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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 124 y 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