Abstract

For decades, the association between antioxidant supplementation and cardiovascular prevention has been controversial. Although there is a solid rationale for this association, based on the role of oxidative stress in cardiovascular pathophysiology, a lack of consistency between studies has slowed the inclusion of antioxidants into preventive cardiology. Understanding the reasons behind this discrepancy requires a rigorous analysis of study designs, results, follow-ups, the intervened population, and the biochemical characteristics of the antioxidants that were tested. On one hand, several early studies were based on inadequate formulations and suboptimal populations.On the other hand, historically, the concept “antioxidant” has been understood as a synonym of free radical scavenger, the paradigm of vitamins C and E. However, antioxidants correspond to a vast set of unrelated substances, some of which exert their effects through different mechanisms and may also have other biological properties that can contribute to cardiovascular protection (pleiotropy). Therefore, inasmuch as many of these substances act through different pathways, intermediate outcomes. (ie, biomarkers of oxidative stress such as lipid peroxidation, among others) are needed to determine whether the beneficial effect in terms of cardiovascular outcomes are attributed to the antioxidant mechanism. Over the past 3 decades, a combination of 2 factors has facilitated the identification of a correlation between certain modes of antioxidant supplementation and cardiovascular prevention. The first was the application of a “translational perspective” to designing some studies, which paid close attention to the chemical, biochemical, and pharmaceutical determinants of the tested antioxidants. The second was a more strategic selection of the populations to intervene, based on accumulated knowledge.