Dietary Vitamin E Intake Was Inversely Associated with Hyperuricemia in US Adults: NHANES 2009-2014

Lixia Zhang, Xiaoyan Shi, Jinran Yu, Peipei Zhang, Ping Ma, Yongye Sun

Ann Nutr Metab . 2020 Sep 21;1-7. doi: 10.1159/000509628. Online ahead of print.


Introduction: Current evidence on the association between dietary vitamin E intake and hyperuricemia risk is limited and conflicting.

Objective: The aim of the study was to assess the association of dietary vitamin E intake with hyperuricemia in US adults.

Methods: We conducted a cross-sectional study using data from the National Health and Nutrition Examination Survey, 2009-2014. Dietary vitamin E intake was evaluated through two 24-h dietary recall interviews. Logistic regression and restricted cubic spline models were used to examine the association between dietary vitamin E intake and hyperuricemia.

Results: Overall, 12,869 participants were included. The prevalence of hyperuricemia was 19.35%. After adjustment for age, gender, BMI, race, educational level, smoking status, alcohol consumption, physical activity, total daily energy intake, total cholesterol, protein intake, glomerular filtration rate, serum Cr, use of uric acid drugs, and drug abuse, the odds ratio (95% confidence interval) of hyperuricemia for the highest tertile of dietary vitamin E intake was 0.77 (0.63-0.96) compared with that of the lowest tertile. In men, dietary vitamin E intake and hyperuricemia were negatively correlated. In stratified analyses by age (20-39, 40-59, and ≥60 years), dietary vitamin E intake was inversely associated with hyperuricemia only among participants aged ≥60 years. Dose-response analyses showed that dietary vitamin E intake was inversely associated with hyperuricemia in a nonlinear manner.

Conclusion: Dietary vitamin E intake was negatively correlated with hyperuricemia in US adults, especially among males and participants aged ≥60 years.

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Vitamin E is necessary for zebrafish nervous system development

Brian Head, Jane La Du, Robyn L Tanguay, Chrissa Kioussi, Maret G Traber

Sci Rep . 2020 Sep 21;10(1):15028. doi: 10.1038/s41598-020-71760-x.


Vitamin E (VitE) deficiency results in embryonic lethality. Knockdown of the gene ttpa encoding for the VitE regulatory protein [α-tocopherol transfer protein (α-TTP)] in zebrafish embryos causes death within 24 h post-fertilization (hpf). To test the hypothesis that VitE, not just α-TTP, is necessary for nervous system development, adult 5D strain zebrafish, fed either VitE sufficient (E+) or deficient (E-) diets, were spawned to obtain E+ and E- embryos, which were subjected to RNA in situ hybridization and RT-qPCR. Ttpa was expressed ubiquitously in embryos up to 12 hpf. Early gastrulation (6 hpf) assessed by goosecoid expression was unaffected by VitE status. By 24 hpf, embryos expressed ttpa in brain ventricle borders, which showed abnormal closure in E- embryos. They also displayed disrupted patterns of paired box 2a (pax2a) and SRY-box transcription factor 10 (sox10) expression in the midbrain-hindbrain boundary, spinal cord and dorsal root ganglia. In E- embryos, the collagen sheath notochord markers (col2a1a and col9a2) appeared bent. Severe developmental errors in E- embryos were characterized by improper nervous system patterning of the usually carefully programmed transcriptional signals. Histological analysis also showed developmental defects in the formation of the fore-, mid- and hindbrain and somites of E- embryos at 24 hpf. Ttpa expression profile was not altered by the VitE status demonstrating that VitE itself, and not ttpa, is required for development of the brain and peripheral nervous system in this vertebrate embryo model.

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Interaction between and impact of IL-6 genotype and alpha-tocopherol levels on periodontal condition in aging individuals

Akihiro Yoshihara, Noboru Kaneko, Akane Miyamoto, Kaname Nohno

J Periodontal Res . 2020 Sep 20. doi: 10.1111/jre.12802. Online ahead of print.


Background and objectives: Few studies have assessed the possible interaction between and impact of IL-6 variants and serum α-tocopherol levels on periodontal condition in older individuals. Here, we assessed the relationship between IL-6 variants and serum α-tocopherol levels on periodontal condition by considering effect modification.

Material and methods: Among the study participants, 359 who were 71 years of age underwent a dental examination, biochemical analysis, and interview. After dividing the participants into tertiles based on serum α-tocopherol levels, we conducted Poisson regression analysis to compare the prevalence rate ratio (PRR) for periodontal disease markers with the IL-6 genotype (rs1800796) based on each tertile adjusted by the number of teeth present (offset).

Results: The PRRs of the IL-6 genotype for periodontal condition (probing pocket depth [PPD], clinical attachment level [CAL], and bleeding on probing [BOP]) which were adjusted by the number of teeth present (offset) were 1.17 (P < .001), 1.37 (P < .001), and 1.08 (P = .048), respectively. In addition, a significant association was found between the reciprocal number of PRRs of the IL-6 genotype and three serum α-tocopherol levels. The adjusted PRRs (± standard error) of the IL-6 genotypes for PPD were 0.48 (0.12) for the first group (P < .001), 1.54 (0.04) for the second group (P < .001), and 2.11 (0.03) for the third group (P < .001); similar tendencies were seen for CAL and BOP.

Conclusion: The results of this study suggest a potential association between the IL-6 genotype and periodontal condition in relation to serum antioxidant concentrations.

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Pentoxifylline and tocopherol protocol to treat medication-related osteonecrosis of the jaw: A systematic literature review

Rafael Correia Cavalcante, Guilherme Tomasetti

J Craniomaxillofac Surg . 2020 Sep 18;S1010-5182(20)30206-7. doi: 10.1016/j.jcms.2020.09.008. Online ahead of print.


Purpose: Medication-related osteonecrosis of the jaw (MRONJ) is a previously described debilitating condition in which patients experience progressive bone destruction in the maxilla and/or mandible after exposure to certain drugs. Clinical management of MRONJ remains controversial, with no established guidelines. The aim of our study was to conduct a literature review on the effectiveness of pentoxifylline (PTX) and tocopherol (PENTO protocol) on MRONJ.

Study design: A literature review was conducted, using two different scientific databases, to evaluate the effects of PTX and tocopherol on MRONJ.

Discussion: PENTO protocol prescription to treat MRONJ was reported to be well tolerated, with minimal side-effects, and non-expensive when compared with other non-surgical treatment modalities. It was shown to relieve painful symptoms in all patients, and significant new bone formation was observed at final follow-up.

Conclusion: Observational and case-series studies have demonstrated that pentoxifylline and tocopherol are potentially useful in the non-surgical management of MRONJ.

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Vitamin C and E Treatment Blunts Sprint Interval Training-Induced Changes in Inflammatory Mediator-, Calcium-, and Mitochondria-Related Signaling in Recreationally Active Elderly Humans

Victoria L Wyckelsma, Tomas Venckunas, Marius Brazaitis, Stefano Gastaldello, Audrius Snieckus, Nerijus Eimantas, Neringa Baranauskiene, Andrejus Subocius, Albertas Skurvydas, Mati Pääsuke, Helena Gapeyeva, Priit Kaasik, Reedik Pääsuke, Jaak Jürimäe, Brigitte A Graf, Bengt Kayser, Nicolas Place, Daniel C Andersson, Sigitas Kamandulis, Håkan Westerblad

Antioxidants (Basel) . 2020 Sep 17;9(9):E879. doi: 10.3390/antiox9090879.


Sprint interval training (SIT) has emerged as a time-efficient training regimen for young individuals. Here, we studied whether SIT is effective also in elderly individuals and whether the training response was affected by treatment with the antioxidants vitamin C and E. Recreationally active elderly (mean age 65) men received either vitamin C (1 g/day) and vitamin E (235 mg/day) or placebo. Training consisted of nine SIT sessions (three sessions/week for three weeks of 4-6 repetitions of 30-s all-out cycling sprints) interposed by 4 min rest. Vastus lateralis muscle biopsies were taken before, 1 h after, and 24 h after the first and last SIT sessions. At the end of the three weeks of training, SIT-induced changes in relative mRNA expression of reactive oxygen/nitrogen species (ROS)- and mitochondria-related proteins, inflammatory mediators, and the sarcoplasmic reticulum Ca2+ channel, the ryanodine receptor 1 (RyR1), were blunted in the vitamin treated group. Western blots frequently showed a major (>50%) decrease in the full-length expression of RyR1 24 h after SIT sessions; in the trained state, vitamin treatment seemed to provide protection against this severe RyR1 modification. Power at exhaustion during an incremental cycling test was increased by ~5% at the end of the training period, whereas maximal oxygen uptake remained unchanged; vitamin treatment did not affect these measures. In conclusion, treatment with the antioxidants vitamin C and E blunts SIT-induced cellular signaling in skeletal muscle of elderly individuals, while the present training regimen was too short or too intense for the changes in signaling to be translated into a clear-cut change in physical performance.

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Effect of vitamin E on low density lipoprotein oxidation at lysosomal pH

Hadeel K M Alboaklah, David S Leake

Free Radic Res . 2020 Sep 16;1-11. doi: 10.1080/10715762.2020.1817912. Online ahead of print.


Many cholesterol-laden foam cells in atherosclerotic lesions are macrophages and much of their cholesterol is present in their lysosomes and derived from low density lipoprotein (LDL). LDL oxidation has been proposed to be involved in the pathogenesis of atherosclerosis. We have shown previously that LDL can be oxidised in the lysosomes of macrophages. α-Tocopherol has been shown to inhibit LDL oxidation in vitro, but did not protect against cardiovascular disease in large clinical trials. We have therefore investigated the effect of α-tocopherol on LDL oxidation at lysosomal pH (about pH 4.5). LDL was enriched with α-tocopherol by incubating human plasma with α-tocopherol followed by LDL isolation by ultracentrifugation. The α-tocopherol content of LDL was increased from 14.4 ± 0.2 to 24.3 ± 0.3 nmol/mg protein. LDL oxidation was assessed by measuring the formation of conjugated dienes at 234 nm and oxidised lipids (cholesteryl linoleate hydroperoxide and 7-ketocholesterol) by HPLC. As expected, LDL enriched with α-tocopherol was oxidised more slowly than control LDL by Cu2+ at pH 7.4, but was not protected against oxidation by Cu2+ or Fe3+ or a low concentration of Fe2+ at pH 4.5 (it was sometimes oxidised faster by α-tocopherol with Cu2+ or Fe3+ at pH 4.5). α-Tocopherol-enriched LDL reduced Cu2+ and Fe3+ into the more pro-oxidant Cu+ and Fe2+ faster than did control LDL at pH 4.5. These findings might help to explain why the large clinical trials of α-tocopherol did not protect against cardiovascular disease.

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Brain α-Tocopherol Concentration and Stereoisomer Profile Alter Hippocampal Gene Expression in Weanling Mice

Justin S Rhodes, Catarina Rendeiro, Jonathan G Mun, Kristy Du, Pragya Thaman, Amanda Snyder, Heinrich Pinardo, Jenny Drnevich, Sriram Chandrasekaran, Chron-Si Lai, Karen J Schimpf, Matthew J Kuchan

J Nutr . 2020 Sep 16;nxaa249. doi: 10.1093/jn/nxaa249. Online ahead of print.


Background: Alpha-tocopherol (αT), the bioactive constituent of vitamin E, is essential for fertility and neurological development. Synthetic αT (8 stereoisomers; all rac-αT) is added to infant formula at higher concentrations than natural αT (RRR-αT only) to adjust for bio-potency differences, but its effects on brain development are poorly understood.

Objectives: The objective was to determine the impact of bio-potency-adjusted dietary all rac-αT versus RRR-αT, fed to dams, on the hippocampal gene expression in weanling mice.

Methods: Male/female pairs of C57BL/6J mice were fed AIN 93-G containing RRR-αT (NAT) or all rac-αT (SYN) at 37.5 or 75 IU/kg (n = 10/group) throughout gestation and lactation. Male pups were euthanized at 21 days. Half the brain was evaluated for the αT concentration and stereoisomer distribution. The hippocampus was dissected from the other half, and RNA was extracted and sequenced. Milk αT was analyzed in separate dams.

Results: A total of 797 differentially expressed genes (DEGs) were identified in the hippocampi across the 4 dietary groups, at a false discovery rate of 10%. Comparing the NAT-37.5 group to the NAT-75 group or the SYN-37.5 group to the SYN-75 group, small differences in brain αT concentrations (10%; P < 0.05) led to subtle changes (<10%) in gene expression of 600 (NAT) or 487 genes (SYN), which were statistically significant. Marked differences in brain αT stereoisomer profiles (P < 0.0001) had a small effect on fewer genes (NAT-37.5 vs. SYN-37.5, 179; NAT-75 vs. SYN-75, 182). Most of the DEGs were involved in transcription regulation and synapse formation. A network analysis constructed around known vitamin E interacting proteins (VIPs) revealed a group of 32 DEGs between NAT-37.5 vs. SYN-37.5, explained by expression of the gene for the VIP, protein kinase C zeta (Pkcz).

Conclusions: In weanling mouse hippocampi, a network of genes involved in transcription regulation and synapse formation was differentially affected by dam diet αT concentration and source: all rac-αT or RRR-αT.

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Protective effect of vitamin E on sperm quality and in vitro fertilizing potential and testosterone concentration in polyvinyl chloride treated male rats

Abbas Sadeghi, Farah Farokhi, Ali Shalizar-Jalali, Gholamreza Najafi

Vet Res Forum . Summer 2020;11(3):257-263. doi: 10.30466/vrf.2019.91184.2206. Epub 2020 Sep 15.


Polyvinyl chloride (PVC) has toxic effects through the induction of oxidative stress in the body and testicles. Vitamin E (Vit E) is a dietary compound that functions as an antioxidant scavenging toxic free radicals. The present study aimed to probe the protective effect of Vit E against PVC-induced reprotoxicity in male rats. In this experimental study, 24 male rats were randomly divided into four groups (n=6) including control, Vit E (150 mg kg-1 per day; orally), PVC (1000 mg kg-1 per day; orally) and PVC + Vit E. After 40 days, rats were euthanized and epididymal sperms characteristics, embryo development and malondialdehyde (MDA) and testosterone levels were examined. The PVC decreased sperm count, motility and viability as well as testosterone level and increased sperms with damaged chromatin in comparison with controls. Also, the percentages of fertilization, two-cell embryos and blastocysts as well as MDA levels were decreased in PVC-treated rats. However, Vit E improved PVC-induced alterations in aforesaid parameters. The results indicated that PVC can reduce fertility potential in male rats probably through androgen and sperm quality and quantity reductions, while Vit E can exert protective effects in PVC-related reproductive toxicities.

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Reply “Comment on: Food for Bone: Evidence for a Role for Delta-Tocotrienol in the Physiological Control of Osteoblast Migration. Int. J. Mol. Sci. 2020, 21, 4661”

Lavinia Casati, Francesca Pagani, Roberto Maggi, Francesco Ferrucci, Valeria Sibilia

Int J Mol Sci . 2020 Sep 12;21(18):E6675. doi: 10.3390/ijms21186675.

Dear Editor,
We have carefully read the Letter to the Editor by Pang and Chin related to our paper entitled “Food for bone: evidence for a role for delta-tocotrienol in the physiological control of osteoblast migration” [1] published in the International Journal of Molecular Science.
We have some issues regarding the points raised by the authors.
  • The paper from Shen and colleagues 2018 [2] clearly shows the effect of dietary supplementation of tocotrienol in the suppression of bone resorption, probably mediated by the reduction of oxidative stress. Our statement “osteoporosis has been correlated with low intake, and serum levels of TTs” refers to this paper. We disagree with the authors that “dietary tocotrienol level has not been shown to correlate with bone health, probably due to the absence of a reliable dietary questionnaire that could assess the tocotrienol intake”, since Shen and colleagues (2018) have reported that a 12 week annatto-derived tocotrienol supplementation, previously used to examine the effects of tocotrienol on bone turnover, resulted in a significant increase in serum delta-tocotrienol levels in postmenopausal osteoporotic women [2].

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Comment on: Food for Bone: Evidence for a Role for Delta-Tocotrienol in the Physiological Control of Osteoblast Migration. Int. J. Mol. Sci. 2020, 21, 4661

Kok-Lun Pang, Kok-Yong Chin

Int J Mol Sci . 2020 Sep 12;21(18):E6674. doi: 10.3390/ijms21186674.

Dear Editor,
We applaud the innovative work by Casati et al., which explored the effects of delta-tocotrienol (δ-TT) in promoting osteoblast migration [1]. Vitamin E is reported as a nutrient important for maintaining bone health in epidemiological studies [2]. However, the statement “osteoporosis has been correlated with low intake, and serum levels of TTs” is inaccurate because dietary tocotrienol level has not been shown to correlate with bone health, probably due to the absence of a reliable dietary questionnaire that could assess the tocotrienol intake. Nevertheless, there is an abundance of preclinical evidence on the beneficial skeletal effects of tocotrienol. Most in vitro studies focus on the differentiation of osteoblasts, while the animal studies used bone cellular histomorphometry to quantify the bone cells in osteopenic rats treated with tocotrienol [3,4]. The work by Casati et al. is the first that focuses on the influence of tocotrienol on osteoblast migration, which plays an essential role in fracture healing. More accurately, mesenchymal stem cells migrated to the fracture site during fibrovascular phase and callus formation will differentiate into osteoblasts and perform bone formation [5]. A previous study also showed that particles incorporated with annatto tocotrienol rich in δ-TT could enhance callus strength of male rats with long bone fracture fixed with plate and screws [6]. The finding of δ-TT enhances the transcriptional activities of β-catenin also echoes our previous study, which demonstrated that annatto tocotrienol supplementation (60 mg/kg/day for 2 months) increased beta-catenin gene expression in the bone of orchidectomized rats [7].