Some of the impacts of vitamin E deficiency include neurodegeneration, demyelination and ataxia, indicating that vitamin E is critical in nerve and brain function.  There are 8 structural congeners of vitamin E, however, a-tocopherol is the most abundant and biologically active form in the diet.  Synthetic vitamin E is composed of all 8 stereoisomers and these mixtures are not as potent as the natural form.  Absorption of a-tocopherol relies upon a-tocopherol transfer protein, which preferentially binds to certain isomers.  Because of this binding preference, it is not clear if biopotency of the natural and synthetic a-tocopherol are different for various biological processes and within certain tissues, such as the brain.  Rhodes and colleagues explored the impact of different concentrations and forms of a-tocopherol on gene expression in the brains of developing mouse fetuses.  Their study outcomes are reported in the December 2020 issue of The Journal of Nutrition.

Mouse dams were provided diets containing 37.5 or 75 IU/kg of either natural or synthetic a-tocopherol throughout gestation and lactation.  The brain from 21 day old male pups was used to measure a-tocopherol concentration and stereoisomer distributions, and the hippocampus was used to measure gene expression.

There were distinct differences in the stereoisomer profiles in the brains caused by the type of a-tocopherol, but there were only small differences in the a-tocopherol concentrations caused by elevated levels in the diet.  When gene expression patterns were compared for each level of a-tocopherol within the natural and synthetic source diets, there were subtle changes in the expression (600 and 487 genes, respectively).  When comparing the natural and synthetic source of a-tocopherol at a set diet level (37.5 or 75 IU/kg), there were fewer differentially expressed genes.  Of the genes differentially expressed, most were involved in transcription regulation and synapse formation.  The authors concluded that the source and level of a-tocopherol in the diet of pregnant and lactating mice affects genes involved in brain development and function within the hippocampus.

In a commentary on this article, Traber notes the importance of this work as little is known about how the brain acquires vitamin E or how it is trafficked within the brain to various structures.  In addition, the molecular mechanisms involved in embryogenesis and neurodevelopment linked to vitamin E are unknown.  The activity of a-tocopherol transfer protein and metabolism of vitamin E serve to allow the body to retain a-tocopherol.  Based on the fact that many of the differentially expressed genes were attributed to the distribution of synthetic a-tocopherol stereoisomers, Traber suggests that more work is needed to understand the critical role of vitamin E in neurodevelopment.


Rhodes JS, Rendeiro C, Mun JG, Du K, Thaman P, Snyder A, Pinardo H, Drnevich J, Chandrasekaran S, Lai C-S, Schimpf KJ, Kuchan MJ.  Brain a-tocopherol concentration and stereoisomer profile alter hippocampal gene expression in weanling mice.  The Journal of Nutrition, Volume 150, Issue 12, December 2020, Pages 3075–3085,

Traber MG. Brain-E, does it equate to brainy? The Journal of Nutrition, Volume 150, Issue 12, December 2020, Pages 3049–3050,

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