A Randomized Controlled Clinical Trial Investigating the Effects of Omega-3 Fatty Acids and Vitamin E Co-Supplementation on Biomarkers of Oxidative Stress, Inflammation and Pregnancy Outcomes in Gestational Diabetes.

Jamilian M, Hashemi Dizaji S, Bahmani F, Taghizadeh M, Memarzadeh MR, Karamali M, Akbari M, Asemi Z.

Can J Diabetes. 2016 Nov 21. pii: S1499-2671(16)30266-0. doi: 10.1016/j.jcjd.2016.09.004. [Epub ahead of print]


Limited data are available for assessing the effects of omega-3 fatty acids and vitamin E co-supplementation on metabolic profiles and pregnancy outcomes in gestational diabetes (GDM). This study was designed to determine the effects of omega-3 fatty acids and vitamin E co-supplementation on biomarkers of oxidative stress, inflammation and pregnancy outcomes in women with GDM.

This randomized, double-blind, placebo-controlled clinical trial was conducted in 60 patients with GDM who were not taking oral hypoglycemic agents. Patients were randomly allocated to intake either 1000 mg omega-3 fatty acids from flaxseed oil plus 400 IU vitamin E supplements (n=30) or placebo (n=30) for 6 weeks. Fasting blood samples were obtained from the women at the beginning of the study and after the 6-week intervention to quantify related markers.

After 6 weeks of intervention, omega-3 fatty acids and vitamin E co-supplementation, compared with the placebo, resulted in a significant rise in total antioxidant capacity (TAC) (+187.5±224.9 vs. -32.5±136.1 mmol/L; p<0.001); nitric oxide (NO) (+5.0±7.7 vs. -12.0±28.0 µmol/L; p=0.002) and a significant decrease in plasma malondialdehyde (MDA) concentrations (-0.1±0.9 vs. +0.6±1.4 µmol/L; p=0.03). Co-supplementation with omega-3 fatty acids and vitamin E showed no detectable changes in plasma glutathione and serum high-sensitivity C-reactive protein levels. Joint omega-3 fatty acids and vitamin E supplementation resulted in lower incidences of hyperbilirubinemia in newborns (10.3% vs. 33.3%; p=0.03).

Overall, omega-3 fatty acids and vitamin E co-supplementation for 6 weeks in women with GDM had beneficial effects on plasma TAC, MDA and NO and on the incidence of the newborns’ hyperbilirubinemia.

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Role of Endogenous and Exogenous Tocopherols in the Lipid Stability of Marine Oil Systems: A Review.

Suárez-Jiménez GM, López-Saiz CM, Ramírez-Guerra HE, Ezquerra-Brauer JM, Ruiz-Cruz S, Torres-Arreola W.

Int J Mol Sci. 2016 Nov 24;17(12). pii: E1968.


In marine organisms primarily intended for human consumption, the quality of the muscle and the extracted oils may be affected by lipid oxidation during storage, even at low temperatures. This has led to a search for alternatives to maintain quality. In this sense, antioxidant compounds have been used to prevent such lipid deterioration. Among the most used compounds are tocopherols, which, due to their natural origin, have become an excellent alternative to prevent or retard lipid oxidation and maintain the quality of marine products. Tocopherols as antioxidants have been studied both exogenously and endogenously. Exogenous tocopherols are often used by incorporating them into plastic packaging films or adding them directly to fish oil. It has been observed that exogenous tocopherols incorporated in low concentrations maintain the quality of both muscle and the extracted oils during food storage. However, it has been reported that tocopherols applied at higher concentrations act as a prooxidant molecule, probably because their reactions with singlet oxygen may generate free radicals and cause the oxidation of polyunsaturated fatty acids in fish oils. However, when tocopherols are included in a fish diet (endogenous tocopherols), the antioxidant effect on the muscle lipids is more effective due to their incorporation into the membrane lipids, which can help extend the shelf life of seafood by reducing the lipid deterioration that occurs due to antioxidant synergy with other phenolic compounds used supplements in fish muscle. This review focuses on the most important studies in this field and highlights the potential of using tocopherols as antioxidants in marine oils.

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Nasal mucosa healing after endoscopic sinus surgery in chronic rhinosinusitis of elderly patients: role of topic alpha-tocopherol acetate.

Testa D, Marcuccio G, Panin G, Bianco A, Tafuri D, Thyrion FZ, Nunziata M, Piombino P, Guerra G, Motta G.

Aging Clin Exp Res. 2016 Nov 25. [Epub ahead of print]


Chronic rhinosinusitis (CRS) in European country ranges in elderly patients from 4.5 to 12% of population and has a significant effect on quality of life. In these patients, rhinosinusitis is linked to immune functions changes with age and to mucosal paraphysiological alterations such as crusting formations with atrophic epithelium, variations of nasal airflow and modifications of the mucociliary clearance. Failure of medical treatments leads to surgery in patients with persistent symptoms and radiographic signs of CRS. The choice of appropriate post-surgical topic treatments is important for healing time and for preventing mucosal complications such as synechiae, crusting formation and atrophy with secondary bacterial and fungal infections. The aim of this study is to definite the effects of topic alpha-tocopherol acetate administration on nasal mucosa healing after endoscopic sinus surgery in CRS of elderly patients. In this study were included 32 patients, mean age 68.6, who underwent FESS because affected by CRS not responsive to medical treatments. After surgical treatment, we distinguish two groups basing on local nasal therapy. In our research, we observed that alpha-tocopherol acetate has no contraindications and side effects. In conclusion, our study showed the effectiveness of alpha-tocopherol acetate topic treatment in elderly patients affected by CRS after FESS, in improving and speeding up the process of restoring the sinonasal mucosa, compared to another topic medication.

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Protective Effects of α-Tocopherol, γ-Tocopherol and Oleic Acid, Three Compounds of Olive Oils, and No Effect of Trolox, on 7-Ketocholesterol-Induced Mitochondrial and Peroxisomal Dysfunction in Microglial BV-2 Cells.

Debbabi M, Nury T, Zarrouk A, Mekahli N, Bezine M, Sghaier R, Grégoire S, Martine L, Durand P, Camus E, Vejux A, Jabrane A, Bretillon L, Prost M, Moreau T, Ammou SB, Hammami M, Lizard G.

Int J Mol Sci. 2016 Nov 25;17(12). pii: E1973.


Lipid peroxidation products, such as 7-ketocholesterol (7KC), may be increased in the body fluids and tissues of patients with neurodegenerative diseases and trigger microglial dysfunction involved in neurodegeneration. It is therefore important to identify synthetic and natural molecules able to impair the toxic effects of 7KC. We determined the impact of 7KC on murine microglial BV-2 cells, especially its ability to trigger mitochondrial and peroxisomal dysfunction, and evaluated the protective effects of α- and γ-tocopherol, Trolox, and oleic acid (OA). Multiple complementary chemical assays, flow cytometric and biochemical methods were used to evaluate the antioxidant and cytoprotective properties of these molecules. According to various complementary assays to estimate antioxidant activity, only α-, and γ-tocopherol, and Trolox had antioxidant properties. However, only α-tocopherol, γ-tocopherol and OA were able to impair 7KC-induced loss of mitochondrial transmembrane potential, which is associated with increased permeability to propidium iodide, an indicator of cell death. In addition, α-and γ-tocopherol, and OA were able to prevent the decrease in Abcd3 protein levels, which allows the measurement of peroxisomal mass, and in mRNA levels of Abcd1 and Abcd2, which encode for two transporters involved in peroxisomal β-oxidation. Thus, 7KC-induced side effects are associated with mitochondrial and peroxisomal dysfunction which can be inversed by natural compounds, thus supporting the hypothesis that the composition of the diet can act on the function of organelles involved in neurodegenerative diseases.

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Klotho sensitive regulation of dendritic cell functions by vitamin E.

Xuan NT, Trang PT, Van Phong N, Toan NL, Trung DM, Bac ND, Nguyen VL, Hoang NH, Van Hai N.

Biol Res. 2016 Nov 24;49(1):45.


Dendritic cells (DCs) are the most potent professional antigen-presenting cells for naive T cells to link innate and acquired immunity. Klotho, an anti-aging protein, participates in the regulation of Ca2+ dependent migration in DCs. Vitamin E (VitE) is an essential antioxidant to protect cells from damage and elicits its inhibitory effects on NF-κB-mediated inflammatory response. However, the roles of VitE on mouse DC functions and the contribution of klotho to those effects both are unknown. The present study explored the effects of VitE on klotho expression, maturation, ROS production and migration in DCs.

The mouse bone marrow cells were isolated and cultured with GM-CSF to attain bone marrow-derived DCs (BMDCs). Cells were stimulated with LPS (100 ng/ml) in the presence or absence of VitE (500 µM). RT-PCR and immunoprecipitation methods were employed to determine klotho expression, ELISA to determine cytokine release, flow cytometry to analyze number of CD86+CD11c+cells, the intracellular expression of cytokines and reactive oxygen species (ROS) production and a transwell migration assay to trace migration.

Klotho transcript level and this hormone secretion in DC supernatant were enhanced by VitE treatment and further increased in the presence of NF-κB inhibitor Bay 11-7082 (10 µM). Moreover, VitE treatment inhibited IL-12p70 protein expression of, ROS accumulation in and CCL21-dependent migration of LPS-triggered mature DCs, these effects were reversed following klotho silencing.

The up-regulation of klotho by VitE could contribute to the inhibitory effects of VitE on NF-κB-mediated DC functional maturation. The events might contribute to immunotherapeutic effect of VitE on the pathophysiology of klotho-related disease.

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δ-Tocopherol inhibits receptor tyrosine kinase-induced AKT activation in prostate cancer cells.

Wang H, Hong J, Yang CS.

Mol Carcinog. 2016 Nov;55(11):1728-1738. doi: 10.1002/mc.22422.


The cancer preventive activity of vitamin E is suggested by epidemiological studies and supported by animal studies with vitamin Eforms, γ-tocopherol and δ-tocopherol (δ-T). Several recent large-scale cancer prevention trials with high dose of α-tocopherol, however, yielded disappointing results. Whether vitamin E prevents or promotes cancer is a serious concern. A better understanding of the molecular mechanisms of action of the different forms of tocopherols would enhance our understanding of this topic. In this study, we demonstrated that δ-T was the most effective tocopherol form in inhibiting prostate cancer cell growth, by inducing cell cycle arrest and apoptosis. By profiling the effects of δ-T on the cell signaling using the phospho-kinase array, we found that the most inhibited target was the phosphorylation of AKT on T308. Further study on the activation of AKT by EGFR and IGFR revealed that δ-T attenuated the EGF/IGF-induced activation of AKT (via the phosphorylation of AKT on T308 induced by the activation of PIK3). Expression of dominant active PIK3 and AKT in prostate cancer cell line DU145 in which PIK3, AKT, and PTEN are wild type caused the cells to be reflectory to the inhibition of δ-T, supporting that δ-T inhibits the PIK3-mediated activation of AKT. Our data also suggest that δ-T interferes with the EGF-induced EGFR internalization, which leads to the inhibition of the receptor tyrosine kinase-dependent activation of AKT. In summary, our results revealed a novel mechanism of δ-T in inhibiting prostate cancer cell growth, supporting the cancer preventive activity δ-T.

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Vitamin E and the risk of pneumonia: using the I 2 statistic to quantify heterogeneity within a controlled trial.

Hemilä H.

Br J Nutr. 2016 Nov;116(9):1530-1536.


Analyses in nutritional epidemiology usually assume a uniform effect of a nutrient. Previously, four subgroups of the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study of Finnish male smokers aged 50-69 years were identified in which vitamin E supplementation either significantly increased or decreased the risk of pneumonia. The purpose of this present study was to quantify the level of true heterogeneity in the effect of vitamin E on pneumonia incidence using the I 2 statistic. The I 2 value estimates the percentage of total variation across studies that is explained by true differences in the treatment effect rather than by chance, with a range from 0 to 100 %. The I 2 statistic for the effect of vitamin E supplementation on pneumonia risk for five subgroups of the ATBC population was 89 % (95 % CI 78, 95 %), indicating that essentially all heterogeneity was true variation in vitamin E effect instead of chance variation. The I 2 statistic for heterogeneity in vitamin E effects on pneumonia risk was 92 % (95 % CI 80, 97 %) for three other ATBC subgroups defined by smoking level and leisure-time exercise level. Vitamin E decreased pneumonia risk by 69 % among participants who had the least exposure to smoking and exercised during leisure time (7·6 % of the ATBC participants), and vitamin E increased pneumonia risk by 68 % among those who had the highest exposure to smoking and did not exercise (22 % of the ATBC participants). These findings refute there being a uniform effect of vitamin E supplementation on the risk of pneumonia.

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Protection against arsenic-induced hematological and hepatic anomalies by supplementation of vitamin C and vitamin E in adult male rats.

Mondal R, Biswas S, Chatterjee A, Mishra R, Mukhopadhyay A, Bhadra RK, Mukhopadhyay PK.

J Basic Clin Physiol Pharmacol. 2016 Nov 1;27(6):643-652. doi: 10.1515/jbcpp-2016-0020.


Chronic arsenic exposure via contaminated drinking water is a global environmental health problem associated with hematological, hepatic and many serious systemic disorders. This study on adult male rats evaluated the protective effects of vitamin E (VE) and vitamin C (VC) against arsenic-mediated hematological and hepatic toxicities. As a result, the present investigation offers strong evidence regarding the protective efficacy of co-administration of VC and VE against hematotoxicity and hepatotoxicity in adult male rats caused by chronic arsenic exposure.

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High concentration of vitamin E supplementation in sow diet during the last week of gestation and lactation affects the immunological variables and antioxidative parameters in piglets.

Wang L, Xu X, Su G, Shi B, Shan A.

J Dairy Res. 2016 Nov 11:1-6. [Epub ahead of print]


An experiment was conducted to investigate the effects of a high concentration of vitamin E supplementation in sow diet during the last week of gestation and lactation on the performance, milk composition, and vital immunological variables and antioxidative parameters in sows and piglets. The experiment started on day 107 of gestation and lasted until the piglets were weaned on day 21 of lactation. 48 sows were divided into two groups and fed either a basal diet with 44 IU/kg of vitamin E or a basal diet supplemented with additional vitamin E, total content of 250 IU/kg. Sow milk and blood samples were obtained on day 0 (farrowing) and on day 21 of lactation. One 21-day-old piglet per litter was selected to collect plasma. Results showed that supplementation of the maternal diet with 250 IU/kg vitamin E improved the average daily gain (ADG) and weaning weight of piglets (P < 0·05), and the concentrations of immunoglobulin G (IgG) and immunoglobulin A (IgA) in sow plasma, colostrum and milk. The concentrations of fat in the colostrum and milk were significantly increased by supplementation with 250 IU/kg of vitamin E (P < 0·05). The level of plasma IgG, IgA, total antioxidant capacity (T-AOC) and catalase (CAT) were all higher (P < 0·05) in piglets from sows that were fed 250 IU/kg of vitamin Ethan in those from the control group. The high concentration of vitamin E supplementation to the sows enhanced the concentrations of α-tocopherol in the sow milk and plasma as well as piglet plasma (P < 0·05). In conclusion, the addition to the maternal diet of vitamin E at high concentration improved the weight of piglets at weaning, and enhanced humoral immune function and antioxidant activity in sows and piglets.

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Short term effects of palm-tocotrienol and palm-carotenes on vascular function and cardiovascular disease risk: A randomised controlled trial.

Stonehouse W, Brinkworth GD, Thompson CH, Abeywardena MY.

Atherosclerosis. 2016 Nov;254:205-214. doi: 10.1016/j.atherosclerosis.2016.10.027.


In vitro, ex vivo and animal studies suggest palm-based tocotrienols and carotenes enhance vascular function, but limited data in humans exists. The aim was to examine the effects of palm-tocotrienols (TRF- 80) and palm-carotene (CC-60) supplementation on vascular function and cardiovascular disease (CVD) risk factors in adults at increased risk of impaired vascular function. In conclusion, CC-60 and TRF-80 supplementation increased bioavailability of palm-based carotenes and tocotrienols but had no effects, superior or detrimental, on vascular function or CVD risk factors.

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