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Association of measures of body fat with serum alpha-tocopherol and its metabolites in middle-aged individuals.
Meulmeester, FL, Luo, J, Martens, LG, Ashrafi, N, de Mutsert, R, Mook-Kanamori, DO, Lamb, HJ, Rosendaal, FR, Willems van Dijk, K, Mills, K, et al
Nutrition, metabolism, and cardiovascular diseases : NMCD. 2021;(8):2407-2415
Abstract
BACKGROUND AND AIMS The accumulation of fat increases the formation of lipid peroxides, which are partly scavenged by alpha-tocopherol (α-TOH). Here, we aimed to investigate the associations between different measures of (abdominal) fat and levels of urinary α-TOH metabolites in middle-aged individuals. METHODS AND RESULTS In this cross-sectional analysis in the Netherlands Epidemiology of Obesity study (N = 511, 53% women; mean [SD] age of 55 [6.1] years), serum α-TOH and α-TOH metabolites from 24-h urine were measured as alpha-tocopheronolactone hydroquinone (α-TLHQ, oxidized) and alpha-carboxymethyl-hydroxychroman (α-CEHC, enzymatically converted) using liquid-chromatography-tandem mass spectrometry. Body mass index and total body fat were measured, and abdominal subcutaneous and visceral adipose tissue (aSAT and VAT) were assessed using magnetic resonance imaging. Using multivariable-adjusted linear regression analyses, we analysed the associations of BMI, TBF, aSAT and VAT with levels of urinary α-TOH metabolites, adjusted for confounders. We observed no evidence for associations between body fat measures and serum α-TOH. Higher BMI and TBF were associated with lower urinary levels of TLHQ (0.95 [95%CI: 0.90, 1.00] and 0.94 [0.88, 1.01] times per SD, respectively) and with lower TLHQ relative to CEHC (0.93 [0.90, 0.98] and 0.93 [0.87, 0.98] times per SD, respectively). We observed similar associations for VAT (TLHQ: 0.94 [0.89, 0.99] times per SD), but not for aSAT. CONCLUSIONS Opposite to our research hypothesis, higher abdominal adiposity was moderately associated with lower levels of oxidized α-TOH metabolites, which might reflect lower vitamin E antioxidative activity in individuals with higher abdominal fat instead.
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Evaluation the Effects of Alpha-tocopherol in Comparison with N-acetylcystein for Prevention of Contrast Induced Nephropathy (CIN) in CKD Patients.
Samadi, K, Naghibi, M, Shabestari, M, Sharifipour, F, Khajeh Dalooee, M, Raeesi, V, Moosavi Nik, S, Samadi, M
Iranian journal of kidney diseases. 2020;(1):26-30
Abstract
INTRODUCTION Contrast induced nephropathy (CIN), a well-known complication of using radio contrast media, dramatically increases the likelihood of patient morbidity and mortality following coronary angiography. As there is no specific treatment for CIN, prevention could be the best strategy to address this issue. Since now, the only approved preventing strategy was hydration with normal saline while antioxidant agents as a new yet unapproved remedy for this purpose could be applied .The present study was conducted to examine the effect of alpha tocopherol in CIN prevention. METHODS This prospective controlled trial was carried out on 201 patients with chronic kidney disease (eGFR < 60 cc/min) underwent coronary angiography. We assigned three groups of CKD patients: 72 patients who received prophylaxis administration with isotonic saline (Group A), 66 patients with isotonic saline plus N-acetylcysteine (1200mg twice a day) for 2 days (Group B) and 63 patients who received isotonic saline plus daily alpha tocopherol (600 IU once daily from one day before till 2 days after angiography) for 4 days (Group C). The contrast media in all three groups was nonionic iso-osmolal agent, Visipaque. RESULTS Even though CIN didn't developed in any of the three aforementioned groups but there was statistically significant reduction in eGFR from baseline in all three groups (P < .001). Moreover, We found no statistically significant difference in GFR reduction between three studied groups. CONCLUSION Administration of alpha tocopherol has no additive beneficial effect over isotonic saline in CIN prevention in CKD patients.
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Associations of α- and γ-tocopherol during early life with lung function in childhood.
Kumar, R, Ferrie, RP, Balmert, LC, Kienzl, M, Rifas-Shiman, SL, Gold, DR, Sordillo, JE, Kleinman, K, Camargo, CA, Litonjua, AA, et al
The Journal of allergy and clinical immunology. 2020;(6):1349-1357.e3
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Abstract
BACKGROUND Tocopherol isoforms may regulate child lung growth and spirometric measures. OBJECTIVE 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. METHODS 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. RESULTS 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. CONCLUSION 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.
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AS03-Adjuvanted H5N1 Avian Influenza Vaccine Modulates Early Innate Immune Signatures in Human Peripheral Blood Mononuclear Cells.
Howard, LM, Goll, JB, Jensen, TL, Hoek, KL, Prasad, N, Gelber, CE, Levy, SE, Joyce, S, Link, AJ, Creech, CB, et al
The Journal of infectious diseases. 2019;(11):1786-1798
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BACKGROUND Adjuvant System 03 (AS03) markedly enhances responses to influenza A/H5N1 vaccines, but the mechanisms of this enhancement are incompletely understood. METHODS Using ribonucleic acid sequencing on peripheral blood mononuclear cells (PBMCs) from AS03-adjuvanted and unadjuvanted inactivated H5N1 vaccine recipients, we identified differentially expressed genes, enriched pathways, and genes that correlated with serologic responses. We compared bulk PBMC findings with our previously published assessments of flow-sorted immune cell types. RESULTS AS03-adjuvanted vaccine induced the strongest differential signals on day 1 postvaccination, activating multiple innate immune pathways including interferon and JAK-STAT signaling, Fcγ receptor (FcγR)-mediated phagocytosis, and antigen processing and presentation. Changes in signal transduction and immunoglobulin genes predicted peak hemagglutinin inhibition (HAI) titers. Compared with individual immune cell types, activated PBMC genes and pathways were most similar to innate immune cells. However, several pathways were unique to PBMCs, and several pathways identified in individual cell types were absent in PBMCs. CONCLUSIONS Transcriptomic analysis of PBMCs after AS03-adjuvanted H5N1 vaccination revealed early activation of innate immune signaling, including a 5- to 8-fold upregulation of FcγR1A/1B/1C genes. Several early gene responses were correlated with HAI titer, indicating links with the adaptive immune response. Although PBMCs and cell-specific results shared key innate immune signals, unique signals were identified by both approaches.
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Comparing the effects of vitamin E tocotrienol-rich fraction supplementation and α-tocopherol supplementation on gene expression in healthy older adults.
Ghani, SMA, Goon, JA, Azman, NHEN, Zakaria, SNA, Hamid, Z, Ngah, WZW
Clinics (Sao Paulo, Brazil). 2019;:e688
Abstract
OBJECTIVES This study aims to compare the differential gene expression resulting from tocotrienol-rich fraction and α-tocopherol supplementation in healthy older adults. METHODS A total of 71 eligible subjects aged 50 to 55 years from Gombak and Kuala Lumpur, Malaysia, were divided into three groups and supplemented with placebo (n=23), α-tocopherol (n=24) or tocotrienol-rich fraction (n=24). Blood samples were collected at baseline and at 3 and 6 months of supplementation for microarray analysis. RESULTS The number of genes altered by α-tocopherol was higher after 6 months (1,410) than after 3 months (273) of supplementation. α-Tocopherol altered the expression of more genes in males (952) than in females (731). Similarly, tocotrienol-rich fraction modulated the expression of more genes after 6 months (1,084) than after 3 months (596) and affected more genes in males (899) than in females (781). α-Tocopherol supplementation modulated pathways involving the response to stress and stimuli, the immune response, the response to hypoxia and bacteria, the metabolism of toxins and xenobiotics, mitosis, and synaptic transmission as well as activated the mitogen-activated protein kinase and complement pathways after 6 months. However, tocotrienol-rich fraction supplementation affected pathways such as the signal transduction, apoptosis, nuclear factor kappa B kinase, cascade extracellular signal-regulated kinase-1 and extracellular signal-regulated kinase-2, immune response, response to drug, cell adhesion, multicellular organismal development and G protein signaling pathways. CONCLUSION Supplementation with either α-tocopherol or tocotrienol-rich fraction affected the immune and drug response and the cell adhesion and signal transduction pathways but modulated other pathways differently after 6 months of supplementation, with sex-specific responses.
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Multiple Micronutrient Powder Reduces Vitamin E Deficiency in Brazilian Children: A Pragmatic, Controlled Clinical Trial.
M C Lobo, L, M Schincaglia, R, G Peixoto, MDR, C M Hadler, MC
Nutrients. 2019;(11)
Abstract
Multiple micronutrient powder supplementation is a health promotion strategy, but data on its effectiveness regarding vitamin E are rare. The objective was to evaluate the impact of home fortification with powdered micronutrients on α-tocopherol concentrations, growth, and inflammation in Brazilian children aged 6-15 months. This is a pragmatic, controlled clinical trial, in which the intervention group received micronutrient powder sachets for up to 3 months. Vitamin E deficiency was considered when α-tocopherol was less than 11.6 µmol/L. The Poisson regression model was used to estimate adjusted values for prevalence ratios (PR) for the outcome variable. A total of 224 children participated in the study. The intervention group had a higher median α-tocopherol level (17.2 versus 3.6 µmol/L; p < 0.001) and an 82.0% reduction in the prevalence of vitamin deficiency (PR = 0.18; 95% CI 0.11-0.30) when compared with the control group. Consumption of multiple micronutrients in powder increases serum α-tocopherol concentrations, promotes better linear growth, and reduces morbidity in children.
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Metabolic syndrome increases dietary α-tocopherol requirements as assessed using urinary and plasma vitamin E catabolites: a double-blind, crossover clinical trial.
Traber, MG, Mah, E, Leonard, SW, Bobe, G, Bruno, RS
The American journal of clinical nutrition. 2017;(3):571-579
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Background: Vitamin E supplementation improves liver histology in patients with nonalcoholic steatohepatitis, which is a manifestation of the metabolic syndrome (MetS). We reported previously that α-tocopherol bioavailability in healthy adults is higher than in those with MetS, thereby suggesting that the latter group has increased requirements.Objective: We hypothesized that α-tocopherol catabolites α-carboxyethyl hydroxychromanol (α-CEHC) and α-carboxymethylbutyl hydroxychromanol (α-CMBHC) are useful biomarkers of α-tocopherol status.Design: Adults (healthy or with MetS; n = 10/group) completed a double-blind, crossover clinical trial with four 72-h interventions during which they co-ingested 15 mg hexadeuterium-labeled RRR-α-tocopherol (d6-α-T) with nonfat, reduced-fat, whole, or soy milk. During each intervention, we measured α-CEHC and α-CMBHC excretions in three 8-h urine collections (0-24 h) and plasma α-tocopherol, α-CEHC, and α-CMBHC concentrations at various times ≤72 h.Results: During the first 24 h, participants with MetS compared with healthy adults excreted 41% less α-CEHC (all values are least-squares means ± SEMs: 0.6 ± 0.1 compared with 1.0 ± 0.1 μmol/g creatinine, respectively; P = 0.002), 63% less hexadeuterium-labeled (d6)-α-CEHC (0.04 ± 0.02 compared with 0.13 ± 0.02 μmol/g creatinine, respectively; P = 0.002), and 58% less d6-α-CMBHC (0.017 ± 0.004 compared with 0.041 ± 0.004 μmol/g creatinine, respectively; P = 0.0009) and had 52% lower plasma d6-α-CEHC areas under the concentration curves [area under the curve from 0 to 24 h (AUC0-24h): 27.7 ± 7.9 compared with 58.4 ± 7.9 nmol/L × h, respectively; P = 0.01]. d6-α-CEHC peaked before d6-α-T in 77 of 80 paired plasma concentration curves. Urinary d6-α-CEHC 24-h concentrations were associated with the plasma AUC0-24 h of d6-α-T (r = 0.53, P = 0.02) and d6-α-CEHC (r = 0.72, P = 0.0003), and with urinary d6-α-CMBHC (r = 0.88, P < 0.0001), and inversely with the plasma inflammation biomarkers C-reactive protein (r = -0.70, P = 0.0006), interleukin-10 (r = -0.59, P = 0.007), and interleukin-6 (r = -0.54, P = 0.01).Conclusion: Urinary α-CEHC and α-CMBHC are useful biomarkers to noninvasively assess α-tocopherol adequacy, especially in populations with MetS-associated hepatic dysfunction that likely impairs α-tocopherol trafficking. This trial was registered at clinicaltrials.gov as NCT01787591.
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Associations between Specific Redox Biomarkers and Age in a Large European Cohort: The MARK-AGE Project.
Weber, D, Stuetz, W, Toussaint, O, Debacq-Chainiaux, F, Dollé, MET, Jansen, E, Gonos, ES, Franceschi, C, Sikora, E, Hervonen, A, et al
Oxidative medicine and cellular longevity. 2017;:1401452
Abstract
Oxidative stress and antioxidants play a role in age-related diseases and in the aging process. We here present data on protein carbonyls, 3-nitrotyrosine, malondialdehyde, and cellular and plasma antioxidants (glutathione, cysteine, ascorbic acid, uric acid, α-tocopherol, and lycopene) and their relation with age in the European multicenter study MARK-AGE. To avoid confounding, only data from countries which recruited subjects from all three study groups (five of eight centers) and only participants aged ≥55 years were selected resulting in data from 1559 participants. These included subjects from (1) the general population, (2) members from long-living families, and (3) their spouses. In addition, 683 middle-aged reference participants (35-54 years) served as a control. After adjustment for age, BMI, smoking status, gender, and country, there were differences in protein carbonyls, malondialdehyde, 3-nitrotyrosine, α-tocopherol, cysteine, and glutathione between the 3 study groups. Protein carbonyls and 3-nitrotyrosine as well as cysteine, uric acid, and lycopene were identified as independent biomarkers with the highest correlation with age. Interestingly, from all antioxidants measured, only lycopene was lower in all aged groups and from the oxidative stress biomarkers, only 3-nitrotyrosine was increased in the descendants from long-living families compared to the middle-aged control group. We conclude that both lifestyle and genetics may be important contributors to redox biomarkers in an aging population.
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Colorectal Adenomas in Participants of the SELECT Randomized Trial of Selenium and Vitamin E for Prostate Cancer Prevention.
Lance, P, Alberts, DS, Thompson, PA, Fales, L, Wang, F, San Jose, J, Jacobs, ET, Goodman, PJ, Darke, AK, Yee, M, et al
Cancer prevention research (Philadelphia, Pa.). 2017;(1):45-54
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Selenium and vitamin E micronutrients have been advocated for the prevention of colorectal cancer. Colorectal adenoma occurrence was used as a surrogate for colorectal cancer in an ancillary study to the Selenium and Vitamin E Cancer Prevention Trial (SELECT) for prostate cancer prevention. The primary objective was to measure the effect of selenium (as selenomethionine) on colorectal adenomas occurrence, with the effect of vitamin E (as α-tocopherol) supplementation on colorectal adenoma occurrence considered as a secondary objective. Participants who underwent lower endoscopy while in SELECT were identified from a subgroup of the 35,533 men randomized in the trial. Adenoma occurrence was ascertained from the endoscopy and pathology reports for these procedures. Relative Risk (RR) estimates and 95% confidence intervals (CI) of adenoma occurrence were generated comparing those randomized to selenium versus placebo and to vitamin E versus placebo based on the full factorial design. Evaluable endoscopy information was obtained for 6,546 participants, of whom 2,286 had 1+ adenomas. Apart from 21 flexible sigmoidoscopies, all the procedures yielding adenomas were colonoscopies. Adenomas occurred in 34.2% and 35.7%, respectively, of participants whose intervention included or did not include selenium. Compared with placebo, the RR for adenoma occurrence in participants randomized to selenium was 0.96 (95% CI, 0.90-1.02; P = 0.194). Vitamin E did not affect adenoma occurrence compared with placebo (RR = 1.03; 95% CI, 0.96-1.10; P = 0.38). Neither selenium nor vitamin E supplementation can be recommended for colorectal adenoma prevention. Cancer Prev Res; 10(1); 45-54. ©2016 AACR.
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Activated and Micronized Zeolite in the Modulation of Cellular Oxidative Stress in Mexican Smokers: A Randomized Clinical Trial.
Atitlán-Gil, A, Bretón-de la Loza, MM, Jiménez-Ortega, JC, Belefant-Miller, H, Betanzos-Cabrera, G
Revista de investigacion clinica; organo del Hospital de Enfermedades de la Nutricion. 2017;(3):146-151
Abstract
BACKGROUND Activated and micronized zeolites are used as detoxifying agents in humans. Detoxification is attributed to their ability to reduce lipid peroxidation by scavenging free radicals. OBJECTIVE To evaluate activated and micronized zeolites as modulators of cellular oxidative stress in Mexican smokers without lung diseases. METHODS Randomized clinical trial. Subjects were randomly divided into three groups: activated and micronized zeolites, n = 29; vitamin E, an accepted antioxidant, n = 29; and maltodextrin as control, n = 27. Each group received the corresponding supplementation, dissolved in water, once a day for 30 days as follows: activated and micronized zeolites, 5.4 g activated and micronized zeolite; vitamin E, 400 mg D-alpha tocopheryl acetate; and maltodextrin, 250 mg of maltodextrin. The thiobarbituric acid reactive substances assay was used to screen for lipid peroxidation. Catalase activity, plasma antioxidant capacity, and hydrogen peroxide levels were also measured. Results were analyzed by a one-way ANOVA and post hoc test of Bonferroni. RESULTS Subjects administered activated and micronized zeolites had equivalent antioxidant activities as subjects administered vitamin E. CONCLUSIONS Activated and micronized zeolites may be useful as a modulator of oxidative stress in smokers. However, inclusion of a comparison group of non-smokers would be useful in future studies to assess the degree to which zeolites reverse the oxidant stress.