CHAPTER 17. Vitamin E Deficiency and Inadequacy; Insights Using Zebrafish, Lipidomics and Metabolomics

Vitamin E (α-tocopherol, VitE) deficiency has been recognized for about 100 years to cause neurologic developmental failures and fetal death. Thus, VitE is a critical player in the biochemical and physiological networks that prevent the dysregulation of neurogenesis. The major concepts that are described herein include: (1) the antioxidant function of VitE along with glutathione to protect against peroxidative damage, (2) the recognition that highly peroxidizable lipids are necessary for nervous system development and (3) the interrelationships between phosphatidyl choline regulation, the choline/methylation cycle and the folate cycle. The discoveries from VitE deficient (E−) zebrafish show that oxidative and metabolic damage, along with behavioral and morphological abnormalities, are caused by inadequate VitE status. Prior to the onset of morphological abnormalities, E− embryos experience dysregulation of choline status, methylation patterns and energy generation with glucose depletion. Given the importance of healthy fetuses, the lack of understanding of VitE's role in regulation of embryogenesis represents a critical lack of knowledge about this key nutrient. Remarkably, most women have inadequate intakes of both VitE and choline, suggesting that inadequacy of one might potentiate the inadequacy of the other. Importantly, VitE inadequacy drives secondary deficiencies that cause developmental defects, especially neural tube defects. Specifically, the relationship of VitE, oxidative damage and metabolic control systems involved in neurogenesis are described.