Naturally occurring vitamin E, comprised of four forms each of tocopherols and tocotrienols, are synthesized solely by photosynthetic organisms and function primarily as antioxidants. These different forms vary in their biological availability and in their physiological and chemical activities. Tocopherols and tocotrienols play important roles in the oxidative stability of vegetable oils and in the nutritional quality of crop plants for human and livestock diets. The isolation of genes for nearly all the steps in tocopherol and tocotrienol biosynthesis has facilitated efforts to alter metabolic flux through these pathways in plant cells. Herein we review the recent work done in the field, focusing on branch points and metabolic engineering to enhance and alter vitamin E content and composition in oilseed crops.

To elucidate the transepithelial transport characteristics of lipophilic compounds, the cellular uptake of tocopherol and tocotrienol isomers were investigated in Caco2 cell monolayer models. These vitamin E isomers formed mixed micelles consisting of bile salts, lysophospholipids, free fatty acid, and 2-monoacylglycerols, then the micelles were supplied to Caco2 cells. The initial accumulation of tocotrienol isomers in Caco2 cells was larger than those of corresponding tocopherol isomers. There was little difference among the cellular accumulations of four tocopherol isomers. These findings suggested that the difference between the molecular structures of the C16 hydrocarbon chain tail in tocopherol and tocotrienol was strongly responsible for the rapid epithelial transport into the Caco2 cells membranes rather than the difference in the molecular structures of their chromanol head groups. Furthermore, the secretion of alpha-tocopherol and gamma-tocotrienol from Caco2 cells was investigated using Caco2 cells plated on a transwell. The time courses of their secretions from Caco2 cells showed that the initial secretion rate of gamma-tocotrienol was also larger than that of alpha-tocopherol. To investigate the intestinal uptake of alpha-tocopherol and gamma-tocotrienol in vivo, the mice were fed single doses of alpha-tocopherol or gamma-tocotrienol with triolein. The gamma-tocotrienol responded faster in plasma than alpha-tocopherol, although the maximal level of gamma-tocotrienol was lower than that of alpha-tocopherol. This suggested that the intestinal uptake properties of administered alpha-tocopherol and gamma-tocotrienol would characterize their plasma level transitions in mice.

A rapid analytical method including pressurized liquid extraction (PLE) and liquid chromatography-electrospray ionisation-mass spectrometry (LC-ESI-MS) has been developed for the determination of tocopherols and tocotrienols in cereals. The pressurized liquid extraction parameters were optimized in order to maximize the extraction efficiency. The use of methanol as extraction solvent at a temperature of 50 degrees C and a pressure of 110 bar, using one cycle of extraction with a static time of 5 min, provided the best results. A good LC separation was achieved using a C(18) column and a solution of 6.0 mM ammonia in methanol/water (97:3, v/v) as the mobile phase at a flow rate of 0.2 mL min(-1). MS coupling with an ESI interface in the negative ion mode was used as the detection technique. In the present work, it is shown that the addition of a base to the mobile phase is required to enhance the ionization of tocopherols and tocotrienols in negative ion mode electrospray ionization. The applicability of the method to cereal samples was confirmed. The reproducibility of the procedure was good, with relative standard deviations in the 6-10% range. The recoveries of added tocopherols from cereal samples ranged from 91 to 109%.

 

Because of the individual biological effects and the uncertain or missing information on levels of tocopherols (T) and tocotrienols (T3) in foods frequently consumed in Hawaii, 79 food items (50 in duplicate) were analyzed for alpha-, beta-, gamma-, and delta-tocopherol (alphaT, betaT, gammaT, and deltaT) and alpha-, beta-, gamma-, and delta-tocotrienol (alphaT3, betaT3, gammaT3, and deltaT3) in addition to alpha-tocopheryl acetate (alphaTac). Foods from local markets were stored according to usual household habits, freeze-dried, homogenized, and extracted three times with hexane containing butylated hydroxytoluene as a preservative and tocol as an internal standard. A normal-phase high-pressure liquid chromatography system was applied with fluorescence and photodiode array detection that resulted in baseline separation of all eight analytes and the internal standard tocol (To). The sum of all E vitamer concentrations, or total E vitamers (TEV), in all foods analyzed ranged an average from 0.6 to 828 mg/kg (T < or = 542 mg/kg and T3 < or = 432 mg/kg) and showed the following ranges: oils, 497-828 mg/kg (mainly alphaT and gammaT); margarines, 359-457 mg/kg (mainly gammaT); salad dressings, 20-291 mg/kg (mainly gammaT, except alphaT when soy oil was the main ingredient); cookies, 54-138 mg/kg (mainly gammaT); snacks, 101-220 mg/kg (mainly gammaT); nuts, 22-201 mg/kg (mainly alphaT); vegetables, 2-152 mg/kg (mainly alphaT); pasta, 24-90 mg/kg; cereals, 4-56 mg/kg (mainly betaT3 followed by alphaT); fish, 2-39 mg/kg (mainly alphaT); fried tofu, 64 mg/kg (mainly gammaT); breads, 20-22 mg/kg (mainly betaT3); fat-free mayonnaise, 5 mg/kg (mainly alphaT); poi (fermented taro root), 2 mg/kg (mostly alphaT); and fruits, 2 (papaya) to 13 mg/kg (canned pumpkin) with alphaT predominating. Cereals fortified with alphaTac ranked third and eighth among all foods assayed regarding alphaT and TEV levels, respectively. As compared to the few data available in the literature, our values agreed with some (corn flakes, mango fruit, fat-free mayonnaise, dry-roasted macadamia nuts, dry-roasted peanuts, mixed nuts, spaghetti/marinara pasta sauce, oils, and red bell pepper) but differed for many other items. Our results provide new information on the E vitamer content in foods, emphasize the vast differences of bioactivities of individual E vitamers, and confirm the need for analyses of foods consumed in specific study populations.

To examine the distribution of rice bran tocotrienol (T3), we gave rice bran T3 to rats after considering an acceptable daily intake of vitamin E for humans. Male SD rats (5 weeks of age) were fed for 3 weeks on a commercial diet containing 6.4 mg of vitamin E per 100 g wt and additively received vitamin E or the vehicle (vitamin E-free corn oil) by oral intubation. The animals were randomly divided into 4 groups depending on the type of test diet: control (vehicle), non-T3 (no T3 + 4.3 mg of tocopherol (TOC)/kg body weight (b.w.)/day), low-T3 (0.8 mg T3 + 3.5 mg TOC/kg b.w./day), and high-T3 (3.2 mg T3 + 1.1 mg TOC/kg b.w./day). The control rats and rats in the non-T3, low-T3, and high-T3 groups took 4.3 and 8.6 mg of vitamin E/kg b.w./day, respectively. Rice bran gamma-T3 was significantly distributed to the adipose tissue and increased from 1.1 to 10.2 nmol/g of adipose tissue according to the rice bran T3 intake.

Tocochromanols encompass a group of compounds with vitamin E activity essential for human nutrition. They accumulate in photooxidative organisms, e.g. in some algae and in plants, where they localize to thylakoid membranes and plastoglobules of chloroplasts. Tocochromanols contain a polar chromanol head group with a long isoprenoid side chain. Depending on the nature of the isoprenoid chain, tocopherols (containing a phytyl chain) or tocotrienols (geranylgeranyl chain) can be distinguished in plants. The tocochromanol biosynthetic pathway has been studied in Arabidopsis and Synechocystis in recent years, and the respective mutants and genes were isolated. Mutant characterization revealed that tocopherol protects lipids in photosynthetic membranes and in seeds against oxidative stress. In addition to its antioxidant characteristics, tocopherol was shown be involved in non-antioxidant functions such as primary carbohydrate metabolism. A considerable proportion of tocopherol is synthesized from free phytol suggesting that excess amounts of phytol released from chlorophyll breakdown during stress or senescence might be deposited in the form of tocopherol in chloroplasts.

Rice bran is abundant in bioactive compounds including tocotrienol (T3, unsaturated vitamin E). T3 has been reported about its potential functionalities (i.e., antiangiogenic effect), so much attention has been paid on usability of rice bran T3. Hence, we developed a rapid screening method for T3-rich rice bran by one-step equilibrium direct solvent extraction followed by normal phase high-performance liquid chromatography (HPLC). The method gave high-extraction rate of rice bran T3 and tocopherol (above 90%), and the determination of vitamin E by HPLC was completed within 15 min. Using the method, an average of total T3 content in 109 kinds of rice bran samples was 830 mug/g dry wt. Kouchi-Akamai, Joushuu, and Wataribune were found as the T3-rich rice bran varieties (1350-1430 microg T3/g dry wt). According to T3 ratio against total vitamin E (wt %), the average ratio was 61%. Hirayama, Moritawase, and Kaneko were found as the varieties having the highest T3 ratio (80-86%). Since T3 content in Koshihikari rice bran (the leading variety in Japan) was a little above the average, we cross-fertilized Koshihikari with T3-rich varieties and found that T3 content or ratio in F1 was improved compared with Koshihikari. The varieties found rich in T3 could be used for nutraceutical purpose.

More than 80 years after the discovery of the essentiality of vitamin E for mammals, the molecular basis of its action is still an enigma. From the eight different forms of vitamin E, only alpha-tocopherol is retained in the body. This is in part due to the specific selection of RRR-alpha-tocopherol by the alpha-tocopherol transfer protein and in part by its low rate of degradation and elimination compared with the other vitamers. Since the tocopherols have comparable antioxidant properties and some tocotrienols are even more effective in scavenging radicals, the antioxidant capacity cannot be the explanation for its essentiality, at least not the only one. In the last decade, a high number of so-called novel functions of almost all forms of vitamin E have been described, including regulation of cellular signalling and gene expression. alpha-Tocopherol appears to be most involved in gene regulation, whereas gamma-tocopherol appears to be highly effective in preventing cancer-related processes. Tocotrienols appear to be effective in amelioration of neurodegeneration. Most of the novel functions of individual forms of vitamin E have been demonstrated in vitro only and require in vivo confirmation. The distinct bioactivities of the various vitamers are discussed, considering their metabolism and the potential functions of metabolites.

BACKGROUND: The detection of tocotrienols in human plasma has proven elusive, and it is hypothesized that they are rapidly assimilated and redistributed in various mammalian tissues.

OBJECTIVE: The primary study objective was to evaluate the postprandial fate of tocotrienols and alpha-tocopherol in human plasma and lipoproteins.

DESIGN: Seven healthy volunteers (4 males, 3 females) were administered a single dose of vitamin E [1011 mg palm tocotrienol-rich fraction (TRF) or 1074 mg alpha-tocopherol] after a 7-d conditioning period with a tocotrienol-free diet. Blood was sampled at baseline (fasted) and 2, 4, 5, 6, 8, and 24 h after supplementation. Concentrations of tocopherol and tocotrienol isomers in plasma, triacylglycerol-rich particles (TRPs), LDLs, and HDLs were measured at each interval.

RESULTS: After intervention with TRF, plasma tocotrienols peaked at 4 h (4.79 +/- 1.2 microg/mL), whereas alpha-tocopherol peaked at 6 h (13.46 +/- 1.68 microg/mL). Although tocotrienols were similarly detected in TRPs, LDLs, and HDLs, tocotrienol concentrations were significantly lower than alpha-tocopherol concentrations. In comparison, plasma alpha-tocopherol peaked at 8 h (24.3 +/- 5.22 microg/mL) during the alpha-tocopherol treatment and emerged as the major vitamin E isomer detected in plasma and lipoproteins during both the TRF and the alpha-tocopherol treatments.

CONCLUSIONS: Tocotrienols are detected in postprandial plasma, albeit in significantly lower concentrations than is alpha-tocopherol. This finding confirms previous observations that, in the fasted state, tocotrienols are not detected in plasma. Tocotrienol transport in lipoproteins appears to follow complex biochemically mediated pathways within the lipoprotein cascade.

We previously reported that heat pretreatment of corn fiber (150 degrees C, 1 h) caused a tenfold increase in the levels of extractable gamma-tocopherol. The current study was a reinvestigation of the previous effect, using improved methods (HPLC with fluorescence detection, diode-array UV detection, and mass spectrometry) for tocol analysis. Heat pretreatment did not cause an increase in the levels of any of the tocopherols or tocotrienols in corn fiber oil, but lowered the levels of three of the tocols and had no effect on the levels of the other two tocols. Heat pretreatment of corn germ had a similar effect. UV and mass spectra indicated that the peak that we had identified as gamma-tocopherol in our previous report was probably a mixture of oxidation products of triacylglycerols. Thus, heat treatment of corn germ or other corn-oil containing fractions at high temperatures leads to decreases in gamma-tocopherol, gamma-tocotrienol, and delta-tocotrienol and to the production of triacylglycerol oxidation products.