Antioxidants

Antioxidants are key to reducing the impact of oxidative stress.

Antioxidants create a barrier or a shield around the cell to help protect it from being damaged.

Compounds that inhibit oxidation. 

 

Oxidation refers to a chemical reaction that can produce free radicals.

 

Free radicals cam lead to chain reactions that may damage the cells of organisms. 

 

Antioxidants such as thiols or ascorbic acid terminate these chain reactions. 

 

The body maintains oxidative stress with complex systems of overlapping antioxidants, such as glutathione and enzymes, such as catalase and superoxide dismutase, produced internally, or the dietary antioxidants vitamin C and vitamin E.

 

The vast majority of complex life requires oxygen for its existence, oxygen is a highly reactive molecule that damages living organisms by producing reactive oxygen species.

 

The body contains a complex network of antioxidant metabolites and enzymes that work together to prevent oxidative damage to cellular components such as DNA, proteins and lipids.

 

Antioxidant systems either prevent these reactive species from being formed, or remove them before they can damage vital components of the cell.

 

Reactive oxygen species also have useful cellular functions, such as redox signaling. 

 

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

 

Antioxidant dietary supplements have not been shown to improve health.

 

Antioxidant dietary supplements have not been shown to be effective at preventing disease: beta-carotene, vitamin A, and vitamin E supplements have no positive effect on mortality rate or cancer risk.

 

Supplementation with selenium or vitamin E does not reduce the risk of cardiovascular disease.

 

The hypothesis that antioxidant vitamins could prevent chronic diseases is unproven.

 

Common pharmaceuticals and supplements with antioxidant properties may interfere with the efficacy of certain anticancer medications.

 

Strong reducing acids can have antinutrient effects by binding to dietary minerals such as iron and zinc in the gastrointestinal tract and preventing them from being absorbed.

 

Strong reducing acids such as oxalic acid, tannins and phytic acid, which are high in plant-based diets may be associated with mineral deficiencies.

 

Iron deficiencies are not uncommon in diets in countries where less meat is eaten and there is high consumption of phytic acid from beans and unleavened whole grain bread.

 

In The beta-Carotene and Retinol Efficacy Trial (CARET) study of lung cancer patients found that smokers managed with supplements containing beta-carotene and vitamin A had increased rates of lung cancer.

 

Similar harmful effects have been seen in non-smokers: meta-analysis including data from approximately 230,000 patients showed that β-carotene, vitamin A or vitamin E supplementation is associated with increased mortality.

 

In a large number of clinical trials carried out on antioxidant supplements suggest that they have no effect on health, or that they cause a small increase in mortality in elderly or vulnerable populations.

 

Reactive oxygen species produced in cells include hydrogen peroxide (H2O2), hypochlorous acid (HClO), and free radicals such as the hydroxyl radical (·OH) and the superoxide anion (O2−).

 

The hydroxyl radical produced from hydrogen peroxide is very unstable and reacts rapidly and non-specifically with most biological molecules. 

 

Oxidants can damage cells by starting chemical chain reactions such as lipid peroxidation, or by oxidizing DNA or proteins.

 

DNA damage can cause mutations and possibly cancer, if not reversed by DNA repair mechanisms while damage to proteins causes enzyme inhibition, denaturation and protein degradation.

 

Oxygen generates metabolic energy and produces reactive oxygen species.

 

The superoxide anion is produced as a by-product of several steps in the electron transport chain.

 

The reduction of coenzyme Q results in a highly reactive free radical, that is an unstable intermediate that can lead to electron leakage.

 

When  electrons jump directly to oxygen they form the superoxide anion.

 

Antioxidants are classified into two broad divisions: hydrophilic or lipophilic.

 

Water-soluble antioxidants react with oxidants in the cell cytosol and the blood plasma.

 

Lipid-soluble antioxidants protect cell membranes from lipid peroxidation.

 

Antioxidants may be synthesized in the body or obtained from the diet.

 

Antioxidants are present in a wide range of concentrations in body fluids and tissues.

 

The action of one antioxidant may depend on the proper function of other members of the antioxidant system.

 

Antioxidant activity depends 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 act as an antioxidant defense by chelating transition metals and preventing them from catalyzing the production of free radicals in the cell. 

 

This is seen with the ability to sequester iron, which is the function of iron-binding proteins such as transferrin and ferritin.

 

Selenium and zinc are commonly referred to as antioxidant nutrients, but they have no antioxidant action themselves and are instead required for the activity of some antioxidant enzymes.

 

Uric acid is the highest concentration antioxidant in human blood. 

 

Uric acid is an antioxidant oxypurine produced from xanthine by the enzyme xanthine oxidase, and is an intermediate product of purine metabolism.

 

Uric  acid acts as an antioxidant by mitigating the oxidative stress caused by high-altitude hypoxia.

 

Uric acid has the highest concentration of any blood antioxidant and provides over half of the total antioxidant capacity of human serum.

 

Ascorbic acid or vitamin C is a monosaccharide oxidation-reduction (redox) catalyst.

 

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 redox catalyst.

 

Ascorbic acid can reduce, and thereby neutralize, reactive oxygen species such as hydrogen peroxide.

 

Glutathione is a cysteine-containing peptide that 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. 

 

Glutathione is maintained in  cells in the reduced form by the enzyme glutathione reductase.

 

Glutathione  reduces other metabolites and enzyme systems, such as ascorbate in the glutathione-ascorbate cycle, glutathione peroxidases and glutaredoxins, as well as reacting directly with oxidants.

 

Glutathione is one of the most important cellular antioxidants related to its high cell concentration and its central role in maintaining the cell’s redox state.

 

Vitamin E: a set of eight related tocopherols and tocotrienols, which are fat-soluble vitamins with antioxidant properties.

 

α-tocopherol form is the most important lipid-soluble antioxidant.

 

α-tocopherol protects membranes from oxidation by reacting with lipid radicals produced in the lipid peroxidation chain reaction, removing the free radical intermediates and prevents the propagation reaction from continuing. 

 

α-tocopherol, but not water-soluble antioxidants, efficiently protects glutathione peroxidase 4 deficient cells from cell death.

 

Antioxidants that are reducing agents can act as pro-oxidants. 

 

Vitamin C by oxidizing polypeptides, has the most  antioxidant action in the human body.

 

Uric acid  also has direct and indirect pro-oxidant properties.

 

Agents which are normally considered antioxidants can act as conditional pro-oxidants and actually increase oxidative stress. 

 

Ascorbate, uric acid and sulfhydryl amino acids such as homocysteine. are medically important conditional pro-oxidants.

 

Cells  protect against oxidative stress by an interacting network of antioxidant enzymes.

 

Superoxide dismutases (SODs) are a enzymes that are present in almost all aerobic cells and in extracellular fluids, and catalyze the breakdown of the superoxide anion into oxygen and hydrogen peroxide.

 

Superoxide dismutase enzymes contain metal ion cofactors: copper, zinc, manganese or iron. 

 

The copper/zinc SOD is present in the cytosol, while manganese SOD is present in the mitochondrion.

 

A third form of SOD exists in extracellular fluids.

 

The mitochondrial isozyme seems to be the most biologically important of these three.

 

Catalases are enzymes that catalyse the conversion of hydrogen peroxide to water and oxygen, using either an iron or manganese cofactor.

 

Oxidative stress is thought to contribute to the development of diseases that include: Alzheimer’s disease.

 

Parkinson’s disease, diabetes, rheumatoid arthritis, and neurodegeneration in motor neuron diseases.

 

Low density lipoprotein (LDL) oxidation triggers the process of atherogenesis, which results in atherosclerosis, and cardiovascular disease.

 

Oxidative damage in DNA can cause cancer. 

 

The antioxidant enzymes superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, glutathione S-transferase and others protect DNA from oxidative stress. 

 

Polymorphisms in these enzymes are associated with DNA damage and subsequently the individual’s risk of cancer susceptibility.

 

Antioxidants are used as food additives to help delay  food deterioration. 

 

Exposure to oxygen and sunlight are the two main factors in the oxidation of food.

 

Packaging of fresh fruits and vegetables contains about 8% oxygen atmosphere. 

 

Antioxidants are a class of preservatives as oxidation reactions occur relatively rapidly in frozen or refrigerated food.

 

Such preservatives include natural antioxidants such as ascorbic acid and tocopherols as well as synthetic antioxidants.

 

The most common food molecules attacked by oxidation are unsaturated fats.

 

Oxidation causes unsaturated fats to turn rancid.

 

Oxidized lipids are often discolored and have unpleasant tastes such as metallic or sulfurous flavors.

 

Fats are preserved by smoking, salting or fermenting. 

 

Fruits are sprayed with sulfurous antioxidants prior to air drying. 

 

Oxidation is often catalyzed by metals, and that 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.

 

Antioxidant preservatives are added to fat based cosmetics such as lipstick and moisturizers to prevent rancidity.

 

Antioxidants are frequently added to industrial products: fuels and lubricants to prevent oxidation, in gasolines to prevent the polymerization, and in rubbers, plastics and adhesives that causes a loss of strength and flexibility in these materials.

 

Oxidation and UV degradation are also frequently linked, mainly because UV radiation creates free radicals by bond breakage. 

 

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

 

Antioxidant vitamins are found in vegetables, fruits, eggs, legumes and nuts. 

 

Antioxidant vitamins A, C, and E can be destroyed by long-term storage or prolonged cooking.

 

Cooking and food processing can also increase the bioavailability of antioxidants, such as some carotenoids in vegetables.

 

Processed food contains fewer antioxidant vitamins than fresh and uncooked foods, as preparation exposes food to heat and oxygen.

 

Foods containing high levels of antioxidant vitamins: 

 

Vitamin C-Fresh or frozen fruits and vegetables

 

Vitamin E -Vegetable oils, nuts, and seeds

 

Carotenoids-Fruit, vegetables and eggs.

 

Some antioxidants are not obtained from the diet, are made in the body: 

 

Ubiquinol (coenzyme Q) is poorly absorbed from the gut and is made through the mevalonate pathway.

 

Glutathione made from amino acids. 

 

Glutathione in the gut is broken down to free cysteine, glycine and glutamic acid before being absorbed.

 

Large amounts of sulfur-containing amino acids such as acetylcysteine can increase glutathione, but 

 

evidence exists that eating high levels of these glutathione precursors is beneficial for healthy adults is absent.

 

Vitamin E, beta-carotene and vitamin C usage after an average follow-up of 4.2 years did not prevent prostate cancer.

High density lipoprotein (HDL) exerts antiatherogenic influence by antioxidant properties.

In a review of 78 randomized trials using antioxidant supplements: beta-carotene, vitamin A, vitamin C, vitamin D, and selenium versus placebo or no intervention is not associated with lower all cause mortality (Bjelakovic G et al).

In the above studies beta-carotene, vitamin E, and higher doses of vitamin A may be associated with higher all cause mortality.