Vitamin E: Not only a single stereoisomer

• Published in: Free radical biology & medicine 2024-03, Vol.215, p.106-111
• Main Authors: Eggersdorfer, M., Schmidt, K., Péter, S., Richards, J., Winklhofer-Roob, B., Hahn, A., Obermüller-Jevic, U.
• Format: Article
• Language: English
• Subjects: alpha-Tocopherol - pharmacology; Antioxidants - chemistry; Antioxidants - pharmacology; Humans; Stereoisomerism; Vitamin E - metabolism; Vitamin E - pharmacology; Vitamin E Deficiency - drug therapy
• ISSN: 0891-5849; 1873-4596
• DOI: 10.1016/j.freeradbiomed.2024.02.013

The recent publication by Azzi and colleagues puts forth the argument that only RRR-α-tocopherol should be considered as vitamin E from a physiological point of view. They base their argument primarily on the assertion that only this form has been used to treat stark vitamin E deficiency in humans (known as AVED, or Ataxia with Vitamin E Deficiency). Azzi et al. also argue that other chemically similar molecules, such as tocopherols other than α-tocopherol and tocotrienols do not provide vitamin E activity. Azzi and colleagues are correct on this second point. An investigation into the biological activities of vitamin E, and the mechanisms behind these activities, confirms that physiological vitamin E activity is limited to certain α-tocopherol forms. However, it is also clear that these activities are not restricted only to the RRR-form but include other 2R-forms as well. Indeed, the α-tocopherol transfer protein (α-TTP), which is critical to mediate vitamin E trafficking and biological activity, and genetic defects of which lead to vitamin E deficiency, binds well to all 2R-forms of α-tocopherol. Furthermore, both RRR-α-tocopherol and the other 2R-forms are maintained in human plasma and distributed to tissues and organs, whereas the 2S-stereoisomers are excreted quickly. As such, in recent years the definition of vitamin E including both 2R- and RRR-α-tocopherol has gained both broad scientific and regulatory acceptance. Consistent with this understanding, we provide evidence that AVED has indeed been treated successfully with forms in addition to RRR-α-tocopherol, again arguing against the restriction of the definition to RRR-α-tocopherol only. Finally, we provide evidence against any safety concerns utilizing the currently accepted definition of vitamin E. •Physiological vitamin E activity is limited to α-tocopherol forms with 2R stereochemistry.•The α-tocopherol transfer protein (α-TTP), which is critical to mediate vitamin E trafficking and biological activity binds well to all 2R-forms of α-tocopherol.•The definition of vitamin E including both 2R- and RRR-α-tocopherol has gained both broad scientific and regulatory acceptance.