The Role of Vitamin E Isoforms and Metabolites in Cancer Prevention: Mechanistic Insights into Sphingolipid Metabolism Modulation.

Natural forms of vitamin E include four tocopherols and four tocotrienols (α, β, γ, and δ), which are essential as lipophilic antioxidants. Among these eight isoforms, α-tocopherol (αT), the predominant form of vitamin E found in tissues, has traditionally received the most attention in disease prevention research due to its robust antioxidant activity. However, recent studies suggest that other forms of vitamin E exhibit distinct and potentially more potent beneficial activities in disease prevention and treatment. These non-αT forms of vitamin E are metabolized in vivo, producing various metabolites, including 13'-carboxychromanol, though their biological roles remain largely unknown. Notably, sphingolipids, known for their significant roles in cancer biology, may be involved in the anticancer effects of vitamin E through the modulation of sphingolipid metabolism. This review focuses on the diverse biological activities of different vitamin E forms and their metabolites, particularly their anticancer effects, while highlighting the underlying mechanisms, including their novel impact on regulating sphingolipid pathways. By elucidating these interactions, we aim to provide a deeper understanding on the multifaceted roles of vitamin E in cancer prevention and therapy.