Oral Cancer Prevention: The Case for Carotenoids and Anti-Oxidant Nutrients

Abstract

The most convincing evidence for a preventive role for any modality is obviously demonstration of incidence reduction produced by that modality. However, cancer prevention trials with cancer incidence as an endpoint have logistic problems rendering them essentially impossible to conduct for most malignancies. Hence a workable strategy often involves analysis of other, indirect lines of evidence to reach conclusions. For oral cancer, dietary epidemiologic evidence points to a protective role for foods rich in carotenoids. Other anti-oxidants, such as vitamin C, are also implicated. Similarly, laboratory evidence points to a carcinogenesis inhibitory role for both retinoids and carotenoids. Clinical studies have targeted premalignant lesions, i.e., oral leukoplakia. For over two decades the efficacy of retinoids, natural and synthetic, has been known. Nevertheless, it has been difficult to translate this into a recommendation for prevention because of the toxicity of retinoids. The synthetic retinoid most often used in these trials is 13-cis-retinoic acid. This compound is toxic even at very low doses (0.1 mg/kg/day), particularly when given over several weeks to months. Hence, although effective, it cannot be advocated for prevention or oral cavity cancer. Studies with nontoxic antioxidants, such as beta-carotene, are much more recent. Early results are promising in that beta-carotene, alone or in combination with other nutrients, can reverse oral leukoplakia without toxicity in short-term trials. Studies currently under way will demonstrate whether durable remissions can be obtained using this strategy. It should be emphasized that such long-term trials are problematic to conduct with the toxic retinoids because the risks of prolonged exposure to them outweighs the chance of cancer development in the usual leukoplakia lesion.

Treatment of oral leukoplakia with a low‐dose of beta‐carotene and vitamin C supplements: A randomized controlled trial

“…Beta-carotene has been said to be efficacious against oral leukoplakia in previous studies, 30 although the reported outcomes are diverse; the overall response rates range from 27.5 to 73% [31][32][33][34][35][36] and none had adopted CONSORT guidelines. Table 4 shows the summary of RCTs that reported on systematic chemoprevention trials using retinoids and carotenoids for the treatment of oral leukoplakia.…”

Randomized double-blind trial of beta-carotene and vitamin C in women with minor cervical abnormalities

“…Various studies have found reductions in oral leukoplakia using beta-carotene, especially when combined with retinol, in subjects using tobacco or alcohol (Garewal et al, 1993). However lung cancer rates were slightly higher in Finnish smokers given betacarotene (Alpha-tocopherol Beta-carotene Prevention Study Group, 1994) but overall cancer incidence and death rates were not raised in groups containing fewer smokers (Greenberg et al, 1996;Hennekens et al, 1996).…”

Pigments in Citrus

“…Carotenoids and flavonoids, due to their antioxidant properties and nutritional benefits, have been some of the most studied dietary and therapeutic components in the dietetics and preventive medicine areas, yielding hundreds of publications and reviews [36,39,41,65,66,[122][123][124][125][126]. Much anecdotal or scientific evidence indicate that some of these components may possess potent antioxidant, anti-inflammatory, antiallergic, hypolipidaemic, vasoprotective, and anticarcinogenic properties [127] and protect against oxidative stress, coronary heart diseases, certain cancers, and other age-related diseases.…”