Vitamin E and heart disease: Basic science to clinical intervention trials

A review is presented of studies on the effects of vitamin E on heart disea se, studies encompassing basic science, animal studies, epidemiological and observational studies, and four intervention trials. The in vitro, cellula r, and animal studies, which are impressive both in quantity and quality, l eave no doubt that vitamin E, the most important fat-soluble antioxidant, p rotects animals against a variety of types of oxidative stress. The hypothe sis that links vitamin E to the prevention of cardiovascular disease (CVD) postulates that the oxidation of unsaturated lipids in the low-density lipo protein (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 eviden ce that the ex vivo oxidizability of a subject's LDL is predictive of futur e heart events. This background in basic science and observational studies, coupled with the safely of vitamin E, led to the initiation of clinical in tervention trials. The three trials that have been reported in detail are. on balance, supportive of the proposal that supplemental vitamin E can redu ce the risk for heart disease, and the fourth trial, which has just been re ported, 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 numbe r of medical conditions, including some that are indicative of atherosclero sis (such as intermittent claudication). Vitamin E supplementation also pro duces an improvement in the immune system and protection against diseases o ther than cardiovascular disease (such as prostate cancer). Vitamin E at th e 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 su pplemental vitamin E, about the same number as take aspirin. In fact, one s tudy suggests that aspirin plus vitamin E is more effective than aspirin al one. There are a substantial number of trials involving vitamin E that are in progress. However, it is possible, or even likely, that each condition f or which vitamin E provides benefit will have a unique dose-effect curve. F urthermore, different antioxidants appear to act synergistically, so supple mentation with vitamin E might be more effective if combined with other mic ronutrients. It will be extremely difficult to do trials that adequately pr obe the dose-effect curve for vitamin E for each condition that it might af fect, or to do studies of all the possible combinations of other micronutri ents that might act with vitamin E to improve its effectiveness. Therefore, the scientific community must recognize that there never will be a time wh en the science is "complete." At some point, the weight of the scientific e vidence must be judged adequate; although some may regard it as early to th at judgement now, clearly we are very close. in view of the very low risk o f reasonable supplementation with vitamin E, and the difficulty in obtainin g more than about 30 IU/day from a balanced diet, some supplementation appe ars prudent now. (C) 2000 Elsevier Science Inc.