Cardiovascular disease (CVD) is the leading cause of death in the world and it requires an effective primary prevention approach to face this public health menace.

The hypothesis that oxidative events play a significant role in human atherogenesis has been considered the basis of a wealth of large-scale human observational studies and some clinical trials. The studies and trials have focused on linking the dietary antioxidant vitamins with a protective effect on CVD, one of the most important clinical manifestations of atherosclerosis, suggesting that antioxidant vitamins could help to block the atherogenic process and prevent CVD.

We have recently published a brief review in order to synthesize evidence from scientific literature of the relationship of antioxidants vitamins (specially vitamin C, vitamin E, and betacarotene) and the risk of CVD.

Discrepancies between observational studies and clinical trials

Several observational cohort studies have shown an association between antioxidant vitamins C, E or β-carotene intake either from food or supplements and a protective effect against CVD.

However, the evidence from most clinical trials evaluating single antioxidants, or the combination of a small number of these antioxidant vitamins in supplementation, have yielded disappointing results that are in clear disagreement with prior observational data.

Results from meta-analyses of randomized controlled trials evaluating the effect of antioxidant vitamins on cardiovascular events do not support the recommendation of antioxidant vitamins supplementation. In addition occasional data even discourages the use of these supplements because of the possibility that they may even slightly increase the risks of cardiovascular death.

Post-intervention studies

Longer-term effects after stopping antioxidant supplémentations on cardiovascular outcomes have been studied in some of the main experimental studies of antioxidants and CVD prevention. These studies include the Alpha-tocopherol, Beta-carotene Cancer Prevention Study (ATBC) [Intervention: Alpha-tocopherol versus no alpha-tocopherol, and beta-carotene versus no beta-carotene; 6-year post-trial follow-up; CVD mortality as endpoint], the Beta-Carotene and Retinol Efficacy Trial (CARET) [Intervention: combination of 30 mg of beta-carotene and 25,000 UI of retinol versus placebo; 6-year post-trial follow-up; CVD mortality as endpoint], the Linxian General Population Nutrition Intervention Trial (NIT) [Intervention: vitamin C and molybdenum versus placebo, and selenium, vitamin E, and beta-carotene versus placebo; 10-year post-trial follow-up; stroke mortality as endpoint], and the Supplementation in Vitamins and Mineral Antioxidants (SU.VI.MAX) Study [Intervention: combination of 120 mg vitamin C, 30 mg of vitamin E, 6 mg of beta-carotene, 100 μg of selenium and zinc versus placebo; 5-year post-trial follow-up; ischaemic CVD incidence as endpoint]. None of these post-trial evaluations has shown any significant beneficial effect of antioxidant supplementation in CVD primary prevention.

Conclusions

Research findings on the potential role that antioxidant vitamins supplementation plays in preventing CVD have gone from promising observational studies outcomes to confusing clinical trials and post-intervention studies results. In the light of current evidence, the use of vitamin C, vitamin E or β-carotene routine supplementation as a population-wide strategy for primary prevention of CVD is not sufficiently warranted. Some authors have suggested the need of future studies using more potent antioxidants than vitamins used in prior evaluations, in addition to studies assessing the effect of these antioxidants in different subgroups of participants with characteristics that could affect the individual capacity to prevent oxidative stress.

For the time being, antioxidant-rich foods and diets, such as fruits and vegetables or the Mediterranean diet, rather than high-dose supplementation with single antioxidant compounds, should be recommended to prevent CVD.