Copper (Cu) is a vital mineral essential for many biological processes. The vast majority of all Cu in healthy humans is associated with enzyme prosthetic groups or bound to proteins. Cu homeostasis is tightly regulated through a complex system of Cu transporters and chaperone proteins. Excess or toxicity of Cu, which is associated with the pathogenesis of hepatic disorder, neurodegenerative changes and other disease conditions, can occur when Cu homeostasis is disrupted. The capacity to initiate oxidative damage is most commonly attributed to Cu-induced cellular toxicity. Recently, altered cellular events, including lipid metabolism, gene expression, alpha-synuclein aggregation, activation of acidic sphingomyelinase and release of ceramide, and temporal and spatial distribution of Cu in hepatocytes, as well as Cu-protein interaction in the nerve system, have been suggested to play a role in Cu toxicity. However, whether these changes are independent of, or secondary to, an altered cellular redox state of Cu remain to be elucidated.

Superoxide, a key precursor of important reactive oxygen/nitrogen species (ROS/RNS), may release iron from its protein complex. By mediating the generation and/level of superoxide, vitamin E, the most important fat-soluble antioxidant and free radical scavenger, may exert its antioxidant function by limiting the formation of reactive hydroxyl radicals and peroxynitrite. The antioxidant function of vitamin E is augmented by GSH peroxidase and related metabolic systems which respond adaptively and compensatively to oxidative stress. By mediating the levels of ROS/RNS, vitamin E may also modulate the activation and/or expression of redox-sensitive biological response modifiers, and thereby attenuate the cellular events leading to the onset and development of aging and other degenerative disorders. Earlier epidemiological data and retrospective studies show an association between increased intake of vitamin E and reduced risk of cardiovascular disease, cancer, and other disorders. However, subsequent prospective randomized placebo-controlled studies and interventional trials have provided inconsistent findings. Data available from recent large-scale interventional trials suggest that vitamin E supplements at high doses are not beneficial.Keywords: Vitamin E, tocopherols, superoxide, biological function, health benefit. INTRODUCTIONVitamin E is referred to all tocol (tocopherol) and tocotrienol derivatives qualitatively exhibiting the biological activity of RRR-α-tocopherol. There are four tocopherols (α-, β-, γ-and δ-) and four tocotrienols (α-, β-, γ-and δ-) that occur naturally, differing in the number and position of methyl groups on the chroman ring [1,2]. Vitamin E was discovered 90 years ago, and a number of species-dependent and organ-specific deficiency symptoms of vitamin E were reported later [3,4]. However, due to the lack of clinically defined deficient syndromes attributable to vitamin E and the difficult to produce vitamin E deficiency in adults, its essentiality for humans was established only after the discovery of α-tocopherol transfer protein decades later [2,[5][6][7][8]. The transfer protein binds RRR-α-tocopherol preferentially over other forms/isomers of tocopherols, and enhances its transfer and return to the liver. The presence of α-tocopherol transfer protein is largely responsible for higher biological activity of RRR-α-form than other forms/isomers.