Year : 2009 | Volume
: 21 | Issue : 1 | Page : 1--6
Antioxidants: Enhancing oral and general health
Arvind Shetti, Vaishali Keluskar, Ashish Aggarwal
Department of Oral Medicine, Diagnosis and Radiology, KLE'S V. K. Institute of Dental Sciences, Belgaum, Karnataka, India
Department of Oral Medicine and Radiology, KLE«SQ»S V. K. Institute of Dental Sciences, Belgaum, Karnataka
Free radicals and antioxidant therapy have attracted a great deal of attention in recent years. Antioxidants are compounds that destroy the free radicals in the body, thereby preventing harmful oxidation-reduction reactions. Antioxidants are critical for maintaining optimum health and well-being. The best sources of antioxidants are fruits and vegetables, which provide a variety of antioxidants such as Vitamins A, C, E, and carotenoids. Currently available data are compatible with the notion that these vitamins act as chemopreventives against some important cancers, e.g., carotenoids for lung cancer, ascorbic acid for salivary gland cancer, tocopherols for head and neck cancers, etc. Thus, a greater consumption of fruits and vegetables should be encouraged as they are the natural sources of these chemopreventive antioxidants along with other protective factors packaged by nature.
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Shetti A, Keluskar V, Aggarwal A. Antioxidants: Enhancing oral and general health.J Indian Acad Oral Med Radiol 2009;21:1-6
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Shetti A, Keluskar V, Aggarwal A. Antioxidants: Enhancing oral and general health. J Indian Acad Oral Med Radiol [serial online] 2009 [cited 2021 Apr 12 ];21:1-6
Available from: https://www.jiaomr.in/text.asp?2009/21/1/1/57770
Antioxidants are substances that are capable of counteracting the damaging, but normal, effects of the physiological process of oxidation in animal tissue. Antioxidants are nutrients (vitamins and minerals) as well as enzymes (proteins in the body that assist in chemical reactions).
Concept of Free Radicals
Free radicals are chemically active atoms that have a charge due to an excess or deficient number of electrons. Free radicals containing oxygen, known as reactive oxygen species (ROS), are the most biologically significant free radicals. ROS include the radicals superoxide and hydroxyl. Free radicals and other reactive oxygen species are derived either from normal essential metabolic processes in the human body or from external sources such as exposure to X-rays, ozone, cigarette smoking, air pollutants, and industrial chemicals. Because they have one or more unpaired electrons, free radicals are highly unstable. They scavenge the body to grab or donate electrons, thereby damaging cells, proteins, and DNA.
Diseases Caused by Free Radicals [Figure 1]
The Antioxidant Process
Antioxidants block the process of oxidation by neutralizing free radicals. In doing so, the antioxidants themselves become oxidized. Because of this, there is a constant need to replenish our antioxidant resources. The effectiveness of any given antioxidant in the body depends on which free radical is involved, how and where it is generated, and the target of damage. Thus, an antioxidant in one particular system may protect against free radicals, while in another it could have no effect at all.
Types of Antioxidants
Vitamin E is the major antioxidant in all cellular membranes and it protects polyunsaturated fatty acids against oxidation.  Because it is fat-soluble, it safeguards cell membranes from damage by free radicals. Alpha-tocopherol also protects the fats in low-density lipoproteins from oxidation.
Vitamin C scavenges free radicals that are in an aqueous environment, such as inside the cells. It is believed to be the most important antioxidant in extracellular fluids and it has many known intracellular activities as well.  Vitamin C works synergistically with Vitamin E to quench free radicals.
Beta-carotene is the best quencher of singlet oxygen (an energized but uncharged form of oxygen that is toxic to cells). Beta-carotene is also especially used for scavenging free radicals in areas of low oxygen concentration.
Selenium is a trace element. It forms the active site of several antioxidant enzymes including glutathione peroxidase. Similar to selenium, the minerals manganese and zinc are trace elements that form an essential part of various antioxidant enzymes.
Superoxide dismutase, catalase, and glutathione peroxidase serve as your primary line of defense [Chart 1] in destroying free radicals [Figure 2] and [Figure 3].
Mechanism of Action of Antioxidants
Antioxidants neutralise free radicals by donating one of their electrons, which ends the electron stealing reaction. The antioxidant nutrient, however, does not become a free radical by donating an electron because they are stable in either form. Important antioxidants include the following:
Chain breaking or scavenging ones, such as Vitamin E (alpha tocopherol), Vitamin C (ascorbic acid), or Vitamin A (beta carotene)Preventative antioxidants that function largely by sequestering transition metal ions and preventing Fenton reactions and are therefore largely proteins by nature (e.g., albumin, transferring, or lactoferrin)
Lycopene is one of the most potent antioxidants primarily present in tomatoes.  Lycopene has been hypothesized to prevent carcinogenesis and atherogenesis by protecting critical cellular biomolecules, including lipids, lipoproteins, proteins, and DNA. ,, In recent studies, serum and tissue levels of lycopene were shown to be inversely associated with the risk of breast cancer, prostate cancer, coronary heart disease,  and oral premalignant lesions. According to various studies, lycopene, when given in the dosage of 4-8 mg/day orally for 3 months,  leads to the reversal of dysplastic changes in leukoplakia and when given in the dosage of 16 mg/day  leads to substantials increase in the mouth opening in oral submucous fibrosis. Estimating the daily intake of lycopene has been difficult due to the variability of reported values in the food sources. On average, the daily intake of lycopene is estimated to be 3.7 mg  [Figure 4] and [Figure 5].
The carotenoids are a group of red, orange, and yellow pigments found in fruits and vegetables.  These include b-carotene (carrots), lycopene (tomatoes), and lutein (spinach).  Carotenes have an excellent property of free radical trapping, especially peroxyl and hydroxyl radicals, which are involved in the genesis of cancers and aging. Beta carotene also increases cell mediated immune responses due to increased monocyte expression and increased activity of the tumor necrosis factor alpha. Serum beta carotene levels have been shown to decrease in various oral premalignant lesions and conditions and its supplementation (30 mg/day)  have led to the regression of the lesions.
These are non nutrient compounds that have biological activity inside the human body. They provide colors, taste, and aromas to the fruits and vegetables. They mimic hormones and suppress the development of diseases. Phenolic compounds such as flavonoids have been demonstrated to have anti-inflammatory, anti-allergenic, anti-viral, anti-aging, and anti-carcinogenic activity. , In addition to an antioxidant effect, flavonoid compounds may exert protection against heart disease through the inhibition of cyclooxygenase and lipoxygenase activities in platelets and macrophages  [Figure 6]and [Figure 7].
Therapeutic Use of Antioxidants for Oral Lesions
The possible uses of antioxidants for oral mucosal lesions include the following:
Prevention of lesions in high-risk individuals with mucosa that clinically appears normal with no history of either premalignant or malignant lesionThe treatment of premalignant oral lesionsIn patients who have had either premalignant or malignant oral lesions that have been successfully treated, in order to prevent recurrence of the treated initial lesion or to prevent the development of a second or a separate primary
Antioxidants and the Prevention of Cancer
Antioxidants play a role in the later stages of cancer development. DNA damage is considered to be one of the most important contributors to cancer. Much of this damage is oxidative in nature. Antioxidants may be able to cause the regression of premalignant lesions or inhibit their development into cancer. Preliminary studies have indicated that some antioxidants, particularly ß-carotene, may be of benefit in the treatment of precancerous conditions such as oral leukoplakia, which may be a precursor to oral cancer.  Some antioxidant nutrients may protect against cancer through mechanisms other than their antioxidant properties. For example, carotenoids may both enhance immune function and increase gap junctional communication (a type of interaction between cells that inhibits cell proliferation); both of these actions may be relevant to cancer prevention.  In general, high intake of fruits and vegetables are associated with a protective effect against cancer. Both biochemical and epidemiologic studies have indicated that antioxidant nutrients may have important protective effects in the prevention of human cancer [Figure 8].
Protective Roles of Micronutrients in Carcinogenesis
Nutrients and their functions
Precursor of Vitamin A
Anti-oxidant and free radical scavenging
Immunomodulation, stimulation of increase in the numbers of T-helper and NK cells as well as cells with IL-2 receptors
Inhibition of mutagenesis
Inhibition of cancer cell growth
2. Vitamin A (retinoids)
Inhibits keratinization and terminal differentiation of epidermal cells
Enhancement of cellular immunity
Arrest/reverse leukoplakia progression
Induction of cytotoxic and cytostatic effects on cancer cells
Influence DNA, RNA, and gene expression
Interfere with carcinogenic stimulation and binding
3. Vitamin E (A-tocopherol)
Free radical scavenging
Maintenance of membrane integrity, immune function
Inhibition of cancer cell growth/differentiation
Inhibits mutagenicity and nitrosamine formation
Inhibition of DNA and RNA, protein synthesis in cancer cells
4. Vitamin C (ascorbic acid)
Reduces vitamin E degradation
Enhances chemotaxis, phagocytosis, collagen synthesis
Inhibits nitrosamine formation
Enhances detoxification via cytochrome P450
Blocks formation of fecal mutagens
Reduces oncogene expression
Efficacy of a Mixture of Antioxidant Vitamins
Individual antioxidant vitamins produce varying degrees of tumor regression only at very high doses, which frequently causes toxicity, especially with retinoid derivatives. At lower doses, they may be ineffective or stimulate the growth of cancer cells. Therefore, the use of single vitamins in cancer treatment has no biological or clinical merit. Lower doses of individual vitamins 13-cis-retinoic acid, sodium ascorbate, d-a-tocopheryl succinate, and polar carotenoids without any b-carotene as part of a mixture can be used in cancer treatment and thereby avoid the possibility of the toxicity seen with the single vitamins at higher doses, or growth stimulation seen at lower doses. 
Choices of Antioxidants
Different antioxidants show substantially different antioxidant effectiveness in different fats, oils, and food systems due to different molecular structures. We should consider the safety, effectiveness, odor, color, convenience of antioxidant incorporation to foods, stability to pH and food processing, availability, and cost of the particular antioxidant before prescribing it to the patient.
Controversial Areas in Antioxidants Therapy
Current literature reports that a half century of data demonstrates the lack of predictability of antioxidant therapy and it has not been validated by the scientific method. Widespread use of antioxidants has failed to quell the current pandemic of cancer, diabetes, and cardiovascular disease or to stop or reverse the aging process. Antioxidant therapy in human reproductive medicine is controversial. High doses of Vitamin A may have embryotoxic and teratogenic effects.  Large doses of ascorbic acid may be associated with the inhibition of ovarian steroidogenesis and increased probability of abortion. 
Protection against free radicals can be enhanced by an ample intake of dietary antioxidants, of which the best studied are Vitamin E, Vitamin C, and carotenoids. Substantial evidence indicates that foods containing antioxidants and possibly in particular the antioxidant nutrients may be of major importance in disease prevention. Efforts should be made to ensure an optimum intake of foods containing these important molecules. Finally, it can be concluded that the following sayings ring true:
"REACH FOR A CARROT BEFORE CANCER REACHES YOU"
"A CARROT A DAY KEEPS CANCER AWAY"
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