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Model of the antioxidant metabolite glutathione. The yellow sphere is the redox-active sulfur atom that provides antioxidant activity, while the red, blue, white, and dark grey spheres represent oxygen, nitrogen, hydrogen, and carbon atoms, respectively.

An antioxidant is a molecule that inhibits the oxidation of other molecules. Oxidation is a chemical reaction involving the loss of electrons or an increase in oxidation state. 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]

Substituted phenols and derivatives of phenylenediamine are common antioxidants used to inhibit gum formation in gasoline (petrol).

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, vitamin A, and vitamin E as well as enzymes such as catalase, superoxide dismutase and various peroxidases. Insufficient levels of antioxidants, or inhibition of the antioxidant enzymes, cause oxidative stress and may damage or kill cells. Oxidative stress is damage to cell structure and cell function by overly reactive oxygen-containing molecules and chronic excessive inflammation. Oxidative stress seems to play a significant role in many human diseases, including cancers. The use of antioxidants in pharmacology is intensively studied, particularly as treatments for stroke and neurodegenerative diseases. For these reasons, oxidative stress can be considered to be both the cause and the consequence of some diseases.

Antioxidants are widely used in dietary supplements and have been investigated for the prevention of diseases such as cancer, coronary heart disease and even altitude sickness.[2] Although initial studies suggested that antioxidant supplements might promote health, later large clinical trials of antioxidant supplements including beta-carotene, vitamin A, and vitamin E singly or in different combinations suggest that supplementation has no effect on mortality or possibly increases it.[3][4][5] Randomized clinical trials of antioxidants including beta carotene, vitamin E, vitamin C and selenium have shown no effect on cancer risk or have increased cancer risk associated with supplementation.[6][7][8][9][10][11][12] Supplementation with selenium or vitamin E does not reduce the risk of cardiovascular disease.[13][14]

Antioxidants also have many industrial uses, such as preservatives in food and cosmetics and to prevent the degradation of rubber and gasoline.[15]


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.[16] Originally, the term antioxidant specifically referred to a chemical that prevented the consumption of oxygen. In the late 19th and early 20th centuries, extensive study concentrated on the use 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.[17]

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.[18] 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.[19][20] 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.[21] 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.[22]

Oxidative challenge in biology[edit]

Further information: Oxidative stress
The structure of the antioxidant vitamin ascorbic acid (vitamin C).

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.[23] 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][24] 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][23] However, reactive oxygen species also have useful cellular functions, such as redox signaling. Thus, the function of antioxidant systems is not to remove oxidants entirely, but instead to keep them at an optimum level.[25]

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).[26] 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.[27] 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,[28][29] while damage to proteins causes enzyme inhibition, denaturation and protein degradation.[30]

The use of oxygen as part of the process for generating metabolic energy produces reactive oxygen species.[31] In this process, the superoxide anion is produced as a by-product of several steps in the electron transport chain.[32] 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.[33] Peroxide is also produced from the oxidation of reduced flavoproteins, such as complex I.[34] However, although these enzymes can produce oxidants, the relative importance of the electron transfer chain to other processes that generate peroxide is unclear.[35][36] In plants, algae, and cyanobacteria, reactive oxygen species are also produced during photosynthesis,[37] particularly under conditions of high light intensity.[38] This effect is partly offset by the involvement of carotenoids in photoinhibition, and in algae and cyanobacteria, by large amount of iodide and selenium,[39] which involves these antioxidants reacting with over-reduced forms of the photosynthetic reaction centres to prevent the production of reactive oxygen species.[40][41]



Antioxidants are classified into two broad divisions, depending on whether they are soluble in water (hydrophilic) or in lipids (lipophilic). 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.[24] 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.[42]

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.[43][44] The action of one antioxidant may therefore depend on the proper function of other members of the antioxidant system.[24] 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.[24]

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.[36] 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)[45] Concentration in liver tissue (μmol/kg)
Ascorbic acid (vitamin C) Water 50 – 60[46] 260 (human)[47]
Glutathione Water 4[48] 6,400 (human)[47]
Lipoic acid Water 0.1 – 0.7[49] 4 – 5 (rat)[50]
Uric acid Water 200 – 400[51] 1,600 (human)[47]
Carotenes Lipid β-carotene: 0.5 – 1[52]

retinol (vitamin A): 1 – 3[53]

5 (human, total carotenoids)[54]
α-Tocopherol (vitamin E) Lipid 10 – 40[53] 50 (human)[47]
Ubiquinol (coenzyme Q) Lipid 5[55] 200 (human)[56]

Uric acid[edit]

Uric acid is by far the highest concentration antioxidant in human blood. Uric acid (UA) is an antioxidant oxypurine produced from xanthine by the enzyme xanthine oxidase, and is an intermediate product of purine metabolism.[57] In almost all land animals, urate oxidase further catalyzes the oxidation of uric acid to allantoin,[58] but in humans and most higher primates, the urate oxidase gene is nonfunctional, so that UA is not further broken down.[58][59] The evolutionary reasons for this loss of urate conversion to allantoin remain the topic of active speculation.[60][61] The antioxidant effects of uric acid have led researchers to suggest this mutation was beneficial to early primates and humans.[61][62] Studies of high altitude acclimatization support the hypothesis that urate acts as an antioxidant by mitigating the oxidative stress caused by high-altitude hypoxia.[63] 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.[64] Studies of UA's antioxidant mechanism support this proposal.[65]

With respect to multiple sclerosis, Gwen Scott explains the significance of uric acid as an antioxidant 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."[64][66][67] In sum, while the mechanism of UA as an antioxidant is well-supported, the claim that its levels affect MS risk is still controversial,[68][69] and requires more research.

Likewise, UA has the highest concentration of any blood antioxidant[51] and provides over half of the total antioxidant capacity of human serum.[70] Uric acid's antioxidant activities are also complex, given that it does not react with some oxidants, such as superoxide, but does act against peroxynitrite,[71] peroxides, and hypochlorous acid.[57] Concerns over elevated UA's contribution to gout must be considered as one of many risk factors.[72] 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).[73] Many of these aforementioned studies determined UA's antioxidant actions within normal physiological levels,[63][71] and some found antioxidant activity at levels as high as 285 μmol/L.[74]

Ascorbic acid (vitamin C)[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.[75] Most other animals are able to produce this compound in their bodies and do not require it in their diets.[76] 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.[77][78] Ascorbic acid is a redox catalyst which can reduce, and thereby neutralize, reactive oxygen species such as hydrogen peroxide.[79] 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.[80] Ascorbic acid is present at high levels in all parts of plants and can reach concentrations of 20 millimolar in chloroplasts.[81]


The free radical mechanism of lipid peroxidation.

Glutathione is a cysteine-containing peptide found in most forms of aerobic life.[82] It is not required in the diet and is instead synthesized in cells from its constituent amino acids.[83] 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.[77] 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.[82] In some organisms glutathione is replaced by other thiols, such as by mycothiol in the Actinomycetes, bacillithiol in some Gram-positive bacteria,[84][85] or by trypanothione in the Kinetoplastids.[86][87]


Melatonin is a powerful antioxidant.[88] Melatonin easily crosses cell membranes and the blood–brain barrier.[89] 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.[90]

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.[91][92] Of these, α-tocopherol has been most studied as it has the highest bioavailability, with the body preferentially absorbing and metabolising this form.[93]

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.[91][94] 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.[95] 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.[96] 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,[97][98] 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.[99][100] 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,[93] and tocotrienols may be important in protecting neurons from damage.[101]

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,[102] however, it will also reduce metal ions that generate free radicals through the Fenton reaction.[103][104]

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 is 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.[103][105] However, less data is available for other dietary antioxidants, such as vitamin E,[106] or the polyphenols.[107][108] Likewise, the pathogenesis of diseases involving hyperuricemia likely involve uric acid's direct and indirect pro-oxidant properties.

That is, paradoxically, agents which are normally considered antioxidants can act as conditional pro-oxidants and actually increase oxidative stress. Besides ascorbate, medically important conditional pro-oxidants include uric acid and sulfhydryl amino acids such as homocysteine. Typically, this involves some transition-series metal such as copper or iron as catalyst. The potential role of the pro-oxidant role of uric acid in (e.g.) atherosclerosis and ischemic stroke is considered above. Another example is the postulated role of homocysteine in atherosclerosis.

Potential of antioxidant supplements to damage health[edit]

Some antioxidant supplements may promote disease and increase mortality in humans.[108][109] Hypothetically, free radicals induce an endogenous response that protects against exogenous radicals (and possibly other toxic compounds).[110] 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.[111] 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.[108][109]

Enzyme systems[edit]

Enzymatic pathway for detoxification of reactive oxygen species.


As with the chemical antioxidants, cells are protected against oxidative stress by an interacting network of antioxidant enzymes.[1][23] 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.[112]

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.[113][114] SOD enzymes are present in almost all aerobic cells and in extracellular fluids.[115] 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.[114] There also exists a third form of SOD in extracellular fluids, which contains copper and zinc in its active sites.[116] The mitochondrial isozyme seems to be the most biologically important of these three, since mice lacking this enzyme die soon after birth.[117] 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).[112][118] 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.[119]

Catalases are enzymes that catalyse the conversion of hydrogen peroxide to water and oxygen, using either an iron or manganese cofactor.[120][121] This protein is localized to peroxisomes in most eukaryotic cells.[122] 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.[123] 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.[124][125]

Decameric structure of AhpC, a bacterial 2-cysteine peroxiredoxin from Salmonella typhimurium.[126]

Peroxiredoxins are peroxidases that catalyze the reduction of hydrogen peroxide, organic hydroperoxides, as well as peroxynitrite.[127] They are divided into three classes: typical 2-cysteine peroxiredoxins; atypical 2-cysteine peroxiredoxins; and 1-cysteine peroxiredoxins.[128] 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.[129] Over-oxidation of this cysteine residue in peroxiredoxins inactivates these enzymes, but this can be reversed by the action of sulfiredoxin.[130] 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.[131][132][133]

Thioredoxin and glutathione systems[edit]

The thioredoxin system contains the 12-kDa protein thioredoxin and its companion thioredoxin reductase.[134] Proteins related to thioredoxin are present in all sequenced organisms. Plants, such as Arabidopsis thaliana, have a particularly great diversity of isoforms.[135] 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.[136] After being oxidized, the active thioredoxin is regenerated by the action of thioredoxin reductase, using NADPH as an electron donor.[137]

The glutathione system includes glutathione, glutathione reductase, glutathione peroxidases and glutathione S-transferases.[82] This system is found in animals, plants and microorganisms.[82][138] 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.[139] 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,[140] but they are hypersensitive to induced oxidative stress.[141] In addition, the glutathione S-transferases show high activity with lipid peroxides.[142] These enzymes are at particularly high levels in the liver and also serve in detoxification metabolism.[143]

Oxidative stress in disease[edit]

Oxidative stress is thought to contribute to the development of a wide range of diseases including Alzheimer's disease,[144][145] Parkinson's disease,[146] the pathologies caused by diabetes,[147][148] rheumatoid arthritis,[149] and neurodegeneration in motor neuron diseases.[150] 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;[26] 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.[151][152]

Oxidative damage in DNA can cause cancer. 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.[153]

A low calorie diet extends median and maximum lifespan in many animals. This effect may involve a reduction in oxidative stress.[154] While there is some evidence to support the role of oxidative stress in aging in model organisms such as Drosophila melanogaster and Caenorhabditis elegans,[155][156] the evidence in mammals is less clear.[157][158][159] Indeed, a 2009 review of experiments in mice concluded that almost all manipulations of antioxidant systems had no effect on aging.[160] Diets high in fruit and vegetables, which are high in antioxidants, promote health and reduce the effects of aging; 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.[161][162] 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, and it may be these other effects that are the real reason these compounds are important in human nutrition.[99][163]

Potential health effects[edit]


Based on the favorable effect observed for methylprednisolone in patients with head injury, a number of experimental therapeutics have been designed with the goal of providing neuroprotection or other therapeutic effects via an antioxidant mechanism. Tirilazad mesylate is an anti-oxidant steroid derivative that was designed to inhibit the lipid peroxidation observed and believed to play a key role in neuronal death in stroke and head injury. It demonstrated activity in preclinical models of head injury and stroke.[164] Clinical trials demonstrated no effect on mortality or other outcomes in subarachnoid haemorrhage,[165] and worsened results in ischemic stroke.[166]

Similarly, the designed antioxidant NXY-059 exhibited efficacy in animal models, but failed to improve stroke outcomes in a clinical trial.[167] As of November 2014, other antioxidants are being studied as potential neuroprotectants.[168]

Common pharmaceuticals (and supplements) with antioxidant properties may interfere with the efficacy of certain anticancer drugs and radiation.[169][170]

Relation to diet[edit]

Structure of resveratrol under study for its potential as a dietary antioxidant

People who eat fruits and vegetables appear to have a lower risk of heart disease, some neurological diseases,[171] and some cancers.[172] Since fruits and vegetables happen to be good sources of nutrients and phytochemicals, this suggested that antioxidant compounds might lower risk against several diseases.

Antioxidants have been investigated as possible treatments for neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis,[173][174] and as a way to prevent noise-induced hearing loss.[175] In general these trials have shown ambiguous effects on patient outcomes.[176][177][178]

Although some levels of antioxidant vitamins in the diet are required for good health, there is considerable doubt as to whether antioxidant supplements are beneficial or harmful; and if they are actually beneficial, which antioxidant(s) are needed and in what amounts.[171][179][180] 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.[181] 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.[182][183]

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.[184] The suggestion that increased life expectancy comes from increased oxidative stress conflicts with results seen in the yeast Saccharomyces cerevisiae,[185] and the situation in mammals is even less clear.[157][158][159] Nevertheless, antioxidant supplements do not appear to increase life expectancy in humans.[186]

Physical exercise[edit]

During exercise, oxygen consumption can increase by a factor of more than 10.[187] 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.[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]

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] Other studies found no such effects, and some research suggests that supplementation with amounts as high as 1000 mg inhibits recovery.[195]

A review published in Sports Medicine looked at 150 studies on antioxidant supplementation during exercise. The review found that even studies that found a reduction in oxidative stress failed to demonstrate benefits to performance or prevention of muscle damage. Some studies indicated that antioxidant supplementation could work against the cardiovascular benefits of exercise.[196]

Adverse effects[edit]

Structure of the metal chelator phytic acid.

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.[197] Notable examples are oxalic acid, tannins and phytic acid, which are high in plant-based diets.[198] 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.[199]

Foods Reducing acid present
Cocoa bean and chocolate, spinach, turnip and rhubarb.[200] Oxalic acid
Whole grains, maize, legumes.[201] Phytic acid
Tea, beans, cabbage.[200][202] 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.[203] 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.[204] 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.[205] Subsequent studies confirmed these adverse effects.[206]

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.[109] 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. 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.[207] 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.[208] These two publications are consistent with some previous meta-analyzes that also suggested that Vitamin E supplementation increased mortality,[209] and that antioxidant supplements increased the risk of colon cancer.[210] 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 all-cause mortality.[211][212][213][214] 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.[109][171][179]

While antioxidant supplementation is widely used in attempts to prevent the development of cancer, antioxidants may interfere with cancer treatments,[215] 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 (and pharmaceuticals) could decrease the effectiveness of radiotherapy and chemotherapy.[169][216][217] On the other hand, other reviews have suggested that antioxidants could reduce side effects or increase survival times.[218][219]

Measurement and levels in food[edit]

Fruits and vegetables are good sources of antioxidant vitamins.

Antioxidant vitamins are found in vegetables, fruits, eggs, legumes and nuts. Vitamins A, C or E can be destroyed by long-term storage or prolonged cooking.[220] 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.[221] Processed food contains fewer antioxidant vitamins than fresh and uncooked foods, as preparation exposes food to heat and oxygen.[222]

Antioxidant vitamins Foods containing high levels of antioxidant vitamins[202][223][224]
Vitamin C (ascorbic acid) Fresh or frozen fruits and vegetables
Vitamin E (tocopherols, tocotrienols) Vegetable oils, nuts and seeds
Carotenoids (carotenes as provitamin A) Fruit, vegetables and eggs

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.[56] 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.[225][226] Although large amounts of sulfur-containing amino acids such as acetylcysteine can increase glutathione,[227] no evidence exists that eating high levels of these glutathione precursors is beneficial for healthy adults.[228] 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.[227][229]

Other compounds in the diet can alter the levels of antioxidants by acting as pro-oxidants whereby consuming the compound may cause oxidative stress, possibly resulting in higher levels of antioxidant enzymes.[181]

Invalidation of ORAC[edit]

Measurement of antioxidant content in food is not a straightforward process, as this is a diverse group of compounds with different reactivities to various reactive oxygen species. In food science, the oxygen radical absorbance capacity (ORAC) used to be the industry standard for antioxidant strength of whole foods, juices and food additives.[230][231] However, the United States Department of Agriculture (USDA) withdrew these ratings in 2012 as biologically invalid, stating that no physiological proof in vivo existed to support the free-radical theory, especially for polyphenols.[232] Consequently, the ORAC method, derived only from in vitro experiments, is no longer considered relevant to human diets or biology.

Alternative in vitro measurements include the Folin-Ciocalteu reagent, and the Trolox equivalent antioxidant capacity assay.[233]

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.[234] 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.[235] 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).[236][237]

The most common molecules attacked by oxidation are unsaturated fats; oxidation causes them to turn rancid.[238] 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.[239] Antioxidant preservatives are also added to fat-based cosmetics such as lipstick and moisturizers to prevent rancidity.

Industrial uses[edit]

Antioxidants are frequently added to industrial products. A common use is as stabilizers in fuels and lubricants to prevent oxidation, and in gasolines to prevent the polymerization that leads to the formation of engine-fouling residues.[240] In 2007, the worldwide market for industrial antioxidants had a total volume of around 0.88 million tons. This created a revenue of circa 3.7 billion US-dollars (2.4 billion Euros).[241]

They are widely used to prevent the oxidative degradation of polymers such as rubbers, plastics and adhesives that causes a loss of strength and flexibility in these materials.[242] Polymers containing double bonds in their main chains, such as natural rubber and polybutadiene, are especially susceptible to oxidation and ozonolysis. They can be protected by antiozonants. Solid polymer products start to crack on exposed surfaces as the material degrades and the chains break. The mode of cracking varies between oxygen and ozone attack, the former causing a "crazy paving" effect, while ozone attack produces deeper cracks aligned at right angles to the tensile strain in the product. Oxidation and UV degradation are also frequently linked, mainly because UV radiation creates free radicals by bond breakage. The free radicals then react with oxygen to produce peroxy radicals which cause yet further damage, often in a chain reaction. Other polymers susceptible to oxidation include polypropylene and polyethylene. The former is more sensitive owing to the presence of secondary carbon atoms present in every repeat unit. Attack occurs at this point because the free radical formed is more stable than one formed on a primary carbon atom. Oxidation of polyethylene tends to occur at weak links in the chain, such as branch points in low density polyethylene.

Fuel additive Components[243] Applications[243]
AO-22 N,N'-di-2-butyl-1,4-phenylenediamine Turbine oils, transformer oils, hydraulic fluids, waxes, and greases
AO-24 N,N'-di-2-butyl-1,4-phenylenediamine Low-temperature oils
AO-29 2,6-di-tert-butyl-4-methylphenol Turbine oils, transformer oils, hydraulic fluids, waxes, greases, and gasolines
AO-30 2,4-dimethyl-6-tert-butylphenol Jet fuels and gasolines, including aviation gasolines
AO-31 2,4-dimethyl-6-tert-butylphenol Jet fuels and gasolines, including aviation gasolines
AO-32 2,4-dimethyl-6-tert-butylphenol and 2,6-di-tert-butyl-4-methylphenol Jet fuels and gasolines, including aviation gasolines
AO-37 2,6-di-tert-butylphenol Jet fuels and gasolines, widely approved for aviation fuels

See also[edit]


  1. ^ a b c d e f Sies, Helmut (1997). "Oxidative stress: Oxidants and antioxidants". Experimental physiology 82 (2): 291–5. doi:10.1113/expphysiol.1997.sp004024. PMID 9129943. 
  2. ^ Baillie, J.K.; Thompson, A.A.R.; Irving, J.B.; Bates, M.G.D.; Sutherland, A.I.; MacNee, W.; Maxwell, S.R.J.; Webb, D.J. (2009). "Oral antioxidant supplementation does not prevent acute mountain sickness: double blind, randomized placebo-controlled trial". QJM 102 (5): 341–8. doi:10.1093/qjmed/hcp026. PMID 19273551. 
  3. ^ Bjelakovic G, Nikolova D, Gluud C (2013). "Meta-regression analyses, meta-analyses, and trial sequential analyses of the effects of supplementation with beta-carotene, vitamin A, and vitamin E singly or in different combinations on all-cause mortality: do we have evidence for lack of harm?". PLoS ONE 8 (9): e74558. doi:10.1371/journal.pone.0074558. PMC 3765487. PMID 24040282. 
  4. ^ Abner EL, Schmitt FA, Mendiondo MS, Marcum JL, Kryscio RJ (July 2011). "Vitamin E and all-cause mortality: a meta-analysis". Curr Aging Sci 4 (2): 158–70. doi:10.2174/1874609811104020158. PMC 4030744. PMID 21235492. 
  5. ^ Bjelakovic G; Nikolova, D; Gluud, LL; Simonetti, RG; 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. doi:10.1001/jama.297.8.842. PMID 17327526. 
  6. ^ Vinceti M, Dennert G, Crespi CM et al. (2014). "Selenium for preventing cancer". Cochrane Database Syst Rev 3: CD005195. doi:10.1002/14651858.CD005195.pub3. PMID 24683040. 
  7. ^ Pais R, Dumitraşcu DL (2013). "Do antioxidants prevent colorectal cancer? A meta-analysis". Rom J Intern Med 51 (3-4): 152–63. PMID 24620628. 
  8. ^ Cortés-Jofré M, Rueda JR, Corsini-Muñoz G, Fonseca-Cortés C, Caraballoso M, Bonfill Cosp X (2012). "Drugs for preventing lung cancer in healthy people". Cochrane Database Syst Rev 10: CD002141. doi:10.1002/14651858.CD002141.pub2. PMID 23076895. 
  9. ^ Jeon YJ, Myung SK, Lee EH et al. (November 2011). "Effects of beta-carotene supplements on cancer prevention: meta-analysis of randomized controlled trials". Nutr Cancer 63 (8): 1196–207. doi:10.1080/01635581.2011.607541. PMID 21981610. 
  10. ^ Jiang L, Yang KH, Tian JH et al. (2010). "Efficacy of antioxidant vitamins and selenium supplement in prostate cancer prevention: a meta-analysis of randomized controlled trials". Nutr Cancer 62 (6): 719–27. doi:10.1080/01635581.2010.494335. PMID 20661819. 
  11. ^ Bjelakovic G, Nikolova D, Simonetti RG, Gluud C (September 2008). "Systematic review: primary and secondary prevention of gastrointestinal cancers with antioxidant supplements". Aliment. Pharmacol. Ther. 28 (6): 689–703. doi:10.1111/j.1365-2036.2008.03785.x. PMID 19145725. 
  12. ^ Bardia A, Tleyjeh IM, Cerhan JR et al. (January 2008). "Efficacy of antioxidant supplementation in reducing primary cancer incidence and mortality: systematic review and meta-analysis". Mayo Clin. Proc. 83 (1): 23–34. doi:10.4065/83.1.23. PMID 18173999. 
  13. ^ Rees K, Hartley L, Day C, Flowers N, Clarke A, Stranges S (2013). "Selenium supplementation for the primary prevention of cardiovascular disease". Cochrane Database Syst Rev 1: CD009671. doi:10.1002/14651858.CD009671.pub2. PMID 23440843. 
  14. ^ Shekelle PG, Morton SC, Jungvig LK et al. (April 2004). "Effect of supplemental vitamin E for the prevention and treatment of cardiovascular disease". J Gen Intern Med 19 (4): 380–9. doi:10.1111/j.1525-1497.2004.30090.x. PMC 1492195. PMID 15061748. 
  15. ^ Dabelstein, Werner; Reglitzky, Arno; Schütze, Andrea; Reders, Klaus (2007). "Automotive Fuels". Ullmann's Encyclopedia of Industrial Chemistry. doi:10.1002/14356007.a16_719.pub2. ISBN 3527306730. 
  16. ^ Benzie, I (2003). "Evolution of dietary antioxidants". Comparative Biochemistry and Physiology 136 (1): 113–26. doi:10.1016/S1095-6433(02)00368-9. PMID 14527634. 
  17. ^ Mattill, H A (1947). "Antioxidants". Annual Review of Biochemistry 16: 177–92. doi:10.1146/ PMID 20259061. 
  18. ^ German, JB (1999). "Food processing and lipid oxidation". Advances in experimental medicine and biology. Advances in Experimental Medicine and Biology 459: 23–50. doi:10.1007/978-1-4615-4853-9_3. ISBN 978-0-306-46051-7. PMID 10335367. 
  19. ^ Jacob, RA (1996). "Three eras of vitamin C discovery". Sub-cellular biochemistry. Subcellular Biochemistry 25: 1–16. doi:10.1007/978-1-4613-0325-1_1. ISBN 978-1-4613-7998-0. PMID 8821966. 
  20. ^ Knight, JA (1998). "Free radicals: Their history and current status in aging and disease". Annals of Clinical and Laboratory Science 28 (6): 331–46. PMID 9846200. 
  21. ^ Moureu, Charles; Dufraisse, Charles (1922). "Sur l'autoxydation: Les antioxygènes". Comptes Rendus des Séances et Mémoires de la Société de Biologie (in French) 86: 321–322. 
  22. ^ Wolf, George (2005). "The discovery of the antioxidant function of vitamin E: The contribution of Henry A. Mattill". The Journal of nutrition 135 (3): 363–6. PMID 15735064. 
  23. ^ a b c Davies, KJ (1995). "Oxidative stress: The paradox of aerobic life". Biochemical Society Symposia 61: 1–31. PMID 8660387. 
  24. ^ a b c d Vertuani, Silvia; Angusti, Angela; Manfredini, Stefano (2004). "The Antioxidants and Pro-Antioxidants Network: An Overview". Current Pharmaceutical Design 10 (14): 1677–94. doi:10.2174/1381612043384655. PMID 15134565. 
  25. ^ Rhee, S. G. (2006). "CELL SIGNALING: H2O2, a Necessary Evil for Cell Signaling". Science 312 (5782): 1882–3. doi:10.1126/science.1130481. PMID 16809515. 
  26. ^ a b Valko, M; Leibfritz, D; Moncol, J; Cronin, M; Mazur, M; Telser, J (2007). "Free radicals and antioxidants in normal physiological functions and human disease". The International Journal of Biochemistry & Cell Biology 39 (1): 44–84. doi:10.1016/j.biocel.2006.07.001. PMID 16978905. 
  27. ^ Stohs, S; Bagchi, D (1995). "Oxidative mechanisms in the toxicity of metal ions". Free Radical Biology and Medicine 18 (2): 321–36. doi:10.1016/0891-5849(94)00159-H. PMID 7744317. 
  28. ^ Nakabeppu, Yusaku; Sakumi, Kunihiko; Sakamoto, Katsumi; Tsuchimoto, Daisuke; Tsuzuki, Teruhisa; Nakatsu, Yoshimichi (2006). "Mutagenesis and carcinogenesis caused by the oxidation of nucleic acids". Biological Chemistry 387 (4): 373–9. doi:10.1515/BC.2006.050. PMID 16606334. 
  29. ^ Valko, Marian; Izakovic, Mario; Mazur, Milan; Rhodes, Christopher J.; Telser, Joshua (2004). "Role of oxygen radicals in DNA damage and cancer incidence". Molecular and Cellular Biochemistry 266 (1–2): 37–56. doi:10.1023/B:MCBI.0000049134.69131.89. PMID 15646026. 
  30. ^ Stadtman, E. (1992). "Protein oxidation and aging". Science 257 (5074): 1220–4. Bibcode:1992Sci...257.1220S. doi:10.1126/science.1355616. PMID 1355616. 
  31. ^ Raha, S; Robinson, BH (2000). "Mitochondria, oxygen free radicals, disease and ageing". Trends in Biochemical Sciences 25 (10): 502–8. doi:10.1016/S0968-0004(00)01674-1. PMID 11050436. 
  32. ^ Lenaz, Giorgio (2001). "The Mitochondrial Production of Reactive Oxygen Species: Mechanisms and Implications in Human Pathology". IUBMB Life 52 (3–5): 159–64. doi:10.1080/15216540152845957. PMID 11798028. 
  33. ^ Finkel, Toren; Holbrook, Nikki J. (2000). "Oxidants, oxidative stress and the biology of ageing". Nature 408 (6809): 239–47. doi:10.1038/35041687. PMID 11089981. 
  34. ^ Hirst, Judy; King, Martin S.; Pryde, Kenneth R. (2008). "The production of reactive oxygen species by complex I". Biochemical Society Transactions 36 (5): 976–80. doi:10.1042/BST0360976. 
  35. ^ Seaver, L. C.; Imlay, JA (2004). "Are Respiratory Enzymes the Primary Sources of Intracellular Hydrogen Peroxide?". Journal of Biological Chemistry 279 (47): 48742–50. doi:10.1074/jbc.M408754200. PMID 15361522. 
  36. ^ a b Imlay, James A. (2003). "Pathways Ofoxidativedamage". Annual Review of Microbiology 57: 395–418. doi:10.1146/annurev.micro.57.030502.090938. PMID 14527285. 
  37. ^ Demmig-Adams, B.; Adams, W. W. III (2002). "Antioxidants in Photosynthesis and Human Nutrition". Science 298 (5601): 2149–53. Bibcode:2002Sci...298.2149D. doi:10.1126/science.1078002. PMID 12481128. 
  38. ^ Krieger-Liszkay, A. (2004). "Singlet oxygen production in photosynthesis". Journal of Experimental Botany 56 (411): 337–46. doi:10.1093/jxb/erh237. PMID 15310815. 
  39. ^ Küpper FC; Carpenter LJ; McFiggans GB et al. (2008). "Iodide accumulation provides kelp with an inorganic antioxidant impacting atmospheric chemistry" (FREE FULL TEXT). Proceedings of the National Academy of Sciences of the United States of America 105 (19): 6954–8. Bibcode:2008PNAS..105.6954K. doi:10.1073/pnas.0709959105. PMC 2383960. PMID 18458346. 
  40. ^ Szabó, Ildikó; Bergantino, Elisabetta; Giacometti, Giorgio Mario (2005). "Light and oxygenic photosynthesis: Energy dissipation as a protection mechanism against photo-oxidation". EMBO Reports 6 (7): 629–34. doi:10.1038/sj.embor.7400460. PMC 1369118. PMID 15995679. 
  41. ^ Kerfeld, C (2004). "Water-soluble carotenoid proteins of cyanobacteria". Archives of Biochemistry and Biophysics 430 (1): 2–9. doi:10.1016/ PMID 15325905. 
  42. ^ Miller, RA; Britigan, BE (1997). "Role of oxidants in microbial pathophysiology". Clinical Microbiology Reviews 10 (1): 1–18. PMC 172912. PMID 8993856. 
  43. ^ Chaudiere, J; Ferrari-Iliou, R (1999). "Intracellular Antioxidants: From Chemical to Biochemical Mechanisms". Food and Chemical Toxicology 37 (9–10): 949–62. doi:10.1016/S0278-6915(99)00090-3. PMID 10541450. 
  44. ^ Sies, Helmut (1993). "Strategies of antioxidant defense". European Journal of Biochemistry 215 (2): 213–9. doi:10.1111/j.1432-1033.1993.tb18025.x. PMID 7688300. 
  45. ^ 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". Proceedings of the National Academy of Sciences of the United States of America 78 (11): 6858–62. Bibcode:1981PNAS...78.6858A. doi:10.1073/pnas.78.11.6858. PMC 349151. PMID 6947260. 
  46. ^ Khaw, Kay-Tee; Woodhouse, Peter (1995). "Interrelation of vitamin C, infection, haemostatic factors, and cardiovascular disease". BMJ 310 (6994): 1559–63. doi:10.1136/bmj.310.6994.1559. PMC 2549940. PMID 7787643. 
  47. ^ a b c d Evelson, P; Travacio, M; Repetto, M; Escobar, J; Llesuy, S; Lissi, EA (2001). "Evaluation of Total Reactive Antioxidant Potential (TRAP) of Tissue Homogenates and Their Cytosols". Archives of Biochemistry and Biophysics 388 (2): 261–6. doi:10.1006/abbi.2001.2292. PMID 11368163. 
  48. ^ Morrison, John A.; Jacobsen, Donald W.; Sprecher, Dennis L.; Robinson, Killian; Khoury, Philip; Daniels, Stephen R. (1999). "Serum glutathione in adolescent males predicts parental coronary heart disease". Circulation 100 (22): 2244–7. doi:10.1161/01.CIR.100.22.2244. PMID 10577998. 
  49. ^ Teichert, J; Preiss, R (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. PMID 1490813. 
  50. ^ Akiba, S; Matsugo, S; Packer, L; Konishi, T (1998). "Assay of Protein-Bound Lipoic Acid in Tissues by a New Enzymatic Method". Analytical Biochemistry 258 (2): 299–304. doi:10.1006/abio.1998.2615. PMID 9570844. 
  51. ^ a b Glantzounis, G. K.; Tsimoyiannis, E. C.; Kappas, A. M.; Galaris, D. A. (2005). "Uric Acid and Oxidative Stress". Current Pharmaceutical Design 11 (32): 4145–51. doi:10.2174/138161205774913255. PMID 16375736. 
  52. ^ El-Sohemy, Ahmed; Baylin, Ana; Kabagambe, Edmond; Ascherio, Alberto; Spiegelman, Donna; Campos, Hannia (2002). "Individual carotenoid concentrations in adipose tissue and plasma as biomarkers of dietary intake". The American journal of clinical nutrition 76 (1): 172–9. PMID 12081831. 
  53. ^ a b Sowell, Anne L.; Huff, Daniel L.; Yeager, Patricia R.; Caudill, Samuel P.; Gunter, Elaine W. (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. PMID 8131277. 
  54. ^ Stahl, W; Schwarz, W; Sundquist, AR; Sies, H (1992). "cis-trans isomers of lycopene and ?-carotene in human serum and tissues". Archives of Biochemistry and Biophysics 294 (1): 173–7. doi:10.1016/0003-9861(92)90153-N. PMID 1550343. 
  55. ^ Zita, ČEstmír; Overvad, Kim; Mortensen, Svend Aage; Sindberg, Christian Dan; Moesgaard, Sven; Hunter, Douglas A. (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. doi:10.1002/biof.5520180221. PMID 14695934. 
  56. ^ a b Turunen, Mikael; Olsson, Jerker; Dallner, Gustav (2004). "Metabolism and function of coenzyme Q". Biochimica et Biophysica Acta 1660 (1–2): 171–99. doi:10.1016/j.bbamem.2003.11.012. PMID 14757233. 
  57. ^ a b Enomoto, Atsushi; Endou, Hitoshi (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. doi:10.1007/s10157-005-0368-5. PMID 16189627. 
  58. ^ a b Wu, X.; Lee, CC; Muzny, DM; Caskey, CT (1989). "Urate Oxidase: Primary Structure and Evolutionary Implications". Proceedings of the National Academy of Sciences of the United States of America 86 (23): 9412–6. Bibcode:1989PNAS...86.9412W. doi:10.1073/pnas.86.23.9412. PMC 298506. PMID 2594778. 
  59. ^ Wu, Xiangwei; Muzny, Donna M.; Lee, Cheng; Caskey, C. (1992). "Two independent mutational events in the loss of urate oxidase during hominoid evolution". Journal of Molecular Evolution 34 (1): 78–84. doi:10.1007/BF00163854. PMID 1556746. 
  60. ^ Alvarez-Lario, B.; Macarrón-Vicente, J. (2010). "Uric acid and evolution". Rheumatology 49 (11): 2010–5. doi:10.1093/rheumatology/keq204. PMID 20627967. 
  61. ^ a b Watanabe, S.; Kang, DH; Feng, L; Nakagawa, T; Kanellis, J; Lan, H; Mazzali, M; Johnson, RJ (2002). "Uric Acid, Hominoid Evolution, and the Pathogenesis of Salt-Sensitivity". Hypertension 40 (3): 355–60. doi:10.1161/01.HYP.0000028589.66335.AA. PMID 12215479. 
  62. ^ Johnson, Richard J.; Andrews, Peter; Benner, Steven A.; Oliver, William (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. PMC 2917125. PMID 20697570. 
  63. ^ a b Baillie, J. K.; Bates, M. G. D.; Thompson, A. A. R.; Waring, W. S.; Partridge, R. W.; Schnopp, M. F.; Simpson, A.; Gulliver-Sloan, F.; Maxwell, S. R. J.; Webb, DJ (2007). "Endogenous Urate Production Augments Plasma Antioxidant Capacity in Healthy Lowland Subjects Exposed to High Altitude". Chest 131 (5): 1473–8. doi:10.1378/chest.06-2235. PMID 17494796. 
  64. ^ a b Hooper, DC; Scott, GS; Zborek, A; Mikheeva, T; Kean, RB; Koprowski, H; Spitsin, SV (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. PMID 10744626. 
  65. ^ Santos, C; Anjos, EI; Augusto, O (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. doi:10.1006/abbi.1999.1491. PMID 10600166. 
  66. ^ Scott, G. S.; Spitsin, S. V.; Kean, R. B.; Mikheeva, T.; Koprowski, H.; Hooper, D. C. (2002). "Therapeutic intervention in experimental allergic encephalomyelitis by administration of uric acid precursors". Proceedings of the National Academy of Sciences of the United States of America 99 (25): 16303–8. Bibcode:2002PNAS...9916303S. doi:10.1073/pnas.212645999. PMC 138606. PMID 12451183. 
  67. ^ Fuhua Peng, F; Zhang, B; Zhong, X; Li, J; Xu, G; Hu, X; Qiu, W; Pei, Z (2007). "Serum uric acid levels of patients with multiple sclerosis and other neurological diseases". Multiple Sclerosis 14 (2): 188–96. doi:10.1177/1352458507082143. PMID 17942520. 
  68. ^ Massa, Jennifer; O'Reilly, E.; Munger, K. L.; Delorenze, G. N.; Ascherio, A. (2009). "Serum uric acid and risk of multiple sclerosis". Journal of Neurology 256 (10): 1643–8. doi:10.1007/s00415-009-5170-y. PMC 2834535. PMID 19468784. 
  69. ^ Amorini, Angela M.; Petzold, Axel; Tavazzi, Barbara; Eikelenboom, Judith; Keir, Geoffrey; Belli, Antonio; Giovannoni, Gavin; Di Pietro, Valentina; Polman, Chris; d'Urso, Serafina; Vagnozzi, Roberto; Uitdehaag, Bernard; Lazzarino, Giuseppe (2009). "Increase of uric acid and purine compounds in biological fluids of multiple sclerosis patients". Clinical Biochemistry 42 (10–11): 1001–6. doi:10.1016/j.clinbiochem.2009.03.020. PMID 19341721. 
  70. ^ Becker, B (1993). "Towards the physiological function of uric acid". Free Radical Biology and Medicine 14 (6): 615–31. doi:10.1016/0891-5849(93)90143-I. PMID 8325534. 
  71. ^ a b Sautin, Yuri; Johnson, Richard (2008). "Uric Acid: The Oxidant-Antioxidant Paradox". Nucleosides, Nucleotides and Nucleic Acids 27 (6): 608–19. doi:10.1080/15257770802138558. 
  72. ^ Eggebeen, Aaron T (2007). "Gout: An update". American family physician 76 (6): 801–8. PMID 17910294. 
  73. ^ Campion, E; Glynn, RJ; Delabry, LO (1987). "Asymptomatic hyperuricemia. Risks and consequences in the normative aging study*1". The American Journal of Medicine 82 (3): 421–6. doi:10.1016/0002-9343(87)90441-4. PMID 3826098. 
  74. ^ Nazarewicz, Rafal R.; Ziolkowski, Wieslaw; Vaccaro, Patrick S.; Ghafourifar, Pedram (2007). "Effect of Short-Term Ketogenic Diet on Redox Status of Human Blood". Rejuvenation Research 10 (4): 435–40. doi:10.1089/rej.2007.0540. PMID 17663642. 
  75. ^ Smirnoff, Nicholas (2001). "L-Ascorbic acid biosynthesis". Vitamins and hormones. Vitamins & Hormones 61: 241–66. doi:10.1016/S0083-6729(01)61008-2. ISBN 978-0-12-709861-6. PMID 11153268. 
  76. ^ Linster, Carole L.; Van Schaftingen, Emile (2007). "Vitamin C". FEBS Journal 274 (1): 1–22. doi:10.1111/j.1742-4658.2006.05607.x. PMID 17222174. 
  77. ^ a b Meister, Alton (1994). "Glutathione-ascorbic acid antioxidant system in animals". The Journal of Biological Chemistry 269 (13): 9397–400. PMID 8144521. 
  78. ^ Wells, William W.; Xu, Dian Peng; Yang, Yanfeng; Rocque, Pamela A. (1990). "Mammalian thioltransferase (glutaredoxin) and protein disulfide isomerase have dehydroascorbate reductase activity". The Journal of Biological Chemistry 265 (26): 15361–4. PMID 2394726. 
  79. ^ Padayatty, Sebastian J.; Katz, Arie; Wang, Yaohui; Eck, Peter; Kwon, Oran; Lee, Je-Hyuk; Chen, Shenglin; Corpe, Christopher; Dutta, Anand; Dutta, SK; Levine, M (2003). "Vitamin C as an antioxidant: evaluation of its role in disease prevention". Journal of the American College of Nutrition 22 (1): 18–35. doi:10.1080/07315724.2003.10719272. PMID 12569111. 
  80. ^ Shigeoka, S.; Ishikawa, T; Tamoi, M; Miyagawa, Y; Takeda, T; Yabuta, Y; Yoshimura, K (2002). "Regulation and function of ascorbate peroxidase isoenzymes". Journal of Experimental Botany 53 (372): 1305–19. doi:10.1093/jexbot/53.372.1305. PMID 11997377. 
  81. ^ Smirnoff, Nicholas; Wheeler, Glen L. (2000). "Ascorbic Acid in Plants: Biosynthesis and Function". Critical Reviews in Biochemistry and Molecular Biology 35 (4): 291–314. doi:10.1080/10409230008984166. PMID 11005203. 
  82. ^ a b c d Meister, A; Anderson, M E (1983). "Glutathione". Annual Review of Biochemistry 52: 711–60. doi:10.1146/ PMID 6137189. 
  83. ^ Meister, Alton (1988). "Glutathione metabolism and its selective modification". The Journal of Biological Chemistry 263 (33): 17205–8. PMID 3053703. 
  84. ^ Gaballa A; Newton GL; Antelmann H et al. (2010). "Biosynthesis and functions of bacillithiol, a major low-molecular-weight thiol in Bacilli". Proceedings of the National Academy of Sciences of the United States of America 107 (14): 6482–6. doi:10.1073/pnas.1000928107. PMC 2851989. PMID 20308541. 
  85. ^ Newton GL, Rawat M, La Clair JJ, Jothivasan VK, Budiarto T, Hamilton CJ, Claiborne A, Helmann JD, Fahey RC (2009). "Bacillithiol is an antioxidant thiol produced in Bacilli". Nature Chemical Biology 5 (9): 625–627. doi:10.1038/nchembio.189. ISSN 1552-4450. PMC 3510479. PMID 19578333. 
  86. ^ Fahey, Robert C. (2001). "Novelthiols Ofprokaryotes". Annual Review of Microbiology 55: 333–56. doi:10.1146/annurev.micro.55.1.333. PMID 11544359. 
  87. ^ Fairlamb, A H; Cerami, A (1992). "Metabolism and Functions of Trypanothione in the Kinetoplastida". Annual Review of Microbiology 46: 695–729. doi:10.1146/annurev.mi.46.100192.003403. PMID 1444271. 
  88. ^ Tan, Dun-Xian; Manchester, Lucien C.; Terron, Maria P.; Flores, Luis J.; Reiter, Russel J. (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. doi:10.1111/j.1600-079X.2006.00407.x. PMID 17198536. 
  89. ^ Reiter, Russel J.; Paredes, Sergio D.; Manchester, Lucien C.; Tan, Dan-Xian (2009). "Reducing oxidative/nitrosative stress: A newly-discovered genre for melatonin". Critical Reviews in Biochemistry and Molecular Biology 44 (4): 175–200. doi:10.1080/10409230903044914. PMID 19635037. 
  90. ^ Tan, Dun-Xian; Manchester, Lucien C.; Reiter, Russel J.; Qi, Wen-Bo; Karbownik, Malgorzata; Calvo, Juan R. (2000). "Significance of Melatonin in Antioxidative Defense System: Reactions and Products". Neurosignals 9 (3–4): 137–59. doi:10.1159/000014635. PMID 10899700. 
  91. ^ a b Herrera, E.; Barbas, C. (2001). "Vitamin E: Action, metabolism and perspectives". Journal of Physiology and Biochemistry 57 (2): 43–56. doi:10.1007/BF03179812. PMID 11579997. 
  92. ^ Packer, Lester; Weber, Stefan U.; Rimbach, Gerald (2001). "Molecular aspects of alpha-tocotrienol antioxidant action and cell signalling". The Journal of nutrition 131 (2): 369S–73S. PMID 11160563. 
  93. ^ a b Brigelius-Flohé, Regina; Traber, Maret G. (1999). "Vitamin E: Function and metabolism". The FASEB Journal 13 (10): 1145–55. PMID 10385606. 
  94. ^ Traber, Maret G.; Atkinson, Jeffrey (2007). "Vitamin E, antioxidant and nothing more". Free Radical Biology and Medicine 43 (1): 4–15. doi:10.1016/j.freeradbiomed.2007.03.024. PMC 2040110. PMID 17561088. 
  95. ^ Wang, Xiaoyuan; Quinn, Peter J. (1999). "Vitamin E and its function in membranes". Progress in Lipid Research 38 (4): 309–36. doi:10.1016/S0163-7827(99)00008-9. PMID 10793887. 
  96. ^ Seiler, Alexander; Schneider, Manuela; Förster, Heidi; Roth, Stephan; Wirth, Eva K.; Culmsee, Carsten; Plesnila, Nikolaus; Kremmer, Elisabeth; Rådmark, Olof; Wurst, Wolfgang; Bornkamm, Georg W.; Schweizer, Ulrich; Conrad, Marcus (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. doi:10.1016/j.cmet.2008.07.005. PMID 18762024. 
  97. ^ Brigelius-Flohé, Regina; Davies, Kelvin J.A. (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. doi:10.1016/j.freeradbiomed.2007.05.016. PMID 17561087. 
  98. ^ Atkinson, Jeffrey; Epand, Raquel F.; Epand, Richard M. (2008). "Tocopherols and tocotrienols in membranes: A critical review". Free Radical Biology and Medicine 44 (5): 739–64. doi:10.1016/j.freeradbiomed.2007.11.010. PMID 18160049. 
  99. ^ a b Azzi, Angelo (2007). "Molecular mechanism of α-tocopherol action". Free Radical Biology and Medicine 43 (1): 16–21. doi:10.1016/j.freeradbiomed.2007.03.013. PMID 17561089. 
  100. ^ Zingg, Jean-Marc; Azzi, Angelo (2004). "Non-antioxidant activities of vitamin E". Current medicinal chemistry 11 (9): 1113–33. doi:10.2174/0929867043365332. PMID 15134510. 
  101. ^ Sen, Chandan K.; Khanna, Savita; Roy, Sashwati (2006). "Tocotrienols: Vitamin E beyond tocopherols". Life Sciences 78 (18): 2088–98. doi:10.1016/j.lfs.2005.12.001. PMC 1790869. PMID 16458936. 
  102. ^ 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. doi:10.1080/10715760500104025. PMID 16036346. 
  103. ^ a b Carr A, Frei B (1999). "Does vitamin C act as a pro-oxidant under physiological conditions?". FASEB J. 13 (9): 1007–24. PMID 10336883. 
  104. ^ Stohs SJ, Bagchi D (1995). "Oxidative mechanisms in the toxicity of metal ions". Free Radic. Biol. Med. 18 (2): 321–36. doi:10.1016/0891-5849(94)00159-H. PMID 7744317. 
  105. ^ Valko M, Morris H, Cronin MT (2005). "Metals, toxicity and oxidative stress". Curr. Med. Chem. 12 (10): 1161–208. doi:10.2174/0929867053764635. PMID 15892631. 
  106. ^ Schneider C (2005). "Chemistry and biology of vitamin E". Mol Nutr Food Res 49 (1): 7–30. doi:10.1002/mnfr.200400049. PMID 15580660. 
  107. ^ 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. doi:10.1016/ PMID 18284912. 
  108. ^ a b c Ristow M, Zarse K (2010). "How increased oxidative stress promotes longevity and metabolic health: the concept of mitochondrial hormesis (mitohormesis)". Experimental Gerontology 45 (6): 410–418. doi:10.1016/j.exger.2010.03.014. PMID 20350594. 
  109. ^ a b c d 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. doi:10.1001/jama.297.8.842. PMID 17327526. 
  110. ^ Tapia, P (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. doi:10.1016/j.mehy.2005.09.009. PMID 16242247. 
  111. ^ 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. doi:10.1016/j.cmet.2007.08.011. PMID 17908557. 
  112. ^ a b Ho YS, Magnenat JL, Gargano M, Cao J (1998). "The nature of antioxidant defense mechanisms: a lesson from transgenic studies". Environ. Health Perspect. 106 (Suppl 5): 1219–28. doi:10.2307/3433989. JSTOR 3433989. PMC 1533365. PMID 9788901. 
  113. ^ 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. doi:10.1016/S0891-5849(02)00905-X. PMID 12126755. 
  114. ^ a b 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. doi:10.3109/10409238709083738. PMID 3315461. 
  115. ^ Johnson F, Giulivi C (2005). "Superoxide dismutases and their impact upon human health". Mol Aspects Med 26 (4–5): 340–52. doi:10.1016/j.mam.2005.07.006. PMID 16099495. 
  116. ^ Nozik-Grayck E, Suliman H, Piantadosi C (2005). "Extracellular superoxide dismutase". Int J Biochem Cell Biol 37 (12): 2466–71. doi:10.1016/j.biocel.2005.06.012. PMID 16087389. 
  117. ^ 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. doi:10.1038/ng0298-159. PMID 9462746. 
  118. ^ 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. doi:10.1038/ng0596-43. PMID 8673102. 
  119. ^ 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. doi:10.1016/S0891-5849(97)00112-3. PMID 9214590. 
  120. ^ Chelikani P, Fita I, Loewen P (2004). "Diversity of structures and properties among catalases". Cell Mol Life Sci 61 (2): 192–208. doi:10.1007/s00018-003-3206-5. PMID 14745498. 
  121. ^ 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. doi:10.1016/S0079-6107(98)00058-3. PMID 10446501. 
  122. ^ 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. doi:10.1016/0891-5849(92)90150-F. PMID 1334030. 
  123. ^ 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. doi:10.1016/S0162-0134(02)00390-2. PMID 12121759. 
  124. ^ Mueller S, Riedel H, Stremmel W (1997). "Direct evidence for catalase as the predominant H2O2 -removing enzyme in human erythrocytes". Blood 90 (12): 4973–8. PMID 9389716. 
  125. ^ Ogata M (1991). "Acatalasemia". Hum Genet 86 (4): 331–40. doi:10.1007/BF00201829. PMID 1999334. 
  126. ^ 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. doi:10.1021/bi050448i. PMC 3832347. PMID 16060667.  PDB 1YEX
  127. ^ 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. doi:10.1016/j.freeradbiomed.2005.02.026. PMID 15917183. 
  128. ^ Wood Z, Schröder E, Robin Harris J, Poole L (2003). "Structure, mechanism and regulation of peroxiredoxins". Trends Biochem Sci 28 (1): 32–40. doi:10.1016/S0968-0004(02)00003-8. PMID 12517450. 
  129. ^ 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. doi:10.1021/bi992025k. PMID 10569923. 
  130. ^ Jönsson TJ, Lowther WT (2007). "The peroxiredoxin repair proteins". Sub-cellular biochemistry. Subcellular Biochemistry 44: 115–41. doi:10.1007/978-1-4020-6051-9_6. ISBN 978-1-4020-6050-2. PMC 2391273. PMID 18084892. 
  131. ^ 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. doi:10.1038/nature01819. PMID 12891360. 
  132. ^ 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. doi:10.1182/blood-2002-08-2548. PMID 12586629. 
  133. ^ 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. doi:10.1093/jxb/erj160. PMID 16606633. 
  134. ^ Nordberg J, Arner ES (2001). "Reactive oxygen species, antioxidants, and the mammalian thioredoxin system". Free Radic Biol Med 31 (11): 1287–312. doi:10.1016/S0891-5849(01)00724-9. PMID 11728801. 
  135. ^ Vieira Dos Santos C, Rey P (2006). "Plant thioredoxins are key actors in the oxidative stress response". Trends Plant Sci 11 (7): 329–34. doi:10.1016/j.tplants.2006.05.005. PMID 16782394. 
  136. ^ Arnér E, Holmgren A (2000). "Physiological functions of thioredoxin and thioredoxin reductase". Eur J Biochem 267 (20): 6102–9. doi:10.1046/j.1432-1327.2000.01701.x. PMID 11012661. 
  137. ^ Mustacich D, Powis G (2000). "Thioredoxin reductase". Biochem J 346 (Pt 1): 1–8. doi:10.1042/0264-6021:3460001. PMC 1220815. PMID 10657232. 
  138. ^ 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. PMID 8736785. 
  139. ^ Brigelius-Flohé R (1999). "Tissue-specific functions of individual glutathione peroxidases". Free Radic Biol Med 27 (9–10): 951–65. doi:10.1016/S0891-5849(99)00173-2. PMID 10569628. 
  140. ^ 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. doi:10.1074/jbc.272.26.16644. PMID 9195979. 
  141. ^ 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. doi:10.1074/jbc.273.35.22528. PMID 9712879. 
  142. ^ 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. doi:10.1089/152308604322899350. PMID 15025930. 
  143. ^ Hayes J, Flanagan J, Jowsey I (2005). "Glutathione transferases". Annu Rev Pharmacol Toxicol 45: 51–88. doi:10.1146/annurev.pharmtox.45.120403.095857. PMID 15822171. 
  144. ^ Christen Y (2000). "Oxidative stress and Alzheimer disease". Am J Clin Nutr 71 (2): 621S–629S. PMID 10681270. 
  145. ^ 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. doi:10.1097/ PMID 16825950. 
  146. ^ Wood-Kaczmar A, Gandhi S, Wood N (2006). "Understanding the molecular causes of Parkinson's disease". Trends Mol Med 12 (11): 521–8. doi:10.1016/j.molmed.2006.09.007. PMID 17027339. 
  147. ^ Davì G, Falco A, Patrono C (2005). "Lipid peroxidation in diabetes mellitus". Antioxid Redox Signal 7 (1–2): 256–68. doi:10.1089/ars.2005.7.256. PMID 15650413. 
  148. ^ Giugliano D, Ceriello A, Paolisso G (1996). "Oxidative stress and diabetic vascular complications". Diabetes Care 19 (3): 257–67. doi:10.2337/diacare.19.3.257. PMID 8742574. 
  149. ^ Hitchon C, El-Gabalawy H (2004). "Oxidation in rheumatoid arthritis". Arthritis Res Ther 6 (6): 265–78. doi:10.1186/ar1447. PMC 1064874. PMID 15535839. 
  150. ^ Cookson M, Shaw P (1999). "Oxidative stress and motor neurone disease". Brain Pathol 9 (1): 165–86. doi:10.1111/j.1750-3639.1999.tb00217.x. PMID 9989458. 
  151. ^ Van Gaal L, Mertens I, De Block C (2006). "Mechanisms linking obesity with cardiovascular disease". Nature 444 (7121): 875–80. Bibcode:2006Natur.444..875V. doi:10.1038/nature05487. PMID 17167476. 
  152. ^ Aviram M (2000). "Review of human studies on oxidative damage and antioxidant protection related to cardiovascular diseases". Free Radic Res. 33 Suppl: S85–97. PMID 11191279. 
  153. ^ Khan MA, Tania M, Zhang D, Chen H (2010). "Antioxidant enzymes and cancer". Chin J Cancer Res 22 (2): 87–92. doi:10.1007/s11670-010-0087-7. 
  154. ^ 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". Proceedings of the National Academy of Sciences of the United States of America 103 (6): 1768–1773. Bibcode:2006PNAS..103.1768L. doi:10.1073/pnas.0510452103. PMC 1413655. PMID 16446459. 
  155. ^ Larsen P (1993). "Aging and resistance to oxidative damage in Caenorhabditis elegans". Proceedings of the National Academy of Sciences of the United States of America 90 (19): 8905–9. Bibcode:1993PNAS...90.8905L. doi:10.1073/pnas.90.19.8905. PMC 47469. PMID 8415630. 
  156. ^ Helfand S, Rogina B (2003). "Genetics of aging in the fruit fly, Drosophila melanogaster". Annu Rev Genet 37: 329–48. doi:10.1146/annurev.genet.37.040103.095211. PMID 14616064. 
  157. ^ a b 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. doi:10.1016/S0891-5849(02)00886-9. PMID 12208343. 
  158. ^ a b Sohal R (2002). "Role of oxidative stress and protein oxidation in the aging process". Free Radic Biol Med 33 (1): 37–44. doi:10.1016/S0891-5849(02)00856-0. PMID 12086680. 
  159. ^ a b Rattan S (2006). "Theories of biological aging: genes, proteins, and free radicals". Free Radic Res 40 (12): 1230–8. doi:10.1080/10715760600911303. PMID 17090411. 
  160. ^ Pérez, Viviana I.; Bokov, A; Van Remmen, H; Mele, J; Ran, Q; Ikeno, Y; Richardson, A (2009). "Is the oxidative stress theory of aging dead?". Biochimica et Biophysica Acta (BBA) – General Subjects 1790 (10): 1005–1014. doi:10.1016/j.bbagen.2009.06.003. PMC 2789432. PMID 19524016. Retrieved 14 September 2009. 
  161. ^ Thomas D (2004). "Vitamins in health and aging". Clin Geriatr Med 20 (2): 259–74. doi:10.1016/j.cger.2004.02.001. PMID 15182881. 
  162. ^ Ward J (1998). "Should antioxidant vitamins be routinely recommended for older people?". Drugs Aging 12 (3): 169–75. doi:10.2165/00002512-199812030-00001. PMID 9534018. 
  163. ^ Aggarwal BB, Shishodia S (2006). "Molecular targets of dietary agents for prevention and therapy of cancer". Biochem. Pharmacol. 71 (10): 1397–421. doi:10.1016/j.bcp.2006.02.009. PMID 16563357. 
  164. ^ Sena E, Wheble P, Sandercock P, Macleod M (February 2007). "Systematic review and meta-analysis of the efficacy of tirilazad in experimental stroke". Stroke 38 (2): 388–94. doi:10.1161/01.STR.0000254462.75851.22. PMID 17204689. 
  165. ^ Zhang S, Wang L, Liu M, Wu B (2010). "Tirilazad for aneurysmal subarachnoid haemorrhage". Cochrane Database Syst Rev (2): CD006778. doi:10.1002/14651858.CD006778.pub2. PMID 20166088. 
  166. ^ Bath PM, Iddenden R, Bath FJ, Orgogozo JM (2001). "Tirilazad for acute ischaemic stroke". Cochrane Database Syst Rev (4): CD002087. doi:10.1002/14651858.CD002087. PMID 11687138. 
  167. ^ Bath PM, Gray LJ, Bath AJ, Buchan A, Miyata T, Green AR (August 2009). "Effects of NXY-059 in experimental stroke: an individual animal meta-analysis". Br. J. Pharmacol. 157 (7): 1157–71. doi:10.1111/j.1476-5381.2009.00196.x. PMC 2743834. PMID 19422398. 
  168. ^ Green AR, Ashwood T (April 2005). "Free radical trapping as a therapeutic approach to neuroprotection in stroke: experimental and clinical studies with NXY-059 and free radical scavengers". Curr Drug Targets CNS Neurol Disord 4 (2): 109–18. doi:10.2174/1568007053544156. PMID 15857295. 
  169. ^ a b Lemmo, W (2014). "Potential interactions of prescription and over-the-counter medications having antioxidant capabilities with radiation and chemotherapy". Int J of Cancer. doi:10.1002/ijc.29208. PMID 25220632. 
  170. ^ D'Andrea GM (2005). "Use of antioxidants during chemotherapy and radiotherapy should be avoided". CA Cancer J Clin 55 (5): 319–21. doi:10.3322/canjclin.55.5.319. PMID 16166076. 
  171. ^ a b c 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. doi:10.1079/PHN2003543. PMID 15153272. 
  172. ^ Food, Nutrition, Physical Activity, and the Prevention of Cancer: a Global Perspective. World Cancer Research Fund (2007). ISBN 978-0-9722522-2-5.
  173. ^ 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. doi:10.2174/1568007033482959. PMID 12769802. 
  174. ^ Rao A, Balachandran B (2002). "Role of oxidative stress and antioxidants in neurodegenerative diseases". Nutr Neurosci 5 (5): 291–309. doi:10.1080/1028415021000033767. PMID 12385592. 
  175. ^ 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. doi:10.1016/j.heares.2006.10.008. PMID 17184943. 
  176. ^ Crichton GE, Bryan J, Murphy KJ (September 2013). "Dietary antioxidants, cognitive function and dementia--a systematic review". Plant Foods Hum Nutr 68 (3): 279–92. doi:10.1007/s11130-013-0370-0. PMID 23881465. 
  177. ^ Takeda A, Nyssen OP, Syed A, Jansen E, Bueno-de-Mesquita B, Gallo V (2014). "Vitamin A and carotenoids and the risk of Parkinson's disease: a systematic review and meta-analysis". Neuroepidemiology 42 (1): 25–38. doi:10.1159/000355849. PMID 24356061. 
  178. ^ Harrison FE (2012). "A critical review of vitamin C for the prevention of age-related cognitive decline and Alzheimer's disease". J. Alzheimers Dis. 29 (4): 711–26. doi:10.3233/JAD-2012-111853. PMC 3727637. PMID 22366772. 
  179. ^ a b Shenkin A (2006). "The key role of micronutrients". Clin Nutr 25 (1): 1–13. doi:10.1016/j.clnu.2005.11.006. PMID 16376462. 
  180. ^ Woodside J, McCall D, McGartland C, Young I (2005). "Micronutrients: dietary intake v. supplement use". Proc Nutr Soc 64 (4): 543–53. doi:10.1079/PNS2005464. PMID 16313697. 
  181. ^ a b Hail N, Cortes M, Drake EN, Spallholz JE (2008). "Cancer chemoprevention: a radical perspective". Free Radic. Biol. Med. 45 (2): 97–110. doi:10.1016/j.freeradbiomed.2008.04.004. PMID 18454943. 
  182. ^ Williams RJ, Spencer JP, Rice-Evans C (2004). "Flavonoids: antioxidants or signalling molecules?". Free Radical Biology & Medicine 36 (7): 838–49. doi:10.1016/j.freeradbiomed.2004.01.001. PMID 15019969. 
  183. ^ Virgili F, Marino M (2008). "Regulation of cellular signals from nutritional molecules: a specific role for phytochemicals, beyond antioxidant activity". Free Radical Biology & Medicine 45 (9): 1205–16. doi:10.1016/j.freeradbiomed.2008.08.001. PMID 18762244. 
  184. ^ 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. doi:10.1016/j.cmet.2007.08.011. PMID 17908557. 
  185. ^ 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. doi:10.1074/jbc.M408918200. PMID 15383542. 
  186. ^ Green GA (2008). "Review: antioxidant supplements do not reduce all-cause mortality in primary or secondary prevention". Evid Based Med 13 (6): 177. doi:10.1136/ebm.13.6.177. PMID 19043035. 
  187. ^ 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. doi:10.2165/00007256-199621030-00005. PMID 8776010. 
  188. ^ Tiidus P (1998). "Radical species in inflammation and overtraining". Can J Physiol Pharmacol 76 (5): 533–8. doi:10.1139/cjpp-76-5-533. PMID 9839079. 
  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. PMID 8067452. 
  190. ^ Leeuwenburgh C, Heinecke J (2001). "Oxidative stress and antioxidants in exercise". Curr Med Chem 8 (7): 829–38. doi:10.2174/0929867013372896. PMID 11375753. 
  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. doi:10.2165/00007256-200029020-00001. PMID 10701711. 
  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. doi:10.1249/01.mss.0000188579.36272.f6. PMID 16394956. 
  193. ^ Peake J (2003). "Vitamin C: effects of exercise and requirements with training". Int J Sport Nutr Exerc Metab 13 (2): 125–51. PMID 12945825. 
  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. doi:10.1007/BF00376459. PMID 8299614. 
  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. doi:10.1079/BJN20061732. PMID 16611389. 
  196. ^ Gavura, Scott. "Antioxidants and Exercise: More Harm Than Good?". Science Based Medicine. Retrieved 19 December 2011. 
  197. ^ Hurrell R (2003). "Influence of vegetable protein sources on trace element and mineral bioavailability". J Nutr 133 (9): 2973S–7S. PMID 12949395. 
  198. ^ Hunt J (2003). "Bioavailability of iron, zinc, and other trace minerals from vegetarian diets". Am J Clin Nutr 78 (3 Suppl): 633S–639S. PMID 12936958. 
  199. ^ 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. doi:10.1079/PNS2006489. PMID 16672077. 
  200. ^ a b 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. doi:10.1007/BF01088275. PMID 8577655. 
  201. ^ Sandberg A (2002). "Bioavailability of minerals in legumes". Br J Nutr 88 (Suppl 3): S281–5. doi:10.1079/BJN/2002718. PMID 12498628. 
  202. ^ a b Beecher G (2003). "Overview of dietary flavonoids: nomenclature, occurrence and intake". J Nutr 133 (10): 3248S–3254S. PMID 14519822. 
  203. ^ 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. doi:10.1111/j.1365-2184.2006.00384.x. PMID 16872360. 
  204. ^ 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. PMID 7429760. 
  205. ^ 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. doi:10.1093/jnci/88.21.1550. PMID 8901853. 
  206. ^ Albanes D (1999). "Beta-carotene and lung cancer: a case study". Am J Clin Nutr 69 (6): 1345S–50S. PMID 10359235. 
  207. ^ Study Citing Antioxidant Vitamin Risks Based On Flawed Methodology, Experts Argue News release from Oregon State University published on ScienceDaily. Retrieved 19 April 2007
  208. ^ Bjelakovic, G; D Nikolova; L L Gluud; R G Simonetti; C Gluud (2008). Bjelakovic, Goran, ed. "Antioxidant supplements for prevention of mortality in healthy participants and patients with various diseases". Cochrane database of systematic reviews (Online) (2): CD007176. doi:10.1002/14651858.CD007176. ISSN 1469-493X. PMID 18425980. 
  209. ^ 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". Annals of Internal Medicine 142 (1): 37–46. doi:10.7326/0003-4819-142-1-200501040-00110. PMID 15537682. 
  210. ^ 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. doi:10.1111/j.1365-2036.2006.02970.x. PMID 16842454. 
  211. ^ 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. doi:10.1001/archinte.164.21.2335. PMID 15557412. 
  212. ^ Caraballoso M, Sacristan M, Serra C, Bonfill X (2003). Caraballoso, Magali, ed. "Drugs for preventing lung cancer in healthy people". Cochrane Database Syst Rev (2): CD002141. doi:10.1002/14651858.CD002141. PMID 12804424. 
  213. ^ 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. doi:10.1111/j.1365-2036.2006.02970.x. PMID 16842454. 
  214. ^ 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. doi:10.1111/j.1525-1497.2006.00483.x. PMC 1924689. PMID 16808775. 
  215. ^ Schumacker P (2006). "Reactive oxygen species in cancer cells: Live by the sword, die by the sword". Cancer Cell 10 (3): 175–6. doi:10.1016/j.ccr.2006.08.015. PMID 16959608. 
  216. ^ Seifried H, McDonald S, Anderson D, Greenwald P, Milner J (2003). "The antioxidant conundrum in cancer". Cancer Res 63 (15): 4295–8. PMID 12907593. 
  217. ^ Lawenda BD, Kelly KM, Ladas EJ, Sagar SM, Vickers A, Blumberg JB (2008). "Should supplemental antioxidant administration be avoided during chemotherapy and radiation therapy?". J. Natl. Cancer Inst. 100 (11): 773–83. doi:10.1093/jnci/djn148. PMID 18505970. 
  218. ^ Block KI, Koch AC, Mead MN, Tothy PK, Newman RA, Gyllenhaal C (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. doi:10.1002/ijc.23754. PMID 18623084. 
  219. ^ Block KI, Koch AC, Mead MN, Tothy PK, Newman RA, Gyllenhaal C (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. doi:10.1016/j.ctrv.2007.01.005. PMID 17367938. 
  220. ^ Rodriguez-Amaya D (2003). "Food carotenoids: analysis, composition and alterations during storage and processing of foods". Forum Nutr 56: 35–7. PMID 15806788. 
  221. ^ Maiani G, Periago Castón MJ, Catasta G (2008). "Carotenoids: Actual knowledge on food sources, intakes, stability and bioavailability and their protective role in humans". Mol Nutr Food Res 53: S194–218. doi:10.1002/mnfr.200800053. PMID 19035552. 
  222. ^ Henry C, Heppell N (2002). "Nutritional losses and gains during processing: future problems and issues". Proc Nutr Soc 61 (1): 145–8. doi:10.1079/PNS2001142. PMID 12002789. 
  223. ^ "Antioxidants and Cancer Prevention: Fact Sheet". National Cancer Institute. Archived from the original on 4 March 2007. Retrieved 27 February 2007. 
  224. ^ Ortega RM (2006). "Importance of functional foods in the Mediterranean diet". Public Health Nutr 9 (8A): 1136–40. doi:10.1017/S1368980007668530. PMID 17378953. 
  225. ^ Witschi A, Reddy S, Stofer B, Lauterburg B (1992). "The systemic availability of oral glutathione". Eur J Clin Pharmacol 43 (6): 667–9. doi:10.1007/BF02284971. PMID 1362956. 
  226. ^ 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. doi:10.1080/01635589409514302. PMID 8183721. 
  227. ^ a b Dodd S, Dean O, Copolov DL, Malhi GS, Berk M (2008). "N-acetylcysteine for antioxidant therapy: pharmacology and clinical utility". Expert Opin Biol Ther 8 (12): 1955–62. doi:10.1517/14728220802517901. PMID 18990082. 
  228. ^ van de Poll MC, Dejong CH, Soeters PB (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. PMID 16702341. 
  229. ^ Wu G, Fang YZ, Yang S, Lupton JR, Turner ND (2004). "Glutathione metabolism and its implications for health". J. Nutr. 134 (3): 489–92. PMID 14988435. 
  230. ^ Cao G, Alessio H, Cutler R (1993). "Oxygen-radical absorbance capacity assay for antioxidants". Free Radic Biol Med 14 (3): 303–11. doi:10.1016/0891-5849(93)90027-R. PMID 8458588. 
  231. ^ 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". Journal of Agricultural and Food Chemistry 49 (10): 4619–26. doi:10.1021/jf010586o. PMID 11599998. 
  232. ^ "Withdrawn: Oxygen Radical Absorbance Capacity (ORAC) of Selected Foods, Release 2 (2010)". United States Department of Agriculture, Agricultural Research Service. 16 May 2012. Retrieved 13 June 2012. 
  233. ^ Prior R, Wu X, Schaich K (2005). "Standardized methods for the determination of antioxidant capacity and phenolics in foods and dietary supplements". Journal of Agricultural and Food Chemistry 53 (10): 4290–302. doi:10.1021/jf0502698. PMID 15884874. 
  234. ^ Kader A, Zagory D, Kerbel E (1989). "Modified atmosphere packaging of fruits and vegetables". Crit Rev Food Sci Nutr 28 (1): 1–30. doi:10.1080/10408398909527490. PMID 2647417. 
  235. ^ 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. PMID 1184900. 
  236. ^ Iverson F (1995). "Phenolic antioxidants: Health Protection Branch studies on butylated hydroxyanisole". Cancer Lett 93 (1): 49–54. doi:10.1016/0304-3835(95)03787-W. PMID 7600543. 
  237. ^ "E number index". UK food guide. Archived from the original on 4 March 2007. Retrieved 5 March 2007. 
  238. ^ Robards K, Kerr A, Patsalides E (1988). "Rancidity and its measurement in edible oils and snack foods. A review". Analyst 113 (2): 213–24. Bibcode:1988Ana...113..213R. doi:10.1039/an9881300213. PMID 3288002. 
  239. ^ 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". Journal of Agricultural and Food Chemistry 52 (13): 4072–9. doi:10.1021/jf049806z. PMID 15212450. 
  240. ^ Boozer, Charles E.; Hammond, George S.; Hamilton, Chester E.; Sen, Jyotirindra N. (1955). "Air Oxidation of Hydrocarbons.1II. The Stoichiometry and Fate of Inhibitors in Benzene and Chlorobenzene". Journal of the American Chemical Society 77 (12): 3233–7. Bibcode:1955JAChS..77.1678G. doi:10.1021/ja01617a026. 
  241. ^ "Market Study: Antioxidants". Ceresana Research. 
  242. ^ "Why use Antioxidants?". SpecialChem Adhesives. Archived from the original on 11 February 2007. Retrieved 27 February 2007. 
  243. ^ a b "Fuel antioxidants". Innospec Chemicals. Archived from the original on 15 October 2006. Retrieved 27 February 2007. 

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

External links[edit]