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antioxidants and free radicals
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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, PhDJohns Hopkins University
Section A
Antioxidant Nutrients
4
Antioxidant Nutrients
Ascorbic acidAlpha-tocopherolBeta-caroteneSeleniumManganese
5
Oxidants and Antioxidants
AntioxidantsFree radical scavengers:−Extracellular/
circulating−Cellular
CytosolicMembrane-bound
Pro-OxidantsSubstrate oxidationAntimicrobial defenseRadiationSunlightIonized compoundsAgingOxygen
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 Hydroxyl radical
(good guy) (bad guy)
7
Examples of Free Radicals and their Half-Lives
Hydroxyl radical HO• 1 x 10-9 sec.Singlet oxygen 1 1 x 10-6
Alkoxyl radical RO• 1 x 10-6
Peroxyl radical ROO• 7Semiquinone radical Q•- days
O2
8
Free Radical Formation
Oxidation of substrates with high oxygen affinity (for example, fatty acids)Microbial lysisEnvironmental exposure (sunlight, radiation, high-oxygen levels)
9
Antioxidant Systems of Physiological Relevance in Humans
Water-Soluble− Ascorbate− Glutathione− Urate− Bilirubin
10
Antioxidant Systems of Physiological Relevance in Humans
Lipid-soluble− Alpha-tocopherol− Beta-carotene− Lycopene− Lutein− Zeaxanthin− Ubiquinol-10
11
Antioxidant Systems in Cells
12
Antioxidant Defense Processes
Prevention—Balance between oxidative load and antioxidant functionInterception—Local antioxidant levelsRepair—Mostly enzymatic
13
Antioxidant Defense Processes
Prevention—Vitamin E, ascorbic acid, beta-caroteneInterception—Vitamin E, glutathione, superoxide dismutaseRepair—DNA repair system, reductases
14
Role of Nutrients in Antioxidant Systems
Vitamin E− Protects lipids from the cell membrane bilayer from
attack by free radicalsVitamin C− Quenches 1 in cytosol− Recycles vitamin E after it captures free radicals
O2
15
Role of Nutrients in Antioxidant Systems
Carotenoids− Beta-carotene quenches 1 ; may also inhibit free-radical-
generating reactions− Autoregenerate with release of thermal energy
O2
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)
17
Antioxidant Mechanism of Vitamin E
LOO•LOOHk ~ 102
Chainreaction!
•
Vitamin C
18
“Protective” Intake Levels of Antioxidant Nutrients
Protectivelevel* RDA
Vitamin C >600 mg 60Vitamin E >200 IU 10Selenium 70–120 µg 70
* Daily intakes associated with a risk reduction of 25% or more
Section B
Diet and Chronic Diseases
20
Evolution of the Human Diet
15–20
50–70
15–20
10–15
60–75
10–155
12
25–30
40+
20
Fat
Sugar
Starch
Protein
Hunter-Gatherers
PeasantAgriculturists
Modern Affluent Societies
140
5–1560–120
1020
Salt (g/day)Fiber (g/day)
21
Nutrition Transition Fat Consumption Patterns—Japan
05
101520253035404550
% F
at E
nerg
y
1946 1950 1955 1960 1965 1970 1975 1980 1990
Notes Available
22
Diet Constituents Implicated on Disease Risk
Fats CholesterolFiberAntioxidant vitamins and mineralsSugar
ProteinCalcium and vitamin DFolic acidIron
23
Criteria for Diet-Disease Relationships
Strength of associationDose-response relationshipTemporally correct associationConsistency of associationSpecificity of associationBiological plausibility
185-01Notes Available
24
Dietary Fat Intake and Breast Cancer-Related Deaths
Notes Available
25
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
26
Diet and Blood Pressure
SodiumCalciumPotassiumMagnesiumAlcohol
27
The DASH Study
120
122
124
126
128
130
132
BL 1 2 3 4 5 6 7
Weeks
Syst
olic
BP
Control
Fruits and Veg.
DASH diet
Notes Available
28
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
Section C
Fats and Cardiovascular Disease
30
Serum Cholesterol and Coronary Heart Disease
0
25
50
75
100
125
<204 205-234 235-264 265-294 >295
Serum Cholesterol (mg/100mL)
CH
D In
cide
nce
Notes Available
31
Cholesterol and CVD
The cholesterol hypothesis of coronary heart diseaseDietary cholesterol, blood cholesterol, and atherosclerosisDietary factors affecting blood cholesterol levelsNon-dietary factors affecting blood cholesterol levels
32
Serum LDL and CHD Risk
0
0.5
1
1.5
2
2.5
1 2 3 4 5
Serum LDL (mg/dL)
Cor
onar
y H
eart
Dis
ease
R
elat
ive
Ris
k
menwomen
200 300 400 500 600
Notes Available
33
Serum HDL and CHD
0
50
100
150
200
20 30 40 50 60 70 75+
Serum HDL Concentration (mg/dL)
Mor
bidi
ty R
atio
menwomen
Notes Available
34
Diet and Atherosclerosis
Low-fat diets− Lower blood cholesterol but also tend to lower LDL and
HDLLow-saturated, high-monounsaturated diets− Lower blood cholesterol and LDL, tend to increase HDL
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
36
Dietary Factors Affecting Blood Cholesterol
Increase− Saturated fat− Cholesterol− Trans fatty acids
Decrease− Monounsaturated fat− PUFA (fish oil)− Fiber
37
Non-Dietary Factors Affecting Blood Cholesterol
Increase− Smoking− Excess body fat− Alcohol
Decrease− Exercise− Estrogens
38
Other Nutrients Associated with Risk of CHD
Folic acidVitamins andIron
B6 B12
39
Folate and Vitamin B: Interrelationships
Homocysteine
Methionine
Methyl-THF
THF
5,10-methylene-THF
B6
B12
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.