Vitamin E: protective role of a Janus molecule

Since the discovery of vitamin E in 1922, its deficiency has been associate d with various disorders, particularly atherosclerosis, ischemic heart dise ase, and the development of different types of cancer. A neurological syndr ome associated with vitamin E deficiency resembling Friedreich ataxia has a lso been described. Whereas epidemiological studies have indicated the role of vitamin E in preventing the progression of atherosclerosis and cancer, intervention trials have produced contradictory results, indicating strong protection in some cases and no significant effect in others. Although it i s commonly believed that phenolic compounds like vitamin E exert only a pro tective role against free radical damage, antioxidant molecules can exert o ther biological functions. For instance, the antioxidant activity of 17-bet a -estradiol is not related to its role in determining secondary sexual cha racters, and the antioxidant capacity of all-trans-retinal is distinguished from its role in rhodopsin and vision. Thus, it is not unusual that alpha -tocopherol (the most active form of vitamin E) has properties independent of its antioxidant/radical scavenging ability. The Roman god Janus, shown i n ancient coins as having two faces in one body, inspired the designation o f 'Janus molecules' for these substances. The new biochemical face of vitam in E was first described in 1991, with an inhibitory effect on cell prolife ration and protein kinase C activity. After a decade, this nonantioxidant r ole of vitamin E is well established, as confirmed by authoritative studies of signal transduction and gene regulation. More recently, a tocopherol bi nding protein with possible receptor function has been discovered. Despite such important developments in understanding the molecular mechanism and th e targets of vitamin E, its new Janus face is not fully elucidated. Greater knowledge of the molecular events related to vitamin E will help in select ing the parameters for clinical intervention studies such as population typ e, dose response effects, and possible synergism with other compounds.