The naturally occurring α-tocopherol stereoisomer RRR-α-tocopherol is predominant in the human infant brain.

Kuchan MJ, Jensen SK, Johnson EJ, Lieblein-Boff JC.

Br J Nutr. 2016 Jul;116(1):126-31. doi: 10.1017/S0007114516001719.

Abstract

α-Tocopherol is the principal source of vitamin E, an essential nutrient that plays a crucial role in maintaining healthy brain function. Infant formula is routinely supplemented with synthetic α-tocopherol, a racaemic mixture of eight stereoisomers with less bioactivity than the natural stereoisomer RRR-α-tocopherol. α-Tocopherol stereoisomer profiles have not been previously reported in the human brain. In the present study, we analysed total α-tocopherol and α-tocopherol stereoisomers in the frontal cortex (FC), hippocampus (HPC) and visual cortex (VC) of infants (n 36) who died of sudden infant death syndrome or other conditions. RRR-α-tocopherol was the predominant stereoisomer in all brain regions (P<0·0001) and samples, despite a large intra-decedent range in total α-tocopherol(5-17 μg/g). Mean RRR-α-tocopherol concentrations in FC, HPC and VC were 10·5, 6·8 and 5·5 μg/g, respectively. In contrast, mean levels of the synthetic stereoisomers were RRS, 1-1·5; RSR, 0·8-1·0; RSS, 0·7-0·9; and Σ2S 0·2-0·3 μg/g. Samples from all but two decedents contained measurable levels of the synthetic stereoisomers, but the intra-decedent variation was large. The ratio of RRR:the sum of the synthetic 2R stereoisomers (RRS+RSR+RSS) averaged 2·5, 2·3 and 2·4 in FC, HPC and VC, respectively, and ranged from 1 to at least 4·7, indicating that infant brain discriminates against synthetic 2R stereoisomers in favour of RRR. These findings reveal that RRR-α-tocopherol is the predominant stereoisomer in infant brain. These data also indicate that the infant brain discriminates against the synthetic 2R stereoisomers, but is unable to do so completely. On the basis of these findings, investigation into the impact of α-tocopherol stereoisomers on neurodevelopment is warranted.

Kim SK, Im GJ, An YS, Lee SH, Jung HH, Park SY.

Int J Pediatr Otorhinolaryngol. 2016 Jul;86:9-14. doi: 10.1016/j.ijporl.2016.04.008.

Abstract

Alpha-tocopherol is a class of methylated phenols, known as fat-soluble antioxidants, and is a different form of vitamin E, which reduces free radicals and acts as an antioxidant. We hypothesized that the antioxidative effect of α-tocopherol could protect against cisplastin-induced cytotoxicity, and thus evaluated its effects on cisplatin-induced ototoxicity in HEI-OC1 auditory cells. As a result, D-α-tocopherol succinate significantly reduced a cisplatin-induced hair cell loss in HEI-OC1 cell lines. These effects were mediated by its scavenging activity against reactive oxygen species (ROS) and inhibition of apoptosis.

A Systematic Review of Global Alpha-Tocopherol Status as Assessed by Nutritional Intake Levels and Blood Serum Concentrations.

Péter S, Friedel A, Roos FF, Wyss A, Eggersdorfer M, Hoffmann K, Weber P.

Int J Vitam Nutr Res. 2016 Jul 14:1-21. [Epub ahead of print]

Abstract

The purpose of this study is to systematically review the published literature reporting vitamin E intake levels and serum concentrations in order to obtain a global overview of α-tocopherol status. Articles published between 2000 and 2012 were considered; 176 articles referring to 132 single studies were included. Applying an RDA (recommended daily allowance) of 15 mg/day and EAR (estimated average requirement) of 12 mg/day to all populations with a minimum age of 14 years, 82 and 61% of mean and median data points were below the RDA and the EAR, respectively. Regarding serum concentrations, globally 13% of the included data points were below the functional deficiency threshold concentration of 12 μmol/L, mostly for newborns and children. Several prospective observational studies suggest that a serum α-tocopherol concentration of ≥30 μmol/L has beneficial effects on human health. Of the reported study populations and subpopulations, only 21% reached this threshold globally. This systematic review suggests that the α-tocopherol status is inadequate in a substantial part of the studied populations.

Jansen E, Viezeliene D, Beekhof P, Gremmer E, Ivanov L.

Int J Mol Sci. 2016 Jul 19;17(7). pii: E1166. doi: 10.3390/ijms17071166.

Abstract

A multivitamin and mineral supplementation study of 6 weeks was conducted with male and female mice. The control group received a standard dose of vitamins and minerals of 1× the Recommended Daily Intake (RDI), whereas a second group received 3× RDI. A third group received a high dose of vitamin E (25× RDI), close to the upper limit of toxicity (UL), but still recommended and considered to be harmless and beneficial. The high dose of vitamin E caused a number of beneficial, but also adverse effects. Different biomarkers of tissue toxicity, oxidative stress related processes and inflammation were determined. These biomarkers did not change in plasma and erythrocytes to a large extent. In the liver of male mice, some beneficial effects were observed by a lower concentration of several biomarkers of inflammation. However, in the kidney of male mice, a number of biomarkers increased substantially with the higher dose of vitamin E, indicating tissue toxicity and an increased level of inflammation. Since this dose of vitamin E, which is lower than the UL, cause some adverse effects, even after a short exposure period, further studies are required to reconsider the UL for vitamin E.

Wu YM, Xue ZW, Zhang LL, Gao NM, Du XM, Zhang XY, Zhang ZH, Zhang ZG.

Adv Clin Exp Med. 2016 Jul-Aug;25(4):643-8. doi: 10.17219/acem/41191.

Abstract

Bronchial asthma is one of the world’s most common chronic disorders dangerous to human health. It has been hypothesized that the increased number of asthma sufferers may be due to changing antioxidant intake or vitamin deficiency. However, the influence of vitamins on asthma has rarely been considered. The aim of this study was to explore the effects of γ-tocopherols, a specific form of vitamin E, on asthma remission together with the possible mechanism behind the process. The cell counting results showed that γ-tocopherols possesses the capability to reduce the number of eosinophils. Moreover, the exudation of inflammatory cells together with the hyperplasia of goblet cells was also found to experience significant inhibition when treated with γ-tocopherols. Furthermore, the high levels of eotaxin and IL-4 in the asthma group were evidently reduced under the treatment of γ-tocopherols which was comparable with hexadecadrol. In conclusion, γ-tocopherols can remit asthma by regulating the level of eotaxin and IL-4. Moreover, γ-tocopherols may be regarded as a potential candidate for asthma treatment after much deeper explorations.

Björkblom B, Wibom C, Jonsson P, Mörén L, Andersson U, Johannesen TB, Langseth H, Antti H, Melin B.

Oncotarget. 2016 Jun 14;7(24):37043-37053. doi: 10.18632/oncotarget.9242.

Abstract

Glioblastoma is associated with poor prognosis with a median survival of one year. High doses of ionizing radiation is the only established exogenous risk factor. To explore new potential biological risk factors for glioblastoma, we investigated alterations in metabolite concentrations in pre-diagnosed serum samples from glioblastoma patients diagnosed up to 22 years after sample collection, and undiseased controls. The study points out a latent biomarker for future glioblastoma consisting of nine metabolites (γ-tocopherol, α-tocopherol, erythritol, erythronic acid, myo-inositol, cystine, 2-keto-L-gluconic acid, hypoxanthine and xanthine) involved in antioxidant metabolism. We detected significantly higher serum concentrations of α-tocopherol (p=0.0018) and γ-tocopherol(p=0.0009) in future glioblastoma cases. Compared to their matched controls, the cases showed a significant average fold increase of α- and γ-tocopherol levels: 1.2 for α-T (p=0.018) and 1.6 for γ-T (p=0.003). These tocopherol levels were associated with a glioblastoma odds ratio of 1.7 (α-T, 95% CI:1.0-3.0) and 2.1 (γ-T, 95% CI:1.2-3.8). Our exploratory metabolomics study detected elevated serum levels of a panel of molecules with antioxidant properties as well as oxidative stress generated compounds. Additional studies are necessary to confirm the association between the observed serum metabolite pattern and future glioblastoma development.

Melo LR, Clemente HA, Bezerra DF, Dantas RC, Ramalho HM, Dimenstein R.

J Pediatr (Rio J). 2016 Jun 18. pii: S0021-7557(16)30059-6. doi: 10.1016/j.jped.2016.03.007. [Epub ahead of print]

Abstract

This study aims to evaluate the effect of maternal supplementation with vitamin E on the concentration of α-tocopherol in colostrum and its supply to the newborn. Study results show that maternal vitamin E supplementation increases the supply of the vitamin to the infant by providing more than twice the Recommended Daily Intake.

Pham J, Nayel A, Hoang C, Elbayoumi T.

Drug Deliv. 2016 Jun;23(5):1514-24. doi: 10.3109/10717544.2014.966925.

Abstract

The potent anti-proliferative and pro-apoptotic actions of tocotrienols (T3) against cancer, but not normal tissues, have been hampered by their limited systemic bioavailabilty. Recent expansive development of diverse nanoemulsion (NE) vehicles emphasized their vast potential to improve the effective dosing of different clinical and experimental drugs of lipophilic nature, such as T3. The emphasis of the present work is to develop a pharmaceutically scalable, low-energy nano-emulsification approach for optimized incorporation of T3-rich palm oil (Tocomin®), possessing anticancer activity as a potential cutaneous delivery platform for adjunctive therapy of skin carcinomas, either alone or in combination with other chemotherapeutic agents. Different Tocomin®-NEs, obtained with different homogenization strategies, were screened based on physicochemical uniformity (droplet size, charge and polydispersity) and subjected to stress physical stability testing, along with chemical content analysis (≥90% Tocomin® – incorporation efficiency). Adopted hybrid nano-emulsification of Tocomin®, correlated with highest preservation of DPPH-radical scavenging capacity of active T3 in prototype formulation, Tocomin®-NE, which effectively permeated diffusion cell membranes 4-folds higher than propyleneglycol (PG)-admixed Tocomin® control. Against two different cell models of human cutaneous carcinoma, Tocomin®-hybrid NE demonstrated significantly stronger cytotoxic profiles (p ≤ 0.01), visible in both concentration- and time- dependent manners, with at least 5-folds lower IC50 values, compared to those estimated for the closest Tocomin®-control. The proposed hybrid nano-emulsified formulation of Tocomin® provides simple and stable delivery platform, for effective topical application against keratinocyte tumors.

Peh HY, Tan WS, Liao W, Wong WS.

Pharmacol Ther. 2016 Jun;162:152-69. doi: 10.1016/j.pharmthera.2015.12.003. Review.

Abstract

The discovery of vitamin E (α-tocopherol) began in 1922 as a vital component required in reproduction. Today, there are eight naturally occurring vitamin E isoforms, namely α-, β-, γ- and δ-tocopherol and α-, β-, γ- and δ-tocotrienol. Vitamin E is potent antioxidants, capable of neutralizing free radicals directly by donating hydrogen from its chromanol ring. α-Tocopherol is regarded the dominant form in vitamin E as the α-tocopherol transfer protein in the liver binds mainly α-tocopherol, thus preventing its degradation. That contributed to the oversight of tocotrienols and resulted in less than 3% of all vitamin E publications studying tocotrienols. Nevertheless, tocotrienols have been shown to possess superior antioxidant and anti-inflammatory properties over α-tocopherol. In particular, inhibition of 3-hydroxy-3-methylglutaryl-coenzyme A reductase to lower cholesterol, attenuating inflammation via downregulation of transcription factor NF-κB activation, and potent radioprotectant against radiation damage are some properties unique to tocotrienols, not tocopherols. Aside from cancer, vitamin E has also been shown protective in bone, cardiovascular, eye, nephrological and neurological diseases. In light of the different pharmacological properties of tocopherols and tocotrienols, it becomes critical to specify which vitamin E isoform(s) are being studied in any future vitamin E publications. This review provides an update on vitamin E therapeutic potentials, protective effects and modes of action beyond cancer, with comparison of tocopherols against tocotrienols. With the concerted efforts in synthesizing novel vitamin E analogs and clinical pharmacology of vitamin E, it is likely that certain vitamin E isoform(s) will be therapeutic agents against human diseases besides cancer.

Farzollahi M, Tayefi-Nasrabadi H, Mohammadnejad D, Abedelahi A.

J Obstet Gynaecol Res. 2016 May;42(5):526-35. doi: 10.1111/jog.12933.

Abstract

The aim of this study was to evaluate the effects of preventive vitamin E (α-tocopherol) on antral follicle development and embryogenesis of oocytes obtained after vitrification of mouse ovarian tissue. Female Balb/c mice were killed by cervical dislocation after the injection of pregnant mare’s serum gonadotrophin (10 IU) and their ovaries were randomly divided into three groups: control or non-vitrified (n = 10), vitrification 1 (5, 10% ethylene glycol + 5, 10% dimethylsulfoxide) (n = 15), and vitrification 2 (10, 15% ethylene glycol + 10, 15% dimethylsulfoxide) (n = 15) with ascending concentration of cryoprotectants. After toxicity tests and vitrification-warming, mechanically isolated antral follicles were cultured in α-minimum essential medium, which was supplemented with or without α-tocopherol (100 μM). The follicular maturation rates and embryo development were collected and assessed. Also, the viability, morphology and ultrastructure of derived antral follicles from vitrified ovaries were analyzed. Results showed the morphology and ultrastructure of follicles were well preserved in the vitrified groups and α-tocopherol supplementation of culture media significantly increased the proportion of oocytes that reached metaphase II blastocyst rates compared to non-α-tocopherol supplemented media (P < 0.01). In conclusion, Vitamin E improves in vitro maturation rates and blastocyst rates of oocytes that are isolated from vitrified ovarian tissue.