Cardiovascular diseases (CVD) cause about 1/3 of global deaths. Therefore, new strategies for the prevention and treatment of cardiovascular events are highly sought-after. Vitamin E is known for significant antioxidative and anti-inflammatory properties, and has been studied in the prevention of CVD, supported by findings that vitamin E deficiency is associated with increased risk of cardiovascular events. However, randomized controlled trials in humans reveal conflicting and ultimately disappointing results regarding the reduction of cardiovascular events with vitamin E supplementation. As we discuss in detail, this outcome is strongly affected by study design, cohort selection, co-morbidities, genetic variations, age, and gender. For effective chronic primary and secondary prevention by vitamin E, oxidative and inflammatory status might not have been sufficiently antagonized. In contrast, acute administration of vitamin E may be more translatable into positive clinical outcomes. In patients with myocardial infarction (MI), which is associated with severe oxidative and inflammatory reactions, decreased plasma levels of vitamin E have been found. The offsetting of this acute vitamin E deficiency via short-term treatment in MI has shown promising results, and, thus, acute medication, rather than chronic supplementation, with vitamin E might revitalize vitamin E therapy and even provide positive clinical outcomes.
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