INTERVENTION STUDIES
Most intervention trials have shown no benefit or even adverse effects on cardiovascular disease.
- The ATBC study (alpha-tocopherol beta-carotene prevention study) showed a 43% increase in CVD.
- The CARET study (beta-carotene and retinol efficacy trial) showed a 26% higher fatal CHD risk, in addition to a significant increase in cancer incidence.
Exception: The ATBC study showed a protective effect of vitamin E on prostate cancer.
We will return to this topic in the e-lecture Other micronutrients in relation to cancer in particular.
 |
Other studies showing adverse effects:
- Waters et al, 2002, JAMA 288, 2431-2440
Women’s Angiographic vitamin and Estrogen (WAVE) trial
- Cheung et al Arterioscler Thromb vasc. Biol 21, 1320-1325, 2001
- Brown et al N. Eng J. Med. 345, 2001, 1583-1592.
- Recent meta-analysis study of more than 135000 participants in 19 published clinical trials (increased mortality who took >400U per day) (Miller et al Ann Int. Med. 142, 2005)
Why have trials failed to show beneficial effect of vitamin E?
- Too high dose? (may alter xenobitics)
- Pro-oxidant effects?
- Wrong target group?
- Wrong theory?
 |
SUMMARY
- Vitamin E requirement in humans is limited to RRR α-tocopherol
- Liver controls plasma vitamin E concentrations; αTTP facilitates α-tocopherol secretion into plasma
- It is retained in the plasma and tissues by several binding proteins and transport proteins
- Vitamin E deficiency results from genetic defects in these proteins
- Apart from the antioxidant activity, vitamin E regulates several genes responsible for atherosclerosis, cell cycle, and inflammation
- Vitamin E is metabolised via activation of SXR (PXR) activationg xenobiotic metabolising enzymes, and thus possibly interferring with drug metabolism and therapeutic efficacy
- Human studies are required for determining its RDA values and the roles of gene polymorphisms of tocopherol binding proteins
 |