• Provides key nutrients needed by the body to neutralize free radicals.• Helps protect against cellular damage. May exhibit anti-aging benefits.• Super ORAC (Primary) Antioxidants are the body’s own natural defense against free radicals.• They scavenge or ‘mop’ them up before they have a chance to harm cells.
Slow or prevent damage to body cells May improve immune function and lower risk for infection and cancer Carotenoids – beta carotene (familiar) Vitamin C Vitamin E Found in colorful fruits/veggies and grains
The free radical diseases•Cancer initiation and promotion isassociated with chromosomal defectsand oncogene activation. It is possiblethat endogenous free radical reactions,like those initiated by ionizing radiation,may result in tumour formation.
The free radical diseases•Atherosclerosis may be due to freeradical reactions involving diet-derivedlipids in the arterial wall and serum toyield peroxides and other substances.These compounds induce endothelialcell injury and produce changes in thearterial walls .
Antioxidants•vitamin E•vitamin C•carotenoids
vitamin E•Vitamin E is a fat-soluble substancepresent in all cellular membranes and ismainly stored in adipose tissue, the liverand muscle. Vitamin E is a principalantioxidant in the body and protectspolyunsaturated fatty acids in cellmembranes from peroxidation.
Vitamin E and cancer•Besides being a free radical scavenger,vitamin E at high intakes enhances thebodys immune responses. Vitamin E alsoinhibits the conversion of nitrites in thestomach to nitrosamines, which arecancer promoters.
Vitamin E and cardiovascular disease•Vitamin E intakes are associated withlowered risk of angina and mortality fromheart disease.
Vitamin E and neurological disorders•Supplementation with vitamin C andE might be of benefit in slowing theprogression of Parkinsons disease.
Vitamin C•Vitamin C, or ascorbic acid, is a water-soluble vitamin. This vitamin is a freeradical scavenger, it is considered to beone of the most important antioxidants inextra cellular fluids. Its protective effectsextend to cancer, coronary artery disease,arthritis and aging.
Vitamin C and cancer•Vitamin C is effective in protecting tissuesagainst oxidative damage. It suppresses theformation of carcinogens. Numerous studieshave reported the protective effect of fruit andvegetable consumption on incidence ofcancer . This is mainly attributed to theprotective effect of vitamin C against cancer.
Vitamin C and cardiovascular disease•Vitamin C may lower total cholesterol inthe blood, thus reducing the risk ofcardiovascular disease. Coronary heartdisease mortality is higher in those withblood vitamin C levels that are near or inthe deficient range.
Vitamin C and cataracts•High intake of fruits and vegetableswhich are rich sources of ascorbic acidappear to be protective too. In severalstudies, cataract patients were shown tohave low vitamin C and E intakes andlow plasma vitamin C levels.
Carotenoids•Carotenoids are a group of red, orangeand yellow pigments found in plantfoods, particularly fruits and vegetables.• Some carotenoids like b-carotene actas a precursor of vitamin A; others donot.
Superoxide Dismutase (SOD) is essential for the body and is: A metalloprotein – containing several sub units organised around a metallic group And most importantly An enzyme – the antioxidant enzyme SOD eliminates, in a continuous way, superoxideradicals, precursors of other oxygen reactive forms (secondary free radicals)
SOD acts at the source. It is the first and one of themajor components of the body’s antioxidant system.SOD is a powerful and efficient antioxidant: • 1 iu SOD eliminates 1μmol superoxide/min and SOD has an active lifespan of several days! • In the end, billions of superoxide molecules destroyed SOD is a primary antioxidant and possibly our most important one
Reactive oxygen species: formation of secondary free radicalsHydroxyl radical induces the formation ofsecondary free radicals: • Secondary free radicals or organic peroxides are very toxic • They increase oxidative reactions which are propagated from one to the next • They are directly responsible for cell alterations and destruction • They indirectly participate in the inflammation process
Antioxidant systems: the primary antioxidantsThe primary antioxidants: • are endogenous molecules • act at the source (where free radicals are created) • are enzymes which continuously eliminate the free radicals just formed: - SOD eliminates the superoxide ion - catalase and the glutathione peroxidase eliminate hydrogen peroxide
Antioxidant systems: the secondary antioxidantsThe secondary antioxidants • are exogenous molecules, carried by food (vitamins A, C, E, polyphenols…) • they scavenge the secondary free radicals • one molecule of a secondary antioxidant traps one free radical molecule – a 1:1 relationship
Oxidants and antioxidants in the bodyUnder normal circumstances andconditions, the body’s endogenousantioxidant systems are able to neutralizethe oxidant (free radical) molecules Therefore → no oxidative stress means → no cell damage
Oxidative stress… …is the result of an imbalance between oxidant and antioxidant production increase of free radicals→ antioxidant systems overpowered
Oxidative stress: consequencesA break in the equilibrium caused by… • UVA and B • Stress, overwork, diet • Pollution, chemicals, cigarettes • Chronic inflammation … puts the body into oxidative stress: → attacks on cell constituents (cell membranes, protein, lipids DNA) Only solution: we must combat free radicals
Lipid L• O2 (LH) OH• H2O Fe 2+ LOO• H2O2 1 O2 UV light heme Fe H2O, H+ CoQ H + O2 O2-• HOO• NADPH H+ or CoQ Figure 5. Pathways for the formation of reactive oxygen species Singlet oxygen lipid radical Peroxyl radical Haber-Weiss Superoxide reaction; lipid peroxyl radical anion Superoxide Fenton reaction radical dismutase
The fight against secondary free radicals……occurs with the secondary antioxidants (vitamins A,C, E, polyphenols etc) BUT antioxidants (acting 1 against 1) are quickly outnumbered and cannot eliminate a continuous and strong production of free radicals
Secondary antioxidants are vital but just slow down the oxidative stress– we need to do something extra…
Functions of Pentose Phosphate Pathway 1) NADPH for biosynthetic pathways (e.g., synthesis of fatty acids and cholesterol); 2) NADPH for maintaining glutathione in its reduced state . 3) Pentose sugar for synthesis of nucleic acids
Table 1. Reactive Oxygen Species and Antioxidants that Reduce ThemReactive Species AntioxidantSinglet oxygen 1O2 Vitamin A, vitamin ESuperoxide radical (O2-•) superoxide dismutase, vitamin CHydrogen peroxide(H2O2) Catalase; glutathione peroxidasePeroxyl radical (ROO•) Vitamin C, vitamin ELipid peroxyl radical Vitamin E(LOO•)Hydroxyl radical (OH•) Vitamin C
NUTRITIONAL CORRELATE: SELENIUM selenocysteine in glutathione peroxidase intake may be related to lower cancer mortality • cancer patients have lower plasma Se levels • risk may be higher in those with low Se intake • AZCC study – reduced incidence of prostate, colon, lung cancers toxicity (> 1 mg/day) results in hair loss, GI upset,nerve damage
Medical Scenario:If the antioxidant protective system in the redblood cell becomes defective, hemolyticanemia occurs; that is red blood cells undergohemolysis and their concentration in the blooddecreases. Such is the case if g luc o s e 6 -p ho s p ha te d e hy d ro g e na s e is defective in thepentose phosphate pathway. In individualswhose glucose 6-phosphate dehydrogenase isdefective, there is insufficient NADPH producedin red blood cells to maintain the ratio ofreduced glutathione to oxidized glutathione atits normal value of well over 100. Hence,