Method of Action of Vitamin E

Method of Action of Vitamin E

The chemical formula of alpha tocopherol is C29H5002. At least 8 compounds having vitamin E activity have been isolated from plant sources. All have a 6-chromonal ring structure and a side chain. The tocols have a phytol side chain, whereas the trienols have a similar structure, with double bonds at the 3', 7', and 11' positions of the side chain. Both tocols and trienols occur as a variety of isomers which differ from one another by the number and location of methyl groups on the chromonal ring. Alpha tocopherol is the most active form and the side chain is essential for full biological activity of vitamin E.

Vitamin E has more than one mechanism in the body. One of the most well established mechanisms is its capacity to destroy free radicals generated as a part of the oxidation reaction in the human body or by exogenous agents. This antioxidation mechanism of vitamin E has been demonstrated both in vitro and in vivo. Vitamin E has been shown to stabilize membranes by physiochemical interaction between its phytol side chain and the fatty acid chain of polyunsaturated phospholipids. It inhibits the synthesis of prostaglandins and prevents platelet aggregation in vitro and in vivo. There are some data which show that vitamin E reduces the synthesis of thromboxane and increases the formation of prostacyclin. Thromboxane is considered the most potent platelet aggregating factor; therefore, further study on the role of vitamin E in regulating the metabolism of arachidonic acid is needed.

Recent studies show that alpha tocopheryl succinate treatment induces cell differentiation in some cancer (melanoma cells in vitro); however, it inhibits the growth of other tumor cells (murine neuroblastoma, rat glioma and human prostrate) in vitro. On the other hand, alpha tocopherol, alpha tocopheryl acetate and alpha tocopheryl nicotinate at similar concentrations were ineffective. However butylated hydroxyanisole (BHA) and butylated hydroxytoluene (BHT), which have antioxidant properties similar to those of vitamin E, were only partially effective in producing the above changes. Thus the effects of vitamin E succinate on cancer cells, in part, are mediated by its antioxidant mechanism. Alpha tocopherol also causes differentiation of mouse myeloid leukemia in vitro.

Recent in vitro studies have demonstrated a novel mechanism of action of vitamin E in which its antioxidant role is not involved. Vitamin E succinate treatment of cancer cells (neuroblastoma) and normal fibroblasts (murine L-cells) inhibits prostaglandin (PG) E1- and PGA2- stimulated adenylate cyclase (converts ATP to adenosine 3', 5'-cyclic monophosphate) activity. This effect is primarily due to an inhibition of the catalytic protein activity of adenylate cyclase. Because of the involvement of prostaglandins in the carcinogenic events, it has been proposed that one of the mechanisms of cancer prevention by vitamin E may involve a reduction in adenylate cyclase response to prostaglandins. Since the production of excess of prostaglandins is associated with suppression of the immune system and platelet aggregation, the above mechanism of vitamin E may be involved in vitamin E-induced stimulation immunity and inhibition of platelet aggregation. In a recent study, it has been observed that vitamin E treatment of neuroblastoma cells increases the expression of c-mye gene (normal cellular gene) by about five-fold (Sharna & Prasad, unpublished observation). This is the first demonstration that vitamin E can enhance the transcription of a particular sequence of DNA. The significance of this observation in the control of growth, differentiation and malignancy is unknown at this time

The relative efficacy of natural and synthetic forms of vitamin E has not been adequately studied. In vitro experimental systems, the natural and synthetic forms of vitamin E were equally effective in causing growth inhibition of neuroblastoma an melanoma cells. However, d-form of vitamin E was more potent than dl-form in inhibiting the growth of glioma cells.

The studies discussed in this chapter show that vitamin E has a direct role in the regulation of gene expression both at the levels of transcription and translation. The maximal potential of vitamin E for maintaining an optimal health and for disease prevention remains to be determined. The above goal cannot be realized until we know how vitamin E works on cellular molecular levels. Future vitamin E research will focus on this issue and at the same time will continue to emphasize the evaluation of the role of vitamin E in human health and disease prevention and treatment.