Moderate intake of docosahexaenoic acid raises plasma and platelet vitamin E levels in cystic fibrosis patients.

Véricel E, Mazur S, Colas R, Delaup V, Calzada C, Reix P, Durieu I, Lagarde M, Bellon G.

Prostaglandins Leukot Essent Fatty Acids. 2016 Dec;115:41-47. doi: 10.1016/j.plefa.2016.10.008. Epub 2016 Oct 18.

Abstract

Patients with cystic fibrosis have increased oxidative stress and impaired antioxidant systems. Moderate intake of docosahexaenoic acid (DHA) may favor the lowering of oxidative stress. In this randomized, double-blind, cross-over study, DHA or placebo capsules, were given daily to 10 patients, 5mg/kg for 2 weeks then 10mg/kg DHA for the next 2 weeks (or placebo). After 9 weeks of wash-out, patients took placebo or DHA capsules. Biomarkers of lipid peroxidation and vitamin E were measured at baseline, and after 2 and 4 weeks of treatment in each phase. The proportions of DHA increased both in plasma and platelet lipids after DHA supplementations. The lipid peroxidation markers did not significantly decrease, in spite of a trend, after the first and/or the second dose of DHA but plasma and platelet vitamin E amounts increased significantly after DHA supplementation. Our findings reinforce the antioxidant potential of moderate DHA intake in subjects displaying increased oxidative stress.

Thomas Mock J, Chaudhari K, Sidhu A, Sumien N.

Exp Gerontol. 2016 Dec 8. pii: S0531-5565(16)30578-2. doi: 10.1016/j.exger.2016.12.008. [Epub ahead of print]

Abstract

Age-related declines in motor and cognitive function have been associated with increases in oxidative stress. Accordingly, interventions capable of reducing the oxidative burden would be capable of preventing or reducing functional declines occurring during aging. Popular interventions such as antioxidant intake and moderate exercise are often recommended to attain healthy aging and have the capacity to alter redox burden. This review is intended to summarize the outcomes of antioxidant supplementation (more specifically of vitamins C and E) and exercise training on motor and cognitive declines during aging, and on measures of oxidative stress. Additionally, we will address whether co-implementation of these two types of interventions can potentially further their individual benefits. Together, these studies highlight the importance of using translationally-relevant parameters for interventions and to study their combined outcomes on healthy brain aging.

Barker T, Henriksen VT, Rogers VE, Momberger NG, Rasmussen GL, Trawick RH.

Cytokine. 2016 Dec;88:108-114. doi: 10.1016/j.cyto.2016.08.025. Epub 2016 Sep 1.

Abstract

The purpose of this study was to identify if circulating interleukin (IL)-6 and γ-tocopherol (γT) fluctuate with vitamin D status in subjects with an underlying knee joint injury or disease. We hypothesized that low vitamin D associates with an increase in plasma γT while serum IL-6 remains unchanged in subjects with an underlying knee joint trauma or disease. Fifty-four subjects scheduled to undergo primary, unilateral anterior cruciate ligament reconstructive surgery (ACL; n=27) or total knee arthroplasty (TKA; n=27) were studied. Circulating γT, α-tocopherol (αT), lipids (cholesterol and triglycerides), IL-6, and 25-hydroxyvitamin D (25(OH)D) were measured in fasting blood samples obtained prior to surgery. Subjects were classified as vitamin D deficient, insufficient, or sufficient if they had a serum 25(OH)D concentration <50, 50-75, or >75nM, respectively. The majority (57%) of the subjects possessed a serum 25(OH)D less than 50nM. Circulating cholesterol, triglycerides, and IL-6 were not significantly (all p>0.05) different between vitamin D status groups. However, lipid corrected αT was significantly (p<0.05) decreased and both lipid- and non-lipid-corrected plasma γT concentrations were significantly (both p<0.05) increased with low serum 25(OH)D (i.e., <50nM). A significant (p<0.05) multi-variate analysis revealed that an increase in plasma γT per lipids was significantly (p<0.05) predicted by a decrease in serum 25(OH)D but not by a decrease in plasma αT per lipids. We conclude that low vitamin D associates with an increase in plasma γT but not IL-6 in subjects with an underlying joint injury or disease.

Neuerburg C, Loer T, Mittlmeier L, Polan C, Farkas Z, Holdt LM, Utzschneider S, Schwiesau J, Grupp TM, Böcker W, Aszodi A, Wedemeyer C, Kammerlander C.

Int J Mol Med. 2016 Dec;38(6):1652-1660. doi: 10.3892/ijmm.2016.2780. Epub 2016 Oct 18.

Abstract

Aseptic loosening mediated by wear particle-induced osteolysis (PIO) remains the major cause of implant loosening in endoprosthetic surgery. The development of new vitamin E (α-tocopherol)-blended ultra-high molecular weight polyethylene (VE-UHMWPE) with increased oxidation resistance and improved mechanical properties has raised hopes. Furthermore, regenerative approaches may be opened, as vitamin E supplementation has shown neuroprotective characteristics mediated via calcitonin gene-related peptide (CGRP), which is known to affect bone remodeling in PIO. Therefore, the present study aimed to further clarify the impact of VE-UHMWPE wear particles on the osseous microenvironment and to identify the potential modulatory pathways involved. Using an established murine calvaria model, mice were subjected to sham operation (SHAM group), or treated with UHMWPE or VE-UHMWPE particles for different experimental durations (7, 14 and 28 days; n=6/group). Morphometric analysis by micro-computed tomography detected significant (p<0.01) and comparable signs of PIO in all particle-treated groups, whereas markers of inflammation [tumor necrosis factor (TNF)-α/tartrate resistant acid phosphatase (TRAP) staining] and bone remodeling [Dickkopf-related protein 1 (DKK-1)/osteoprotegerin (OPG)] were most affected in the early stages following surgery. Taking the present data into account, VE-UHMWPE appears to have a promising biocompatibility and increased ageing resistance. According to the α-CGRP serum levels and immunohistochemistry, the impact of vitamin E on neuropeptidergic signaling and its chance for regenerative approaches requires further investigation.

Finno CJ, Bordbari MH, Valberg SJ, Lee D, Herron J, Hines K, Monsour T, Scott E, Bannasch DL, Mickelson J, Xu L.

Free Radic Biol Med. 2016 Dec;101:261-271. doi: 10.1016/j.freeradbiomed.2016.10.009. Epub 2016 Oct 15.

Abstract

Specific spontaneous heritable neurodegenerative diseases have been associated with lower serum and cerebrospinal fluid α-tocopherol (α-TOH) concentrations. Equine neuroaxonal dystrophy (eNAD) has similar histologic lesions to human ataxia with vitamin E deficiency caused by mutations in the α-TOH transfer protein gene (TTPA). Mutations in TTPA are not present with eNAD and the molecular basis remains unknown. Given the neuropathologic phenotypic similarity of the conditions, we assessed the molecular basis of eNAD by global transcriptome sequencing of the cervical spinal cord. Differential gene expression analysis identified 157 significantly (FDR<0.05) dysregulated transcripts within the spinal cord of eNAD-affected horses. Statistical enrichment analysis identified significant downregulation of the ionotropic and metabotropic group III glutamate receptor, synaptic vesicle trafficking and cholesterol biosynthesis pathways. Gene co-expression analysis identified one module of upregulated genes significantly associated with the eNAD phenotype that included the liver X receptor (LXR) targets CYP7A1, APOE, PLTP and ABCA1. Validation of CYP7A1 and APOE dysregulation was performed in an independent biologic group and CYP7A1 was found to be additionally upregulated in the medulla oblongata of eNAD horses. Evidence of LXR activation supports a role for modulation of oxysterol-dependent LXR transcription factor activity by tocopherols. We hypothesize that the protective role of α-TOH in eNAD may reside in its ability to prevent oxysterol accumulation and subsequent activation of the LXR in order to decrease lipid peroxidation associated neurodegeneration.

Capó X, Martorell M, Busquets-Cortés C, Sureda A, Riera J, Drobnic F, Tur JA, Pons A.

Food Funct. 2016 Dec 7;7(12):4920-4934.

Abstract

Functional beverages based on almonds and olive oil and enriched with α-tocopherol and docosahexaenoic acid (DHA) could be useful in modulating oxidative stress and enhancing physical performance in sportsmen. The aim of this work was to evaluate the effects of supplementation with functional beverages on physical performance, plasma and erythrocyte fatty acids’ and polyphenol handling, oxidative and nitrative damage, and antioxidant and mitochondrial gene expression in young and senior athletes. Athletes performed maximal exercise tests before and after one month of dietary supplementation and blood samples were taken immediately before and one hour after each test. The beverages did not alter performance parameters during maximal exercise. Supplementation increased polyunsaturated and reduced saturated plasma fatty acids while increasing the DHA erythrocyte content; it maintained basal plasma and blood polyphenol levels, but increased the blood cell polyphenol concentration in senior athletes. Supplementation protects against oxidative damage although it enhances nitrative damage in young athletes. The beverages enhance the gene expression of antioxidant enzymes in peripheral blood mononuclear cells after exercise in young athletes.

Zhang J, Hu X, Zhang J.

Osteoporos Int. 2016 Dec 1. [Epub ahead of print]

Abstract

Mixed findings regarding effects of vitamin E on bone metabolism existed. We were the first to find a negative association between serum α-tocopherol concentration and bone mineral density in the US elderly population. Using vitamin E supplement as α-tocopherol to promote bone health was not warranted at this time. The aim of the study is to examine the associations between serum vitamin E (α-tocopherol and γ-tocopherol) status and bone mineral density (BMD) among the US elderly population. This study found a negative association between serum α-tocopherol concentration and femoral neck BMD in the US elderly population, suggesting a harmful effect of α-tocopherol on bone health. Future studies are warranted to further examine the dose-response relationships between individual vitamin E isomers and bone metabolism.

Algayadh IG, Dronamraju V, Sylvester PW.

Biol Pharm Bull. 2016;39(12):1974-1982.

Abstract

The majority of breast cancer deaths result from the progression of this disease to a metastatic phenotype. Rac1 and Cdc42 are Rho family members that together with their downstream effectors, Wiskott-Aldrich Syndrome protein-family verprolin-homologous protein 2 (WAVE2) and Arp2/3, play an important role in cytoskeletal reorganization and the formation of membrane protrusions that promote cancer cell migration and invasion. γ-Tocotrienol, is a natural isoform within the vitamin E family of compounds that inhibits breast cancer cell growth and progression by suppressing various signaling pathways involved in mitogenic signaling and metastatic progression. Studies were conducted to examine the effects of γ-tocotrienol on Rac1/WAVE2 signaling dependent migration and invasion in highly metastatic mouse +SA and human MDA-MB-231 mammary cancer cells. Exposure to γ-tocotrienol resulted in a dose-responsive decrease in Rac1/WAVE2 signaling as characterized by a suppression in the levels of Rac1/Cdc42, phospho-Rac1/Cdc42, WAVE2, Arp2, and Arp3 expression. Additional studies also demonstrated that similar treatment with γ-tocotrienol resulted in a significant reduction in tumor cell migration and invasion. Taken together, these findings indicate that γ-tocotrienol treatment effectively inhibits Rac1/WAVE2 signaling and reduces metastatic phenotypic expression in mammary cancer cells, suggesting that γ-tocotrienol may provide some benefit as a novel therapeutic approach in the treatment of metastatic breast cancer.

Shiozawa N, Sugahara R, Namiki K, Sato C, Ando A, Sato A, Virgona N, Yano T.

Anticancer Drugs. 2016 Dec 6. [Epub ahead of print]

Abstract

Prostate cancer (PCa) is one of the most common cancers in Western countries and acquires a malignant phenotype, androgen-independent growth. PCa under hypoxia often has resistance to chemotherapy and radiotherapy. However, an effective therapy against PCa under hypoxia has not yet been established. In this report, we investigated the inhibitory effect of a redox-silent analogue of tocotrienol on the survival of a human androgen-independent PCa cell line (PC3) under hypoxia. We found that the redox-silent analogue exerted a cytotoxic effect on PC3 cells in a dose-dependent manner irrespective of either hypoxia or normoxia. Moreover, under hypoxia, the analogue dose dependently reduced the protein levels of hypoxia-inducible factor (HIF)-1α and HIF-2α. In addition, a specific inhibitor toward HIF-1α induced cytotoxicity on PC3 cells, whereas selective inhibition of HIF-2α exerted no effect. Furthermore, suppression of HIFs levels by the analogue in hypoxic PC3 cells was closely associated with the inactivation of Fyn, a member of the nonreceptor tyrosine kinase family, as confirmed by the action of a specific inhibitor toward the kinase (PP2). Taken together, these results suggest that the tocotrienol analogue could inhibit the survival of PC3 cells under hypoxia, mainly by the inhibition of Fyn/HIF-1α signaling, and this may lead to the establishment of a new effective therapy for androgen-independent PCa.

Eitsuka T, Tatewaki N, Nishida H, Nakagawa K, Miyazawa T.

J Nutr Sci Vitaminol (Tokyo). 2016;62(5):281-287.

Abstract

Rice bran is a rich source of functional compounds, including tocotrienol (T3) and ferulic acid (FA). We previously investigated the anti-cancer properties of T3, and reported on the potent inhibitory effects of δ-T3 on angiogenesis and telomerase activity. In this study, we examined the synergistic suppressive effects of the combination of δ-T3 and FA on telomerase activity in DLD-1 human colorectal adenocarcinoma cells. Co-treatment with δ-T3 and FA significantly decreased cellular telomerase activity compared to treatment with δ-T3 alone, whereas FA alone had no inhibitory effect. Co-treatment with δ-T3 and FA also synergistically down-regulated the expression of human telomerase reverse transcriptase (hTERT), the catalytic subunit of telomerase, indicating that the enzymatic activity of telomerase is controlled at the transcriptional level. FA significantly increased the intracellular concentration of δ-T3, suggesting that FA improved the bioavailability of δ-T3, thereby increasing the inhibitory potency of δ-T3 on telomerase. FA may be a promising candidate for augmenting the anti-cancer activity of δ-T3.