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Year : 2014  |  Volume : 3  |  Issue : 3  |  Page : 208-210

Oral leukoplakia: Role of antioxidants - helpful versus harmful

1 Department of Oral and Maxillofacial Surgery, D. J. College of Dental Sciences and Research, Modinagar, Ghaziabad, India
2 Department of Oral Pathology and Microbiology, D. J. College of Dental Sciences and Research, Modinagar, Ghaziabad, India
3 Department of Pedodontia, Subharti Dental College, Meerut, Uttar Pradesh, India

Date of Web Publication13-Aug-2014

Correspondence Address:
Raghav Agarwal
Department of Oral and Maxillofacial Surgery, D. J. College of Dental Sciences and Research, Modinagar, Ghaziabad, Uttar Pradesh
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/2278-344X.138611

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How to cite this article:
Agarwal R, Rajpal K, Grover N, Chhabra R. Oral leukoplakia: Role of antioxidants - helpful versus harmful. Int J Health Allied Sci 2014;3:208-10

How to cite this URL:
Agarwal R, Rajpal K, Grover N, Chhabra R. Oral leukoplakia: Role of antioxidants - helpful versus harmful. Int J Health Allied Sci [serial online] 2014 [cited 2020 Feb 25];3:208-10. Available from: http://www.ijhas.in/text.asp?2014/3/3/208/138611


Oral premalignant lesions and early stage malignancies often arise as subtle lesions and require an alert clinician with a high index of suspicion, especially if any of the risk factors are present. Presence of a precursor (premalignant) lesion subsequently developing into oral squamous cell carcinoma is well-established.

In developing nations like India oral health is often ignored. This reduces the natural benefit of identifying a serious problem in its inception. The condition then flourishes and takes devastating forms. It is now known that even the clinically "normal" appearing mucosa in a patient harboring a precancerous lesion may have dysplasia on the contra lateral anatomic site or molecular aberrations in other oral mucosal sites suggestive of a pathway to malignant transformation, and that cancer could subsequently arise in apparently normal tissue. [1]

In a recently held WHO workshop, it has been recommended to abandon the distinction between potentially malignant lesions and potentially malignant conditions and to use the term "potentially malignant disorders" instead. [2]

Owing to the seriousness associated with these disorders any indication of their presence in the oral cavity shouldn't be overlooked. Managing these disorders efficiently requires a well aware clinician who is informed about the pros and cons of prevalent treatment modalities and can select the best possible option.

In recent years, the focus is shifting from surgical toward medical therapy. By this communication, we are reviewing the currently available medical aids, which are said to be effective in handling these disorders. There is serious need to treat any such premalignant disorder as Waldron and Shafer examined 3256 biopsy specimens from intraoral white lesions. They determined that 19.9% showed some degree of epithelial dysplasia, and 3.1% showed a frankly invasive tumor. On an average, 5-18% of epithelial dysplasias become malignant. [3] Oral leukoplakia has an annual malignant transformation rate of 0.1-17%. [4] The malignant transformation rate of oral leukoplakia is between 3.6% and 17.5%. [5]

Proliferative verrucous leukoplakia, has a high rate of malignant transformation (70.3%) to verrucous carcinoma or squamous cell carcinoma. [5]

Mortality rates for oral cancer have not changed in spite of the professional awareness of precancerous lesions, and their potential risk of becoming malignant. Moreover, these lesions present to us the possibility of observable changes in the oral mucosa weeks and months prior to the onset of cancer and because the survival rate is directly related to the stage of malignancy at the time of diagnosis, prevention and early detection are vital to decrease the incidence and improve the survival odds of individuals who develop the disease.

It is increasingly proposed that reactive oxygen species (ROS) and reactive nitrogen species play a key role in human cancer development, [6] Other mechanisms include ROS such as malondialdehyde, nitroxide, lipid peroxidation, and decreased activities of antioxidants including glutathione, ascorbic acid (AA), glutathione peroxidise, glutathione reductase, superoxide dismutase, and catalase associated with tobacco users and potentially malignant disorders, produce both phenotypic, and genotypic alterations, which may progress to cancer. [7]

Experimental studies show that antioxidant vitamins and some phytochemicals selectively induce apoptosis in cancer cells, but not in normal cells and prevent angiogenesis and metastatic spread, suggesting a potential role for antioxidants as adjuvant in cancer therapy. [8]

Thus, the use of antioxidants at early stages becomes utmost essential for prevention of malignant transformation [7] and evidence is growing that antioxidants may prevent or delay the onset of some types of cancer. [6]

Nonsurgical treatment may also be considered for the management of oral leukoplakia as this modality offers minimal adverse effects to patients, especially for patients with widespread lesion that involves a large area of the oral mucosa or patients with medical problems and consequently, high surgical risks. In addition, potential advantages of the nonsurgical treatment of OL include easy application that does not require treatment at a medical center and relative low cost. [3]

13-cis-retinoic acid (13-cRA) or vitamin A has always been the treatment of choice for many practitioners. Hong et al. [9] did a randomized controlled trial at MD Anderson Hospital in Houston, in which he followed 44 patients with oral leukoplakias who were treated with 1-2 mg/kg/day of 13-cRA for 3 months; 32 nearly 67% of the patients had more than a 50% reduction in lesion size, but 79% experienced a variety of side-effects.

The function of carotenoids is accomplished through a ligation between beta-carotene and oxygen, which is an unstable reactive molecule, thus diminishing the damaging effects of free radicals. [4] The use of beta-carotene has been recommended in order to prevent oral leukoplakia and possibly oral cancer. Trials using b-carotene demonstrated reductions (up to 71%) in the occurrence of oral leukoplakia and mucosal dysplasia to a much lesser degree than that observed with 13-cRA. [10]

Lycopene has the uncommon feature of becoming bound to chemical species that react to oxygen, thus being the most efficient biological antioxidizing agent. Lycopene also has the capacity to modify intercellular exchange junctions, and this is considered to be an anticancer mechanism. [4]

L-ascorbic acid (vitamin C) has antioxidizing properties and reacts with superoxide produced as a result of the cells normal metabolic processes; this inactivation of superoxide inhibits the formation of nitrosamines during protein digestion and helps avoid damage to DNA and cellular proteins. [4] L-AA toxicity does not occur, since vitamin is water-soluble and a decrease in absorption efficiency occurs when consumption exceeds 180 mg/day. [4]

Treatment of lesions with low grade dysplasia is always been a controversy. Low grade dysplasia might regress by itself or can progress to malignant stages. Path which they will take is uncertain, thus ignoring them poses a degree of risk.

Research in humans has not demonstrated convincingly that taking antioxidants supplements can help reduce the risk of developing cancer and some have even shown an increased risk of some cancers. As quoted in National Cancer Institute Fact sheet web site on January 16, 2014. [11]

Until date, there is only few evidence [7] of effective treatment in preventing malignant transformation of leukoplakia. Treatments may be effective in the resolution of lesion; however, relapses and adverse effects are common.

However, the big opposition to the medical treatment that has always haunted the authors before and even today is indeed whether antioxidants that protect normal cells from acute and long-term free radical damage may afford the same protection to tumor cells and hinder the overall outcome of cancer therapy. [7]

It is convinced from many relevant studies conducted in lung cancer/gastric cancer, supplementation with antioxidant micronutrients is not an effective tool for cancer control in high-risk patients.

Antioxidants many times act as an adjunctive aid in treatment of dysplastic lesions. Antioxidants decreased the toxicities of specific therapies in cancer. [12]

Since the cause of carcinogenesis is multifactorial and the level of intervention by antioxidants is still controversial a need for more controlled research is deeply felt.

  References Top

1.Braakhuis BJ, Tabor MP, Kummer JA, Leemans CR, Brakenhoff RH. A genetic explanation of Slaughter′s concept of field cancerization: Evidence and clinical implications. Cancer Res 2003;63:1727-30.  Back to cited text no. 1
2.Warnakulasuriya S, Johnson NW, van der Waal I. Nomenclature and classification of potentially malignant disorders of the oral mucosa. J Oral Pathol Med 2007;36:575-80.  Back to cited text no. 2
3.Waldron CA, Shafer WG. Leukoplakia revisited. A clinicopathologic study 3256 oral leukoplakias. Cancer 1975;36:1386-92.  Back to cited text no. 3
4.Ribeiro AS, Salles PR, da Silva TA, Mesquita RA. A review of the nonsurgical treatment of oral leukoplakia. Int J Dent 2010;2010:186018.  Back to cited text no. 4
5.Hsue SS, Wang WC, Chen CH, Lin CC, Chen YK, Lin LM. Malignant transformation in 1458 patients with potentially malignant oral mucosal disorders: A follow-up study based in a Taiwanese hospital. J Oral Pathol Med 2007;36:25-9.  Back to cited text no. 5
6.Wiseman H, Halliwell B. Damage to DNA by reactive oxygen and nitrogen species: Role in inflammatory disease and progression to cancer. Biochem J 1996;313:17-29.  Back to cited text no. 6
7.Uma Maheswari TN. Treatment of oral leukoplakia with antioxidants: A systematic review. Int J Pharm Bio Sci 2013;4:33-41.  Back to cited text no. 7
8.Borek C. Dietary antioxidants and human cancer. Integr Cancer Ther 2004;3:333-41.  Back to cited text no. 8
9.Hong WK, Endicott J, Itri LM, Doos W, Batsakis JG, Bell R, et al. 13-cis-retinoic acid in the treatment of oral leukoplakia. N Engl J Med 1986;315:1501-5.  Back to cited text no. 9
10.Malaker K, Anderson BJ, Beecroft WA, Hodson DI. Management of oral mucosal dysplasia with beta-carotene retinoic acid: A pilot cross-over study. Cancer Detect Prev 1991;15:335-40.  Back to cited text no. 10
11.Available from: http://www.cancer.gov/cancertopics/factsheet/prevention/antioxidants.  Back to cited text no. 11
12.Lawenda BD, Kelly KM, Ladas EJ, Sagar SM, Vickers A, Blumberg JB. Should supplemental antioxidant administration be avoided during chemotherapy and radiation therapy? J Natl Cancer Inst 2008;100:773-83.  Back to cited text no. 12

This article has been cited by
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Asian Pacific Journal of Tropical Medicine. 2017;
[Pubmed] | [DOI]


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