Leukoplakia

Also indexed as: Oral Leukoplakia

Leukoplakia is a common, potentially pre-cancerous disease of the mouth. Despite the increased risk associated with having leukoplakia, many people with this condition never get oral cancer.

People with leukoplakia are typically middle-aged and older adults; men are more likely than women to develop the disease. The risk is much higher in smokers and users of smokeless tobacco than in people who do not use tobacco products of any kind. Betel nut chewers in Asia are also at high risk. People infected with HIV or Epstein-Barr virus are at high risk for a particular form of this condition, called hairy leukoplakia, which requires treatment with antiviral medication. Another variation of this disease, proliferative verrucous leukoplakia, is much more likely to progress to cancer than are other forms. Genetic predisposition may be responsible for some cases of leukoplakia.1

Checklist for Leukoplakia

Rating Nutritional Supplements Herbs
3Stars Beta-carotene
Vitamin A		  
2Stars Vitamin E Green tea
1Star Vitamin C  
3Stars Reliable and relatively consistent scientific data showing a substantial health benefit.
2Stars Contradictory, insufficient, or preliminary studies suggesting a health benefit or minimal health benefit.
1Star An herb is primarily supported by traditional use, or the herb or supplement has little scientific support and/or minimal health benefit.

What are the symptoms of leukoplakia? People with leukoplakia may notice a white patch on their tongue, gums, cheek, or roof of the mouth.

How is it treated? Conventional treatment is usually directed at any underlying medical conditions. In severe cases, doctors may recommend oral antiviral medication (e.g., oral acyclovir [Zovirax®], famciclovir [Famvir®], and zidovudine [AZT®]).

Dietary changes that may be helpful: Some,2 3 but not all,4 preliminary studies find that people who drink alcohol are more likely to have leukoplakia compared with nondrinkers. Even though it has not been proven that abstaining from alcohol aids in the healing of leukoplakia, people with this condition should, nonetheless, reduce their intake.

Preliminary reports have found that low dietary levels of vitamin C and fiber,5 vitamin A,6 or, according to one study, many different nutrients,7 are associated with an increased risk of leukoplakia. Except for vitamin A (see below), the effect of increasing intake of these nutrients in people with leukoplakia has not been studied.

Rare reports of leukoplakia triggered by food allergies have appeared.8 People with leukoplakia should discuss the issue of food allergies with a healthcare professional.

Lifestyle changes that may be helpful: Tobacco use of any kind greatly increases the risk of leukoplakia. People with leukoplakia must avoid all tobacco products.

Nutritional supplements that may be helpful: Beta-carotene is the most widely used supplement in the treatment of leukoplakia. In a clinical trial of betel nut chewers with leukoplakia, supplementation with 150,000 IU of beta-carotene twice per week for six months significantly increased the remission rate compared with placebo (14.8% vs. 3.0%).9 The effectiveness of beta-carotene for treating leukoplakia was also confirmed in a double-blind trial that used 100,000 IU per day for six months.10 In one trial, supplementation with 33, 333 IU of beta-carotene per day, alone or combined with 50 IU of vitamin E, was reported not to reduce the incidence of leukoplakia.11 These results have also been observed in smaller trials.12 13

Drug therapy with a synthetic, prescription form of vitamin A (known as Accutane®, isotretinoin, and 13-cis retinoic acid) has been reported to be more effective than treatment with 50,000 IU per day of beta-carotene.14 However, because of the potential toxicity of the vitamin A-like drug, it may be preferable to treat leukoplakia with beta-carotene, which is much safer.

Before the research on beta-carotene was published, vitamin A was used to treat leukoplakia.15 One group of researchers reported that vitamin A (28,500 IU per day) was more effective than beta-carotene in treating people with leukoplakia.16 Another trial found that the combination of 150,000 IU per week of beta-carotene plus 100,000 IU per week of vitamin A led to a significant increase in remission time compared to beta carotene alone in betel nut chewers.17 Women who are or who could become pregnant should not take 100,000 IU of vitamin A per week without medical supervision.

According to a review of clinical trials, the combination of beta-carotene and vitamin E has led to complete or partial remissions in six of eight trials studying people with leukoplakia.18 In one trial, administration of 50,000 IU of beta-carotene, 1 gram of vitamin C, and 800 IU of vitamin E per day for nine months led to improvement in 56% of people with leukoplakia, with stronger effects in those who also stopped using tobacco and alcohol.19 In a double-blind trial, a group of men with leukoplakia was given a combination of vitamin A (100,000 IU per week), beta-carotene approximately 67,000 IU per day), and vitamin E (80 IU per week).20 A 38% decrease in the incidence of leukoplakia was observed after six months of treatment.

Although vitamin E has been used in successful trials in which patients are also given beta-carotene, few trials have investigated the effects of vitamin E when taken by itself. One trial used 400 IU of vitamin E two times per day.21 After 24 weeks, 46% showed some improvement in signs or symptoms of leukoplakia or related conditions and 21% showed microscopic evidence of improvement.

Are there any side effects or interactions? Refer to the individual supplement for information about any side effects or interactions.

Herbs that may be helpful: In a double-blind trial, people with leukoplakia took 3 grams per day of a mixture of whole green tea, green tea polyphenols, and green tea pigments orally and also painted the mixture of the tea on their lesions three times per day for six months.22 Those in the green tea group had significant improvement in the healing of their lesions.

Are there any side effects or interactions? Refer to the individual herb for information about any side effects or interactions.

References:

1. Bartsch H, Rojas M, Nair U, et al. Genetic cancer susceptibility and DNA adducts: studies in smokers, tobacco chewers, and coke oven workers. Cancer Detect Prev 1999;23:445–53.

2. Gupta PC. Epidemiologic study of the association between alcohol habits and oral leukoplakia. Community Dent Oral Epidemiol 1984;12:47–50.

3. Macigo FG, Mwaniki DL, Guthua SW. Influence of dose and cessation of kiraiku, cigarettes and alcohol use on the risk of developing oral leukoplakia. Eur J Oral Sci 1996;104:498–502.

4. Evstifeeva TV, Zaridze DG. Nass use, cigarette smoking, alcohol consumption and risk of oral and oesophageal precancer. Eur J Cancer B Oral Oncol 1992;28B:29–35.

5. Gupta PC, Hebert JR, Bhonsle RB, et al. Dietary factors in oral leukoplakia and submucous fibrosis in a population-based case control study in Gujarat, India. Oral Dis 1998;4:200–6.

6. Cianfriglia F, Manieri A, Di Gregorio DA, Di Iorio AM. Retinol dietary intake and oral leukoplakia development. J Exp Clin Cancer Res 1998;17:331–6.

7. Ramaswamy G, Rao VR, Kumaraswamy SV, Anantha N. Serum vitamins’ status in oral leukoplakias--a preliminary study. Eur J Cancer B Oral Oncol 1996;32B:120–2.

8. Mihail RC. Oral leukoplakia caused by cinnamon food allergy. J Otolaryngol 1992 Oct:366–7.

9. Stich HF, Rosin MP, Hornby AP, et al. Remission of oral leukoplakias and micronuclei in tobacco/betel quid chewers treated with beta-carotene and with beta-carotene plus vitamin A. Int J Cancer 1988;42:195–9.

10. Garewal HS, Katz RV, Meyskens F, et al. β-Carotene produces sustained remission in patients with oral leukoplakia. Arch Otolaryngol Head Neck Surg 1999;125:1305–10.

11. Liede K, Hietanen J, Saxen L, et al. Long-term supplementation with alpha-tocopherol and beta-carotene and prevalence of oral mucosal lesions in smokers. Oral Dis 1998;4:78–83.

12. Toma S, Benso S, Albanese E, et al. Treatment of oral leukoplakia with beta-carotene. Oncology 1992;49:77–81.

13. Garewal HS, Meyskens FL Jr, Killen D, et al. Response of oral leukoplakia to beta-carotene. J Clin Oncol 1990;8:1715–20.

14. Lippman SM, Batsakis JG, Toth BB, et al. Comparison of low-dose isotretinoin with beta carotene to prevent oral carcinogenesis. N Engl J Med 1993;328:15–20.

15. Johnson J, Ringsdorf W, Cheraskin E. Relationship of vitamin A and oral leukoplakia. Arch Derm 1963;88:607–12.

16. Stich HF, Mathews B, Sankaranarayanan R, Nair MK. Remission of precancerous lesions in the oral cavity of tobacco chewers and maintenance of the protective effect of β-carotene or vitamin A. Am J Clin Nutr 1991;53:298S–304S.

17. Stich HF, Rosin MP, Hornby AP, et al. Remission of oral leukoplakias and micronuclei in tobacco/betel quid chewers treated with beta-carotene and with beta-carotene plus vitamin A. Int J Cancer 1988;42:195–9.

18. Garewal H. Antioxidants in oral cancer prevention. Am J Clin Nutr 1995;62(suppl):1410S–6S [review].

19. Kaugars GE, Silverman S Jr, Lovas JG, et al. A clinical trial of antioxidant supplements in the treatment of oral leukoplakia. Oral Surg Oral Med Oral Pathol 1994 Oct;78:462–8.

20. Zaridze D, Evstifeeva T, Boyle P. Chemoprevention of oral leukoplakia and chronic esophagitis in an area of high incidence of oral and esophageal cancer. Ann Epidemiol 1993;3:225–34.

21. Benner SE, Winn RJ, Lippman SM, et al. Regression of oral leukoplakia with alpha-tocopherol: a community clinical oncology program chemoprevention study. J Natl Cancer Inst 1993;85:44–7.

22. Li N, Sun Z, Han C, Chen J. The chemopreventive effects of tea on human oral precancerous mucosa lesions. Proc Soc Exp Biol Med 1999;220:218–24.