From HandWiki
Short description: Compound that inhibits the oxidation of other molecules
Structure of the antioxidant, glutathione

Antioxidants are compounds that inhibit oxidation (usually occurring as autoxidation), a chemical reaction that can produce free radicals. This can lead to polymerization and other chain reactions. They are frequently added to industrial products, such as fuels and lubricants, to prevent oxidation, and to foods to prevent spoilage, in particular the rancidification of oils and fats. In cells, antioxidants such as glutathione, mycothiol or bacillithiol, and enzyme systems like superoxide dismutase, can prevent damage from oxidative stress.

The only dietary antioxidants are vitamins A, C, and E, but the term antioxidant has also been applied to numerous other dietary compounds that only have antioxidant properties in vitro, with little evidence for antioxidant properties in vivo.[1] Dietary supplements marketed as antioxidants have not been shown to maintain health or prevent disease in humans.[2]


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.[3] 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.[4]

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.[5] 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 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.[6][7] 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.[8] 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.[9]

Uses in technology

Food preservatives

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.[10] 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.[11] 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).[12][13]

The most common molecules attacked by oxidation are unsaturated fats; oxidation causes them to turn rancid.[14] 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.[15] Antioxidant stabilizers are also added to fat-based cosmetics such as lipstick and moisturizers to prevent rancidity.[16]

Industrial uses

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

Antioxidants are frequently added to industrial products. In 2014, the worldwide market for natural and synthetic antioxidants was US$2.25 billion with a forecast of growth to $3.25 billion by 2020.[17] A common use is as stabilizers in fuels and additives in lubricants, to prevent oxidation and polymerization that leads to the formation of engine-fouling residues.[18]

Fuel additive Components[19] Applications[19]
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 (BHT) 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

Antioxidant polymer stabilizers are widely used to prevent the degradation of polymers such as rubbers, plastics and adhesives that causes a loss of strength and flexibility in these materials.[20] 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. Oxidation can be accelerated by UV radiation in natural sunlight to cause photo-oxidation. Various specialised light stabilisers, such as HALS may be added to plastics to prevent this. Synthetic phenolic[21] and aminic[22] antioxidants are increasingly being identified as potential human and eviromental health hazards.

Oxidative challenge in biology

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 element 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.[24][25] In general, antioxidant systems either prevent these reactive species from being formed, or remove them before they can damage vital components of the cell.[23][24] 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.[26]

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).[27] 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.[28] These oxidants can damage cells by starting chemical chain reactions such as lipid peroxidation, or by oxidizing DNA or proteins.[24] Damage to DNA can cause mutations and possibly cancer, if not reversed by DNA repair mechanisms,[29][30] while damage to proteins causes enzyme inhibition, denaturation and protein degradation.[31]

The use of oxygen as part of the process for generating metabolic energy produces reactive oxygen species.[32] In this process, the superoxide anion is produced as a by-product of several steps in the electron transport chain.[33] 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.[34] Peroxide is also produced from the oxidation of reduced flavoproteins, such as complex I.[35] However, although these enzymes can produce oxidants, the relative importance of the electron transfer chain to other processes that generate peroxide is unclear.[36][37] In plants, algae, and cyanobacteria, reactive oxygen species are also produced during photosynthesis,[38] particularly under conditions of high light intensity.[39] This effect is partly offset by the involvement of carotenoids in photoinhibition, and in algae and cyanobacteria, by large amount of iodide and selenium,[40] which involves these antioxidants reacting with over-reduced forms of the photosynthetic reaction centres to prevent the production of reactive oxygen species.[41][42]

Examples of bioactive antioxidant compounds

Physiological 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.[24] These compounds may be synthesized in the body or obtained from the diet.[25] 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 systemically distributed (see table below). Some antioxidants are only found in a few organisms, and can be pathogens or virulence factors.[43]

The interactions between these different antioxidants may be synergistic and interdependent.[44][45] The action of one antioxidant may therefore depend on the proper function of other members of the antioxidant system.[25] 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.[25]

Some compounds contribute to antioxidant defense by chelating transition metals and preventing them from catalyzing the production of free radicals in the cell. The ability to sequester iron for iron-binding proteins, such as transferrin and ferritin, is one such function.[37] Selenium and zinc are commonly referred to as antioxidant minerals, but these chemical elements have no antioxidant action themselves, but rather are required for the activity of antioxidant enzymes, such as glutathione reductase and superoxide dismutase. (See also selenium in biology and zinc in biology.)

Antioxidant Solubility Concentration in human serum (μM) 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

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]

Uric acid has the highest concentration of any blood antioxidant[51] and provides over half of the total antioxidant capacity of human serum.[64] 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,[65] peroxides, and hypochlorous acid.[57] Concerns over elevated UA's contribution to gout must be considered one of many risk factors.[66] 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).[67] Many of these aforementioned studies determined UA's antioxidant actions within normal physiological levels,[63][65] and some found antioxidant activity at levels as high as 285 μmol/L.[68]

Vitamin C

Ascorbic acid or vitamin C is a monosaccharide oxidation-reduction (redox) catalyst found in both animals and plants.[69] As one of the enzymes needed to make ascorbic acid has been lost by mutation during primate evolution, humans must obtain it from their diet; it is therefore a dietary vitamin.[69][70] Most other animals are able to produce this compound in their bodies and do not require it in their diets.[71] Ascorbic acid is required for the conversion of the procollagen to collagen by oxidizing proline residues to hydroxyproline.[69] In other cells, it is maintained in its reduced form by reaction with glutathione, which can be catalysed by protein disulfide isomerase and glutaredoxins.[72][73] Ascorbic acid is a redox catalyst which can reduce, and thereby neutralize, reactive oxygen species such as hydrogen peroxide.[69][74] In addition to its direct antioxidant effects, ascorbic acid is also a substrate for the redox enzyme ascorbate peroxidase, a function that is used in stress resistance in plants.[75] Ascorbic acid is present at high levels in all parts of plants and can reach concentrations of 20 millimolar in chloroplasts.[76]


The free radical mechanism of lipid peroxidation

Glutathione is a cysteine-containing peptide found in most forms of aerobic life.[77] It is not required in the diet and is instead synthesized in cells from its constituent amino acids.[78] 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.[72] 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.[77] In some organisms glutathione is replaced by other thiols, such as by mycothiol in the Actinomycetes, bacillithiol in some gram-positive bacteria,[79][80] or by trypanothione in the Kinetoplastids.[81][82]

Vitamin E

Vitamin E is the collective name for a set of eight related tocopherols and tocotrienols, which are fat-soluble vitamins with antioxidant properties.[83][84] Of these, α-tocopherol has been most studied as it has the highest bioavailability, with the body preferentially absorbing and metabolising this form.[85]

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.[83][86] 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.[87] 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.[88] 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,[89][90] 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.[91][92] 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,[85] and tocotrienols may be important in protecting neurons from damage.[93]

Pro-oxidant activities

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;[94] however, it will also reduce metal ions that generate free radicals through the Fenton reaction.[28][95]

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.[95]

Enzyme systems

[math]\ce{ \underset{Oxygen}{O2} -> \underset{Superoxide}{*O2^-} ->[\ce{Superoxide \atop dismutase}] \underset{Hydrogen \atop peroxide}{H2O2} ->[\ce{Peroxidases \atop catalase}] \underset{Water}{H2O} }[/math]
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.[23][24] 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.[96]

Superoxide dismutase, catalase, and peroxiredoxins

Superoxide dismutases (SODs) are a class of closely related enzymes that catalyze the breakdown of the superoxide anion into oxygen and hydrogen peroxide.[97][98] SOD enzymes are present in almost all aerobic cells and in extracellular fluids.[99] 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.[98] There also exists a third form of SOD in extracellular fluids, which contains copper and zinc in its active sites.[100] The mitochondrial isozyme seems to be the most biologically important of these three, since mice lacking this enzyme die soon after birth.[101] 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).[96][102] 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.[103]

Catalases are enzymes that catalyse the conversion of hydrogen peroxide to water and oxygen, using either an iron or manganese cofactor.[104][105] This protein is localized to peroxisomes in most eukaryotic cells.[106] 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.[107] Despite its apparent importance in hydrogen peroxide removal, humans with genetic deficiency of catalase — "acatalasemia" — or mice genetically engineered to lack catalase completely, experience few ill effects.[108][109]

Decameric structure of AhpC, a bacterial 2-cysteine peroxiredoxin from Salmonella typhimurium[110]

Peroxiredoxins are peroxidases that catalyze the reduction of hydrogen peroxide, organic hydroperoxides, as well as peroxynitrite.[111] They are divided into three classes: typical 2-cysteine peroxiredoxins; atypical 2-cysteine peroxiredoxins; and 1-cysteine peroxiredoxins.[112] 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.[113] Over-oxidation of this cysteine residue in peroxiredoxins inactivates these enzymes, but this can be reversed by the action of sulfiredoxin.[114] Peroxiredoxins seem to be important in antioxidant metabolism, as mice lacking peroxiredoxin 1 or 2 have shortened lifespans and develop hemolytic anaemia, while plants use peroxiredoxins to remove hydrogen peroxide generated in chloroplasts.[115][116][117]

Thioredoxin and glutathione systems

The thioredoxin system contains the 12-kDa protein thioredoxin and its companion thioredoxin reductase.[118] Proteins related to thioredoxin are present in all sequenced organisms. Plants, such as Arabidopsis thaliana, have a particularly great diversity of isoforms.[119] 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.[120] After being oxidized, the active thioredoxin is regenerated by the action of thioredoxin reductase, using NADPH as an electron donor.[121]

The glutathione system includes glutathione, glutathione reductase, glutathione peroxidases, and glutathione S-transferases.[77] This system is found in animals, plants and microorganisms.[77][122] 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.[123] 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,[124] but they are hypersensitive to induced oxidative stress.[125] In addition, the glutathione S-transferases show high activity with lipid peroxides.[126] These enzymes are at particularly high levels in the liver and also serve in detoxification metabolism.[127]

Health research

Relation to diet

The dietary antioxidant vitamins A, C, and E are essential and required in specific daily amounts to prevent diseases.[2][128][129] Polyphenols, which have antioxidant properties in vitro due to their free hydroxy groups,[130] are extensively metabolized by catechol-O-methyltransferase which methylates free hydroxyl groups, and thereby prevents them from acting as antioxidants in vivo.[131][132]


Common pharmaceuticals (and supplements) with antioxidant properties may interfere with the efficacy of certain anticancer medication and radiation therapy.[133]

Adverse effects

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.[134] Examples are oxalic acid, tannins and phytic acid, which are high in plant-based diets.[135] 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. However, germination, soaking, or microbial fermentation are all household strategies that reduce the phytate and polyphenol content of unrefined cereal. Increases in Fe, Zn and Ca absorption have been reported in adults fed dephytinized cereals compared with cereals containing their native phytate.[136]

Foods Reducing acid present
Cocoa bean and chocolate, spinach, turnip and rhubarb[137] Oxalic acid
Whole grains, maize, legumes[138] Phytic acid
Tea, beans, cabbage[137][139] Tannins

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.[140] Subsequent studies confirmed these adverse effects.[141] These harmful effects may also be seen in non-smokers, as one 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.[142] No health risk was seen when all the randomized controlled studies were examined together, but an increase in mortality was detected when only high-quality and low-bias risk trials were examined separately.[143] As the majority of these low-bias trials dealt with either elderly people, or people with disease, these results may not apply to the general population.[144] This meta-analysis was later repeated and extended by the same authors, confirming the previous results.[143] These two publications are consistent with some previous meta-analyses that also suggested that vitamin E supplementation increased mortality,[145] and that antioxidant supplements increased the risk of colon cancer.[146] Beta-carotene may also increase lung cancer.[146][147] 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.[128][148][142]

Levels in food

Fruits and vegetables are good sources of antioxidant vitamins C and E.

Antioxidant vitamins are found in vegetables, fruits, eggs, legumes and nuts. Vitamins A, C, and E can be destroyed by long-term storage or prolonged cooking.[149] 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.[150] Processed food contains fewer antioxidant vitamins than fresh and uncooked foods, as preparation exposes food to heat and oxygen.[151]

Antioxidant vitamins Foods containing high levels of antioxidant vitamins[139][152][153]
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 obtained from the diet, but instead are made in the body. For example, ubiquinol (coenzyme Q) is poorly absorbed from the gut and is made 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 intake has little effect on the concentration of glutathione in the body.[154][155] Although large amounts of sulfur-containing amino acids such as acetylcysteine can increase glutathione,[156] no evidence exists that eating high levels of these glutathione precursors is beneficial for healthy adults.[157]

Measurement and invalidation of ORAC

Measurement of polyphenol and carotenoid content in food is not a straightforward process, as antioxidants collectively are a diverse group of compounds with different reactivities to various reactive oxygen species. In food science analyses in vitro, the oxygen radical absorbance capacity (ORAC) was once an industry standard for estimating antioxidant strength of whole foods, juices and food additives, mainly from the presence of polyphenols.[158][159] Earlier measurements and ratings by the United States Department of Agriculture were withdrawn in 2012 as biologically irrelevant to human health, referring to an absence of physiological evidence for polyphenols having antioxidant properties in vivo.[1] Consequently, the ORAC method, derived only from in vitro experiments, is no longer considered relevant to human diets or biology, as of 2010.[1]

Alternative in vitro measurements of antioxidant content in foods – also based on the presence of polyphenols – include the Folin-Ciocalteu reagent, and the Trolox equivalent antioxidant capacity assay.[160]


  1. 1.0 1.1 1.2 "Withdrawn: Oxygen Radical Absorbance Capacity (ORAC) of Selected Foods, Release 2 (2010)". United States Department of Agriculture, Agricultural Research Service. 16 May 2012. 
  2. 2.0 2.1 "Antioxidants: In Depth" (in en). NCCIH. November 2013. 
  3. "Evolution of dietary antioxidants". Comparative Biochemistry and Physiology A 136 (1): 113–26. September 2003. doi:10.1016/S1095-6433(02)00368-9. PMID 14527634. 
  4. "Antioxidants". Annual Review of Biochemistry 16: 177–92. 1947. doi:10.1146/ PMID 20259061. 
  5. "Food Processing and Lipid Oxidation". Impact of Processing on Food Safety. Advances in Experimental Medicine and Biology. 459. 1999. pp. 23–50. doi:10.1007/978-1-4615-4853-9_3. ISBN 978-0-306-46051-7. 
  6. Three eras of vitamin C discovery. Subcellular Biochemistry. 25. 1996. pp. 1–16. doi:10.1007/978-1-4613-0325-1_1. ISBN 978-1-4613-7998-0. 
  7. "Free radicals: their history and current status in aging and disease". Annals of Clinical and Laboratory Science 28 (6): 331–46. 1998. PMID 9846200. 
  8. "Sur l'autoxydation: Les antioxygènes" (in fr). Comptes Rendus des Séances et Mémoires de la Société de Biologie 86: 321–322. 1922. 
  9. "The discovery of the antioxidant function of vitamin E: the contribution of Henry A. Mattill". The Journal of Nutrition 135 (3): 363–6. March 2005. doi:10.1093/jn/135.3.363. PMID 15735064. 
  10. "Modified atmosphere packaging of fruits and vegetables". Critical Reviews in Food Science and Nutrition 28 (1): 1–30. 1989. doi:10.1080/10408398909527490. PMID 2647417. 
  11. "Chilled food systems. Effects of chilled holding on quality of beef loaves". Journal of the American Dietetic Association 67 (6): 552–7. December 1975. doi:10.1016/S0002-8223(21)14836-9. PMID 1184900. 
  12. "Phenolic antioxidants: Health Protection Branch studies on butylated hydroxyanisole". Cancer Letters 93 (1): 49–54. June 1995. doi:10.1016/0304-3835(95)03787-W. PMID 7600543. 
  13. "E number index". UK food guide. 
  14. "Rancidity and its measurement in edible oils and snack foods. A review". The Analyst 113 (2): 213–24. February 1988. doi:10.1039/an9881300213. PMID 3288002. Bibcode1988Ana...113..213R. 
  15. "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. June 2004. doi:10.1021/jf049806z. PMID 15212450. 
  16. "Final report on the amended safety assessment of Propyl Gallate.". International Journal of Toxicology 26 (3_suppl): 89–118. 2007. doi:10.1080/10915810701663176. PMID 18080874. "Propyl Gallate is a generally recognized as safe (GRAS) antioxidant to protect fats, oils, and fat-containing food from rancidity that results from the formation of peroxides.". 
  17. "Global Antioxidants (Natural and Synthetic) Market Poised to Surge From USD 2.25 Billion in 2014 to USD 3.25 Billion by 2020, Growing at 5.5% CAGR". GlobalNewswire, El Segundo, CA. 19 January 2016. 
  18. "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. 1955. doi:10.1021/ja01617a026. 
  19. 19.0 19.1 "Fuel antioxidants". Innospec Chemicals. 
  20. "Why use Antioxidants?". SpecialChem Adhesives. 
  21. Liu, Runzeng; Mabury, Scott A. (6 October 2020). "Synthetic Phenolic Antioxidants: A Review of Environmental Occurrence, Fate, Human Exposure, and Toxicity". Environmental Science & Technology 54 (19): 11706–11719. doi:10.1021/acs.est.0c05077. PMID 32915564. 
  22. Xu, Jing; Hao, Yanfen; Yang, Zhiruo; Li, Wenjuan; Xie, Wenjing; Huang, Yani; Wang, Deliang; He, Yuqing et al. (7 November 2022). "Rubber Antioxidants and Their Transformation Products: Environmental Occurrence and Potential Impact". International Journal of Environmental Research and Public Health 19 (21): 14595. doi:10.3390/ijerph192114595. PMID 36361475. 
  23. 23.0 23.1 23.2 "Oxidative stress: the paradox of aerobic life". Biochemical Society Symposium 61: 1–31. 1995. doi:10.1042/bss0610001. PMID 8660387. 
  24. 24.0 24.1 24.2 24.3 24.4 "Oxidative stress: oxidants and antioxidants". Experimental Physiology 82 (2): 291–5. March 1997. doi:10.1113/expphysiol.1997.sp004024. PMID 9129943. 
  25. 25.0 25.1 25.2 25.3 "The antioxidants and pro-antioxidants network: an overview". Current Pharmaceutical Design 10 (14): 1677–94. 2004. doi:10.2174/1381612043384655. PMID 15134565. 
  26. "Cell signaling. H2O2, a necessary evil for cell signaling". Science 312 (5782): 1882–3. June 2006. doi:10.1126/science.1130481. PMID 16809515. 
  27. "Free radicals and antioxidants in normal physiological functions and human disease". The International Journal of Biochemistry & Cell Biology 39 (1): 44–84. 2007. doi:10.1016/j.biocel.2006.07.001. PMID 16978905. 
  28. 28.0 28.1 "Oxidative mechanisms in the toxicity of metal ions". Free Radical Biology & Medicine 18 (2): 321–36. February 1995. doi:10.1016/0891-5849(94)00159-H. PMID 7744317. 
  29. "Mutagenesis and carcinogenesis caused by the oxidation of nucleic acids". Biological Chemistry 387 (4): 373–9. April 2006. doi:10.1515/BC.2006.050. PMID 16606334. 
  30. "Role of oxygen radicals in DNA damage and cancer incidence". Molecular and Cellular Biochemistry 266 (1–2): 37–56. November 2004. doi:10.1023/B:MCBI.0000049134.69131.89. PMID 15646026. 
  31. "Protein oxidation and aging". Science 257 (5074): 1220–4. August 1992. doi:10.1126/science.1355616. PMID 1355616. Bibcode1992Sci...257.1220S. 
  32. "Mitochondria, oxygen free radicals, disease and ageing". Trends in Biochemical Sciences 25 (10): 502–8. October 2000. doi:10.1016/S0968-0004(00)01674-1. PMID 11050436. 
  33. "The mitochondrial production of reactive oxygen species: mechanisms and implications in human pathology". IUBMB Life 52 (3–5): 159–64. 2001. doi:10.1080/15216540152845957. PMID 11798028. 
  34. "Oxidants, oxidative stress and the biology of ageing". Nature 408 (6809): 239–47. November 2000. doi:10.1038/35041687. PMID 11089981. Bibcode2000Natur.408..239F. 
  35. "The production of reactive oxygen species by complex I". Biochemical Society Transactions 36 (Pt 5): 976–80. October 2008. doi:10.1042/BST0360976. PMID 18793173. 
  36. "Are respiratory enzymes the primary sources of intracellular hydrogen peroxide?". The Journal of Biological Chemistry 279 (47): 48742–50. November 2004. doi:10.1074/jbc.M408754200. PMID 15361522. 
  37. 37.0 37.1 "Pathways of oxidative damage". Annual Review of Microbiology 57: 395–418. 2003. doi:10.1146/annurev.micro.57.030502.090938. PMID 14527285. 
  38. "Antioxidants in photosynthesis and human nutrition". Science 298 (5601): 2149–53. December 2002. doi:10.1126/science.1078002. PMID 12481128. Bibcode2002Sci...298.2149D. 
  39. "Singlet oxygen production in photosynthesis". Journal of Experimental Botany 56 (411): 337–46. January 2005. doi:10.1093/jxb/erh237. PMID 15310815. 
  40. "Iodide accumulation provides kelp with an inorganic antioxidant impacting atmospheric chemistry". Proceedings of the National Academy of Sciences 105 (19): 6954–6958. 2008. doi:10.1073/pnas.0709959105. ISSN 0027-8424. PMID 18458346. Bibcode2008PNAS..105.6954K. 
  41. "Light and oxygenic photosynthesis: energy dissipation as a protection mechanism against photo-oxidation". EMBO Reports 6 (7): 629–34. July 2005. doi:10.1038/sj.embor.7400460. PMID 15995679. 
  42. "Water-soluble carotenoid proteins of cyanobacteria". Archives of Biochemistry and Biophysics 430 (1): 2–9. October 2004. doi:10.1016/ PMID 15325905. 
  43. "Role of oxidants in microbial pathophysiology". Clinical Microbiology Reviews 10 (1): 1–18. January 1997. doi:10.1128/CMR.10.1.1. PMID 8993856. 
  44. "Intracellular antioxidants: from chemical to biochemical mechanisms". Food and Chemical Toxicology 37 (9–10): 949–62. 1999. doi:10.1016/S0278-6915(99)00090-3. PMID 10541450. 
  45. "Strategies of antioxidant defense". European Journal of Biochemistry 215 (2): 213–9. July 1993. doi:10.1111/j.1432-1033.1993.tb18025.x. PMID 7688300. 
  46. "Interrelation of vitamin C, infection, haemostatic factors, and cardiovascular disease". BMJ 310 (6994): 1559–63. June 1995. doi:10.1136/bmj.310.6994.1559. PMID 7787643. 
  47. 47.0 47.1 47.2 47.3 "Evaluation of total reactive antioxidant potential (TRAP) of tissue homogenates and their cytosols". Archives of Biochemistry and Biophysics 388 (2): 261–6. April 2001. doi:10.1006/abbi.2001.2292. PMID 11368163. 
  48. "Serum glutathione in adolescent males predicts parental coronary heart disease". Circulation 100 (22): 2244–7. November 1999. doi:10.1161/01.CIR.100.22.2244. PMID 10577998. 
  49. "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. November 1992. PMID 1490813. 
  50. "Assay of protein-bound lipoic acid in tissues by a new enzymatic method". Analytical Biochemistry 258 (2): 299–304. May 1998. doi:10.1006/abio.1998.2615. PMID 9570844. 
  51. 51.0 51.1 "Uric acid and oxidative stress". Current Pharmaceutical Design 11 (32): 4145–51. 2005. doi:10.2174/138161205774913255. PMID 16375736. 
  52. "Individual carotenoid concentrations in adipose tissue and plasma as biomarkers of dietary intake". The American Journal of Clinical Nutrition 76 (1): 172–9. July 2002. doi:10.1093/ajcn/76.1.172. PMID 12081831. 
  53. 53.0 53.1 "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. March 1994. doi:10.1093/clinchem/40.3.411. PMID 8131277. 
  54. "cis-trans isomers of lycopene and beta-carotene in human serum and tissues". Archives of Biochemistry and Biophysics 294 (1): 173–7. April 1992. doi:10.1016/0003-9861(92)90153-N. PMID 1550343. 
  55. "Serum coenzyme Q10 concentrations 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. 2003. doi:10.1002/biof.5520180221. PMID 14695934. 
  56. 56.0 56.1 "Metabolism and function of coenzyme Q". Biochimica et Biophysica Acta (BBA) - Biomembranes 1660 (1–2): 171–99. January 2004. doi:10.1016/j.bbamem.2003.11.012. PMID 14757233. 
  57. 57.0 57.1 "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. September 2005. doi:10.1007/s10157-005-0368-5. PMID 16189627. 
  58. 58.0 58.1 "Urate oxidase: primary structure and evolutionary implications". Proceedings of the National Academy of Sciences of the United States of America 86 (23): 9412–6. December 1989. doi:10.1073/pnas.86.23.9412. PMID 2594778. Bibcode1989PNAS...86.9412W. 
  59. "Two independent mutational events in the loss of urate oxidase during hominoid evolution". Journal of Molecular Evolution 34 (1): 78–84. January 1992. doi:10.1007/BF00163854. PMID 1556746. Bibcode1992JMolE..34...78W. 
  60. "Uric acid and evolution". Rheumatology 49 (11): 2010–5. November 2010. doi:10.1093/rheumatology/keq204. PMID 20627967. 
  61. 61.0 61.1 "Uric acid, hominoid evolution, and the pathogenesis of salt-sensitivity". Hypertension 40 (3): 355–60. September 2002. doi:10.1161/01.HYP.0000028589.66335.AA. PMID 12215479. 
  62. "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. 2010. PMID 20697570. 
  63. 63.0 63.1 "Endogenous urate production augments plasma antioxidant capacity in healthy lowland subjects exposed to high altitude". Chest 131 (5): 1473–8. May 2007. doi:10.1378/chest.06-2235. PMID 17494796. 
  64. "Towards the physiological function of uric acid". Free Radical Biology & Medicine 14 (6): 615–31. June 1993. doi:10.1016/0891-5849(93)90143-I. PMID 8325534. 
  65. 65.0 65.1 "Uric acid: the oxidant-antioxidant paradox". Nucleosides, Nucleotides & Nucleic Acids 27 (6): 608–19. June 2008. doi:10.1080/15257770802138558. PMID 18600514. 
  66. "Gout: an update". American Family Physician 76 (6): 801–8. September 2007. PMID 17910294. 
  67. "Asymptomatic hyperuricemia. Risks and consequences in the Normative Aging Study". The American Journal of Medicine 82 (3): 421–6. March 1987. doi:10.1016/0002-9343(87)90441-4. PMID 3826098. 
  68. "Effect of short-term ketogenic diet on redox status of human blood". Rejuvenation Research 10 (4): 435–40. December 2007. doi:10.1089/rej.2007.0540. PMID 17663642. 
  69. 69.0 69.1 69.2 69.3 "Vitamin C". Micronutrient Information Center, Linus Pauling Institute, Oregon State University, Corvallis, OR. 1 July 2018. 
  70. "L-ascorbic acid biosynthesis". Cofactor Biosynthesis. Vitamins & Hormones. 61. 2001. pp. 241–66. doi:10.1016/S0083-6729(01)61008-2. ISBN 978-0-12-709861-6. 
  71. "Vitamin C. Biosynthesis, recycling and degradation in mammals". The FEBS Journal 274 (1): 1–22. January 2007. doi:10.1111/j.1742-4658.2006.05607.x. PMID 17222174. 
  72. 72.0 72.1 "Glutathione-ascorbic acid antioxidant system in animals". The Journal of Biological Chemistry 269 (13): 9397–400. April 1994. doi:10.1016/S0021-9258(17)36891-6. PMID 8144521. 
  73. "Mammalian thioltransferase (glutaredoxin) and protein disulfide isomerase have dehydroascorbate reductase activity". The Journal of Biological Chemistry 265 (26): 15361–4. September 1990. doi:10.1016/S0021-9258(18)55401-6. PMID 2394726. 
  74. "Vitamin C as an antioxidant: evaluation of its role in disease prevention". Journal of the American College of Nutrition 22 (1): 18–35. February 2003. doi:10.1080/07315724.2003.10719272. PMID 12569111. 
  75. "Regulation and function of ascorbate peroxidase isoenzymes". Journal of Experimental Botany 53 (372): 1305–19. May 2002. doi:10.1093/jexbot/53.372.1305. PMID 11997377. 
  76. "Ascorbic acid in plants: biosynthesis and function". Critical Reviews in Biochemistry and Molecular Biology 35 (4): 291–314. 2000. doi:10.1080/10409230008984166. PMID 11005203. 
  77. 77.0 77.1 77.2 77.3 "Glutathione". Annual Review of Biochemistry 52: 711–60. 1983. doi:10.1146/ PMID 6137189. 
  78. "Glutathione metabolism and its selective modification". The Journal of Biological Chemistry 263 (33): 17205–8. November 1988. doi:10.1016/S0021-9258(19)77815-6. PMID 3053703. 
  79. "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. April 2010. doi:10.1073/pnas.1000928107. PMID 20308541. Bibcode2010PNAS..107.6482G. 
  80. "Bacillithiol is an antioxidant thiol produced in Bacilli". Nature Chemical Biology 5 (9): 625–627. September 2009. doi:10.1038/nchembio.189. PMID 19578333. 
  81. "Novel thiols of prokaryotes". Annual Review of Microbiology 55: 333–56. 2001. doi:10.1146/annurev.micro.55.1.333. PMID 11544359. 
  82. "Metabolism and functions of trypanothione in the Kinetoplastida". Annual Review of Microbiology 46: 695–729. 1992. doi:10.1146/annurev.mi.46.100192.003403. PMID 1444271. 
  83. 83.0 83.1 "Vitamin E: action, metabolism and perspectives". Journal of Physiology and Biochemistry 57 (2): 43–56. March 2001. doi:10.1007/BF03179812. PMID 11579997. 
  84. "Molecular aspects of alpha-tocotrienol antioxidant action and cell signalling". The Journal of Nutrition 131 (2): 369S–73S. February 2001. doi:10.1093/jn/131.2.369S. PMID 11160563. 
  85. 85.0 85.1 "Vitamin E: function and metabolism". FASEB Journal 13 (10): 1145–55. July 1999. doi:10.1096/fasebj.13.10.1145. PMID 10385606. 
  86. "Vitamin E, antioxidant and nothing more". Free Radical Biology & Medicine 43 (1): 4–15. July 2007. doi:10.1016/j.freeradbiomed.2007.03.024. PMID 17561088. 
  87. "Vitamin E and its function in membranes". Progress in Lipid Research 38 (4): 309–36. July 1999. doi:10.1016/S0163-7827(99)00008-9. PMID 10793887. 
  88. "Glutathione peroxidase 4 senses and translates oxidative stress into 12/15-lipoxygenase dependent- and AIF-mediated cell death". Cell Metabolism 8 (3): 237–48. September 2008. doi:10.1016/j.cmet.2008.07.005. PMID 18762024. 
  89. "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 alpha-tocopherol action" by A. Azzi and "Vitamin E, antioxidant and nothing more" by M. Traber and J. Atkinson". Free Radical Biology & Medicine 43 (1): 2–3. July 2007. doi:10.1016/j.freeradbiomed.2007.05.016. PMID 17561087. 
  90. "Tocopherols and tocotrienols in membranes: a critical review". Free Radical Biology & Medicine 44 (5): 739–64. March 2008. doi:10.1016/j.freeradbiomed.2007.11.010. PMID 18160049. 
  91. "Molecular mechanism of alpha-tocopherol action". Free Radical Biology & Medicine 43 (1): 16–21. July 2007. doi:10.1016/j.freeradbiomed.2007.03.013. PMID 17561089. 
  92. "Non-antioxidant activities of vitamin E". Current Medicinal Chemistry 11 (9): 1113–33. May 2004. doi:10.2174/0929867043365332. PMID 15134510. 
  93. "Tocotrienols: Vitamin E beyond tocopherols". Life Sciences 78 (18): 2088–98. March 2006. doi:10.1016/j.lfs.2005.12.001. PMID 16458936. 
  94. "Review: When is an antioxidant not an antioxidant? A review of novel actions and reactions of vitamin C". Free Radical Research 39 (7): 671–86. July 2005. doi:10.1080/10715760500104025. PMID 16036346. 
  95. 95.0 95.1 "Does vitamin C act as a pro-oxidant under physiological conditions?". FASEB Journal 13 (9): 1007–24. June 1999. doi:10.1096/fasebj.13.9.1007. PMID 10336883. 
  96. 96.0 96.1 "The nature of antioxidant defense mechanisms: a lesson from transgenic studies". Environmental Health Perspectives 106 (Suppl 5): 1219–28. October 1998. doi:10.2307/3433989. PMID 9788901. 
  97. "Superoxide dismutase multigene family: a comparison of the CuZn-SOD (SOD1), Mn-SOD (SOD2), and EC-SOD (SOD3) gene structures, evolution, and expression". Free Radical Biology & Medicine 33 (3): 337–49. August 2002. doi:10.1016/S0891-5849(02)00905-X. PMID 12126755. 
  98. 98.0 98.1 "Aspects of the structure, function, and applications of superoxide dismutase". CRC Critical Reviews in Biochemistry 22 (2): 111–80. 1987. doi:10.3109/10409238709083738. PMID 3315461. 
  99. "Superoxide dismutases and their impact upon human health". Molecular Aspects of Medicine 26 (4–5): 340–52. 2005. doi:10.1016/j.mam.2005.07.006. PMID 16099495. 
  100. "Extracellular superoxide dismutase". The International Journal of Biochemistry & Cell Biology 37 (12): 2466–71. December 2005. doi:10.1016/j.biocel.2005.06.012. PMID 16087389. 
  101. "A novel neurological phenotype in mice lacking mitochondrial manganese superoxide dismutase". Nature Genetics 18 (2): 159–63. February 1998. doi:10.1038/ng0298-159. PMID 9462746. 
  102. "Motor neurons in Cu/Zn superoxide dismutase-deficient mice develop normally but exhibit enhanced cell death after axonal injury". Nature Genetics 13 (1): 43–7. May 1996. doi:10.1038/ng0596-43. PMID 8673102. 
  103. "The regulation and function of tobacco superoxide dismutases". Free Radical Biology & Medicine 23 (3): 515–20. 1997. doi:10.1016/S0891-5849(97)00112-3. PMID 9214590. 
  104. "Diversity of structures and properties among catalases". Cellular and Molecular Life Sciences 61 (2): 192–208. January 2004. doi:10.1007/s00018-003-3206-5. PMID 14745498. 
  105. "Understanding the structure and function of catalases: clues from molecular evolution and in vitro mutagenesis". Progress in Biophysics and Molecular Biology 72 (1): 19–66. 1999. doi:10.1016/S0079-6107(98)00058-3. PMID 10446501. 
  106. "Metabolism of oxygen radicals in peroxisomes and cellular implications". Free Radical Biology & Medicine 13 (5): 557–80. November 1992. doi:10.1016/0891-5849(92)90150-F. PMID 1334030. 
  107. "Mechanisms of compound I formation in heme peroxidases". Journal of Inorganic Biochemistry 91 (1): 27–34. July 2002. doi:10.1016/S0162-0134(02)00390-2. PMID 12121759. 
  108. "Direct evidence for catalase as the predominant H2O2 -removing enzyme in human erythrocytes". Blood 90 (12): 4973–8. December 1997. doi:10.1182/blood.V90.12.4973. PMID 9389716. 
  109. "Acatalasemia". Human Genetics 86 (4): 331–40. February 1991. doi:10.1007/BF00201829. PMID 1999334. 
  110. "Analysis of the link between enzymatic activity and oligomeric state in AhpC, a bacterial peroxiredoxin". Biochemistry 44 (31): 10583–92. 2005. doi:10.1021/bi050448i. PMID 16060667.  PDB 1YEX
  111. "Peroxiredoxins: a historical overview and speculative preview of novel mechanisms and emerging concepts in cell signaling". Free Radical Biology & Medicine 38 (12): 1543–52. June 2005. doi:10.1016/j.freeradbiomed.2005.02.026. PMID 15917183. 
  112. "Structure, mechanism and regulation of peroxiredoxins". Trends in Biochemical Sciences 28 (1): 32–40. January 2003. doi:10.1016/S0968-0004(02)00003-8. PMID 12517450. 
  113. "Protein-sulfenic acids: diverse roles for an unlikely player in enzyme catalysis and redox regulation". Biochemistry 38 (47): 15407–16. November 1999. doi:10.1021/bi992025k. PMID 10569923. 
  114. "The peroxiredoxin repair proteins". Peroxiredoxin Systems. Subcellular Biochemistry. 44. 2007. pp. 115–41. doi:10.1007/978-1-4020-6051-9_6. ISBN 978-1-4020-6050-2. 
  115. "Essential role for the peroxiredoxin Prdx1 in erythrocyte antioxidant defence and tumour suppression". Nature 424 (6948): 561–5. July 2003. doi:10.1038/nature01819. PMID 12891360. Bibcode2003Natur.424..561N. 
  116. "Peroxiredoxin II is essential for sustaining life span of erythrocytes in mice". Blood 101 (12): 5033–8. June 2003. doi:10.1182/blood-2002-08-2548. PMID 12586629. 
  117. "The function of peroxiredoxins in plant organelle redox metabolism". Journal of Experimental Botany 57 (8): 1697–709. 2006. doi:10.1093/jxb/erj160. PMID 16606633. 
  118. "Reactive oxygen species, antioxidants, and the mammalian thioredoxin system". Free Radical Biology & Medicine 31 (11): 1287–312. December 2001. doi:10.1016/S0891-5849(01)00724-9. PMID 11728801. 
  119. "Plant thioredoxins are key actors in the oxidative stress response". Trends in Plant Science 11 (7): 329–34. July 2006. doi:10.1016/j.tplants.2006.05.005. PMID 16782394. 
  120. "Physiological functions of thioredoxin and thioredoxin reductase". European Journal of Biochemistry 267 (20): 6102–9. October 2000. doi:10.1046/j.1432-1327.2000.01701.x. PMID 11012661. 
  121. "Thioredoxin reductase". The Biochemical Journal 346 (1): 1–8. February 2000. doi:10.1042/0264-6021:3460001. PMID 10657232. 
  122. "Manipulation of glutathione metabolism in transgenic plants". Biochemical Society Transactions 24 (2): 465–9. May 1996. doi:10.1042/bst0240465. PMID 8736785. 
  123. "Tissue-specific functions of individual glutathione peroxidases". Free Radical Biology & Medicine 27 (9–10): 951–65. November 1999. doi:10.1016/S0891-5849(99)00173-2. PMID 10569628. 
  124. "Mice deficient in cellular glutathione peroxidase develop normally and show no increased sensitivity to hyperoxia". The Journal of Biological Chemistry 272 (26): 16644–51. June 1997. doi:10.1074/jbc.272.26.16644. PMID 9195979. 
  125. "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". The Journal of Biological Chemistry 273 (35): 22528–36. August 1998. doi:10.1074/jbc.273.35.22528. PMID 9712879. 
  126. "Antioxidant role of glutathione S-transferases: protection against oxidant toxicity and regulation of stress-mediated apoptosis". Antioxidants & Redox Signaling 6 (2): 289–300. April 2004. doi:10.1089/152308604322899350. PMID 15025930. 
  127. "Glutathione transferases". Annual Review of Pharmacology and Toxicology 45: 51–88. 2005. doi:10.1146/annurev.pharmtox.45.120403.095857. PMID 15822171. 
  128. 128.0 128.1 "A review of the epidemiological evidence for the 'antioxidant hypothesis'". Public Health Nutrition 7 (3): 407–22. May 2004. doi:10.1079/PHN2003543. PMID 15153272. 
  129. Food, Nutrition, Physical Activity, and the Prevention of Cancer: a Global Perspective . World Cancer Research Fund (2007). ISBN:978-0-9722522-2-5.
  130. Rice-Evans, Catherine A.; Miller, Nicholas J.; Paganga, George (1996). "Structure-antioxidant activity relationships of flavonoids and phenolic acids" (in en). Free Radical Biology and Medicine 20 (7): 933–956. doi:10.1016/0891-5849(95)02227-9. PMID 8743980. 
  131. "Dietary (poly)phenolics in human health: structures, bioavailability, and evidence of protective effects against chronic diseases". Antioxidants & Redox Signaling 18 (14): 1818–1892. May 2013. doi:10.1089/ars.2012.4581. PMID 22794138. 
  132. "Flavonoids". Linus Pauling Institute, Oregon State University, Corvallis. 2016. 
  133. "Potential interactions of prescription and over-the-counter medications having antioxidant capabilities with radiation and chemotherapy". International Journal of Cancer 137 (11): 2525–33. September 2014. doi:10.1002/ijc.29208. PMID 25220632. 
  134. "Influence of vegetable protein sources on trace element and mineral bioavailability". The Journal of Nutrition 133 (9): 2973S–7S. September 2003. doi:10.1093/jn/133.9.2973S. PMID 12949395. 
  135. "Bioavailability of iron, zinc, and other trace minerals from vegetarian diets". The American Journal of Clinical Nutrition 78 (3 Suppl): 633S–639S. September 2003. doi:10.1093/ajcn/78.3.633S. PMID 12936958. 
  136. "Improving the bioavailability of nutrients in plant foods at the household level". The Proceedings of the Nutrition Society 65 (2): 160–8. May 2006. doi:10.1079/PNS2006489. PMID 16672077. 
  137. 137.0 137.1 "Effect of blanching on the content of antinutritional factors in selected vegetables". Plant Foods for Human Nutrition 47 (4): 361–7. June 1995. doi:10.1007/BF01088275. PMID 8577655. 
  138. "Bioavailability of minerals in legumes". The British Journal of Nutrition 88 (Suppl 3): S281–5. December 2002. doi:10.1079/BJN/2002718. PMID 12498628. 
  139. 139.0 139.1 "Overview of dietary flavonoids: nomenclature, occurrence and intake". The Journal of Nutrition 133 (10): 3248S–3254S. October 2003. doi:10.1093/jn/133.10.3248S. PMID 14519822. 
  140. "Risk factors for lung cancer and for intervention effects in CARET, the Beta-Carotene and Retinol Efficacy Trial". Journal of the National Cancer Institute 88 (21): 1550–9. November 1996. doi:10.1093/jnci/88.21.1550. PMID 8901853. 
  141. "Beta-carotene and lung cancer: a case study". The American Journal of Clinical Nutrition 69 (6): 1345S–50S. June 1999. doi:10.1093/ajcn/69.6.1345S. PMID 10359235. 
  142. 142.0 142.1 "Mortality in randomized trials of antioxidant supplements for primary and secondary prevention: systematic review and meta-analysis". JAMA 297 (8): 842–57. February 2007. doi:10.1001/jama.297.8.842. PMID 17327526. 
  143. 143.0 143.1 "Antioxidant supplements for prevention of mortality in healthy participants and patients with various diseases". The Cochrane Database of Systematic Reviews 2012 (3): CD007176. 14 March 2012. doi:10.1002/14651858.CD007176.pub2. PMID 22419320. 
  144. Study Citing Antioxidant Vitamin Risks Based On Flawed Methodology, Experts Argue News release from Oregon State University published on ScienceDaily. Retrieved 19 April 2007
  145. "Meta-analysis: high-dosage vitamin E supplementation may increase all-cause mortality". Annals of Internal Medicine 142 (1): 37–46. January 2005. doi:10.7326/0003-4819-142-1-200501040-00110. PMID 15537682. 
  146. 146.0 146.1 "Meta-analysis: antioxidant supplements for primary and secondary prevention of colorectal adenoma". Alimentary Pharmacology & Therapeutics 24 (2): 281–91. July 2006. doi:10.1111/j.1365-2036.2006.02970.x. PMID 16842454. 
  147. "Drugs for preventing lung cancer in healthy people". The Cochrane Database of Systematic Reviews 2020 (3): CD002141. March 2020. doi:10.1002/14651858.CD002141.pub3. PMID 32130738. 
  148. "The key role of micronutrients". Clinical Nutrition 25 (1): 1–13. February 2006. doi:10.1016/j.clnu.2005.11.006. PMID 16376462. 
  149. "Food carotenoids: analysis, composition and alterations during storage and processing of foods". Forum of Nutrition 56: 35–7. 2003. PMID 15806788. 
  150. "Carotenoids: actual knowledge on food sources, intakes, stability and bioavailability and their protective role in humans". Molecular Nutrition & Food Research 53 (Suppl 2): S194–218. September 2009. doi:10.1002/mnfr.200800053. PMID 19035552. Retrieved 18 April 2017. 
  151. "Nutritional losses and gains during processing: future problems and issues". The Proceedings of the Nutrition Society 61 (1): 145–8. February 2002. doi:10.1079/PNS2001142. PMID 12002789. 
  152. "Antioxidants and Cancer Prevention: Fact Sheet". National Cancer Institute. 
  153. "Importance of functional foods in the Mediterranean diet". Public Health Nutrition 9 (8A): 1136–40. December 2006. doi:10.1017/S1368980007668530. PMID 17378953. 
  154. "The systemic availability of oral glutathione". European Journal of Clinical Pharmacology 43 (6): 667–9. 1992. doi:10.1007/BF02284971. PMID 1362956. 
  155. "Dietary glutathione intake in humans and the relationship between intake and plasma total glutathione level". Nutrition and Cancer 21 (1): 33–46. 1994. doi:10.1080/01635589409514302. PMID 8183721. 
  156. "N-acetylcysteine for antioxidant therapy: pharmacology and clinical utility". Expert Opinion on Biological Therapy 8 (12): 1955–62. December 2008. doi:10.1517/14728220802517901. PMID 18990082. 
  157. "Adequate range for sulfur-containing amino acids and biomarkers for their excess: lessons from enteral and parenteral nutrition". The Journal of Nutrition 136 (6 Suppl): 1694S–1700S. June 2006. doi:10.1093/jn/136.6.1694S. PMID 16702341. 
  158. "Oxygen-radical absorbance capacity assay for antioxidants". Free Radical Biology & Medicine 14 (3): 303–11. March 1993. doi:10.1016/0891-5849(93)90027-R. PMID 8458588. 
  159. "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. October 2001. doi:10.1021/jf010586o. PMID 11599998. 
  160. "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. May 2005. doi:10.1021/jf0502698. PMID 15884874. Retrieved 24 October 2017. 

Further reading

External links