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Antioxidant Nutrients
Benjamin Caballero, MD, PhD
Johns Hopkins University

Section A
Antioxidant Nutrients

Antioxidant Nutrients

Ascorbic acid
Alpha-tocopherol
Beta-carotene
Selenium
Manganese

Oxidants and Antioxidants

Pro-Oxidants
Substrate oxidation
Antimicrobial defense
Radiation
Sunlight
Ionized compounds
Aging
Oxygen

Antioxidants
Free radical scavengers:
Extracellular/
circulating
Cellular
X Cytosolic
X Membrane-bound

What Is a Free Radical?

An unbound compound (i.e., free) having one or more

unpaired electrons

O H

Hydroxyl group

Hydroxyl radical

(good guy)

(bad guy)

Examples of Free Radicals and their Half-Lives

Hydroxyl radical
Singlet oxygen
Alkoxyl radical
RO
Peroxyl radical
Semiquinone radical Q-

HO
1

O2

ROO

1 x 10-9 sec.
1 x 10-6
1 x 10-6
7
days

Free Radical Formation

Oxidation of substrates with high oxygen affinity (for

example, fatty acids)
Microbial lysis
Environmental exposure (sunlight, radiation, high-oxygen
levels)

Antioxidant Systems of Physiological Relevance in Humans

Water-Soluble
Ascorbate
Glutathione
Urate
Bilirubin

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

PreventionBalance between oxidative load and

antioxidant function
InterceptionLocal antioxidant levels
RepairMostly enzymatic

12

Antioxidant Defense Processes

PreventionVitamin E, ascorbic acid, beta-carotene

InterceptionVitamin E, glutathione, superoxide dismutase
RepairDNA 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
Quenches 1O2 in cytosol
Recycles vitamin E after it captures free radicals

14

Role of Nutrients in Antioxidant Systems

Carotenoids
Beta-carotene quenches 1O2; may also inhibit free-radicalgenerating 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

LOOH

k ~ 102

LOO

Chain
reaction!

Vitamin C
17

Protective Intake Levels of Antioxidant Nutrients

Vitamin C
Vitamin E
Selenium

Protective
level*

RDA

>600 mg
>200 IU
70120 g

60
10
70

* Daily intakes associated with a risk reduction of 25% or more

18

Section B
Diet and Chronic Diseases

Evolution of the Human Diet

HunterGatherers

1520

5070

1520
Salt (g/day) 1
Fiber (g/day) 40

Peasant
Modern Affluent
Agriculturists
Societies

1015
5

40+

6075

20

Sugar

2530

Starch

1015

12

Protein

515
60120

10
20

Fat

20

Nutrition Transition Fat Consumption PatternsJapan

50

% Fat Energy

45
40
35
30
25
20
15
10
5
0
1946 1950 1955 1960 1965 1970 1975 1980 1990

Notes Available

21

Diet Constituents Implicated on Disease Risk

Fats
Cholesterol
Fiber
Antioxidant vitamins and
minerals
Sugar

Protein
Calcium and vitamin D
Folic acid
Iron

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

1834 >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

S y s to lic B P

132
130

Control

128

Fruits and Veg.

126
124

DASH diet

122
120
BL

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)

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

CHD Incidence

125
100
75
50
25
0
< 204

205-234

235-264

265-294

> 295

Serum C holesterol (m g/100m L )

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

Coronary Heart Disease

Relative Risk

Serum LDL and CHD Risk

2.5
2
1.5

men
women

1
0.5
0
200
1

300
2

400
3

500
4

5600

Serum LDL (mg/dL)

Notes Available

32

Serum HDL and CHD

Morbidity Ratio

200

150

m en
wom en

100

50

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 B6 and B12
Iron

38

Folate and Vitamin B: Interrelationships

Homocysteine

Methyl-THF

B 12
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