Outcomes of intervention studies
Most of the large randomized controlled studies that have attempted to prevent the onset of chronic diseases like cardiovascular disease through the administration of antioxidant micronutrients revealed no uniform, significant risk reduction among study participants. However, since participants in most of these studies already had adequate supplies of micronutrients like vitamins C and E as well as beta-carotene, the studies merely confirmed that consuming amounts of micronutrients over and above the recommended intakes brings no additional benefits for the general population. Moreover, in the randomized controlled studies the participants selected usually had a health problem already. As a rule, it proved impossible to substantiate the hope of preventing further exacerbation of chronic diseases through an intervention with antioxidant micronutrients.
Whereas in an earlier intervention study (1) of patients with a previous history of coronary heart problems it was possible to reduce the number of further infarctions by administration of large doses of vitamin E, neither the Heart Outcomes Prevention Evaluation Study (HOPE) nor the Heart Protection Study (HPS) showed a risk reduction for cardiovascular disease with large doses of vitamin E or a combination of vitamins E, C and beta-carotene (2, 3). For the SU.VI.Max-Study conducted in France, 13,017 participants received either a combination of 120 mg vitamin C, 30 mg vitamin E, 6 mg beta-carotene, 100 μg selenium and 20 mg zinc or placebo for a period of 7.5 years (4). While a reduction in all-cause mortality was observed for the men, no such results were found for the women. The authors suspected that the lower baseline plasma levels of antioxidant micronutrients measured in male participants could be at least partly responsible for the divergence in study outcomes. In the Antioxidant Supplementation in Atherosclerosis Prevention (ASAP) study 520 men and women, smokers and non-smokers received either 180 mg of vitamin E, 500 mg of vitamin C or a combination of both vitamins or placebo for a period of 3 years (5). While neither the vitamin E nor the vitamin C group revealed any effect, in the combination group the progress of carotid atherosclerosis was slowed considerably. In the Italian GISSI Study (6) patients who had already been treated for myocardial infarction were given 300 mg of vitamin E or 1 g of omega-3 fatty acids (PUFA), a combination of the two or a placebo in addition to their usual medication. Deaths due to cardiovascular events were significantly reduced in the PUFA group in the subsequent 3.5 years. In contrast, in the vitamin E group only sudden death was reduced, by 35 percent. Between 1992 and 2004, 39,876 healthy American women aged over 45 were included in the 10-year Women’s Health Study (7). They were given either 600 IU (400 mg) vitamin E every second day or placebo or aspirin. Cardiovascular deaths were reduced by 24 percent in the vitamin E group, while in the over-65 group a 26 percent reduction in cardiovascular disease was found. Unfortunately, participants’ plasma levels were not measured in this study; it was merely mentioned that 38.4 percent of the women in the placebo group had taken a multivitamin preparation.