Elsevier

Molecular Aspects of Medicine

Volume 28, Issues 5–6, October–December 2007, Pages 400-422
Molecular Aspects of Medicine

Review
Vitamin E: An overview of major research directions

https://doi.org/10.1016/j.mam.2007.05.004Get rights and content

Abstract

During the last 90 years since the discovery of vitamin E, research has focused on different properties of this molecule, the focus often depending on the specific techniques and scientific knowledge present at each time. Originally discovered as a dietary factor essential for reproduction in rats, vitamin E has revealed in the meantime many more important molecular properties, such as the scavenging of reactive oxygen and nitrogen species with consequent prevention of oxidative damage associated with many diseases, or the modulation of signal transduction and gene expression in antioxidant and non-antioxidant manners. Research over the last 30 years has also resolved the biosynthesis and occurrence of vitamin E in plants, the proteins involved in the cellular uptake, tissue distribution and metabolism, and defined a congenital recessive neurological disease, ataxia with vitamin E deficiency (AVED), characterized by impaired enrichment of α-tocopherol in plasma as a result of mutations in the liver α-tocopherol transfer gene. This review is giving a brief introduction about vitamin E by following the major research directions since its discovery with a historical perspective.

Introduction

During the last almost 90 years since its discovery, research on vitamin E has focused on different properties of this molecule, the focus often depending on the specific techniques and scientific knowledge present at each time. For giving a brief overview and introduction about vitamin E for this special issue of “Molecular Aspects of Medicine”, it is therefore most convenient to follow the major research directions with a historical perspective (Fig. 1 and Table 1).

Section snippets

Discovery of vitamin E

Vitamin E has been discovered as “factor X” by Evans and Bishop while investigating dietary factors that are essential for reproduction in rats (Evans and Bishop, 1922). Similar experiments were performed by Sure, who then called the substance “vitamin E” (Sure, 1924). At about the same time Mattill and Conklin investigated whether milk represents a “perfect food”, and they came to the conclusion that milk may contain a substance that inhibited reproduction (Mattill and Conklin, 1920). Notably,

Research on the chemical structure of vitamin E

Natural vitamin E comprises eight different forms, the α-, β-, γ-, and δ-tocopherols and the α-, β-, γ-, and δ-tocotrienols (Fig. 2). The tocotrienols have an unsaturated isoprenoid side chain, whereas the tocopherols contain a trimethyltridecyl tail with three chiral centres which naturally occur in the RRR configuration. Only recently novel natural vitamin E analogues have been discovered; palm oil contains also small amounts of α-tocomonoenol, and some marine organisms contain also marine

Research on the biosynthesis of vitamin E in plants

The tocopherols are exclusively synthesized in photosynthetic organisms including higher plants; significant amounts are found in all green tissues but predominantly occur in seeds. Plant derived oils represent the major sources of vitamin E in the human diet, and because these oils contain the four tocopherols in different relative amounts, the overall intake of each vitamin E analogue depends in large on the dietary oil preferences in different countries (reviewed in Zingg and Azzi (2004)).

Research on the chemical properties of vitamin E

It was already discovered early on that vitamin E can chemically prevent the oxidation of lipids (Cummings and Mattill, 1931, Olcott and Emerson, 1937); further biochemical studies into the antioxidant action of vitamin E were mainly initiated by Tappel and colleagues (Tappel and Zalkin, 1960, Tappel, 1954, Tappel, 1955).

To date it is known that the overall antioxidant activity of the four tocopherols is more or less similar; however, clear individual chemical, physical and biological effects

Research on the cellular uptake, transport and tissue distribution of vitamin E

A relationship between neurologic dysfunction and vitamin E deficiency in patients with chronic steatorrhea was first described by Binder et al. (1967). Harding et al. described a young woman with spinocerebellar degeneration thought to be due to a selective defect in vitamin E absorption, without any evidence of fat malabsorption (Harding et al., 1985), and similar findings were reported later in several further patients. Traber et al. demonstrated a defect in the incorporation of α-tocopherol

Research on the metabolism of vitamin E

Excess α-tocopherol and the other tocopherol and tocotrienol analogues are extensively metabolized before excretion (reviewed in Brigelius-Flohe, 2003, Pfluger et al., 2004). This finding suggests that the organism maintains the correct vitamin E level by selective retention of a certain amount of α-tocopherol, and by specific metabolism of all the other tocopherols, the tocotrienols, and of the excess α-tocopherol. As reviewed in this issue (Wu and Croft, 2007), specific metabolic enzymes are

Research on cellular effects of vitamin E

The essentiality of vitamin E was originally defined by the ability to prevent fetal resorption in rats resulting from a vitamin E deficient diet; since rancid lard (oxidized animal fat) was present in that diet, the essential function of vitamin E in this assay was mainly attributed to its action as chain-breaking antioxidant in the lipid phase (Section 2). In humans, some of the symptoms of vitamin E deficiency, such as increased lipofuscinosis most likely originate from the lack of

Research on vitamin E analogues

Since the natural vitamin E analogues are relatively unstable, several stabilized vitamin E derivatives have been synthesized for usage in supplements and cosmetics (reviewed in Cerecetto and Lopez, 2007, Zingg, 2007b). Whereas these derivatives may have advantages for processing, storage and absorption, they usually are rapidly converted to the natural forms by intestinal or epidermal esterases, and thus can be considered to be pro-vitamins, ultimately performing the same functions in the body

Research on health benefits of vitamin E

Potential health benefits of vitamin E supplementation that are in addition to the essential effects on reproduction were suggested already in the 1950s. In particular, the neurological symptoms associated with vitamin E deficiency were reported to improve with vitamin E supplementation (Binder et al., 1967, Harding et al., 1985). Although therapeutic properties of vitamin E against cardiovascular disease were proposed very early (Vogelsang and Shute, 1946), they remained controversial until a

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