Antioxidant

Antioxidant

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Encyclopedia
An antioxidant is a molecule
Molecule
A molecule is an electrically neutral group of at least two atoms held together by covalent chemical bonds. Molecules are distinguished from ions by their electrical charge...

 capable of inhibiting the oxidation
Redox
Redox reactions describe all chemical reactions in which atoms have their oxidation state changed....

 of other molecules. Oxidation is a chemical reaction
Chemical reaction
A chemical reaction is a process that leads to the transformation of one set of chemical substances to another. Chemical reactions can be either spontaneous, requiring no input of energy, or non-spontaneous, typically following the input of some type of energy, such as heat, light or electricity...

 that transfers electron
Electron
The electron is a subatomic particle with a negative elementary electric charge. It has no known components or substructure; in other words, it is generally thought to be an elementary particle. An electron has a mass that is approximately 1/1836 that of the proton...

s or hydrogen from a substance to an oxidizing agent
Oxidizing agent
An oxidizing agent can be defined as a substance that removes electrons from another reactant in a redox chemical reaction...

. Oxidation reactions can produce free radical
Radical (chemistry)
Radicals are atoms, molecules, or ions with unpaired electrons on an open shell configuration. Free radicals may have positive, negative, or zero charge...

s. In turn, these radicals can start chain reaction
Chain reaction
A chain reaction is a sequence of reactions where a reactive product or by-product causes additional reactions to take place. In a chain reaction, positive feedback leads to a self-amplifying chain of events....

s. When the chain reaction occurs in a cell
Cell (biology)
The cell is the basic structural and functional unit of all known living organisms. It is the smallest unit of life that is classified as a living thing, and is often called the building block of life. The Alberts text discusses how the "cellular building blocks" move to shape developing embryos....

, it can cause damage or death to the cell. When the chain reaction occurs in a purified monomer, it produces a polymer resin, such as a plastic
Thermoplastic
Thermoplastic, also known as a thermosoftening plastic, is a polymer that turns to a liquid when heated and freezes to a very glassy state when cooled sufficiently...

, a synthetic fiber
Synthetic fiber
Synthetic fibers are the result of extensive research by scientists to improve on naturally occurring animal and plant fibers. In general, synthetic fibers are created by forcing, usually through extrusion, fiber forming materials through holes into the air, forming a thread...

, or an oil paint film
Drying oil
A drying oil is an oil that hardens to a tough, solid film after a period of exposure to air. The oil hardens through a chemical reaction in which the components crosslink by the action of oxygen . Drying oils are a key component of oil paint and some varnishes...

. Antioxidants terminate these chain reactions by removing free radical intermediates, and inhibit other oxidation reactions. They do this by being oxidized themselves, so antioxidants are often reducing agent
Reducing agent
A reducing agent is the element or compound in a reduction-oxidation reaction that donates an electron to another species; however, since the reducer loses an electron we say it is "oxidized"...

s such as thiol
Thiol
In organic chemistry, a thiol is an organosulfur compound that contains a carbon-bonded sulfhydryl group...

s, ascorbic acid
Ascorbic acid
Ascorbic acid is a naturally occurring organic compound with antioxidant properties. It is a white solid, but impure samples can appear yellowish. It dissolves well in water to give mildly acidic solutions. Ascorbic acid is one form of vitamin C. The name is derived from a- and scorbutus , the...

, or polyphenol
Polyphenol antioxidant
A polyphenol antioxidant is a type of antioxidant containing a polyphenolic substructure. Numbering over 4,000 distinct species, many of these compounds have antioxidant activity in vitro but are unlikely to have antioxidant roles in vivo...

s.

Antioxidants are important additives in gasoline. These antioxidants prevent the formation of gums that interfere with the operation of internal combustion engines.
Although oxidation reactions are crucial for life, they can also be damaging; plant
Plant
Plants are living organisms belonging to the kingdom Plantae. Precise definitions of the kingdom vary, but as the term is used here, plants include familiar organisms such as trees, flowers, herbs, bushes, grasses, vines, ferns, mosses, and green algae. The group is also called green plants or...

s and animal
Animal
Animals are a major group of multicellular, eukaryotic organisms of the kingdom Animalia or Metazoa. Their body plan eventually becomes fixed as they develop, although some undergo a process of metamorphosis later on in their life. Most animals are motile, meaning they can move spontaneously and...

s maintain complex systems of multiple types of antioxidants, such as glutathione
Glutathione
Glutathione is a tripeptide that contains an unusual peptide linkage between the amine group of cysteine and the carboxyl group of the glutamate side-chain...

, vitamin C
Vitamin C
Vitamin C or L-ascorbic acid or L-ascorbate is an essential nutrient for humans and certain other animal species. In living organisms ascorbate acts as an antioxidant by protecting the body against oxidative stress...

, and vitamin E
Vitamin E
Vitamin E is used to refer to a group of fat-soluble compounds that include both tocopherols and tocotrienols. There are many different forms of vitamin E, of which γ-tocopherol is the most common in the North American diet. γ-Tocopherol can be found in corn oil, soybean oil, margarine and dressings...

 as well as enzyme
Enzyme
Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...

s such as catalase
Catalase
Catalase is a common enzyme found in nearly all living organisms that are exposed to oxygen, where it catalyzes the decomposition of hydrogen peroxide to water and oxygen...

, superoxide dismutase
Superoxide dismutase
Superoxide dismutases are a class of enzymes that catalyze the dismutation of superoxide into oxygen and hydrogen peroxide. As such, they are an important antioxidant defense in nearly all cells exposed to oxygen...

 and various peroxidase
Peroxidase
Peroxidases are a large family of enzymes that typically catalyze a reaction of the form:For many of these enzymes the optimal substrate is hydrogen peroxide, but others are more active with organic hydroperoxides such as lipid peroxides...

s. Low levels of antioxidants, or inhibition
Enzyme inhibitor
An enzyme inhibitor is a molecule that binds to enzymes and decreases their activity. Since blocking an enzyme's activity can kill a pathogen or correct a metabolic imbalance, many drugs are enzyme inhibitors. They are also used as herbicides and pesticides...

 of the antioxidant enzymes, cause oxidative stress
Oxidative stress
Oxidative stress represents an imbalance between the production and manifestation of reactive oxygen species and a biological system's ability to readily detoxify the reactive intermediates or to repair the resulting damage...

 and may damage or kill cells.

As oxidative stress appears to be an important part of many human diseases, the use of antioxidants in pharmacology
Pharmacology
Pharmacology is the branch of medicine and biology concerned with the study of drug action. More specifically, it is the study of the interactions that occur between a living organism and chemicals that affect normal or abnormal biochemical function...

 is intensively studied, particularly as treatments for stroke
Stroke
A stroke, previously known medically as a cerebrovascular accident , is the rapidly developing loss of brain function due to disturbance in the blood supply to the brain. This can be due to ischemia caused by blockage , or a hemorrhage...

 and neurodegenerative diseases. However, it is unknown whether oxidative stress is the cause or the consequence of disease.

Antioxidants are widely used as ingredients in dietary supplements and have been investigated for the prevention of diseases such as cancer
Cancer
Cancer , known medically as a malignant neoplasm, is a large group of different diseases, all involving unregulated cell growth. In cancer, cells divide and grow uncontrollably, forming malignant tumors, and invade nearby parts of the body. The cancer may also spread to more distant parts of the...

, coronary heart disease
Coronary heart disease
Coronary artery disease is the end result of the accumulation of atheromatous plaques within the walls of the coronary arteries that supply the myocardium with oxygen and nutrients. It is sometimes also called coronary heart disease...

 and even altitude sickness
Altitude sickness
Altitude sickness—also known as acute mountain sickness , altitude illness, hypobaropathy, or soroche—is a pathological effect of high altitude on humans, caused by acute exposure to low partial pressure of oxygen at high altitude...

. Although initial studies suggested that antioxidant supplements might promote health, later large clinical trial
Clinical trial
Clinical trials are a set of procedures in medical research and drug development that are conducted to allow safety and efficacy data to be collected for health interventions...

s did not detect any benefit and suggested instead that excess supplementation is harmful. In addition to these uses of natural antioxidants in medicine, these compounds have many industrial uses, such as preservatives in food and cosmetics and preventing the degradation of rubber
Rubber
Natural rubber, also called India rubber or caoutchouc, is an elastomer that was originally derived from latex, a milky colloid produced by some plants. The plants would be ‘tapped’, that is, an incision made into the bark of the tree and the sticky, milk colored latex sap collected and refined...

 and gasoline
Gasoline
Gasoline , or petrol , is a toxic, translucent, petroleum-derived liquid that is primarily used as a fuel in internal combustion engines. It consists mostly of organic compounds obtained by the fractional distillation of petroleum, enhanced with a variety of additives. Some gasolines also contain...

.

History


As part of their adaptation from marine life, terrestrial plants began producing non-marine antioxidants such as ascorbic acid
Ascorbic acid
Ascorbic acid is a naturally occurring organic compound with antioxidant properties. It is a white solid, but impure samples can appear yellowish. It dissolves well in water to give mildly acidic solutions. Ascorbic acid is one form of vitamin C. The name is derived from a- and scorbutus , the...

 (Vitamin C
Vitamin C
Vitamin C or L-ascorbic acid or L-ascorbate is an essential nutrient for humans and certain other animal species. In living organisms ascorbate acts as an antioxidant by protecting the body against oxidative stress...

), polyphenol
Polyphenol antioxidant
A polyphenol antioxidant is a type of antioxidant containing a polyphenolic substructure. Numbering over 4,000 distinct species, many of these compounds have antioxidant activity in vitro but are unlikely to have antioxidant roles in vivo...

s and tocopherol
Tocopherol
Tocopherols are a class of chemical compounds of which many have vitamin E activity. It is a series of organic compounds consisting of various methylated phenols...

s. The evolution of angiosperm plants between 50 and 200 million years ago resulted in the development of many antioxidant pigments — particularly during the Jurassic
Jurassic
The Jurassic is a geologic period and system that extends from about Mya to  Mya, that is, from the end of the Triassic to the beginning of the Cretaceous. The Jurassic constitutes the middle period of the Mesozoic era, also known as the age of reptiles. The start of the period is marked by...

 period — as chemical defences against reactive oxygen species
Reactive oxygen species
Reactive oxygen species are chemically reactive molecules containing oxygen. Examples include oxygen ions and peroxides. Reactive oxygen species are highly reactive due to the presence of unpaired valence shell electrons....

 that are byproducts of photosynthesis
Photosynthesis
Photosynthesis is a chemical process that converts carbon dioxide into organic compounds, especially sugars, using the energy from sunlight. Photosynthesis occurs in plants, algae, and many species of bacteria, but not in archaea. Photosynthetic organisms are called photoautotrophs, since they can...

. The term antioxidant originally was used to refer specifically to a chemical that prevented the consumption of oxygen. In the late 19th and early 20th centuries, extensive study was devoted to the uses of antioxidants in important industrial processes, such as the prevention of metal corrosion
Corrosion
Corrosion is the disintegration of an engineered material into its constituent atoms due to chemical reactions with its surroundings. In the most common use of the word, this means electrochemical oxidation of metals in reaction with an oxidant such as oxygen...

, the vulcanization
Vulcanization
Vulcanization or vulcanisation is a chemical process for converting rubber or related polymers into more durable materials via the addition of sulfur or other equivalent "curatives." These additives modify the polymer by forming crosslinks between individual polymer chains. Vulcanized material is...

 of rubber, and the polymerization
Polymerization
In polymer chemistry, polymerization is a process of reacting monomer molecules together in a chemical reaction to form three-dimensional networks or polymer chains...

 of fuels in the fouling
Fouling
Fouling refers to the accumulation of unwanted material on solid surfaces, most often in an aquatic environment. The fouling material can consist of either living organisms or a non-living substance...

 of internal combustion engine
Internal combustion engine
The internal combustion engine is an engine in which the combustion of a fuel occurs with an oxidizer in a combustion chamber. In an internal combustion engine, the expansion of the high-temperature and high -pressure gases produced by combustion apply direct force to some component of the engine...

s.

Early research on the role of antioxidants in biology focused on their use in preventing the oxidation of unsaturated fat
Unsaturated fat
An unsaturated fat is a fat or fatty acid in which there is at least one double bond within the fatty acid chain. A fat molecule is monounsaturated if it contains one double bond, and polyunsaturated if it contains more than one double bond. Where double bonds are formed, hydrogen atoms are...

s, which is the cause of rancidity. Antioxidant activity could be measured simply by placing the fat in a closed container with oxygen and measuring the rate of oxygen consumption. However, it was the identification of vitamins A
Vitamin A
Vitamin A is a vitamin that is needed by the retina of the eye in the form of a specific metabolite, the light-absorbing molecule retinal, that is necessary for both low-light and color vision...

, C
Vitamin C
Vitamin C or L-ascorbic acid or L-ascorbate is an essential nutrient for humans and certain other animal species. In living organisms ascorbate acts as an antioxidant by protecting the body against oxidative stress...

, and E
Vitamin E
Vitamin E is used to refer to a group of fat-soluble compounds that include both tocopherols and tocotrienols. There are many different forms of vitamin E, of which γ-tocopherol is the most common in the North American diet. γ-Tocopherol can be found in corn oil, soybean oil, margarine and dressings...

 as antioxidants that revolutionized the field and led to the realization of the importance of antioxidants in the biochemistry of living organisms
Organism
In biology, an organism is any contiguous living system . In at least some form, all organisms are capable of response to stimuli, reproduction, growth and development, and maintenance of homoeostasis as a stable whole.An organism may either be unicellular or, as in the case of humans, comprise...

.

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. Research into how vitamin E
Vitamin E
Vitamin E is used to refer to a group of fat-soluble compounds that include both tocopherols and tocotrienols. There are many different forms of vitamin E, of which γ-tocopherol is the most common in the North American diet. γ-Tocopherol can be found in corn oil, soybean oil, margarine and dressings...

 prevents the process of lipid peroxidation
Lipid peroxidation
Lipid peroxidation refers to the oxidative degradation of lipids. It is the process in which free radicals "steal" electrons from the lipids in cell membranes, resulting in cell damage. This process proceeds by a free radical chain reaction mechanism...

 led to the identification of antioxidants as reducing agents that prevent oxidative reactions, often by scavenging
Scavenger (chemistry)
A scavenger in chemistry is a chemical substance added to a mixture in order to remove or inactivate impurities or unwanted reaction products. Their use is wide-ranged:...

 reactive oxygen species
Reactive oxygen species
Reactive oxygen species are chemically reactive molecules containing oxygen. Examples include oxygen ions and peroxides. Reactive oxygen species are highly reactive due to the presence of unpaired valence shell electrons....

 before they can damage cells.

The oxidative challenge in biology


A paradox
Paradox
Similar to Circular reasoning, A paradox is a seemingly true statement or group of statements that lead to a contradiction or a situation which seems to defy logic or intuition...

 in metabolism
Metabolism
Metabolism is the set of chemical reactions that happen in the cells of living organisms to sustain life. These processes allow organisms to grow and reproduce, maintain their structures, and respond to their environments. Metabolism is usually divided into two categories...

 is that while the vast majority of complex life on Earth
Life on Earth
Life on Earth: A Natural History by David Attenborough is a television natural history series made by the BBC in association with Warner Bros. and Reiner Moritz Productions...

 requires oxygen
Oxygen
Oxygen is the element with atomic number 8 and represented by the symbol O. Its name derives from the Greek roots ὀξύς and -γενής , because at the time of naming, it was mistakenly thought that all acids required oxygen in their composition...

 for its existence, oxygen is a highly reactive molecule that damages living organisms by producing reactive oxygen species
Reactive oxygen species
Reactive oxygen species are chemically reactive molecules containing oxygen. Examples include oxygen ions and peroxides. Reactive oxygen species are highly reactive due to the presence of unpaired valence shell electrons....

. Consequently, organisms contain a complex network of antioxidant metabolite
Metabolite
Metabolites are the intermediates and products of metabolism. The term metabolite is usually restricted to small molecules. A primary metabolite is directly involved in normal growth, development, and reproduction. Alcohol is an example of a primary metabolite produced in large-scale by industrial...

s and enzyme
Enzyme
Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...

s that work together to prevent oxidative damage to cellular components such as DNA
DNA
Deoxyribonucleic acid is a nucleic acid that contains the genetic instructions used in the development and functioning of all known living organisms . The DNA segments that carry this genetic information are called genes, but other DNA sequences have structural purposes, or are involved in...

, protein
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...

s and lipid
Lipid
Lipids constitute a broad group of naturally occurring molecules that include fats, waxes, sterols, fat-soluble vitamins , monoglycerides, diglycerides, triglycerides, phospholipids, and others...

s. In general, antioxidant systems either prevent these reactive species from being formed, or remove them before they can damage vital components of the cell. However, since reactive oxygen species do have useful functions in cells, such as redox signaling
Redox signaling
Redox signaling is when free radicals, reactive oxygen species , and other electronically activated species such as nitric oxide act as biological messengers. Arguably, hydrogen sulfide and carbon monoxide are also redox signaling molecules...

, the function of antioxidant systems is not to remove oxidants entirely, but instead to keep them at an optimum level.

The reactive oxygen species produced in cells include hydrogen peroxide
Hydrogen peroxide
Hydrogen peroxide is the simplest peroxide and an oxidizer. Hydrogen peroxide is a clear liquid, slightly more viscous than water. In dilute solution, it appears colorless. With its oxidizing properties, hydrogen peroxide is often used as a bleach or cleaning agent...

 (H2O2), hypochlorous acid
Hypochlorous acid
Hypochlorous acid is a weak acid with the chemical formula HClO. It forms when chlorine dissolves in water. It cannot be isolated in pure form due to rapid equilibration with its precursor...

 (HClO), and free radicals such as the hydroxyl radical
Hydroxyl radical
The hydroxyl radical, •OH, is the neutral form of the hydroxide ion . Hydroxyl radicals are highly reactive and consequently short-lived; however, they form an important part of radical chemistry. Most notably hydroxyl radicals are produced from the decomposition of hydroperoxides or, in...

 (·OH) and the superoxide anion
Superoxide
A superoxide, also known by the obsolete name hyperoxide, is a compound that possesses the superoxide anion with the chemical formula O2−. The systematic name of the anion is dioxide. It is important as the product of the one-electron reduction of dioxygen O2, which occurs widely in nature...

 (O2). The hydroxyl radical is particularly unstable and will react rapidly and non-specifically with most biological molecules. This species is produced from hydrogen peroxide in metal-catalyzed
Catalysis
Catalysis is the change in rate of a chemical reaction due to the participation of a substance called a catalyst. Unlike other reagents that participate in the chemical reaction, a catalyst is not consumed by the reaction itself. A catalyst may participate in multiple chemical transformations....

 redox reactions such as the Fenton reaction. These oxidants can damage cells by starting chemical chain reactions such as lipid peroxidation, or by oxidizing DNA or proteins. Damage to DNA can cause mutation
Mutation
In molecular biology and genetics, mutations are changes in a genomic sequence: the DNA sequence of a cell's genome or the DNA or RNA sequence of a virus. They can be defined as sudden and spontaneous changes in the cell. Mutations are caused by radiation, viruses, transposons and mutagenic...

s and possibly cancer
Cancer
Cancer , known medically as a malignant neoplasm, is a large group of different diseases, all involving unregulated cell growth. In cancer, cells divide and grow uncontrollably, forming malignant tumors, and invade nearby parts of the body. The cancer may also spread to more distant parts of the...

, if not reversed by DNA repair
DNA repair
DNA repair refers to a collection of processes by which a cell identifies and corrects damage to the DNA molecules that encode its genome. In human cells, both normal metabolic activities and environmental factors such as UV light and radiation can cause DNA damage, resulting in as many as 1...

 mechanisms, while damage to protein
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...

s causes enzyme inhibition, denaturation
Denaturation (biochemistry)
Denaturation is a process in which proteins or nucleic acids lose their tertiary structure and secondary structure by application of some external stress or compound, such as a strong acid or base, a concentrated inorganic salt, an organic solvent , or heat...

 and protein degradation
Proteasome
Proteasomes are very large protein complexes inside all eukaryotes and archaea, and in some bacteria.  In eukaryotes, they are located in the nucleus and the cytoplasm.  The main function of the proteasome is to degrade unneeded or damaged proteins by proteolysis, a chemical reaction that breaks...

.

The use of oxygen as part of the process for generating metabolic energy produces reactive oxygen species. In this process, the superoxide anion is produced as a by-product
By-product
A by-product is a secondary product derived from a manufacturing process or chemical reaction. It is not the primary product or service being produced.A by-product can be useful and marketable or it can be considered waste....

 of several steps in the electron transport chain
Electron transport chain
An electron transport chain couples electron transfer between an electron donor and an electron acceptor with the transfer of H+ ions across a membrane. The resulting electrochemical proton gradient is used to generate chemical energy in the form of adenosine triphosphate...

. Particularly important is the reduction of coenzyme Q
Coenzyme Q
Coenzyme Q10, also known as ubiquinone, ubidecarenone, coenzyme Q, and abbreviated at times to CoQ10 , CoQ, Q10, or Q, is a 1,4-benzoquinone, where Q refers to the quinone chemical group, and 10 refers to the number of isoprenyl chemical subunits in its tail.This oil-soluble, vitamin-like substance...

 in complex III, since a highly reactive free radical is formed as an intermediate (Q·). This unstable intermediate can lead to electron "leakage", when electrons jump directly to oxygen and form the superoxide anion, instead of moving through the normal series of well-controlled reactions of the electron transport chain. Peroxide is also produced from the oxidation of reduced flavoprotein
Flavoprotein
Flavoproteins are proteins that contain a nucleic acid derivative of riboflavin: the flavin adenine dinucleotide or flavin mononucleotide ....

s, such as complex I. However, although these enzymes can produce oxidants, the relative importance of the electron transfer chain to other processes that generate peroxide is unclear. In plant
Plant
Plants are living organisms belonging to the kingdom Plantae. Precise definitions of the kingdom vary, but as the term is used here, plants include familiar organisms such as trees, flowers, herbs, bushes, grasses, vines, ferns, mosses, and green algae. The group is also called green plants or...

s, algae
Algae
Algae are a large and diverse group of simple, typically autotrophic organisms, ranging from unicellular to multicellular forms, such as the giant kelps that grow to 65 meters in length. They are photosynthetic like plants, and "simple" because their tissues are not organized into the many...

, and cyanobacteria, reactive oxygen species are also produced during photosynthesis
Photosynthesis
Photosynthesis is a chemical process that converts carbon dioxide into organic compounds, especially sugars, using the energy from sunlight. Photosynthesis occurs in plants, algae, and many species of bacteria, but not in archaea. Photosynthetic organisms are called photoautotrophs, since they can...

, particularly under conditions of high light intensity
Irradiance
Irradiance is the power of electromagnetic radiation per unit area incident on a surface. Radiant emittance or radiant exitance is the power per unit area radiated by a surface. The SI units for all of these quantities are watts per square meter , while the cgs units are ergs per square centimeter...

. This effect is partly offset by the involvement of carotenoid
Carotenoid
Carotenoids are tetraterpenoid organic pigments that are naturally occurring in the chloroplasts and chromoplasts of plants and some other photosynthetic organisms like algae, some bacteria, and some types of fungus. Carotenoids can be synthesized fats and other basic organic metabolic building...

s in photoinhibition
Photoinhibition
Photoinhibition is light-induced reduction in the photosynthetic capacity of a plant, alga, or cyanobacterium. Photosystem II is more sensitive to light than the rest of the photosynthetic machinery, and most researchers define the term as light-induced damage to PSII...

, which involves these antioxidants reacting with over-reduced forms of the photosynthetic reaction centre
Photosynthetic reaction centre
A photosynthetic reaction center is a complex of several proteins, pigments and other co-factors assembled together to execute the primary energy conversion reactions of photosynthesis...

s to prevent the production of reactive oxygen species.

Overview


Antioxidants are classified into two broad divisions, depending on whether they are soluble in water
Water
Water is a chemical substance with the chemical formula H2O. A water molecule contains one oxygen and two hydrogen atoms connected by covalent bonds. Water is a liquid at ambient conditions, but it often co-exists on Earth with its solid state, ice, and gaseous state . Water also exists in a...

 (hydrophilic
Hydrophile
A hydrophile, from the Greek "water" and φιλια "love," is a molecule or other molecular entity that is attracted to, and tends to be dissolved by water. A hydrophilic molecule or portion of a molecule is one that has a tendency to interact with or be dissolved by, water and other polar substances...

) or in lipids (hydrophobic
Hydrophobe
In chemistry, hydrophobicity is the physical property of a molecule that is repelled from a mass of water....

). In general, water-soluble antioxidants react with oxidants in the cell cytosol
Cytosol
The cytosol or intracellular fluid is the liquid found inside cells, that is separated into compartments by membranes. For example, the mitochondrial matrix separates the mitochondrion into compartments....

 and the blood plasma
Blood plasma
Blood plasma is the straw-colored liquid component of blood in which the blood cells in whole blood are normally suspended. It makes up about 55% of the total blood volume. It is the intravascular fluid part of extracellular fluid...

, while lipid-soluble antioxidants protect cell membrane
Cell membrane
The cell membrane or plasma membrane is a biological membrane that separates the interior of all cells from the outside environment. The cell membrane is selectively permeable to ions and organic molecules and controls the movement of substances in and out of cells. It basically protects the cell...

s from lipid peroxidation. These compounds may be synthesized in the body or obtained from the diet. The different antioxidants are present at a wide range of concentrations in body fluids
Bodily fluid
Body fluid or bodily fluids are liquids originating from inside the bodies of living people. They include fluids that are excreted or secreted from the body as well as body water that normally is not.Body fluids include:-Body fluids and health:...

 and tissues, with some such as glutathione or ubiquinone mostly present within cells, while others such as uric acid
Uric acid
Uric acid is a heterocyclic compound of carbon, nitrogen, oxygen, and hydrogen with the formula C5H4N4O3. It forms ions and salts known as urates and acid urates such as ammonium acid urate. Uric acid is created when the body breaks down purine nucleotides. High blood concentrations of uric acid...

 are more evenly distributed (see table below). Some antioxidants are only found in a few organisms and these compounds can be important in pathogen
Pathogen
A pathogen gignomai "I give birth to") or infectious agent — colloquially, a germ — is a microbe or microorganism such as a virus, bacterium, prion, or fungus that causes disease in its animal or plant host...

s and can be virulence factor
Virulence factor
Virulence factors are molecules expressed and secreted by pathogens that enable them to achieve the following:* colonization of a niche in the host...

s.

The relative importance and interactions between these different antioxidants is a very complex question, with the various metabolites and enzyme systems having synergistic
Synergy
Synergy may be defined as two or more things functioning together to produce a result not independently obtainable.The term synergy comes from the Greek word from , , meaning "working together".-Definitions and usages:...

 and interdependent effects on one another. The action of one antioxidant may therefore depend on the proper function of other members of the antioxidant system. 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.

Some compounds contribute to antioxidant defense by chelating
Chelation
Chelation is the formation or presence of two or more separate coordinate bonds between apolydentate ligand and a single central atom....

 transition metal
Transition metal
The term transition metal has two possible meanings:*The IUPAC definition states that a transition metal is "an element whose atom has an incomplete d sub-shell, or which can give rise to cations with an incomplete d sub-shell." Group 12 elements are not transition metals in this definition.*Some...

s and preventing them from catalyzing the production of free radicals in the cell. Particularly important is the ability to sequester iron
Iron
Iron is a chemical element with the symbol Fe and atomic number 26. It is a metal in the first transition series. It is the most common element forming the planet Earth as a whole, forming much of Earth's outer and inner core. It is the fourth most common element in the Earth's crust...

, which is the function of iron-binding proteins
Iron-binding proteins
Iron-binding proteins are carrier proteins and metalloproteins which play many important roles in metabolism.They bind Iron and can therefore inhibit microbial growth. Two iron-binding proteins are lactoferrin and transferrin....

 such as transferrin
Transferrin
Transferrins are iron-binding blood plasma glycoproteins that control the level of free iron in biological fluids. In humans, it is encoded by the TF gene.Transferrin is a glycoprotein that binds iron very tightly but reversibly...

 and ferritin
Ferritin
Ferritin is a ubiquitous intracellular protein that stores iron and releases it in a controlled fashion. The amount of ferritin stored reflects the amount of iron stored. The protein is produced by almost all living organisms, including bacteria, algae and higher plants, and animals...

. Selenium
Selenium
Selenium is a chemical element with atomic number 34, chemical symbol Se, and an atomic mass of 78.96. It is a nonmetal, whose properties are intermediate between those of adjacent chalcogen elements sulfur and tellurium...

 and zinc
Zinc
Zinc , or spelter , is a metallic chemical element; it has the symbol Zn and atomic number 30. It is the first element in group 12 of the periodic table. Zinc is, in some respects, chemically similar to magnesium, because its ion is of similar size and its only common oxidation state is +2...

 are commonly referred to as antioxidant nutrients, but these chemical element
Chemical element
A chemical element is a pure chemical substance consisting of one type of atom distinguished by its atomic number, which is the number of protons in its nucleus. Familiar examples of elements include carbon, oxygen, aluminum, iron, copper, gold, mercury, and lead.As of November 2011, 118 elements...

s have no antioxidant action themselves and are instead required for the activity of some antioxidant enzymes, as is discussed below.
Antioxidant metabolite Solubility Concentration in human serum (μM) Concentration in liver tissue (μmol/kg)
Ascorbic acid
Ascorbic acid
Ascorbic acid is a naturally occurring organic compound with antioxidant properties. It is a white solid, but impure samples can appear yellowish. It dissolves well in water to give mildly acidic solutions. Ascorbic acid is one form of vitamin C. The name is derived from a- and scorbutus , the...

 (vitamin C
Vitamin C
Vitamin C or L-ascorbic acid or L-ascorbate is an essential nutrient for humans and certain other animal species. In living organisms ascorbate acts as an antioxidant by protecting the body against oxidative stress...

)
Water 50 – 60 260 (human)
Glutathione
Glutathione
Glutathione is a tripeptide that contains an unusual peptide linkage between the amine group of cysteine and the carboxyl group of the glutamate side-chain...

Water 4 6,400 (human)
Lipoic acid
Lipoic acid
Lipoic acid , also known as α-lipoic acid and Alpha Lipoic Acid is an organosulfur compound derived from octanoic acid. LA contains two vicinal sulfur atoms attached via a disulfide bond and is thus considered to be oxidized...

Water 0.1 – 0.7 4 – 5 (rat)
Uric acid
Uric acid
Uric acid is a heterocyclic compound of carbon, nitrogen, oxygen, and hydrogen with the formula C5H4N4O3. It forms ions and salts known as urates and acid urates such as ammonium acid urate. Uric acid is created when the body breaks down purine nucleotides. High blood concentrations of uric acid...

Water 200 – 400 1,600 (human)
Carotene
Carotene
The term carotene is used for several related unsaturated hydrocarbon substances having the formula C40Hx, which are synthesized by plants but cannot be made by animals. Carotene is an orange photosynthetic pigment important for photosynthesis. Carotenes are all coloured to the human eye...

s
Lipid β-carotene
Carotene
The term carotene is used for several related unsaturated hydrocarbon substances having the formula C40Hx, which are synthesized by plants but cannot be made by animals. Carotene is an orange photosynthetic pigment important for photosynthesis. Carotenes are all coloured to the human eye...

: 0.5 – 1
retinol
Retinol
Retinol is one of the animal forms of vitamin A. It is a diterpenoid and an alcohol. It is convertible to other forms of vitamin A, and the retinyl ester derivative of the alcohol serves as the storage form of the vitamin in animals....

 (vitamin A): 1 – 3
5 (human, total carotenoids)
α-Tocopherol
Tocopherol
Tocopherols are a class of chemical compounds of which many have vitamin E activity. It is a series of organic compounds consisting of various methylated phenols...

 (vitamin E)
Lipid 10 – 40 50 (human)
Ubiquinol
Coenzyme Q
Coenzyme Q10, also known as ubiquinone, ubidecarenone, coenzyme Q, and abbreviated at times to CoQ10 , CoQ, Q10, or Q, is a 1,4-benzoquinone, where Q refers to the quinone chemical group, and 10 refers to the number of isoprenyl chemical subunits in its tail.This oil-soluble, vitamin-like substance...

 (coenzyme Q)
Lipid 5 200 (human)

Uric acid


Uric acid (UA) is an oxypurine produced from xanthine
Xanthine
Xanthine , is a purine base found in most human body tissues and fluids and in other organisms. A number of stimulants are derived from xanthine, including caffeine and theobromine....

 by the enzyme xanthine oxidase
Xanthine oxidase
Xanthine oxidase Xanthine oxidase Xanthine oxidase (XO (sometimes 'XAO'), a form of xanthine oxidoreductase that generates reactive oxygen species. Is an enzyme that catalyzes the oxidation of hypoxanthine to xanthine and can further catalyze the oxidation of xanthine to uric acid...

, and is an intermediate product of purine
Purine
A purine is a heterocyclic aromatic organic compound, consisting of a pyrimidine ring fused to an imidazole ring. Purines, including substituted purines and their tautomers, are the most widely distributed kind of nitrogen-containing heterocycle in nature....

 metabolism. In almost all land animals, Urate oxidase
Urate oxidase
The enzyme urate oxidase , or uricase or factor-independent urate hydroxylase, catalyzes the oxidation of uric acid to 5-hydroxyisourate:-Structure:...

 further catalyzes the oxidation of uric acid to allantoin
Allantoin
Allantoin is a chemical compound with formula C4H6N4O3. It is also called 5-ureidohydantoin or glyoxyldiureide. It is a diureide of glyoxylic acid....

. In humans and most higher primates, though, the UA gene is present, but nonfunctional so that UA is not further processed. The evolutionary reasons for this loss of urate converstion to allantoin remain the topic of active speculation, but the antioxidant effects of uric acid have led researchers to suggest this mutation was beneficial to early primates and humans. Studies of high altitude acclimatization support the hypothesis that urate acts as an antioxidant by mitigating the oxidative stress caused by high-altitude hypoxia. In animal studies that investigate diseases facilitated by oxidative stress, introduction of UA both prevents the disease or reduces it, leading researchers to propose this is due to UA's antioxidant properties. Studies of UA's antioxidant mechanism have supported this proposal. Gwen Scott explains the significance of these findings by proposing that "Serum UA levels are inversely associated with the incidence of MS
Multiple sclerosis
Multiple sclerosis is an inflammatory disease in which the fatty myelin sheaths around the axons of the brain and spinal cord are damaged, leading to demyelination and scarring as well as a broad spectrum of signs and symptoms...

 in humans because MS patients have low serum UA levels and individuals with hyperuricemia (gout) rarely develop the disease. Moreover, the administration of UA is therapeutic in experimental allergic encephalomyelitis (EAE), an animal model of MS."
While the mechanism of UA as an antioxidant is well-supported, the claim that its levels affect MS risk is still controversial, and requires more research. When compared to other antioxidants, UA has the highest concentration of any in the blood and provides about half of the total antioxidant capacity of human serum. Uric acid's antioxidant activities are also complex, given that it does not react with all oxidants, such as superoxide
Superoxide
A superoxide, also known by the obsolete name hyperoxide, is a compound that possesses the superoxide anion with the chemical formula O2−. The systematic name of the anion is dioxide. It is important as the product of the one-electron reduction of dioxygen O2, which occurs widely in nature...

 but does act against peroxynitrite
Peroxynitrite
Peroxynitrite is the anion with the formula ONOO−. It is an unstable structural isomer of nitrate, NO3−, which has the same formula but a different structure. Although peroxynitrous acid is highly reactive, its conjugate base peroxynitrite is stable in basic solution...

, peroxides, and hypochlorous acid
Hypochlorous acid
Hypochlorous acid is a weak acid with the chemical formula HClO. It forms when chlorine dissolves in water. It cannot be isolated in pure form due to rapid equilibration with its precursor...

. Concerns over elevated UA's contribution to gout
Gout
Gout is a medical condition usually characterized by recurrent attacks of acute inflammatory arthritis—a red, tender, hot, swollen joint. The metatarsal-phalangeal joint at the base of the big toe is the most commonly affected . However, it may also present as tophi, kidney stones, or urate...

 must be considered as one of many risk factors. By itself, UA-related risk of gout at high levels (415-530 μmol/L) is only 0.5% per year with an increase to 4.5% per year at UA supersaturation levels
Supersaturation
The term supersaturation refers to a solution that contains more of the dissolved material than could be dissolved by the solvent under normal circumstances...

 (535+ μmol/L). Many of these aforementioned studies determined UA's antioxidant actions within normal physiological levels, and some found antioxidant activity at levels as high as 285 μmol/L. The effects of uric acid in conditions such as stroke
Stroke
A stroke, previously known medically as a cerebrovascular accident , is the rapidly developing loss of brain function due to disturbance in the blood supply to the brain. This can be due to ischemia caused by blockage , or a hemorrhage...

 and heart attack
Myocardial infarction
Myocardial infarction or acute myocardial infarction , commonly known as a heart attack, results from the interruption of blood supply to a part of the heart, causing heart cells to die...

s are still not well understood, with some studies linking higher levels of uric acid with increased mortality and other, more careful studies showing no association. This apparent effect might be due to uric acid being activated as a defense mechanism against oxidative stress, but instead acting as a pro-oxidant in cases where metabolic derangements shift its production well outside of normal levels.

Ascorbic acid


Ascorbic acid
Ascorbic acid
Ascorbic acid is a naturally occurring organic compound with antioxidant properties. It is a white solid, but impure samples can appear yellowish. It dissolves well in water to give mildly acidic solutions. Ascorbic acid is one form of vitamin C. The name is derived from a- and scorbutus , the...

 or "vitamin C
Vitamin C
Vitamin C or L-ascorbic acid or L-ascorbate is an essential nutrient for humans and certain other animal species. In living organisms ascorbate acts as an antioxidant by protecting the body against oxidative stress...

" is a monosaccharide
Monosaccharide
Monosaccharides are the most basic units of biologically important carbohydrates. They are the simplest form of sugar and are usually colorless, water-soluble, crystalline solids. Some monosaccharides have a sweet taste. Examples of monosaccharides include glucose , fructose , galactose, xylose...

 oxidation-reduction (redox
Redox
Redox reactions describe all chemical reactions in which atoms have their oxidation state changed....

) catalyst found in both animals and plants. As one of the enzymes needed to make ascorbic acid has been lost by mutation
Mutation
In molecular biology and genetics, mutations are changes in a genomic sequence: the DNA sequence of a cell's genome or the DNA or RNA sequence of a virus. They can be defined as sudden and spontaneous changes in the cell. Mutations are caused by radiation, viruses, transposons and mutagenic...

 during primate
Primate
A primate is a mammal of the order Primates , which contains prosimians and simians. Primates arose from ancestors that lived in the trees of tropical forests; many primate characteristics represent adaptations to life in this challenging three-dimensional environment...

 evolution
Evolution
Evolution is any change across successive generations in the heritable characteristics of biological populations. Evolutionary processes give rise to diversity at every level of biological organisation, including species, individual organisms and molecules such as DNA and proteins.Life on Earth...

, humans must obtain it from the diet; it is therefore a vitamin. Most other animals are able to produce this compound in their bodies and do not require it in their diets. Ascorbic acid is required for the conversion of the procollagen to collagen
Collagen
Collagen is a group of naturally occurring proteins found in animals, especially in the flesh and connective tissues of mammals. It is the main component of connective tissue, and is the most abundant protein in mammals, making up about 25% to 35% of the whole-body protein content...

 by oxidizing proline
Proline
Proline is an α-amino acid, one of the twenty DNA-encoded amino acids. Its codons are CCU, CCC, CCA, and CCG. It is not an essential amino acid, which means that the human body can synthesize it. It is unique among the 20 protein-forming amino acids in that the α-amino group is secondary...

 residues to hydroxyproline
Hydroxyproline
-4-Hydroxyproline, or L-hydroxyproline , is a common non-proteinogenic amino acid, abbreviated as HYP, e.g., in Protein Data Bank.-Structure and discovery:...

. In other cells, it is maintained in its reduced form
Reduced form
In statistics, and particularly in econometrics, the reduced form of a system of equations is the result of solving the system for the endogenous variables. This gives the latter as a function of the exogenous variables, if any...

 by reaction with glutathione, which can be catalysed by protein disulfide isomerase
Protein disulfide isomerase
Protein disulfide isomerase or PDI is an enzyme in the endoplasmic reticulum in eukaryotes that catalyzes the formation and breakage of disulfide bonds between cysteine residues within proteins as they fold...

 and glutaredoxin
Glutaredoxin
Glutaredoxins are small redox enzymes of approximately one hundred amino-acid residues that use glutathione as a cofactor. Glutaredoxins are oxidized by substrates, and reduced non-enzymatically by glutathione. In contrast to thioredoxins, which are reduced by thioredoxin reductase, no...

s. Ascorbic acid is redox catalyst which can reduce, and thereby neutralize, reactive oxygen species such as hydrogen peroxide. In addition to its direct antioxidant effects, ascorbic acid is also a substrate
Substrate (biochemistry)
In biochemistry, a substrate is a molecule upon which an enzyme acts. Enzymes catalyze chemical reactions involving the substrate. In the case of a single substrate, the substrate binds with the enzyme active site, and an enzyme-substrate complex is formed. The substrate is transformed into one or...

 for the redox enzyme ascorbate peroxidase
Ascorbate peroxidase
Ascorbate peroxidases are enzymes that detoxify peroxides such as hydrogen peroxide using ascorbate as a substrate. The reaction they catalyse is the transfer of electrons from ascorbate to a peroxide, producing dehydroascorbate and water as products.Ascorbate + Hydrogen peroxide →...

, a function that is particularly important in stress resistance in plants. Ascorbic acid is present at high levels in all parts of plants and can reach concentrations of 20 millimolar in chloroplast
Chloroplast
Chloroplasts are organelles found in plant cells and other eukaryotic organisms that conduct photosynthesis. Chloroplasts capture light energy to conserve free energy in the form of ATP and reduce NADP to NADPH through a complex set of processes called photosynthesis.Chloroplasts are green...

s.

Glutathione


Glutathione
Glutathione
Glutathione is a tripeptide that contains an unusual peptide linkage between the amine group of cysteine and the carboxyl group of the glutamate side-chain...

 is a cysteine
Cysteine
Cysteine is an α-amino acid with the chemical formula HO2CCHCH2SH. It is a non-essential amino acid, which means that it is biosynthesized in humans. Its codons are UGU and UGC. The side chain on cysteine is thiol, which is polar and thus cysteine is usually classified as a hydrophilic amino acid...

-containing peptide
Peptide
Peptides are short polymers of amino acid monomers linked by peptide bonds. They are distinguished from proteins on the basis of size, typically containing less than 50 monomer units. The shortest peptides are dipeptides, consisting of two amino acids joined by a single peptide bond...

 found in most forms of aerobic life. It is not required in the diet and is instead synthesized in cells from its constituent amino acid
Amino acid
Amino acids are molecules containing an amine group, a carboxylic acid group and a side-chain that varies between different amino acids. The key elements of an amino acid are carbon, hydrogen, oxygen, and nitrogen...

s. Glutathione has antioxidant properties since the thiol
Thiol
In organic chemistry, a thiol is an organosulfur compound that contains a carbon-bonded sulfhydryl group...

 group in its cysteine
Cysteine
Cysteine is an α-amino acid with the chemical formula HO2CCHCH2SH. It is a non-essential amino acid, which means that it is biosynthesized in humans. Its codons are UGU and UGC. The side chain on cysteine is thiol, which is polar and thus cysteine is usually classified as a hydrophilic amino acid...

 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
Glutathione reductase
Glutathione reductase, also known as GSR or GR, is an enzyme that reduces glutathione disulfide to the sulfhydryl form GSH, which is an important cellular antioxidant....

 and in turn reduces other metabolites and enzyme systems, such as ascorbate in the glutathione-ascorbate cycle
Glutathione-ascorbate cycle
The glutathione-ascorbate cycle is a metabolic pathway that detoxifies hydrogen peroxide , which is a reactive oxygen species that is produced as a waste product in metabolism...

, glutathione peroxidase
Glutathione peroxidase
Glutathione peroxidase is the general name of an enzyme family with peroxidase activity whose main biological role is to protect the organism from oxidative damage...

s and glutaredoxin
Glutaredoxin
Glutaredoxins are small redox enzymes of approximately one hundred amino-acid residues that use glutathione as a cofactor. Glutaredoxins are oxidized by substrates, and reduced non-enzymatically by glutathione. In contrast to thioredoxins, which are reduced by thioredoxin reductase, no...

s, as well as reacting directly with oxidants. 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. In some organisms glutathione is replaced by other thiols, such as by mycothiol
Mycothiol
Mycothiol is an unusual thiol compound found in the Actinobacteria. It is composed of a cysteine residue with an acetylated amino group linked to glucosamine, which is then linked to inositol. The oxidized, disulfide form of mycothiol is called mycothione, and is reduced to mycothiol by the...

 in the Actinomycetes, bacillithiol
Bacillithiol
Bacillithiol is a thiol compound found in Bacillus species. Chemically, it is a glycoside formed between L-cysteinyl-D-glucosamine and malic acid...

 in some Gram-positive bacteria, or by trypanothione
Trypanothione
Trypanothione is an unusual form of glutathione containing two molecules of glutathione joined by a spermidine linker. It is found in parasitic protozoa such as leishmania and trypanosomes. These protozoal parasites are the cause of leishmaniasis, sleeping sickness and Chagas' disease....

 in the Kinetoplastid
Kinetoplastid
The kinetoplastids are a group of single-cell flagellate protozoa, including a number of parasites responsible for serious diseases in humans and other animals, as well as various forms found in soil and aquatic environments...

s.

Melatonin


Melatonin
Melatonin
Melatonin , also known chemically as N-acetyl-5-methoxytryptamine, is a naturally occurring compound found in animals, plants, and microbes...

 is a powerful antioxidant. Melatonin easily crosses cell membranes and the blood-brain barrier
Blood-brain barrier
The blood–brain barrier is a separation of circulating blood and the brain extracellular fluid in the central nervous system . It occurs along all capillaries and consists of tight junctions around the capillaries that do not exist in normal circulation. Endothelial cells restrict the diffusion...

. Unlike other antioxidants, melatonin does not undergo redox cycling, which is the ability of a molecule to undergo repeated reduction and oxidation. Redox cycling may allow other antioxidants (such as vitamin C) to act as pro-oxidant
Pro-oxidant
Pro-oxidants are chemicals that induce oxidative stress, through either creating reactive oxygen species or inhibiting antioxidant systems. The oxidative stress produced by these chemicals can damage cells and tissues...

s and promote free radical formation. Melatonin, once oxidized, cannot be reduced to its former state because it forms several stable end-products upon reacting with free radicals. Therefore, it has been referred to as a terminal (or suicidal) antioxidant.

Tocopherols and tocotrienols (vitamin E)


Vitamin E
Vitamin E
Vitamin E is used to refer to a group of fat-soluble compounds that include both tocopherols and tocotrienols. There are many different forms of vitamin E, of which γ-tocopherol is the most common in the North American diet. γ-Tocopherol can be found in corn oil, soybean oil, margarine and dressings...

 is the collective name for a set of eight related tocopherol
Tocopherol
Tocopherols are a class of chemical compounds of which many have vitamin E activity. It is a series of organic compounds consisting of various methylated phenols...

s and tocotrienol
Tocotrienol
Tocotrienols are members of the vitamin E family. An essential nutrient for the body, vitamin E is made up of four tocopherols and four tocotrienols . The slight difference between tocotrienols and tocopherols lie in the unsaturated side chain having three double bonds in its farnesyl isoprenoid...

s, which are fat-soluble vitamins with antioxidant properties. Of these, α-tocopherol has been most studied as it has the highest bioavailability
Bioavailability
In pharmacology, bioavailability is a subcategory of absorption and is used to describe the fraction of an administered dose of unchanged drug that reaches the systemic circulation, one of the principal pharmacokinetic properties of drugs. By definition, when a medication is administered...

, with the body preferentially absorbing and metabolising this form.

It has been claimed that the α-tocopherol form is the most important lipid-soluble antioxidant, and that it protects membranes from oxidation by reacting with lipid radicals produced in the lipid peroxidation chain reaction. 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. This is in line with findings showing that α-tocopherol, but not water-soluble antioxidants, efficiently protects glutathione peroxidase 4 (GPX4
GPX4
Glutathione peroxidase 4, also known as GPX4, is an enzyme that in humans is encoded by the GPX4 gene. GPX4 is a phospholipid hydroperoxidase that protects cells against membrane lipid peroxidation.- Function :...

)-deficient cells from cell death. GPx4 is the only known enzyme that efficiently reduces lipid-hydroperoxides within biological membranes.

However, the roles and importance of the various forms of vitamin E are presently unclear, and it has even been suggested that the most important function of α-tocopherol is as a signaling molecule
Cell signaling
Cell signaling is part of a complex system of communication that governs basic cellular activities and coordinates cell actions. The ability of cells to perceive and correctly respond to their microenvironment is the basis of development, tissue repair, and immunity as well as normal tissue...

, with this molecule having no significant role in antioxidant metabolism. The functions of the other forms of vitamin E are even less well-understood, although γ-tocopherol is a nucleophile
Nucleophile
A nucleophile is a species that donates an electron-pair to an electrophile to form a chemical bond in a reaction. All molecules or ions with a free pair of electrons can act as nucleophiles. Because nucleophiles donate electrons, they are by definition Lewis bases.Nucleophilic describes the...

 that may react with electrophilic
Electrophile
In general electrophiles are positively charged species that are attracted to an electron rich centre. In chemistry, an electrophile is a reagent attracted to electrons that participates in a chemical reaction by accepting an electron pair in order to bond to a nucleophile...

 mutagens, and tocotrienols may be important in protecting neuron
Neuron
A neuron is an electrically excitable cell that processes and transmits information by electrical and chemical signaling. Chemical signaling occurs via synapses, specialized connections with other cells. Neurons connect to each other to form networks. Neurons are the core components of the nervous...

s from damage.

Pro-oxidant activities


Antioxidants that are reducing agents can also act as pro-oxidants. For example, vitamin C has antioxidant activity when it reduces oxidizing substances such as hydrogen peroxide, however, it will also reduce metal ions that generate free radicals through the Fenton reaction
Fenton's reagent
Fenton's reagent is a solution of hydrogen peroxide and an iron catalyst that is used to oxidize contaminants or waste waters. Fenton's reagent can be used to destroy organic compounds such as trichloroethylene and tetrachloroethylene ....

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


The relative importance of the antioxidant and pro-oxidant activities of antioxidants are an area of current research, but vitamin C, which exerts its effects as a vitamin by oxidizing polypeptides, appears to have a mostly antioxidant action in the human body. However, less data is available for other dietary antioxidants, such as vitamin E, or the polyphenol
Polyphenol antioxidant
A polyphenol antioxidant is a type of antioxidant containing a polyphenolic substructure. Numbering over 4,000 distinct species, many of these compounds have antioxidant activity in vitro but are unlikely to have antioxidant roles in vivo...

s.

Potential of antioxidant supplements to damage health


There is evidence that antioxidant supplements promote disease and increase mortality in humans. It was previously proposed on a hypothetical basis that free radicals may induce an endogenous response culminating in more effective adaptations which protect against exogenous radicals (and possibly other toxic compounds). Recent experimental evidence strongly suggests that this is indeed the case, and that such induction of endogenous free radical production extends the life span
Life expectancy
Life expectancy is the expected number of years of life remaining at a given age. It is denoted by ex, which means the average number of subsequent years of life for someone now aged x, according to a particular mortality experience...

 of Caenorhabditis elegans
Caenorhabditis elegans
Caenorhabditis elegans is a free-living, transparent nematode , about 1 mm in length, which lives in temperate soil environments. Research into the molecular and developmental biology of C. elegans was begun in 1974 by Sydney Brenner and it has since been used extensively as a model...

. Most importantly, this induction of life span is prevented by antioxidants, providing direct evidence that toxic radicals may mitohormetically exert life extending and health promoting effects.

Enzyme systems



Overview


As with the chemical antioxidants, cells are protected against oxidative stress by an interacting network of antioxidant enzymes. Here, the superoxide released by processes such as oxidative phosphorylation
Oxidative phosphorylation
Oxidative phosphorylation is a metabolic pathway that uses energy released by the oxidation of nutrients to produce adenosine triphosphate . Although the many forms of life on earth use a range of different nutrients, almost all aerobic organisms carry out oxidative phosphorylation to produce ATP,...

 is first converted to hydrogen peroxide and then further reduced to give water. This detoxification pathway is the result of multiple enzymes, with superoxide dismutases catalysing the first step and then catalases and various peroxidases removing hydrogen peroxide. As with antioxidant metabolites, the contributions of these enzymes to antioxidant defenses can be hard to separate from one another, but the generation of transgenic mice
Genetically modified organism
A genetically modified organism or genetically engineered organism is an organism whose genetic material has been altered using genetic engineering techniques. These techniques, generally known as recombinant DNA technology, use DNA molecules from different sources, which are combined into one...

 lacking just one antioxidant enzyme can be informative.

Superoxide dismutase, catalase and peroxiredoxins


Superoxide dismutase
Superoxide dismutase
Superoxide dismutases are a class of enzymes that catalyze the dismutation of superoxide into oxygen and hydrogen peroxide. As such, they are an important antioxidant defense in nearly all cells exposed to oxygen...

s (SODs) are a class of closely related enzymes that catalyze the breakdown of the superoxide anion into oxygen and hydrogen peroxide. SOD enzymes are present in almost all aerobic cells and in extracellular fluids. Superoxide dismutase enzymes contain metal ion cofactors that, depending on the isozyme, can be copper
Copper
Copper is a chemical element with the symbol Cu and atomic number 29. It is a ductile metal with very high thermal and electrical conductivity. Pure copper is soft and malleable; an exposed surface has a reddish-orange tarnish...

, zinc, manganese
Manganese
Manganese is a chemical element, designated by the symbol Mn. It has the atomic number 25. It is found as a free element in nature , and in many minerals...

 or iron
Iron
Iron is a chemical element with the symbol Fe and atomic number 26. It is a metal in the first transition series. It is the most common element forming the planet Earth as a whole, forming much of Earth's outer and inner core. It is the fourth most common element in the Earth's crust...

. In humans, the copper/zinc SOD is present in the cytosol
Cytosol
The cytosol or intracellular fluid is the liquid found inside cells, that is separated into compartments by membranes. For example, the mitochondrial matrix separates the mitochondrion into compartments....

, while manganese SOD is present in the mitochondrion
Mitochondrion
In cell biology, a mitochondrion is a membrane-enclosed organelle found in most eukaryotic cells. These organelles range from 0.5 to 1.0 micrometers in diameter...

. There also exists a third form of SOD in extracellular fluid
Extracellular fluid
Extracellular fluid usually denotes all body fluid outside of cells. The remainder is called intracellular fluid.In some animals, including mammals, the extracellular fluid can be divided into two major subcompartments, interstitial fluid and blood plasma...

s, which contains copper and zinc in its active sites. The mitochondrial isozyme seems to be the most biologically important of these three, since mice lacking this enzyme die soon after birth. In contrast, the mice lacking copper/zinc SOD (Sod1) are viable but have numerous pathologies and a reduced lifespan (see article on superoxide
Superoxide
A superoxide, also known by the obsolete name hyperoxide, is a compound that possesses the superoxide anion with the chemical formula O2−. The systematic name of the anion is dioxide. It is important as the product of the one-electron reduction of dioxygen O2, which occurs widely in nature...

), while mice without the extracellular SOD have minimal defects (sensitive to hyperoxia
Hyperoxia
Hyperoxia is excess oxygen or higher than normal partial pressure of oxygen.In medicine, it refers to excess oxygen in the lungs or other body tissues, which can be caused by breathing air or oxygen at pressures greater than normal atmospheric pressure...

). In plants, SOD isozymes are present in the cytosol and mitochondria, with an iron SOD found in chloroplast
Chloroplast
Chloroplasts are organelles found in plant cells and other eukaryotic organisms that conduct photosynthesis. Chloroplasts capture light energy to conserve free energy in the form of ATP and reduce NADP to NADPH through a complex set of processes called photosynthesis.Chloroplasts are green...

s that is absent from vertebrate
Vertebrate
Vertebrates are animals that are members of the subphylum Vertebrata . Vertebrates are the largest group of chordates, with currently about 58,000 species described. Vertebrates include the jawless fishes, bony fishes, sharks and rays, amphibians, reptiles, mammals, and birds...

s and yeast
Yeast
Yeasts are eukaryotic micro-organisms classified in the kingdom Fungi, with 1,500 species currently described estimated to be only 1% of all fungal species. Most reproduce asexually by mitosis, and many do so by an asymmetric division process called budding...

.

Catalase
Catalase
Catalase is a common enzyme found in nearly all living organisms that are exposed to oxygen, where it catalyzes the decomposition of hydrogen peroxide to water and oxygen...

s are enzymes that catalyse the conversion of hydrogen peroxide to water and oxygen, using either an iron or manganese cofactor. This protein is localized to peroxisome
Peroxisome
Peroxisomes are organelles found in virtually all eukaryotic cells. They are involved in the catabolism of very long chain fatty acids, branched chain fatty acids, D-amino acids, polyamines, and biosynthesis of plasmalogens, etherphospholipids critical for the normal function of mammalian brains...

s in most eukaryotic
Eukaryote
A eukaryote is an organism whose cells contain complex structures enclosed within membranes. Eukaryotes may more formally be referred to as the taxon Eukarya or Eukaryota. The defining membrane-bound structure that sets eukaryotic cells apart from prokaryotic cells is the nucleus, or nuclear...

 cells. Catalase is an unusual enzyme since, although hydrogen peroxide is its only substrate, it follows a ping-pong mechanism
Enzyme kinetics
Enzyme kinetics is the study of the chemical reactions that are catalysed by enzymes. In enzyme kinetics, the reaction rate is measured and the effects of varying the conditions of the reaction investigated...

. 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. Despite its apparent importance in hydrogen peroxide removal, humans with genetic deficiency of catalase — "acatalasemia" — or mice genetically engineered
Genetic engineering
Genetic engineering, also called genetic modification, is the direct human manipulation of an organism's genome using modern DNA technology. It involves the introduction of foreign DNA or synthetic genes into the organism of interest...

 to lack catalase completely, suffer few ill effects.

Peroxiredoxin
Peroxiredoxin
Peroxiredoxins are a ubiquitous family of antioxidant enzymes that also control cytokine-induced peroxide levels and thereby mediate signal transduction in mammalian cells.- Classification :...

s are peroxidases that catalyze the reduction of hydrogen peroxide, organic hydroperoxide
Organic peroxide
Organic peroxides are organic compounds containing the peroxide functional group . If the R' is hydrogen, the compound is called an organic hydroperoxide. Peresters have general structure RCOOR. The O-O bond easily breaks and forms free radicals of the form RO·...

s, as well as peroxynitrite
Peroxynitrite
Peroxynitrite is the anion with the formula ONOO−. It is an unstable structural isomer of nitrate, NO3−, which has the same formula but a different structure. Although peroxynitrous acid is highly reactive, its conjugate base peroxynitrite is stable in basic solution...

. They are divided into three classes: typical 2-cysteine peroxiredoxins; atypical 2-cysteine peroxiredoxins; and 1-cysteine peroxiredoxins. These enzymes share the same basic catalytic mechanism, in which a redox-active cysteine (the peroxidatic cysteine) in the active site
Active site
In biology the active site is part of an enzyme where substrates bind and undergo a chemical reaction. The majority of enzymes are proteins but RNA enzymes called ribozymes also exist. The active site of an enzyme is usually found in a cleft or pocket that is lined by amino acid residues that...

 is oxidized to a sulfenic acid
Sulfenic acid
A sulfenic acid is an organosulfur compound and oxoacid with the general formula RSOH, where R ≠ H. Simple sulfenic acids, such as methanesulfenic acid, CH3SOH, are highly reactive and cannot be isolated in solution. In the gas phase the lifetime of methanesulfenic acid is about one minute...

 by the peroxide substrate. Over-oxidation of this cysteine residue in peroxiredoxins inactivates these enzymes, but this can be reversed by the action of sulfiredoxin
Sulfiredoxin
In enzymology, a sulfiredoxin is an enzyme that catalyzes the chemical reactionThe 3 substrates of this enzyme are peroxiredoxin-, ATP, and a thiol, whereas its 4 products are peroxiredoxin-, ADP, phosphate, and a disulfide.This enzyme is involved in antioxidant metabolism by re-activating...

. Peroxiredoxins seem to be important in antioxidant metabolism, as mice lacking peroxiredoxin 1 or 2 have shortened lifespan and suffer from hemolytic anaemia, while plants use peroxiredoxins to remove hydrogen peroxide generated in chloroplasts.

Thioredoxin and glutathione systems


The thioredoxin
Thioredoxin
Thioredoxin is a class of small redox proteins known to be present in all organisms. It plays a role in many important biological processes. In humans, it is encoded by the TXN gene. Loss-of-function mutation of either of the two human thioredoxin genes is lethal at the four-cell stage of the...

 system contains the 12-kDa
Atomic mass unit
The unified atomic mass unit or dalton is a unit that is used for indicating mass on an atomic or molecular scale. It is defined as one twelfth of the rest mass of an unbound neutral atom of carbon-12 in its nuclear and electronic ground state, and has a value of...

 protein thioredoxin and its companion thioredoxin reductase
Thioredoxin reductase
Thioredoxin Reductases are the only known enzymes to reduce thioredoxin . Two classes of thioredoxin reductase have been identified: one class in bacteria and some eukaryotes and one in animals. Both classes are flavoproteins which function as homodimers...

. Proteins related to thioredoxin are present in all sequenced organisms. Plants, such as Arabidopsis thaliana
Arabidopsis thaliana
Arabidopsis thaliana is a small flowering plant native to Europe, Asia, and northwestern Africa. A spring annual with a relatively short life cycle, arabidopsis is popular as a model organism in plant biology and genetics...

,
have a particularly great diversity of isoforms. The active site of thioredoxin consists of two neighboring
Vicinal (chemistry)
In chemistry vicinal stands for any two functional groups bonded to two adjacent carbon atoms. For example the molecule 2,3-dibromobutane carries two vicinal bromine atoms and 1,3-dibromobutane does not....

 cysteines, as part of a highly conserved CXXC motif
Sequence motif
In genetics, a sequence motif is a nucleotide or amino-acid sequence pattern that is widespread and has, or is conjectured to have, a biological significance...

, that can cycle between an active dithiol form (reduced) and an oxidized disulfide
Disulfide
In chemistry, a disulfide usually refers to the structural unit composed of a linked pair of sulfur atoms. Disulfide usually refer to a chemical compound that contains a disulfide bond, such as diphenyl disulfide, C6H5S-SC6H5....

 form. In its active state, thioredoxin acts as an efficient reducing agent, scavenging reactive oxygen species and maintaining other proteins in their reduced state. After being oxidized, the active thioredoxin is regenerated by the action of thioredoxin reductase, using NADPH as an electron donor
Electron donor
An electron donor is a chemical entity that donates electrons to another compound. It is a reducing agent that, by virtue of its donating electrons, is itself oxidized in the process....

.

The glutathione
Glutathione
Glutathione is a tripeptide that contains an unusual peptide linkage between the amine group of cysteine and the carboxyl group of the glutamate side-chain...

 system includes glutathione, glutathione reductase
Glutathione reductase
Glutathione reductase, also known as GSR or GR, is an enzyme that reduces glutathione disulfide to the sulfhydryl form GSH, which is an important cellular antioxidant....

, glutathione peroxidase
Glutathione peroxidase
Glutathione peroxidase is the general name of an enzyme family with peroxidase activity whose main biological role is to protect the organism from oxidative damage...

s and glutathione S-transferases
Glutathione S-transferase
Enzymes of the glutathione S-transferase family are composed of many cytosolic, mitochondrial, and microsomal proteins. GSTs are present in eukaryotes and in prokaryotes, where they catalyze a variety of reactions and accept endogenous and xenobiotic substrates.GSTs can constitute up to 10% of...

. This system is found in animals, plants and microorganisms. Glutathione peroxidase is an enzyme containing four selenium
Selenium
Selenium is a chemical element with atomic number 34, chemical symbol Se, and an atomic mass of 78.96. It is a nonmetal, whose properties are intermediate between those of adjacent chalcogen elements sulfur and tellurium...

-cofactor
Cofactor (biochemistry)
A cofactor is a non-protein chemical compound that is bound to a protein and is required for the protein's biological activity. These proteins are commonly enzymes, and cofactors can be considered "helper molecules" that assist in biochemical transformations....

s that catalyzes the breakdown of hydrogen peroxide and organic hydroperoxides. There are at least four different glutathione peroxidase isozyme
Isozyme
Isozymes are enzymes that differ in amino acid sequence but catalyze the same chemical reaction. These enzymes usually display different kinetic parameters Isozymes (also known as isoenzymes) are enzymes that differ in amino acid sequence but catalyze the same chemical reaction. These enzymes...

s in animals. 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, but they are hypersensitive to induced oxidative stress. In addition, the glutathione S-transferases show high activity with lipid peroxides. These enzymes are at particularly high levels in the liver and also serve in detoxification metabolism.

Oxidative stress in disease


Oxidative stress is thought to contribute to the development of a wide range of diseases including Alzheimer's disease
Alzheimer's disease
Alzheimer's disease also known in medical literature as Alzheimer disease is the most common form of dementia. There is no cure for the disease, which worsens as it progresses, and eventually leads to death...

, Parkinson's disease
Parkinson's disease
Parkinson's disease is a degenerative disorder of the central nervous system...

, the pathologies caused by diabetes, rheumatoid arthritis
Rheumatoid arthritis
Rheumatoid arthritis is a chronic, systemic inflammatory disorder that may affect many tissues and organs, but principally attacks synovial joints. The process produces an inflammatory response of the synovium secondary to hyperplasia of synovial cells, excess synovial fluid, and the development...

, and neurodegeneration
Neurodegeneration
Neurodegeneration is the umbrella term for the progressive loss of structure or function of neurons, including death of neurons. Many neurodegenerative diseases including Parkinson’s, Alzheimer’s, and Huntington’s occur as a result of neurodegenerative processes. As research progresses, many...

 in motor neuron diseases. In many of these cases, it is unclear if oxidants trigger the disease, or if they are produced as a secondary consequence of the disease and from general tissue damage; One case in which this link is particularly well-understood is the role of oxidative stress in cardiovascular disease
Cardiovascular disease
Heart disease or cardiovascular disease are the class of diseases that involve the heart or blood vessels . While the term technically refers to any disease that affects the cardiovascular system , it is usually used to refer to those related to atherosclerosis...

. Here, low density lipoprotein
Low density lipoprotein
Low-density lipoprotein is one of the five major groups of lipoproteins, which in order of size, largest to smallest, are chylomicrons, VLDL, IDL, LDL, and HDL, that enable transport of cholesterol within the water-based bloodstream...

 (LDL) oxidation appears to trigger the process of atherogenesis, which results in atherosclerosis
Atherosclerosis
Atherosclerosis is a condition in which an artery wall thickens as a result of the accumulation of fatty materials such as cholesterol...

, and finally cardiovascular disease.

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

A low calorie diet
Calorie restriction
Caloric restriction , or calorie restriction, is a dietary regimen that restricts calorie intake, where the baseline for the restriction varies, usually being the previous, unrestricted, intake of the subjects...

 extends median and maximum lifespan
Maximum life span
Maximum life span is a measure of the maximum amount of time one or more members of a population has been observed to survive between birth and death.Most living species have at least one upper limit on the number of times cells can divide...

 in many animals. This effect may involve a reduction in oxidative stress. While there is some evidence to support the role of oxidative stress in aging in model organisms such as Drosophila melanogaster
Drosophila melanogaster
Drosophila melanogaster is a species of Diptera, or the order of flies, in the family Drosophilidae. The species is known generally as the common fruit fly or vinegar fly. Starting from Charles W...

and Caenorhabditis elegans
Caenorhabditis elegans
Caenorhabditis elegans is a free-living, transparent nematode , about 1 mm in length, which lives in temperate soil environments. Research into the molecular and developmental biology of C. elegans was begun in 1974 by Sydney Brenner and it has since been used extensively as a model...

, the evidence in mammals is less clear. Indeed, a 2009 review of experiments in mice concluded that almost all manipulations of antioxidant systems had no effect on aging. Diets high in fruit and vegetables, which are high in antioxidants, promote health and reduce the effects of aging, however antioxidant vitamin supplementation has no detectable effect on the aging process, so the effects of fruit and vegetables may be unrelated to their antioxidant contents. One reason for this might be the fact that consuming antioxidant molecules such as polyphenols and vitamin E will produce changes in other parts of metabolism, so it may be these other effects that are the real reason these compounds are important in human nutrition
Nutrition
Nutrition is the provision, to cells and organisms, of the materials necessary to support life. Many common health problems can be prevented or alleviated with a healthy diet....

.

Disease treatment


The brain
Brain
The brain is the center of the nervous system in all vertebrate and most invertebrate animals—only a few primitive invertebrates such as sponges, jellyfish, sea squirts and starfishes do not have one. It is located in the head, usually close to primary sensory apparatus such as vision, hearing,...

 is uniquely vulnerable to oxidative injury, due to its high metabolic rate and elevated levels of polyunsaturated lipids, the target of lipid peroxidation. Consequently, antioxidants are commonly used as medication
Medication
A pharmaceutical drug, also referred to as medicine, medication or medicament, can be loosely defined as any chemical substance intended for use in the medical diagnosis, cure, treatment, or prevention of disease.- Classification :...

s to treat various forms of brain injury. Here, superoxide dismutase mimetics, sodium thiopental
Sodium thiopental
Sodium thiopental, better known as Sodium Pentothal , thiopental, thiopentone sodium, or Trapanal , is a rapid-onset short-acting barbiturate general anaesthetic...

 and propofol
Propofol
Propofol is a short-acting, intravenously administered hypnotic agent. Its uses include the induction and maintenance of general anesthesia, sedation for mechanically ventilated adults, and procedural sedation. Propofol is also commonly used in veterinary medicine...

 are used to treat reperfusion injury
Reperfusion injury
Reperfusion injury is the tissue damage caused when blood supply returns to the tissue after a period of ischemia or lack of oxygen. The absence of oxygen and nutrients from blood during the ischemic period creates a condition in which the restoration of circulation results in inflammation and...

 and traumatic brain injury
Traumatic brain injury
Traumatic brain injury , also known as intracranial injury, occurs when an external force traumatically injures the brain. TBI can be classified based on severity, mechanism , or other features...

, while the experimental drug NXY-059
NXY-059
Disufenton sodium is the disulfonyl derivative of the neuroprotective spin trap phenylbutynitrone or "PBN". It was under development at the drug company AstraZeneca. A 2005 phase-3 clinical trial called "SAINT-1" reported some efficacy in the acute treatment of ischemia injury due to stroke...

 and ebselen
Ebselen
Ebselen or 2-phenyl-1, 2-benzisoselenazol-3-one , is a mimic of glutathione peroxidase and can also react with peroxynitrite...

 are being applied in the treatment of stroke. These compounds appear to prevent oxidative stress in neurons and prevent apoptosis
Apoptosis
Apoptosis is the process of programmed cell death that may occur in multicellular organisms. Biochemical events lead to characteristic cell changes and death. These changes include blebbing, cell shrinkage, nuclear fragmentation, chromatin condensation, and chromosomal DNA fragmentation...

 and neurological damage. Antioxidants are also being investigated as possible treatments for neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis
Amyotrophic lateral sclerosis
Amyotrophic lateral sclerosis , also referred to as Lou Gehrig's disease, is a form of motor neuron disease caused by the degeneration of upper and lower neurons, located in the ventral horn of the spinal cord and the cortical neurons that provide their efferent input...

, and as a way to prevent noise-induced hearing loss. Targeted antioxidants may lead to better medicinal effects. Mitochondria-targeted ubiquinone, for example, may prevent damage to the liver caused by excessive alcohol.

Disease prevention


People who eat fruits and vegetables have a lower risk of heart disease
Heart disease
Heart disease, cardiac disease or cardiopathy is an umbrella term for a variety of diseases affecting the heart. , it is the leading cause of death in the United States, England, Canada and Wales, accounting for 25.4% of the total deaths in the United States.-Types:-Coronary heart disease:Coronary...

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

It is thought that oxidation of low density lipoprotein in the blood contributes to heart disease, and initial observational studies
Observational study
In epidemiology and statistics, an observational study draws inferences about the possible effect of a treatment on subjects, where the assignment of subjects into a treated group versus a control group is outside the control of the investigator...

 found that people taking Vitamin E supplements had a lower risk of developing heart disease. Consequently, at least seven large clinical trials were conducted to test the effects of antioxidant supplement with Vitamin E, in doses ranging from 50 to per day. None of these trials found a statistically significant
Statistical significance
In statistics, a result is called statistically significant if it is unlikely to have occurred by chance. The phrase test of significance was coined by Ronald Fisher....

 effect of Vitamin E on overall number of deaths or on deaths due to heart disease. Further studies have also been negative. It is not clear if the doses used in these trials or in most dietary supplements are capable of producing any significant decrease in oxidative stress. Overall, despite the clear role of oxidative stress in cardiovascular disease, controlled studies using antioxidant vitamins have observed no reduction in either the risk of developing heart disease, or the rate of progression of existing disease.

While several trials have investigated supplements with high doses of antioxidants, the "Supplémentation en Vitamines et Mineraux Antioxydants" (SU.VI.MAX) study tested the effect of supplementation with doses comparable to those in a healthy diet
Healthy diet
A healthy diet is one that helps maintain or improve general health. It is important for lowering many chronic health risks, such as obesity, heart disease, diabetes, hypertension and cancer. A healthy diet involves consuming appropriate amounts of all essential nutrients and an adequate amount of...

. Over 12,500 French men and women took either low-dose antioxidants ( of ascorbic acid, of vitamin E, of beta carotene, 100 µg of selenium, and of zinc) or placebo
Placebo
A placebo is a simulated or otherwise medically ineffectual treatment for a disease or other medical condition intended to deceive the recipient...

 pills for an average of 7.5 years. The study concluded that low-dose antioxidant supplementation lowered total cancer incidence and all-cause mortality in men but not in women. Supplementation may be effective in men only because of their lower baseline status of certain antioxidants, especially of beta carotene.

Many nutraceutical
Nutraceutical
Nutraceutical, a portmanteau of the words “nutrition” and “pharmaceutical”, is a food or food product that reportedly provides health and medical benefits, including the prevention and treatment of disease. Health Canada defines the term as "a product isolated or purified from foods that is...

 and health food companies sell formulations of antioxidants as dietary supplements and these are widely used in industrialized countries
Developed country
A developed country is a country that has a high level of development according to some criteria. Which criteria, and which countries are classified as being developed, is a contentious issue...

. These supplements may include specific antioxidant chemicals, like the polyphenol
Polyphenol antioxidant
A polyphenol antioxidant is a type of antioxidant containing a polyphenolic substructure. Numbering over 4,000 distinct species, many of these compounds have antioxidant activity in vitro but are unlikely to have antioxidant roles in vivo...

, resveratrol
Resveratrol
Resveratrol is a stilbenoid, a type of natural phenol, and a phytoalexin produced naturally by several plants when under attack by pathogens such as bacteria or fungi....

 (from grape seeds or knotweed
Polygonum
Polygonum is a genus in the Polygonaceae family. Common names include knotweed, knotgrass, bistort, tear-thumb, mile-a-minute, and several others. In the Middle English glossary of herbs "Alphita" , it was known as ars-smerte. There have been various opinions about how broadly the genus should be...

 roots), combinations of antioxidants, like the "ACES" products that contain beta carotene (provitamin A), vitamin C, vitamin E and Selenium, or herbs that contain antioxidants - such as green tea
Green tea
Green tea is made solely from the leaves of Camellia sinensis that have undergone minimal oxidation during processing. Green tea originates from China and has become associated with many cultures throughout Asia. It has recently become more widespread in the West, where black tea is traditionally...

 and jiaogulan
Jiaogulan
Gynostemma pentaphyllum, also called jiaogulan is an herbaceous vine of the family Cucurbitaceae indigenous to the southern reaches of China, northern Vietnam, southern Korea, and Japan. Jiaogulan is best known as an herbal medicine reputed to have powerful antioxidant and adaptogenic effects...

. Although some levels of antioxidant vitamins and minerals in the diet are required for good health, there is considerable doubt as to whether these antioxidant supplements are beneficial or harmful, and if they are actually beneficial, which antioxidant(s) are needed and in what amounts. Indeed, some authors argue that the hypothesis that antioxidants could prevent chronic diseases has now been disproved and that the idea was misguided from the beginning. Rather, dietary polyphenols may have non-antioxidant roles in minute concentrations that affect cell-to-cell signaling, receptor
Receptor (biochemistry)
In biochemistry, a receptor is a molecule found on the surface of a cell, which receives specific chemical signals from neighbouring cells or the wider environment within an organism...

 sensitivity, inflammatory enzyme
Enzyme
Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...

 activity or gene regulation.

For overall life expectancy
Life expectancy
Life expectancy is the expected number of years of life remaining at a given age. It is denoted by ex, which means the average number of subsequent years of life for someone now aged x, according to a particular mortality experience...

, it has even been suggested that moderate levels of oxidative stress may increase lifespan in the worm Caenorhabditis elegans, by inducing a protective response to increased levels of reactive oxygen species. The suggestion that increased life expectancy comes from increased oxidative stress conflicts with results seen in the yeast Saccharomyces cerevisiae
Saccharomyces cerevisiae
Saccharomyces cerevisiae is a species of yeast. It is perhaps the most useful yeast, having been instrumental to baking and brewing since ancient times. It is believed that it was originally isolated from the skin of grapes...

, and the situation in mammals is even less clear. Nevertheless, antioxidant supplements do not appear to increase life expectancy in humans.

Physical exercise


During exercise, oxygen consumption can increase by a factor of more than 10. This leads to a large increase in the production of oxidants and results in damage that contributes to muscular fatigue during and after exercise. The inflammatory response
Delayed onset muscle soreness
Delayed onset muscle soreness , also called muscle fever, is the pain and stiffness felt in muscles several hours to days after unaccustomed or strenuous exercise. The soreness is felt most strongly 24 to 72 hours after the exercise. It is caused by eccentric exercise...

 that occurs after strenuous exercise is also associated with oxidative stress, especially in the 24 hours after an exercise session. The immune system response to the damage done by exercise peaks 2 to 7 days after exercise, which is the period during which most of the adaptation that leads to greater fitness occurs. During this process, free radicals are produced by neutrophils to remove damaged tissue. As a result, excessive antioxidant levels may inhibit recovery and adaptation mechanisms. Antioxidant supplements may also prevent any of the health gains that normally come from exercise, such as increased insulin sensitivity.

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

However, no benefits for physical performance to athletes are seen with vitamin E supplementation. Indeed, despite its key role in preventing lipid membrane
Lipid bilayer
The lipid bilayer is a thin membrane made of two layers of lipid molecules. These membranes are flat sheets that form a continuous barrier around cells. The cell membrane of almost all living organisms and many viruses are made of a lipid bilayer, as are the membranes surrounding the cell nucleus...

 peroxidation, 6 weeks of vitamin E supplementation had no effect on muscle damage in ultramarathon runners. Although there appears to be no increased requirement for vitamin C in athletes, there is some evidence that vitamin C supplementation increased the amount of intense exercise that can be done and vitamin C supplementation before strenuous exercise may reduce the amount of muscle damage. However, other studies found no such effects, and some research suggests that supplementation with amounts as high as inhibits recovery.

Adverse effects


Relatively strong reducing acids can have antinutrient
Antinutrient
Antinutrients are natural or synthetic compounds that interfere with the absorption of nutrients. Nutrition studies focus on those antinutrients commonly found in food sources and beverages....

 effects by binding to dietary mineral
Dietary mineral
Dietary minerals are the chemical elements required by living organisms, other than the four elements carbon, hydrogen, nitrogen, and oxygen present in common organic molecules. Examples of mineral elements include calcium, magnesium, potassium, sodium, zinc, and iodine...

s such as iron and zinc in the gastrointestinal tract
Gastrointestinal tract
The human gastrointestinal tract refers to the stomach and intestine, and sometimes to all the structures from the mouth to the anus. ....

 and preventing them from being absorbed. Notable examples are oxalic acid
Oxalic acid
Oxalic acid is an organic compound with the formula H2C2O4. This colourless solid is a dicarboxylic acid. In terms of acid strength, it is about 3,000 times stronger than acetic acid. Oxalic acid is a reducing agent and its conjugate base, known as oxalate , is a chelating agent for metal cations...

, tannin
Tannin
A tannin is an astringent, bitter plant polyphenolic compound that binds to and precipitates proteins and various other organic compounds including amino acids and alkaloids.The term tannin refers to the use of...

s and phytic acid
Phytic acid
Phytic acid is the principal storage form of phosphorus in many plant tissues, especially bran and seeds. Phytate is not digestible to humans or nonruminant animals, however, so it is not a source of either inositol or phosphate if eaten directly...

, which are high in plant-based diets. Calcium
Calcium
Calcium is the chemical element with the symbol Ca and atomic number 20. It has an atomic mass of 40.078 amu. Calcium is a soft gray alkaline earth metal, and is the fifth-most-abundant element by mass in the Earth's crust...

 and iron deficiencies are not uncommon in diets in developing countries
Developing country
A developing country, also known as a less-developed country, is a nation with a low level of material well-being. Since no single definition of the term developing country is recognized internationally, the levels of development may vary widely within so-called developing countries...

 where less meat is eaten and there is high consumption of phytic acid from beans and unleavened whole grain
Whole grain
Whole grains are cereal grains that contain cereal germ, endosperm, and bran, in contrast to refined grains, which retain only the endosperm. Whole grains can generally be sprouted while refined grains generally will not sprout. Whole-meal products are made by grinding whole grains in order to make...

 bread.
Foods Reducing acid present
Cocoa bean and chocolate
Chocolate
Chocolate is a raw or processed food produced from the seed of the tropical Theobroma cacao tree. Cacao has been cultivated for at least three millennia in Mexico, Central and South America. Its earliest documented use is around 1100 BC...

, spinach
Spinach
Spinach is an edible flowering plant in the family of Amaranthaceae. It is native to central and southwestern Asia. It is an annual plant , which grows to a height of up to 30 cm. Spinach may survive over winter in temperate regions...

, turnip
Turnip
The turnip or white turnip is a root vegetable commonly grown in temperate climates worldwide for its white, bulbous taproot. Small, tender varieties are grown for human consumption, while larger varieties are grown as feed for livestock...

 and rhubarb
Rhubarb
Rhubarb is a group of plants that belong to the genus Rheum in the family Polygonaceae. They are herbaceous perennial plants growing from short, thick rhizomes. They have large leaves that are somewhat triangular-shaped with long fleshy petioles...

.
Oxalic acid
Oxalic acid
Oxalic acid is an organic compound with the formula H2C2O4. This colourless solid is a dicarboxylic acid. In terms of acid strength, it is about 3,000 times stronger than acetic acid. Oxalic acid is a reducing agent and its conjugate base, known as oxalate , is a chelating agent for metal cations...

Whole grains, maize
Maize
Maize known in many English-speaking countries as corn or mielie/mealie, is a grain domesticated by indigenous peoples in Mesoamerica in prehistoric times. The leafy stalk produces ears which contain seeds called kernels. Though technically a grain, maize kernels are used in cooking as a vegetable...

, legumes.
Phytic acid
Phytic acid
Phytic acid is the principal storage form of phosphorus in many plant tissues, especially bran and seeds. Phytate is not digestible to humans or nonruminant animals, however, so it is not a source of either inositol or phosphate if eaten directly...

Tea
Tea
Tea is an aromatic beverage prepared by adding cured leaves of the Camellia sinensis plant to hot water. The term also refers to the plant itself. After water, tea is the most widely consumed beverage in the world...

, beans, cabbage
Cabbage
Cabbage is a popular cultivar of the species Brassica oleracea Linne of the Family Brassicaceae and is a leafy green vegetable...

.
Tannins


Nonpolar antioxidants such as eugenol
Eugenol
Eugenol is a phenylpropene, an allyl chain-substituted guaiacol. Eugenol is a member of the phenylpropanoids class of chemical compounds. It is a clear to pale yellow oily liquid extracted from certain essential oils especially from clove oil, nutmeg, cinnamon, basil and bay leaf. It is slightly...

—a major component of oil of cloves
Oil of cloves
Oil of cloves, also known as clove oil, is an essential oil from the clove plant, Syzygium aromaticum.* CAS number: 8000-34-8It is a natural analgaesic and antiseptic used primarily in dentistry for its main ingredient eugenol...

—have toxicity limits that can be exceeded with the misuse of undiluted essential oil
Essential oil
An essential oil is a concentrated hydrophobic liquid containing volatile aroma compounds from plants. Essential oils are also known as volatile oils, ethereal oils or aetherolea, or simply as the "oil of" the plant from which they were extracted, such as oil of clove...

s. Toxicity associated with high doses of water-soluble antioxidants such as ascorbic acid are less of a concern, as these compounds can be excreted rapidly in urine
Urine
Urine is a typically sterile liquid by-product of the body that is secreted by the kidneys through a process called urination and excreted through the urethra. Cellular metabolism generates numerous by-products, many rich in nitrogen, that require elimination from the bloodstream...

. More seriously, very high doses of some antioxidants may have harmful long-term effects. The beta-Carotene and Retinol Efficacy Trial (CARET) study of lung cancer
Lung cancer
Lung cancer is a disease characterized by uncontrolled cell growth in tissues of the lung. If left untreated, this growth can spread beyond the lung in a process called metastasis into nearby tissue and, eventually, into other parts of the body. Most cancers that start in lung, known as primary...

 patients found that smokers given supplements containing beta-carotene and vitamin A had increased rates of lung cancer. Subsequent studies confirmed these adverse effects.

These harmful effects may also be seen in non-smokers, as a recent meta-analysis
Meta-analysis
In statistics, a meta-analysis combines the results of several studies that address a set of related research hypotheses. In its simplest form, this is normally by identification of a common measure of effect size, for which a weighted average might be the output of a meta-analyses. Here the...

 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. No health risk was seen when all the randomized controlled studies were examined together, but an increase in mortality was detected only when the high-quality and low-bias risk trials were examined separately. However, as the majority of these low-bias trials dealt with either elderly people
Old age
Old age consists of ages nearing or surpassing the average life span of human beings, and thus the end of the human life cycle...

, or people already suffering disease, these results may not apply to the general population. This meta-analysis was later repeated and extended by the same authors, with the new analysis published by the Cochrane Collaboration
Cochrane Collaboration
The Cochrane Collaboration is a group of over 28,000 volunteers in more than 100 countries who review the effects of health care interventions tested in biomedical randomized controlled trials. A few more recent reviews have also studied the results of non-randomized, observational studies...

; confirming the previous results. These two publications are consistent with some previous meta-analyzes that also suggested that Vitamin E supplementation increased mortality, and that antioxidant supplements increased the risk of colon cancer
Colorectal cancer
Colorectal cancer, commonly known as bowel cancer, is a cancer caused by uncontrolled cell growth , in the colon, rectum, or vermiform appendix. Colorectal cancer is clinically distinct from anal cancer, which affects the anus....

. However, the results of this meta-analysis are inconsistent with other studies such as the SU.VI.MAX trial, which suggested that antioxidants have no effect on cause-all mortality. 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.

While antioxidant supplementation is widely used in attempts to prevent the development of cancer, it has been proposed that antioxidants may, paradoxically, interfere with cancer treatments. This was thought to occur since the environment of cancer cells causes high levels of oxidative stress, making these cells more susceptible to the further oxidative stress induced by treatments. As a result, by reducing the redox stress in cancer cells, antioxidant supplements could decrease the effectiveness of radiotherapy and chemotherapy
Chemotherapy
Chemotherapy is the treatment of cancer with an antineoplastic drug or with a combination of such drugs into a standardized treatment regimen....

. On the other hand, other reviews have suggested that antioxidants could reduce side effect
Adverse effect
In medicine, an adverse effect is a harmful and undesired effect resulting from a medication or other intervention such as surgery.An adverse effect may be termed a "side effect", when judged to be secondary to a main or therapeutic effect. If it results from an unsuitable or incorrect dosage or...

s or increase survival times.

Measurement and levels in food


Measurement of antioxidants is not a straightforward process, as this is a diverse group of compounds with different reactivities to different reactive oxygen species. In food science
Food science
Food science is a study concerned with all technical aspects of foods, beginning with harvesting or slaughtering, and ending with its cooking and consumption, an ideology commonly referred to as "from field to fork"...

, the oxygen radical absorbance capacity
Oxygen radical absorbance capacity
Oxygen Radical Absorbance Capacity is a method of measuring antioxidant capacities in biological samples in vitro.A wide variety of foods has been tested using this method, with certain spices, berries and legumes rated highly. There exists no physiological proof in vivo that free-radical theory...

 (ORAC) has become the current industry standard for assessing antioxidant strength of whole foods, juices and food additives. Other measurement tests include the Folin-Ciocalteu reagent
Folin-Ciocalteu reagent
The Folin–Ciocalteu reagent or Folin's phenol reagent or Folin–Denis reagent, also called the Gallic Acid Equivalence method , is a mixture of phosphomolybdate and phosphotungstate used for the colorimetric assay of phenolic and polyphenolic antioxidants...

, and the Trolox equivalent antioxidant capacity
Trolox equivalent antioxidant capacity
Trolox equivalent antioxidant capacity measures the antioxidant capacity of a given substance, as compared to the standard, Trolox. Most commonly, antioxidant capacity is measured using the ABTS Decolorization Assay...

 assay.

Antioxidants are found in varying amounts in foods such as vegetables, fruits, grain cereals, eggs, meat, legumes and nuts. Some antioxidants such as lycopene
Lycopene
Lycopene is a bright red carotene and carotenoid pigment and phytochemical found in tomatoes and other red fruits and vegetables, such as red carrots, watermelons and papayas...

 and ascorbic acid can be destroyed by long-term storage or prolonged cooking. Other antioxidant compounds are more stable, such as the polyphenolic antioxidants in foods such as whole-wheat cereals and tea. The effects of cooking and food processing are complex, as these processes can also increase the bioavailability
Bioavailability
In pharmacology, bioavailability is a subcategory of absorption and is used to describe the fraction of an administered dose of unchanged drug that reaches the systemic circulation, one of the principal pharmacokinetic properties of drugs. By definition, when a medication is administered...

 of antioxidants, such as some carotenoids in vegetables. In general, processed foods contain fewer antioxidants than fresh and uncooked foods, since the preparation processes may expose the food to oxygen.
Antioxidant compounds Foods containing high levels of these antioxidants
Vitamin C (ascorbic acid) Fresh Fruits and vegetables
Vitamin E (tocopherols, tocotrienols) Vegetable oils
Polyphenolic antioxidants (resveratrol
Resveratrol
Resveratrol is a stilbenoid, a type of natural phenol, and a phytoalexin produced naturally by several plants when under attack by pathogens such as bacteria or fungi....

, flavonoid
Flavonoid
Flavonoids , are a class of plant secondary metabolites....

s)
Tea
Tea
Tea is an aromatic beverage prepared by adding cured leaves of the Camellia sinensis plant to hot water. The term also refers to the plant itself. After water, tea is the most widely consumed beverage in the world...

, coffee
Coffee
Coffee is a brewed beverage with a dark,init brooo acidic flavor prepared from the roasted seeds of the coffee plant, colloquially called coffee beans. The beans are found in coffee cherries, which grow on trees cultivated in over 70 countries, primarily in equatorial Latin America, Southeast Asia,...

, soy, fruit
Fruit
In broad terms, a fruit is a structure of a plant that contains its seeds.The term has different meanings dependent on context. In non-technical usage, such as food preparation, fruit normally means the fleshy seed-associated structures of certain plants that are sweet and edible in the raw state,...

, olive oil
Olive oil
Olive oil is an oil obtained from the olive , a traditional tree crop of the Mediterranean Basin. It is commonly used in cooking, cosmetics, pharmaceuticals, and soaps and as a fuel for traditional oil lamps...

, chocolate
Chocolate
Chocolate is a raw or processed food produced from the seed of the tropical Theobroma cacao tree. Cacao has been cultivated for at least three millennia in Mexico, Central and South America. Its earliest documented use is around 1100 BC...

, cinnamon
Cinnamon
Cinnamon is a spice obtained from the inner bark of several trees from the genus Cinnamomum that is used in both sweet and savoury foods...

, oregano
Oregano
Oregano – scientifically named Origanum vulgare by Carolus Linnaeus – is a common species of Origanum, a genus of the mint family . It is native to warm-temperate western and southwestern Eurasia and the Mediterranean region.Oregano is a perennial herb, growing from 20–80 cm tall,...

 and red wine
Carotenoid
Carotenoid
Carotenoids are tetraterpenoid organic pigments that are naturally occurring in the chloroplasts and chromoplasts of plants and some other photosynthetic organisms like algae, some bacteria, and some types of fungus. Carotenoids can be synthesized fats and other basic organic metabolic building...

s (lycopene, carotenes, lutein
Lutein
Lutein is a xanthophyll and one of 600 known naturally occurring carotenoids. Lutein is synthesized only by plants and like other xanthophylls is found in high quantities in green leafy vegetables such as spinach and kale...

)
Fruit, vegetables and eggs.


Other antioxidants are not vitamins and are instead made in the body. For example, ubiquinol
Ubiquinol
Ubiquinol is an electron-rich form of coenzyme Q10.The natural ubiquinol form of coenzyme Q10 is 2,3-dimethoxy-5-methyl-6-poly prenyl-1,4-benzoquinol, where the polyprenylated side chain is 9-10 units long in mammals...

 (coenzyme Q) is poorly absorbed from the gut and is made in humans through the mevalonate pathway. Another example is glutathione
Glutathione
Glutathione is a tripeptide that contains an unusual peptide linkage between the amine group of cysteine and the carboxyl group of the glutamate side-chain...

, which is made from amino acids. As any glutathione in the gut is broken down to free cysteine, glycine
Glycine
Glycine is an organic compound with the formula NH2CH2COOH. Having a hydrogen substituent as its 'side chain', glycine is the smallest of the 20 amino acids commonly found in proteins. Its codons are GGU, GGC, GGA, GGG cf. the genetic code.Glycine is a colourless, sweet-tasting crystalline solid...

 and glutamic acid
Glutamic acid
Glutamic acid is one of the 20 proteinogenic amino acids, and its codons are GAA and GAG. It is a non-essential amino acid. The carboxylate anions and salts of glutamic acid are known as glutamates...

 before being absorbed, even large oral doses have little effect on the concentration of glutathione in the body. Although large amounts of sulfur-containing amino acids such as acetylcysteine can increase glutathione, no evidence exists that eating high levels of these glutathione precursors is beneficial for healthy adults. Supplying more of these precursors may be useful as part of the treatment of some diseases, such as acute respiratory distress syndrome
Acute respiratory distress syndrome
Acute respiratory distress syndrome , also known as respiratory distress syndrome or adult respiratory distress syndrome is a serious reaction to various forms of injuries to the lung....

, protein-energy malnutrition
Protein-energy malnutrition
Protein-energy malnutrition refers to a form of malnutrition where there is inadequate protein intake.Types include:* Kwashiorkor...

, or preventing the liver damage produced by paracetamol
Paracetamol
Paracetamol INN , or acetaminophen USAN , is a widely used over-the-counter analgesic and antipyretic . It is commonly used for the relief of headaches and other minor aches and pains and is a major ingredient in numerous cold and flu remedies...

 overdose.

Other compounds in the diet can alter the levels of antioxidants by acting as pro-oxidant
Pro-oxidant
Pro-oxidants are chemicals that induce oxidative stress, through either creating reactive oxygen species or inhibiting antioxidant systems. The oxidative stress produced by these chemicals can damage cells and tissues...

s. Here, consuming the compound causes oxidative stress, which the body responds to by inducing higher levels of antioxidant defenses such as antioxidant enzymes. Some of these compounds, such as isothiocyanate
Isothiocyanate
Isothiocyanate is the chemical group –N=C=S, formed by substituting sulfur for oxygen in the isocyanate group. Many natural isothiocyanates from plants are produced by enzymatic conversion of metabolites called glucosinolates. These natural isothiocyanates, such as allyl isothiocyanate, are also...

s and curcumin
Curcumin
Curcumin is the principal curcuminoid of the popular Indian spice turmeric, which is a member of the ginger family . The other two curcuminoids are desmethoxycurcumin and bis-desmethoxycurcumin. The curcuminoids are natural phenols and are responsible for the yellow color of turmeric...

, may be chemopreventive
Chemoprophylaxis
Chemoprophylaxis refers to the administration of a medication for the purpose of preventing disease or infection. Antibiotics, for example, may be administered to patients with disorders of immune system function to prevent bacterial infections...

 agents that either block the transformation of abnormal cells into cancerous cells, or even kill existing cancer cells.

Food preservatives


Antioxidants are used as food additive
Food additive
Food additives are substances added to food to preserve flavor or enhance its taste and appearance.Some additives have been used for centuries; for example, preserving food by pickling , salting, as with bacon, preserving sweets or using sulfur dioxide as in some wines...

s to help guard against food deterioration
Preservative
A preservative is a naturally occurring or synthetically produced substance that is added to products such as foods, pharmaceuticals, paints, biological samples, wood, etc. to prevent decomposition by microbial growth or by undesirable chemical changes....

. 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
Respiration (physiology)
'In physiology, respiration is defined as the transport of oxygen from the outside air to the cells within tissues, and the transport of carbon dioxide in the opposite direction...

, storing plant materials in anaerobic
Anaerobic respiration
Anaerobic respiration is a form of respiration using electron acceptors other than oxygen. Although oxygen is not used as the final electron acceptor, the process still uses a respiratory electron transport chain; it is respiration without oxygen...

 conditions produces unpleasant flavors and unappealing colors. Consequently, packaging of fresh fruits and vegetables contains an ~8% oxygen atmosphere. Antioxidants are an especially important class of preservatives as, unlike bacteria
Bacteria
Bacteria are a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria have a wide range of shapes, ranging from spheres to rods and spirals...

l or fungal
Fungus
A fungus is a member of a large group of eukaryotic organisms that includes microorganisms such as yeasts and molds , as well as the more familiar mushrooms. These organisms are classified as a kingdom, Fungi, which is separate from plants, animals, and bacteria...

 spoilage, oxidation reactions still occur relatively rapidly in frozen or refrigerated food. These preservatives include natural antioxidants such as ascorbic acid (AA, E300) and tocopherols (E306), as well as synthetic antioxidants such as propyl gallate
Propyl gallate
Propyl gallate, or propyl 3,4,5-trihydroxybenzoate is an ester formed by the condensation of gallic acid and propanol. Since 1948, this antioxidant has been added to foods containing oils and fats to prevent oxidation. As a food additive, it is used under the E number E310.-Description:Propyl...

 (PG, E310), tertiary butylhydroquinone
Tert-Butylhydroquinone
tert-Butylhydroquinone is an aromatic organic compound which is a type of phenol. It is a derivative of hydroquinone, substituted with tert-butyl group.-Applications:...

 (TBHQ), butylated hydroxyanisole
Butylated hydroxyanisole
Butylated hydroxyanisole is an antioxidant consisting of a mixture of two isomeric organic compounds, 2-tert-butyl-4-hydroxyanisole and 3-tert-butyl-4-hydroxyanisole. It is prepared from 4-methoxyphenol and isobutylene. It is a waxy solid used as a food additive with the E number E320...

 (BHA, E320) and butylated hydroxytoluene
Butylated hydroxytoluene
Butylated hydroxytoluene , also known as butylhydroxytoluene, is a lipophilic organic compound that is primarily used as an antioxidant food additive as well as an antioxidant additive in cosmetics, pharmaceuticals, jet fuels, rubber, petroleum products, electrical transformer oil, and embalming...

 (BHT, E321).

The most common molecules attacked by oxidation are unsaturated fats; oxidation causes them to turn rancid
Rancidification
Rancidification is the chemical decomposition of fats, oils and other lipids . When these processes occur in food, undesirable odors and flavors can result. In some cases, however, the flavors can be desirable . In processed meats, these flavors are collectively known as "warmed over flavor"...

. Since oxidized lipids are often discolored and usually have unpleasant tastes such as metallic or sulfur
Sulfur
Sulfur or sulphur is the chemical element with atomic number 16. In the periodic table it is represented by the symbol S. It is an abundant, multivalent non-metal. Under normal conditions, sulfur atoms form cyclic octatomic molecules with chemical formula S8. Elemental sulfur is a bright yellow...

ous flavors, it is important to avoid oxidation in fat-rich foods. Thus, these foods are rarely preserved by drying; instead, they are preserved by smoking
Smoking (cooking technique)
Smoking is the process of flavoring, cooking, or preserving food by exposing it to the smoke from burning or smoldering plant materials, most often wood...

, salting
Salting (food)
Salting is the preservation of food with dry edible salt. It is related to pickling . It is one of the oldest methods of preserving food, and two historically significant salt-cured foods are dried and salted cod and salt-cured meat.Salting is used because most bacteria, fungi and other potentially...

 or fermenting
Fermentation (food)
Fermentation in food processing typically is the conversion of carbohydrates to alcohols and carbon dioxide or organic acids using yeasts, bacteria, or a combination thereof, under anaerobic conditions. Fermentation in simple terms is the chemical conversion of sugars into ethanol...

. Even less fatty foods such as fruits are sprayed with sulfurous antioxidants prior to air drying. Oxidation is often catalyzed by metals, which is why fats such as butter should never be wrapped in aluminium foil
Aluminium foil
Aluminium foil is aluminium prepared in thin metal leaves, with a thickness less than , thinner gauges down to are also commonly used. In the USA, foils are commonly gauged in mils. Standard household foil is typically thick and heavy duty household foil is typically .The foil is pliable, and...

 or kept in metal containers. Some fatty foods such as olive oil are partially protected from oxidation by their natural content of antioxidants, but remain sensitive to photooxidation. Antioxidant preservatives are also added to fat-based cosmetics
Cosmetics
Cosmetics are substances used to enhance the appearance or odor of the human body. Cosmetics include skin-care creams, lotions, powders, perfumes, lipsticks, fingernail and toe nail polish, eye and facial makeup, towelettes, permanent waves, colored contact lenses, hair colors, hair sprays and...

 such as lipstick
Lipstick
Lipstick is a cosmetic product containing pigments, oils, waxes, and emollients that applies color, texture, and protection to the lips. Many varieties of lipstick are known. As with most other types of makeup, lipstick is typically, but not exclusively, worn by women...

 and moisturizer
Moisturizer
Moisturizers or emollients are complex mixtures of chemical agents specially designed to make the external layers of the skin softer and more pliable, by increasing its hydration by reducing evaporation. Naturally occurring skin lipids and sterols as well as artificial or natural oils,...

s to prevent rancidity.

Industrial uses


Antioxidants are frequently added to industrial products. A common use is as stabilizers
Gasoline additive
Gasoline additives increase gasoline's octane rating or act as corrosion inhibitors or lubricants, thus allowing the use of higher compression ratios for greater efficiency and power, however some carry heavy environmental risks...

 in fuel
Fuel
Fuel is any material that stores energy that can later be extracted to perform mechanical work in a controlled manner. Most fuels used by humans undergo combustion, a redox reaction in which a combustible substance releases energy after it ignites and reacts with the oxygen in the air...

s and lubricant
Lubricant
A lubricant is a substance introduced to reduce friction between moving surfaces. It may also have the function of transporting foreign particles and of distributing heat...

s to prevent oxidation, and in gasolines to prevent the polymerization that leads to the formation of engine-fouling residues. In 2007, the worldwide market for industrial antioxidants had a total volume of around 0.88 million tons. This created a revenue of circa 3.7 billion US-dollars (2.4 billion Euros).

They are widely used to prevent the oxidative degradation of polymers such as rubbers, plastic
Plastic
A plastic material is any of a wide range of synthetic or semi-synthetic organic solids used in the manufacture of industrial products. Plastics are typically polymers of high molecular mass, and may contain other substances to improve performance and/or reduce production costs...

s and adhesive
Adhesive
An adhesive, or glue, is a mixture in a liquid or semi-liquid state that adheres or bonds items together. Adhesives may come from either natural or synthetic sources. The types of materials that can be bonded are vast but they are especially useful for bonding thin materials...

s that causes a loss of strength and flexibility in these materials. Polymers containing double bonds in their main chains, such as such as natural rubber and polybutadiene
Polybutadiene
Polybutadiene is a synthetic rubber that is a polymer formed from the polymerization process of the monomer 1,3-butadiene.It has a high resistance to wear and is used especially in the manufacture of tires, which consumes about 70% of the production...

, are especially susceptible to oxidation and ozonolysis
Ozonolysis
Ozonolysis is the cleavage of an alkene or alkyne with ozone to form organic compounds in which the multiple carbon–carbon bond has been replaced by a double bond to oxygen...

. They can be protected by antiozonant
Antiozonant
An antiozonant, also known as anti-ozonant, is a chemical compound that prevents or slows down the degradation of material caused by ozone gas in the air...

s. Solid polymer products start to crack on exposed surfaces as the material degrades and the chains break. The mode of cracking varies between oxygen and ozone
Ozone
Ozone , or trioxygen, is a triatomic molecule, consisting of three oxygen atoms. It is an allotrope of oxygen that is much less stable than the diatomic allotrope...

 attack, the former causing a "crazy paving" effect, while ozone attack produces deeper cracks aligned at right angles to the tensile strain in the product. Oxidation and UV degradation
UV degradation
Many natural and synthetic polymers are attacked by ultra-violet radiation and products made using these materials may crack or disintegrate . The problem is known as UV degradation, and is a common problem in products exposed to sunlight...

 are also frequently linked, mainly because UV radiation creates free radicals by bond breakage. The free radicals then react with oxygen to produce peroxy radicals which cause yet further damage, often in a chain reaction
Chain reaction
A chain reaction is a sequence of reactions where a reactive product or by-product causes additional reactions to take place. In a chain reaction, positive feedback leads to a self-amplifying chain of events....

. Other polymers susceptible to oxidation include polypropylene
Polypropylene
Polypropylene , also known as polypropene, is a thermoplastic polymer used in a wide variety of applications including packaging, textiles , stationery, plastic parts and reusable containers of various types, laboratory equipment, loudspeakers, automotive components, and polymer banknotes...

 and polyethylene
Polyethylene
Polyethylene or polythene is the most widely used plastic, with an annual production of approximately 80 million metric tons...

. The former is more sensitive owing to the presence of secondary carbon atoms present in every repeat unit. Attack occurs at this point because the free radical formed is more stable than one formed on a primary carbon atom. Oxidation of polyethylene tends to occur at weak links in the chain, such as branch points in low density polyethylene
Low density polyethylene
Low-density polyethylene is a thermoplastic made from petroleum. It was the first grade of polyethylene, produced in 1933 by Imperial Chemical Industries using a high pressure process via free radical polymerization. Its manufacture employs the same method today. LDPE is commonly recycled and has...

.
Fuel additive Components Applications
AO-22 N,N'-di-2-butyl-1,4-phenylenediamine
N,N'-Di-2-butyl-1,4-phenylenediamine
N,N-Di-2-butyl-1,4-phenylenediamine is an aromatic amine used industrially as an antioxidant to prevent degradation of turbine oils, transformer oils, hydraulic fluids, lubricants, waxes, and greases. It is particularly effective for hydrocarbon products produced by cracking or pyrolysis, which are...

Turbine oils, transformer oil
Transformer oil
Transformer oil or insulating oil is usually a highly-refined mineral oil that is stable at high temperatures and has excellent electrical insulating properties. It is used in oil-filled transformers, some types of high voltage capacitors, fluorescent lamp ballasts, and some types of high voltage...

s, hydraulic fluid
Hydraulic fluid
Hydraulic fluids, also called hydraulic liquids, are the medium by which power is transferred in hydraulic machinery. Common hydraulic fluids are based on mineral oil or water...

s, wax
Wax
thumb|right|[[Cetyl palmitate]], a typical wax ester.Wax refers to a class of chemical compounds that are plastic near ambient temperatures. Characteristically, they melt above 45 °C to give a low viscosity liquid. Waxes are insoluble in water but soluble in organic, nonpolar solvents...

es, and greases
Grease (lubricant)
The term grease is used to describe semisolid lubricants. Although the word grease is also used to describe rendered fat of animals, in the context of lubrication, grease typically applies to a material consisting of a soap emulsified with mineral or vegetable oil...

AO-24 N,N'-di-2-butyl-1,4-phenylenediamine Low-temperature oils
AO-29 2,6-di-tert-butyl-4-methylphenol Turbine oils, transformer oils, hydraulic fluids, waxes, greases, and gasolines
AO-30 2,4-dimethyl-6-tert-butylphenol
2,4-Dimethyl-6-tert-butylphenol
2,4-Dimethyl-6-tert-butylphenol is an alkylated phenol used industrially as an antioxidant, e.g. to prevent gumming in fuels, and as an ultraviolet stabilizer. It is used in jet fuels, gasolines, and avgas. It is a clear liquid with melting point 21-23 °C and boiling point 248-249 °C. It is also...

Jet fuel
Jet fuel
Jet fuel is a type of aviation fuel designed for use in aircraft powered by gas-turbine engines. It is clear to straw-colored in appearance. The most commonly used fuels for commercial aviation are Jet A and Jet A-1 which are produced to a standardized international specification...

s and gasolines, including aviation gasolines
AO-31 2,4-dimethyl-6-tert-butylphenol Jet fuels and gasolines, including aviation gasolines
AO-32 2,4-dimethyl-6-tert-butylphenol and 2,6-di-tert-butyl-4-methylphenol Jet fuels and gasolines, including aviation gasolines
AO-37 2,6-di-tert-butylphenol
2,6-Di-tert-butylphenol
2,6-Di-tert-butylphenol is an organic compound with the structural formula 2,6-2C6H3OH. This colourless solid alkylated phenol and its derivatives are used industrially as UV stabilizer and an antioxidant for hydrocarbon-based products ranging from petrochemicals to plastics...

Jet fuels and gasolines, widely approved for aviation fuel
Aviation fuel
Aviation fuel is a specialized type of petroleum-based fuel used to power aircraft. It is generally of a higher quality than fuels used in less critical applications, such as heating or road transport, and often contains additives to reduce the risk of icing or explosion due to high temperatures,...

s

See also



  • Forensic engineering
    Forensic engineering
    Forensic engineering is the investigation of materials, products, structures or components that fail or do not operate or function as intended, causing personal injury or damage to property. The consequences of failure are dealt with by the law of product liability. The field also deals with...

  • Mitohormesis - Hormesis
    Hormesis
    Hormesis is the term for generally favorable biological responses to low exposures to toxins and other stressors. A pollutant or toxin showing hormesis thus has the opposite effect in small doses as in large doses...

  • Nootropic
    Nootropic
    Nootropics , also referred to as smart drugs, brain steroids, memory enhancers, cognitive enhancers, and intelligence enhancers, are drugs, supplements, nutraceuticals, and functional foods that improve mental functions such as cognition, memory, intelligence, motivation, attention, and concentration...

  • Polymer degradation
    Polymer degradation
    Polymer degradation is a change in the properties—tensile strength, colour, shape, etc.—of a polymer or polymer-based product under the influence of one or more environmental factors such as heat, light or chemicals such as acids, alkalis and some salts...

  • Superfood
    Superfood
    Superfood is a term used by various people in a wide variety of manners and contexts. For example, it is sometimes used to describe food with high phytonutrient content that may confer health benefits as a result...



Further reading


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


External links