Systems Carotenoids 1 − Beta-carotene quenches O2; may also inhibit free-radical- generating reactions − Autoregenerate with release of thermal energy 15 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 Antioxidant Mechanism of Vitamin E 2 k ~ 10 Chain LOOH LOO• reaction! • Vitamin C 17 “Protective” Intake Levels of Antioxidant Nutrients Protective level* RDA Vitamin C >600 mg 60 Vitamin E >200 IU 10 Selenium 70–120 µg 70 * Daily intakes associated with a risk reduction of 25% or more 18 Section B Diet and Chronic Diseases Evolution of the Human Diet Hunter- Peasant Modern Affluent Gatherers Agriculturists Societies 15–20 10–15 Fat 5 40+ 50–70 60–75 20 Sugar 25–30 Starch 15–20 10–15 12 Protein Salt (g/day) 1 5–15 10 Fiber (g/day) 40 60–120 20 20 Nutrition Transition Fat Consumption Patterns—Japan 50 45 40 35 gy r e 30 n E 25 t 20 Fa % 15 10 5 0 1946 1950 1955 1960 1965 1970 1975 1980 1990 Notes Available 21 Diet Constituents Implicated on Disease Risk Fats Protein Cholesterol Calcium and vitamin D Fiber Folic acid Antioxidant vitamins and Iron minerals Sugar 22 Criteria for Diet-Disease Relationships Strength of association Dose-response relationship Temporally correct association Consistency of association Specificity of association Biological plausibility Notes Available 185-01 23 Dietary Fat Intake and Breast Cancer-Related Deaths Notes Available 24 Fish Consumption and Risk of CVD Fish Consumption, g/day 0 <18 18–34 >35 MI 1.0 0.88 0.76 0.56 CHD 1.0 0.88 0.84 0.62 CVD 1.0 0.94 0.89 0.74 All causes 1.0 1.02 0.98 0.85 Notes Available 25 Diet and Blood Pressure Sodium Calcium Potassium Magnesium Alcohol 26 The DASH Study 132 130 Control P 128 B Fruits and Veg. lic 126 o t s y 124 DASH diet S 122 120 BL1234567 Weeks Notes Available 27 Dietary Patterns and Blood Pressure: The DASH Diet Control F & V DASH Fat (% cal) 36 36 26 Cholesterol (mg) 233 184 150 Fiber (g) 9 31 31 Potassium (mg) 1752 4101 4415 Magnesium (mg) 176 423 480 Calcium (mg) 443 534 1265 Sodium (mg) 3028 2816 2859 28 Section C Fats and Cardiovascular Disease Serum Cholesterol and Coronary Heart Disease 125 100 e nc 75 de i c n I 50 D H C 25 0 <204 205-234 235-264 265-294 >295 Serum Cholesterol (mg/100mL) Notes Available 30 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 Serum LDL and CHD Risk 2.5 sease 2 i sk i D t 1.5 men ear ve R i t H women a 1 y l e R 0.5 onar r o C 0 20012345300 400 500 600 Serum LDL (mg/dL) Notes Available 32 Serum HDL and CHD 200 150 tio a R men ity 100 id women rb o 50 M 0 20 30 40 50 60 70 75+ Serum HDL Concentration (mg/dL) Notes Available 33 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 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 Dietary Factors Affecting Blood Cholesterol Increase − Saturated fat − Cholesterol − Trans fatty acids Decrease − Monounsaturated fat − PUFA (fish oil) − Fiber 36 Non-Dietary Factors Affecting Blood Cholesterol Increase − Smoking − Excess body fat − Alcohol Decrease − Exercise − Estrogens 37 Other Nutrients Associated with Risk of CHD Folic acid Vitamins B 6 and B12 Iron 38 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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