Utilization of vitamin E

Natural (RRR) or synthetic (all-rac) forms of alpha-tocopherol are available (usually as acetate esters) for use as vitamin E supplements. In animal tests, the natural stereoisomer, RRR-alpha-tocopheryl acetate, is 1.36 times more biologically potent than all-rac-alpha-tocopheryl acetate, an equimolar mixture of eight stereoisomers [8,15,40-43]. The higher biologic activity of natural compared with synthetic vitamin E does not result from differences in antioxidant activity [2,3], but could hypothetically be explained by differences in (1) absorption, (2) plasma transport, (3) delivery to tissues, or (4) metabolism. These possibilities will be considered in this review.     

Beyond vitamin E supplementation: an alternative strategy to improve vitamin E status

Vitamin E has many reported health effects and is recognized as the most important lipid-soluble, chain-breaking antioxidant in the body. Vitamin E has also been reported to play a regulatory role in cell signalling and gene expression. Epidemiological studies show that high blood concentrations of vitamin E are associated with a decreased risk of cardiovascular diseases and certain cancers. Yet, high doses of supplemental vitamin E have been associated with an elevated risk of heart failure and all-cause mortality. Therefore, establishing alternative strategies to improve vitamin E status without potentially increasing mortality risk may prove important for optimal nutrition. To identify dietary phenolic compounds capable of increasing blood and tissue concentrations of vitamin E, selected polyphenols were incorporated into standardized, semi-synthetic diets and fed to male Sprague-Dawley rats for 4 weeks. Blood plasma and liver tissue concentrations of alpha-T and gamma-Twere determined. The flavanols (+)-catechin and (-)-epicatechin, the flavonol quercetin, and the synthetic preservative butylated hydroxytoluene (BHT) markedly elevated the amount of alpha-T in plasma and liver. The sesame lignan sesamin and cereal alkylresorcinols substantially increased the concentrations of gamma-T, but not alpha-T, in the liver. Sesamin also increased gamma-T concentrations in plasma. In order to study the impact of selected polyphenols on the enzymatic degradation of vitamin E, HepG2 cells were incubated together with phenolic compounds in the presence of tocopherols and the formation of metabolites was determined. Sesamin, at concentrations as low as 2 microM, almost completely inhibited tocopherol side-chain degradation and cereal alkylresorcinols inhibited it, dose-dependently (5-20 microM), by 20-80%. BHT, quercetin, (-)-epicatechin, and (+)-catechin had no effect on tocopherol-omega-hydroxylase activity in HepG2 cells. In order to confirm the inhibition of gamma-T metabolism by sesame lignans in humans, sesame oil or corn oil muffins together with deuterium-labelled d6-alpha-Tand d2-gamma-Twere given to volunteers. Urine samples were collected for 72 h and analysed for deuterated and non-deuterated tocopherol metabolites. Consumption of sesame oil muffins significantly reduced the urinary excretion of d2-gamma-CEHC and total (sum of labelled and unlabelled) gamma-CEHC. Overall, the findings from these studies show that the tested dietary phenolic compounds increase vitamin E concentrations through different mechanisms and, thus, have the potential to improve vitamin E status without the use of vitamin E supplements.     

Disruption of P450-mediated vitamin E hydroxylase activities alters vitamin E status in tocopherol supplemented mice and reveals extra-hepatic vitamin E metabolism

The widely conserved preferential accumulation of α-tocopherol (α-TOH) in tissues occurs, in part, from selective postabsorptive catabolism of non-α-TOH forms via the vitamin E-ω-oxidation pathway. We previously showed that global disruption of CYP4F14, the major but not the only mouse TOH-ω-hydroxylase, resulted in hyper-accumulation of γ-TOH in mice fed a soybean oil diet. In the current study, supplementation of Cyp4f14^−/− mice with high levels of δ- and γ-TOH exacerbated tissue enrichment of these forms of vitamin E. However, at high dietary levels of TOH, mechanisms other than ω-hydroxylation dominate in resisting diet-induced accumulation of non-α-TOH. These include TOH metabolism via ω-1/ω-2 oxidation and fecal elimination of unmetabolized TOH. The ω-1 and ω-2 fecal metabolites of γ- and α-TOH were observed in human fecal material. Mice lacking all liver microsomal CYP activity due to disruption of cytochrome P450 reductase revealed the presence of extra-hepatic ω-, ω-1, and ω-2 TOH hydroxylase activities. TOH-ω-hydroxylase activity was exhibited by microsomes from mouse and human small intestine; murine activity was entirely due to CYP4F14. These findings shed new light on the role of TOH-ω-hydroxylase activity and other mechanisms in resisting diet-induced accumulation of tissue TOH and further characterize vitamin E metabolism in mice and humans.     

Quantitation of rat liver vitamin E metabolites by LC-MS during high-dose vitamin E administration

To evaluate vitamin E metabolism, a method was developed to quantitate liver alpha- and gamma-tocopherol metabolites, alpha-carboxyethyl hydroxychroman [alpha-CEHC; 2,5,7,8-tetramethyl-2-(2'-carboxyethyl)-6-hydroxychroman] and gamma-CEHC [2,7,8-trimethyl-2-(2'-carboxyethyl)-6-hydroxychroman], respectively. Vitamin E supraenriched livers were obtained from rats that were injected with vitamin E daily for 18 days. Liver samples (approximately 50 mg) were homogenized, homogenate CEHC-conjugates were hydrolyzed, CEHCs were extracted with ethyl ether, and then CEHCs were quantitated using liquid chromatography-mass spectrometry (LC-MS). Precision, based on intersample variability, ranged from 1% to 3%. Recovery of alpha- and gamma-CEHCs added to liver homogenates ranged from 77% to 87%. Detection limits of alpha- and gamma-CEHC were 20 fmol, with a linear detector response from 0.025 to 20 pmol injected. Corresponding with an increase in liver alpha-tocopherol, the MS peak for liver alpha-CEHC (mass-to-charge ratio 277.8) increased 80-fold (0.18 +/- 0.01 to 15 +/- 2 nmol/g). Liver alpha-CEHC concentrations were correlated with serum alpha-CEHC, liver alpha-tocopherol, and serum alpha-tocopherol (P < 0.001 for each comparison). alpha-CEHC represented 0.5-1% of the liver alpha-tocopherol concentration. Thus, LC-MS can be successfully used to quantitate alpha- and gamma-CEHC in liver samples. These data suggest that in times of excess liver alpha-tocopherol, increased metabolism of alpha-tocopherol to alpha-CEHC occurs.     

Complexity of vitamin E metabolism

Bioavailability of vitamin E is influenced by several factors, most are highlighted in this review. While gender, age and genetic constitution influence vitamin E bioavailability but cannot be modified, life-style and intake of vitamin E can be. Numerous factors must be taken into account however, i.e., when vitamin E is orally administrated, the food matrix may contain competing nutrients. The complex metabolic processes comprise intestinal absorption, vascular transport, hepatic sorting by intracellular binding proteins, such as the significant α-tocopherol-transfer protein, and hepatic metabolism. The coordinated changes involved in the hepatic metabolism of vitamin E provide an effective physiological pathway to protect tissues against the excessive accumulation of, in particular, non-α-tocopherol forms. Metabolism of vitamin E begins with one cycle of CYP4F2/CYP3A4-dependent ω-hydroxylation followed by five cycles of subsequent β-oxidation, and forms the water-soluble end-product carboxyethylhydroxychroman. All known hepatic metabolites can be conjugated and are excreted, depending on the length of their sidechain, either via urine or feces. The physiological handling of vitamin E underlies kinetics which vary between the different vitamin E forms. Here, saturation of the side-chain and also substitution of the chromanol ring system are important. Most of the metabolic reactions and processes that are involved with vitamin E are also shared by other fat soluble vitamins. Influencing interactions with other nutrients such as vitamin K or pharmaceuticals are also covered by this review. All these processes modulate the formation of vitamin E metabolites and their concentrations in tissues and body fluids. Differences in metabolism might be responsible for the discrepancies that have been observed in studies performed in vivo and in vitro using vitamin E as a supplement or nutrient. To evaluate individual vitamin E status, the analytical procedures used for detecting and quantifying vitamin E and its metabolites are crucial. The latest methods in analytics are presented.     

天然维生素E的研究进展

维生素E是一类脂溶性、具抗氧化功能的维生素,按其来源可分为天然维生素E和人工合成维生素E.对天然维生素E的功能、生物合成途径以及相关酶基因的研究方面进行了综述.其中,维生素E合成相关酶基因已经克隆及定位,尤其VTE5的发现,为生育酚合成研究开辟了一条新途径.人们已经开始利用基因工程技术研究提高植物天然维生素E产量的方法.     

Serum vitamin A and vitamin E concentrations after parenteral vitamin A administration in sheep

Twenty primiparous dairy sheep of the Mytilene breed, which were fed with a ration deficient in vitamin A and carotenes, were divided into 2 groups of 10 animals each after a 2-month adaptation period. The animals of group A were administered vitamin A palmitate by intramuscular injection (3500 IU/kg bodyweight), while the animals of group B were used as controls and received only the vehicle of the preparation without vitamin A. Serum vitamin A concentrations increased significantly in the animals of group A compared to the animals of group B (P < 0.01) from the first 24 h post-injection and remained significantly high for 8 days, and at 10 days post-injection they reached the pre-injection levels. The serum vitamin E concentration declined significantly (P < 0.05) in the animals of group A compared to the animals of group B for 8 days, when they reached the pre-injection levels. No changes in serum vitamins A and E levels in the animals of the 2 groups were observed 20 days after the injection of vitamin A.     

Membrane permeability changes with vitamin A/vitamin E mixed bilayers

Vitamin A (all trans-retinol) enhances the permeability of egg phosphatidylcholine liposomes to glucose, urea, and erythritol while vitamin E (α-tocopherol) decreases permeability to the same solutes. Egg phosphatidylcholine bilayers containing both vitamin A and vitamin E are shown to have an altered permeability more similar to that affected by vitamin E alone. The membrane stabilizing effect of vitamin E appears dominant over the membrane destabilizing effect of vitamin A.