Acute effects of a single dose of tocotrienols on insulinemic and inflammatory responses in metabolic syndrome subjects after a high-fat challenge.

Che HL, Kanthimathi MS, Loganathan R, Yuen KH, Tan AT, Selvaduray KR, Nesaretnam K, Teng KT.

Eur J Clin Nutr. 2016 Oct 19. doi: 10.1038/ejcn.2016.200. [Epub ahead of print]

Abstract

Evident shows that tocotrienols potentially reverse various chronic disease progressions caused by the metabolic syndrome. We aimed to investigate the acute effects of a single-dose supplementation of gamma and delta tocotrienols (γδ-T3, 1:4 ratio) compared with those in placebo on the insulinemic, anti-inflammatory and anti-thrombogenic responses in metabolic syndrome subjects. Results show Plasma vitamin E levels reflected the absorption of γδ-T3 after treatments. Postprandial changes in serum C-peptide, serum insulin, plasma glucose, triacylglycerol, non-esterified fatty acid and adiponectin did not differ between treatments, with women displaying delayed increase in the aforementioned markers. No significant difference between treatments was observed for plasma cytokines (interleukin-1 beta, interleukin-6 and tumor necrosis factor alpha) and thrombogenic markers (plasminogen activator inhibitor type 1 and D-dimer). In summary, Supplementation of a single dose of γδ-T3 did not change the insulinemic, anti-inflammatory and anti-thrombogenic responses in metabolic syndrome subjects.

Gavin PD, El-Tamimy M, Keah HH, Boyd BJ.

Drug Deliv Transl Res. 2016 Sep 26. [Epub ahead of print]

Abstract

Transdermal drug delivery is a useful route of administration that avoids first-pass metabolism and more invasive delivery options. However, many drugs require enhancers to enable sufficient drug absorption to reach therapeutic effect. Alpha-tocopheryl phosphate (TP) and di-alpha-tocopheryl phosphate (T2P) are two phosphorylated forms of vitamin E which form tocopheryl phosphate mixture (TPM) when combined, and have been proposed to enhance the dermal and transdermal delivery of actives of interest. Here, we report the physicochemical characteristics and morphological properties of TPM formulations, including particle size, deformability and morphology, and its ability to facilitate the transport of carnosine, vitamin D3, CoEnzyme Q10 and caffeine into, and across, the skin. Results demonstrate that TPM self-assembles to form vesicular structures in hydroethanolic solutions ranging in mean size from 101 to 162 nM depending on the amount of TPM and ethanol present in the formulation. The ratio of TP to T2P in TPM formulations altered vesicle size and elasticity, with vesicles high in TP found to be more deformable than those rich in T2P. TPM produced a significant (p < 0.05) 2.4-3.4-fold increase in the absorption of carnosine, vitamin D3, CoEnzyme Q10 and caffeine into, or through, the skin. The TPM delivery platform was able to deliver a diverse range of actives with differing size and solubility profiles and therefore has significant potential to expand the number and types of drugs available for topical application and transdermal delivery.

Muddineti OS, Ghosh B, Biswas S.

Expert Opin Drug Deliv. 2016 Sep 6:1-12. [Epub ahead of print]

Abstract

Owing to the complexity of cancer pathogenesis, conventional chemotherapy can be an inadequate method of killing cancer cells effectively. Nanoparticle-based drug delivery systems have been widely exploited pre-clinically in recent years. Incorporation of vitamin-E in nanocarriers have the advantage of (1) improving the hydrophobicity of the drug delivery system, thereby improving the solubility of the loaded poorly soluble anticancer drugs, (2) enhancing the biocompatibility of the polymeric drug carriers, and (3) improving the anticancer potential of the chemotherapeutic agents by reversing the cellular drug resistance via simultaneous administration. In addition to being a powerful antioxidant, vitamin E demonstrated its anticancer potential by inducing apoptosis in various cancer cell lines. Various vitamin E analogs have proven their ability to cause marked inhibition of drug efflux transporters. The review discusses the potential of incorporating vitamin E in the polymeric micelles which are designed to carry poorly water-soluble anticancer drugs. Current applications of various vitamin E-based polymeric micelles with emphasis on the use of α-tocopherol, D-α-tocopheryl succinate (α-TOS) and its conjugates such as D-α-tocopheryl polyethylene glycol-succinate (TPGS) in micellar system is delineated. Advantages of utilizing polymeric micelles for drug delivery and the challenges to treat cancer, including multiple drug resistance have been discussed.

Kamezaki C, Nakashima A, Yamada A, Uenishi S, Ishibashi H, Shibuya N, Hama S, Hosoi S, Yamashita E, Kogure K.

J Clin Biochem Nutr. 2016 Sep;59(2):100-106. Epub 2016 Sep 1.

Abstract

Astaxanthin and vitamin E are both effective antioxidants that are frequently used in cosmetics, as food additives, and in to prevent oxidative damage. A combination of astaxanthin and vitamin E would be expected to show an additive anntioxidative effect. In this study, liposomes co-encapsulating astaxanthin and the vitamin E derivatives α-tocopherol (α-T) or tocotrienols (T3) were prepared, and the antioxidative activity of these liposomes toward singlet oxygen and hydroxyl radical was evaluated in vitro. Liposomes co-encapsulating astaxanthin and α-T showed no additive anntioxidative effect, while the actual scavenging activity of liposomes co-encapsulating astaxanthin and T3 was higher than the calculated additive activity. To clarify why this synergistic effect occurs, the most stable structure of astaxanthin in the presence of α-T or α-T3 was calculated. Only α-T3 was predicted to form hydrogen bonding with astaxanthin, and the astaxanthin polyene chain would partially interact with the α-T3 triene chain, which could explain why there was a synergistic effect between astaxanthin and T3 but not α-T. In conclusion, co-encapsulation of astaxanthin and T3 induces synergistic scavenging activity by intermolecular interactions between the two antioxidants.

Cuerq C, Restier L, Drai J, Blond E, Roux A, Charriere S, Michalski MC, Di Filippo M, Levy E, Lachaux A, Peretti N.

Orphanet J Rare Dis. 2016 Aug 12;11(1):114. doi: 10.1186/s13023-016-0498-8.

Abstract

Chylomicron 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. Summary, this 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 Edeficiency 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.

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.

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.

Liu X, Gujarathi S, Zhang X, Shao L, Boerma M, Compadre CM, Crooks PA, Hauer-Jensen M, Zhou D, Zheng G.

Tetrahedron. 2016 Jul;72(27-28):4001-4006.

Abstract

A group of side chain partially saturated tocotrienol analogues, namely tocoflexols, have been previously designed in an effort to improve the pharmacokinetic properties of tocotrienols. (2R,8′S,3′E,11′E)-δ-Tocodienol (1) was predicted to be a high value tocoflexol for further pharmacological evaluation. We now report here an efficient 8-step synthetic route to compound 1 utilizing naturally-occurring δ-tocotrienol as a starting material (24% total yield). The key step in the synthesis is oxidative olefin cleavage of δ-tocotrienol to afford the chroman core of 1 with retention of chirality at the C-2 stereocenter.

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.

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.