Vitamin E metabolism

The aim of this paper is to provide an overview of vitamin E metabolism. The topics covered include: major classes of vitamin E metabolites; their production pathways and route of excretion; possible biological activities of vitamin E metabolites; and use of vitamin E metabolites as markers of oxidant generation. Recent investigations into vitamin E metabolism have also highlighted important new areas of research, such as the potential for high dose vitamin E supplementation to interfere with drug metabolism, as well as alternative methods to alter vitamin E bioavailability in vivo. These issues will also be discussed in the review.     

Vitamin E and apoptosis

The literature data concerning the participation of tocopherol in apoptosis are discussed. Acting as antioxidant this vitamin exerts a complex effect on apoptosis mechanisms. Its action on this process is caused by involvement of some different mechanisms transducing the apoptotic signal. Among them are caspase and Fas-receptor activation, sphingosine metabolism, processes carried out in nuclei and mitochondria and signal transduction pathways. The specific mechanisms connected with interaction of this vitamin with tocopherol-binding proteins may be also involved in this vitamin action.     

Vitamin E and genome stability

Free radicals and reactive oxygen species (ROS) which are generated continuously cause mutagenic alterations resulting in cancer, aging and abnormalities in the nervous system. Accumulating evidence indicates that Vitamin E, the most potent lipid peroxyl radical scavenger, may reduce free radical induced chromosomal damages through inhibition of free radical formation, and activation of endonuclease that can be triggered by intracellular oxidative stress, and by increasing the rate of removal of damaged DNA. Although some studies suggest a potential usefulness of Vitamin E in the prevention of mutagenic effects caused by genotoxic free radicals, other studies report no effects. Thus the data are not conclusive enough to be used as a basis to change the current recommended dietary allowances (RDA). Future research should address molecular mechanisms underlying the protective effects of Vitamin E and develop appropriate biologically relevant biomarkers of DNA damage to further help in determining the dietary levels of Vitamin E needed to protect the genetic pool from internally and externally induced DNA damages.     

Vitamin E and transfer proteins

PURPOSE OF REVIEW: Recently, the intracellular transport as well as cellular uptake and excretion of alpha-tocopherol, the major representative of vitamin E, have been elucidated. RECENT FINDINGS: Alpha-tocopherol transfer protein has been identified as the major intracellular transport protein for vitamin E, mediating alpha-tocopherol secretion into the plasma via a non-Golgi-dependent pathway, while other binding proteins seem to play a less important role. New information has accumulated concerning the role of this protein in the transport and supply of vitamin E to tissues such as the central nervous system and the feto-maternal unit. The scavenger receptor class B type I receptor, a membrane-bound protein, is capable of transferring vitamin E into the cell, while the ATP-binding cassette transporter A1 can excrete vitamin E out of the cell. Advances in the area of vitamin E metabolism have shown that alpha-CEHC (2,5,7,8-tetramethyl-2-(2'-carboxyethyl)-6-hydroxychroman) and gamma-CEHC (2,7,8-trimethyl-2-(2'-carboxyethyl)-6-hydroxychroman) are formed by a cytochrome p450-mediated process, important for alpha and gamma-tocopherol excretion. SUMMARY: Insights into the regulation of vitamin E transport and metabolism on the cellular level have made enormous advances, showing the complex interplay of influx, trafficking, efflux and metabolism of this crucial antioxidant.     

Vitamin E bioavailability in humans

It is important to understand factors that can influence vitamin E bioavailability, particularly in populations with increased risk of coronary heart disease such as cigarette smokers. There is also a need to clarify the bioavailability of natural and synthetic vitamin E, which is currently a subject of some controversy. Previous studies using a competitive uptake approach have found bioavailability ratios of natural:synthetic vitamin E close to 2:1, differing from the accepted biopotency ratio of 1.36:1. We used a non-competitive uptake approach to compare the plasma biokinetics of deuterated natural (RRR) and synthetic (all rac) alpha-tocopheryl acetate in smokers and non-smokers. The study was comprised of two 4-week treatments with 400 mg/d (either RRR-alpha-tocopheryl or all rac-alpha-tocopheryl acetates), with a 12-week washout period between. Prior to and after each treatment subjects underwent a 48 h biokinetic protocol with 150 mg deuterated alpha-tocopheryl acetate in either the RRR or all rac form. Smokers had a lower deuterated alpha-tocopherol AUC than did non-smokers following administration of RRR, but there was no difference following administration of all rac. The ratio RRR:all rac from AUCs and C(max) was 1.3:1 in non-smokers and 0.9:1 in smokers. Following vitamin E supplementation, deuterated tocopherol AUCs were lower in both groups. These data suggest that non-smokers and smokers differ in their handling of vitamin E, that the relative bioavailability of natural and synthetic vitamin E is close to the currently accepted biopotency ratio of 1.36:1, and that following supplementation the ability of the plasma to take up newly absorbed vitamin E is decreased.     

Vitamin E and neurodegenerative diseases

Vitamin E is essential for neurological function. This fact, together with a growing body of evidence indicating that neurodegenerative processes are associated with oxidative stress, lead to the convincing idea that several neurological disorders may be prevented and/or cured by the antioxidant properties of vitamin E.

In this review, some aspects related to the role of vitamin E against Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis and ataxia with vitamin E deficiency will be presented.