Vitamin E and cancer prevention: Studies with different forms of tocopherols and tocotrienols.

alpha-Tocopherol (alpha-T) is the major form of vitamin E (VE) in animals and has the highest activity in carrying out the essential antioxidant functions of VE. Because of the involvement of oxidative stress in carcinogenesis, the cancer prevention activity of alpha-T has been studied extensively. Lower VE intake or nutritional status has been shown to be associated with increased cancer risk, and supplementation of alpha-T to populations with VE insufficiency has shown beneficial effects in lowering the cancer risk in some intervention studies. However, several large intervention studies with alpha-T conducted in North America have not demonstrated a cancer prevention effect. More recent studies have centered on the gamma- and delta-forms of tocopherols and tocotrienols (T3). In comparison with alpha-T, these forms have much lower systemic bioavailability but have shown stronger cancer-preventive activities in many studies in animal models and cell lines. gamma-T3 and delta-T3 generally have even higher activities than gamma-T and delta-T. In this article, we review recent results from human and laboratory studies on the cancer-preventive activities of different forms of tocopherols and tocotrienols, at nutritional and pharmacological levels. We aim to elucidate the possible mechanisms of the preventive actions and discuss the possible application of the available information for human cancer prevention by different VE forms.