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Review
. 2025 May-Jun;15(3):484-492.
doi: 10.1016/j.jobcr.2025.03.001. Epub 2025 Mar 11.

Antioxidants for the management of oral leukoplakia: A systematic review of randomized controlled trials

Divya Gopinath  1 , Sara Ibrahim Waki  2 , Kwok Fu Cheah  3 , Swagatika Panda  4
Affiliations
Review

Antioxidants for the management of oral leukoplakia: A systematic review of randomized controlled trials

Divya Gopinath et al. J Oral Biol Craniofac Res. 2025 May-Jun.

Abstract

Introduction: Oral leukoplakia (OL) is a potentially malignant disorder characterized by non-scrabble white lesions that may turn into invasive carcinoma if left untreated. Few antioxidant treatments have shown promising results in the regression of lesions and prevention of their progression to carcinoma. We aim to summarize the current evidence on the effectiveness of antioxidants in the management of OL.

Materials and methods: The present systematic review followed PRISMA guidelines and involved a thorough search of three scientific databases: PubMed, Scopus, and Cochrane. We used specific algorithms related to the keywords "antioxidant" and "Oral leukoplakia" to identify randomized controlled trials (RCTs) that have explored the utility of antioxidants in the management of OL. The risk of bias assessment was conducted using the Cochrane risk of bias tool (ROB 2.0), ensuring the reliability of our findings.

Results: Out of 2490 articles retrieved, only thirteen RCTs involving 1147 participants fulfilled the inclusion criteria. Lycopene was found to be the most consistently effective antioxidant, showing significant effectiveness in reducing lesion size, both in oral and topical forms. The trials incorporating other antioxidants, including vitamin A, vitamin C, β-carotene, and curcumin, demonstrated mixed results. Severe heterogeneity was detected in treatment forms, dosage, administration frequency, treatment duration, and follow-up time among all included trials.

Conclusion: Lycopene may play a significant role in the non-surgical management of OL. Future research with large-scale, well-designed, randomized controlled trials with standardized dosing, delivery methods, and outcome measures is mandatory to provide more robust evidence on the available antioxidant therapy for OL.

Keywords: Antioxidant treatment; Leukoplakia; OPMD; Oral; Premalignant oral lesion.

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Conflict of interest statement

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Figures

Image 1
Graphical abstract
Fig. 1
Fig. 1
Prisma flow chart of the review process.
Fig. 2
Fig. 2
Risk of Bias of the included trials.
See this image and copyright information in PMC

References

    1. Warnakulasuriya S. Oral potentially malignant disorders: a comprehensive review on clinical aspects and management. Oral Oncol. 2020;102 doi: 10.1016/j.oraloncology.2019.104550. - DOI - PubMed
    1. Zhang C., Li B., Zeng X., Hu X., Hua H. The global prevalence of oral leukoplakia: a systematic review and meta-analysis from 1996 to 2022. BMC Oral Health. 2023;23(1):645. doi: 10.1186/s12903-023-03342-y. - DOI - PMC - PubMed
    1. Speight P.M., Khurram S.A., Kujan O. Oral potentially malignant disorders: risk of progression to malignancy. Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology. 2018;125(6):612–627. doi: 10.1016/j.oooo.2017.12.011. - DOI - PubMed
    1. Maserejian N.N., Joshipura K.J., Rosner B.A., Giovannucci E., Zavras A.I. Prospective study of alcohol consumption and risk of oral premalignant lesions in men. Cancer Epidemiol Biomarkers Prev. 2006;15(4):774–781. doi: 10.1158/1055-9965.EPI-05-0842. - DOI - PubMed
    1. Ranganathan K., Kavitha L. Clinical aspects of oral cancer and potentially malignant disorders in South and Southeast Asia. Oral Dis. 2024 doi: 10.1111/odi.15008. Published online May 30. - DOI - PubMed

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