Natural forms of vitamin E: metabolism, antioxidant, and anti-inflammatory activities and their role in disease prevention and therapy

The vitamin E family consists of four tocopherols and four tocotrienols. alpha-Tocopherol (alpha T) is the predominant form of vitamin E in tissues and its deficiency leads to ataxia in humans. However, results from many clinical studies do not support a protective role of aT in disease prevention in people with adequate nutrient status. On the other hand, recent mechanistic studies indicate that other forms of vitamin E, such as gamma-tocopherol (gamma T), delta-tocopherol, and gamma-tocotrienol, have unique antioxidant and anti-inflammatory properties that are superior to those of alpha T in prevention and therapy against chronic diseases. These vitamin E forms scavenge reactive nitrogen species, inhibit cyclooxygenase- and 5-lipoxygenase-catalyzed eicosanoids, and suppress proinflammatory signaling such as NF-kappa B and STAT3/6. Unlike alpha T, other vitamin E forms are significantly metabolized to carboxychromanols via cytochrome P450-initiated side-chain omega-oxidation. Long-chain carboxychromanols, especially 13'-carboxychromanols, are shown to have stronger anti-inflammatory effects than unmetabolized vitamins and may therefore contribute to the beneficial effects of vitamin E forms in vivo. Consistent with mechanistic findings, animal and human studies show that gamma T and tocotrienols may be useful against inflammation-associated diseases. This review focuses on non-alpha T forms of vitamin E with respect to their metabolism, anti-inflammatory effects and mechanisms, and in vivo efficacy in preclinical models as well as human clinical intervention studies. (C) 2014 Elsevier Inc. All rights reserved.