An Antioxidant is a molecule capable of slowing or preventing the oxidation of other molecules. Oxidation is a chemical reaction that transfers electrons from a substance to an oxidizing agent.
Oxidation reactions can produce free radicals, which start chain reactions that damage cells. Antioxidants terminate these chain reactions by removing radical intermediates, and inhibit other oxidation reactions by being oxidized themselves. As a result, antioxidants are often reducing agents such as thiols or polyphenols.
Although oxidation reactions are crucial for life, they can also be damaging; hence, plants and animals maintain complex systems of multiple types of antioxidants, such as glutathione, vitamin C, and vitamin E as well as enzymes such as catalase, superoxide dismutase and various peroxidases.
Low levels of antioxidants, or inhibition of the antioxidant enzymes causes oxidative stress and may damage or kill cells.
As oxidative stress has been associated with the pathogenesis of many human diseases, the use of antioxidants in pharmacology is intensively studied, particularly as treatments for stroke and neurodegenerative diseases.
However, it is unknown whether oxidative stress is the cause or the consequence of such diseases.
Antioxidants are also widely used as ingredients in dietary supplements in the hope of maintaining health and preventing diseases such as cancer and coronary heart disease.
Although some studies have suggested antioxidant supplements have health benefits, other large clinical trials did not detect any benefit for the formulations tested, and excess supplementation may occasionally be harmful. In addition to these uses in medicine, antioxidants have many industrial uses, such as preservatives in food and cosmetics and preventing the degradation of rubber and gasoline.
Sources of Antioxidants
Ascorbic acid (VITAMIN C)
Ascorbic acid or "vitamin C" is a monosaccharide antioxidant found in both animals and plants. As it cannot be synthesised in humans and must be obtained from the diet, it is a vitamin.
Most other animals are able to produce this compound in their bodies and do not require it in their diets.In cells, it is maintained in its reduced form by reaction with glutathione, which can be catalysed by protein disulfide isomerase and glutaredoxins.
Ascorbic acid is a reducing agent and 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 for the antioxidant enzyme ascorbate peroxidase, a function that is particularly important in stress resistance in plants.
Glutathione
The free radical mechanism of lipid peroxidation.
Glutathione is a cysteine-containing peptide found in most forms of aerobic life.It is not required in the diet and is instead synthesized in cells from its constituent amino acids.
Glutathione has antioxidant properties since the thiol group in its cysteine moiety is a reducing agent and can be reversibly oxidized and reduced. In cells, glutathione is maintained in the reduced form by the enzyme glutathione reductase and in turn reduces other metabolites and enzyme systems 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.
Melatonin
Melatonin is a powerful antioxidant that can easily cross cell membranes and the blood-brain barrier. Unlike other antioxidants, melatonin does not undergo redox cycling, which is the ability of a molecule to undergo repeated reduction and oxidation. Redox cycling may allow other antioxidants (such as vitamin C) to act as pro-oxidants and promote free radical formation.
Melatonin, once oxidized, cannot be reduced to its former state because it forms several stable end-products upon reacting with free radicals. Therefore, it has been referred to as a terminal (or suicidal) antioxidant.
Tocopherols and tocotrienols (vitamin E)
Vitamin E is the collective name for a set of eight related tocopherols and tocotrienols, which are fat-soluble antioxidant vitamins Of these, α-tocopherol has been most studied as it has the highest bioavailability, with the body preferentially absorbing and metabolising this form.
The α-tocopherol form is the most important lipid-soluble antioxidant and protects cell membranes against oxidation by reacting with the lipid radicals produced in the lipid peroxidation chain reaction.
This removes the free radical intermediates and prevents the propagation reaction from continuing. The oxidised α-tocopheroxyl radicals produced in this process may be recycled back to the active reduced form through reduction by ascorbate, retinol or ubiquinol.
The functions of the other forms of vitamin E are less well-studied, although γ-tocopherol is a nucleophile that may react with electrophilic mutagens, and tocotrienols may have a specialised role in neuroprotection.
Disease treatment
The brain is uniquely vulnerable to oxidative injury, due to its high metabolic rate and elevated levels of polyunsaturated lipids, the target of lipid peroxidation.
Consequently, antioxidants are commonly used as medications to treat various forms of brain injury. Here, superoxide dismutase mimetics, sodium thiopental and propofol are used to treat reperfusion injury and traumatic brain injury,while the experimental drug NXY-059 and ebselen are being applied in the treatment of stroke.
These compounds appear to prevent oxidative stress in neurons and prevent apoptosis and neurological damage. Antioxidants are also being investigated as possible treatments for neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis.
Disease prevention
Antioxidants can cancel out the cell-damaging effects of free radicals, and people who eat fruits and vegetables rich in polyphenols and anthocyanins have a lower risk of cancer, heart disease and some neurological diseases.
This observation suggested that these compounds might prevent conditions such as macular degeneration, suppressed immunity due to poor nutrition, and neurodegeneration, which are caused by oxidative stress.
However, despite the clear role of oxidative stress in cardiovascular disease, controlled studies using antioxidant vitamins have observed no clear reduction in the risk or progression of heart disease. This suggests that other substances in fruit and vegetables (possibly flavonoids) at least partially explain the better cardiovascular health of those who consume more fruit and vegetables.
It is thought that oxidation of low density lipoprotein in the blood contributes to heart disease, and initial observational studies found that people taking Vitamin E supplements had a lower risk of developing heart disease.
Consequently, at least seven large clinical trials were conducted to test the effects of antioxidant supplement with Vitamin E, in doses ranging from 50 to 600 mg per day. However, none of these trials found a statistically significant effect of Vitamin E on overall number of deaths or on deaths due to heart 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.
Over 12,500 French men and women took either low-dose antioxidants (120 mg of ascorbic acid, 30 mg of vitamin E, 6 mg of beta carotene, 100 μg of selenium, and 20 mg of zinc) or placebo pills for an average of 7.5 years.
The investigators found there was no statistically significant effect of the antioxidants on overall survival, cancer, or heart disease. However, a subgroup analysis showed a 31% reduction in the risk of cancer in men, but not women.
Many nutraceutical and health food companies now sell formulations of antioxidants as dietary supplements and these are widely used in industrialized countries.
These supplements may include specific antioxidant chemicals, like resveratrol (from grape seeds), combinations of antioxidants, like the "ACES" products that contain beta carotene (provitamin A), vitamin C, vitamin E and Selenium, or speciality herbs that are known to contain antioxidants such as green tea and jiaogulan. Although some levels of antioxidant vitamins and minerals in the diet are required for good health, there is considerable doubt as to whether antioxidant supplementation is beneficial, and if so, which antioxidant(s) are beneficial and in what amounts.
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 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 damage done by exercise peaks 2 to 7 days after exercise, the period during which adaptation resulting in greater fitness is greatest.
During this process, free radicals are produced by neutrophils to remove damaged tissue. As a result, excessive antioxidant levels have the potential to inhibit recovery and adaptation mechanisms.
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 deal with the increased oxidative stress.
It is possible that 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 to athletes are seen with vitamin A or E supplementation.
For example, despite its key role in preventing lipid membrane 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 1000 mg inhibits recovery.
Food preservatives
Antioxidants are used as food additives to help guard against food deterioration.
Exposure to oxygen and sunlight are the two main factors in the oxidation of food, so food is preserved by keeping in the dark and sealing it in containers or even coating it in wax, as with cucumbers.
However, as oxygen is also important for plant respiration, storing plant materials in anaerobic conditions produces unpleasant flavors and unappealing colors.
Consequently, packaging of fresh fruits and vegetables contains an ~8% oxygen atmosphere. Antioxidants are an especially important class of preservatives as, unlike bacterial or fungal spoilage, oxidation reactions still occur relatively rapidly in frozen or refrigerated food.
These preservatives include ascorbic acid (AA, E300), propyl gallate (PG, E310), tocopherols (E306), tertiary butylhydroquinone (TBHQ), butylated hydroxyanisole (BHA, E320) and butylated hydroxytoluene (BHT, E321).
The most common molecules attacked by oxidation are unsaturated fats; oxidation causes them to turn rancid.
Since oxidized lipids are often discolored and usually have unpleasant tastes such as metallic or sulfurous flavors, it is important to avoid oxidation in fat-rich foods. Thus, these foods are rarely preserved by drying; instead, they are preserved by smoking, salting or fermenting.
Even less fatty foods such as fruits are sprayed with sulfurous antioxidants prior to air drying. Oxidation is often catalyzed by metals, which is why fats such as butter should never be wrapped in aluminium foil or kept in metal containers.
Some fatty foods such as olive oil are partially protected from oxidation by their natural content of antioxidants, but remain sensitive to photooxidation.
Industrial uses
Some antioxidants are added to industrial products.
A common use is as stabilizers in fuels and lubricants to prevent oxidation, and in gasolines to prevent the polymerization that leads to the formation of engine-fouling residues.
They are also used to prevent the oxidative degradation of rubber, plastics and adhesives that causes a loss of strength and flexibility in these materials.
Antioxidant preservatives are also added to fat-based cosmetics such as lipstick and moisturizers to prevent rancidity.
