Brain-E, Does It Equate to Brainy?
Comparisons of natural and synthetic vitamin E during pregnancy and lactation in mice for their studies on gene regulation in offspring brain vitamin E represent an important step forward in understanding how the brain acquires vitamin E, how it is trafficked within the brain, or how thebrain compared with other tissues more effectively retainsitamin E during deficiency.
Abstract
The molecular mechanisms for the human vitamin E (α-tocopherol) requirement are unknown. In this issue of The Journal of Nutrition, Rhodes et al. (1) compared natural and synthetic vitamin E during pregnancy and lactation in mice for their studies on gene regulation in offspring brain vitamin E. These studies represent an important step forward because it is unknown how the brain acquires vitamin E, how it is trafficked within the brain, or how the brain compared with other tissues more effectively retains vitamin E during deficiency (2). Vitamin E is a fat-soluble antioxidant that has gained new significance as an antiferroptotic agent, preventing programmed cell death caused by lipid peroxidation (3). Importantly, vitamin E deficiency enhances ferroptosis in the brain, especially the hippocampus (4). In 1922, vitamin E was identified in experiments in which it was found to be necessary for pregnant rats to carry their infants to term (5). Molecular mechanisms during embryogenesis and neurodevelopment are unknown, but low serum vitamin E concentrations early in human pregnancy are associated with increased miscarriage (6). Estimates of inadequate dietary vitamin E intakes exceed 80% of the global ≥14-y-old population (7) and 96% of American women (8). The 2015 Dietary Guidelines for Americans reported that vitamin E remains an under-consumed nutrient (9). The vitamin E international unit (IU) was defined because natural and synthetic α-tocopherol had the same antioxidant activities, but different biological activities. Therefore, the IU was defined on the basis of the requirement for vitamin E during embryogenesis using the now obsolete rat “fetal resorption assay.”The definition of the IU was deemed necessary because 1) chemically synthesized α-tocopherol contains 8 different stereoisomers and 2) plants make 8 different molecules with “vitamin E” antioxidant activity. This latter point was emphasized in the 1968 RDAs (10) because the American diet contains high amounts of γ -tocopherol, a form of vitamin E found in soybean, corn, and cottonseed oils (11). The expectation was that there was conversion between forms and that other vitamin E forms could substitute for α-tocopherol. However, more recent evidence shows that only plants can convert the 7 non-α-tocopherol forms to α-tocopherol.