ABSTRACT

In this review, we briefly describe the nature and origins of free radicals, and how these species cause intracellular damage, especially during ethanol metabolism. We then describe how alpha-tocopherol (ATC) has been employed in both experimental and clinical studies to reverse or ameliorate free radical-induced tissue damage in a variety of disorders. Most recent research data has focussed on the effects of ATC on the cardiovascular system, but as this review will illustrate, ATC has also been reported to have a protective role in diseases affecting a variety of tissues, including neurological disorders [1-6]. Thus, ATC can prevent cellular damage induced by exposure of rat cerebellar granule cells to cholesterol oxides in vitro [7]. However, the relationship between ATC intake, overall antioxidant intake and diet quality is complex, for example being related to social class [8], dietary intake of milk and fruit sugar [9], body mass index (BMI) and fat intake [10]. Life-style habits such as smoking also influence ATC status [11], although some studies (with small numbers of observations) have shown no correlation [12]. Studies on vitamin supplementation in the elderly have also shown that the physically active are more likely to take ATC (along with vitamin C and calcium) than their non-physically active counterparts [13]. Overall, the data on the potential therapeutic benefits of ATC intake suggest that even though it can increase anti-oxidant capacity and reduce lipid peroxidation in vitro, it may not halt disease progression or influence indices of tissue pathology in all instances. These conflicting findings probably reflect the fact that major diseases have complex etiologies in which free radical damage and/or changes in antioxidant status may represent only a single facet of the disease process. In many studies, alterations in free radical levels and/or scavenging antioxidants are measured without consideration of their functional effects. For example, dietary selenium deficiency reduces muscle glutathione peroxidase activity, but has no appreciable effects on endurance capacity in exercise, which triggers an increase in the generation of ROS [14]. We therefore conclude that the therapeutic role of this antioxidant is currently equivocal.