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File:Glutathione-3D-vdW.png

An antioxidant is a molecule capable of inhibiting the oxidation of other molecules. Oxidation is a chemical reaction that transfers electrons or hydrogen from a substance to an oxidizing agent. Oxidation reactions can produce free radicals. In turn, these radicals can start chain reactions. When the chain reaction occurs in a cell, it can cause damage or death to the cell. Antioxidants terminate these chain reactions by removing free radical intermediates, and inhibit other oxidation reactions. They do this by being oxidized themselves, so antioxidants are often reducing agents such as thiols, ascorbic acid, or polyphenols.[1]

Although oxidation reactions are crucial for life, they can also be damaging; plants and animals maintain complex systems of multiple types of antioxidants, such as glutathione, vitamin C, and vitamin E as well as enzymes such as catalase, superoxide dismutase and various peroxidases. Low levels of antioxidants, or inhibition of the antioxidant enzymes, cause oxidative stress and may damage or kill cells.

As oxidative stress appears to be an important part of many human diseases, the use of antioxidants in pharmacology is intensively studied, particularly as treatments for stroke and neurodegenerative diseases. However, it is unknown whether oxidative stress is the cause or the consequence of disease.

Antioxidants are widely used as ingredients in dietary supplements and have been investigated for the prevention of diseases such as cancer, coronary heart disease and even altitude sickness. Although initial studies suggested that antioxidant supplements might promote health, later large clinical trials did not detect any benefit and suggested instead that excess supplementation is harmful.[2][3] (Concerning the previous studies cited the first only shows that antioxidant supplements were not effective in helping against "mountain sickness", and in the second study showed that the supplements beta carotene, vitamin A, and vitamin E, "singly or combined, significantly increased mortality." Though it says that "Most trials investigated the effects of supplements administered at higher doses than those commonly found in a balanced diet" whereas it says "Vitamin C and selenium had no significant effect on mortality.") In addition to these uses of natural antioxidants in medicine, these compounds have many industrial uses, such as preservatives in food and cosmetics and preventing the degradation of rubber and gasoline.

History Edit

As part of their adaptation from marine life, terrestrial plants began producing non-marine antioxidants such as ascorbic acid (Vitamin C), polyphenols and tocopherols. The evolution of angiosperm plants between 50 and 200 million years ago resulted in the development of many antioxidant pigments — particularly during the Jurassic period — as chemical defences against reactive oxygen species that are byproducts of photosynthesis.[4][5] The term antioxidant originally was used to refer specifically to a chemical that prevented the consumption of oxygen. In the late 19th and early 20th centuries, extensive study was devoted to the uses of antioxidants in important industrial processes, such as the prevention of metal corrosion, the vulcanization of rubber, and the polymerization of fuels in the fouling of internal combustion engines.[6]

Early research on the role of antioxidants in biology focused on their use in preventing the oxidation of unsaturated fats, which is the cause of rancidity.[7] Antioxidant activity could be measured simply by placing the fat in a closed container with oxygen and measuring the rate of oxygen consumption. However, it was the identification of vitamins A, C, and E as antioxidants that revolutionized the field and led to the realization of the importance of antioxidants in the biochemistry of living organisms.[8][9]

The possible mechanisms of action of antioxidants were first explored when it was recognized that a substance with anti-oxidative activity is likely to be one that is itself readily oxidized.[10] Research into how vitamin E prevents the process of lipid peroxidation led to the identification of antioxidants as reducing agents that prevent oxidative reactions, often by scavenging reactive oxygen species before they can damage cells.[11]

The oxidative challenge in biology Edit

Further information: Oxidative stress
File:L-ascorbic-acid-3D-balls.png

A paradox in metabolism is that while the vast majority of complex life on Earth requires oxygen for its existence, oxygen is a highly reactive molecule that damages living organisms by producing reactive oxygen species.[12] Consequently, organisms contain a complex network of antioxidant metabolites and enzymes that work together to prevent oxidative damage to cellular components such as DNA, proteins and lipids.[1][13] In general, antioxidant systems either prevent these reactive species from being formed, or remove them before they can damage vital components of the cell.[1][12] However, since reactive oxygen species do have useful functions in cells, such as redox signaling, the function of antioxidant systems is not to remove oxidants entirely, but instead to keep them at an optimum level.[14]

The reactive oxygen species produced in cells include hydrogen peroxide (H2O2), hypochlorous acid (HClO), and free radicals such as the hydroxyl radical (·OH) and the superoxide anion (O2).[15] The hydroxyl radical is particularly unstable and will react rapidly and non-specifically with most biological molecules. This species is produced from hydrogen peroxide in metal-catalyzed redox reactions such as the Fenton reaction.[16] These oxidants can damage cells by starting chemical chain reactions such as lipid peroxidation, or by oxidizing DNA or proteins.[1] Damage to DNA can cause mutations and possibly cancer, if not reversed by DNA repair mechanisms,[17][18] while damage to proteins causes enzyme inhibition, denaturation and protein degradation.[19]

The use of oxygen as part of the process for generating metabolic energy produces reactive oxygen species.[20] In this process, the superoxide anion is produced as a by-product of several steps in the electron transport chain.[21] Particularly important is the reduction of coenzyme Q in complex III, since a highly reactive free radical is formed as an intermediate (Q·). This unstable intermediate can lead to electron "leakage", when electrons jump directly to oxygen and form the superoxide anion, instead of moving through the normal series of well-controlled reactions of the electron transport chain.[22] Peroxide is also produced from the oxidation of reduced flavoproteins, such as complex I.[23] However, although these enzymes can produce oxidants, the relative importance of the electron transfer chain to other processes that generate peroxide is unclear.[24][25] In plants, algae, and cyanobacteria, reactive oxygen species are also produced during photosynthesis,[26] particularly under conditions of high light intensity.[27] This effect is partly offset by the involvement of carotenoids in photoinhibition, which involves these antioxidants reacting with over-reduced forms of the photosynthetic reaction centres to prevent the production of reactive oxygen species.[28][29]

Metabolites Edit

Overview Edit

Antioxidants are classified into two broad divisions, depending on whether they are soluble in water (hydrophilic) or in lipids (hydrophobic). In general, water-soluble antioxidants react with oxidants in the cell cytosol and the blood plasma, while lipid-soluble antioxidants protect cell membranes from lipid peroxidation.[1] These compounds may be synthesized in the body or obtained from the diet.[13] The different antioxidants are present at a wide range of concentrations in body fluids and tissues, with some such as glutathione or ubiquinone mostly present within cells, while others such as uric acid are more evenly distributed (see table below). Some antioxidants are only found in a few organisms and these compounds can be important in pathogens and can be virulence factors.[30]

The relative importance and interactions between these different antioxidants is a very complex question, with the various metabolites and enzyme systems having synergistic and interdependent effects on one another.[31][32] The action of one antioxidant may therefore depend on the proper function of other members of the antioxidant system.[13] The amount of protection provided by any one antioxidant will also depend on its concentration, its reactivity towards the particular reactive oxygen species being considered, and the status of the antioxidants with which it interacts.[13]

Some compounds contribute to antioxidant defense by chelating transition metals and preventing them from catalyzing the production of free radicals in the cell. Particularly important is the ability to sequester iron, which is the function of iron-binding proteins such as transferrin and ferritin.[25] Selenium and zinc are commonly referred to as antioxidant nutrients, but these chemical elements have no antioxidant action themselves and are instead required for the activity of some antioxidant enzymes, as is discussed below.

Antioxidant metabolite Solubility Concentration in human serum (μM)[33] Concentration in liver tissue (μmol/kg)
Ascorbic acid (vitamin C) Water 50 – 60[34] 260 (human)[35]
Glutathione Water 4[36] 6,400 (human)[35]
Lipoic acid Water 0.1 – 0.7[37] 4 – 5 (rat)[38]
Uric acid Water 200 – 400[39] 1,600 (human)[35]
Carotenes Lipid β-carotene: 0.5 – 1[40]

retinol (vitamin A): 1 – 3[41]

5 (human, total carotenoids)[42]
α-Tocopherol (vitamin E) Lipid 10 – 40[41] 50 (human)[35]
Ubiquinol (coenzyme Q) Lipid 5[43] 200 (human)[44]

Uric acid Edit

Uric acid (UA) is an oxypurine produced from xanthine by the enzyme xanthine oxidase, and is an intermediate product of purine metabolism.[45] In almost all land animals, Urate oxidase further catalyzes the oxidation of uric acid to allantoin.[46] In humans and most higher primates, though, the UA gene is present, but nonfunctional so that UA is not further processed.[46][47] The evolutionary reasons for this loss of urate converstion to allantoin remain the topic of active speculation,[48][49] but the antioxidant effects of uric acid have led researchers to suggest this mutation was beneficial to early primates and humans.[49][50] Studies of high altitude acclimatization support the hypothesis that urate acts as an antioxidant by mitigating the oxidative stress caused by high-altitude hypoxia.[51] In animal studies that investigate diseases facilitated by oxidative stress, introduction of UA both prevents the disease or reduces it, leading researchers to propose this is due to UA's antioxidant properties.[52] Studies of UA's antioxidant mechanism have supported this proposal.[53] Gwen Scott explains the significance of these findings by proposing that "Serum UA levels are inversely associated with the incidence of MS in humans because MS patients have low serum UA levels and individuals with hyperuricemia (gout) rarely develop the disease. Moreover, the administration of UA is therapeutic in experimental allergic encephalomyelitis (EAE), an animal model of MS."[52][54][55] While the mechanism of UA as an antioxidant is well-supported, the claim that its levels affect MS risk is still controversial,[56][57] and requires more research. When compared to other antioxidants, UA has the highest concentration of any in the blood[39] and provides about half of the total antioxidant capacity of human serum.[58] Uric acid's antioxidant activities are also complex, given that it does not react with all oxidants, such as superoxide but does act against peroxynitrite,[59] peroxides, and hypochlorous acid.[45] Concerns over elevated UA's contribution to gout must be considered as one of many risk factors.[60] By itself, UA-related risk of gout at high levels (415-530 μmol/L) is only 0.5% per year with an increase to 4.5% per year at UA supersaturation levels (535+ μmol/L).[61] Many of these aforementioned studies determined UA's antioxidant actions within normal physiological levels,[51][59] and some found antioxidant activity at levels as high as 285 μmol/L.[62] The effects of uric acid in conditions such as stroke and heart attacks are still not well understood, with some studies linking higher levels of uric acid with increased mortality[63][64] and other, more careful studies showing no association.[59] This apparent effect might be due to uric acid being activated as a defense mechanism against oxidative stress, but instead acting as a pro-oxidant in cases where metabolic derangements shift its production well outside of normal levels.[59][63][64]

Ascorbic acid Edit

Ascorbic acid or "vitamin C" is a monosaccharide oxidation-reduction (redox) catalyst found in both animals and plants. As one of the enzymes needed to make ascorbic acid has been lost by mutation during primate evolution, humans must obtain it from the diet; it is therefore a vitamin.[65] Most other animals are able to produce this compound in their bodies and do not require it in their diets.[66] Ascorbic acid is required for the conversion of the procollagen to collagen by oxidizing proline residues to hydroxyproline. In other cells, it is maintained in its reduced form by reaction with glutathione, which can be catalysed by protein disulfide isomerase and glutaredoxins.[67][68] Ascorbic acid is redox catalyst which can reduce, and thereby neutralize, reactive oxygen species such as hydrogen peroxide.[69] In addition to its direct antioxidant effects, ascorbic acid is also a substrate for the redox enzyme ascorbate peroxidase, a function that is particularly important in stress resistance in plants.[70] Ascorbic acid is present at high levels in all parts of plants and can reach concentrations of 20 millimolar in chloroplasts.[71]

Glutathione Edit

File:Lipid peroxidation.svg

Glutathione is a cysteine-containing peptide found in most forms of aerobic life.[72] It is not required in the diet and is instead synthesized in cells from its constituent amino acids.[73] Glutathione has antioxidant properties since the thiol group in its cysteine moiety is a reducing agent and can be reversibly oxidized and reduced. In cells, glutathione is maintained in the reduced form by the enzyme glutathione reductase and in turn reduces other metabolites and enzyme systems, such as ascorbate in the glutathione-ascorbate cycle, glutathione peroxidases and glutaredoxins, as well as reacting directly with oxidants.[67] Due to its high concentration and its central role in maintaining the cell's redox state, glutathione is one of the most important cellular antioxidants.[72] In some organisms glutathione is replaced by other thiols, such as by mycothiol in the Actinomycetes, bacillithiol in some Gram-positive bacteria,[74][75] or by trypanothione in the Kinetoplastids.[76][77]

Melatonin Edit

Melatonin is a powerful antioxidant and, unlike conventional antioxidants such as vitamins C and E and glutathione, it is both produced in the human body and is acquired in the diet (fruits, vegetables, cereals and herbs etc., contain melatonin).[78] Melatonin easily crosses cell membranes and the blood-brain barrier.[79] Unlike other antioxidants, melatonin does not undergo redox cycling, which is the ability of a molecule to undergo repeated reduction and oxidation. Redox cycling may allow other antioxidants (such as vitamin C) to act as pro-oxidants and promote free radical formation. Melatonin, once oxidized, cannot be reduced to its former state because it forms several stable end-products upon reacting with free radicals. Therefore, it has been referred to as a terminal (or suicidal) antioxidant.[80]

Tocopherols and tocotrienols (vitamin E) Edit

Vitamin E is the collective name for a set of eight related tocopherols and tocotrienols, which are fat-soluble vitamins with antioxidant properties.[81][82] Of these, α-tocopherol has been most studied as it has the highest bioavailability, with the body preferentially absorbing and metabolising this form.[83]

It has been claimed that the α-tocopherol form is the most important lipid-soluble antioxidant, and that it protects membranes from oxidation by reacting with lipid radicals produced in the lipid peroxidation chain reaction.[81][84] This removes the free radical intermediates and prevents the propagation reaction from continuing. This reaction produces oxidised α-tocopheroxyl radicals that can be recycled back to the active reduced form through reduction by other antioxidants, such as ascorbate, retinol or ubiquinol.[85] This is in line with findings showing that α-tocopherol, but not water-soluble antioxidants, efficiently protects glutathione peroxidase 4 (GPX4)-deficient cells from cell death.[86] GPx4 is the only known enzyme that efficiently reduces lipid-hydroperoxides within biological membranes.

However, the roles and importance of the various forms of vitamin E are presently unclear,[87][88] and it has even been suggested that the most important function of α-tocopherol is as a signaling molecule, with this molecule having no significant role in antioxidant metabolism.[89][90] The functions of the other forms of vitamin E are even less well-understood, although γ-tocopherol is a nucleophile that may react with electrophilic mutagens,[83] and tocotrienols may be important in protecting neurons from damage.[91]

Pro-oxidant activities Edit

Further information: Pro-oxidant

Antioxidants that are reducing agents can also act as pro-oxidants. For example, vitamin C has antioxidant activity when it reduces oxidizing substances such as hydrogen peroxide,[92] however, it will also reduce metal ions that generate free radicals through the Fenton reaction.[93][94]

2 Fe3+ + Ascorbate → 2 Fe2+ + Dehydroascorbate
2 Fe2+ + 2 H2O2 → 2 Fe3+ + 2 OH· + 2 OH

The relative importance of the antioxidant and pro-oxidant activities of antioxidants are an area of current research, but vitamin C, which exerts its effects as a vitamin by oxidizing polypeptides, appears to have a mostly antioxidant action in the human body.[93][95] However, less data is available for other dietary antioxidants, such as vitamin E,[96] or the polyphenols.[97][98]

Potential of antioxidant supplements to damage healthEdit

There is evidence that antioxidant supplements promote disease and increase mortality in humans.[98][99] It was previously proposed on a hypothetical basis that free radicals may induce an endogenous response culminating in more effective adaptations which protect against exogenous radicals (and possibly other toxic compounds).[100] Recent experimental evidence strongly suggests that this is indeed the case, and that such induction of endogenous free radical production extends the life span of Caenorhabditis elegans.[101] Most importantly, this induction of life span is prevented by antioxidants, providing direct evidence that toxic radicals may mitohormetically exert life extending and health promoting effects.[98][99]

Enzyme systems Edit

File:Antioxidant pathway.svg

Overview Edit

As with the chemical antioxidants, cells are protected against oxidative stress by an interacting network of antioxidant enzymes.[1][12] Here, the superoxide released by processes such as oxidative phosphorylation is first converted to hydrogen peroxide and then further reduced to give water. This detoxification pathway is the result of multiple enzymes, with superoxide dismutases catalysing the first step and then catalases and various peroxidases removing hydrogen peroxide. As with antioxidant metabolites, the contributions of these enzymes to antioxidant defenses can be hard to separate from one another, but the generation of transgenic mice lacking just one antioxidant enzyme can be informative.[102]

Superoxide dismutase, catalase and peroxiredoxins Edit

Superoxide dismutases (SODs) are a class of closely related enzymes that catalyze the breakdown of the superoxide anion into oxygen and hydrogen peroxide.[103][104] SOD enzymes are present in almost all aerobic cells and in extracellular fluids.[105] Superoxide dismutase enzymes contain metal ion cofactors that, depending on the isozyme, can be copper, zinc, manganese or iron. In humans, the copper/zinc SOD is present in the cytosol, while manganese SOD is present in the mitochondrion.[104] There also exists a third form of SOD in extracellular fluids, which contains copper and zinc in its active sites.[106] The mitochondrial isozyme seems to be the most biologically important of these three, since mice lacking this enzyme die soon after birth.[107] In contrast, the mice lacking copper/zinc SOD (Sod1) are viable but have numerous pathologies and a reduced lifespan (see article on superoxide), while mice without the extracellular SOD have minimal defects (sensitive to hyperoxia).[102][108] In plants, SOD isozymes are present in the cytosol and mitochondria, with an iron SOD found in chloroplasts that is absent from vertebrates and yeast.[109]

Catalases are enzymes that catalyse the conversion of hydrogen peroxide to water and oxygen, using either an iron or manganese cofactor.[110][111] This protein is localized to peroxisomes in most eukaryotic cells.[112] Catalase is an unusual enzyme since, although hydrogen peroxide is its only substrate, it follows a ping-pong mechanism. Here, its cofactor is oxidised by one molecule of hydrogen peroxide and then regenerated by transferring the bound oxygen to a second molecule of substrate.[113] Despite its apparent importance in hydrogen peroxide removal, humans with genetic deficiency of catalase — "acatalasemia" — or mice genetically engineered to lack catalase completely, suffer few ill effects.[114][115]

File:Peroxiredoxin.png

Peroxiredoxins are peroxidases that catalyze the reduction of hydrogen peroxide, organic hydroperoxides, as well as peroxynitrite.[117] They are divided into three classes: typical 2-cysteine peroxiredoxins; atypical 2-cysteine peroxiredoxins; and 1-cysteine peroxiredoxins.[118] These enzymes share the same basic catalytic mechanism, in which a redox-active cysteine (the peroxidatic cysteine) in the active site is oxidized to a sulfenic acid by the peroxide substrate.[119] Over-oxidation of this cysteine residue in peroxiredoxins inactivates these enzymes, but this can be reversed by the action of sulfiredoxin.[120] Peroxiredoxins seem to be important in antioxidant metabolism, as mice lacking peroxiredoxin 1 or 2 have shortened lifespan and suffer from hemolytic anaemia, while plants use peroxiredoxins to remove hydrogen peroxide generated in chloroplasts.[121][122][123]

Thioredoxin and glutathione systems Edit

The thioredoxin system contains the 12-kDa protein thioredoxin and its companion thioredoxin reductase.[124] Proteins related to thioredoxin are present in all sequenced organisms. Plants, such as Arabidopsis thaliana, have a particularly great diversity of isoforms.[125] The active site of thioredoxin consists of two neighboring cysteines, as part of a highly conserved CXXC motif, that can cycle between an active dithiol form (reduced) and an oxidized disulfide form. In its active state, thioredoxin acts as an efficient reducing agent, scavenging reactive oxygen species and maintaining other proteins in their reduced state.[126] After being oxidized, the active thioredoxin is regenerated by the action of thioredoxin reductase, using NADPH as an electron donor.[127]

The glutathione system includes glutathione, glutathione reductase, glutathione peroxidases and glutathione S-transferases.[72] This system is found in animals, plants and microorganisms.[72][128] Glutathione peroxidase is an enzyme containing four selenium-cofactors that catalyzes the breakdown of hydrogen peroxide and organic hydroperoxides. There are at least four different glutathione peroxidase isozymes in animals.[129] Glutathione peroxidase 1 is the most abundant and is a very efficient scavenger of hydrogen peroxide, while glutathione peroxidase 4 is most active with lipid hydroperoxides. Surprisingly, glutathione peroxidase 1 is dispensable, as mice lacking this enzyme have normal lifespans,[130] but they are hypersensitive to induced oxidative stress.[131] In addition, the glutathione S-transferases show high activity with lipid peroxides.[132] These enzymes are at particularly high levels in the liver and also serve in detoxification metabolism.[133]

Oxidative stress in disease Edit

Further information: Pathology, Free-radical theory of aging, Oxidative stress

Oxidative stress is thought to contribute to the development of a wide range of diseases including Alzheimer's disease,[134][135] Parkinson's disease,[136] the pathologies caused by diabetes,[137][138] rheumatoid arthritis,[139] and neurodegeneration in motor neuron diseases.[140] In many of these cases, it is unclear if oxidants trigger the disease, or if they are produced as a secondary consequence of the disease and from general tissue damage;[15] One case in which this link is particularly well-understood is the role of oxidative stress in cardiovascular disease. Here, low density lipoprotein (LDL) oxidation appears to trigger the process of atherogenesis, which results in atherosclerosis, and finally cardiovascular disease.[141][142]

Oxidative damage in DNA can cause cancer. However, several antioxidant enzymes such as superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, glutathione S-transferase etc. protect DNA from oxidative stress. It has been proposed that polymorphisms in these enzymes are associated with DNA damage and subsequently the individual’s risk of cancer susceptibility.[143]

A low calorie diet extends median and maximum lifespan in many animals. This effect may involve a reduction in oxidative stress.[144] While there is some evidence to support the role of oxidative stress in aging in model organisms such as Drosophila melanogaster and Caenorhabditis elegans,[145][146] the evidence in mammals is less clear.[147][148][149] Indeed, a 2009 review of experiments in mice concluded that almost all manipulations of antioxidant systems had no effect on aging.[150] Diets high in fruit and vegetables, which are high in antioxidants, promote health and reduce the effects of aging, however antioxidant vitamin supplementation has no detectable effect on the aging process, so the effects of fruit and vegetables may be unrelated to their antioxidant contents.[151][152] One reason for this might be the fact that consuming antioxidant molecules such as polyphenols and vitamin E will produce changes in other parts of metabolism, so it may be these other effects that are the real reason these compounds are important in human nutrition.[89][153]

Health effects Edit

Disease treatment Edit

The brain is uniquely vulnerable to oxidative injury, due to its high metabolic rate and elevated levels of polyunsaturated lipids, the target of lipid peroxidation.[154] Consequently, antioxidants are commonly used as medications to treat various forms of brain injury. Here, superoxide dismutase mimetics,[155] sodium thiopental and propofol are used to treat reperfusion injury and traumatic brain injury,[156] while the experimental drug NXY-059[157][158] and ebselen[159] are being applied in the treatment of stroke. These compounds appear to prevent oxidative stress in neurons and prevent apoptosis and neurological damage. Antioxidants are also being investigated as possible treatments for neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis,[160][161] and as a way to prevent noise-induced hearing loss.[162] Targeted antioxidants may lead to better medicinal effects. Mitochondria-targeted ubiquinone, for example, may prevent damage to the liver caused by excessive alcohol.[163]

Disease prevention Edit

File:Resveratrol.svg

People who eat fruits and vegetables have a lower risk of heart disease and some neurological diseases,[164] and there is evidence that some types of vegetables, and fruits in general, protect against some cancers.[165] Since fruits and vegetables happen to be good sources of antioxidants, this suggested that antioxidants might prevent some types of diseases. This idea has been tested in clinical trials and does not seem to be true, as antioxidant supplements have no clear effect on the risk of chronic diseases such as cancer and heart disease.[164][166] This suggests that these health benefits come from other substances in fruits and vegetables (possibly flavonoids), or come from a complex mix of substances.[167][168]

It is thought that oxidation of low density lipoprotein in the blood contributes to heart disease, and initial observational studies found that people taking Vitamin E supplements had a lower risk of developing heart disease.[169] Consequently, at least seven large clinical trials were conducted to test the effects of antioxidant supplement with Vitamin E, in doses ranging from 50 to 600 mg per day. None of these trials found a statistically significant effect of Vitamin E on overall number of deaths or on deaths due to heart disease.[170] Further studies have also been negative.[171][172] It is not clear if the doses used in these trials or in most dietary supplements are capable of producing any significant decrease in oxidative stress.[173] Overall, despite the clear role of oxidative stress in cardiovascular disease, controlled studies using antioxidant vitamins have observed no reduction in either the risk of developing heart disease, or the rate of progression of existing disease.[174][175]

While several trials have investigated supplements with high doses of antioxidants, the "Supplémentation en Vitamines et Mineraux Antioxydants" (SU.VI.MAX) study tested the effect of supplementation with doses comparable to those in a healthy diet.[176] Over 12,500 French men and women took either low-dose antioxidants (120 mg of ascorbic acid, 30 mg of vitamin E, 6 mg of beta carotene, 100 µg of selenium, and 20 mg of zinc) or placebo pills for an average of 7.5 years. The study concluded that low-dose antioxidant supplementation lowered total cancer incidence and all-cause mortality in men but not in women. Supplementation may be effective in men only because of their lower baseline status of certain antioxidants, especially of beta carotene.

Many nutraceutical and health food companies sell formulations of antioxidants as dietary supplements and these are widely used in industrialized countries.[177] These supplements may include specific antioxidant chemicals, like the polyphenol, resveratrol (from grape seeds or knotweed roots),[178] combinations of antioxidants, like the "ACES" products that contain beta carotene (provitamin A), vitamin C, vitamin E and Selenium, or herbs that contain antioxidants - such as green tea and jiaogulan. Although some levels of antioxidant vitamins and minerals in the diet are required for good health, there is considerable doubt as to whether these antioxidant supplements are beneficial or harmful, and if they are actually beneficial, which antioxidant(s) are needed and in what amounts.[164][166][179] Indeed, some authors argue that the hypothesis that antioxidants could prevent chronic diseases has now been disproved and that the idea was misguided from the beginning.[180] Rather, dietary polyphenols may have non-antioxidant roles in minute concentrations that affect cell-to-cell signaling, receptor sensitivity, inflammatory enzyme activity or gene regulation.[181][182]

For overall life expectancy, it has even been suggested that moderate levels of oxidative stress may increase lifespan in the worm Caenorhabditis elegans, by inducing a protective response to increased levels of reactive oxygen species.[183] The suggestion that increased life expectancy comes from increased oxidative stress conflicts with results seen in the yeast Saccharomyces cerevisiae,[184] and the situation in mammals is even less clear.[147][148][149] Nevertheless, antioxidant supplements do not appear to increase life expectancy in humans.[185]

Physical exercise Edit

During exercise, oxygen consumption can increase by a factor of more than 10.[186] This leads to a large increase in the production of oxidants and results in damage that contributes to muscular fatigue during and after exercise. The inflammatory response that occurs after strenuous exercise is also associated with oxidative stress, especially in the 24 hours after an exercise session. The immune system response to the damage done by exercise peaks 2 to 7 days after exercise, which is the period during which most of the adaptation that leads to greater fitness occurs. During this process, free radicals are produced by neutrophils to remove damaged tissue. As a result, excessive antioxidant levels may inhibit recovery and adaptation mechanisms.[187] Antioxidant supplements may also prevent any of the health gains that normally come from exercise, such as increased insulin sensitivity.[188]

The evidence for benefits from antioxidant supplementation in vigorous exercise is mixed. There is strong evidence that one of the adaptations resulting from exercise is a strengthening of the body's antioxidant defenses, particularly the glutathione system, to regulate the increased oxidative stress.[189] This effect may be to some extent protective against diseases which are associated with oxidative stress, which would provide a partial explanation for the lower incidence of major diseases and better health of those who undertake regular exercise.[190]

However, no benefits for physical performance to athletes are seen with vitamin E supplementation.[191] Indeed, despite its key role in preventing lipid membrane peroxidation, 6 weeks of vitamin E supplementation had no effect on muscle damage in ultramarathon runners.[192] Although there appears to be no increased requirement for vitamin C in athletes, there is some evidence that vitamin C supplementation increased the amount of intense exercise that can be done and vitamin C supplementation before strenuous exercise may reduce the amount of muscle damage.[193][194] However, other studies found no such effects, and some research suggests that supplementation with amounts as high as 1000 mg inhibits recovery.[195]

Adverse effects Edit

File:Phytate.png

Relatively strong reducing acids can have antinutrient effects by binding to dietary minerals such as iron and zinc in the gastrointestinal tract and preventing them from being absorbed.[196] Notable examples are oxalic acid, tannins and phytic acid, which are high in plant-based diets.[197] Calcium and iron deficiencies are not uncommon in diets in developing countries where less meat is eaten and there is high consumption of phytic acid from beans and unleavened whole grain bread.[198]

Foods Reducing acid present
Cocoa bean and chocolate, spinach, turnip and rhubarb.[199] Oxalic acid
Whole grains, maize, legumes.[200] Phytic acid
Tea, beans, cabbage.[199][201] Tannins

Nonpolar antioxidants such as eugenol—a major component of oil of cloves—have toxicity limits that can be exceeded with the misuse of undiluted essential oils.[202] Toxicity associated with high doses of water-soluble antioxidants such as ascorbic acid are less of a concern, as these compounds can be excreted rapidly in urine.[203] More seriously, very high doses of some antioxidants may have harmful long-term effects. The beta-Carotene and Retinol Efficacy Trial (CARET) study of lung cancer patients found that smokers given supplements containing beta-carotene and vitamin A had increased rates of lung cancer.[204] Subsequent studies confirmed these adverse effects.[205]

These harmful effects may also be seen in non-smokers, as a recent meta-analysis including data from approximately 230,000 patients showed that β-carotene, vitamin A or vitamin E supplementation is associated with increased mortality but saw no significant effect from vitamin C.[99] No health risk was seen when all the randomized controlled studies were examined together, but an increase in mortality was detected only when the high-quality and low-bias risk trials were examined separately. However, as the majority of these low-bias trials dealt with either elderly people, or people already suffering disease, these results may not apply to the general population.[206] This meta-analysis was later repeated and extended by the same authors, with the new analysis published by the Cochrane Collaboration; confirming the previous results.[207] These two publications are consistent with some previous meta-analyzes that also suggested that Vitamin E supplementation increased mortality,[208] and that antioxidant supplements increased the risk of colon cancer.[209] However, the results of this meta-analysis are inconsistent with other studies such as the SU.VI.MAX trial, which suggested that antioxidants have no effect on cause-all mortality.[176][210][211][212] Overall, the large number of clinical trials carried out on antioxidant supplements suggest that either these products have no effect on health, or that they cause a small increase in mortality in elderly or vulnerable populations.[99][164][166]

While antioxidant supplementation is widely used in attempts to prevent the development of cancer, it has been proposed that antioxidants may, paradoxically, interfere with cancer treatments.[213] This was thought to occur since the environment of cancer cells causes high levels of oxidative stress, making these cells more susceptible to the further oxidative stress induced by treatments. As a result, by reducing the redox stress in cancer cells, antioxidant supplements could decrease the effectiveness of radiotherapy and chemotherapy.[214][215] On the other hand, other reviews have suggested that antioxidants could reduce side effects or increase survival times.[216][217]

Measurement and levels in food Edit

Further information: List of antioxidants in food, Polyphenol antioxidants
File:Vegetarian diet.jpg

Measurement of antioxidants is not a straightforward process, as this is a diverse group of compounds with different reactivities to different reactive oxygen species. In food science, the oxygen radical absorbance capacity (ORAC) has become the current industry standard for assessing antioxidant strength of whole foods, juices and food additives.[218][219] Other measurement tests include the Folin-Ciocalteu reagent, and the Trolox equivalent antioxidant capacity assay.[220]

Antioxidants are found in varying amounts in foods such as vegetables, fruits, grain cereals, eggs, meat, legumes and nuts. Some antioxidants such as lycopene and ascorbic acid can be destroyed by long-term storage or prolonged cooking.[221][222] Other antioxidant compounds are more stable, such as the polyphenolic antioxidants in foods such as whole-wheat cereals and tea.[223][224] The effects of cooking and food processing are complex, as these processes can also increase the bioavailability of antioxidants, such as some carotenoids in vegetables.[225] In general, processed foods contain fewer antioxidants than fresh and uncooked foods, since the preparation processes may expose the food to oxygen.[226]

Antioxidant compounds Foods containing high levels of these antioxidants[201][227][228]
Vitamin C (ascorbic acid) Fresh Fruits and vegetables
Vitamin E (tocopherols, tocotrienols) Vegetable oils
Polyphenolic antioxidants (resveratrol, flavonoids) Tea, coffee, soy, fruit, olive oil, chocolate, cinnamon, oregano and red wine
Carotenoids (lycopene, carotenes, lutein) Fruit, vegetables and eggs.[229]

Other antioxidants are not vitamins and are instead made in the body. For example, ubiquinol (coenzyme Q) is poorly absorbed from the gut and is made in humans through the mevalonate pathway.[44] Another example is glutathione, which is made from amino acids. As any glutathione in the gut is broken down to free cysteine, glycine and glutamic acid before being absorbed, even large oral doses have little effect on the concentration of glutathione in the body.[230][231] Although large amounts of sulfur-containing amino acids such as acetylcysteine can increase glutathione,[232] no evidence exists that eating high levels of these glutathione precursors is beneficial for healthy adults.[233] Supplying more of these precursors may be useful as part of the treatment of some diseases, such as acute respiratory distress syndrome, protein-energy malnutrition, or preventing the liver damage produced by paracetamol overdose.[232][234]

Other compounds in the diet can alter the levels of antioxidants by acting as pro-oxidants. Here, consuming the compound causes oxidative stress, which the body responds to by inducing higher levels of antioxidant defenses such as antioxidant enzymes.[180] Some of these compounds, such as isothiocyanates and curcumin, may be chemopreventive agents that either block the transformation of abnormal cells into cancerous cells, or even kill existing cancer cells.[180][235]

Uses in technology Edit

Food preservatives Edit

Antioxidants are used as food additives to help guard against food deterioration. Exposure to oxygen and sunlight are the two main factors in the oxidation of food, so food is preserved by keeping in the dark and sealing it in containers or even coating it in wax, as with cucumbers. However, as oxygen is also important for plant respiration, storing plant materials in anaerobic conditions produces unpleasant flavors and unappealing colors.[236] Consequently, packaging of fresh fruits and vegetables contains an ~8% oxygen atmosphere. Antioxidants are an especially important class of preservatives as, unlike bacterial or fungal spoilage, oxidation reactions still occur relatively rapidly in frozen or refrigerated food.[237] These preservatives include natural antioxidants such as ascorbic acid (AA, E300) and tocopherols (E306), as well as synthetic antioxidants such as propyl gallate (PG, E310), tertiary butylhydroquinone (TBHQ), butylated hydroxyanisole (BHA, E320) and butylated hydroxytoluene (BHT, E321).[238][239]

The most common molecules attacked by oxidation are unsaturated fats; oxidation causes them to turn rancid.[240] Since oxidized lipids are often discolored and usually have unpleasant tastes such as metallic or sulfurous flavors, it is important to avoid oxidation in fat-rich foods. Thus, these foods are rarely preserved by drying; instead, they are preserved by smoking, salting or fermenting. Even less fatty foods such as fruits are sprayed with sulfurous antioxidants prior to air drying. Oxidation is often catalyzed by metals, which is why fats such as butter should never be wrapped in aluminium foil or kept in metal containers. Some fatty foods such as olive oil are partially protected from oxidation by their natural content of antioxidants, but remain sensitive to photooxidation.[241] Antioxidant preservatives are also added to fat-based cosmetics such as lipstick and moisturizers to prevent rancidity.

See also Edit

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ReferencesEdit

  1. 1.0 1.1 1.2 1.3 1.4 1.5 (1997). Oxidative stress: Oxidants and antioxidants. Experimental physiology 82 (2): 291–5.
  2. (2009). Oral antioxidant supplementation does not prevent acute mountain sickness: double blind, randomized placebo-controlled trial. QJM 102 (5): 341–8.
  3. Bjelakovic G (2007). Mortality in randomized trials of antioxidant supplements for primary and secondary prevention: systematic review and meta-analysis. JAMA 297 (8): 842–57.
  4. (2003). Evolution of dietary antioxidants. Comparative Biochemistry and Physiology 136 (1): 113–26.
  5. (2000). Environmental Iodine Deficiency: A Challenge to the Evolution of Terrestrial Life?. Thyroid 10 (8): 727–9.
  6. (1947). Antioxidants. Annual Review of Biochemistry 16: 177–92.
  7. (1999). Food processing and lipid oxidation. Advances in experimental medicine and biology 459: 23–50.
  8. (1996). Three eras of vitamin C discovery. Sub-cellular biochemistry 25: 1–16.
  9. (1998). Free radicals: Their history and current status in aging and disease. Annals of clinical and laboratory science 28 (6): 331–46.
  10. (1922). {{{title}}}. Comptes Rendus des Séances et Mémoires de la Société de Biologie 86.[verification needed]
  11. (2005). The discovery of the antioxidant function of vitamin E: The contribution of Henry A. Mattill. The Journal of nutrition 135 (3): 363–6.
  12. 12.0 12.1 12.2 (1995). Oxidative stress: The paradox of aerobic life. Biochemical Society Symposia 61: 1–31.
  13. 13.0 13.1 13.2 13.3 (2004). The Antioxidants and Pro-Antioxidants Network: An Overview. Current Pharmaceutical Design 10 (14): 1677–94.
  14. (2006). CELL SIGNALING: H2O2, a Necessary Evil for Cell Signaling. Science 312 (5782): 1882–3.
  15. 15.0 15.1 (2007). Free radicals and antioxidants in normal physiological functions and human disease. The International Journal of Biochemistry & Cell Biology 39 (1): 44–84.
  16. (1995). Oxidative mechanisms in the toxicity of metal ions. Free Radical Biology and Medicine 18 (2): 321–36.
  17. (2006). Mutagenesis and carcinogenesis caused by the oxidation of nucleic acids. Biological Chemistry 387 (4): 373–9.
  18. (2004). Role of oxygen radicals in DNA damage and cancer incidence. Molecular and Cellular Biochemistry 266 (1–2): 37–56.
  19. (1992). Protein oxidation and aging. Science 257 (5074): 1220–4.
  20. (2000). Mitochondria, oxygen free radicals, disease and ageing. Trends in Biochemical Sciences 25 (10): 502–8.
  21. (2001). The Mitochondrial Production of Reactive Oxygen Species: Mechanisms and Implications in Human Pathology. IUBMB Life 52 (3–5): 159–64.
  22. (2000). Oxidants, oxidative stress and the biology of ageing. Nature 408 (6809): 239–47.
  23. (2008). The production of reactive oxygen species by complex I. Biochemical Society Transactions 36 (5): 976–80.
  24. (2004). Are Respiratory Enzymes the Primary Sources of Intracellular Hydrogen Peroxide?. Journal of Biological Chemistry 279 (47): 48742–50.
  25. 25.0 25.1 (2003). Pathways Ofoxidativedamage. Annual Review of Microbiology 57: 395–418.
  26. (2002). Antioxidants in Photosynthesis and Human Nutrition. Science 298 (5601): 2149–53.
  27. (2004). Singlet oxygen production in photosynthesis. Journal of Experimental Botany 56 (411): 337–46.
  28. (2005). Light and oxygenic photosynthesis: Energy dissipation as a protection mechanism against photo-oxidation. EMBO reports 6 (7): 629–34.
  29. (2004). Water-soluble carotenoid proteins of cyanobacteria. Archives of Biochemistry and Biophysics 430 (1): 2–9.
  30. (1997). Role of oxidants in microbial pathophysiology. Clinical microbiology reviews 10 (1): 1–18.
  31. (1999). Intracellular Antioxidants: From Chemical to Biochemical Mechanisms. Food and Chemical Toxicology 37 (9–10): 949–62.
  32. (1993). Strategies of antioxidant defense. European Journal of Biochemistry 215 (2): 213–9.
  33. Ames B, Cathcart R, Schwiers E, Hochstein P (1981). Uric acid provides an antioxidant defense in humans against oxidant- and radical-caused aging and cancer: a hypothesis. Proc Natl Acad Sci USA 78 (11): 6858–62.
  34. (1995). Interrelation of vitamin C, infection, haemostatic factors, and cardiovascular disease. BMJ 310 (6994): 1559–63.
  35. 35.0 35.1 35.2 35.3 (2001). Evaluation of Total Reactive Antioxidant Potential (TRAP) of Tissue Homogenates and Their Cytosols. Archives of Biochemistry and Biophysics 388 (2): 261–6.
  36. (1999). Serum glutathione in adolescent males predicts parental coronary heart disease. Circulation 100 (22): 2244–7.
  37. (1992). HPLC-methods for determination of lipoic acid and its reduced form in human plasma. International journal of clinical pharmacology, therapy, and toxicology 30 (11): 511–2.
  38. (1998). Assay of Protein-Bound Lipoic Acid in Tissues by a New Enzymatic Method. Analytical Biochemistry 258 (2): 299–304.
  39. 39.0 39.1 (2005). Uric Acid and Oxidative Stress. Current Pharmaceutical Design 11 (32): 4145–51.
  40. (2002). Individual carotenoid concentrations in adipose tissue and plasma as biomarkers of dietary intake. The American journal of clinical nutrition 76 (1): 172–9.
  41. 41.0 41.1 (1994). Retinol, alpha-tocopherol, lutein/zeaxanthin, beta-cryptoxanthin, lycopene, alpha-carotene, trans-beta-carotene, and four retinyl esters in serum determined simultaneously by reversed-phase HPLC with multiwavelength detection. Clinical chemistry 40 (3): 411–6.
  42. (1992). cis-trans isomers of lycopene and ?-carotene in human serum and tissues. Archives of Biochemistry and Biophysics 294 (1): 173–7.
  43. (2003). Serum coenzyme Q10concentrations in healthy men supplemented with 30 mg or 100 mg coenzyme Q10 for two months in a randomised controlled study. BioFactors 18 (1–4): 185–93.
  44. 44.0 44.1 (2004). Metabolism and function of coenzyme Q. Biochimica et Biophysica Acta 1660 (1–2): 171–99.
  45. 45.0 45.1 (2005). Roles of organic anion transporters (OATs) and a urate transporter (URAT1) in the pathophysiology of human disease. Clinical and Experimental Nephrology 9 (3): 195–205.
  46. 46.0 46.1 (1989). Urate Oxidase: Primary Structure and Evolutionary Implications. Proceedings of the National Academy of Sciences 86 (23): 9412–6.
  47. (1992). Two independent mutational events in the loss of urate oxidase during hominoid evolution. Journal of Molecular Evolution 34 (1): 78–84.
  48. (2010). Uric acid and evolution. Rheumatology 49 (11): 2010–5.
  49. 49.0 49.1 (2002). Uric Acid, Hominoid Evolution, and the Pathogenesis of Salt-Sensitivity. Hypertension 40 (3): 355–60.
  50. (2010). Theodore E. Woodward award. The evolution of obesity: Insights from the mid-Miocene. Transactions of the American Clinical and Climatological Association 121: 295–305; discussion 305–8.
  51. 51.0 51.1 (2007). Endogenous Urate Production Augments Plasma Antioxidant Capacity in Healthy Lowland Subjects Exposed to High Altitude. Chest 131 (5): 1473–8.
  52. 52.0 52.1 (2000). Uric acid, a peroxynitrite scavenger, inhibits CNS inflammation, blood-CNS barrier permeability changes, and tissue damage in a mouse model of multiple sclerosis. The FASEB journal 14 (5): 691–8.
  53. (1999). Uric Acid Oxidation by Peroxynitrite: Multiple Reactions, Free Radical Formation, and Amplification of Lipid Oxidation. Archives of Biochemistry and Biophysics 372 (2): 285–94.
  54. (2002). Therapeutic intervention in experimental allergic encephalomyelitis by administration of uric acid precursors. Proceedings of the National Academy of Sciences 99 (25): 16303–8.
  55. (2007). Serum uric acid levels of patients with multiple sclerosis and other neurological diseases. Multiple Sclerosis 14 (2): 188–96.
  56. (2009). Serum uric acid and risk of multiple sclerosis. Journal of Neurology 256 (10): 1643–8.
  57. (2009). Increase of uric acid and purine compounds in biological fluids of multiple sclerosis patients. Clinical Biochemistry 42 (10–11): 1001–6.
  58. (1993). Towards the physiological function of uric acid. Free Radical Biology and Medicine 14 (6): 615–31.
  59. 59.0 59.1 59.2 59.3 (2008). Uric Acid: The Oxidant-Antioxidant Paradox. Nucleosides, Nucleotides and Nucleic Acids 27 (6): 608–19.
  60. Eggebeen, Aaron T (2007). Gout: An update. American family physician 76 (6): 801–8.
  61. (1987). Asymptomatic hyperuricemia. Risks and consequences in the normative aging study*1. The American Journal of Medicine 82 (3): 421–6.
  62. (2007). Effect of Short-Term Ketogenic Diet on Redox Status of Human Blood. Rejuvenation Research 10 (4): 435–40.
  63. 63.0 63.1 (2008). The Role of Uric Acid in Stroke. The Neurologist 14 (4): 238–42.
  64. 64.0 64.1 (2007). Uric acid and oxidative stress: Relative impact on cardiovascular risk. Nutrition, Metabolism and Cardiovascular Diseases 17 (6): 409–14.
  65. (2001). L-Ascorbic acid biosynthesis. Vitamins and hormones 61: 241–66.
  66. (2007). Vitamin C. FEBS Journal 274 (1): 1–22.
  67. 67.0 67.1 (1994). Glutathione-ascorbic acid antioxidant system in animals. The Journal of biological chemistry 269 (13): 9397–400.
  68. (1990). Mammalian thioltransferase (glutaredoxin) and protein disulfide isomerase have dehydroascorbate reductase activity. The Journal of biological chemistry 265 (26): 15361–4.
  69. (2003). Vitamin C as an antioxidant: evaluation of its role in disease prevention. Journal of the American College of Nutrition 22 (1): 18–35.
  70. (2002). Regulation and function of ascorbate peroxidase isoenzymes. Journal of Experimental Botany 53 (372): 1305–19.
  71. (2000). Ascorbic Acid in Plants: Biosynthesis and Function. Critical Reviews in Biochemistry and Molecular Biology 35 (4): 291–314.
  72. 72.0 72.1 72.2 72.3 (1983). Glutathione. Annual Review of Biochemistry 52: 711–60.
  73. (1988). Glutathione metabolism and its selective modification. The Journal of biological chemistry 263 (33): 17205–8.
  74. Gaballa A (April 2010). Biosynthesis and functions of bacillithiol, a major low-molecular-weight thiol in Bacilli. Proc. Natl. Acad. Sci. U.S.A. 107 (14): 6482–6.
  75. PMID 19578333 (PMID 19578333)
    Citation will be completed automatically in a few minutes. Jump the queue or expand by hand
  76. (2001). Novelthiols Ofprokaryotes. Annual Review of Microbiology 55: 333–56.
  77. (1992). Metabolism and Functions of Trypanothione in the Kinetoplastida. Annual Review of Microbiology 46: 695–729.
  78. (2007). One molecule, many derivatives: A never-ending interaction of melatonin with reactive oxygen and nitrogen species?. Journal of Pineal Research 42 (1): 28–42.
  79. (2009). Reducing oxidative/nitrosative stress: A newly-discovered genre for melatonin. Critical Reviews in Biochemistry and Molecular Biology 44 (4): 175–200.
  80. (2000). Significance of Melatonin in Antioxidative Defense System: Reactions and Products. Neurosignals 9 (3–4): 137–59.
  81. 81.0 81.1 (2001). Vitamin E: Action, metabolism and perspectives. Journal of Physiology and Biochemistry 57 (2): 43–56.
  82. (2001). Molecular aspects of alpha-tocotrienol antioxidant action and cell signalling. The Journal of nutrition 131 (2): 369S–73S.
  83. 83.0 83.1 (1999). Vitamin E: Function and metabolism. The FASEB journal 13 (10): 1145–55.
  84. (2007). Vitamin E, antioxidant and nothing more. Free Radical Biology and Medicine 43 (1): 4–15.
  85. (1999). Vitamin E and its function in membranes. Progress in Lipid Research 38 (4): 309–36.
  86. (2008). Glutathione Peroxidase 4 Senses and Translates Oxidative Stress into 12/15-Lipoxygenase Dependent- and AIF-Mediated Cell Death. Cell Metabolism 8 (3): 237–48.
  87. (2007). Is vitamin E an antioxidant, a regulator of signal transduction and gene expression, or a 'junk' food? Comments on the two accompanying papers: 'Molecular mechanism of α-tocopherol action' by A. Azzi and 'Vitamin E, antioxidant and nothing more' by M. Traber and J. Atkinson. Free Radical Biology and Medicine 43 (1): 2–3.
  88. (2008). Tocopherols and tocotrienols in membranes: A critical review. Free Radical Biology and Medicine 44 (5): 739–64.
  89. 89.0 89.1 (2007). Molecular mechanism of α-tocopherol action. Free Radical Biology and Medicine 43 (1): 16–21.
  90. (2004). Non-antioxidant activities of vitamin E. Current medicinal chemistry 11 (9): 1113–33.
  91. (2006). Tocotrienols: Vitamin E beyond tocopherols. Life Sciences 78 (18): 2088–98.
  92. Duarte TL, Lunec J (2005). Review: When is an antioxidant not an antioxidant? A review of novel actions and reactions of vitamin C. Free Radic. Res. 39 (7): 671–86.
  93. 93.0 93.1 Carr A, Frei B (1 June 1999). Does vitamin C act as a pro-oxidant under physiological conditions?. FASEB J. 13 (9): 1007–24.
  94. Stohs SJ, Bagchi D (1995). Oxidative mechanisms in the toxicity of metal ions. Free Radic. Biol. Med. 18 (2): 321–36.
  95. Valko M, Morris H, Cronin MT (2005). Metals, toxicity and oxidative stress. Curr. Med. Chem. 12 (10): 1161–208.
  96. Schneider C (2005). Chemistry and biology of vitamin E. Mol Nutr Food Res 49 (1): 7–30.
  97. Halliwell, B. (2008). Are polyphenols antioxidants or pro-oxidants? What do we learn from cell culture and in vivo studies?. Archives of Biochemistry and Biophysics 476 (2): 107–112.
  98. 98.0 98.1 98.2 PMID 20350594 (PMID 20350594)
    Citation will be completed automatically in a few minutes. Jump the queue or expand by hand
  99. 99.0 99.1 99.2 99.3 Bjelakovic G, Nikolova D, Gluud L, Simonetti R, Gluud C (2007). Mortality in Randomized Trials of Antioxidant Supplements for Primary and Secondary Prevention: Systematic Review and Meta-analysis. JAMA 297 (8): 842–57.
  100. (2006). Sublethal mitochondrial stress with an attendant stoichiometric augmentation of reactive oxygen species may precipitate many of the beneficial alterations in cellular physiology produced by caloric restriction, intermittent fasting, exercise and dietary phytonutrients: "Mitohormesis" for health and vitality. Medical Hypotheses 66 (4): 832–43.
  101. Schulz TJ, Zarse K, Voigt A, Urban N, Birringer M, Ristow M (2007). Glucose restriction extends Caenorhabditis elegans life span by inducing mitochondrial respiration and increasing oxidative stress. Cell Metab. 6 (4): 280–93.
  102. 102.0 102.1 Ho YS, Magnenat JL, Gargano M, Cao J (1 October 1998). The nature of antioxidant defense mechanisms: a lesson from transgenic studies. Environ. Health Perspect. 106 (Suppl 5): 1219–28.
  103. Zelko I, Mariani T, Folz R (2002). Superoxide dismutase multigene family: a comparison of the CuZn-SOD (SOD1), Mn-SOD (SOD2), and EC-SOD (SOD3) gene structures, evolution, and expression. Free Radic Biol Med 33 (3): 337–49.
  104. 104.0 104.1 Bannister J, Bannister W, Rotilio G (1987). Aspects of the structure, function, and applications of superoxide dismutase. CRC Crit Rev Biochem 22 (2): 111–80.
  105. Johnson F, Giulivi C (2005). Superoxide dismutases and their impact upon human health. Mol Aspects Med 26 (4–5): 340–52.
  106. Nozik-Grayck E, Suliman H, Piantadosi C (2005). Extracellular superoxide dismutase. Int J Biochem Cell Biol 37 (12): 2466–71.
  107. Melov S, Schneider J, Day B, Hinerfeld D, Coskun P, Mirra S, Crapo J, Wallace D (1998). A novel neurological phenotype in mice lacking mitochondrial manganese superoxide dismutase. Nat Genet 18 (2): 159–63.
  108. Reaume A, Elliott J, Hoffman E, Kowall N, Ferrante R, Siwek D, Wilcox H, Flood D, Beal M, Brown R, Scott R, Snider W (1996). Motor neurons in Cu/Zn superoxide dismutase-deficient mice develop normally but exhibit enhanced cell death after axonal injury. Nat Genet 13 (1): 43–7.
  109. Van Camp W, Inzé D, Van Montagu M (1997). The regulation and function of tobacco superoxide dismutases. Free Radic Biol Med 23 (3): 515–20.
  110. Chelikani P, Fita I, Loewen P (2004). Diversity of structures and properties among catalases. Cell Mol Life Sci 61 (2): 192–208.
  111. Zámocký M, Koller F (1999). Understanding the structure and function of catalases: clues from molecular evolution and in vitro mutagenesis. Prog Biophys Mol Biol 72 (1): 19–66.
  112. del Río L, Sandalio L, Palma J, Bueno P, Corpas F (1992). Metabolism of oxygen radicals in peroxisomes and cellular implications. Free Radic Biol Med 13 (5): 557–80.
  113. Hiner A, Raven E, Thorneley R, García-Cánovas F, Rodríguez-López J (2002). Mechanisms of compound I formation in heme peroxidases. J Inorg Biochem 91 (1): 27–34.
  114. Mueller S, Riedel H, Stremmel W (15 December 1997). Direct evidence for catalase as the predominant H2O2 -removing enzyme in human erythrocytes. Blood 90 (12): 4973–8.
  115. Ogata M (1991). Acatalasemia. Hum Genet 86 (4): 331–40.
  116. Parsonage D, Youngblood D, Sarma G, Wood Z, Karplus P, Poole L (2005). Analysis of the link between enzymatic activity and oligomeric state in AhpC, a bacterial peroxiredoxin. Biochemistry 44 (31): 10583–92. PDB 1YEX
  117. Rhee S, Chae H, Kim K (2005). Peroxiredoxins: a historical overview and speculative preview of novel mechanisms and emerging concepts in cell signaling. Free Radic Biol Med 38 (12): 1543–52.
  118. Wood Z, Schröder E, Robin Harris J, Poole L (2003). Structure, mechanism and regulation of peroxiredoxins. Trends Biochem Sci 28 (1): 32–40.
  119. Claiborne A, Yeh J, Mallett T, Luba J, Crane E, Charrier V, Parsonage D (1999). Protein-sulfenic acids: diverse roles for an unlikely player in enzyme catalysis and redox regulation. Biochemistry 38 (47): 15407–16.
  120. Jönsson TJ, Lowther WT (2007). The peroxiredoxin repair proteins. Sub-cellular biochemistry 44: 115–41.
  121. Neumann C, Krause D, Carman C, Das S, Dubey D, Abraham J, Bronson R, Fujiwara Y, Orkin S, Van Etten R (2003). Essential role for the peroxiredoxin Prdx1 in erythrocyte antioxidant defence and tumour suppression. Nature 424 (6948): 561–5.
  122. Lee T, Kim S, Yu S, Kim S, Park D, Moon H, Dho S, Kwon K, Kwon H, Han Y, Jeong S, Kang S, Shin H, Lee K, Rhee S, Yu D (2003). Peroxiredoxin II is essential for sustaining life span of erythrocytes in mice. Blood 101 (12): 5033–8.
  123. Dietz K, Jacob S, Oelze M, Laxa M, Tognetti V, de Miranda S, Baier M, Finkemeier I (2006). The function of peroxiredoxins in plant organelle redox metabolism. J Exp Bot 57 (8): 1697–709.
  124. Nordberg J, Arner ES (2001). Reactive oxygen species, antioxidants, and the mammalian thioredoxin system. Free Radic Biol Med 31 (11): 1287–312.
  125. Vieira Dos Santos C, Rey P (2006). Plant thioredoxins are key actors in the oxidative stress response. Trends Plant Sci 11 (7): 329–34.
  126. Arnér E, Holmgren A (2000). Physiological functions of thioredoxin and thioredoxin reductase. Eur J Biochem 267 (20): 6102–9.
  127. Mustacich D, Powis G (2000). Thioredoxin reductase. Biochem J 346 (Pt 1): 1–8.
  128. Creissen G, Broadbent P, Stevens R, Wellburn A, Mullineaux P (1996). Manipulation of glutathione metabolism in transgenic plants. Biochem Soc Trans 24 (2): 465–9.
  129. Brigelius-Flohé R (1999). Tissue-specific functions of individual glutathione peroxidases. Free Radic Biol Med 27 (9–10): 951–65.
  130. Ho Y, Magnenat J, Bronson R, Cao J, Gargano M, Sugawara M, Funk C (1997). Mice deficient in cellular glutathione peroxidase develop normally and show no increased sensitivity to hyperoxia. J Biol Chem 272 (26): 16644–51.
  131. de Haan J, Bladier C, Griffiths P, Kelner M, O'Shea R, Cheung N, Bronson R, Silvestro M, Wild S, Zheng S, Beart P, Hertzog P, Kola I (1998). Mice with a homozygous null mutation for the most abundant glutathione peroxidase, Gpx1, show increased susceptibility to the oxidative stress-inducing agents paraquat and hydrogen peroxide. J Biol Chem 273 (35): 22528–36.
  132. Sharma R, Yang Y, Sharma A, Awasthi S, Awasthi Y (2004). Antioxidant role of glutathione S-transferases: protection against oxidant toxicity and regulation of stress-mediated apoptosis. Antioxid Redox Signal 6 (2): 289–300.
  133. Hayes J, Flanagan J, Jowsey I (2005). Glutathione transferases. Annu Rev Pharmacol Toxicol 45: 51–88.
  134. Christen Y (1 February 2000). Oxidative stress and Alzheimer disease. Am J Clin Nutr 71 (2): 621S–629S.
  135. Nunomura A, Castellani R, Zhu X, Moreira P, Perry G, Smith M (2006). Involvement of oxidative stress in Alzheimer disease. J Neuropathol Exp Neurol 65 (7): 631–41.
  136. Wood-Kaczmar A, Gandhi S, Wood N (2006). Understanding the molecular causes of Parkinson's disease. Trends Mol Med 12 (11): 521–8.
  137. Davì G, Falco A, Patrono C (2005). Lipid peroxidation in diabetes mellitus. Antioxid Redox Signal 7 (1–2): 256–68.
  138. Giugliano D, Ceriello A, Paolisso G (1996). Oxidative stress and diabetic vascular complications. Diabetes Care 19 (3): 257–67.
  139. Hitchon C, El-Gabalawy H (2004). Oxidation in rheumatoid arthritis. Arthritis Res Ther 6 (6): 265–78.
  140. Cookson M, Shaw P (1999). Oxidative stress and motor neurone disease. Brain Pathol 9 (1): 165–86.
  141. Van Gaal L, Mertens I, De Block C (2006). Mechanisms linking obesity with cardiovascular disease. Nature 444 (7121): 875–80.
  142. Aviram M (2000). Review of human studies on oxidative damage and antioxidant protection related to cardiovascular diseases. Free Radic Res 33 Suppl: S85–97.
  143. Khan MA, Tania M, Zhang D, Chen H (2010). Antioxidant enzymes and cancer. Chin J Cancer Res 22 (2): 87–92.
  144. G. López-Lluch, N. Hunt, B. Jones, M. Zhu, H. Jamieson, S. Hilmer, M. V. Cascajo, J. Allard, D. K. Ingram, P. Navas, and R. de Cabo (2006). Calorie restriction induces mitochondrial biogenesis and bioenergetic efficiency. Proc Natl Acad Sci USA 103 (6): 1768–1773.
  145. Larsen P (1993). Aging and resistance to oxidative damage in Caenorhabditis elegans. Proc Natl Acad Sci USA 90 (19): 8905–9.
  146. Helfand S, Rogina B (2003). Genetics of aging in the fruit fly, Drosophila melanogaster. Annu Rev Genet 37: 329–48.
  147. 147.0 147.1 Sohal R, Mockett R, Orr W (2002). Mechanisms of aging: an appraisal of the oxidative stress hypothesis. Free Radic Biol Med 33 (5): 575–86.
  148. 148.0 148.1 Sohal R (2002). Role of oxidative stress and protein oxidation in the aging process. Free Radic Biol Med 33 (1): 37–44.
  149. 149.0 149.1 Rattan S (2006). Theories of biological aging: genes, proteins, and free radicals. Free Radic Res 40 (12): 1230–8.
  150. Pérez, Viviana I. (2009). Is the oxidative stress theory of aging dead?. Biochimica et Biophysica Acta (BBA) - General Subjects 1790 (10): 1005–1014.
  151. Thomas D (2004). Vitamins in health and aging. Clin Geriatr Med 20 (2): 259–74.
  152. Ward J (1998). Should antioxidant vitamins be routinely recommended for older people?. Drugs Aging 12 (3): 169–75.
  153. Aggarwal BB, Shishodia S (2006). Molecular targets of dietary agents for prevention and therapy of cancer. Biochem. Pharmacol. 71 (10): 1397–421.
  154. Reiter R (1995). Oxidative processes and antioxidative defense mechanisms in the aging brain. FASEB J 9 (7): 526–33.
  155. Warner D, Sheng H, Batinić-Haberle I (2004). Oxidants, antioxidants and the ischemic brain. J Exp Biol 207 (Pt 18): 3221–31.
  156. Wilson J, Gelb A (2002). Free radicals, antioxidants, and neurologic injury: possible relationship to cerebral protection by anesthetics. J Neurosurg Anesthesiol 14 (1): 66–79.
  157. Lees K, Davalos A, Davis S, Diener H, Grotta J, Lyden P, Shuaib A, Ashwood T, Hardemark H, Wasiewski W, Emeribe U, Zivin J (2006). Additional outcomes and subgroup analyses of NXY-059 for acute ischemic stroke in the SAINT I trial. Stroke 37 (12): 2970–8.
  158. Lees K, Zivin J, Ashwood T, Davalos A, Davis S, Diener H, Grotta J, Lyden P, Shuaib A, Hårdemark H, Wasiewski W (2006). NXY-059 for acute ischemic stroke. N Engl J Med 354 (6): 588–600.
  159. Yamaguchi T, Sano K, Takakura K, Saito I, Shinohara Y, Asano T, Yasuhara H (1 January 1998). Ebselen in acute ischemic stroke: a placebo-controlled, double-blind clinical trial. Ebselen Study Group. Stroke 29 (1): 12–7.
  160. Di Matteo V, Esposito E (2003). Biochemical and therapeutic effects of antioxidants in the treatment of Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis. Curr Drug Targets CNS Neurol Disord 2 (2): 95–107.
  161. Rao A, Balachandran B (2002). Role of oxidative stress and antioxidants in neurodegenerative diseases. Nutr Neurosci 5 (5): 291–309.
  162. Kopke RD, Jackson RL, Coleman JK, Liu J, Bielefeld EC, Balough BJ (2007). NAC for noise: from the bench top to the clinic. Hear. Res. 226 (1–2): 114–25.
  163. Antioxidant may prevent alcohol-induced liver disease. e! Science News. URL accessed on 2011-10-09.
  164. 164.0 164.1 164.2 164.3 Stanner SA, Hughes J, Kelly CN, Buttriss J (2004). A review of the epidemiological evidence for the 'antioxidant hypothesis'. Public Health Nutr 7 (3): 407–22.
  165. Food, Nutrition, Physical Activity, and the Prevention of Cancer: a Global Perspective. World Cancer Research Fund (2007). ISBN 978-0-9722522-2-5.
  166. 166.0 166.1 166.2 Shenkin A (2006). The key role of micronutrients. Clin Nutr 25 (1): 1–13.
  167. Cherubini A, Vigna G, Zuliani G, Ruggiero C, Senin U, Fellin R (2005). Role of antioxidants in atherosclerosis: epidemiological and clinical update. Curr Pharm Des 11 (16): 2017–32.
  168. Lotito SB, Frei B (2006). Consumption of flavonoid-rich foods and increased plasma antioxidant capacity in humans: cause, consequence, or epiphenomenon?. Free Radic. Biol. Med. 41 (12): 1727–46.
  169. Rimm EB, Stampfer MJ, Ascherio A, Giovannucci E, Colditz GA, Willett WC (1993). Vitamin E consumption and the risk of coronary heart disease in men. N Engl J Med 328 (20): 1450–6.
  170. Vivekananthan DP, Penn MS, Sapp SK, Hsu A, Topol EJ (2003). Use of antioxidant vitamins for the prevention of cardiovascular disease: meta-analysis of randomised trials. Lancet 361 (9374): 2017–23.
  171. Sesso HD, Buring JE, Christen WG (November 2008). Vitamins E and C in the prevention of cardiovascular disease in men: the Physicians' Health Study II randomized controlled trial. JAMA 300 (18): 2123–33.
  172. Lee IM, Cook NR, Gaziano JM (July 2005). Vitamin E in the primary prevention of cardiovascular disease and cancer: the Women's Health Study: a randomized controlled trial. JAMA 294 (1): 56–65.
  173. Roberts LJ, Oates JA, Linton MF (2007). The relationship between dose of vitamin E and suppression of oxidative stress in humans. Free Radic. Biol. Med. 43 (10): 1388–93.
  174. Bleys J, Miller E, Pastor-Barriuso R, Appel L, Guallar E (2006). Vitamin-mineral supplementation and the progression of atherosclerosis: a meta-analysis of randomized controlled trials. Am. J. Clin. Nutr. 84 (4): 880–7; quiz 954–5.
  175. Cook NR, Albert CM, Gaziano JM (2007). A randomized factorial trial of vitamins C and E and beta carotene in the secondary prevention of cardiovascular events in women: results from the Women's Antioxidant Cardiovascular Study. Arch. Intern. Med. 167 (15): 1610–8.
  176. 176.0 176.1 Hercberg S, Galan P, Preziosi P, Bertrais S, Mennen L, Malvy D, Roussel AM, Favier A, Briancon S (2004). The SU.VI.MAX Study: a randomized, placebo-controlled trial of the health effects of antioxidant vitamins and minerals. Arch Intern Med 164 (21): 2335–42.
  177. Radimer K, Bindewald B, Hughes J, Ervin B, Swanson C, Picciano M (2004). Dietary supplement use by US adults: data from the National Health and Nutrition Examination Survey, 1999–2000. Am J Epidemiol 160 (4): 339–49.
  178. Latruffe N, Delmas D, Jannin B, Cherkaoui Malki M, Passilly-Degrace P, Berlot JP (December 2002). Molecular analysis on the chemopreventive properties of resveratrol, a plant polyphenol microcomponent. Int. J. Mol. Med. 10 (6): 755–60.
  179. Woodside J, McCall D, McGartland C, Young I (2005). Micronutrients: dietary intake v. supplement use. Proc Nutr Soc 64 (4): 543–53.
  180. 180.0 180.1 180.2 Hail N, Cortes M, Drake EN, Spallholz JE (July 2008). Cancer chemoprevention: a radical perspective. Free Radic. Biol. Med. 45 (2): 97–110.
  181. Williams RJ, Spencer JP, Rice-Evans C (April 2004). Flavonoids: antioxidants or signalling molecules?. Free Radical Biology & Medicine 36 (7): 838–49.
  182. Virgili F, Marino M (November 2008). Regulation of cellular signals from nutritional molecules: a specific role for phytochemicals, beyond antioxidant activity. Free Radical Biology & Medicine 45 (9): 1205–16.
  183. Schulz TJ, Zarse K, Voigt A, Urban N, Birringer M, Ristow M (2007). Glucose Restriction Extends Caenorhabditis elegans Life Span by Inducing Mitochondrial Respiration and Increasing Oxidative Stress. Cell Metab. 6 (4): 280–93.
  184. Barros MH, Bandy B, Tahara EB, Kowaltowski AJ (2004). Higher respiratory activity decreases mitochondrial reactive oxygen release and increases life span in Saccharomyces cerevisiae. J. Biol. Chem. 279 (48): 49883–8.
  185. Green GA (December 2008). Review: antioxidant supplements do not reduce all-cause mortality in primary or secondary prevention. Evid Based Med 13 (6).
  186. Dekkers J, van Doornen L, Kemper H (1996). The role of antioxidant vitamins and enzymes in the prevention of exercise-induced muscle damage. Sports Med 21 (3): 213–38.
  187. Tiidus P (1998). Radical species in inflammation and overtraining. Can J Physiol Pharmacol 76 (5): 533–8.
  188. Ristow M, Zarse K, Oberbach A (May 2009). Antioxidants prevent health-promoting effects of physical exercise in humans. Proc. Natl. Acad. Sci. U.S.A. 106 (21): 8665–70.
  189. Leeuwenburgh C, Fiebig R, Chandwaney R, Ji L (1994). Aging and exercise training in skeletal muscle: responses of glutathione and antioxidant enzyme systems. Am J Physiol 267 (2 Pt 2): R439–45.
  190. Leeuwenburgh C, Heinecke J (2001). Oxidative stress and antioxidants in exercise. Curr Med Chem 8 (7): 829–38.
  191. Takanami Y, Iwane H, Kawai Y, Shimomitsu T (2000). Vitamin E supplementation and endurance exercise: are there benefits?. Sports Med 29 (2): 73–83.
  192. Mastaloudis A, Traber M, Carstensen K, Widrick J (2006). Antioxidants did not prevent muscle damage in response to an ultramarathon run. Med Sci Sports Exerc 38 (1): 72–80.
  193. Peake J (2003). Vitamin C: effects of exercise and requirements with training. Int J Sport Nutr Exerc Metab 13 (2): 125–51.
  194. Jakeman P, Maxwell S (1993). Effect of antioxidant vitamin supplementation on muscle function after eccentric exercise. Eur J Appl Physiol Occup Physiol 67 (5): 426–30.
  195. Close G, Ashton T, Cable T, Doran D, Holloway C, McArdle F, MacLaren D (2006). Ascorbic acid supplementation does not attenuate post-exercise muscle soreness following muscle-damaging exercise but may delay the recovery process. Br J Nutr 95 (5): 976–81.
  196. Hurrell R (1 September 2003). Influence of vegetable protein sources on trace element and mineral bioavailability. J Nutr 133 (9): 2973S–7S.
  197. Hunt J (1 September 2003). Bioavailability of iron, zinc, and other trace minerals from vegetarian diets. Am J Clin Nutr 78 (3 Suppl): 633S–639S.
  198. Gibson R, Perlas L, Hotz C (2006). Improving the bioavailability of nutrients in plant foods at the household level. Proc Nutr Soc 65 (2): 160–8.
  199. 199.0 199.1 Mosha T, Gaga H, Pace R, Laswai H, Mtebe K (1995). Effect of blanching on the content of antinutritional factors in selected vegetables. Plant Foods Hum Nutr 47 (4): 361–7.
  200. Sandberg A (2002). Bioavailability of minerals in legumes. Br J Nutr 88 (Suppl 3): S281–5.
  201. 201.0 201.1 Beecher G (1 October 2003). Overview of dietary flavonoids: nomenclature, occurrence and intake. J Nutr 133 (10): 3248S–3254S.
  202. Prashar A, Locke I, Evans C (2006). Cytotoxicity of clove (Syzygium aromaticum) oil and its major components to human skin cells. Cell Prolif 39 (4): 241–8.
  203. Hornig D, Vuilleumier J, Hartmann D (1980). Absorption of large, single, oral intakes of ascorbic acid. Int J Vitam Nutr Res 50 (3): 309–14.
  204. Omenn G, Goodman G, Thornquist M, Balmes J, Cullen M, Glass A, Keogh J, Meyskens F, Valanis B, Williams J, Barnhart S, Cherniack M, Brodkin C, Hammar S (1996). Risk factors for lung cancer and for intervention effects in CARET, the Beta-Carotene and Retinol Efficacy Trial. J Natl Cancer Inst 88 (21): 1550–9.
  205. Albanes D (1 June 1999). Beta-carotene and lung cancer: a case study. Am J Clin Nutr 69 (6): 1345S–50S.
  206. Study Citing Antioxidant Vitamin Risks Based On Flawed Methodology, Experts Argue News release from Oregon State University published on ScienceDaily, Accessed 19 April 2007
  207. Bjelakovic G, Nikolova D, Gluud LL, Simonetti RG, Gluud C (2008). Antioxidant supplements for prevention of mortality in healthy participants and patients with various diseases. Cochrane Database of Systematic Reviews (2): CD007176.
  208. Miller E, Pastor-Barriuso R, Dalal D, Riemersma R, Appel L, Guallar E (2005). Meta-analysis: high-dosage vitamin E supplementation may increase all-cause mortality. Ann Intern Med 142 (1): 37–46.
  209. Bjelakovic G, Nagorni A, Nikolova D, Simonetti R, Bjelakovic M, Gluud C (2006). Meta-analysis: antioxidant supplements for primary and secondary prevention of colorectal adenoma. Aliment Pharmacol Ther 24 (2): 281–91.
  210. Caraballoso M, Sacristan M, Serra C, Bonfill X (2003). Drugs for preventing lung cancer in healthy people. Cochrane Database Syst Rev (2): CD002141.
  211. Bjelakovic G, Nagorni A, Nikolova D, Simonetti R, Bjelakovic M, Gluud C (2006). Meta-analysis: antioxidant supplements for primary and secondary prevention of colorectal adenoma. Aliment. Pharmacol. Ther. 24 (2): 281–91.
  212. Coulter I, Hardy M, Morton S, Hilton L, Tu W, Valentine D, Shekelle P (2006). Antioxidants vitamin C and vitamin e for the prevention and treatment of cancer. Journal of general internal medicine: official journal of the Society for Research and Education in Primary Care Internal Medicine 21 (7): 735–44.
  213. Schumacker P (2006). Reactive oxygen species in cancer cells: Live by the sword, die by the sword. Cancer Cell 10 (3): 175–6.
  214. Seifried H, McDonald S, Anderson D, Greenwald P, Milner J (1 August 2003). The antioxidant conundrum in cancer. Cancer Res 63 (15): 4295–8.
  215. Lawenda BD, Kelly KM, Ladas EJ, Sagar SM, Vickers A, Blumberg JB (June 2008). Should supplemental antioxidant administration be avoided during chemotherapy and radiation therapy?. J. Natl. Cancer Inst. 100 (11): 773–83.
  216. Block KI, Koch AC, Mead MN, Tothy PK, Newman RA, Gyllenhaal C (September 2008). Impact of antioxidant supplementation on chemotherapeutic toxicity: a systematic review of the evidence from randomized controlled trials. Int. J. Cancer 123 (6): 1227–39.
  217. Block KI, Koch AC, Mead MN, Tothy PK, Newman RA, Gyllenhaal C (August 2007). Impact of antioxidant supplementation on chemotherapeutic efficacy: a systematic review of the evidence from randomized controlled trials. Cancer Treat. Rev. 33 (5): 407–18.
  218. Cao G, Alessio H, Cutler R (1993). Oxygen-radical absorbance capacity assay for antioxidants. Free Radic Biol Med 14 (3): 303–11.
  219. Ou B, Hampsch-Woodill M, Prior R (2001). Development and validation of an improved oxygen radical absorbance capacity assay using fluorescein as the fluorescent probe. J Agric Food Chem 49 (10): 4619–26.
  220. Prior R, Wu X, Schaich K (2005). Standardized methods for the determination of antioxidant capacity and phenolics in foods and dietary supplements. J Agric Food Chem 53 (10): 4290–302.
  221. Xianquan S, Shi J, Kakuda Y, Yueming J (2005). Stability of lycopene during food processing and storage. J Med Food 8 (4): 413–22.
  222. Rodriguez-Amaya D (2003). Food carotenoids: analysis, composition and alterations during storage and processing of foods. Forum Nutr 56: 35–7.
  223. Baublis A, Lu C, Clydesdale F, Decker E (1 June 2000). Potential of wheat-based breakfast cereals as a source of dietary antioxidants. J Am Coll Nutr 19 (3 Suppl): 308S–311S.
  224. Rietveld A, Wiseman S (1 October 2003). Antioxidant effects of tea: evidence from human clinical trials. J Nutr 133 (10): 3285S–3292S.
  225. Maiani G, Periago Castón MJ, Catasta G (November 2008). Carotenoids: Actual knowledge on food sources, intakes, stability and bioavailability and their protective role in humans. Mol Nutr Food Res 53: S194–218.
  226. Henry C, Heppell N (2002). Nutritional losses and gains during processing: future problems and issues. Proc Nutr Soc 61 (1): 145–8.
  227. Antioxidants and Cancer Prevention: Fact Sheet. National Cancer Institute. URL accessed on 2007-02-27.
  228. Ortega RM (2006). Importance of functional foods in the Mediterranean diet. Public Health Nutr 9 (8A): 1136–40.
  229. Goodrow EF, Wilson TA, Houde SC (October 2006). Consumption of one egg per day increases serum lutein and zeaxanthin concentrations in older adults without altering serum lipid and lipoprotein cholesterol concentrations. J. Nutr. 136 (10): 2519–24.
  230. Witschi A, Reddy S, Stofer B, Lauterburg B (1992). The systemic availability of oral glutathione. Eur J Clin Pharmacol 43 (6): 667–9.
  231. Flagg EW, Coates RJ, Eley JW (1994). Dietary glutathione intake in humans and the relationship between intake and plasma total glutathione level. Nutr Cancer 21 (1): 33–46.
  232. 232.0 232.1 Dodd S, Dean O, Copolov DL, Malhi GS, Berk M (December 2008). N-acetylcysteine for antioxidant therapy: pharmacology and clinical utility. Expert Opin Biol Ther 8 (12): 1955–62.
  233. van de Poll MC, Dejong CH, Soeters PB (June 2006). Adequate range for sulfur-containing amino acids and biomarkers for their excess: lessons from enteral and parenteral nutrition. J. Nutr. 136 (6 Suppl): 1694S–1700S.
  234. Wu G, Fang YZ, Yang S, Lupton JR, Turner ND (March 2004). Glutathione metabolism and its implications for health. J. Nutr. 134 (3): 489–92.
  235. Pan MH, Ho CT (November 2008). Chemopreventive effects of natural dietary compounds on cancer development. Chem Soc Rev 37 (11): 2558–74.
  236. Kader A, Zagory D, Kerbel E (1989). Modified atmosphere packaging of fruits and vegetables. Crit Rev Food Sci Nutr 28 (1): 1–30.
  237. Zallen E, Hitchcock M, Goertz G (1975). Chilled food systems. Effects of chilled holding on quality of beef loaves. J Am Diet Assoc 67 (6): 552–7.
  238. Iverson F (1995). Phenolic antioxidants: Health Protection Branch studies on butylated hydroxyanisole. Cancer Lett 93 (1): 49–54.
  239. E number index. UK food guide. URL accessed on 2007-03-05.
  240. Robards K, Kerr A, Patsalides E (1988). Rancidity and its measurement in edible oils and snack foods. A review. Analyst 113 (2): 213–24.
  241. Del Carlo M, Sacchetti G, Di Mattia C, Compagnone D, Mastrocola D, Liberatore L, Cichelli A (2004). Contribution of the phenolic fraction to the antioxidant activity and oxidative stability of olive oil. J Agric Food Chem 52 (13): 4072–9.

Further reading Edit

  • Nick Lane Oxygen: The Molecule That Made the World (Oxford University Press, 2003) ISBN 0-19-860783-0
  • Barry Halliwell and John M.C. Gutteridge Free Radicals in Biology and Medicine(Oxford University Press, 2007) ISBN 0-19-856869-X
  • Jan Pokorny, Nelly Yanishlieva and Michael H. Gordon Antioxidants in Food: Practical Applications (CRC Press Inc, 2001) ISBN 0-8493-1222-1


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