A review is presented of studies on the effects of vitamin E on heart disease, 
studies encompassing basic science, animal studies, epidemiological and 
observational studies, and four intervention trials. The in vitro, cellular, and 
animal studies, which are impressive both in quantity and quality, leave no 
doubt that vitamin E, the most important fat-soluble antioxidant, protects 
animals against a variety of types of oxidative stress. The hypothesis that 
links vitamin E to the prevention of cardiovascular disease (CVD) postulates 
that the oxidation of unsaturated lipids in the low-density lipoprotein (LDL) 
particle initiates a complex sequence of events that leads to the development of 
atherosclerotic plaque. This hypothesis is supported by numerous studies in 
vitro, in animals, and in humans. There is some evidence that the ex vivo 
oxidizability of a subject's LDL is predictive of future heart events. This 
background in basic science and observational studies, coupled with the safety 
of vitamin E, led to the initiation of clinical intervention trials. The three 
trials that have been reported in detail are, on balance, supportive of the 
proposal that supplemental vitamin E can reduce the risk for heart disease, and 
the fourth trial, which has just been reported, showed small, but not 
statistically significant, benefits. Subgroup analyses of cohorts from the older 
three trials, as well as evidence from smaller trials, indicate that vitamin E 
provides protection against a number of medical conditions, including some that 
are indicative of atherosclerosis (such as intermittent claudication). Vitamin E 
supplementation also produces an improvement in the immune system and protection 
against diseases other than cardiovascular disease (such as prostate cancer). 
Vitamin E at the supplemental levels being used in the current trials, 100 to 
800 IU/d, is safe, and there is little likelihood that increased risk will be 
found for those taking supplements. About one half of American cardiologists 
take supplemental vitamin E, about the same number as take aspirin. In fact, one 
study suggests that aspirin plus vitamin E is more effective than aspirin alone. 
There are a substantial number of trials involving vitamin E that are in 
progress. However, it is possible, or even likely, that each condition for which 
vitamin E provides benefit will have a unique dose-effect curve. Furthermore, 
different antioxidants appear to act synergistically, so supplementation with 
vitamin E might be more effective if combined with other micronutrients. It will 
be extremely difficult to do trials that adequately probe the dose-effect curve 
for vitamin E for each condition that it might affect, or to do studies of all 
the possible combinations of other micronutrients that might act with vitamin E 
to improve its effectiveness. Therefore, the scientific community must recognize 
that there never will be a time when the science is "complete." At some point, 
the weight of the scientific evidence must be judged adequate; although some may 
regard it as early to that judgement now, clearly we are very close. In view of 
the very low risk of reasonable supplementation with vitamin E, and the 
difficulty in obtaining more than about 30 IU/day from a balanced diet, some 
supplementation appears prudent now.