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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Are Vitamin E Supplementation Beneficial for Female Gynaecology Health and Diseases?

Nur Amira Md Amin, Siti Hamimah Sheikh Abdul Kadir, Akmal Hisyam Arshad, Norhaslinda Abdul Aziz, Nurul Alimah Abdul Nasir, Normala Ab Latip

Molecules . 2022 Mar 15;27(6):1896. doi: 10.3390/molecules27061896.


Vitamin E is known as an essential vitamin, and many studies had demonstrated the importance of vitamin E throughout the reproductive process, such as miscarriage, premature birth, preeclampsia, and intrauterine growth restriction, which could be caused by a lack of vitamin E during pregnancy. Its potent antioxidant properties can counteract the oxidative stress induced by oxygen free radicals and imbalance of oxidative-antioxidant levels, hence it may play a role in maintaining the normal function of the female reproductive system. Despite the fact that vitamin E is acknowledged as the substance needed for reproduction, its beneficial effects on female fertility, gynaecological health, and diseases are still poorly understood and lacking. Therefore, the goal of this paper is to provide a summary of the known roles of vitamin E supplementation in women for gynaecological health and reproductive-related diseases, as well as its future perspective.

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The Protective Effects of γ-Tocotrienol on Muscle Stem Cells Through Inhibiting Reactive Oxidative Stress Production

Shuo Yang, Juan Yang, Huiwen Zhao, Rong Deng, Hancheng Fan, Jinfu Zhang, Zihao Yang, Huihong Zeng, Bohai Kuang, Lijian Shao

Front Cell Dev Biol . 2022 Mar 15;10:820520. doi: 10.3389/fcell.2022.820520. eCollection 2022.


Pseudotrophic muscular dystrophy is a common clinical skeletal muscle necrotic disease, among which Duchenne muscular dystrophy (DMD) is the predominant. For such diseases, there is no clinically effective treatment, which is only symptomatic or palliative treatment. Oxidative stress and chronic inflammation are common pathological features of DMD. In recent years, it has been found that the pathophysiological changes of skeletal muscle in DMD mice are related to muscle stem cell failure. In the present study, we established a DMD mice model and provided tocotrienol (γ-tocotrienol, GT3), an antioxidant compound, to explore the relationship between the physiological state of muscle stem cells and oxidative stress. The results showed that the application of GT3 can reduce ROS production and cellular proliferation in the muscle stem cells of DMD mice, which is beneficial to promote the recovery of muscle stem cell function in DMD mice. GT3 treatment improved the differentiation ability of muscle stem cells in DMD mice with increasing numbers of MyoD+ cells. GT3 application significantly decreased percentages of CD45+ cells and PDGFRα+ fibro-adipogenic progenitors in the tibialis anterior of DMD mice, indicating that the increased inflammation and fibro-adipogenic progenitors were attenuated in GT3-treated DMD mice. These data suggest that increased ROS production causes dysfunctional muscle stem cell in DMD mice, which might provide a new avenue to treat DMD patients in the clinic.

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Dietary Vitamin E intake is associated with a reduced risk of developing digestive diseases and NAFLD

Eleonora Scorletti, Kate Townsend Creasy, Marijana Vujkovic, Mara Vell, Inuk Zandvakili, Daniel J Rader, Kai Markus Schneider, Carolin V Schneider

Am J Gastroenterol . 2022 Mar 14. doi: 10.14309/ajg.0000000000001726. Online ahead of print.


Introduction: Vitamin E supplementation is recommended for the treatment of non-alcoholic fatty liver disease (NAFLD) for nondiabetic patients, but its preventative effects are unclear.

Methods: We assessed dietary Vitamin E intake with disease phenotypes and evaluated Vitamin E levels with the development of NAFLD.

Results: Data from >210,000 participants demonstrate that increased dietary Vitamin E associates with reduced rates of several gastrointestinal diseases and reduced overall mortality. Diabetic and overweight subjects with increased Vitamin E intake have fewer NAFLD diagnoses.

Conclusion: Our findings reveal the relevance of Vitamin E consumption for several gastrointestinal diseases and warrant further mechanistic and therapeutic investigations.

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Alpha-tocotrienol enhances arborization of primary hippocampal neurons via upregulation of Bcl-xL

Han-A Park, Kristi M Crowe-White, Lukasz Ciesla, Madison Scott, Sydni Bannerman, Abigail U Davis, Bishnu Adhikari, Garrett Burnett, Katheryn Broman, Khondoker Adeba Ferdous, Kimberly H Lackey, Pawel Licznerski, Elizabeth A Jonas

Nutr Res . 2022 Mar 7;101:31-42. doi: 10.1016/j.nutres.2022.02.007. Online ahead of print.


Alpha-tocotrienol (α-TCT) is a member of the vitamin E family. It has been reported to protect the brain against various pathologies including cerebral ischemia and neurodegeneration. However, it is still unclear if α-TCT exhibits beneficial effects during brain development. We hypothesized that treatment with α-TCT improves intracellular redox homeostasis supporting normal development of neurons. We found that primary hippocampal neurons isolated from rat feti grown in α-TCT-containing media achieved greater levels of neurite complexity compared to ethanol-treated control neurons. Neurons were treated with 1 μM α-TCT for 3 weeks, and media were replaced with fresh α-TCT every week. Treatment with α-TCT increased α-TCT levels (26 pmol/mg protein) in the cells, whereas the control neurons did not contain α-TCT. α-TCT-treated neurons produced adenosine triphosphate (ATP) at a higher rate and increased ATP retention at neurites, supporting formation of neurite branches. Although treatment with α-TCT alone did not change neuronal viability, neurons grown in α-TCT were more resistant to death at maturity. We further found that messenger RNA and protein levels of B-cell lymphoma-extra large (Bcl-xL) are increased by α-TCT treatment without inducing posttranslational cleavage of Bcl-xL. Bcl-xL is known to enhance mitochondrial energy production, which improves neuronal function including neurite outgrowth and neurotransmission. Therefore α-TCT-mediated Bcl-xL upregulation may be the central mechanism of neuroprotection seen in the α-TCT-treated group. In summary, treatment with α-TCT upregulates Bcl-xL and increases ATP levels at neurites. This correlates with increased neurite branching during development and with protection of mature neurons against oxidative stress.

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Potential “Therapeutic” Effects of Tocotrienol-Rich Fraction (TRF) and Carotene “Against” Bleomycin-Induced Pulmonary Fibrosis in Rats via TGF-β/Smad, PI3K/Akt/mTOR and NF-κB Signaling Pathways

Yifei Lu, Yihan Zhang, Zhenyu Pan, Chao Yang, Lin Chen, Yuanyuan Wang, Dengfeng Xu, Hui Xia, Shaokang Wang, Shiqing Chen, Yoong Jun Hao, Guiju Sun

Nutrients . 2022 Mar 5;14(5):1094. doi: 10.3390/nu14051094.


Background: Pulmonary fibrosis (PF) is a chronic, progressive, and, ultimately, terminal interstitial disease caused by a variety of factors, ranging from genetics, bacterial, and viral infections, to drugs and other influences. Varying degrees of PF and its rapid progress have been widely reported in post-COVID-19 patients and there is consequently an urgent need to develop an appropriate, cost-effective approach for the prevention and management of PF.

Aim: The potential “therapeutic” effect of the tocotrienol-rich fraction (TRF) and carotene against bleomycin (BLM)-induced lung fibrosis was investigated in rats via the modulation of TGF-β/Smad, PI3K/Akt/mTOR, and NF-κB signaling pathways.

Design/methods: Lung fibrosis was induced in Sprague-Dawley rats by a single intratracheal BLM (5 mg/kg) injection. These rats were subsequently treated with TRF (50, 100, and 200 mg/kg body wt/day), carotene (10 mg/kg body wt/day), or a combination of TRF (200 mg/kg body wt/day) and carotene (10 mg/kg body wt/day) for 28 days by gavage administration. A group of normal rats was provided with saline as a substitute for BLM as the control. Lung function and biochemical, histopathological, and molecular alterations were studied in the lung tissues.

Results: Both the TRF and carotene treatments were found to significantly restore the BLM-induced alterations in anti-inflammatory and antioxidant functions. The treatments appeared to show pneumoprotective effects through the upregulation of antioxidant status, downregulation of MMP-7 and inflammatory cytokine expressions, and reduction in collagen accumulation (hydroxyproline). We demonstrated that TRF and carotene ameliorate BLM-induced lung injuries through the inhibition of apoptosis, the induction of TGF-β1/Smad, PI3K/Akt/mTOR, and NF-κB signaling pathways. Furthermore, the increased expression levels were shown to be significantly and dose-dependently downregulated by TRF (50, 100, and 200 mg/kg body wt/day) treatment in high probability. The histopathological findings further confirmed that the TRF and carotene treatments had significantly attenuated the BLM-induced lung injury in rats.

Conclusion: The results of this study clearly indicate the ability of TRF and carotene to restore the antioxidant system and to inhibit proinflammatory cytokines. These findings, thus, revealed the potential of TRF and carotene as preventive candidates for the treatment of PF in the future.

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