A hundred years have passed since vitamin E was identified as an essential micronutrient for mammals. Since then, many biological functions of vitamin E have been unraveled in both cell and animal models, including antioxidant and anti-inflammatory properties, as well as regulatory activities on cell signaling and gene expression. However, the bioavailability and physiological functions of vitamin E have been considerably shown to depend on lifestyle, genetic factors, and individual health conditions. Another important facet that has been considered less so far is the endogenous interaction with other nutrients. Accumulating evidence indicates that the interaction between vitamin E and other nutrients, especially those that are enriched by supplementation in humans, may explain at least some of the discrepancies observed in clinical trials. Meanwhile, increasing evidence suggests that the different forms of vitamin E metabolites and derivates also exhibit physiological activities, which are more potent and mediated via different pathways compared to the respective vitamin E precursors. In this review, possible molecular mechanisms between vitamin E and other nutritional factors are discussed and their potential impact on physiological and pathophysiological processes is evaluated using published co-supplementation studies.
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