Although the tocopherol content in food has been shown to be inversely associated with mortality from cardiovascular disease, dietary supplementation with α-tocopherol alone has a modest protective effect. The lack of natural tocopherols such as γ- and δ-tocopherol most vitamin E preparations may be a limiting factor for promoting health. Although α-tocopherol and γ-tocopherol are 2 principle tocopherols in vegetable oils, the latter is in greater abundance in the edible oils processed in the United States. In contrast to α-tocopherol, γ-tocopherol has biologic activity that potentially protects against chronic diseases such as inflammation. Evidence indicates that the mixed tocopherols found in native vegetable oils afford additive and synergistic activities that support their broader beneficial biologic functions. Both γ- and δ-tocopherol may be necessary for preventing lipid peroxidation and in counteracting the prooxidant effect of α-tocopherol. Moreover, all tocopherols except β-tocopherol inhibit smooth muscle proliferation. In our research, a preparation of mixed tocopherols, containing γ-, δ-, and α-tocopherol (5:2:1), has been shown to have better antioxidant and anti-inflammatory actions than ga-tocopherol alone. This mixture did not have any adverse effects in a limited number of preliminary clinical investigations. Thus, among the tocopherols, ga-tocopherol is not the only important isomer for human health. Based on the evidence in this review, further research and additional clinical studies should be conducted on mixed tocopherol preparations.