Nutrition and Oral Medicine (Nutrition and Health)

216 Part IV / Select Diseases and Conditions13-cis-retinoic acid, fenretinide, and etretinate, but these will not be discussed furtherbecause they are outside the focus of this chapter. The naturally occurring agents haveincluded vitamins A, C, and E, -carotene, and selenium, which are generally administeredas pills or capsules at high supplemental levels.Most chemoprevention trials of oral premalignancy have focused on vitamin A and-carotene, and both nutrients have been shown to reverse oral leukoplakia (51–56).Many of these trials, however, were not placebo controlled and should be interpretedcautiously. In addition, vitamin A administered at high doses is often accompanied bytoxic side effects.One study has reported on the effectiveness of -carotene in preventing second primaryand recurrent cancers among persons diagnosed with a previous stage I or IIcarcinoma of the head and neck (57). In that randomized clinical trial and after a meanfollow-up of 51 mo, the -carotene group experienced a 30% decrease in the risk ofsecond or recurrent head and neck cancers, a 15% reduction in total mortality, but a 45%increase in the risk of lung cancer, although none of those findings were statisticallysignificant. The increased risk of lung cancer associated with -carotene supplementationhas also been observed in earlier cancer chemoprevention trials focusing on endpointsother than OPC (58,59) and underscores the fact that there is still much to learnregarding the role of nutrients in cancer and cancer prevention.6. CONCLUSIONS AND RECOMMENDATIONS FOR CLINICIANSAround the world, OPC affects hundreds of thousands of individuals each year. In theUnited States and other Western countries, tobacco use and alcohol consumption are theprimary causative agents, although at least some aspects of diet and nutrition also appearto play an important role. Most studies investigating a link between diet and OPC, andto a lesser extent precancer, have reported a protective effect associated with the consumptionof fruits and vegetables. Some investigations also suggest that the consumptionof whole-grain foods as well as a diet high in fiber intake may also be protective.Studies investigating specific dietary micronutrients in relation to OPC have most oftenidentified vitamin C as being associated with a reduced risk. In addition, persons withhigh serum levels of -carotene have been found to have reduced risks of OPC evenwhen the blood was taken years before the diagnosis of OPC. It is not clear, however,whether these micronutrients are directly responsible for the risk reduction, or whetherthey are markers for some other responsible factor. Multivitamins have not emerged asprotective in terms of OPC, and while two case–control studies have suggested thatvitamin E supplementation could be protective, it is too early to recommend this supplementto patients. Finally, although various potential oral cancer chemopreventive agentshave been and are being evaluated for their effectiveness and safety, the use of theseagents remains experimental at this time.7. SOURCES FOR ADDITIONAL INFORMATIONFurther information regarding diet and nutrition in relation to OPC can be obtained byaccessing the websites for the National Cancer Institute and the American Cancer Society(ACS).