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Protective effects of vitamin E forms (alpha-tocopherol, gamma-tocopherol and d-alpha-tocopherol polyethylene glycol 1000 succinate) on retinal edema during ischemia-reperfusion injury in the guinea pig retina.

PURPOSE: The purpose of this study is to provide evidence that free radical damage is a component of retinal ischemia-reperfusion (I/R) injury, and to determine whether alpha-tocopherol, gamma-tocopherol and d-alpha-tocopherol polyethylene glycol 1000 succinate (TPGS) can protect the retina from this injury. METHODS: The right eyes of 40 male guinea pigs weighing 500-600 g were used. The animals were randomly assigned to group 1 (control), group 2 (I/R), group 3 (I/R plus alpha-tocopherol), group 4 (I/R plus gamma-tocopherol) and group 5 (I/R plus TPGS). Groups 3, 4 and 5 received four subcutaneous injections at six-hour intervals for total dosage of 800 IU/kg alpha-tocopherol, 1000 IU/kg gamma-tocopherol and 750 IU/kg TPGS, respectively. The first dose of each substance was administered 5 minutes before retinal ischemia. Retinal ischemia was induced for 90 minutes, then followed by reperfusion for 24 hours. Injections of three substances were repeated at 6, 12 and 18 hours during reperfusion. The animals were killed at 24 hours of reperfusion. Sagittal sections of 4 microm were cut and stained with hematoxylin and eosin for light microscopic evaluation. The average thickness (edema) of the inner plexiform layer for each eye was measured in sagittal sections near the optic nerve and expressed in microns. RESULTS: All the three substances showed statistically significant protection against the formation of retinal edema during ischemia-reperfusion injury. The mean thickness of the inner plexiform layer were 15.0, 25.44, 19.81, 21.38 and 20.88 microm in control, I/R, I/R plus alpha-tocopherol, I/R plus gamma-tocopherol and I/R plus TPGS groups, respectively. The results showed that the thickness of the inner plexiform layer in group 1 (control) was significantly lower than the other groups (p<0.001). The inner plexiform layer was thicker in the I/R group than with I/R plus alpha-tocopherol (p<0.001), I/R plus gamma-tocopherol (p<0.001) and I/R plus TPGS (p<0.01). The inner plexiform layer was not thicker in the I/R plus TPGS group than in the I/R plus alpha-tocopherol and I/R plus gamma-tocopherol groups. Compared to the I/R plus alpha-tocopherol group, the inner plexiform layer was significantly thicker in the I/R plus gamma-tocopherol group (p<0.01). CONCLUSIONS: The results from these experiments indicate that vitamin E forms have protective effects on the retina during retinal ischemia-reperfusion injury, but, the effects of alpha-tocopherol and TPGS appear to be much greater than that of gamma-tocopherol.

Animals↗

Alpha-tocopherol modulates Cyp3a expression, increases gamma-CEHC production, and limits tissue gamma-tocopherol accumulation in mice fed high gamma-tocopherol diets.

Although all forms of vitamin E are absorbed, the liver preferentially secretes alpha-, but not gamma-tocopherol, into plasma. Liver alpha-tocopherol secretion is under the control of the alpha-tocopherol transfer protein (TTP). Therefore, to assess gamma-tocopherol bioactivities Ttpa-/-, +/- and +/+ mice were fed for 5 weeks diets containing gamma-tocopherol 550 (gamma-T550), gamma-tocopherol 60 (gamma-T60) mg/kg that also contained trace amounts of alpha-tocopherol, a vitamin E-deficient diet, or a control diet. Plasma and tissues from mice fed gamma-T550 diets were found to contain similar gamma- and alpha-tocopherol concentrations despite the high dietary gamma-tocopherol content; nervous tissues contained almost no gamma-tocopherol. Liver vitamin E metabolites (carboxyethyl hydroxychromans, CEHCs) were also measured. In mice with widely ranging liver alpha- (from 0.7 to 16 nmol/g) and gamma-tocopherol concentrations (0 to 13 nmol/g), hepatic alpha-CEHC was undetectable, but gamma-CEHC concentrations (0.1 to 0.8 nmol/g) were correlated with both alpha- and gamma-tocopherol concentrations (P < 0.004). Hepatic cytochrome P450s (CYPs) involved in vitamin E metabolism, Cyp4f and Cyp3a, were also measured. There were no variations in Cyp4f protein expression as related to diet or mouse genotype. However, Cyp3a was correlated (P < 0.0001) with liver alpha-, but not gamma-tocopherol concentrations. These data support the hypothesis that alpha-tocopherol modulates xenobiotic metabolism by increasing Cyp3a expression, gamma-CEHC formation, and the excretion of both gamma-tocopherol and gamma-CEHC.

Animal Feed↗

Bioavailability of alpha-tocopherol fed with retinol and relative bioavailability of D-alpha-tocopherol or DL-alpha-tocopherol acetate.

Two experiments were conducted to examine the effects of the form of alpha-tocopherol or interactions of alpha-tocopherol with vitamin A on its bioavailability. In Experiment 1, Holstein steers were fed a diet that was low in vitamins A and E for 1 mo; then, steers were blocked by body weight (X = 97.5 kg) and assigned randomly to one of four oral treatments: 1) no added vitamins, 2) 442 mg of retinyl acetate, 3) 1342 mg of D-alpha-tocopherol, or 4) 442 mg of retinyl acetate and 1342 mg of D-alpha-tocopherol. Each treatment was given as a pulse dose. Blood was sampled over a 36-h period. Concentrations of plasma retinyl palmitate peaked at 2 to 6 h postsupplementation for all calves and then peaked again at 22 to 28 h for calves receiving vitamin supplements. Concentrations of plasma alpha-tocopherol peaked earliest with D-alpha-tocopherol supplementation alone at 12 to 20 h after supplementation, but simultaneous supplementation with retinyl acetate resulted in lower plasma alpha-tocopherol concentrations. Plasma retinyl palmitate decreased during peak alpha-tocopherol concentrations. In Experiment 2, blood and tissue were analyzed after a single gastric tube administration of a powder (DL-alpha-tocopheryl acetate) or a liquid (D-alpha-tocopherol) form of vitamin E to Holstein calves. Plasma and kidney concentrations of alpha-tocopherol were higher when calves were fed D-alpha-tocopherol than when calves were fed the DL-alpha-tocopherol acetate form. Concentrations in the liver, spleen, adipose tissue, heart, muscle, cellular blood fraction, and gut did not differ between the two forms.

Animals↗

Selective accumulation of alpha-tocopherol in Drosophila is associated with cytochrome P450 tocopherol-omega-hydroxylase activity but not alpha-tocopherol transfer protein.

Humans and other mammals actively discriminate among the various forms of vitamin E to selectively retain alpha-tocopherol, but the phylogenetic breadth of this trait is unknown. We sought to determine if the fruit fly, Drosophila melanogaster, similarly discriminates and if so by what mechanism. Larvae and adult flies fed diets containing predominantly gamma- and delta-tocopherols were enriched in alpha-tocopherol. Inclusion in the diet of piperonyl butoxide (PBO), an insect cytochrome P450 inhibitor and inhibitor of tocopherol-omega-hydroxylase activity, greatly elevated tissue levels of delta-tocopherol but not alpha-tocopherol. Drosophila microsomes exhibited tocopherol-omega-hydroxylase activity in the order of delta-T > gamma-T >> alpha-T, a pattern consistent with the effect of PBO in vivo. To determine if selectivity involved alpha-tocopherol transfer protein (alpha-TTP), adult flies were fed an equimolar mixture of d3-RRR- and d6-all-racemic alpha-tocopherol. Flies exhibited a d3/d6 ratio of 1.03, demonstrating an inability to discriminate on the basis of phytyl tail stereochemistry, a hallmark of alpha-TTP activity. We conclude that Drosophila preferentially accumulates alpha-tocopherol via a mechanism involving cytochrome P450 tocopherol-omega-hydroxylase-mediated catabolism of other tocopherols, but not a mammalian-like alpha-TTP. The selective pressure favoring this trait and its remarkable conservation from insects to humans requires elucidation.

Animals↗

Alterations in tocopherol cyclase activity in transgenic and mutant plants of Arabidopsis affect tocopherol content, tocopherol composition, and oxidative stress.

Tocopherol belongs to the Vitamin E class of lipid soluble antioxidants that are essential for human nutrition. In plants, tocopherol is synthesized in plastids where it protects membranes from oxidative degradation by reactive oxygen species. Tocopherol cyclase (VTE1) catalyzes the penultimate step of tocopherol synthesis, and an Arabidopsis (Arabidopsis thaliana) mutant deficient in VTE1 (vte1) is totally devoid of tocopherol. Overexpression of VTE1 resulted in an increase in total tocopherol of at least 7-fold in leaves, and a dramatic shift from alpha-tocopherol to gamma-tocopherol. Expression studies demonstrated that indeed VTE1 is a major limiting factor of tocopherol synthesis in leaves. Tocopherol deficiency in vte1 resulted in the increase in ascorbate and glutathione, whereas accumulation of tocopherol in VTE1 overexpressing plants led to a decrease in ascorbate and glutathione. Deficiency in one antioxidant in vte1, vtc1 (ascorbate deficient), or cad2 (glutathione deficient) led to increased oxidative stress and to the concomitant increase in alternative antioxidants. Double mutants of vte1 were generated with vtc1 and cad2. Whereas growth, chlorophyll content, and photosynthetic quantum yield were very similar to wild type in vte1, vtc1, cad2, or vte1vtc1, they were reduced in vte1cad2, indicating that the simultaneous loss of tocopherol and glutathione results in moderate oxidative stress that affects the stability and the efficiency of the photosynthetic apparatus.

Arabidopsis↗

Human adipose alpha-tocopherol and gamma-tocopherol kinetics during and after 1 y of alpha-tocopherol supplementation.

Alpha-tocopherol and gamma-tocopherol were monitored in human adipose by using needle biopsies in four subjects during a 1-y supplementation trial with 800 mg all-rac-alpha-tocopherol/d, and for 1 additional year after cessation of supplement. Some increase in adipose alpha-tocopherol (per milligram adipose cholesterol) and a more consistent decrease in gamma-tocopherol were observed during the supplementation period. The alpha-tocopherol/gamma-tocopherol ratio rose consistently during supplementation and fell only gradually after the supplement was stopped. We estimate that > or = 2 y are required for the alpha-tocopherol/gamma-tocopherol ratio to reach a new steady state after a change in alpha-tocopherol intake. In a cross-sectional measurement in five subjects who reported long-term use of alpha-tocopherol supplements (> or = 250 mg/d), and in five other subjects who reported no supplement use, the adipose alpha-tocopherol/gamma-tocopherol ratio clearly discriminated between the two groups (P < 0.002). This ratio may be of value in ranking individuals according to long-term alpha-tocopherol intake.

Adipose Tissue↗

Comparative evaluation of the antioxidant activity of alpha-tocopherol, alpha-tocopherol polyethylene glycol 1000 succinate and alpha-tocopherol succinate in isolated hepatocytes and liver microsomal suspensions.

The antioxidant activity of alpha-tocopherol polyethylene glycol 1000 succinate (TPGS) and of alpha-tocopherol succinate (TS) has been examined in isolated hepatocytes and microsomal fractions from rat liver. Both TPGS and TS require esterase activity to yield free alpha-tocopherol and, hence, antioxidant activity. TPGS and TS consistently exerted a more effective antioxidant protection than an equivalent amount of directly-added free alpha-tocopherol. The low antioxidant efficiency of directly added free alpha-tocopherol in such water-based experimental systems as used here seems to be due to its extreme hydrophobicity. TPGS, on the other hand, is an extremely hydrophilic compound that is being examined as a useful source of alpha-tocopherol in certain clinical situations and is here shown to be a convenient and effective source for experimental studies into lipid peroxidation and antioxidant mechanisms.

Animals↗

Red blood cell tocopherol and liver tocopherol in hyperlipemic rats as compared with plasma tocopherol.

In rats with hyperlipemia induced by Triton WR-1339, changes in tocopherol concentrations in plasma and RBC were compared with those in the liver and its subcellular fractions, microsomes and mitochondria. After daily injection with Triton, plasma total lipids at 3 days and 7 days, respectively, showed elevations 6.5 times and 15 times as high as those in the control rats, and triglycerides showed the most predominant elevation. With the hyperlipemia, the concentrations of tocopherol in RBC and the subcellular fractions decreased, as plasma lipids and plasma tocopherol increased, while no change occurred in tocopherol concentrations in liver homogenates. The changes in the ratio of tocopherol to total lipids in plasma coincided with changes in tocopherol concentrations in the RBC and subcellular fractions.

Animals↗

Stopped-flow investigation of antioxidant activity of tocopherols. Finding of new tocopherol derivatives having higher antioxidant activity than alpha-tocopherol.

Second-order rate constants, kappa s, for H-atom abstraction by phenoxyl radicals from five tocopherol (vitamin E) derivatives have been measured spectrophotometrically at 25.0 degrees C by the stopped-flow method, as a model reaction of tocopherols with unstable free radicals (LOO., LO., and HO.) in biological systems. Three new tocopherol derivatives with a five-membered heterocyclic ring were found to be 1.9-2.1 times more active than the alpha-tocopherol which has the highest antioxidant activity among natural tocopherols. The proton hyperfine splittings for the five tocopheroxyl radicals derived from these tocopherols by the reaction with phenoxyl were also determined by ESR measurements.

Antioxidants↗

Comparison of plasma alpha- and gamma-tocopherols after oral and intramuscular administration of RRR-alpha-tocopherol or RRR-gamma-tocopherol to weanling pigs.

Equimolar amounts of either RRR-alpha-tocopherol (alpha-TOH) or RRR-gamma-tocopherol (gamma-TOH) were given as single doses orally and, as water-based emulsions, by intramuscular (i.m.) injection to weanling pigs. Venous blood was sampled at regular intervals and plasma was analyzed for comparison of alpha-TOH and gamma-TOH kinetics. Irrespective of the method of application no significant differences were found between alpha-TOH and gamma-TOH in (a) the maximum increase above initial concentration (delta C), (b) the time of peak concentration (tmax), and (c) the time from half-maximum concentrations on the ascending and the descending parts of the plasma curve. However, alpha-TOH was retained longer in plasma than gamma-TOH, and the areas-under-curve from Oh to 24 h and from Oh to 48 h (AUC0-24 and AUC0-48) were significantly greater for alpha-TOH. In diarrheic pigs given oral gamma-TOH, tmax was prolonged, delta C was lower and AUC0-24 and AUC0-48 were reduced compared with healthy pigs (p less than 0.05). The results indicate that pigs absorb both vitamers to a similar extent but that gamma-TOH is eliminated from plasma more rapidly.

Absorption↗

Supplementation with mixed tocopherols increases serum and blood cell gamma-tocopherol but does not alter biomarkers of platelet activation in subjects with type 2 diabetes.

BACKGROUND: Some studies have shown potential benefit of vitamin E on platelet function, but several clinical trials failed to show improved cardiovascular outcome with alpha-tocopherol supplementation. Gamma-tocopherol, a major dietary form of vitamin E, may have protective properties different from those of alpha-tocopherol. OBJECTIVE: We compared the effects of supplementation with alpha-tocopherol (500 mg) and a gamma-tocopherol-rich compound (500 mg, containing 60% gamma-tocopherol) on serum and cellular tocopherol concentrations, urinary tocopherol metabolite excretion, and in vivo platelet activation in subjects with type 2 diabetes. DESIGN: Fifty-eight subjects were randomly assigned to receive either 500 mg alpha-tocopherol/d, 500 mg mixed tocopherols/d, or matching placebo. Serum, erythrocyte, and platelet tocopherol and urinary metabolite concentrations were measured at baseline and after the 6-wk intervention. Soluble CD40 ligand, urinary 11-dehydro-thromboxane B2, serum thromboxane B2, soluble P-selectin, and von Willebrand factor were measured as biomarkers of in vivo platelet activation. RESULTS: Serum alpha-tocopherol increased with both tocopherol treatments. Serum and cellular gamma-tocopherol increased 4-fold (P < 0.001) in the mixed tocopherol group, whereas red blood cell gamma-tocopherol decreased significantly after alpha-tocopherol supplementation. Excretion of alpha-carboxyethyl-hydroxychroman increased significantly after supplementation with alpha-tocopherol and mixed tocopherols. Excretion of gamma-carboxyethyl-hydroxychroman increased significantly after supplementation with mixed tocopherols and after that with alpha-tocopherol, which may reflect the displacement of gamma-tocopherol by alpha-tocopherol due to incorporation of the latter into lipoproteins in the liver. Neither treatment had any significant effect on markers of platelet activation. CONCLUSIONS: Supplementation with alpha-tocopherol decreased red blood cell gamma-tocopherol, whereas mixed tocopherols increased both serum alpha-tocopherol and serum and cellular gamma-tocopherol. Changes in serum tocopherol closely reflect changes in cellular concentrations of tocopherols after supplementation.

Analysis of Variance↗

Effects of various tocopherol-containing diets on tocopherol secretion into bile.

Gamma-tocopherol is abundant in common vegetable oil, but its concentration in plasma and liver is much lower than that of alpha-tocopherol. Discrimination between different forms of tocopherol is thought to take place via the hepatic alpha-tocopherol transfer protein (alpha-TTP). Gamma-tocopherol, with a low binding capacity to alpha-TTP, is thought to be excreted via the bile. Our previous studies showed that gamma-tocopherol administered with sesame seed exhibits significantly higher concentrations in the plasma and liver of rats than gamma-tocopherol alone. Thus, we attempted to confirm whether a much higher amount of gamma-tocopherol rather than alpha-tocopherol would be secreted in the bile, and whether sesame seed would suppress the secretion of gamma-tocopherol. In one experiment, we examined the concentrations of alpha- or gamma-tocopherol in the plasma, liver, and bile of rats fed diets containing 300 mg/kg of alpha-tocopherol, 300 mg/kg of gamma-tocopherol, or 300 mg/kg each of alpha-tocopherol + gamma-tocopherol, and in the other experiment, we compared the gamma-tocopherol concentrations of rats fed a diet of gamma-tocopherol alone to those of rats fed a gamma-tocopherol + sesame seed diet (each diet contained 300 mg/kg gamma-tocopherol). The bile collection was done over 6 h. The gamma-tocopherol concentration in the bile was markedly lower than that of alpha-tocopherol, paralleling the concentrations in the plasma and liver. Intake of alpha-tocopherol and gamma-tocopherol together further lowered the concentration of gamma-tocopherol in the bile as well as in the plasma and liver, compared to the intake of gamma-tocopherol alone. The gamma-tocopherol concentration in the bile, as well as in the plasma and liver, was markedly higher in the sesame seed-fed group than in the gamma-tocopherol alone group. We found that the concentrations of alpha- or gamma-tocopherol in the bile showed a good correlation with the concentrations of alpha- or gamma-tocopherol in the liver, though the concentrations in the bile were substantially lower than those in the liver. These findings suggest that secretion into the bile is not a major metabolic route of alpha- or gamma-tocopherol.

Animals↗

Graded dietary levels of RRR-gamma-tocopherol induce a marked increase in the concentrations of alpha- and gamma-tocopherol in nervous tissues, heart, liver and muscle of vitamin-E-deficient rats.

The effect of dietary RRR-gamma-tocopherol supplementation on serum and tissue alpha- and gamma-tocopherol concentrations was studied in vitamin-E-deficient rats fed diets containing adequate levels of RRR-alpha-tocopherol and graded levels of RRR-gamma-tocopherol over a 60 day period. Feeding rats with a RRR-alpha-tocopherol-supplemented diet induced in forebrain, sciatic endoneurium, skeletal muscle, heart and liver a marked increase in alpha-tocopherol concentration. In contrast, feeding rats with a diet containing the same level of RRR-gamma-tocopherol induced a small increase in gamma-tocopherol concentrations in brain, sciatic endoneurium, skeletal, muscle, heart and liver and a slight but significant decrease in alpha-tocopherol concentration in all tissues examined. In rats fed diets containing a constant level of RRR-alpha-tocopherol and graded levels of RRR-gamma-tocopherol, the concentrations of alpha-tocopherol in all tissues were much higher than those in rats fed a control diet containing RRR-alpha-tocopherol alone. The higher the gamma/alpha ratio, the more the alpha-tocopherol concentrations increased. Significant positive linear regressions were found between the gamma/alpha ratio and the alpha- and gamma-tocopherol concentrations in most of the tissues examined. These results indicate that when gamma-tocopherol was supplied continuously in the diet gamma-tocopherol accumulated significantly in the tissues but to a much smaller extent than when rats were fed with RRR-alpha-tocopherol. These experiments also indicate that gamma-tocopherol did not depress the serum and tissue alpha-tocopherol concentrations. On the contrary, gamma-tocopherol supplements induced a marked increase in alpha-tocopherol concentrations in the serum and tissues. These results suggest that there is a relationship between alpha- and gamma-tocopherol levels in vivo and that the biopotency of alpha-tocopherol should be reevaluated especially when high levels of gamma-tocopherol were present in the diet.

Animals↗

The effect of gamma-tocopherol administration on alpha-tocopherol levels and metabolism in humans.

BACKGROUND: The bioavailability of gamma-tocopherol and metabolites of vitamin E after gamma-tocopherol administration is not well understood. We investigated the effect of gamma-tocopherol administration on the levels and metabolism of alpha- and gamma-tocopherol in healthy volunteers. METHODS: We measured two metabolites of vitamin E (2,5,7,8-tetramethyl-2-(2'-carboxyethyl)-6-hydroxychroman (alpha-CEHC) and 2,7,8-trimethyl-2-(2'-carboxyethyl)-6-hydroxychroman (gamma-CEHC)) in plasma and urine by high-performance liquid chromatography with electrochemical detection (HPLC-ECD) during administration of gamma-tocopherol. Two groups of volunteers were enrolled. The gamma-tocopherol group received two gamma-tocopherol capsules (each containing 186.4 mg of gamma-tocopherol and 5 mg of alpha-tocopherol) for 28 days, while the control group received d-alpha-tocopherol at 5 mg/day, which was the same dose as that given to the gamma-tocopherol group. Blood and urine samples were obtained on days 0, 14, 28, 35, 42, and 56 after the initiation of gamma-tocopherol administration. RESULTS: The plasma gamma-tocopherol concentration increased markedly during administration of gamma-tocopherol and the plasma gamma-CEHC concentration increased along with that of gamma-tocopherol. The plasma alpha-tocopherol concentration decreased significantly during gamma-tocopherol administration. The plasma concentration of alpha-CEHC decreased significantly and urinary excretion of alpha-CEHC tended to increase in the gamma-tocopherol group. Urinary sodium secretion was significantly increased at 1 week after the cessation of gamma-tocopherol administration, but there was no significant difference of urine volume between the two groups. CONCLUSION: Metabolism of alpha-tocopherol is accelerated and the plasma alpha-tocopherol concentration is decreased during gamma-tocopherol administration.

Adult↗

Mechanisms of absorption, transport and tissue uptake of RRR-alpha-tocopherol and d-gamma-tocopherol in the white rat.

The metabolism of alpha- and gamma-tocopherol was studied in three groups of rats that were fed a modified AIN-76 diet containing normal (NE, 0.2 g alpha-tocopherol/kg), high (HE, 1.0 g alpha-tocopherol/kg) or low (LE, less than 0.02 alpha-tocopherol/kg) vitamin E for 3 mo. After 1, 2 and 3 d of an oral dose of 20 mg of alpha-tocopherol, gamma-tocopherol or both, the levels of the two vitamers were measured in plasma and tissues and in some cases in isolated microsomal and mitochondrial fractions from liver. Twenty-four hours after an oral dose of 20 mg gamma-tocopherol the levels of alpha-tocopherol in plasma and tissues remained constant and higher levels of gamma-tocopherol were found in tissues in which low alpha-tocopherol levels could be found such as in the LE group. In spite of this, it was enabled to remain there, after 2 and 3 d gamma-tocopherol had decreased levels in all tissues. When given in combination with alpha-tocopherol, the levels of gamma-tocopherol were lower than when gamma-tocopherol was given alone. Microsomes and mitochondria from livers of LE group bound five and nine times more alpha-tocopherol than gamma-tocopherol in rats dosed with equal amount of alpha- or gamma-tocopherol, respectively. These data indicate that the mechanisms that regulate the metabolism of vitamin E are highly specific for alpha-tocopherol. Moreover, the relative amount of alpha-tocopherol determined the levels of gamma-tocopherol in tissues. However, the retention of gamma-tocopherol in tissues did not depend on the presence of alpha-tocopherol.(ABSTRACT TRUNCATED AT 250 WORDS)

Absorption↗

[Vitamin E: comparison of efficiency of incorporation of alpha-tocopherol in the organs in comparison to gamma-tocopherol].

Refeeding rats deficient in vitamin E with alpha-tocopherol induces increased amount of this compound in brain, cerebellum, sciatic nerve and muscle. This increase is regular with time. The optimum level (corresponding to non-deficient animals) is not reached within 8 weeks after refeeding. Thus recovery is very slow for the nervous tissue (as it has been demonstrated for polyunsaturated fatty acids). In contrast, the optimum level is reached within 2 weeks for liver and serum. Refeeding rat deficient in vitamin E with gamma-tocopherol induces an increase of this compound in the liver, the plateau is reached within 2 weeks, but is clearly lower than the one obtained with alpha-tocopherol : approximately 4 times lower. In the muscle, the uptake is linear with time, the plateau is not reached within 8 weeks, its level is 4 times lower than with alpha-tocopherol. Important point : feeding animals deficient in vitamin E with gamma-tocopherol induces in the nervous system a level of gamma-tocopherol which is not the one of the residual alpha-tocopherol; the plateau is not reached within 8 weeks. In sciatic nerve and cerebellum (but not in the brain) increased amount of gamma-tocopherol as a function of time is parallel with a slight but significant reduction of the residual alpha-tocopherol. In another experiment, rats were fed a diet deficient with vitamin E until 60 days of age. From this age, they received a non deficient diet until 120 days. In all organs, increasing the ratio gamma/alpha tocopherol (with a constant amount of alpha-tocopherol) induces an increase of alpha-tocopherol. This result is unexpected, as it was possible to propose that gamma-tocopherol could reduce alpha-tocopherol utilisation by competition. Conversely, the presence of alpha-tocopherol seems to increase incorporation of gamma-tocopherol, except in brain and sciatic nerve. The presence of gamma-tocopherol seems to induce increased need of alpha-tocopherol. This specificity for alpha-tocopherol is very important in terms of nutrition and pharmacology. In fact, at least to preserve biological membranes, it is important to provide only alpha-tocopherol, and not other molecules.

Animals↗

Distribution of serum concentrations of alpha-tocopherol and gamma-tocopherol in the US population.

BACKGROUND: Although the population distribution of serum concentrations of alpha-tocopherol has been described in the United States, little is known about the distribution of gamma-tocopherol or the ratio of alpha-tocopherol to gamma-tocopherol. OBJECTIVE: Our aim was to describe the distribution of serum concentrations of alpha-tocopherol and gamma-tocopherol in a nationally representative sample of US adults. DESIGN: We reviewed data from 4087 adults aged >/=20 y who participated in the National Health and Nutrition Examination Survey (1999-2000). Concentrations of alpha-tocopherol and gamma-tocopherol were measured by using HPLC with ultraviolet-visible wavelength detection. RESULTS: The arithmetic mean (+/-SEM) of serum concentrations of alpha-tocopherol was 30.09 +/- 0.45 micromol/L, the median was 25.94 micromol/L, and the geometric mean (+/-SEM) was 27.39 +/- 0.38 micromol/L. The arithmetic mean of serum concentrations of gamma-tocopherol was 5.74 +/- 0.22 micromol/L, the median was 5.25 micromol/L, and the geometric mean was 4.79 +/- 0.18 micromol/L. The median ratio of alpha-tocopherol to total cholesterol was 4.93 micromol/mmol, that of gamma-tocopherol to total cholesterol was 1.03 micromol/mmol, and that of alpha-tocopherol to gamma-tocopherol was 4.53 micromol/mmol. Concentrations of alpha-tocopherol increased significantly (P for trend < 0.001) with age and were significantly (P = 0.015) lower in men than in women. African Americans and Mexican Americans had significantly (P < 0.001) lower concentrations of alpha-tocopherol than did whites. The median concentrations of gamma-tocopherol showed a trend with respect to age, did not differ significantly between men and women, and were slightly but nonsignificantly lower in white participants than in African American or Mexican American participants. CONCLUSION: Sociodemographic variations in serum concentrations of alpha-tocopherol and gamma-tocopherol exist among US adults.

Adult↗

Mixed tocopherols have a stronger inhibitory effect on lipid peroxidation than alpha-tocopherol alone.

Intake of vitamin E with food (mixed tocopherols) has been found to counteract the development of atherosclerotic cardiovascular disease, whereas intake of large amounts of pure alpha-tocopherol has shown only a slight or no effect in clinical studies. This study was designed to investigate the effects of alpha-tocopherol alone and a mixed tocopherol preparation (gamma-, delta-, and alpha-tocopherol) on hydrogen peroxide-induced lipid peroxidation in human erythrocytes. Erythrocytes were incubated with different concentrations of alpha-tocopherol or mixed tocopherols and then exposed to hydrogen peroxide. Tocopherol levels and malondialdehyde-thiobarbituric acid-reactive substances were determined by high-performance liquid chromatography and fatty acids by gas chromatography. Incubation of erythrocytes with tocopherols (30-120 microM) increased the tocopherol level in a concentration-dependent manner. The uptake of gamma- and delta-tocopherols was much higher than that of alpha-tocopherol. Hydrogen peroxide strongly increased lipid peroxidation and decreased polyunsaturated fatty acids in erythrocytes. Both alpha-tocopherol and the tocopherol mixture protected the cells from lipid peroxidation, the mixture being much more potent than alpha-tocopherol alone. This study indicates that a mixture of tocopherols has a stronger inhibitory effect on lipid peroxidation induced in human erythrocytes than alpha-tocopherol alone, due to higher uptake of gamma- and delta-tocopherol in the cells.

Adult↗