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ORIGINAL RESEARCH COMMUNICATION |
-tocopherol1,2,3
1 From the Food Technology and Nutrition Unit, Malaysian Palm Oil Board, Selangor, Malaysia (SF, RMN, and KS), and the Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia (HMC)
2 Supported by the Malaysian Palm Oil Board (MPOB) Graduate Research Program Scholarship. 3 Reprints not available. Address correspondence to K Sundram, Food Technology & Nutrition Unit, Malaysian Palm Oil Board (MPOB), PO Box 10620, 50720, Kuala Lumpur, Malaysia. E-mail: kalyana{at}mpob.gov.my.
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ABSTRACT |
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 TOP ABSTRACT INTRODUCTIONSUBJECTS AND METHODSRESULTSDISCUSSIONREFERENCES |
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Objective: The primary study objective was to evaluate the postprandial fate of tocotrienols and 
-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 -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 µg/mL), whereas -tocopherol peaked at 6 h (13.46 ± 1.68 µg/mL). Although tocotrienols were similarly detected in TRPs, LDLs, and HDLs, tocotrienol concentrations were significantly lower than -tocopherol concentrations. In comparison, plasma -tocopherol peaked at 8 h (24.3 ± 5.22 µg/mL) during the -tocopherol treatment and emerged as the major vitamin E isomer detected in plasma and lipoproteins during both the TRF and the -tocopherol treatments.
Conclusions: Tocotrienols are detected in postprandial plasma, albeit in significantly lower concentrations than is -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.
Key Words: Tocotrienols • tocopherols • vitamin E • postprandial plasma
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INTRODUCTION |
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TOPABSTRACTINTRODUCTIONSUBJECTS AND METHODSRESULTSDISCUSSIONREFERENCES |
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-tocopherol are well established, whereas those of the tocotrienols are less well documented. Tocotrienols are present in high concentrations in palm and rice bran oils (7).
Studies have shown that tocotrienols are more efficient in preventing and reducing lipid peroxidation (8-11) because of their suggested higher intramembrane mobility and higher collision rates with free radicals (12). Oxidative damage to rat brain mitochondria (11), liver mitochondria, and cytochrome P-450 (8) was significantly reduced by tocotrienols compared with -tocopherol. Comparisons of the antioxidant effectiveness of tocopherols and tocotrienols in several model systems, however, showed that both have their own advantages in scavenging free radicals (13). Among the suggested antioxidant mechanisms attributed to tocotrienols are greater and uniform distribution in membrane lipid bilayers, interaction of the chromanol ring with lipid radicals, and recycling efficiency from chromanoxyl radicals (8, 9, 12). The hypocholesterolemic effect of tocotrienols was postulated through an ability to suppress 3-hydroxy-3-methylglutaryl coenzyme A reductase activity (14, 15). The therapeutic properties of tocotrienols have been reviewed previously (7, 12, 16, 17).
The absorption of tocotrienols in humans, however, remains unclear. Despite several studies in humans (18-25), the detection of tocotrienols in plasma has proven elusive. Tocotrienols were either not detected or, when detected, were found in very small concentrations compared with -tocopherol. As a result of their rapid disappearance, their effectiveness as a biological antioxidant has been queried. Tocotrienols are also prescribed a low score for their biological activity compared with tocopherols (26). Furthermore, current recommended dietary allowances for vitamin E define human requirements mostly in terms of -tocopherol.
Thus, much controversy remains about the metabolic fate and physiologic effects of tocotrienols (27), which had no favorable effects on serum lipoproteins (19, 20) and platelet function (19) in men with elevated lipid concentrations. Supplementation with synthetic tocotrienyl acetate also had no effect on plasma cholesterol (22). However, Tomeo et al (10) found that palm tocotrienols significantly reduce serum thiobarbituric acid–reactive substances of patients with carotid artery stenosis.
To address these gaps in our knowledge, we conducted a postprandial study to investigate the metabolic fate of palm tocotrienols in circulating plasma in humans. This study (in which a high dose of palm tocotrienols was administered) was designed to trace the disappearance of tocotrienols over the dynamic postprandial period when fat digestion is most active in humans. This was additionally postulated to provide definitive information on the fate of ingested palm tocotrienols compared with -tocopherol.
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SUBJECTS AND METHODS |
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TOPABSTRACTINTRODUCTIONSUBJECTS AND METHODSRESULTSDISCUSSIONREFERENCES |
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All volunteers were normolipemic, nonsmokers, and did not show any clinical symptoms associated with lipid-related cardiovascular disease. Through the administration of a questionnaire and dietary interview, we established that none of the volunteers consumed any vitamin or herbal supplements nor were they taking any prescribed medication. Female volunteers were not pregnant, lactating, or taking contraceptives at the time of enrolment. The study was completed with the following baseline characteristics of the 7 volunteers: (
± SD): age, 25.9 ± 5.01 y; body mass index (in kg/m2), 20.38 ± 1.79; plasma total cholesterol, 5.05 ± 0.52 mmol/L; plasma triacylglycerol, 0.9 ± 0.32 mmol/L; and plasma HDL cholesterol, 1.67 ± 0.47 mmol/L.
Study design
The study was designed to evaluate and elucidate the absorption and metabolic fate of a high dose of palm tocotrienols administered to humans in a postprandial model system. A previously optimized human postprandial study design used in our laboratory was adopted (28). Volunteers were conditioned on a standardized fat-controlled diet (comprising breakfast, lunch, and afternoon high tea) during a run-in period lasting 7 d for each rotation of the postprandial trial. Two rotations during which a palm tocotrienol-rich fraction (TRF) and -tocopherol supplements were administered were carried out, and a wash-out period of 1 wk was allowed between each rotation. All meals were prepared by a trained caterer with corn oil as the dietary fat source, and the same menu was repeated for each rotation. Daily food samples were also analyzed for composition of typical dietary macronutrients, namely, fat, protein, carbohydrate, energy (not reported here), and vitamin E.
Postprandial event
After fasting overnight for 
10 h, the volunteers reported to the laboratory the next morning. Body weight was recorded, and 12 mL of blood was drawn from each volunteer for a fasting, baseline sample.
The volunteers then consumed the standardized test breakfast, which included a weighed portion of fried rice, fried potatoes, a slice of papaya, and tea. This test breakfast contributed a total of 30.5 g dietary fat, which was contributed entirely by corn oil. The volunteers were then immediately instructed to consume the vitamin E supplements: 5 capsules of TRF, which provided 1011 mg vitamin E (-tocopherol, 319 mg; -tocotrienol, 296 mg; ß-tocotrienol, 30 mg; 
-tocotrienol, 284 mg; 
-tocotrienol, 83 mg), or 4 capsules of tocopherols, which provided 1074 mg vitamin E solely as -tocopherol. This entire exercise was completed within 20 min of the first (baseline, 0 h) blood sampling.
Blood samples were then taken sequentially 2, 4, 5, 6, and 8 h after the meal and vitamin E supplement were consumed. Volunteers abstained from consuming any food during this 8-h period but were allowed free access to bottled mineral water. They also refrained from any strenuous activity within these intervals. At the end of the 8-h blood sampling, the volunteers were provided a full cooked meal in which the fat component was contributed solely by corn oil. Late in the evening, they also consumed supper in their homes. On the next day after the subjects had again fasted overnight, a fasting blood sample was drawn from each volunteer to coincide with a 24-h time point.
Blood sampling and biochemical determinations
Blood was collected into blood collection tubes (BD Vacutainer, Franklin Lakes, NJ) containing EDTA as the anticoagulant for lipid and lipoprotein analyses. Blood samples were centrifuged at 3000 x g for 20 min in a refrigerated centrifuge. Plasma was divided into 12 different vials for the measurement of various parameters of interest. All plasma samples (except those intended for lipoprotein separation) were snap-frozen in liquid nitrogen and subsequently stored at –80 °C until analyzed.
Lipoprotein isolation
Lipoproteins were isolated from fresh plasma by sequential ultracentrifugation (29) with a 50.3 Ti rotor (Beckman Instruments Inc, Palo Alto, CA) according to previously established protocols in our laboratory (30). Briefly, 3.0 mL fresh plasma was loaded into an ultracentrifuge tube (Beckman polyallomer bell-top, quick-seal tube, sized 13 x 64 mm, capacity: 6.0 mL) by successive layering with specific density solutions and was centrifuged at 197 042 x g for 21 h. The top fraction (
< 1.006 g/mL), containing triacylglycerol-rich particles (TRPs) was transferred to a tube and adjusted to a total volume of 2 mL. The bottom fraction ( > 1.006 g/mL) was transferred to another tube and adjusted to a total volume of 3 mL with the sample's void solution. This fraction was again loaded into a fresh ultracentrifuge tube, and the same procedures were repeated for isolation of LDLs ( = 1.019) and HDLs ( = 1.063) in predetermined volumes of 2.0 mL.
Lipid variables: plasma total cholesterol and triacylglycerol
Plasma lipids were analyzed by enzymatic procedures by using a Ciba-Corning 550 Express Autoanalyzer (Ciba Corning Diagnostics Corp, Oberlin, OH) with reagents, calibrators, and controls supplied by the manufacturer.
Vitamin E analysis in plasma and lipoprotein fractions
Plasma and lipoprotein fractions were extracted for vitamin E analyses according to the method of Sundram and Nor (31) and were analyzed by HPLC (Agilent 1100 Series from Agilent Technologies Inc, Waldbrohn, Germany). Two normal-phase 5-µm silica columns (4.6 x 250 mm; Agilent Zorbax Rx-SIL, Agilent Technologies Inc, Palo Alto, CA) were fitted in series to enhance the separation of all tocol isomers. The mobile phase consisted of hexane-isopropanol (flow rate of 2 mL/min, pressure of 133 barr) and a run time of 25 min. Contents of the tocopherol and tocotrienol isomers in total plasma and the various lipoprotein fractions were identified by using a fluorescence detector (Agilent 1100 Series, Agilent Technologies) with excitation at 295 nm and emission at 330 nm and were quantified by using authentic tocopherol and tocotrienol standards. Results from both supplementation sessions (TRF and -tocopherol) were compared for their differences in content and distribution of vitamin E in plasma and lipoproteins.
Statistical analysis
Statistical analyses were performed by using SPSS for WINDOWS (version 11.0; SPSS Inc, Chicago, IL). After treatment, each postprandial response variable was analyzed for trend by using repeated-measures analysis of variance (ANOVA). Wilcoxon's signed-ranks test was performed to detect any significant difference between variables of interest. After each postprandial interval, outcomes were compared with the corresponding baseline value (0 h) to detect any significant effect of the vitamin E treatments. Changes were calculated as the difference between values at each postprandial interval (2 to 24 h) and baseline (0 h). Postprandial effects between treatments on plasma profiles were analyzed for their time x treatment interaction by using two-factor repeated-measures ANOVA, whereas postprandial effects on lipoprotein profiles were analyzed their time x treatment x group (lipoproteins) interactions by using three-factor repeated-measures multiple analysis of variance (MANOVA) with an interaction term. Area under the curve (AUC), which was defined as the total postprandial vitamin E response for the 24-h period, was also determined with the area normalized to the baseline concentration. Values were considered significant at P < 0.05.
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RESULTS |
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-tocopherol, 114; -tocopherol, 274; and -tocopherol, 17. The fat content of the standardized fat-controlled diet throughout the 7-d run-in period was 48.0 ± 12.2 g/d and contained 14.9 ± 8.2 mg/d of total vitamin E (4.7 ± 2.7 mg -tocopherol/d, 9.6 ± 5.2 mg -tocopherol/d, and 0.6 ± 0.3 mg -tocopherol/d). The test breakfast contained 30.5 ± 8.2 g fat and 10.7 ± 1.7 mg vitamin E (3.2 ± 0.5 mg -tocopherol, 7.1 ± 1.2 mg -tocopherol, and 0.5 ± 0.07 mg -tocopherol). No tocotrienols were detected in these test diets.
Postprandial lipid responses
Plasma lipids were assessed throughout the postprandial period (Table 1
). Plasma total cholesterol concentrations throughout the postprandial period were significantly lower after the TRF treatment than after the -tocopherol treatment (measured as the AUC). In addition, a significant time x treatment effect was apparent for total cholesterol only. For both treatments, triacylglycerols peaked at 4 h and thereafter declined rapidly and reflected baseline values at 8 h.
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-tocopherol or TRF treatments (Table 2), a significant time x treatment interaction was evident. Plasma vitamin E at baseline for the -tocopherol supplementation was 11.9 ± 0.8 µg/mL. After supplementation with -tocopherol, at 2 h, plasma vitamin E was not significantly different from at baseline. Thereafter, vitamin E concentrations steadily increased and peaked at 8 h. Plasma -tocopherol content at 24 h (18.2 ± 2.5 µg/mL) was higher than that at baseline but was lower than the 8-h maximum (24.3 ± 5.2 µg/mL).
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). Starting from 2 h, plasma vitamin E content was higher than the baseline value throughout the postprandial intervention. Plasma vitamin E peaked at 4 h (17.8 ± 2.7 µg/mL) after TRF supplementation.
Plasma vitamin E composition during the entire 24-h interval was reflected only as -tocopherol by HPLC analysis. No other vitamin E isomers were detected. Supplementation with TRF, however, induced changes in plasma vitamin E composition (Table 3). -Tocopherol remained the predominant plasma vitamin E isomer even when volunteers were supplemented with the tocotrienol-rich TRF. Tocotrienols were not detected in fasting plasma samples at baseline or 24 h after supplementation with TRF. Starting from 2 h, the different tocotrienol isomers along with -tocopherol were detected. -Tocotrienol was the major tocotrienol isomer detected, reflecting the TRF source. All tocotrienols peaked at 4 h and thereafter declined steadily (Table 3). The peak maximums for the tocotrienols (µg/mL) were as follows: total tocotrienols, 4.8 ± 1.2; -tocotrienol, 2.8 ± 0.7; -tocotrienol, 1.6 ± 0.5; -tocotrienol, 0.4 ± 0.1.
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and Table 5). After TRF treatment, all tocotrienol isomers (-, -, -) except ß-tocotrienol were detected in TRP, LDL, and HDL, albeit in significantly lower concentrations than -tocopherol.
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), variations in the distribution of the vitamin E isomers were apparent. In TRP, between 17 ± 3.3% and 34 ± 5.6% and between 15.2 ± 2.8% and 41.3 ± 3.1% of total circulating plasma vitamin E was detected during the TRF and -tocopherol treatments, respectively (Table 4). The 2 treatments, however, did not result in significant differences in TRP vitamin E content at 2, 4, 5, 8, or 24 h. After TRF treatment, only 3.7 ± 1.4% to 8.6 ± 1.5% was detected as tocotrienols ( + + -tocotrienol) throughout the postprandial intervals, and the remaining 15.6 ± 3.4% to 25.5 ± 4.8% was detected as tocopherols, mainly as -tocopherol (Table 5).
TRP tocotrienol content peaked at 4 h and accounted for 8.6 ± 1.5% of total circulating plasma vitamin E concentrations, with -tocotrienol as the major isomer followed by -tocotrienol and -tocotrienol (Table 5). The concentration of TRP tocotrienols was, however, significantly lower than the TRP tocopherol ( + ) content at all time intervals measured.
Distribution of vitamin E in LDL
In LDL, between 28.7 ± 2.2% and 38.6 ± 1.3% and between 29 ± 2.9% and 44.7 ± 1.4% of total circulating plasma vitamin E was detected after the TRF and -tocopherol treatments, respectively (Table 4). The AUC for LDL vitamin E differed significantly (P = 0.043) between treatments, with higher contents after the -tocopherol treatment than after TRF treatment (Table 4).
During -tocopherol treatment, LDL vitamin E was detected only as -tocopherol. During TRF treatment, between 25.7 ± 1.5% and 37.9 ± 2.5% of total circulating vitamin E in LDL was -tocopherol and between 0.7 ± 0.3% and 4.3 ± 1.0% was the tocotrienols (Table 5). No LDL tocotrienols were detected at 0 or 24 h (fasted samples). Unlike TRP, the major tocotrienol in LDL was -tocotrienol at all postprandial intervals, except at 8 h, when -tocotrienol appeared as the major tocotrienol isomer (Table 5).
Distribution of vitamin E in HDL
In HDL, between 36.5 ± 5.8% and 44.8 ± 4.7% and between 29.8 ± 2.2% and 43.3 ± 2.0% of total circulating plasma vitamin E was detected after the TRF and -tocopherol treatments, respectively (Table 4). The AUC for HDL vitamin E differed significantly (P = 0.043) between treatments, with higher contents after the TRF treatment than after the -tocopherol treatment. In HDL, -tocopherol was the predominant isomer detected after both treatments. As shown in Table 5, tocotrienol isomers were detected throughout the whole postprandial interval with the TRF treatment, except at 0 and 24 h (fasting samples). A trend similar to that for TRP was evident in HDL wherein -tocotrienol was the major tocotrienol isomer detected. HDL tocotrienols peaked at 4 h and accounted for 11.7 ± 2.4% of total circulating plasma vitamin E concentrations. The percentage content of tocotrienols was nevertheless significantly lower than that of the tocopherols.
LDL and HDL were the major carriers of tocopherol at 0 and 24 h during -tocopherol treatment. However, after postprandial intervals beginning at 2 h, the concentration of tocopherol in TRP gradually increased, peaked at 4 h, and thereafter steadily declined. In contrast with tocopherol, tocotrienols were mostly transported in TRP and HDL from 2 to 6 h postprandially during TRF treatment, wherein both TRP and HDL tocotrienols peaked at 4 h. HDL was also the major carrier of tocotrienols from 4 to 8 h before tocotrienols were completely cleared from plasma at 24 h.
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DISCUSSION |
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TOPABSTRACTINTRODUCTIONSUBJECTS AND METHODSRESULTSDISCUSSIONREFERENCES |
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-Tocopherol is the major vitamin E isomer in human plasma. The 2000 Institute of Medicine's Recommended Dietary Allowances stipulate vitamin E activity primarily as -tocopherol equivalents (26). Other tocopherol and tocotrienol isomers are assigned lower vitamin E activity. In the current study, -tocopherol was the major vitamin E isomer in plasma and lipoproteins, even when volunteers were challenged with a preparation whose composition was high (70%) in tocotrienols. These findings also reflect previous studies that examined the effect of tocotrienol supplementation in humans (18-24).
The capacity to increase -tocopherol concentrations in plasma is limited (32) because -tocopherol is readily replaced by newly absorbed -tocopherol (33, 34). This may be the rate-limiting step that determines overall incorporation. In this study, 2 vitamin E preparations were supplemented; -tocopherol resulted in increased plasma vitamin E capacity relative to TRF. The detection of tocotrienols in plasma has been elusive. Several human studies found that tocotrienols were either not detected in fasting plasma or when detected occurred in very small concentrations (14, 19-24). Despite long-term supplementation, detection of plasma tocotrienols was not significantly improved, and this may be related to their absorption and transportation. Many of the factors necessary for the absorption of dietary lipids are also required for vitamin E (35). Yap et al (24) showed that absorption of tocotrienols increased significantly when administered with a meal.
In contrast with the findings discussed above, with use of the current approach, tocotrienol isomers (, , and ) from TRF were detected throughout the postprandial interval. Hayes et al (23) detected , , and -tocotrienols in fasted plasma after supplementation with 80 mg tocotrienols and 64 mg tocopherols per day for 10 d. Before this supplementation, -tocotrienol was detected in fasted plasma but it is unclear why only this isomer was thus detected. After supplementation with TRF in our study, -, -, and -tocotrienols were detected after 2 h postprandially. Unlike the findings of Hayes et al (23) but in agreement with previous observations (22, 24), tocotrienols were not detected during the 2 fasting states (baseline and 24 h). The Hayes et al (23) observation may in part be due to the shorter fasting duration (6 h) of their subjects. Had there been an appreciable amount of -tocotrienols in the background diet, the 6-h fast may have been inefficient in clearing circulating tocotrienols, a fact borne out in the current study because tocotrienols were detected up to 8 h postprandially.
Generally, the distribution of vitamin E in fasting plasma depends on the concentration of each lipoprotein fraction (36). Vitamin E, which occurs almost entirely as -tocopherol, is carried mostly in LDL and HDL (23) with its concentration equally distributed among these lipoproteins (36). Our data agree with these observations; at baseline and 24 h after TRF or -tocopherol treatment, LDL and HDL emerged as the major carriers of plasma vitamin E. TRP was also a major carrier of vitamin E in the postprandial states. In addition, apart from -tocopherol, the tocotrienols were detected in appreciable quantities in TRP after TRF supplementation. These results agree with a previous study (9) that reported the presence of tocotrienols in lipoproteins after oral supplementation with tocotrienol capsules.
In our study, -tocotrienol was the major tocotrienol isomer detected in plasma and lipoprotein fractions. Yap et al (24) showed that plasma concentrations of -tocotrienol and -tocotrienol were similar when their subjects were provided supplements that contained 
2-fold the content of -tocotrienol as -tocotrienol. In rat studies (37, 38), absorption of -tocotrienol was preferentially higher than absorption of - and -tocotrienols (37). This has been suggested to result from the differences in the number of methyl groups in the chromanol rings of the tocotrienol molecules, which affect the lipophilicity of the molecule and transportation to the lymphatic system via biological membranes (38). Overall, these data indicate possible biodiscrimination in the absorption of the different tocotrienols.
In contrast with tocopherols, tocotrienols first appeared in lipoproteins at 2 h (or possibly earlier) and disappeared within 24 h of TRF supplementation. No tocotrienols were detected before supplementation or after 24 h. The rapid disappearance of these tocotrienols in lipoproteins indicates that they have a very short duration of absorption and distribution in plasma. Choudhury et al (25) postulated that the low plasma concentration of tocotrienols was due to the interconversion of tocotrienols to tocopherols by bio-hydrogenation. We discount this hypothesis, however, because tocotrienols and tocopherols are structurally differentiated by the presence of an unsaturated phytyl side chain and are not interconvertible in humans (26). Our findings are supported by Yap et al (24), who reported that tocotrienol content declined after 5 h and disappeared at 24 h after supplementation. This could be due to the low affinity of tocotrienols for hepatic -tocopherol transfer protein (-TTP), a mechanism that determines the level of vitamin E in plasma (36, 39, 40). Hosomi et al (39) suggested that the affinity of -TTP toward tocotrienols is significantly less than toward tocopherols. The relative affinity of -tocotrienol for -TTP was ascribed at 12% compared with -tocopherol, which was 100%. Unfortunately, affinities for other tocotrienol isomers ( and ) were not tested. Competition with -tocopherol has been suggested as a factor in reducing the ability of tocotrienols to be recognized by hepatic -TTP (22).
Traber and Kayden (41) postulated that all forms of vitamin E that are not preferentially utilized are excreted in bile and are not recirculated in plasma. During excessive intake of vitamin E, 2 major routes of excretion (tocotrienol may also be considered in such cases) have been suggested: fecal elimination (41) and urinary excretion as the -carboxy-ethyl-hydroxy-chroman (-CEHC) metabolites (42). Schultz et al (42) suggested that increasing doses of vitamin E result in increased urinary excretion of -CEHC. Lodge et al (43) suggested that - and -tocotrienols are metabolized to - and -CEHC, derivatives which are then excreted in urine. Because our volunteers were supplemented with high doses of tocotrienols, this postulation is intriguing, although we did not measure the resulting urinary -CEHC derivatives.
Despite their low affinity for -TTP, tocotrienols may be transferred or incorporated into plasma through lipoprotein exchanges. During chylomicron catabolism, vitamin E molecules can be transferred from chylomicron remnants to circulating HDL. HDL can then transfer the vitamin E molecules to other circulating lipoproteins, such as LDL and VLDL (44, 45). This vitamin E transfer proceeds before the hepatic uptake of chylomicron remnants, during which -TTP preferentially transfers only RRR--tocopherol to VLDL from the liver. These reactions continue with the exchanges of -tocopherol with other circulating lipoproteins, such as LDL and HDL (44). High concentrations of -tocopherol in plasma thus result. This was indirectly apparent, because starting from 2 to 6 h, TRP (containing chylomicron and VLDL) and HDL had a higher concentration of tocotrienols than did LDL. During TRF treatment, most of the tocotrienols were transported by TRP and HDL. Starting from 4 h through to 8 h, tocotrienol content was highest in HDL, intermediate in TRP, and lowest in LDL. In agreement with our findings, it is not impossible that all the tocotrienols are transported in circulating plasma as described by these mechanisms. This explanation helps to clarify why tocotrienols can still be detected in circulating plasma and all lipoproteins, even though their concentrations were low compared with the tocopherols.
The role of -TTP could also explain why -tocopherol was the only isomer detected throughout the postprandial interval during -tocopherol treatment. The affinity of -TTP is low not only for tocotrienols but also for other tocopherol isomers; the relative affinity of -TTP for -tocopherol and -tocopherol has been reported to be 9% and 2%, respectively (39). In our study, volunteers were supplemented with high doses (1074 mg) of -tocopherol. At such high concentrations of -tocopherol and a lack of sufficient dietary - and -tocopherols, there was obviously no competition for -TTP from other vitamin E isomers.
In summary, our findings show that concentrations of plasma and lipoprotein (TRP, LDL, and HDL) tocotrienols were significantly lower than concentrations of tocopherols (mainly -tocopherol), even though volunteers consumed a vitamin E supplement that contained 70% of its composition as tocotrienols. Low absorption and incorporation of tocotrienols into the human circulating system could have implications for the antioxidant capacity of plasma, because tocotrienols were previously reported to have higher antioxidant capacity than tocopherols (8, 9). This is proposed for further examination by using stored plasma from the current study.
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ACKNOWLEDGMENTS |
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The contribution of each author was as follows: SF undertook the overall management of the study and most of the laboratory and statistical analysis and drafting of the manuscript. The work was part of his PhD program. RMN developed the methods for vitamin E HPLC analysis and other related analytic procedures. HMC contributed to the design and subsequent finalization of the manuscript. KS was the overall researcher in charge of the study, having designed the study protocols, primed the laboratory and statistical techniques, and contributed intellectually to the final manuscript. None of the authors had a conflict of interest to declare.
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REFERENCES |
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-tocopherol and -tocotrienol. Free Radic Biol Med 1991;10:263–75.[Medline]-tocotrienol antioxidant action and cell signalling. J Nutr 2001;131:369S–73S.-, -, or -tocotrienyl acetate supplementation of hypercholesterolemic humans. Free Radic Biol Med 2000;29:834–45.[Medline]-, - and -tocotrienols under different food status. J Pharm Pharmacol 2001;53:67–71.[Medline]- and -tocopherol in human subjects fed a fat-rich meal supplemented with fat-soluble vitamins. J Nutr 1989;119:1252–8.-, - and -tocotrienols in rats. J Pharm Pharmacol 2003;55:53–8.[Medline]-tocopherol transfer protein as a determinant of the biological activities of vitamin E analogues. FEBS Lett 1997;409:105–208.[Medline]-tocopherol decreases -tocotrienol but not -tocotrienol concentration in rats. J Nutr 2003;133:428–34.- and -tocotrienols are metabolized to carboxyethyl-hydroxychroman derivatives and excreted in human urine. Lipids 2001;36:43–8.[Medline]This article has been cited by other articles:
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  A. Shibata, K. Nakagawa, P. Sookwong, T. Tsuduki, S. Tomita, H. Shirakawa, M. Komai, and T. Miyazawa Tocotrienol Inhibits Secretion of Angiogenic Factors from Human Colorectal Adenocarcinoma Cells by Suppressing Hypoxia-Inducible Factor-1{alpha} J. Nutr., November 1, 2008; 138(11): 2136 - 2142. [Abstract] [Full Text] [PDF]
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