Cancer preventive dietary antioxidants

An antioxidant is a nutrient that helps inhibit or delay oxidation reactions caused by free radicals (free radical scavengers). Dietary antioxidants are compounds that reduce oxidative damage to the body by free radicals. Dietary antioxidants can safely interact with free radicals and terminate chain reaction of oxidation before vital molecules are damaged. Cell damage caused by free radicals appears to be a major contributor to aging and diseases like cancer and heart disease. Overall free radicals have been implicated in the pathogenesis of at least 50 diseases.  Antioxidants prevent the free radical damage to the delicate lining of one’s blood vessels, to the brain and nervous system and the DNA molecules. Antioxidants repair the cell damage associated with neurodegenerative conditions. They protect human body cells from the ravages of inflammation. Inflammation is known to be associated with increased levels of lipid peroxides and free radicals. Antioxidants play important roles as anti-disease agents and anti-aging agents.The dietary antioxidants such as vitamins A,C and E; carotenoids(i.e., beta-carotene, lutein and lycophene); polyphenols; the mineral selenium; and endogenous antioxidants such as glutathione-elevating agents (n-acetyl cysteine and alpha – lipoic acid), co enzyme Q10 and L-carnitine are essential for cancer prevention.

Definition of antioxidants

The USDA defined antioxidants as “compounds that protect biological systems against the potentially harmful effects of processes or reactions that can cause excessive oxidations.”
The Food and Nutrition Board of the Institute of Medicine (IOM) defined a dietary antioxidant as “a substance in foods that significantly decreases the adverse effects of reactive species such as reactive oxygen and nitrogen species, on normal physiological function in humans.”
The normal functioning of cells is dependent on a proper balance of pro-oxidants and antioxidants. The pro-oxidants promote the release of oxygen to provide energy needed for functioning of normal cells. However antioxidants protect the body from free radical damage. Antioxidants donate electrons to the free radicals and stop the chain reaction.

Reactive oxygen species (ROS)

Reactive oxygen species which encompasses all highly reactive oxygen molecules including free radicals. Free radicals are incomplete, highly unstable and reactive compounds or molecules. Free radicals contain one or more unbound or unpaired electrons. Due to the presence of unpaired electrons, free radicals show considerable degree of reactivity. Free radicals have the potential to attack critical molecules in the body by changing their chemical structures and affecting their functions. Free radicals are like robbers which are deficient in energy. Free radicals attack and snatch energy from other cells to satisfy them. The toxic of reactive oxygen species include the hydroxyl radical, hydrogen peroxide, the superoxide anion radical, nitric oxide radical, singlet oxygen, hypochlorite radical and various lipid peroxides. Reactive oxygen species and free radicals attack cells and lipoproteins to induce oxidation of lipids, proteins, sugars and DNA, which results in membrane damage, protein modification, enzyme deactivation, DNA strand breaks and base modification.

Oxidative stress

Oxidative stress is caused by the imbalance between pro-oxidants and antioxidant mechanisms. Oxidant exposure and antioxidant depletion are general phenomena that together are described as “oxidative stress.” Oxidants occur in various forms.Both chronic and natural and both acute and catastrophic events contribute oxidative stress.  Normal cells maintain a balance between reactive oxygen species (ROS) generation and antioxidant defense mechanism. Any disturbance of this balance produces oxidative stress which damage cellular components and even leads to cell death. Oxidative damage to DNA, proteins and other macromolecules may lead to a wide range of human diseases. The excessive oxidative stress can be due to the impact of several environmental factors such as exposure to pollutants, alcohol, medications, infections, poor diet, toxins, radiation etc.

Types of natural antioxidants

Natural antioxidants may be classified according to their nutritive value or their solubility. The hydrophobic (water hating/ lipid soluble e.g., vitamin E) and the hydrophilic (water loving/ water soluble e.g., vitamin C) is important both as nutrients and as antioxidants. The nutrient antioxidants include vitamins A,C and E, minerals copper, zinc and selenium. The non-nutritive antioxidants can subdivided into lipid soluble (e.g., carotenoids) and water soluble antioxidants (e.g., polyphenols). The examples of lipid-soluble antioxidants are vitamins A and E, carotenoids and lipoic acid. Water -soluble antioxidants include vitamin C, polyphenols and glutathione.  The antioxidants, which can be produced by human body include glutathione, alpha-lipoic acid and CoQ10 (ubiquinone).  
Antioxidant –rich phytochemicals are micro-constituents in plants and agriproducts. They differ from proteins, carbohydrates and lipids, which are macronutrients that are abundant in plants and food products. The type and quantity of antioxidant phytochemicals vary significantly from source to source. The antioxidant capacity of fruits and vegetables depends on the total concentrations of phytochemicals mainly ascorbic acid, phenolic compounds and carotenoids.

Physiologic mechanism of antioxidant activity

The physiologic activity of antioxidants may be divided into 3 categories: preventive antioxidants, chain breaking antioxidants and repair and de novo compounds. The preventive antioxidants are those compounds that reduce the rate of initiation of free radical chain reaction e.g., the selenium – dependent enzyme glutathione peroxidise. Chain – breaking antioxidants interact rapidly with the free radicals after the chain reaction is initiated, converting free radicals to stable forms e.g., vitamin C and E. Vitamin E has been referred to as Nature’s best chain – breaking antioxidants. Vitamin C can be a double-edged sword, where on one edge it is essential for health and acts as an antioxidant and the other edge it promoted pro-oxidant reactions. Repair and de novo compounds include enzymes that directly restore altered molecules to their original state or degrade them to non-functional compounds (catabolic reactions). Β-carotene is an important singlet oxygen and free radical scavenger.

Antioxidant Vitamins

Vitamin A and beta-carotene -Diets high in vitamin A and beta-carotene, the plant form of vitamin A that the body converts to vitamin A, appear to have cancer preventive properties. Those who have diets low in vitamin A and beta-carotene seem to have an increased risk of developing cancer. Both smokers and chewers of tobacco have low levels of vitamin A and increased precancerous cells in the tissues of mouth, throat and lungs. According to the Academy of nutrition and Dietics , carotenoids – rich foods may help prevent prostate cancer.

Vitamin C – Vitamin C has the ability to render harmful free radicals harmless. Vitamin C seems to block the conversion of nitrites in processed foods to nitrosamines, which are thought to be carcinogenic to the stomach, colon and bladder. Vitamin C helps in the formation of collagen and it also takes part in the formation of interferon, a naturally occurring antiviral agent. It regenerates damaged vitamin E to an active form of vitamin E.

Vitamin E – Vitamin E has been promoted as a cancer preventive vitamin because of its apparent ability to stabilize cell membranes and reduce free radicals. Its derivative vitamin E succinate exhibits potent anticancer activity. Vitamin E reduces inflammation and stimulates immune function.

Alpha –lipoic acid – it is a more potent antioxidant than vitamin C or E. It is soluble in both water and lipid; therefore it protects cell membranes and water soluble compounds. It regenerates tissue levels of vitamins C and E and markedly elevates glutathione levels.

Antioxidant mineral

Selenium is the only mineral that functions as an antioxidant.Selenium is a component of the enzyme glutathione peroxidase and is involved in the removal of harmful peroxides. It converts  hydrogen peroxide in the body into water.The sites of action include the blood vessels (endothelium), kidney, liver and erythrocytes.   According to the Academy of Nutrition and Dietics, selenium may reduce cancer risk and promote heart health. The richest sources of selenium include Brazil nuts, meat (particularly liver and kidney), mushrooms, seafood and other protein foods. The RNI for selenium is 75 μg/day for men and 60µg/day for women.

Antioxidant endogenous enzymes

The endogenous antioxidant enzymes include catalase, glutathione peroxidase, and superoxide dismutase. The minerals that are critical components of antioxidant enzymes include copper (as superoxide dismutase), zinc (as superoxide dismutase) and iron (as catalase).

Antioxidant amino acids

There are three amino acids which have antioxidant activity include cysteine, glutathione and methionine. Vegetable sources of proteins such as  nuts, beans and grains are not only provide amino acids but additional nutrients such as fibre, vitamin A and C.

Antioxidant phytochemicals

Antioxidant phytochemicals generally possess one or more hydroxylated aromatic or phenolics rings which contribute to their antioxidant activity e.g., phenolic phytochemicals. More than 800 phenolic substances have been detected in plants.   Protocatechuic, Caffeic, coumaric and chlorogenic acids are phenolic acids found in abundance in fruits and vegetables. Ferulic acid is a phenolic acid commonly found in grains especially in grain bran.Polyphenols are a group of flavonoids, which are divided into anthocyanins, Isoflavones, flavones, flavonols, flavanols and flavanones. Anthocyanins are present in high levels in berries (e.g.,blue berries, black berries, straw berries) and Isoflavones are abundant in beans. The flavonol quercetin is largely present in apples, while catechin, a flavanols, is found in teas and coffees. Grapefruits are rich in flavanones such as naringenin. Tannins are a group of polymerized polyphenolic antioxidants present in berries and red wines. Some antioxidant phytochemicals in grain germ and bran such as tocols and oryzanols are lipid soluble.

Antioxidant mechanism of flavonoids

1. Direct radical scavenging – Flavonoids may act at any stage of free radical formation. They may trap hydroxyl free radicals.
2. Down –regulation of radical generation – Flavonoids react with peroxy radicals to slow their propagation and delay the onset of lipid peroxidation.
3. Elimination of radical precursors – Flavonoids proactively work to eliminate the precursors to free radicals such as hydrogen peroxide thus eliminating them before the initiation of a problem.
4. Metal chelation – Flavonoids prevent radical formation by chelation of transition metals such as iron, preventing iron-induced lipid peroxidation.
5. Inhibition of xanthine oxidase – Flavonoids inhibit pro-peroxidant enzyme xanthine oxidase which prevent the formation of superoxide radicals.
6. Elevation of endogenous antioxidants – Flavonoids elevate body concentration of endogenous antioxidant such as SOD (superoxide dismutase) which themselves eliminate free radicals or their precursors. 

Food sources of antioxidant phytochemicals

Fruits and vegetables are rich in antioxidant nutrients. They are recognized  as important sources of vitamins and mineral micro-nutrients.The green leafy vegetables like spinach, kale and collard beans are loaded with antioxidants such as vitamins C,E,A and selenium. Nuts like almonds, cashews and walnuts are rich in fibre, phytonutrients and antioxidants vitamin E and selenium. Olive oil is very high in phenolic compounds which act as powerful antioxidants. Red wine contains polyphenols that reduce cholesterol, prevent blood colts and lower blood pressure. Turmeric has antioxidant, anti-inflammatory and cholesterol- lowering properties.

Health advice

For optimum health, people should consume on a daily basis at least five portions (80g/portion) of fruits and vegetables (World Cancer Research Fund 1997; Department of Health 1998) or a pound of vegetables a day (World Health Organization).

Some anti-cancer foods

Berries, Beans, Onions, garlic, Cauliflower, Broccoli, Carrots, mushrooms, Grasses like wheat grass, barley grass and fruits like Durian, cranberries.

Benefits of antioxidants

Antioxidants protect our genetic material (DNA) from the attacks of free radicals.  Some antioxidants stop cancer growth or induce cancer cell death (apoptosis). Antioxidants can regulate your body’s gene expression and increase your natural immunity. Certain antioxidants prevent metal radical chelation and toxification (e.g., mercury, arsenic). Antioxidants can repair damaged biomolecules like DNA.

Summary

Polyphenols scavenge carcinogens and mutagens. Carotenoids and ascorbic acids (vitamin C) quench free radicals. Sulphur – containing phytochemicals stimulate DNA repair.  Antioxidants do not have a long half-life in the body and should be maintained and replaced daily. Antioxidants work synergistically in giving protection against free radical damage, so it is better to take smaller doses of several different antioxidants than a large amount of only one.  Antioxidant nutrients work best when they are used consistently and preventively. Antioxidants are naturally occurring in fresh fruits, vegetables and certain spices.