[Vitamin E and coronary heart disease--why the lack of effect in large clinical trials?]

Oxidative modification of low-density lipoprotein (LDL) is likely to play a role in the development of atherosclerosis and coronary heart disease. In vitro studies, animal experiments and several observational investigations suggest that vitamin E is an effective preventive agent. Unfortunately, large clinical studies have failed to confirm these findings.

On the basis of literature studies, I discuss the lack of effect.

The hypothesis that LDL must be oxidised to be really harmful, could be wrong. If oxidised LDL is an important atherogenic factor, vitamin E (alpha-tocopherol) might not be a powerful enough antioxidant, especially in the later stages of atherosclerosis. Maybe one needs to use a mixture of different kinds of vitamin E and co-antioxidants that can regenerate vitamin E to achieve an effect that is powerful enough? The effect of vitamin E might have been masked by n-3 fatty acids in some studies. The most plausible hypothesis is that only people with extraordinarily high oxidative stress will benefit from vitamin E supplementation.

Further research is needed to understand how oxidised LDL and vitamin E affect the development of coronary heart disease. In the meantime it is important to point out that a healthy diet with balanced amounts of antioxidants and enough n-3 fatty acids has been proven effective.