Vitamin A and Beta-Carotene

Historically, vitamin A supplementation and, more recently, beta-carotene supplementation have been clinically effective in the treatment of leukoplakia.^4–9 Stich et al,^8,9 using the micronucleus test to monitor efficacy, were among the first to evaluate vitamin A and beta-carotene for leukoplakia. The micronucleus test is a useful indicator of the neoplastic tendency of epithelial cells because it provides immediate information about genotoxic damage. Micronuclei are formed during chromatid or chromosomal breakage, with the rate of formation tied closely to carcinogenesis in the oral cavity. This rate is a good predictor of cancer, which typically takes years or decades to generate clinically recognizable signs. On the basis of results of the micronucleus test, Stich et al. found that these two dietary factors, particularly beta-carotene, were effective in decreasing the mean proportion of cells with micronuclei on the buccal mucosa in Asian betel nut and tobacco chewers.^8,9 The subjects continued to chew betel nut and tobacco during the study.

The epidemiologic and experimental data documenting the protective effect of carotenoids and retinoids against epithelial cancers are overwhelming. The inverse relationship between serum retinol and carotene levels and cancer incidence holds true for oral carcinomas as well.^10,11

Dosages used in clinical studies testing vitamin A in the treatment of leukoplakia generally were fairly high (i.e., 150,000 to 900,000 IU/day) but extremely effective.^4–7 Since beta-carotene appears to be as effective as retinol in decreasing the levels of micronuclei and has a much higher therapeutic index, beta-carotene should probably be the treatment of choice for this condition. (Note: Vulvar leukoplakia is also responsive to retinol and could therefore respond to beta-carotene as well.)^12,13 However, the only head-to-head comparison study of the two supplements did find an advantage for retinol (see Table 185-1). In this study, 160 men and women with leukoplakia were randomly assigned to receive oral vitamin A (retinyl acetate 300,000 IU/week for 12 months; n = 50), oral beta-carotene (360 mg/week for 12 months; n = 55), or placebo (n = 55).¹⁴ The complete regression rates were 10% in the placebo arm, 52% with vitamin A, and 33% with beta-carotene. Homogeneous leukoplakias and smaller lesions responded better than nonhomogeneous and larger lesions. No major toxicities were observed even in the group given prolonged vitamin A supplementation.

TABLE 185-1 Beta-Carotene Trials