View source for Antioxidant

{{short description|Compound that inhibits the oxidation of other molecules}}
{{pp-move}}
{{Use dmy dates|date=October 2020}}
[[Image:Glutathione-skeletal.svg|thumb|250px|class=skin-invert-image|Structure of the antioxidant [[glutathione]]]]

'''Antioxidants''' are [[Chemical compound|compounds]] that inhibit [[Redox|oxidation]] (usually occurring as [[autoxidation]]), a [[chemical reaction]] that can produce [[Radical (chemistry)|free radicals]]. Autoxidation leads to degradation of organic compounds, including living matter. Antioxidants are frequently added to industrial products, such as [[polymer]]s, [[fuel]]s, and [[lubricant]]s, to extend their usable lifetimes.<ref>{{Cite book |last=Klemchuk |first=Peter P. |title=Ullmann's Encyclopedia of Industrial Chemistry |year=2000 |isbn=3527306730 |chapter=Antioxidants |doi=10.1002/14356007.a03_091}}</ref> Foods are also treated with antioxidants to prevent [[Food spoilage|spoilage]], in particular the [[rancidification]] of [[Vegetable oil|oils]] and [[fat]]s. In [[Cell (biology)|cells]], antioxidants such as [[glutathione]], [[mycothiol]], or [[bacillithiol]], and enzyme systems like [[superoxide dismutase]], can prevent damage from [[oxidative stress]].<ref name="Autox">{{Cite journal |last1=Helberg |first1=Julian |last2=Pratt |first2=Derek A. |year=2021 |title=Autoxidation vs. Antioxidants – the fight for forever |journal=Chemical Society Reviews |volume=50 |issue=13 |pages=7343–7358 |doi=10.1039/D1CS00265A |pmid=34037013 |s2cid=235200305}}</ref>

Known [[diet (nutrition)|dietary]] antioxidants are [[vitamin]]s [[vitamin A|A]], [[vitamin C|C]], and [[vitamin E|E]], but the term has also been applied to various compounds that exhibit antioxidant properties [[in vitro]], with little evidence for antioxidant properties [[in vivo]].<ref name="nih">{{Cite web |date=1 November 2013 |title=Antioxidants: In Depth |url=https://www.nccih.nih.gov/health/antioxidants-in-depth |access-date=17 March 2023 |publisher=National Center for Complementary and Integrative Health, US National Institutes of Health |language=en}}</ref> [[Dietary supplement]]s marketed as antioxidants have not been shown to maintain health or prevent disease in humans.<ref name=nih/><ref>{{Cite journal |last1=Fang |first1=Yun-Zhong |last2=Yang |first2=Sheng |last3=Wu |first3=Guoyao |date=2002 |title=Free radicals, antioxidants, and nutrition |journal=Nutrition |volume=18 |issue=10 |pages=872–879 |doi=10.1016/s0899-9007(02)00916-4 |pmid=12361782}}</ref>

== History ==
As part of their adaptation from marine life, terrestrial plants began producing non-marine antioxidants such as [[ascorbic acid]] ([[vitamin C]]), [[polyphenol]]s, and [[tocopherol]]s. The evolution of [[angiosperm]] plants between 50 and 200 million years ago resulted in the development of many antioxidant pigments&nbsp;– particularly during the [[Jurassic]] period&nbsp;– as chemical defences against [[reactive oxygen species]] that are byproducts of [[photosynthesis]].<ref>{{Cite journal |vauthors=Benzie IF |date=September 2003 |title=Evolution of dietary antioxidants |journal=Comparative Biochemistry and Physiology A |volume=136 |issue=1 |pages=113–26 |doi=10.1016/S1095-6433(02)00368-9 |pmid=14527634 |hdl-access=free |hdl=10397/34754}}</ref> 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 [[sulfur vulcanization|vulcanization]] of rubber, and the [[polymerization]] of fuels in the [[fouling]] of [[internal combustion engine]]s.<ref>{{Cite journal |vauthors=Mattill HA |year=1947 |title=Antioxidants |journal=Annual Review of Biochemistry |volume=16 |pages=177–92 |doi=10.1146/annurev.bi.16.070147.001141 |pmid=20259061}}</ref>

Early research on the role of antioxidants in biology focused on their use in preventing the oxidation of [[unsaturated fat]]s, which is the cause of [[rancidity]].<ref>{{Cite book |title=Impact of Processing on Food Safety |vauthors=German JB |year=1999 |isbn=978-0-306-46051-7 |series=Advances in Experimental Medicine and Biology |volume=459 |pages=23–50 |chapter=Food Processing and Lipid Oxidation |doi=10.1007/978-1-4615-4853-9_3 |pmid=10335367}}</ref> 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 [[Vitamin C|vitamins C]] and [[Vitamin E|E]] as antioxidants that revolutionized the field and led to the realization of the importance of antioxidants in the biochemistry of [[Organism|living organisms]].<ref>{{Cite book |url=https://books.google.com/books?id=kZdtMAEACAAJ |title=Three eras of vitamin C discovery |vauthors=Jacob RA |year=1996 |isbn=978-1-4613-7998-0 |series=Subcellular Biochemistry |volume=25 |pages=1–16 |chapter=Introduction: Three Eras of Vitamin C Discovery |doi=10.1007/978-1-4613-0325-1_1 |pmid=8821966}}</ref><ref>{{Cite journal |vauthors=Knight JA |year=1998 |title=Free radicals: their history and current status in aging and disease |journal=Annals of Clinical and Laboratory Science |volume=28 |issue=6 |pages=331–46 |pmid=9846200}}</ref> 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.<ref>{{Cite journal |vauthors=Moureu C, Dufraisse C |year=1922 |title=Sur l'autoxydation: Les antioxygènes |journal=Comptes Rendus des Séances et Mémoires de la Société de Biologie |language=fr |volume=86 |pages=321–322}}</ref> 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 [[scavenger (chemistry)|scavenging]] [[reactive oxygen species]] before they can damage cells.<ref>{{Cite journal |vauthors=Wolf G |date=March 2005 |title=The discovery of the antioxidant function of vitamin E: the contribution of Henry A. Mattill |journal=The Journal of Nutrition |volume=135 |issue=3 |pages=363–6 |doi=10.1093/jn/135.3.363 |pmid=15735064 |doi-access=free}}</ref>

== Uses in technology ==

=== Food preservatives ===
{{See also|E number#E300–E399 (antioxidants, acidity regulators)}}

Antioxidants are added to food to prevent 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 (physiology)|respiration]], storing plant materials in [[Anaerobic organism#Metabolism|anaerobic]] conditions produces unpleasant flavors and unappealing colors.<ref>{{Cite journal |vauthors=Kader AA, Zagory D, Kerbel EL |year=1989 |title=Modified atmosphere packaging of fruits and vegetables |journal=Critical Reviews in Food Science and Nutrition |volume=28 |issue=1 |pages=1–30 |doi=10.1080/10408398909527490 |pmid=2647417}}</ref> Consequently, packaging of fresh fruits and vegetables contains an ≈8% oxygen atmosphere. Antioxidants are an especially important class of preservatives as, unlike bacterial or [[fungus|fungal]] spoilage, oxidation reactions still occur relatively rapidly in frozen or refrigerated food.<ref>{{Cite journal |vauthors=Zallen EM, Hitchcock MJ, Goertz GE |date=December 1975 |title=Chilled food systems. Effects of chilled holding on quality of beef loaves |journal=Journal of the American Dietetic Association |volume=67 |issue=6 |pages=552–7 |doi=10.1016/S0002-8223(21)14836-9 |pmid=1184900}}</ref> 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), [[tert-Butylhydroquinone|tertiary butylhydroquinone]] (TBHQ), [[butylated hydroxyanisole]] (BHA, E320) and [[butylated hydroxytoluene]] (BHT, E321).<ref>{{Cite journal |vauthors=Iverson F |date=June 1995 |title=Phenolic antioxidants: Health Protection Branch studies on butylated hydroxyanisole |journal=Cancer Letters |volume=93 |issue=1 |pages=49–54 |doi=10.1016/0304-3835(95)03787-W |pmid=7600543}}</ref><ref>{{Cite web |title=E number index |url=http://www.ukfoodguide.net/enumeric.htm#antioxidants |url-status=live |archive-url=https://web.archive.org/web/20070304151341/http://www.ukfoodguide.net/enumeric.htm |archive-date=4 March 2007 |access-date=5 March 2007 |publisher=UK food guide}}</ref>

Unsaturated fats can be highly susceptible to oxidation, causing [[rancidification]].<ref>{{Cite journal |vauthors=Robards K, Kerr AF, Patsalides E |date=February 1988 |title=Rancidity and its Measurement in Edible Oils and Snack Foods. A review |journal=The Analyst |volume=113 |issue=2 |pages=213–24 |bibcode=1988Ana...113..213R |doi=10.1039/an9881300213 |pmid=3288002}}</ref> Oxidized lipids are often discolored and can impart unpleasant tastes and flavors. Thus, these foods are rarely preserved by drying; instead, they are preserved by [[Smoking (cooking technique)|smoking]], [[salting (food)|salting]], or [[fermentation (food)|fermenting]]. Even less fatty foods such as fruits are sprayed with sulfurous antioxidants prior to air drying. Metals catalyse oxidation. Some fatty foods such as olive oil are partially protected from oxidation by their natural content of antioxidants. Fatty foods are sensitive to photooxidation,<ref>{{Cite journal |vauthors=Del Carlo M, Sacchetti G, Di Mattia C, Compagnone D, Mastrocola D, Liberatore L, Cichelli A |date=June 2004 |title=Contribution of the phenolic fraction to the antioxidant activity and oxidative stability of olive oil |journal=Journal of Agricultural and Food Chemistry |volume=52 |issue=13 |pages=4072–9 |doi=10.1021/jf049806z |pmid=15212450|bibcode=2004JAFC...52.4072D }}</ref> which forms [[hydroperoxide]]s by oxidizing unsaturated fatty acids and [[ester]].<ref name=":1">{{Citation |last=Frankel |first=Edwin N. |title=Chapter 3 - Photooxidation of unsaturated fats |date=2012-01-01 |work=Lipid Oxidation (Second Edition) |pages=51–66 |editor-last=Frankel |editor-first=Edwin N. |url=https://www.sciencedirect.com/science/article/pii/B9780953194988500047 |access-date=2023-04-15 |series=Oily Press Lipid Library Series |publisher=Woodhead Publishing |language=en |isbn=978-0-9531949-8-8}}</ref> Exposure to [[Ultraviolet|ultraviolet (UV)]] radiation can cause direct photooxidation and decompose peroxides and [[Carbonyl group|carbonyl]] molecules. These molecules undergo free radical chain reactions, but antioxidants inhibit them by preventing the oxidation processes.<ref name=":1" />

=== Pharmaceutical excipients ===
Some pharmaceutical products require protection from oxidation. A number of antioxidants can be used as [[excipient]]s. [[Sequestrant]]s such as [[disodium EDTA]] can also be used to prevent metal-catalyzed oxidation.<ref>{{cite web |title=Excipients in the dossier for application for marketing authorisation of a medicinal product - Scientific guideline {{!}} European Medicines Agency (EMA) |url=https://www.ema.europa.eu/en/excipients-dossier-application-marketing-authorisation-medicinal-product-scientific-guideline |website=www.ema.europa.eu |language=en |date=1 January 2008}}</ref>

=== Cosmetics preservatives ===
Antioxidant stabilizers are also added to fat-based cosmetics such as lipstick and [[moisturizer]]s to prevent rancidity.<ref>{{Cite journal |date=2007 |title=Final report on the amended safety assessment of Propyl Gallate. |journal=International Journal of Toxicology |volume=26 |issue=3_suppl |pages=89–118 |doi=10.1080/10915810701663176 |pmid=18080874 |s2cid=39562131 |quote=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.}}</ref> Antioxidants in cosmetic products prevent oxidation of active ingredients and lipid content. For example, phenolic antioxidants such as [[(E)-Stilbene|stilbenes]], [[flavonoid]]s, and [[hydroxycinnamic acid]] strongly absorb UV radiation due to the presence of [[chromophore]]s. They reduce oxidative stress from sun exposure by absorbing UV light.<ref>{{Cite journal |last1=Débora |first1=Jackeline |last2=Cleide |first2=Viviane |last3=Luciana |first3=Oliveira |last4=Rosemeire |first4=Aparecida |date=August 7, 2019 |title=Polyphenols as natural antioxidants in cosmetics applications |journal=Journal of Cosmetic Dermatology |volume=19 |issue=1 |pages=33–37 |doi=10.1111/jocd.13093 |pmid=31389656 |s2cid=201156301}}</ref>

=== Industrial uses ===
{{more references|section|date=February 2025}}
[[Image:Antioxidant.png|thumb|right|250px|class=skin-invert-image|Substituted [[phenols]] and derivatives of [[p-Phenylenediamine|phenylenediamine]] are common antioxidants used to inhibit gum formation in gasoline (petrol).]]
[[File:Polymer auto-oxidation.png|250px|right|thumb|The cyclic mechanism of autoxidation, which antioxidants aim to break]]

Antioxidants may be added to industrial products, such as [[Gasoline additive|stabilizers]] in [[fuel]]s and [[Oil additive|additives]] in [[lubricant]]s, to prevent oxidation and polymerization that leads to the formation of engine-fouling residues.<ref>{{Cite journal |vauthors=Boozer CE, Hammond GS, Hamilton CE, Sen JN |year=1955 |title=Air Oxidation of Hydrocarbons.1II. The Stoichiometry and Fate of Inhibitors in Benzene and Chlorobenzene |journal=Journal of the American Chemical Society |volume=77 |issue=12 |pages=3233–7 |doi=10.1021/ja01617a026|bibcode=1955JAChS..77.3233B }}</ref>

{| class="wikitable" style="margin-left: auto; margin-right: auto;"
|-
!Fuel additive
!Components<ref name="innospec">{{Cite web |title=Fuel antioxidants |url=http://www.innospecinc.com/americas/products/fuel_antitoxidants.cfm |archive-url=https://web.archive.org/web/20061015202259/http://www.innospecinc.com/americas/products/fuel_antitoxidants.cfm |archive-date=15 October 2006 |access-date=27 February 2007 |publisher=Innospec Chemicals}}</ref>
!Applications<ref name="innospec" />
|-
| style="text-align:center;" |AO-22
| style="text-align:center;" |[[N,N'-di-2-butyl-1,4-phenylenediamine]]
| style="text-align:center;" |Turbine oils, [[transformer oil]]s, [[hydraulic fluid]]s, [[wax]]es, and [[grease (lubricant)|greases]]
|- style="text-align:center;"
||AO-24
||N,N'-di-2-butyl-1,4-phenylenediamine
||Low-temperature oils
|- style="text-align:center;"
||AO-29
||[[2,6-di-tert-butyl-4-methylphenol]] (BHT)
||Turbine oils, transformer oils, hydraulic fluids, waxes, greases, and gasolines
|- style="text-align:center;"
||AO-30
||[[2,4-dimethyl-6-tert-butylphenol]]
||[[Jet fuel]]s and gasolines, including aviation gasolines
|- style="text-align:center;"
||AO-31
||2,4-dimethyl-6-tert-butylphenol
||Jet fuels and gasolines, including aviation gasolines
|- style="text-align:center;"
||AO-32
||2,4-dimethyl-6-tert-butylphenol and 2,6-di-tert-butyl-4-methylphenol
||Jet fuels and gasolines, including aviation gasolines
|- style="text-align:center;"
||AO-37
||[[2,6-di-tert-butylphenol]]
||Jet fuels and gasolines, widely approved for [[aviation fuel]]s
|}

Antioxidant [[polymer stabilizers]] are widely used to prevent the degradation of [[polymer]]s, such as rubbers, plastics and [[adhesive]]s, that causes a loss of strength and flexibility in these materials.<ref>{{Cite web |title=Why use Antioxidants? |url=http://www.specialchem4adhesives.com/tc/antioxidants/index.aspx?id= |url-status=dead |archive-url=https://web.archive.org/web/20070211063739/http://www.specialchem4adhesives.com/tc/antioxidants/index.aspx?id= |archive-date=11 February 2007 |access-date=27 February 2007 |publisher=SpecialChem Adhesives}}</ref> Polymers containing [[double bond]]s in their main chains, such as [[natural rubber]] and [[polybutadiene]], are especially susceptible to [[oxidation]] and [[ozonolysis]]. They can be protected by [[antiozonant]]s. Oxidation can be accelerated by [[UV radiation]] in natural sunlight to cause [[Photo-oxidation of polymers|photo-oxidation]]. Various specialised light stabilisers, such as [[hindered amine light stabilizers|HALS]] may be added to plastics to prevent this. Antioxidants for polymer materials are:

* Primary antioxidants scavange free radicals formed during the initial (thermal) oxidation process (ROO•), thus preventing chain reactions that lead to polymer degradation. 
** Phenolics: They are more specifically "hindered phenols", which means a bulky group (typically a tert-butyl) is put near the phenol OH.<ref>{{cite web | url=http://www.specialchem4adhesives.com/tc/antioxidants/index.aspx?id=hinderedphenols | archive-url=https://web.archive.org/web/20060529051925/http://www.specialchem4adhesives.com/tc/antioxidants/index.aspx?id=hinderedphenols | archive-date=29 May 2006 | title=Antioxidants Center - Hindered Phenols }}</ref> Examples: [[butylated hydroxytoluene]], [[2,4-Dimethyl-6-tert-butylphenol|2,4-dimethyl-6-''tert''-butylphenol]], [[para tertiary butyl phenol]], [[2,6-Di-tert-butylphenol|2,6-di-tert-butylphenol]], [[1,3,5-Tris(4-(tert-butyl)-3-hydroxy-2,6-dimethylbenzyl)-1,3,5-triazinane-2,4,6-trione]]
** Secondary aromatic amines: Not as hindered, which make them more active. Very few FDA approvals.<ref>{{cite web | url=http://www.specialchem4adhesives.com/tc/antioxidants/index.aspx?id=aromaticamines | archive-url=https://web.archive.org/web/20060529051933/http://www.specialchem4adhesives.com/tc/antioxidants/index.aspx?id=aromaticamines | archive-date=29 May 2006 | title=Antioxidants Center - Secondary Aromatic Amines }}</ref>
** Hindered amine light stabilizers (HALS): Unlike other primary antioxidants, HALS scavenges free radicals generated during photo-oxidation, thus preventing the polymer material from UV radiation.<ref>{{Cite journal |last1=Costa |first1=Tiago |last2=Sampaio-Marques |first2=Belém |last3=Neves |first3=Nuno M. |last4=Aguilar |first4=Helena |last5=Fraga |first5=Alexandra G. |date=2024-06-24 |title=Antimicrobial properties of hindered amine light stabilizers in polymer coating materials and their mechanism of action |journal=Frontiers in Bioengineering and Biotechnology |language=English |volume=12 |doi=10.3389/fbioe.2024.1390513|doi-access=free |issn=2296-4185|pmc=11229053 }}</ref>{{better source|date=February 2025}}
* Secondary antioxidants act to decompose peroxides (ROOH) into non-radical products, thus preventing further generation of free radicals, and contributing to the overall oxidate stability of the polymer. Often used in combination with phenolic antioxidants for syngeristic effects.
** Phosphites: Example: [[tris(2,4-di-tert-butylphenyl)phosphite]].<ref>{{cite web | url=http://www.specialchem4adhesives.com/tc/antioxidants/index.aspx?id=organophosphorus | archive-url=https://web.archive.org/web/20060529051829/http://www.specialchem4adhesives.com/tc/antioxidants/index.aspx?id=organophosphorus | archive-date=29 May 2006 | title=Antioxidants Center - Organophosphorus Compounds }}</ref>
** Thiosynergists: Most of this class are "thio-esters" (not to be confused with [[thioester]]s): an ester of 3,3-thiodipropionic acid.<ref>{{cite web | url=http://www.specialchem4adhesives.com/tc/antioxidants/index.aspx?id=thiosynergists | archive-url=https://web.archive.org/web/20060529051844/http://www.specialchem4adhesives.com/tc/antioxidants/index.aspx?id=thiosynergists | archive-date=29 May 2006 | title=Antioxidants Center - Thiosynergists }}</ref> Other [[thioether]] (R1-S-R2) compounds also have a similar effect.<ref name=chap5/>
* Multifunctional antioxidants: an antioxidant can have both primary and secondary functional groups to act as both. Having multiple functional groups is what "multifunctional" means in chemistry.<ref>{{cite web | url=http://www.specialchem4adhesives.com/tc/antioxidants/index.aspx?id=multiao | archive-url=https://web.archive.org/web/20060510232735/http://www.specialchem4adhesives.com/tc/antioxidants/index.aspx?id=multiao | archive-date=10 May 2006 | title=Multifunctional Antioxidants - Antioxidants Center - SpecialChem4Adhesives }}</ref> The hydroxylamine functional group on its own can act as both.<ref>{{cite web | url=http://www.specialchem4adhesives.com/tc/antioxidants/index.aspx?id=hydroxylamine | archive-url=https://web.archive.org/web/20060510233253/http://www.specialchem4adhesives.com/tc/antioxidants/index.aspx?id=hydroxylamine | archive-date=10 May 2006 | title=Hydroxylamine - Antioxidants Center - SpecialChem4Adhesives }}</ref>
* Radical scavengers: scavenges free radicals to halt the chain reaction. This can be any radical in the oxidation cycle (R•, ROO•, RO•, •OH), though in practice RO• and •OH are too reactive to "trap". Common types include lactones (esp. substituted benzofuranone) and acrylated bis-phenols.<ref>{{cite web | url=http://www.specialchem4adhesives.com/tc/antioxidants/index.aspx?id=acrylatebphenols | archive-url=https://web.archive.org/web/20050419003511/http://www.specialchem4adhesives.com/tc/antioxidants/index.aspx?id=acrylatebphenols | archive-date=19 April 2005 | title=Antioxidants Center - Acrylated Bis-Phenols }}</ref><ref name=chap5>{{cite journal |doi=10.1515/9783110468281-005 |doi-broken-date=14 February 2025 |url=https://www.researchgate.net/publication/324772435}}</ref>

=== Use as pharmaceutical ===
[[File:Probucol.svg|thumb|right|Probucol, which has hindered phenols and thioethers.]]
[[Probucol]] was originally designed as an antioxidant polymer stabilizer for rubber tires. It was later found to reduce [[LDL-C]] levels independently of the [[LDL receptor]] and became a prescription drug. Its approval predated statins by a decade.<ref name="pmid32507832">{{cite journal |vauthors=Yamashita S, Masuda D, Matsuzawa Y |title=New Horizons for Probucol, an Old, Mysterious Drug |journal=Journal of Atherosclerosis and Thrombosis |volume=28 |issue=2 |pages=100–102 |date=February 2021 |pmid=32507832 |pmc=7957029 |doi=10.5551/jat.ED132 |quote=Probucol was developed as an anti-oxidative compound to prevent the degradation of tire rubber and later applied to reduce serum LDL-C levels in patients with hypercholesterolemia.}}</ref>

=== Environmental and health hazards ===
Synthetic phenolic antioxidants (SPAs)<ref>{{Cite journal |last1=Liu |first1=Runzeng |last2=Mabury |first2=Scott A. |date=6 October 2020 |title=Synthetic Phenolic Antioxidants: A Review of Environmental Occurrence, Fate, Human Exposure, and Toxicity |journal=Environmental Science & Technology |volume=54 |issue=19 |pages=11706–11719 |bibcode=2020EnST...5411706L |doi=10.1021/acs.est.0c05077 |pmid=32915564 |s2cid=221637214}}</ref> and aminic antioxidants<ref>{{Cite journal |last1=Xu |first1=Jing |last2=Hao |first2=Yanfen |last3=Yang |first3=Zhiruo |last4=Li |first4=Wenjuan |last5=Xie |first5=Wenjing |last6=Huang |first6=Yani |last7=Wang |first7=Deliang |last8=He |first8=Yuqing |last9=Liang |first9=Yong |last10=Matsiko |first10=Julius |last11=Wang |first11=Pu |date=7 November 2022 |title=Rubber Antioxidants and Their Transformation Products: Environmental Occurrence and Potential Impact |journal=International Journal of Environmental Research and Public Health |volume=19 |issue=21 |pages=14595 |doi=10.3390/ijerph192114595 |pmc=9657274 |pmid=36361475 |doi-access=free}}</ref> have potential human and environmental health hazards. SPAs are common in indoor dust, small air particles, sediment, sewage, river water and wastewater.<ref name=":0">{{Cite journal |last1=Li |first1=Chao |last2=Cui |first2=Xinyi |last3=Chen |first3=Yi |last4=Liao |first4=Chunyang |last5=Ma |first5=Lena Q |date=February 2019 |title=Synthetic phenolic antioxidants and their major metabolites in human fingernail |url=https://www.sciencedirect.com/science/article/pii/S0013935118306029 |journal=Environmental Research |volume=169 |pages=308–314 |bibcode=2019ER....169..308L |doi=10.1016/j.envres.2018.11.020 |pmid=30500685 |s2cid=56486425}}</ref> They are synthesized from phenolic compounds and include [[Butylated hydroxytoluene|2,6-di-tert-butyl-4-methylphenol (BHT)]], 2,6-di-tert-butyl-p-benzoquinone (BHT-Q), [[2,6-Di-tert-butylphenol|2,4-di-tert-butyl-phenol (DBP)]] and [[Butylated hydroxyanisole|3-''tert''-butyl-4-hydroxyanisole (BHA)]]. BHT can cause [[hepatotoxicity]] and damage to the [[endocrine system]] and may increase tumor development rates due to [[Unsymmetrical dimethylhydrazine|1,1-dimethylhydrazine]].<ref>{{Cite journal |last1=Liu |first1=Runzeng |last2=Mabury |first2=Scott A. |date=September 11, 2020 |title=Synthetic Phenolic Antioxidants: A Review of Environmental Occurrence, Fate, Human Exposure, and Toxicity |url=https://pubs.acs.org/doi/full/10.1021/acs.est.0c05077 |journal=Environ. Sci. Technol. |volume=54 |issue=19 |pages=11706–11719 |bibcode=2020EnST...5411706L |doi=10.1021/acs.est.0c05077 |pmid=32915564 |s2cid=221637214}}</ref> BHT-Q can cause DNA damage and mismatches<ref>{{Cite journal |last1=Wang |first1=Wanyi |last2=Xiong |first2=Ping |last3=Zhang |first3=He |last4=Zhu |first4=Qingqing |last5=Liao |first5=Chunyang |last6=Jiang |first6=Guibin |date=2021-10-01 |title=Analysis, occurrence, toxicity and environmental health risks of synthetic phenolic antioxidants: A review |url=https://www.sciencedirect.com/science/article/pii/S0013935121008252 |journal=Environmental Research |language=en |volume=201 |pages=111531 |bibcode=2021ER....20111531W |doi=10.1016/j.envres.2021.111531 |issn=0013-9351 |pmid=34146526}}</ref> through the cleavage process, generating [[superoxide]] radicals.<ref name=":0" /> DBP is toxic to marine life if exposed long-term. Phenolic antioxidants have low biodegradability, but they do not have severe toxicity toward aquatic organisms at low concentrations. Another type of antioxidant, [[Diphenylamine|diphenylamine (DPA)]], is commonly used in the production of commercial, industrial lubricants and rubber products and it also acts as a supplement for automotive engine oils.<ref>{{Cite journal |last1=Zhang |first1=Zi-Feng |last2=Zhang |first2=Xue |last3=Sverko |first3=Ed |last4=Marvin |first4=Christopher H. |last5=Jobst |first5=Karl J. |last6=Smyth |first6=Shirley Anne |last7=Li |first7=Yi-Fan |date=2020-02-11 |title=Determination of Diphenylamine Antioxidants in Wastewater/Biosolids and Sediment |url=https://pubs.acs.org/doi/10.1021/acs.estlett.9b00796 |journal=Environmental Science & Technology Letters |language=en |volume=7 |issue=2 |pages=102–110 |bibcode=2020EnSTL...7..102Z |doi=10.1021/acs.estlett.9b00796 |issn=2328-8930 |s2cid=213719260}}</ref>

== Oxidative challenge in biology ==
{{further|Oxidative stress}}

[[Image:L-ascorbic-acid-3D-balls.png|thumb|right|The structure of the antioxidant [[vitamin]] [[ascorbic acid]] (vitamin C)]]

The vast majority of complex [[life|life on Earth]] requires [[oxygen]] for its metabolism, but this same oxygen is a [[reactive oxygen species|highly reactive element]] that can damage living organisms.<ref name=Autox/><ref name="Davies">{{Cite journal |vauthors=Davies KJ |year=1995 |title=Oxidative stress: the paradox of aerobic life |journal=Biochemical Society Symposium |volume=61 |pages=1–31 |doi=10.1042/bss0610001 |pmid=8660387}}</ref> Organisms contain chemicals and [[enzyme]]s that minimize this oxidative damage without interfering with the beneficial effect of oxygen.<ref name="Sies">{{Cite journal |vauthors=Sies H |date=March 1997 |title=Oxidative stress: oxidants and antioxidants |journal=Experimental Physiology |volume=82 |issue=2 |pages=291–5 |doi=10.1113/expphysiol.1997.sp004024 |pmid=9129943 |s2cid=20240552 |doi-access=free}}</ref><ref name="Vertuani">{{Cite journal |vauthors=Vertuani S, Angusti A, Manfredini S |year=2004 |title=The Antioxidants and Pro-Antioxidants Network: an Overview |journal=Current Pharmaceutical Design |volume=10 |issue=14 |pages=1677–94 |doi=10.2174/1381612043384655 |pmid=15134565}}</ref> In general, antioxidant systems either prevent these reactive species from being formed, or remove them, thus minimizing their damage.<ref name="Davies" /><ref name="Sies" />  Reactive oxygen species can have useful cellular functions, such as [[redox signaling]]. Thus, ideally, antioxidant systems do not remove oxidants entirely, but maintain them at some optimum concentration.<ref>{{Cite journal |vauthors=Rhee SG |date=June 2006 |title=Cell signaling. H2O2, a necessary evil for cell signaling |journal=Science |volume=312 |issue=5782 |pages=1882–3 |doi=10.1126/science.1130481 |pmid=16809515 |s2cid=83598498}}</ref>

Reactive oxygen species produced in cells include [[hydrogen peroxide]] (H<sub>2</sub>O<sub>2</sub>), [[hypochlorous acid]] (HClO), and [[free radical]]s such as the [[hydroxyl radical]] (·OH), and the [[superoxide|superoxide anion]] (O<sub>2</sub><sup>−</sup>).<ref name="emfafb">{{Cite journal |vauthors=Valko M, Leibfritz D, Moncol J, Cronin MT, Mazur M, Telser J |year=2007 |title=Free radicals and antioxidants in normal physiological functions and human disease |journal=The International Journal of Biochemistry & Cell Biology |volume=39 |issue=1 |pages=44–84 |doi=10.1016/j.biocel.2006.07.001 |pmid=16978905}}</ref> 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 [[catalysis|metal-catalyzed]] redox reactions such as the [[Fenton reaction]].<ref name="ReferenceA">{{Cite journal |vauthors=Stohs SJ, Bagchi D |date=February 1995 |title=Oxidative mechanisms in the toxicity of metal ions |url=http://www8.umoncton.ca/umcm-gauthier_didier/bc6423/2SO/Strohs95.pdf |journal=Free Radical Biology & Medicine |type=Submitted manuscript |volume=18 |issue=2 |pages=321–36 |citeseerx=10.1.1.461.6417 |doi=10.1016/0891-5849(94)00159-H |pmid=7744317}}</ref> These oxidants can damage cells by starting chemical chain reactions such as [[lipid peroxidation]], or by oxidizing DNA or proteins.<ref name="Sies" /> Damage to DNA can cause [[mutation]]s and possibly [[cancer]], if not reversed by [[DNA repair]] mechanisms,<ref>{{Cite journal |vauthors=Nakabeppu Y, Sakumi K, Sakamoto K, Tsuchimoto D, Tsuzuki T, Nakatsu Y |date=April 2006 |title=Mutagenesis and carcinogenesis caused by the oxidation of nucleic acids |journal=Biological Chemistry |volume=387 |issue=4 |pages=373–9 |doi=10.1515/BC.2006.050 |pmid=16606334 |s2cid=20217256}}</ref><ref>{{Cite journal |vauthors=Valko M, Izakovic M, Mazur M, Rhodes CJ, Telser J |date=November 2004 |title=Role of oxygen radicals in DNA damage and cancer incidence |journal=Molecular and Cellular Biochemistry |volume=266 |issue=1–2 |pages=37–56 |doi=10.1023/B:MCBI.0000049134.69131.89 |pmid=15646026 |s2cid=207547763}}</ref> while damage to [[protein]]s causes enzyme inhibition, [[denaturation (biochemistry)|denaturation]], and [[proteasome|protein degradation]].<ref>{{Cite journal |vauthors=Stadtman ER |date=August 1992 |title=Protein oxidation and aging |url=https://zenodo.org/record/1230934 |journal=Science |volume=257 |issue=5074 |pages=1220–4 |bibcode=1992Sci...257.1220S |doi=10.1126/science.1355616 |pmid=1355616}}</ref>

The use of oxygen as part of the process for generating metabolic energy produces reactive oxygen species.<ref name="Raha">{{Cite journal |vauthors=Raha S, Robinson BH |date=October 2000 |title=Mitochondria, oxygen free radicals, disease and ageing |journal=Trends in Biochemical Sciences |volume=25 |issue=10 |pages=502–8 |doi=10.1016/S0968-0004(00)01674-1 |pmid=11050436}}</ref> In this process, the superoxide anion is produced as a [[by-product]] of several steps in the [[electron transport chain]].<ref>{{Cite journal |vauthors=Lenaz G |year=2001 |title=The mitochondrial production of reactive oxygen species: mechanisms and implications in human pathology |journal=IUBMB Life |volume=52 |issue=3–5 |pages=159–64 |doi=10.1080/15216540152845957 |pmid=11798028 |s2cid=45366190 |doi-access=free}}</ref> Particularly important is the reduction of [[coenzyme Q]] in [[complex III]], since a highly reactive free radical is formed as an intermediate (Q'''·'''<sup>−</sup>). 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.<ref>{{Cite journal |vauthors=Finkel T, Holbrook NJ |date=November 2000 |title=Oxidants, oxidative stress and the biology of ageing |journal=Nature |volume=408 |issue=6809 |pages=239–47 |bibcode=2000Natur.408..239F |doi=10.1038/35041687 |pmid=11089981 |s2cid=2502238}}</ref> Peroxide is also produced from the oxidation of reduced [[flavoprotein]]s, such as [[complex I]].<ref>{{Cite journal |vauthors=Hirst J, King MS, Pryde KR |date=October 2008 |title=The production of reactive oxygen species by complex I |journal=Biochemical Society Transactions |volume=36 |issue=Pt 5 |pages=976–80 |doi=10.1042/BST0360976 |pmid=18793173}}</ref> However, although these enzymes can produce oxidants, the relative importance of the electron transfer chain to other processes that generate peroxide is unclear.<ref>{{Cite journal |vauthors=Seaver LC, Imlay JA |date=November 2004 |title=Are respiratory enzymes the primary sources of intracellular hydrogen peroxide? |journal=The Journal of Biological Chemistry |volume=279 |issue=47 |pages=48742–50 |doi=10.1074/jbc.M408754200 |pmid=15361522 |doi-access=free}}</ref><ref name="Pathways Ofoxidativedamage">{{Cite journal |vauthors=Imlay JA |year=2003 |title=Pathways of oxidative damage |journal=Annual Review of Microbiology |volume=57 |pages=395–418 |doi=10.1146/annurev.micro.57.030502.090938 |pmid=14527285}}</ref> In plants, [[algae]], and [[cyanobacteria]], reactive oxygen species are also produced during [[photosynthesis]],<ref>{{Cite journal |vauthors=Demmig-Adams B, Adams WW |date=December 2002 |title=Antioxidants in photosynthesis and human nutrition |journal=Science |volume=298 |issue=5601 |pages=2149–53 |bibcode=2002Sci...298.2149D |doi=10.1126/science.1078002 |pmid=12481128 |s2cid=27486669}}</ref> particularly under conditions of high [[irradiance|light intensity]].<ref>{{Cite journal |vauthors=Krieger-Liszkay A |date=January 2005 |title=Singlet oxygen production in photosynthesis |journal=Journal of Experimental Botany |volume=56 |issue=411 |pages=337–46 |citeseerx=10.1.1.327.9651 |doi=10.1093/jxb/erh237 |pmid=15310815}}</ref> This effect is partly offset by the involvement of [[carotenoid]]s in [[photoinhibition]], and in algae and cyanobacteria, by large amount of [[iodide]] and [[selenium]],<ref>{{Cite journal |vauthors=Kupper FC, Carpenter LJ, McFiggans GB, Palmer CJ, Waite TJ, ((Boneberg E-M)), Woitsch S, Weiller M, Abela R, Grolimund D, Potin P, Butler A, Luther GW, ((Kroneck PMH)), Meyer-Klaucke W, Feiters MC |year=2008 |title=Iodide accumulation provides kelp with an inorganic antioxidant impacting atmospheric chemistry |journal=[[Proceedings of the National Academy of Sciences]] |volume=105 |issue=19 |pages=6954–6958 |bibcode=2008PNAS..105.6954K |doi=10.1073/pnas.0709959105 |issn=0027-8424 |pmc=2383960 |pmid=18458346 |doi-access=free}}</ref> which involves these antioxidants reacting with over-reduced forms of the [[photosynthetic reaction centre]]s to prevent the production of reactive oxygen species.<ref>{{Cite journal |vauthors=Szabó I, Bergantino E, Giacometti GM |date=July 2005 |title=Light and oxygenic photosynthesis: energy dissipation as a protection mechanism against photo-oxidation |journal=EMBO Reports |volume=6 |issue=7 |pages=629–34 |doi=10.1038/sj.embor.7400460 |pmc=1369118 |pmid=15995679}}</ref><ref>{{Cite journal |vauthors=Kerfeld CA |date=October 2004 |title=Water-soluble carotenoid proteins of cyanobacteria |url=https://cloudfront.escholarship.org/dist/prd/content/qt3dm533x9/qt3dm533x9.pdf |journal=Archives of Biochemistry and Biophysics |type=Submitted manuscript |volume=430 |issue=1 |pages=2–9 |doi=10.1016/j.abb.2004.03.018 |pmid=15325905 |s2cid=25306222}}</ref>

=== Examples of bioactive antioxidant compounds ===
[[Physiology|Physiological]] antioxidants are classified into two broad divisions, depending on whether they are soluble in water ([[hydrophile|hydrophilic]]) or in lipids ([[Lipophilicity|lipophilic]]). In general, water-soluble antioxidants react with oxidants in the cell [[cytosol]] and the [[blood plasma]], while lipid-soluble antioxidants protect [[cell membrane]]s from [[lipid peroxidation]].<ref name="Sies" /> These compounds may be synthesized in the body or obtained from the diet.<ref name="Vertuani" /> The different antioxidants are present at a wide range of concentrations in [[Bodily fluid|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 [[pathogen]]s or [[virulence factor]]s.<ref>{{Cite journal |vauthors=Miller RA, Britigan BE |date=January 1997 |title=Role of oxidants in microbial pathophysiology |journal=Clinical Microbiology Reviews |volume=10 |issue=1 |pages=1–18 |doi=10.1128/CMR.10.1.1 |pmc=172912 |pmid=8993856}}</ref>

The interactions between these different antioxidants may be [[synergy|synergistic]] and interdependent.<ref>{{Cite journal |vauthors=Chaudière J, Ferrari-Iliou R |year=1999 |title=Intracellular antioxidants: from chemical to biochemical mechanisms |journal=Food and Chemical Toxicology |volume=37 |issue=9–10 |pages=949–62 |doi=10.1016/S0278-6915(99)00090-3 |pmid=10541450}}</ref><ref>{{Cite journal |vauthors=Sies H |date=July 1993 |title=Strategies of antioxidant defense |journal=European Journal of Biochemistry |volume=215 |issue=2 |pages=213–9 |doi=10.1111/j.1432-1033.1993.tb18025.x |pmid=7688300 |doi-access=free}}</ref> The action of one antioxidant may therefore depend on the proper function of other members of the antioxidant system.<ref name="Vertuani" /> 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.<ref name="Vertuani" />

Some compounds contribute to antioxidant defense by [[chelation|chelating]] [[transition metal]]s 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.<ref name="Pathways Ofoxidativedamage" /> [[Selenium]] and [[zinc]] are commonly referred to as ''antioxidant minerals'', but these [[chemical element]]s 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]].)

{| class="wikitable" style="margin-left: auto; margin-right: auto; text-align:center;"
|-
!Antioxidant
!Solubility
!Concentration in human serum ({{abbr|μM|micromolar}})
!Concentration in liver tissue ({{abbr|μmol/kg|micromoles per kilogram}})
|-
| [[Ascorbic acid]] ([[vitamin C]])
| Water
| 50–60<ref>{{Cite journal |vauthors=Khaw KT, Woodhouse P |date=June 1995 |title=Interrelation of vitamin C, infection, haemostatic factors, and cardiovascular disease |journal=BMJ |volume=310 |issue=6994 |pages=1559–63 |doi=10.1136/bmj.310.6994.1559 |pmc=2549940 |pmid=7787643}}</ref>
| 260 (human)<ref name="Evelson">{{Cite journal |vauthors=Evelson P, Travacio M, Repetto M, Escobar J, Llesuy S, Lissi EA |date=April 2001 |title=Evaluation of total reactive antioxidant potential (TRAP) of tissue homogenates and their cytosols |journal=Archives of Biochemistry and Biophysics |volume=388 |issue=2 |pages=261–6 |doi=10.1006/abbi.2001.2292 |pmid=11368163}}</ref>
|-
| [[Glutathione]]
| Water
| 4<ref>{{Cite journal |vauthors=Morrison JA, Jacobsen DW, Sprecher DL, Robinson K, Khoury P, Daniels SR |date=November 1999 |title=Serum glutathione in adolescent males predicts parental coronary heart disease |journal=Circulation |volume=100 |issue=22 |pages=2244–7 |doi=10.1161/01.CIR.100.22.2244 |pmid=10577998 |doi-access=free}}</ref>
| 6,400 (human)<ref name="Evelson" />
|-
| [[Lipoic acid]]
| Water
| 0.1–0.7<ref>{{Cite journal |vauthors=Teichert J, Preiss R |date=November 1992 |title=HPLC-methods for determination of lipoic acid and its reduced form in human plasma |journal=International Journal of Clinical Pharmacology, Therapy, and Toxicology |volume=30 |issue=11 |pages=511–2 |pmid=1490813}}</ref>
| 4–5 (rat)<ref>{{Cite journal |vauthors=Akiba S, Matsugo S, Packer L, Konishi T |date=May 1998 |title=Assay of protein-bound lipoic acid in tissues by a new enzymatic method |journal=Analytical Biochemistry |volume=258 |issue=2 |pages=299–304 |doi=10.1006/abio.1998.2615 |pmid=9570844}}</ref>
|-
| [[Uric acid]]
| Water
| 200–400<ref name="Glantzounis">{{Cite journal |vauthors=Glantzounis GK, Tsimoyiannis EC, Kappas AM, Galaris DA |year=2005 |title=Uric acid and oxidative stress |journal=Current Pharmaceutical Design |volume=11 |issue=32 |pages=4145–51 |doi=10.2174/138161205774913255 |pmid=16375736}}</ref>
| 1,600 (human)<ref name="Evelson" />
|-
| [[Carotene]]s
| Lipid
| [[carotene|β-carotene]]: 0.5–1<ref>{{Cite journal |vauthors=El-Sohemy A, Baylin A, Kabagambe E, Ascherio A, Spiegelman D, Campos H |date=July 2002 |title=Individual carotenoid concentrations in adipose tissue and plasma as biomarkers of dietary intake |journal=The American Journal of Clinical Nutrition |volume=76 |issue=1 |pages=172–9 |doi=10.1093/ajcn/76.1.172 |pmid=12081831 |doi-access=free}}</ref>
[[retinol]] (vitamin A): 1–3<ref name="Sowell">{{Cite journal |vauthors=Sowell AL, Huff DL, Yeager PR, Caudill SP, Gunter EW |date=March 1994 |title=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 |journal=Clinical Chemistry |volume=40 |issue=3 |pages=411–6 |doi=10.1093/clinchem/40.3.411 |pmid=8131277 |doi-access=free}}</ref>
| 5 (human, total carotenoids)<ref>{{Cite journal |vauthors=Stahl W, Schwarz W, Sundquist AR, Sies H |date=April 1992 |title=cis-trans isomers of lycopene and beta-carotene in human serum and tissues |journal=Archives of Biochemistry and Biophysics |volume=294 |issue=1 |pages=173–7 |doi=10.1016/0003-9861(92)90153-N |pmid=1550343}}</ref>
|-
| [[tocopherol|α-Tocopherol]] (vitamin E)
| Lipid
| 10–40<ref name="Sowell" />
| 50 (human)<ref name="Evelson" />
|-
| [[Coenzyme Q|Ubiquinol]] (coenzyme Q)
| Lipid
| 5<ref>{{Cite journal |vauthors=Zita C, Overvad K, Mortensen SA, Sindberg CD, Moesgaard S, Hunter DA |year=2003 |title=Serum coenzyme Q10 concentrations in healthy men supplemented with 30 mg or 100 mg coenzyme Q10 for two months in a randomised controlled study |journal=BioFactors |volume=18 |issue=1–4 |pages=185–93 |doi=10.1002/biof.5520180221 |pmid=14695934 |s2cid=19895215}}</ref>
| 200 (human)<ref name="Turunen">{{Cite journal |vauthors=Turunen M, Olsson J, Dallner G |date=January 2004 |title=Metabolism and function of coenzyme Q |journal=Biochimica et Biophysica Acta (BBA) - Biomembranes |volume=1660 |issue=1–2 |pages=171–99 |doi=10.1016/j.bbamem.2003.11.012 |pmid=14757233 |doi-access=free}}</ref>
|}

==== Uric acid ====
[[Uric acid]] has the highest concentration of any blood antioxidant<ref name="Glantzounis" /> and provides over half of the total antioxidant capacity of human serum.<ref>{{Cite journal |vauthors=Becker BF |date=June 1993 |title=Towards the physiological function of uric acid |journal=Free Radical Biology & Medicine |volume=14 |issue=6 |pages=615–31 |doi=10.1016/0891-5849(93)90143-I |pmid=8325534}}</ref> 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]],<ref name="Sautin2008">{{Cite journal |vauthors=Sautin YY, Johnson RJ |date=June 2008 |title=Uric acid: the oxidant-antioxidant paradox |journal=Nucleosides, Nucleotides & Nucleic Acids |volume=27 |issue=6 |pages=608–19 |doi=10.1080/15257770802138558 |pmc=2895915 |pmid=18600514}}</ref> [[peroxide]]s, and [[hypochlorous acid]].<ref name="Enomoto2005">{{Cite journal |vauthors=Enomoto A, Endou H |date=September 2005 |title=Roles of organic anion transporters (OATs) and a urate transporter (URAT1) in the pathophysiology of human disease |journal=Clinical and Experimental Nephrology |volume=9 |issue=3 |pages=195–205 |doi=10.1007/s10157-005-0368-5 |pmid=16189627 |s2cid=6145651}}</ref> Concerns over elevated UA's contribution to [[gout]] must be considered one of many risk factors.<ref name="Eggebeen2007">{{Cite journal |vauthors=Eggebeen AT |date=September 2007 |title=Gout: an update |url=http://www.aafp.org/link_out?pmid=17910294 |journal=American Family Physician |volume=76 |issue=6 |pages=801–8 |pmid=17910294}}</ref> 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|supersaturation levels]] (535+ μmol/L).<ref name="Campion1987">{{Cite journal |vauthors=Campion EW, Glynn RJ, DeLabry LO |date=March 1987 |title=Asymptomatic hyperuricemia. Risks and consequences in the Normative Aging Study |journal=The American Journal of Medicine |volume=82 |issue=3 |pages=421–6 |doi=10.1016/0002-9343(87)90441-4 |pmid=3826098}}</ref> Many of these aforementioned studies determined UA's antioxidant actions within normal physiological levels,<ref name="Baillie2007">{{Cite journal |vauthors=Baillie JK, Bates MG, Thompson AA, Waring WS, Partridge RW, Schnopp MF, Simpson A, Gulliver-Sloan F, Maxwell SR, Webb DJ |date=May 2007 |title=Endogenous urate production augments plasma antioxidant capacity in healthy lowland subjects exposed to high altitude |journal=Chest |volume=131 |issue=5 |pages=1473–8 |doi=10.1378/chest.06-2235 |pmid=17494796}}</ref><ref name="Sautin2008" /> and some found antioxidant activity at levels as high as 285 μmol/L.<ref name="Nazarewicz2007">{{Cite journal |vauthors=Nazarewicz RR, Ziolkowski W, Vaccaro PS, Ghafourifar P |date=December 2007 |title=Effect of short-term ketogenic diet on redox status of human blood |journal=Rejuvenation Research |volume=10 |issue=4 |pages=435–40 |doi=10.1089/rej.2007.0540 |pmid=17663642}}</ref>

==== Vitamin C ====
[[Ascorbic acid]] or [[vitamin C]], an oxidation-reduction ([[redox]]) [[catalyst]] found in both animals and plants,<ref name="lpi2018">{{Cite web |date=1 July 2018 |title=Vitamin C |url=http://lpi.oregonstate.edu/mic/vitamins/vitamin-C |access-date=19 June 2019 |publisher=Micronutrient Information Center, Linus Pauling Institute, Oregon State University, Corvallis, OR}}</ref> can reduce, and thereby neutralize, reactive oxygen species such as hydrogen peroxide.<ref name="lpi2018" /><ref>{{Cite journal |vauthors=Padayatty SJ, Katz A, Wang Y, Eck P, Kwon O, Lee JH, Chen S, Corpe C, Dutta A, Dutta SK, Levine M |date=February 2003 |title=Vitamin C as an antioxidant: evaluation of its role in disease prevention |url=http://www.jacn.org/cgi/pmidlookup?view=long&pmid=12569111 |journal=Journal of the American College of Nutrition |volume=22 |issue=1 |pages=18–35 |doi=10.1080/07315724.2003.10719272 |pmid=12569111 |s2cid=21196776}}</ref> In addition to its direct antioxidant effects, ascorbic acid is also a [[substrate (biochemistry)|substrate]] for the redox enzyme [[ascorbate peroxidase]], a function that is used in stress resistance in plants.<ref>{{Cite journal |vauthors=Shigeoka S, Ishikawa T, Tamoi M, Miyagawa Y, Takeda T, Yabuta Y, Yoshimura K |date=May 2002 |title=Regulation and function of ascorbate peroxidase isoenzymes |journal=Journal of Experimental Botany |volume=53 |issue=372 |pages=1305–19 |doi=10.1093/jexbot/53.372.1305 |pmid=11997377 |doi-access=free}}</ref> Ascorbic acid is present at high levels in all parts of plants and can reach concentrations of 20&nbsp;[[millimolar]] in [[chloroplast]]s.<ref>{{Cite journal |vauthors=Smirnoff N, Wheeler GL |year=2000 |title=Ascorbic acid in plants: biosynthesis and function |journal=Critical Reviews in Biochemistry and Molecular Biology |volume=35 |issue=4 |pages=291–314 |doi=10.1080/10409230008984166 |pmid=11005203 |s2cid=85060539}}</ref>

==== Glutathione ====
[[Image:Lipid peroxidation.svg|thumb|right|class=skin-invert-image|The [[Radical (chemistry)|free radical]] mechanism of lipid peroxidation]]

[[Glutathione]] has antioxidant properties since the [[thiol]] group in its [[cysteine]] [[moiety (chemistry)|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 peroxidase]]s and [[glutaredoxin]]s, as well as reacting directly with oxidants.<ref name="MeisterA">{{Cite journal |vauthors=Meister A |date=April 1994 |title=Glutathione-ascorbic acid antioxidant system in animals |url=https://www.jbc.org/article/S0021-9258(17)36891-6/pdf |journal=The Journal of Biological Chemistry |volume=269 |issue=13 |pages=9397–400 |doi=10.1016/S0021-9258(17)36891-6 |pmid=8144521 |doi-access=free}}</ref> 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.<ref name="MeisterB">{{Cite journal |vauthors=Meister A, Anderson ME |year=1983 |title=Glutathione |journal=Annual Review of Biochemistry |volume=52 |pages=711–60 |doi=10.1146/annurev.bi.52.070183.003431 |pmid=6137189}}</ref> In some organisms glutathione is replaced by other thiols, such as by [[mycothiol]] in the [[Actinomycete]]s, [[bacillithiol]] in some [[gram-positive bacteria]],<ref name="pmid20308541">{{Cite journal |vauthors=Gaballa A, Newton GL, Antelmann H, Parsonage D, Upton H, Rawat M, Claiborne A, Fahey RC, Helmann JD |date=April 2010 |title=Biosynthesis and functions of bacillithiol, a major low-molecular-weight thiol in Bacilli |journal=Proceedings of the National Academy of Sciences of the United States of America |volume=107 |issue=14 |pages=6482–6 |bibcode=2010PNAS..107.6482G |doi=10.1073/pnas.1000928107 |pmc=2851989 |pmid=20308541 |doi-access=free}}</ref><ref name="Newton">{{Cite journal |vauthors=Newton GL, Rawat M, La Clair JJ, Jothivasan VK, Budiarto T, Hamilton CJ, Claiborne A, Helmann JD, Fahey RC |date=September 2009 |title=Bacillithiol is an antioxidant thiol produced in Bacilli |journal=Nature Chemical Biology |volume=5 |issue=9 |pages=625–627 |doi=10.1038/nchembio.189 |pmc=3510479 |pmid=19578333}}</ref> or by [[trypanothione]] in the [[Kinetoplastida|Kinetoplastids]].<ref>{{Cite journal |vauthors=Fahey RC |year=2001 |title=Novel thiols of prokaryotes |journal=Annual Review of Microbiology |volume=55 |pages=333–56 |doi=10.1146/annurev.micro.55.1.333 |pmid=11544359}}</ref><ref>{{Cite journal |vauthors=Fairlamb AH, Cerami A |year=1992 |title=Metabolism and functions of trypanothione in the Kinetoplastida |journal=Annual Review of Microbiology |volume=46 |pages=695–729 |doi=10.1146/annurev.mi.46.100192.003403 |pmid=1444271}}</ref>

==== Vitamin E ====
[[Vitamin E]] is the collective name for a set of eight related [[tocopherol]]s and [[tocotrienol]]s, which are [[fat-soluble]] vitamins with antioxidant properties.<ref name="Herrera">{{Cite journal |author-link2=Coral Barbas |vauthors=Herrera E, Barbas C |date=March 2001 |title=Vitamin E: action, metabolism and perspectives |journal=Journal of Physiology and Biochemistry |volume=57 |issue=2 |pages=43–56 |doi=10.1007/BF03179812 |pmid=11579997 |s2cid=7272312 |hdl-access=free |hdl=10637/720}}</ref><ref>{{Cite journal |vauthors=Packer L, Weber SU, Rimbach G |date=February 2001 |title=Molecular aspects of alpha-tocotrienol antioxidant action and cell signalling |journal=The Journal of Nutrition |volume=131 |issue=2 |pages=369S–73S |doi=10.1093/jn/131.2.369S |pmid=11160563 |doi-access=free}}</ref> Of these, α-tocopherol has been most studied as it has the highest [[bioavailability]], with the body preferentially absorbing and metabolising this form.<ref name="Brigelius">{{Cite journal |vauthors=Brigelius-Flohé R, Traber MG |date=July 1999 |title=Vitamin E: function and metabolism |journal=FASEB Journal |volume=13 |issue=10 |pages=1145–55 |citeseerx=10.1.1.337.5276 |doi=10.1096/fasebj.13.10.1145 |pmid=10385606 |s2cid=7031925 |doi-access=free}}</ref>

It has been claimed{{by whom|date=September 2024}} 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.<ref name="Herrera" /><ref>{{Cite journal |vauthors=Traber MG, Atkinson J |date=July 2007 |title=Vitamin E, antioxidant and nothing more |journal=Free Radical Biology & Medicine |volume=43 |issue=1 |pages=4–15 |doi=10.1016/j.freeradbiomed.2007.03.024 |pmc=2040110 |pmid=17561088}}</ref> 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.<ref>{{Cite journal |vauthors=Wang X, Quinn PJ |date=July 1999 |title=Vitamin E and its function in membranes |journal=Progress in Lipid Research |volume=38 |issue=4 |pages=309–36 |doi=10.1016/S0163-7827(99)00008-9 |pmid=10793887}}</ref> 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.<ref>{{Cite journal |vauthors=Seiler A, Schneider M, Förster H, Roth S, Wirth EK, Culmsee C, Plesnila N, Kremmer E, Rådmark O, Wurst W, Bornkamm GW, Schweizer U, Conrad M |date=September 2008 |title=Glutathione peroxidase 4 senses and translates oxidative stress into 12/15-lipoxygenase dependent- and AIF-mediated cell death |journal=Cell Metabolism |volume=8 |issue=3 |pages=237–48 |doi=10.1016/j.cmet.2008.07.005 |pmid=18762024 |doi-access=free}}</ref> GPx4 is the only known enzyme that efficiently reduces lipid-hydroperoxides within biological membranes.{{cn|date=November 2024}}

However, the roles and importance of the various forms of vitamin E are presently unclear,<ref>{{Cite journal |vauthors=Brigelius-Flohé R, Davies KJ |date=July 2007 |title=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 |journal=Free Radical Biology & Medicine |volume=43 |issue=1 |pages=2–3 |doi=10.1016/j.freeradbiomed.2007.05.016 |pmid=17561087}}</ref><ref>{{Cite journal |vauthors=Atkinson J, Epand RF, Epand RM |date=March 2008 |title=Tocopherols and tocotrienols in membranes: a critical review |journal=Free Radical Biology & Medicine |volume=44 |issue=5 |pages=739–64 |doi=10.1016/j.freeradbiomed.2007.11.010 |pmid=18160049}}</ref> and it has even been suggested that the most important function of α-tocopherol is as a [[cell signaling|signaling molecule]], with this molecule having no significant role in antioxidant metabolism.<ref name="Azzi">{{Cite journal |vauthors=Azzi A |date=July 2007 |title=Molecular mechanism of alpha-tocopherol action |journal=Free Radical Biology & Medicine |volume=43 |issue=1 |pages=16–21 |doi=10.1016/j.freeradbiomed.2007.03.013 |pmid=17561089}}</ref><ref>{{Cite journal |vauthors=Zingg JM, Azzi A |date=May 2004 |title=Non-antioxidant activities of vitamin E |url=http://www.benthamdirect.org/pages/content.php?CMC/2004/00000011/00000009/0005C.SGM |url-status=dead |journal=Current Medicinal Chemistry |volume=11 |issue=9 |pages=1113–33 |doi=10.2174/0929867043365332 |pmid=15134510 |archive-url=https://web.archive.org/web/20111006103310/http://www.benthamdirect.org/pages/content.php?CMC%2F2004%2F00000011%2F00000009%2F0005C.SGM |archive-date=6 October 2011}}</ref> The functions of the other forms of vitamin E are even less well understood, although γ-tocopherol is a [[nucleophile]] that may react with [[electrophile|electrophilic]] mutagens,<ref name="Brigelius" /> and tocotrienols may be important in protecting [[neuron]]s from damage.<ref>{{Cite journal |vauthors=Sen CK, Khanna S, Roy S |date=March 2006 |title=Tocotrienols: Vitamin E beyond tocopherols |journal=Life Sciences |volume=78 |issue=18 |pages=2088–98 |doi=10.1016/j.lfs.2005.12.001 |pmc=1790869 |pmid=16458936}}</ref>

=== Pro-oxidant activities ===
{{further|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;<ref>{{Cite journal |vauthors=Duarte TL, Lunec J |date=July 2005 |title=Review: When is an antioxidant not an antioxidant? A review of novel actions and reactions of vitamin C |journal=Free Radical Research |volume=39 |issue=7 |pages=671–86 |doi=10.1080/10715760500104025 |pmid=16036346 |s2cid=39962659}}</ref> however, it will also reduce metal ions such as iron and copper<ref name="ReferenceB">{{Cite journal |last1=Shen |first1=Jiaqi |last2=Griffiths |first2=Paul T. |last3=Campbell |first3=Steven J. |last4=Utinger |first4=Battist |last5=Kalberer |first5=Markus |last6=Paulson |first6=Suzanne E. |date=2021-04-01 |title=Ascorbate oxidation by iron, copper and reactive oxygen species: review, model development, and derivation of key rate constants |journal=Scientific Reports |language=en |volume=11 |issue=1 |pages=7417 |bibcode=2021NatSR..11.7417S |doi=10.1038/s41598-021-86477-8 |issn=2045-2322 |pmc=8016884 |pmid=33795736}}</ref> that generate free radicals through the [[Fenton's reagent|Fenton reaction]].<ref name="ReferenceA" /><ref name="Carr">{{Cite journal |vauthors=Carr A, Frei B |date=June 1999 |title=Does vitamin C act as a pro-oxidant under physiological conditions? |journal=FASEB Journal |volume=13 |issue=9 |pages=1007–24 |doi=10.1096/fasebj.13.9.1007 |pmid=10336883 |s2cid=15426564 |doi-access=free}}</ref> While ascorbic acid is effective antioxidant, it can also oxidatively change the flavor and color of food. With the presence of transition metals, there are low concentrations of ascorbic acid that can act as a radical scavenger in the Fenton reaction.<ref name="ReferenceB" />

:2 Fe<sup>3+</sup> + Ascorbate → 2 Fe<sup>2+</sup> + Dehydroascorbate

:2 Fe<sup>2+</sup> + 2 H<sub>2</sub>O<sub>2</sub> → 2 Fe<sup>3+</sup> + 2 OH'''·''' + 2 OH<sup>−</sup>

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.<ref name="Carr" />

=== Enzyme systems ===
{{Image frame|caption=Enzymatic pathway&nbsp;for detoxification of reactive oxygen species
|content=<chem>
\underset{Oxygen}{O2} -> \underset{Superoxide}{*O2^-} ->[\ce{Superoxide \atop dismutase}] \underset{Hydrogen \atop peroxide}{H2O2} ->[\ce{Peroxidases \atop catalase}] \underset{Water}{H2O}
</chem>}}
As with the chemical antioxidants, cells are protected against oxidative stress by an interacting network of antioxidant enzymes.<ref name="Davies" /><ref name="Sies" /> 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 [[Genetically modified organism|transgenic mice]] lacking just one antioxidant enzyme can be informative.<ref name="Magnenat">{{Cite journal |vauthors=Ho YS, Magnenat JL, Gargano M, Cao J |date=October 1998 |title=The nature of antioxidant defense mechanisms: a lesson from transgenic studies |journal=Environmental Health Perspectives |volume=106 |issue=Suppl 5 |pages=1219–28 |doi=10.2307/3433989 |jstor=3433989 |pmc=1533365 |pmid=9788901}}</ref>

==== Superoxide dismutase, catalase, and peroxiredoxins ====
[[Superoxide dismutase]]s (SODs) are a class of closely related enzymes that catalyze the breakdown of the superoxide anion into oxygen and hydrogen peroxide.<ref>{{Cite journal |vauthors=Zelko IN, Mariani TJ, Folz RJ |date=August 2002 |title=Superoxide dismutase multigene family: a comparison of the CuZn-SOD (SOD1), Mn-SOD (SOD2), and EC-SOD (SOD3) gene structures, evolution, and expression |journal=Free Radical Biology & Medicine |volume=33 |issue=3 |pages=337–49 |doi=10.1016/S0891-5849(02)00905-X |pmid=12126755}}</ref><ref name="Bannister">{{Cite journal |vauthors=Bannister JV, Bannister WH, Rotilio G |year=1987 |title=Aspects of the structure, function, and applications of superoxide dismutase |journal=CRC Critical Reviews in Biochemistry |volume=22 |issue=2 |pages=111–80 |doi=10.3109/10409238709083738 |pmid=3315461}}</ref> SOD enzymes are present in almost all aerobic cells and in extracellular fluids.<ref>{{Cite journal |vauthors=Johnson F, Giulivi C |year=2005 |title=Superoxide dismutases and their impact upon human health |journal=Molecular Aspects of Medicine |volume=26 |issue=4–5 |pages=340–52 |doi=10.1016/j.mam.2005.07.006 |pmid=16099495}}</ref> 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]].<ref name="Bannister" /> There also exists a third form of SOD in [[extracellular fluid]]s, which contains copper and zinc in its active sites.<ref>{{Cite journal |vauthors=Nozik-Grayck E, Suliman HB, Piantadosi CA |date=December 2005 |title=Extracellular superoxide dismutase |journal=The International Journal of Biochemistry & Cell Biology |volume=37 |issue=12 |pages=2466–71 |doi=10.1016/j.biocel.2005.06.012 |pmid=16087389}}</ref> The mitochondrial isozyme seems to be the most biologically important of these three, since mice lacking this enzyme die soon after birth.<ref>{{Cite journal |vauthors=Melov S, Schneider JA, Day BJ, Hinerfeld D, Coskun P, Mirra SS, Crapo JD, Wallace DC |date=February 1998 |title=A novel neurological phenotype in mice lacking mitochondrial manganese superoxide dismutase |journal=Nature Genetics |volume=18 |issue=2 |pages=159–63 |doi=10.1038/ng0298-159 |pmid=9462746 |s2cid=20843002}}</ref> 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]]).<ref name="Magnenat" /><ref>{{Cite journal |vauthors=Reaume AG, Elliott JL, Hoffman EK, Kowall NW, Ferrante RJ, Siwek DF, Wilcox HM, Flood DG, Beal MF, Brown RH, Scott RW, Snider WD |date=May 1996 |title=Motor neurons in Cu/Zn superoxide dismutase-deficient mice develop normally but exhibit enhanced cell death after axonal injury |journal=Nature Genetics |volume=13 |issue=1 |pages=43–7 |doi=10.1038/ng0596-43 |pmid=8673102 |s2cid=13070253}}</ref> In plants, SOD isozymes are present in the cytosol and mitochondria, with an iron SOD found in [[chloroplast]]s that is absent from [[vertebrate]]s and [[yeast]].<ref>{{Cite journal |vauthors=Van Camp W, Inzé D, Van Montagu M |year=1997 |title=The regulation and function of tobacco superoxide dismutases |url=https://biblio.ugent.be/publication/183882/file/4172144 |journal=Free Radical Biology & Medicine |volume=23 |issue=3 |pages=515–20 |doi=10.1016/S0891-5849(97)00112-3 |pmid=9214590}}</ref>

[[Catalase]]s are enzymes that catalyse the conversion of hydrogen peroxide to water and oxygen, using either an iron or manganese cofactor.<ref>{{Cite journal |vauthors=Chelikani P, Fita I, Loewen PC |date=January 2004 |title=Diversity of structures and properties among catalases |url=https://digital.csic.es/bitstream/10261/111097/1/accesoRestringido.pdf |journal=Cellular and Molecular Life Sciences |type=Submitted manuscript |volume=61 |issue=2 |pages=192–208 |doi=10.1007/s00018-003-3206-5 |pmc=11138816 |pmid=14745498 |s2cid=4411482 |hdl=10261/111097}}</ref><ref>{{Cite journal |vauthors=Zámocký M, Koller F |year=1999 |title=Understanding the structure and function of catalases: clues from molecular evolution and in vitro mutagenesis |journal=Progress in Biophysics and Molecular Biology |volume=72 |issue=1 |pages=19–66 |doi=10.1016/S0079-6107(98)00058-3 |pmid=10446501 |doi-access=free}}</ref> This protein is localized to [[peroxisome]]s in most [[eukaryote|eukaryotic]] cells.<ref>{{Cite journal |vauthors=del Río LA, Sandalio LM, Palma JM, Bueno P, Corpas FJ |date=November 1992 |title=Metabolism of oxygen radicals in peroxisomes and cellular implications |journal=Free Radical Biology & Medicine |volume=13 |issue=5 |pages=557–80 |doi=10.1016/0891-5849(92)90150-F |pmid=1334030}}</ref> Catalase is an unusual enzyme since, although hydrogen peroxide is its only substrate, it follows a [[enzyme kinetics|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.<ref>{{Cite journal |vauthors=Hiner AN, Raven EL, Thorneley RN, García-Cánovas F, Rodríguez-López JN |date=July 2002 |title=Mechanisms of compound I formation in heme peroxidases |journal=Journal of Inorganic Biochemistry |volume=91 |issue=1 |pages=27–34 |doi=10.1016/S0162-0134(02)00390-2 |pmid=12121759}}</ref> Despite its apparent importance in hydrogen peroxide removal, humans with genetic deficiency of catalase&nbsp;— "[[acatalasemia]]"&nbsp;— or mice [[Genetic engineering|genetically engineered]] to lack catalase completely, experience few ill effects.<ref>{{Cite journal |vauthors=Mueller S, Riedel HD, Stremmel W |date=December 1997 |title=Direct evidence for catalase as the predominant H2O2 -removing enzyme in human erythrocytes |journal=Blood |volume=90 |issue=12 |pages=4973–8 |doi=10.1182/blood.V90.12.4973 |pmid=9389716 |doi-access=free}}</ref><ref>{{Cite journal |vauthors=Ogata M |date=February 1991 |title=Acatalasemia |journal=Human Genetics |volume=86 |issue=4 |pages=331–40 |doi=10.1007/BF00201829 |pmid=1999334 |s2cid=264033871}}</ref>

[[Image:Peroxiredoxin.png|thumb|[[Quaternary structure|Decameric]] structure of AhpC, a [[bacterial]] 2-cysteine [[peroxiredoxin]] from ''[[Salmonella enterica|Salmonella typhimurium]]''<ref>{{Cite journal |vauthors=Parsonage D, Youngblood D, Sarma G, Wood Z, Karplus P, Poole L |year=2005 |title=Analysis of the link between enzymatic activity and oligomeric state in AhpC, a bacterial peroxiredoxin |journal=Biochemistry |volume=44 |issue=31 |pages=10583–92 |doi=10.1021/bi050448i |pmc=3832347 |pmid=16060667}} [http://www.rcsb.org/pdb/explore.do?structureId=1YEX PDB 1YEX]</ref>]]

[[Peroxiredoxin]]s are peroxidases that catalyze the reduction of hydrogen peroxide, [[organic peroxide|organic hydroperoxides]], as well as [[peroxynitrite]].<ref>{{Cite journal |vauthors=Rhee SG, Chae HZ, Kim K |date=June 2005 |title=Peroxiredoxins: a historical overview and speculative preview of novel mechanisms and emerging concepts in cell signaling |journal=Free Radical Biology & Medicine |volume=38 |issue=12 |pages=1543–52 |doi=10.1016/j.freeradbiomed.2005.02.026 |pmid=15917183}}</ref> They are divided into three classes: typical 2-cysteine peroxiredoxins; atypical 2-cysteine peroxiredoxins; and 1-cysteine peroxiredoxins.<ref>{{Cite journal |vauthors=Wood ZA, Schröder E, Robin Harris J, Poole LB |date=January 2003 |title=Structure, mechanism and regulation of peroxiredoxins |journal=Trends in Biochemical Sciences |volume=28 |issue=1 |pages=32–40 |doi=10.1016/S0968-0004(02)00003-8 |pmid=12517450}}</ref> 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.<ref>{{Cite journal |vauthors=Claiborne A, Yeh JI, Mallett TC, Luba J, Crane EJ, Charrier V, Parsonage D |date=November 1999 |title=Protein-sulfenic acids: diverse roles for an unlikely player in enzyme catalysis and redox regulation |journal=Biochemistry |volume=38 |issue=47 |pages=15407–16 |doi=10.1021/bi992025k |pmid=10569923 |s2cid=29055779}}</ref> Over-oxidation of this cysteine residue in peroxiredoxins inactivates these enzymes, but this can be reversed by the action of [[sulfiredoxin]].<ref>{{Cite book |url=https://books.google.com/books?id=gHwEOH7vDmUC |title=Peroxiredoxin Systems |vauthors=Jönsson TJ, Lowther WT |year=2007 |isbn=978-1-4020-6050-2 |series=Subcellular Biochemistry |volume=44 |pages=115–41 |chapter=The peroxiredoxin repair proteins |doi=10.1007/978-1-4020-6051-9_6 |pmc=2391273 |pmid=18084892}}</ref> 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.<ref>{{Cite journal |vauthors=Neumann CA, Krause DS, Carman CV, Das S, Dubey DP, Abraham JL, Bronson RT, Fujiwara Y, Orkin SH, Van Etten RA |date=July 2003 |title=Essential role for the peroxiredoxin Prdx1 in erythrocyte antioxidant defence and tumour suppression |url=https://cloudfront.escholarship.org/dist/prd/content/qt8m75q3ct/qt8m75q3ct.pdf?t=nhvrjt |journal=Nature |volume=424 |issue=6948 |pages=561–5 |bibcode=2003Natur.424..561N |doi=10.1038/nature01819 |pmid=12891360 |s2cid=3570549}}</ref><ref>{{Cite journal |vauthors=Lee TH, Kim SU, Yu SL, Kim SH, Park DS, Moon HB, Dho SH, Kwon KS, Kwon HJ, Han YH, Jeong S, Kang SW, Shin HS, Lee KK, Rhee SG, Yu DY |date=June 2003 |title=Peroxiredoxin II is essential for sustaining life span of erythrocytes in mice |url=http://www.bloodjournal.org/cgi/content/full/101/12/5033 |journal=Blood |volume=101 |issue=12 |pages=5033–8 |doi=10.1182/blood-2002-08-2548 |pmid=12586629 |doi-access=free}}</ref><ref>{{Cite journal |vauthors=Dietz KJ, Jacob S, Oelze ML, Laxa M, Tognetti V, de Miranda SM, Baier M, Finkemeier I |year=2006 |title=The function of peroxiredoxins in plant organelle redox metabolism |journal=Journal of Experimental Botany |volume=57 |issue=8 |pages=1697–709 |doi=10.1093/jxb/erj160 |pmid=16606633 |doi-access=free}}</ref>

==== Thioredoxin and glutathione systems ====
The [[thioredoxin]] system contains the 12-k[[atomic mass unit|Da]] protein thioredoxin and its companion [[thioredoxin reductase]].<ref>{{Cite journal |vauthors=Nordberg J, Arnér ES |date=December 2001 |title=Reactive oxygen species, antioxidants, and the mammalian thioredoxin system |journal=Free Radical Biology & Medicine |volume=31 |issue=11 |pages=1287–312 |doi=10.1016/S0891-5849(01)00724-9 |pmid=11728801}}</ref> Proteins related to thioredoxin are present in all sequenced organisms. Plants, such as ''[[Arabidopsis thaliana]],'' have a particularly great diversity of isoforms.<ref>{{Cite journal |vauthors=Vieira Dos Santos C, Rey P |date=July 2006 |title=Plant thioredoxins are key actors in the oxidative stress response |journal=Trends in Plant Science |volume=11 |issue=7 |pages=329–34 |bibcode=2006TPS....11..329V |doi=10.1016/j.tplants.2006.05.005 |pmid=16782394}}</ref> The active site of thioredoxin consists of two [[vicinal (chemistry)|neighboring]] cysteines, as part of a highly conserved CXXC [[sequence motif|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.<ref>{{Cite journal |vauthors=Arnér ES, Holmgren A |date=October 2000 |title=Physiological functions of thioredoxin and thioredoxin reductase |journal=European Journal of Biochemistry |volume=267 |issue=20 |pages=6102–9 |doi=10.1046/j.1432-1327.2000.01701.x |pmid=11012661 |doi-access=free}}</ref> After being oxidized, the active thioredoxin is regenerated by the action of thioredoxin reductase, using [[NADPH]] as an [[electron donor]].<ref>{{Cite journal |vauthors=Mustacich D, Powis G |date=February 2000 |title=Thioredoxin reductase |journal=The Biochemical Journal |volume=346 |issue=1 |pages=1–8 |doi=10.1042/0264-6021:3460001 |pmc=1220815 |pmid=10657232}}</ref>

The [[glutathione]] system includes glutathione, [[glutathione reductase]], [[glutathione peroxidase]]s, and [[glutathione S-transferase|glutathione ''S''-transferases]].<ref name="MeisterB" /> This system is found in animals, plants and microorganisms.<ref name="MeisterB" /><ref>{{Cite journal |vauthors=Creissen G, Broadbent P, Stevens R, Wellburn AR, Mullineaux P |date=May 1996 |title=Manipulation of glutathione metabolism in transgenic plants |journal=Biochemical Society Transactions |volume=24 |issue=2 |pages=465–9 |doi=10.1042/bst0240465 |pmid=8736785}}</ref> Glutathione peroxidase is an enzyme containing four [[selenium]]-[[cofactor (biochemistry)|cofactors]] that catalyzes the breakdown of hydrogen peroxide and organic hydroperoxides. There are at least four different glutathione peroxidase [[isozyme]]s in animals.<ref>{{Cite journal |vauthors=Brigelius-Flohé R |date=November 1999 |title=Tissue-specific functions of individual glutathione peroxidases |journal=Free Radical Biology & Medicine |volume=27 |issue=9–10 |pages=951–65 |doi=10.1016/S0891-5849(99)00173-2 |pmid=10569628}}</ref> 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,<ref>{{Cite journal |vauthors=Ho YS, Magnenat JL, Bronson RT, Cao J, Gargano M, Sugawara M, Funk CD |date=June 1997 |title=Mice deficient in cellular glutathione peroxidase develop normally and show no increased sensitivity to hyperoxia |journal=The Journal of Biological Chemistry |volume=272 |issue=26 |pages=16644–51 |doi=10.1074/jbc.272.26.16644 |pmid=9195979 |doi-access=free}}</ref> but they are hypersensitive to induced oxidative stress.<ref>{{Cite journal |vauthors=de Haan JB, Bladier C, Griffiths P, Kelner M, O'Shea RD, Cheung NS, Bronson RT, Silvestro MJ, Wild S, Zheng SS, Beart PM, Hertzog PJ, Kola I |date=August 1998 |title=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 |journal=The Journal of Biological Chemistry |volume=273 |issue=35 |pages=22528–36 |doi=10.1074/jbc.273.35.22528 |pmid=9712879 |doi-access=free |hdl-access=free |hdl=10536/DRO/DU:30101410}}</ref> In addition, the glutathione ''S''-transferases show high activity with lipid peroxides.<ref>{{Cite journal |vauthors=Sharma R, Yang Y, Sharma A, Awasthi S, Awasthi YC |date=April 2004 |title=Antioxidant role of glutathione S-transferases: protection against oxidant toxicity and regulation of stress-mediated apoptosis |journal=Antioxidants & Redox Signaling |volume=6 |issue=2 |pages=289–300 |doi=10.1089/152308604322899350 |pmid=15025930}}</ref> These enzymes are at particularly high levels in the liver and also serve in [[detoxification]] metabolism.<ref>{{Cite journal |vauthors=Hayes JD, Flanagan JU, Jowsey IR |year=2005 |title=Glutathione transferases |journal=Annual Review of Pharmacology and Toxicology |volume=45 |pages=51–88 |doi=10.1146/annurev.pharmtox.45.120403.095857 |pmid=15822171}}</ref>

== Health research ==

=== Relation to diet ===

The dietary antioxidant [[vitamin]]s A, C, and E are essential and required in [[Dietary Reference Intake|specific daily amounts]] to prevent diseases.<ref name="nih" /><ref name="Stanner">{{Cite journal |vauthors=Stanner SA, Hughes J, Kelly CN, Buttriss J |date=May 2004 |title=A review of the epidemiological evidence for the 'antioxidant hypothesis' |journal=Public Health Nutrition |volume=7 |issue=3 |pages=407–22 |doi=10.1079/PHN2003543 |pmid=15153272 |doi-access=free}}</ref><ref>''[http://www.dietandcancerreport.org/?p=ER Food, Nutrition, Physical Activity, and the Prevention of Cancer: a Global Perspective] {{Webarchive|url=https://web.archive.org/web/20150923214620/http://www.dietandcancerreport.org/?p=ER|date=23 September 2015}}''. [[World Cancer Research Fund]] (2007). {{ISBN|978-0-9722522-2-5}}.</ref> [[Polyphenol]]s, which have antioxidant properties [[in vitro]] due to their free [[hydroxy group]]s,<ref>{{Cite journal |last1=Rice-Evans |first1=Catherine A. |last2=Miller |first2=Nicholas J. |last3=Paganga |first3=George |date=1996 |title=Structure-antioxidant activity relationships of flavonoids and phenolic acids |url=https://linkinghub.elsevier.com/retrieve/pii/0891584995022279 |journal=Free Radical Biology and Medicine |language=en |volume=20 |issue=7 |pages=933–956 |doi=10.1016/0891-5849(95)02227-9 |pmid=8743980}}</ref> are extensively metabolized by [[catechol-O-methyltransferase]] which methylates free hydroxyl groups, and thereby prevents them from acting as antioxidants in vivo.<ref>{{Cite journal |vauthors=Del Rio D, Rodriguez-Mateos A, Spencer JP, Tognolini M, Borges G, Crozier A |date=May 2013 |title=Dietary (poly)phenolics in human health: structures, bioavailability, and evidence of protective effects against chronic diseases |journal=Antioxidants & Redox Signaling |volume=18 |issue=14 |pages=1818–1892 |doi=10.1089/ars.2012.4581 |pmc=3619154 |pmid=22794138}}</ref><ref name="lpi">{{Cite web |date=2016 |title=Flavonoids |url=http://lpi.oregonstate.edu/mic/dietary-factors/phytochemicals/flavonoids |access-date=24 July 2016 |publisher=Linus Pauling Institute, Oregon State University, Corvallis}}</ref>

===Interactions===
Common pharmaceuticals (and supplements) with antioxidant properties may interfere with the efficacy of certain [[anticancer]] medication and [[radiation therapy]].<ref name="Lemmo, W Potential interactions">{{Cite journal |vauthors=Lemmo W |date=September 2014 |title=Potential interactions of prescription and over-the-counter medications having antioxidant capabilities with radiation and chemotherapy |journal=International Journal of Cancer |volume=137 |issue=11 |pages=2525–33 |doi=10.1002/ijc.29208 |pmid=25220632 |s2cid=205951215 |doi-access=free}}</ref> Pharmaceuticals and supplements that have antioxidant properties suppress the formation of free radicals by inhibiting oxidation processes. [[Radiation therapy]] induce oxidative stress that damages essential components of cancer cells, such as proteins, nucleic acids, and lipids that comprise cell membranes.<ref>{{Cite journal |last1=Forman |first1=Henry Jay |last2=Zhang |first2=Hongqiao |date=June 30, 2021 |title=Targeting oxidative stress in disease: promise and limitations of antioxidant therapy |journal=Nature Reviews Drug Discovery |language=en |volume=20 |issue=9 |pages=689–709 |doi=10.1038/s41573-021-00233-1 |issn=1474-1784 |pmc=8243062 |pmid=34194012}}</ref>

=== Adverse effects ===
{{see also|Antioxidative stress}}
[[Image:Phytate.svg|thumb|right|class=skin-invert-image|Structure of the metal chelator [[phytic acid]]]]

Relatively strong reducing acids can have [[antinutrient]] effects by binding to [[dietary mineral]]s such as [[iron]] and [[zinc]] in the [[Human gastrointestinal tract|gastrointestinal tract]] and preventing them from being absorbed.<ref>{{Cite journal |vauthors=Hurrell RF |date=September 2003 |title=Influence of vegetable protein sources on trace element and mineral bioavailability |journal=The Journal of Nutrition |volume=133 |issue=9 |pages=2973S–7S |doi=10.1093/jn/133.9.2973S |pmid=12949395 |doi-access=free}}</ref> Examples are [[oxalic acid]], [[tannin]]s and [[phytic acid]], which are high in plant-based diets.<ref>{{Cite journal |vauthors=Hunt JR |date=September 2003 |title=Bioavailability of iron, zinc, and other trace minerals from vegetarian diets |journal=The American Journal of Clinical Nutrition |volume=78 |issue=3 Suppl |pages=633S–639S |doi=10.1093/ajcn/78.3.633S |pmid=12936958 |doi-access=free}}</ref> [[Calcium]] and iron deficiencies are not uncommon in diets in [[Developing country|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.<ref>{{Cite journal |vauthors=Gibson RS, Perlas L, Hotz C |date=May 2006 |title=Improving the bioavailability of nutrients in plant foods at the household level |journal=The Proceedings of the Nutrition Society |volume=65 |issue=2 |pages=160–8 |doi=10.1079/PNS2006489 |pmid=16672077 |doi-access=free}}</ref>

{| class="wikitable" style="margin-left: auto; margin-right: auto;"
|-
!Foods
!Reducing acid present
|-
| style="text-align:center;" |[[Cocoa bean]] and chocolate, [[spinach]], [[turnip]] and [[rhubarb]]<ref name="Mosha">{{Cite journal |vauthors=Mosha TC, Gaga HE, Pace RD, Laswai HS, Mtebe K |date=June 1995 |title=Effect of blanching on the content of antinutritional factors in selected vegetables |journal=Plant Foods for Human Nutrition |volume=47 |issue=4 |pages=361–7 |doi=10.1007/BF01088275 |pmid=8577655 |s2cid=1118651}}</ref>
| style="text-align:center;" |[[Oxalic acid]]
|-
| style="text-align:center;" |[[Whole grain]]s, maize, [[legume]]s<ref>{{Cite journal |vauthors=Sandberg AS |date=December 2002 |title=Bioavailability of minerals in legumes |journal=The British Journal of Nutrition |volume=88 |issue=Suppl 3 |pages=S281–5 |doi=10.1079/BJN/2002718 |pmid=12498628 |doi-access=free}}</ref>
| style="text-align:center;" |[[Phytic acid]]
|-
| style="text-align:center;" |Tea, [[bean]]s, [[cabbage]]<ref name="Mosha" /><ref name="Beecher">{{Cite journal |vauthors=Beecher GR |date=October 2003 |title=Overview of dietary flavonoids: nomenclature, occurrence and intake |journal=The Journal of Nutrition |volume=133 |issue=10 |pages=3248S–3254S |doi=10.1093/jn/133.10.3248S |pmid=14519822 |doi-access=free}}</ref>
| style="text-align:center;" |[[Tannin]]s
|}

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.<ref>{{Cite journal |vauthors=Omenn GS, Goodman GE, Thornquist MD, Balmes J, Cullen MR, Glass A, Keogh JP, Meyskens FL, Valanis B, Williams JH, Barnhart S, Cherniack MG, Brodkin CA, Hammar S |date=November 1996 |title=Risk factors for lung cancer and for intervention effects in CARET, the Beta-Carotene and Retinol Efficacy Trial |url=https://academic.oup.com/jnci/article-pdf/88/21/1550/7811338/88-21-1550.pdf |journal=Journal of the National Cancer Institute |volume=88 |issue=21 |pages=1550–9 |doi=10.1093/jnci/88.21.1550 |pmid=8901853 |doi-access=free}}</ref> Subsequent studies confirmed these adverse effects.<ref>{{Cite journal |vauthors=Albanes D |date=June 1999 |title=Beta-carotene and lung cancer: a case study |journal=The American Journal of Clinical Nutrition |volume=69 |issue=6 |pages=1345S–50S |doi=10.1093/ajcn/69.6.1345S |pmid=10359235 |doi-access=free}}</ref> 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.<ref name="Bjelakovic">{{Cite journal |vauthors=Bjelakovic G, Nikolova D, Gluud LL, Simonetti RG, Gluud C |date=February 2007 |title=Mortality in randomized trials of antioxidant supplements for primary and secondary prevention: systematic review and meta-analysis |journal=JAMA |volume=297 |issue=8 |pages=842–57 |doi=10.1001/jama.297.8.842 |pmid=17327526}}</ref> 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.<ref name="Bjelakovic_2012">{{Cite journal |vauthors=Bjelakovic G, Nikolova D, Gluud LL, Simonetti RG, Gluud C |date=14 March 2012 |title=Antioxidant supplements for prevention of mortality in healthy participants and patients with various diseases |journal=The Cochrane Database of Systematic Reviews |volume=2012 |issue=3 |pages=CD007176 |doi=10.1002/14651858.CD007176.pub2 |pmc=8407395 |pmid=22419320 |hdl-access=free |hdl=10138/136201}}</ref> As the majority of these low-bias trials dealt with either [[Old age|elderly people]], or people with disease, these results may not apply to the general population.<ref>[https://www.sciencedaily.com/releases/2007/02/070228172604.htm Study Citing Antioxidant Vitamin Risks Based On Flawed Methodology, Experts Argue] News release from [[Oregon State University]] published on ScienceDaily. Retrieved 19 April 2007</ref> This meta-analysis was later repeated and extended by the same authors, confirming the previous results.<ref name="Bjelakovic_2012" /> These two publications are consistent with some previous meta-analyses that also suggested that vitamin E supplementation increased mortality,<ref>{{Cite journal |vauthors=Miller ER, Pastor-Barriuso R, Dalal D, Riemersma RA, Appel LJ, Guallar E |date=January 2005 |title=Meta-analysis: high-dosage vitamin E supplementation may increase all-cause mortality |journal=Annals of Internal Medicine |volume=142 |issue=1 |pages=37–46 |doi=10.7326/0003-4819-142-1-200501040-00110 |pmid=15537682 |doi-access=free}}</ref> and that antioxidant supplements increased the risk of [[Colorectal cancer|colon cancer]].<ref name="Bjelakovic_2006">{{Cite journal |vauthors=Bjelakovic G, Nagorni A, Nikolova D, Simonetti RG, Bjelakovic M, Gluud C |date=July 2006 |title=Meta-analysis: antioxidant supplements for primary and secondary prevention of colorectal adenoma |journal=Alimentary Pharmacology & Therapeutics |volume=24 |issue=2 |pages=281–91 |doi=10.1111/j.1365-2036.2006.02970.x |pmid=16842454 |s2cid=20452618 |doi-access=free}}</ref> [[Beta-carotene]] may also increase [[lung cancer]].<ref name="Bjelakovic_2006" /><ref>{{Cite journal |vauthors=Cortés-Jofré M, Rueda JR, Asenjo-Lobos C, Madrid E, Bonfill Cosp X |date=March 2020 |title=Drugs for preventing lung cancer in healthy people |journal=The Cochrane Database of Systematic Reviews |volume=2020 |issue=3 |pages=CD002141 |doi=10.1002/14651858.CD002141.pub3 |pmc=7059884 |pmid=32130738}}</ref> 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.<ref name="Stanner" /><ref name="Shenkin">{{Cite journal |vauthors=Shenkin A |date=February 2006 |title=The key role of micronutrients |journal=Clinical Nutrition |volume=25 |issue=1 |pages=1–13 |doi=10.1016/j.clnu.2005.11.006 |pmid=16376462}}</ref><ref name="Bjelakovic" />

=== Exercise and muscle soreness ===
A 2017 review showed that taking antioxidant dietary supplements before or after exercise is unlikely to produce a noticeable reduction in muscle soreness after a person exercises.<ref>{{Cite journal |last1=Ranchordas |first1=Mayur K. |last2=Rogerson |first2=David |last3=Soltani |first3=Hora |last4=Costello |first4=Joseph T. |date=2017-12-14 |title=Antioxidants for preventing and reducing muscle soreness after exercise |journal=The Cochrane Database of Systematic Reviews |volume=2017 |issue=12 |pages=CD009789 |doi=10.1002/14651858.CD009789.pub2 |issn=1469-493X |pmc=6486214 |pmid=29238948}}</ref>

== Levels in food ==
{{further|List of antioxidants in food|Polyphenol antioxidant}}
[[Image:Vegetarian diet.jpg|upright|thumb|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.<ref>{{Cite journal |vauthors=Rodriguez-Amaya DB |year=2003 |title=Food carotenoids: analysis, composition and alterations during storage and processing of foods |journal=Forum of Nutrition |volume=56 |pages=35–7 |pmid=15806788}}</ref> 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.<ref>{{Cite journal |vauthors=Maiani G, Castón MJ, Catasta G, Toti E, Cambrodón IG, Bysted A, Granado-Lorencio F, Olmedilla-Alonso B, Knuthsen P, Valoti M, Böhm V, Mayer-Miebach E, Behsnilian D, Schlemmer U |date=September 2009 |title=Carotenoids: actual knowledge on food sources, intakes, stability and bioavailability and their protective role in humans |url=https://openagrar.bmel-forschung.de/receive/import_mods_00002107 |url-status=dead |journal=Molecular Nutrition & Food Research |volume=53 |issue=Suppl 2 |pages=S194–218 |doi=10.1002/mnfr.200800053 |pmid=19035552 |archive-url=https://web.archive.org/web/20180927113314/https://openagrar.bmel-forschung.de/receive/import_mods_00002107 |archive-date=27 September 2018 |access-date=18 April 2017 |hdl=10261/77697}}</ref> Processed food contains fewer antioxidant vitamins than fresh and uncooked foods, as preparation exposes food to heat and oxygen.<ref>{{Cite journal |vauthors=Henry CJ, Heppell N |date=February 2002 |title=Nutritional losses and gains during processing: future problems and issues |journal=The Proceedings of the Nutrition Society |volume=61 |issue=1 |pages=145–8 |doi=10.1079/PNS2001142 |pmid=12002789 |doi-access=free}}</ref>

{| class="wikitable" style="margin-left: auto; margin-right: auto;"
|-
!Antioxidant vitamins
!Foods containing high levels of antioxidant vitamins<ref name="Beecher" /><ref>{{Cite web |title=Antioxidants and Cancer Prevention: Fact Sheet |url=http://www.cancer.gov/cancertopics/factsheet/antioxidantsprevention |url-status=live |archive-url=https://web.archive.org/web/20070304120554/http://www.cancer.gov/cancertopics/factsheet/antioxidantsprevention |archive-date=4 March 2007 |access-date=27 February 2007 |publisher=National Cancer Institute}}</ref><ref>{{Cite journal |vauthors=Ortega R |date=December 2006 |title=Importance of functional foods in the Mediterranean diet |journal=Public Health Nutrition |volume=9 |issue=8A |pages=1136–40 |doi=10.1017/S1368980007668530 |pmid=17378953 |doi-access=free}}</ref>
|-
| [[Vitamin C]] (ascorbic acid)
| Fresh or frozen fruits and vegetables
|-
| [[Vitamin E]] (tocopherols, tocotrienols)
| [[Vegetable oil]]s, [[nut (fruit)|nuts]], and [[seed]]s
|-
| [[Carotenoid]]s ([[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]].<ref name="Turunen" /> 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.<ref>{{Cite journal |vauthors=Witschi A, Reddy S, Stofer B, Lauterburg BH |year=1992 |title=The systemic availability of oral glutathione |journal=European Journal of Clinical Pharmacology |volume=43 |issue=6 |pages=667–9 |doi=10.1007/BF02284971 |pmid=1362956 |s2cid=27606314}}</ref><ref>{{Cite journal |vauthors=Flagg EW, Coates RJ, Eley JW, Jones DP, Gunter EW, Byers TE, Block GS, Greenberg RS |year=1994 |title=Dietary glutathione intake in humans and the relationship between intake and plasma total glutathione level |journal=Nutrition and Cancer |volume=21 |issue=1 |pages=33–46 |doi=10.1080/01635589409514302 |pmid=8183721}}</ref> Although large amounts of sulfur-containing amino acids such as [[acetylcysteine]] can increase glutathione,<ref name="Dodd">{{Cite journal |vauthors=Dodd S, Dean O, Copolov DL, Malhi GS, Berk M |date=December 2008 |title=N-acetylcysteine for antioxidant therapy: pharmacology and clinical utility |journal=Expert Opinion on Biological Therapy |volume=8 |issue=12 |pages=1955–62 |doi=10.1517/14728220802517901 |pmid=18990082 |s2cid=74736842}}</ref> no evidence exists that eating high levels of these glutathione precursors is beneficial for healthy adults.<ref>{{Cite journal |vauthors=van de Poll MC, Dejong CH, Soeters PB |date=June 2006 |title=Adequate range for sulfur-containing amino acids and biomarkers for their excess: lessons from enteral and parenteral nutrition |journal=The Journal of Nutrition |volume=136 |issue=6 Suppl |pages=1694S–1700S |doi=10.1093/jn/136.6.1694S |pmid=16702341 |doi-access=free}}</ref>

=== 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 [[polyphenol]]s.<ref>{{Cite journal |vauthors=Cao G, Alessio HM, Cutler RG |date=March 1993 |title=Oxygen-radical absorbance capacity assay for antioxidants |url=https://zenodo.org/record/1258621 |journal=Free Radical Biology & Medicine |volume=14 |issue=3 |pages=303–11 |doi=10.1016/0891-5849(93)90027-R |pmid=8458588}}</ref><ref>{{Cite journal |vauthors=Ou B, Hampsch-Woodill M, Prior RL |date=October 2001 |title=Development and validation of an improved oxygen radical absorbance capacity assay using fluorescein as the fluorescent probe |journal=Journal of Agricultural and Food Chemistry |volume=49 |issue=10 |pages=4619–26 |doi=10.1021/jf010586o |pmid=11599998|bibcode=2001JAFC...49.4619O }}</ref> 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]]''.<ref name="USDAx">{{Cite web |date=16 May 2012 |title=Withdrawn: Oxygen Radical Absorbance Capacity (ORAC) of Selected Foods, Release 2 (2010) |url=http://www.ars.usda.gov/services/docs.htm?docid=15866 |access-date=13 June 2012 |publisher=United States Department of Agriculture, Agricultural Research Service}}</ref> Consequently, the ORAC method, derived only from ''in vitro'' experiments, is no longer considered relevant to human diets or [[biology]], as of 2010.<ref name="USDAx" />

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.<ref>{{Cite journal |vauthors=Prior RL, Wu X, Schaich K |date=May 2005 |title=Standardized methods for the determination of antioxidant capacity and phenolics in foods and dietary supplements |url=https://naldc.nal.usda.gov/Policy.pdf |url-status=dead |journal=Journal of Agricultural and Food Chemistry |volume=53 |issue=10 |pages=4290–302 |doi=10.1021/jf0502698 |pmid=15884874 |archive-url=https://web.archive.org/web/20161229203509/https://naldc.nal.usda.gov/Policy.pdf |archive-date=29 December 2016 |access-date=24 October 2017}}</ref>

== References ==
{{reflist}}

==Further reading==
{{refbegin}}
* {{Cite book |title=Free Radicals in Biology and Medicine |vauthors=Halliwell B, Gutteridge JM |date=2015 |publisher=Oxford University Press |isbn=978-0-19-856869-8 |edition=5th}}
* {{Cite book |title=Oxygen: The Molecule That Made the World |vauthors=Lane N |date=2003 |publisher=Oxford University Press |isbn=978-0-19-860783-0}}
* {{Cite book |title=Antioxidants in Food: Practical Applications |vauthors=Pokorny J, Yanishlieva N, Gordon MH |date=2001 |publisher=CRC Press |isbn=978-0-8493-1222-9}}
{{refend}}

==External links==
* {{Commons category-inline|Antioxidants}}

{{Antioxidants}}

[[Category:Anti-aging substances]]
[[Category:Antioxidants| ]]
[[Category:Physiology]]
[[Category:Process chemicals]]
[[Category:Redox]]