Immunomodulatory Effects of α-Tocopherol on the H1N1 Influenza Vaccine: Improving the Potency and Efficacy of the Influenza Vaccine in Aged Mice

Yasaman Eshraghi, Yasaman Vahdani, Pegah Karimi, Meghdad Abdollahpour-Alitappeh, Asghar Abdoli, Morteza Taghizadeh 8, Mehdi Mahdavi

Viral Immunol . 2022 Apr;35(3):244-253. doi: 10.1089/vim.2021.0154.


Declined immune response is the main cause of decreased potency of the influenza vaccine in the elderly, regardless of virus mutations. Herein, we hypothesized that the addition of α-tocopherol to the influenza vaccine formulation might increase vaccine potency and efficacy. Hemagglutinin of the H1N1 virus was formulated in Alum and α-tocopherol, and then aged (16-20-month-old) and young (6-8-week-old) mice were immunized subcutaneously two times with 2-week intervals with 5 μg of different vaccine formulations. Two weeks after the final boosting, IFN-γ and IL-4 cytokines were assessed by using ELISA. Humoral immune responses were assessed by hemagglutination inhibition (HI). In addition, vaccine efficacy was determined by intranasal viral challenge of mice using mouse-adapted H1N1 virus. Our results showed that the new vaccine formulation improved IFN-γ and IL-4 responses in the experimental mice. However, the increase was evident mainly in the aged group and, to some extent, in the young group. Results from the HI assay showed that α-tocopherol in the vaccine formulation could increase HI activity in both young and aged mice. Furthermore, α-tocopherol, as an adjuvant, increased the protectivity of the influenza vaccine in both aged and young groups through the decreased lung viral load and increased survival rate of the experimental mice. In conclusion, it seems that α-tocopherol can not only be used as an appropriate adjuvant for aged people, but also empower old and worn out cells to increase the effectiveness of the vaccine in the elderly.

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The possible effects of α-tocopherol against amiodarone-treated lungs in rats: vimentin detection, lipid peroxidation assay, and histological and ultrastructural evaluations

Mohamed Samir Ahmed Zaki, Attalla F El-Kott, Hussah I M AlGwaiz, Shehata F Shehata, Muhammad Alaa Eldeen, Mohamed Andarawi, Refaat A Eid, Eman M Abd-Ella

Environ Sci Pollut Res Int . 2022 Apr 2. doi: 10.1007/s11356-022-19883-8. Online ahead of print.

The purpose of this study was to learn more about the pathogenesis of amiodarone (AD) on alveoli and also the possible preventive effect of α-tocopherol (α-T) against these hazards. Rats were divided into 4 groups, one of which acted as a control, the second received α-T, the third AD, and the fourth AD and α-T for 2 weeks. Light microscopy (LM), immunohistochemistry, transmission electron microscopy (TEM), and malondialdehyde (MDA) activity were analyzed in sections of lung tissue. Alveoli of lung tissue AD examined with LM showed dilatation of alveolar spaces, aggregation of red blood cells, and narrowing of alveolar septa. When stained with vimentin (VIM), alveoli showed a positive reaction in the majority and a moderate reaction in others. In the pneumocytes of the type II, some cytoplasmic vesicles had been deflated, whereas others contained lamellar bodies, a damaged nucleus, and vesicles in their heterochromatin. In the interstitial space, collagen fibers with aggregation of red blood cells and a disrupted blood-air barrier were detected. In rat lung alveoli treated with AD and α-T, the alveolar septum thickened and the alveolar spaces expanded as estimated. The alveoli of this group had more or less intact type I and II pneumocytes and a better appearance of the blood-air barrier. In the cells of the alveolar lining, the VIM staining leads to a diffuse positive response. Finally, lung parenchyma also improved, suggesting that α-T may help minimize the effects of AD.

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Effects of Vitamin E and Dietary Conditions on the Differentiation and Maturation of Osteoclast

Yoko Fujiwara, Yuko Ko, Mariko Sonoda, Ikuyo Ichi, Tomoko Ishikawa

J Nutr Sci Vitaminol (Tokyo) . 2022;68(1):73-77. doi: 10.3177/jnsv.68.73.


α-Tocopherol is reported to activate the differentiation and fusion of osteoclast, however, it is not clear whether the excessive intake of vitamin E is a risk for osteoporosis. To investigate the effects of vitamin E and the dietary conditions on the osteoclastogenesis, osteoclast differentiation was evaluated using the bone marrow cells collected from mice fed various dietary conditions. Not only α-tocopherol but also γ-tocotrienol activated osteoclast differentiation in mice fed normal diet. Formation of large multinucleated cells was significantly increased by stimulation of nuclear factor-kappa B ligand (RANKL) in mice fed vitamin E deficient diet and was suppressed by the addition of α-tocopherol. Furthermore, there was no effect on bone density and no difference in osteoclast differentiation from the bone marrow cells collected from mice fed a high-fat diet with 0 or 1,000 mg/kg diet of α-tocopherol and tocotrienol, respectively. These results suggest that different type of diet affect the activation of osteoclast by α-tocopherol.

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Fat Grafts Augmented With Vitamin E Improve Volume Retention and Radiation-Induced Fibrosis

Darren B Abbas, Christopher V Lavin, Evan J Fahy, Michelle Griffin, Nicholas J Guardino, Rahim S Nazerali, Dung H Nguyen, Arash Momeni, Michael T Longaker, Derrick C Wan

Aesthet Surg J . 2022 Mar 29;sjac066. doi: 10.1093/asj/sjac066. Online ahead of print.


Background: Treatments for radiation-induced fibrosis range from vitamin E and pentoxifylline systemically to deferoxamine and fat grafting locally. Regarding fat grafting, volume retention hinders its long-term functionality and is affected by two factors: inflammation and necrosis secondary to hypovascularity.

Objective: We aimed to simultaneously improve fat graft retention and radiation-induced fibrosis by integrating vitamin E and pentoxifylline into fat grafts locally.

Methods: Forty adult CD-1 nude male mice at 6 weeks of age underwent scalp irradiation and recovered for four weeks to allow for the development of fibrosis. Mice received 200μL of donor human fat graft to the scalp. Mice were separated into 4 conditions: no grafting, fat graft without treatment, graft treated with pentoxifylline, and graft treated with vitamin E. Fat graft volume retention was monitored in-vivo using microCT scans at weeks 0, 1, 2, 4, 6, and 8 after grafting. Histological and cytokine analysis of the scalp skin and fat grafts were also performed.

Results: Vitamin E (VE) treated grafts had significant improvement in dermal thickness and collagen density of overlying skin compared to all other groups. VE decreased 8-isoprostane and increased CD31 + staining compared to the other grafted groups. Cytokine analysis revealed decreased inflammatory and increased angiogenic markers in both the fat graft and overlying skin of the vitamin E group. Fat graft volume retention was significantly improved in the vitamin E group starting at 1 week post grafting.

Conclusion: Radiation-induced fibrosis and fat graft volume retention are both simultaneously improved with local administration of vitamin E.

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Is vitamin E the only lipid-soluble, chain-breaking antioxidant in human blood plasma and erythrocyte membranes?

G W Burton, A Joyce, K U Ingold

Arch Biochem Biophys . 2022 Mar 28;109195. doi: 10.1016/ Online ahead of print.


Application of a time-tested quantitative method of measuring peroxyl radical production in conjunction with the determination of the stoichiometry of the reaction of peroxyl radicals with α-tocopherol has permitted the conclusion that α-tocopherol is the major lipid-soluble chain-breaking antioxidant in human plasma and red cell membranes.

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Tocotrienols Attenuate White Adipose Tissue Accumulation and Improve Serum Cholesterol Concentration in High-Fat Diet-Treated Mice

Yugo Kato, Yoshinori Aoki, Chikako Kiyose, Koji Fukui

Molecules . 2022 Mar 28;27(7):2188. doi: 10.3390/molecules27072188.


Tocotrienols (T3s), which are vitamin E homologs, have not only antioxidant function but also inhibitory effects on body weight gain and hepatic lipid droplet accumulation. However, the mechanisms of the anti-obesity effects of T3s are not yet understood. In this study, C57BL/6 mice were fed a high-fat diet in the presence or absence of T3s. Treatment with T3s inhibited white adipose tissue accumulation and elevation of serum cholesterol concentrations. Additionally, to clarify the relationship between obesity-induced cognitive dysfunction and the neuroprotective effect of T3s, cognitive function, brain oxidation, and protein expression levels of brain-derived neurotrophic factor (BDNF), which is strongly involved in neuronal growth and differentiation, were measured. Although mice behaviors were improved by oral T3 intake, there were no significant differences in brain oxidation levels and BDNF expression. These results suggest that T3s attenuate obesity via inhibition of body fat and serum cholesterol increase.

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Serum level and clinical significance of vitamin E in pregnant women with allergic rhinitis

Sihai Wu, Aiping Wang

J Chin Med Assoc . 2022 Mar 25. doi: 10.1097/JCMA.0000000000000723. Online ahead of print.


Background: Allergic rhinitis is a frequent disorder during pregnancy, while in children it is triggered by significantly lower serum vitamin E level. This research aimed to investigate whether serum vitamin E level exhibited clinical significance in pregnant women with allergic rhinitis.

Methods: In this study, 37 pregnant women with allergic rhinitis and 35 healthy pregnant women were recruited. Allergic rhinitis severity was analyzed by the Total Nasal Symptom Score (TNSS) questionnaire. Blood samples were collected to evaluate serum vitamin E, interleukin (IL) and total IgE levels.

Results: In pregnant women with allergic rhinitis, serum level of vitamin E was significantly lower than in healthy pregnant women. Serum vitamin E level in pregnant women with allergic rhinitis showed negative correlation with TNSS, IL-13, IL-4, and total IgE levels.

Conclusion: In conclusion, this research has demonstrated that pregnant women with allergic rhinitis showed significantly lower serum level of vitamin E. The decreased vitamin E showed correlation with the pathogenesis of allergic rhinitis in pregnant women.

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Metabolomic analysis of serum alpha-tocopherol among men in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study

Eur J Clin Nutr . 2022 Mar 23. doi: 10.1038/s41430-022-01112-7. Online ahead of print.

Wayne R Lawrence, Jung-Eun Lim, Jiaqi Huang, Joshua N Sampson, Stephanie J Weinstein, Demetrius Albanes


Background/objectives: The role of vitamin E in chronic disease risk remains incompletely understood, particularly in an un-supplemented state, and evidence is sparse regarding the biological actions and pathways involved in its influence on health outcomes. Identifying vitamin-E-associated metabolites through agnostic metabolomics analyses can contribute to elucidating the specific associations and disease etiology. This study aims to investigate the association between circulating metabolites and serum α-tocopherol concentration in an un-supplemented state.

Subjects/methods: Metabolomic analysis of 4,294 male participants was conducted based on pre-supplementation fasting serum in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study. The associations between 1,791 known metabolites measured by ultra-high-performance LC-MS/GC-MS and HPLC-determined α-tocopherol concentration were estimated using multivariable linear regression. Differences in metabolite levels per unit difference in α-tocopherol concentration were calculated as standardized β-coefficients and standard errors.

Results: A total of 252 metabolites were associated with serum α-tocopherol at the Bonferroni-corrected p value (p < 2.79 × 10-5). Most of these metabolites were of lipid and amino acid origin, with the respective subclasses of dicarboxylic fatty acids, and valine, leucine, and isoleucine metabolism, being highly represented. Among lipids, the strongest signals were observed for linoleoyl-arachidonoyl-glycerol (18:2/20:4)[2](β = 0.149; p = 8.65 × 10-146) and sphingomyelin (D18:2/18:1) (β = 0.035; p = 1.36 × 10-30). For amino acids, the strongest signals were aminoadipic acid (β = 0.021; p = 5.01 × 10-13) and l-leucine (β = 0.007; p = 1.05 × 10-12).

Conclusions: The large number of metabolites, particularly lipid and amino acid compounds associated with serum α-tocopherol provide leads regarding potential mechanisms through which vitamin E influences human health, including its role in cardiovascular disease and cancer.

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The Protective Effects of Combination Vitamin E and Swimming Exercise on Memory Impairment Induced by Exposure to Waterpipe Smoke

Karem H Alzoubi, Abdulsalam M Halboup, Omar F Khabour, Mahmoud M Alomari

CNS Neurol Disord Drug Targets . 2022 Mar 18. doi: 10.2174/1871527321666220318113635. Online ahead of print.


Background: Waterpipe smoking (WP) exposure has a negative health impact including memory deficit which was attributed to elevation of oxidative stress. Vitamin E (VitE) or swimming exercise have protective effects that prevent memory impairment. In the current study, the modulation of WP-induced memory impairment by the combined effect of VitE and swimming exercise (SE) was investigated.

Method: Animals were exposed to WP one hour/day, five days per week for four weeks. Simultaneously, VitE (100mg/kg, six days/week for four weeks) was administered via oral gavage, and the rats were given swim exercise one hour/day, five days/week for four weeks. Changes in memory were evaluated using Radial Arm Water Maze (RAWM) and Oxidative stress biomarkers were examined in the hippocampus.

Results: WP exposure induced short-term/long-term memory impairment (p <0.05). This impairment was prevented by a combination of VitE with SE (p <0.05). Additionally, this combination normalized the hippocampal catalase, GPx, GSH/GSSG ratios that were modulated by WP (p <0.05). The combination further reduced TBARs levels below the control group (p <0.05).

Conclusion: WP induced memory impairments were prevented by the combination of VitE with SE. This could be attributed to preserving the hippocampal oxidative mechanism by the combination of VitE and SE during WP exposure.

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