Plasma Α-tocopherol Levels Research Articles

Association between fat-soluble vitamin co-exposure patterns and blood pressure in people with hypertension: a cross-sectional study

BackgroundExisting epidemiological studies investigated the association between a single vitamin and hypertension. However, the potential relationship between the level of circulating multivitamins and blood pressure has not been explored. We aimed to investigate the association between multiple fat-soluble vitamin levels and blood pressure.MethodsA total of 2052 participants with essential hypertension were sampled nationwide. The plasma concentrations of fat-soluble vitamins (A, E, D, and K) were assessed using liquid chromatography coupled with the mass spectrometry method. Participants were categorized into different co-exposure patterns using the unsupervised K-means clustering method. The multiple linear regression model was used for subsequent analyses.ResultsParticipants were classified into two co-exposure patterns of fat-soluble vitamins. The levels of vitamins were relatively low in pattern 1, compared to pattern 2. Participants in pattern 2 had no significantly different blood pressure levels compared to pattern 1. However, the plasma 25-hydroxyvitamin D3 (VD3) levels were negatively associated with SBP (logarithmic 10 transformed) (β = −0.002, 95% CI: −0.004, 0); participants in the fourth α-tocopherol quartile had mean SBP levels that were 1.02% (95% CI: 0.43, 1.61%) greater than those in the lowest quartile (p for trend <0.01). In addition, no significant relationships were found between plasma VA/VK concentrations and blood pressure.DiscussionAlthough no significant association between fat-soluble vitamin co-exposure patterns and blood pressure was found, further analyses could imply that plasma α-tocopherol levels may offset the potential protective effect of plasma VD3 on blood pressure among hypertensive adults. This provided a novel perspective for exploring the joint effects of fat-soluble vitamins on blood pressure. Further studies are warranted to better understand the implications.

Associations of plasma retinol and α-tocopherol levels with skeletal muscle health in Chinese children.

Childhood is a critical period for muscle accumulation. Studies in elders have reported that antioxidant vitamins could improve muscle health. However, limited studies have assessed such associations in children. This study included 243 boys and 183 girls. A seventy-nine-item FFQ was used to investigate dietary nutrients intake. Plasma levels of retinol and α-tocopherol were measured using high-performance liquid chromatography with MS. Dual X-ray absorptiometry was used to assess appendicular skeletal muscle mass (ASM) and total body fat. The ASM index (ASMI) and ASMI Z-score were then calculated. Hand grip strength was measured using a Jamar® Plus+ Hand Dynamometer. Fully adjusted multiple linear regression models showed that for each unit increase in plasma retinol content, ASM, ASMI, left HGS and ASMI Z-score increased by 2·43 × 10-3 kg, 1·33 × 10-3 kg/m2, 3·72 × 10-3 kg and 2·45 × 10-3 in girls, respectively (P < 0·001-0·050). ANCOVA revealed a dose-response relationship between tertiles of plasma retinol level and muscle indicators (Ptrend: 0·001-0·007). The percentage differences between the top and bottom tertiles were 8·38 %, 6·26 %, 13·2 %, 12·1 % and 116 % for ASM, ASMI, left HGS, right HGS and ASMI Z-score in girls, respectively (Pdiff: 0·005-0·020). No such associations were observed in boys. Plasma α-tocopherol levels were not correlated with muscle indicators in either sex. In conclusion, high circulating retinol levels are positively associated with muscle mass and strength in school-age girls.

Response to different sources of vitamin E orally injected and to various doses of vitamin E in calf starter on the plasma vitamin E level in calves around weaning

Calves often face a lower plasma vitamin E level than the recommended level (3 µg/ml for adult cows) after weaning, a level which has been related to a good immune response. Two experiments were performed to determine the most effective source and level of vitamin E to be included in a calf starter to maintain the plasma vitamin E level above the recommended level after weaning. Experiment 1 (Exp 1) and experiment 2 (Exp 2) included a total of 32 and 40 calves, respectively, from 2 weeks before weaning until 2 weeks after weaning. In Exp 1, calves were orally injected a daily dose of different vitamin E sources including, no α-tocopherol (0 dose; Control), 200 mg/d of RRR-α-tocopherol (ALC), 200 mg/d of RRR-α-tocopheryl acetate (ACT), or 200 mg/d of all-rac-α-tocopheryl acetate (SYN). In Exp 2, a dose response study was carried out with 0, 60, 120, and 200 mg/kg of ALC in a pelleted calf starter. Final BW (100 ± 16 and 86 ± 11 kg) and average daily gain (956 ± 303 and 839 ± 176 g/d in Exp 1 and 2, respectively; mean ± SD) were unaffected by either source or level of α-tocopherol. In Exp 1, the plasma RRR-α-tocopherol level was affected by α-tocopherol source (P < 0.001), week (P < 0.001), and interaction between them (P < 0.001). At weaning time, the plasma RRR-α-tocopherol was 2.7, 2.1, 1.1, and 0.8 μg/ml in ALC, ACT, SYN, and Control, respectively. In Exp 2, the plasma α-tocopherol level was affected by ALC dose (P = 0.04), week (P < 0.001), and a tendency for an interaction between them was observed (P = 0.06). At weaning, a 36, 31, and 28% reduction in plasma α-tocopherol level was observed compared to the beginning of the experiment with 0, 60, and 120 mg/kg of ALC, respectively; however, with 200 mg/kg of ALC, a 9% increase in the plasma α-tocopherol level was observed. In addition, 200 mg/kg of ALC was able to maintain plasma α-tocopherol after weaning higher than the recommended level. The results showed that the ALC was the most efficient source of α-tocopherol supplementation to be used in a calf starter. In addition, the 200 mg/kg of ALC in the calf starter was the only effective dose to maintain the postweaning plasma vitamin E concentration at the recommended level after weaning and α-tocopherol similar to that observed before weaning.

Associations of α- and γ-tocopherol during early life with lung function in childhood

Tocopherol isoforms may regulate child lung growth and spirometric measures. Our aim was to determine the extent to which plasma α-tocopherol (α-T) or γ-tocopherol (γ-T) isoform levels in early childhood or in utero are associated with childhood lung function. We included 622 participants in the Project Viva cohort who had lung function at a mid-childhood visit (age 6-10 years). Maternal and child tocopherol isoform levels were measured by HPLC at the second trimester and 3 years of age, respectively. Multivariable linear regression models (adjusted for mid-childhood body mass index z scores, maternal education, smoking in pregnancy, and prenatal particulate matter with diameter of <2.5 micrometers (PM2.5) particulate exposure) stratified by tertiles of child γ-T level were used to assess the association of α-T levels with FEV1 and forced vital capacity (FVC) percent predicted. Similarly, models stratified by child α-T tertile evaluated associations of γ-T levels with lung function. We performed similar analyses with maternal second trimester tocopherol isoform levels. The median maternal second trimester α-T level was 63 μM (interquartile range= 47-82). The median early-childhood level was 25 μM (interquartile range= 20-33 μM). In the lowest tertile of early-childhood γ-T, children with a higher α-T level (per 10 μM) had a higher mid-childhood FEV1 percent predicted (β= 3.09; 95% CI= 0.58-5.59 and a higher FVC percent predicted (β= 2.77; 95% CI= 0.47-5.06). This protective association of α-T was lost at higher γ-T levels. We did not see any consistent associations of second trimester levels of either α-T or γ-T with mid-childhood FEV1 or FVC. When γ-T levels were in the lowest tertile, a higher early-childhood α-T level was associated with better lung function at mid-childhood. Second trimester maternal plasma α-T concentration was 3-fold higher than in the adult nonpregnant female population.

Acrylamide reduces plasma antioxidant vitamin levels in rats due to increased oxidative damage

ABSTRACT Objective Acrylamide is a potentially neurotoxic and carcinogenic chemical and naturally creates during the heating process of carbohydrate-rich foods, such as potato chips and breakfast cereals. Acrylamide might be ingested by people via consuming food that contains it. Therefore, we investigated the effect of acrylamidegiven orally to male and female rats on plasma retinoic acid and α-tocopherol and serum sialic acid and malondialdehyde levels. Method A total of 50 Wistar rats were used (25 female and 25 male, three-four weeks old). The rats of each sex were given 2 and 5mg/kg/day acrylamide via drinking water for 90 days. At the end of the treatment, the animals were euthanized by cervical dislocation. Blood specimens were collected through cardiac puncture, and serum and plasma samples were analysed using the high-performance liquid chromatography technique with a Ultraviolet detector. Results The analysis of the plasma and serum samples revealed that serum sialic acid and malondialdehyde levels in both sexes given 5mg/kg/day acrylamide were significantly increased, and the serum sialic acid levels were higher in female rats given 2mg/kg/day acrylamide. The plasma retinoic acid and α-tocopherol levels significantly decreased in both sexes given only the highest dose. Conclusion The results show that acrylamide causes an increase in oxidative stress and leads to a decrease in the levels of retinoic acid and α-tocopherol which play a role in the defense mechanism against this stress.

Weight loss program is associated with decrease α-tocopherol status in obese adults

Studies on changes in plasma α-tocopherol levels during body fat reduction in obese persons are not clear. The aim of the present study was to assess factors associated with α-tocopherol status in obese people and to examine changes in α-tocopherol status after a 6-week AntioxObesity weight loss program. The study was conducted in 60 overweight or obese adults, aged 18-54 years old. Food intake data were collected using the 3-day record method and a semi-quantitative food-frequency questionnaire. Anthropometric measurements included: height (H), body weight, waist circumference (WC) and hip circumference (HC), body composition: fat mass (FM) and fat-free mass (FFM), subcutaneous fat (SF) and visceral fat (VF). Lipid profile, α-tocopherol concentration, glutathione peroxidase (GPx) activity, total antioxidant capacity (TAC) in plasma and superoxide dismutase (SOD) activity in erythrocytes were determined. Energy, fat, and carbohydrate intakes decreased significantly in all subjects (P<0.001). Body weight, WC, body mass index (BMI), waist-to height ratio (WHtR), and FM, VF and SF decreased significantly during the 6 weeks in all subjects. Plasma α-tocopherol significantly decreased during the program (P=0.006). No changes were observed for SOD activity, but GPx activity and TAC decreased significantly (P=0.001; P=0,023, respectively). Plasma α-tocopherol concentration after 6 weeks of the AntioxObesity program was strongly associated with baseline plasma α-tocopherol, changes in TC, VF and FM. Low α-tocopherol status (<20μmol/L) was found in 78% of the women and 68% of the men, after 6 weeks of the AntioxObesity program. Men were characterized by a greater decrease in weight, BMI, WC, FM, VF, SF and TAC compared to women. A 6-week weight loss program lowered α-tocopherol status in overweight and obese people. Low baseline α-tocopherol status and adiposity in obese adults negatively affected α-tocopherol status after 6 weeks weight loss program. These results, coupled with excessive weight and low α-tocopherol intake, led to the finding that there was an increased risk of oxidative stress diseases in adults on a reduced diet. Long-term dietary restriction program for obese patients should be monitored to avoid α-tocopherol deficiency, and take into account higher dietary α-tocopherol requirements for obese people.

Sex and line differences in biochemical indices and fat soluble vitamins sufficiency in rats on in vivo model of metabolic syndrome

Consumption of diets that are inadequate in energy value to the actual energy expenditure can lead to the development of metabolic syndrome (MS), which has consequences such as type 2 diabetes mellitus, non-alcoholic steatohepatosis, atherosclerosis, gout, allergic diseases. Experimental models of MS are needed to develop new approaches to its dietary and drug correction. The aim of the work was a comparative analysis of functional, biochemical and vitamin markers characterizing the effect of a diet with a high content of fructose (F) on males and females of various rat lines and the selection on this basis of an optimal in vivo MS model. Male and female rats of the outbred Wistar line (W) and the inbred Dark Agouti line (DA) were used in the work number of 16 individuals of each sex and line. The animals of the 1st (control) groups of each sex and line received a balanced semi-synthetic diet according to AIN93, and the animals of the 2nd (experimental) groups - the same diet and 30% solution of F instead of water in the regime of free access. Within 121 days, energy value of diets consumed, the increase in body weight and blood pressure were determined; relative mass of internal organs, biochemical parameters of blood plasma, content of fat-soluble vitamins A and E in blood plasma and liver were determined at withdrawal of animals from experiment. It was shown that, in spite of the increased energy value of the diet in the experimental groups throughout experiment, DA males and females practically did not respond to this by an increase in body weight gain, in contrast to W rats (in particular, females). Consumption of diets with F led to an increase in glucose level irrespective of gender and line, whereas triglyceride level (TG) significantly increased only in the case of W female. Addition of F caused in DA rats of both sexes an increase in the mass of the kidneys, as well as more pronounced, in comparison with W rats manifestation of markers of toxic effects on the liver (increases alanine aminotransferase and γ-glutamyltransferase activity, elevated urea and bilirubin level in blood plasma). In rats of both lines intake of F suppressed the accumulation of retinol palmitate in the liver in terms of its specific content. The total content of α-tocopherol in liver was significantly higher in W compared with DA. At the same time, α-tocopherol levels in blood plasma correlated with TG, and the α-tocopherol/TG ratio significantly decreased in female W receiving F, which were characterized by hyperlipidemia. Thus, the effect of F on W males and, in particular, females, basically corresponded to the classical picture of MS with body weight increasing, elevated blood pressure, glycemia and TG increase, whereas the toxic effect of F prevailed in DA liver and, possibly, kidneys without development of marked dyslipidemia and obesity.

In vivo antioxidative activity of 5,7,4-trihydroxyflavone-7-O-(6-O-[E]-coumaroyl)--glucopyranoside isolated from Panzeria alaschanica

Our objective was to assess in vivo antioxidative potential of 5,7,4'-trihydroxyflavone-7-O-(6''-O-[E]-coumaroyl)-β-glucopyranoside (TFGN) isolated from Panzeria alaschanica in a diabetic rat model. The diabetes and the following oxidative stress were induced by intraperitoneal administration of streptozotocin. The effects of TPGN (60 mg/kg) on the plasma concentration of malondialdehyde (MDA) and plasma fat-soluble antioxidants (co-enzyme Q9, α-and γ-tocopherol) were measured as a parameter of oxidative damage and markers of antioxidant defence, respectively. The level of MDA in plasma was reduced to the same level as in healthy control animals. A significant decrease was observed in the plasma α-tocopherol level in the oxidative stress group compared to the healthy controls. Key words: Panzeria alaschanica, diabetes mellitus model, antioxidant, 5,7,4'-trihydroxyflavone-7-O-(6''-O-[E]-coumaroyl)-β-glucopyranoside.

Establishment of reference values of α-tocopherol in plasma, red blood cells and adipose tissue in healthy children to improve the management of chylomicron retention disease, a rare genetic hypocholesterolemia.

BackgroundChylomicron retention disease (CMRD), a rare genetic hypocholesterolemia, results in neuro-ophtalmologic damages, which can be prevented by high doses of vitamin E during infancy. In these patients, plasma vitamin E concentration is significantly reduced due to defects of chylomicron secretion. Vitamin E in adipose tissue (AT) and red blood cells (RBC) have been proposed as potential relevant biomarkers of vitamin E status but no reference values in children are available. The objectives were (i) to establish age-reference intervals in healthy children for α-tocopherol in plasma, red blood cells (RBC) and adipose tissue (AT) and (ii) to determine the variations of α-tocopherol in patients with CMRD after oral treatment with vitamin E.MethodsThis prospective study included 166 healthy children (1 month - 18 years) and 4 patients with CMRD. Blood and AT were collected in healthy children during a scheduled surgery and in patients before and after a 4-month treatment with α-tocopherol acetate.ResultsThe reference ranges for α-tocopherol were 11.9 - 30 μmol/L in plasma, 2.0 - 7.8 μmol/L packed cells in RBC and 60 - 573 nmol/g in AT. α-tocopherol levels in plasma correlated with those of RBC (r = 0.31; p < 0.01).In patients with CMRD after 4 months treatment, α-tocopherol concentrations remained less than 70 % of the control values in plasma, increased by 180 % to reach normal values in RBC, and remained stable in the normal range in AT.ConclusionThis study establishes pediatric reference intervals for α-tocopherol in plasma, RBC and AT. These values will be beneficial in assessing accurate α-tocopherol status in children and to optimize the monitoring of rare diseases such as CMRD. Our data suggest that RBC α-tocopherol, appears as a relevant biomarker to appreciate the effectiveness of treatment with α-tocopherol in patients with a rare primary hypocholesterolemia. The biopsy of AT could be used at diagnosis to assess the severity of the vitamin E deficiency and periodically after a long duration of vitamin E therapy to assess whether the treatment is effective, based on reference intervals defined in this study.

Age-related changes of vitamin E: α-tocopherol levels in plasma and various tissues of mice and hepatic α-tocopherol transfer protein.

Despite numerous studies on the RRR- and all-rac-α-tocopherol isoform of vitamin E (VE) during aging, this relationship has not been examined in specific tissues. Since α-tocopherol is the most abundant of VE's eight isoforms, and VE is an important antioxidant that impacts the aging process, we analyzed α-tocopherol levels in plasma and tissues of mice at progressive ages. Moreover, we examined protein and mRNA expression levels of hepatic α-tocopherol transfer protein (α-TTP), which specifically binds α-tocopherol, during aging. The α-tocopherol levels in plasma, liver, cerebrum, hippocampus, cerebellum, heart, kidney, epididymal adipose tissue, testis, pancreas, soleus muscle, plantaris muscle, and duodenum from male C57BL/6NCr mice at 3, 6, 12, 18, and 24months of age were determined by HPLC and fluorescence detection. Also, hepatic α-TTP protein and mRNA expression levels were analyzed by Western blot and qPCR, respectively. Tissue-specific, age-related changes of α-tocopherol levels normalized by tissue weight were observed in the liver, cerebrum, hippocampus, cerebellum, heart, kidney, and epididymal adipose tissue. Specifically, α-tocopherol levels in epididymal adipose tissue increased greatly as mice aged from 6 to 24 months. Although hepatic α-TTP protein levels also showed age-related changes, α-TTP mRNA expression levels measured after overnight fasting were not altered. In this study, we determined that α-tocopherol levels and hepatic α-TTP protein levels of mice undergo significant tissue-specific, age-related changes. This is the first report to investigate VE in terms of the α-tocopherol levels in plasma and various tissues of mice and hepatic α-TTP protein levels during aging.

Antioxidant nutrients in plasma of Japanese patients with chronic obstructive pulmonary disease, asthma‐COPD overlap syndrome and bronchial asthma

Few studies to date have investigated the antioxidant nutrients such as vitamin C (ascorbic acid), vitamin E (α-tocopherol), retinol and carotenoids in plasma from patients with pulmonary disease in Japan. To clarify the role of antioxidant nutrients such as vitamin C, vitamin E, retinol and various carotenoids in plasma of Japanese patients with chronic obstructive lung diseases (COPD), asthma-COPD overlap syndrome (ACOS) and/or bronchial asthma (BA), we compared to healthy elderly controls. Ascorbic acid (AA), carotenoids (lutein, zeaxanthin, β-cryptoxanthin, α-carotene, β-carotene and lycopene), retinol and α-tocopherol levels in plasma were determined by using a high performance liquid chromatography. Reduced glutathione (GSH), oxidised glutathione (GSSG) in whole blood and urinary 8-OHdG were also determined. Plasma AA level of COPD subjects was significantly lower than that of healthy elderly people. Conversely, ACOS and BA subjects showed no significant difference from healthy elderly people. Moreover, plasma lycopene and total carotenoid levels and GSH content in blood were significantly lower in COPD subjects than these in healthy elderly people. However, other redox markers such as GSSG, GSH/GSSG ratio and urinary 8-OHdG found no significant differences between COPD, ACOS and BA compared to healthy elderly people. These results suggested that COPD of Japanese patients may develop partly because of oxidative stress derived from a shortage of antioxidant nutrients, especially of AA and lycopene, as well as GSH while this may not be the case in both ACOS and BA.

Dehydroepiandrosterone alters vitamin E status and prevents lipid peroxidation in vitamin E-deficient rats.

In humans, dehydroepiandrosterone and its sulfate ester metabolite DHEA-S are secreted predominantly from the adrenal cortex, and dehydroepiandrosterone is converted to steroid hormones, including androgens and estrogens, and neurosteroid. Dehydroepiandrosterone exerts protective effects against several pathological conditions. Although there are reports on the association between dehydroepiandrosterone and vitamins, the exact relationship between dehydroepiandrosterone and vitamin E remains to be determined. Therefore, we attempted to elucidate the effect of dehydroepiandrosterone on vitamin E status and the expression of various vitamin E-related proteins, including binding proteins, transporters, and cytochrome P450, in vitamin E-deficient rats. Plasma α-tocopherol levels in vitamin E-deficient rats increased in response to dehydroepiandrosterone administration. The expression of hepatic α-tocopherol transfer protein was repressed in vitamin E-deficient rats compared to that in control rats; however, dehydroepiandrosterone administration significantly upregulated this expression. Hepatic expression of CYP4F2, an α-tocopherol metabolizing enzyme, in vitamin E-deficient rats was decreased by dehydroepiandrosterone administration, whereas hepatic expression of ATP-binding cassette transporter A1, an α-tocopherol transporter, was not altered following dehydroepiandrosterone administration. Dehydroepiandrosterone repressed lipid peroxidation in the liver of vitamin E-deficient rats. Therefore, adequate dehydroepiandrosterone supplementation may improve lipid peroxidation under several pathological conditions, and dehydroepiandrosterone may modulate α-tocopherol levels through altered expression of vitamin E-related proteins.

Reply: Understanding the roles of the vitamin E isoforms α- and γ-tocopherol in allergic airway disease.

Reply: Understanding the roles of the vitamin E isoforms α- and γ-tocopherol in allergic airway disease.

Plasma levels of α-tocopherol, -tocopherol and selenium in patients with prostate cancer in Nigeria

Background: Evidence suggests that essential trace metals and vitamins play crucial roles in slowing down the initiation and progression stages of many cancers, but the plausible role of selenium and vitamin E, especially the gamma-tocopherol (γ-tocopherol), against prostate cancer is yet to be ascertained. Aim: To compare levels of selenium, alpha-tocopherol (α-tocopherol) and γ-tocopherol between prostate cancer (PCa) and benign prostatic hyperplasia (BPH) patients. Methods: Twenty (20) prostate cancer (PCa) patients and 25 patients with benign prostatic hyperplasia (BPH) recruited from Urology Clinic of the Department of Surgery, University College Hospital (UCH), Ibadan acted as case and control subjects, respectively. Informed consent was obtained from all participants. The plasma levels of selenium, α-tocopherol and γ-tocopherol were determined by Atomic Absorption Spectrophotometer (AAS) and High Performance Liquid Chromatography (HPLC), respectively. Results: γ-tocopherol levels were significantly higher in BPH patients (control) when compared with PCa patients. Selenium and α-tocopherol levels were lower in PCa patients, but not significant. Conclusion: Plasma low level of γ-tocopherol in PCa patients was statistically significant. This may be a risk factor among adult Nigerian men for the development of prostate cancer. Increased plasma level of -tocopherol through diet or supplementation may reduce the risk and progression of prostate cancer. Key words: Prostate cancer, benign prostatic hyperplasia, γ-tocopherol, α-tocopherol, selenium, trace metals.

The Oral Intake of Organic Germanium, Ge-132, Elevates α-Tocopherol Levels in the Plas-ma and Modulates Hepatic Gene Expression Profiles to Promote Immune Activation in Mice.

The common water-soluble organic germanium compound poly-trans-[(2-carboxyethyl) germasesquioxane] (Ge-132) exhibits activities related to immune responses and antioxidant induction. In this study, we evaluated the antioxidative effect of dietary Ge-132 in the plasma of mice. Male ICR mice (seven mice per group) received an AIN-76 diet with 0.05% Ge-132; three groups received the Ge-132-containing diet for 0, 1 or 4 days. The plasma alpha-tocopherol (α-tocopherol) concentration increased from 6.85 to 9.60 μg/ml after 4 days of Ge-132 intake (p<0.05). We evaluated the changes in hepatic gene expression related to antioxidative activity as well as in the entire expression profile after one day of Ge-132 intake, using DNA microarray technology. We identified 1,220 genes with altered expression levels greater than 1.5-fold (increased or decreased) as a result of Ge-132 intake, and α-tocopherol transfer protein (Ttpa) gene expression was increased 1.62-fold. Immune activation was identified as the category with the most changes (containing 60 Gene Ontology (GO) term biological processes (BPs), 41 genes) via functional clustering analysis of altered gene expression. Ge-132 affected genes in clusters related to ATP production (22 GO term BPs, 21 genes), lipid metabolism (4 GO term BPs, 38 genes) and apoptosis (5 GO term BPs). Many GO term BPs containing these categories were significantly affected by the Ge-132 intake. Oral Ge-132 intake may therefore have increased plasma α-tocopherol levels by up-regulating α-tocopherol transfer protein (Ttpa) gene expression.

Genetic polymorphism of cytochrome P450 4F2, vitamin E level and histological response in adults and children with nonalcoholic fatty liver disease who participated in PIVENS and TONIC clinical trials.

Vitamin E improved liver histology in children and adults with NAFLD who participated in TONIC and PIVENS clinical trials, but with significant inter-individual variability in its efficacy. Cytochrome P450 4F2 (CYP4F2) is the major enzyme metabolizing Vit E, with two common genetic variants (V433M, rs2108622 and W12G, rs3093105) found to alter its activity. We investigated the relationship between CYP4F2 genotypes, α-tocopherol levels and histological improvement in these two trials. V433M and W12G variants were genotyped in TONIC (n = 155) and PIVENS (n = 213) DNA samples. The relationships between CYP4F2 genotypes, plasma α-tocopherol levels at baseline and weeks 48 (w48) and 96 (w96) and histological end points (overall improvement in liver histology and resolution of NASH) were investigated. As a result, the V433M genotype was significantly associated with baseline plasma α-tocopherol in the TONIC trial (p = 0.004), but not in PIVENS. Among those receiving Vit E treatment, CYP4F2 V433M genotype was associated with significantly decreased plasma α-tocopherol levels at w48 (p = 0.003 for PIVENS and p = 0.026 for TONIC) but not at w96. The w96 α-tocopherol level was significantly associated with resolution of NASH (p = 0.006) and overall histology improvement (p = 0.021)in the PIVENS, but not in the TONIC trial. There was no significant association between CYP4F2 genotypes and histological end points in either trial. Our study suggested the a moderate role of CYP4F2 polymorphisms in affecting the pharmacokinetics of Vit E as a therapeutic agent. In addition, there may be age-dependent relationship between CYP4F2 genetic variability and Vit E pharmacokinetics in NAFLD.

α-Tocopherol status and altered expression of α-tocopherol-related proteins in streptozotocin-induced type 1 diabetes in rat models.

Vitamin E plays a critical role as an antioxidant in several pathological conditions, including diabetes, cancer, cardiovascular diseases, and neurodegenerative disorders. Diabetes is a metabolic disorder of glucose due to the lack of adequate insulin production (type 1) or peripheral insulin resistance (type 2). Oxidative stress plays a major role in the pathogenesis of diabetes and its complications. The purpose of the present study was to determine α-tocopherol status and the expression of α-tocopherol-related proteins, including binding proteins and metabolizing enzymes, under streptozotocin (STZ)-induced type 1 diabetes in rat models. In STZ rats, plasma α-tocopherol levels decreased compared to the control rats, whereas hepatic α-tocopherol levels in the STZ rats were significantly increased. CuZn-superoxide dismutase (SOD) gene expression in the liver of STZ rats was markedly decreased, whereas Mn-SOD gene expression remained unaltered. Accelerated lipid peroxidation in the liver of STZ rats was observed and the hepatic expression of α-tocopherol transfer protein (α-TTP) in STZ rats decreased compared to that in the controls. The hepatic expression of cytochrome P450 4F2 (CYP4F2) and CYP3A2 genes in STZ rats also decreased. The reduced expression of hepatic α-TTP and CYP4F2 genes probably leads to decreased plasma α-tocopherol levels and elevated α-tocopherol levels in the liver of STZ rats. The altered expression of hepatic α-tocopherol-related proteins might regulate α-tocopherol status in type 1 diabetes. Determining the mechanism of modulating α-tocopherol status may be helpful in promoting antioxidant therapy in diabetes.

Liver X receptor up-regulates α-tocopherol transfer protein expression and α-tocopherol status

Fat-soluble vitamin E (α-tocopherol) has antioxidant activity. α-Tocopherol transfer protein (α-TTP), a hepatic cytosolic protein, selectively binds α-tocopherol and has an important role regulating circulatory α-tocopherol levels. However, only a few studies have shown the transcriptional regulation of the α-TTP gene. Here, we demonstrate that liver X receptor (LXR) regulates α-TTP expression through direct interaction with the α-TTP gene promoter, and it modulates circulating α-tocopherol levels. LXR belongs to the nuclear receptor superfamily, acts as a ligand-dependent transcription factor for oxysterols and plays an important role in cholesterol metabolism and lipogenesis. We identified an LXR response element (LXRE; DR4, a direct repeat with four-nucleotides spacing) of the human α-TTP gene promoter by using luciferase and electrophoretic mobility shift assays. Mutations in this element abolished activation of this promoter. Moreover, treatment of vitamin E-deficient rats with T0901317, a synthetic LXR ligand, increased α-TTP expression in the liver and cerebrum and increased the plasma α-tocopherol levels. These results indicate that the LXR signaling pathway modulates α-TTP gene expression and plasma α-tocopherol levels. Our observations imply that the LXR signaling pathway might be a useful target for antioxidant properties by controlling the vitamin E status.

Gastric Digestion of Raw and Roasted Almonds In Vivo

Almonds are an important dietary source of lipids, protein, and α-tocopherol. It has been demonstrated that the physical form of almond kernels influences their digestion and absorption, but the role of thermal processes on the digestion of almonds has received little attention. The objectives of this study were to examine the gastric emptying and nutrient composition of gastric chyme from pigs (used as a model for the adult human) fed a single meal of either raw or roasted almonds over a 12-h postprandial period (72 pigs total, 6 pigs at each diet-time combination). Concentrations of glucose, triacylglycerols, and α-tocopherol in peripheral plasma during the 12-h postprandial period were determined. For dry matter and lipid, the gastric emptying profile was not different between raw and roasted almonds. Roasting almonds also did not influence gastric pH, or plasma glucose or triacylglycerols levels. In contrast, the gastric emptying of protein was more rapid for raw almonds compared to roasted almonds (P < 0.01) and intragastric protein content exhibited segregation (P < 0.001) throughout the stomach, with raw almonds having a higher level of segregation compared to roasted almonds. Postprandial plasma α-tocopherol levels were, on average 33% greater (P < 0.001) after consumption of raw almonds, most likely as a result of the higher concentration of α-tocopherol in raw almonds compared to roasted almonds. Roasting of almonds did not influence the overall gastric emptying process, but did lead to differences in the distribution of protein in the stomach and to the gastric emptying of protein.

Low Plasma α-Tocopherol Concentrations and Adverse Clinical Outcomes in Diabetic Hemodialysis Patients

Trials with the antioxidant vitamin E have failed to show benefit in the general population. Considering the different causes of death in ESRD, this study investigated the association between plasma concentrations of α-tocopherol and specific clinical outcomes in diabetic hemodialysis patients. In 1046 diabetic hemodialysis patients (participants of the German Diabetes and Dialysis Study), α-tocopherol was measured in plasma by reversed-phase HPLC. By Cox regression analyses, hazard ratios were determined for prespecified end points according to baseline plasma α-tocopherol levels: sudden death (n=134), myocardial infarction (n=172), stroke (n=89), combined cardiovascular events (n=398), fatal infection (n=107), and all-cause mortality (n=508). Patients had a mean age of 66±8 years, and mean plasma α-tocopherol level was 22.8±9.6 µmol/L. Levels of α-tocopherol were highly correlated to triglycerides (r=0.63, P<0.001). Patients in the lowest α-tocopherol quartile had (in unadjusted analyses) a 79% higher risk of stroke and a 31% higher risk of all-cause mortality compared with patients in the highest quartile. The associations were attenuated after adjustment for confounders (hazard ratiostroke=1.56, 95% confidence interval=0.75-3.25; hazard ratiomortality=1.22, 95% confidence interval=0.89-1.69, respectively). There was no association between α-tocopherol and myocardial infarction, sudden death, or infectious death. Plasma α-tocopherol concentrations were not independently associated with cardiovascular outcomes, infectious deaths, or all-cause mortality in diabetic hemodialysis patients. The lack of association can partly be explained by a confounding influence of malnutrition, which should be considered in the planning of trials to reduce cardiovascular risk in dialysis patients.