Given the assumption that oxidative stress plays a pivotal role in atherogenesis, it could have been predicted that antioxidants will slow or even stop the development of atherotic plaques. The results of the latter prediction were disappointing. Moreover, previous meta-analyses concluded that indiscriminate supplementation of vitamin E at high dose (400 IU or more) results in increased mortality, both cardiovascular and all-cause. This conclusion raised serious criticisms, particularly on the choice of studies for meta-analyses, the end point (mortaLity) and the heterogeneity of the clinicaL studies with respect to both the population and the treatment. In Dr. Dotan's PhD thesis, conducted under my supervision, with the assistance of Drs. Leshno and Pinchuk, we analysed the results of the major cLinicaL studies within a Markov model. Using this approach enabled us to adjust the data for heterogeneities and assess the sensitivity of the outcome to the different affectors. The adjusted data were then used to assess the risk of transitions between predefined health state (healthy, dead or CVD patients, following a cardiac event). We also used a different 'end point', that is the quantity-adjusted life years (QALY), which reflects both morbidity and mortality. The major result of this study is that indiscriminate high dose supplementation of vitamin E is associated with an average loss of about 0.3 QALY. Yet, we think that some specific groups (presumably those that suffer from high oxidative stress) may gain from vitamin E supplementation. The existing data is insufficient to predict who is likely to benefit from vitamin E treatment. Until such data becomes available, we cannot recommend high dose vitamin E supplementation.