Antioxidant effects of vitamin E and risk of cardiovascular disease in women with obesity – A narrative review

Anna Maria Rychter, Szymon Hryhorowicz, Ryszard Słomski, Agnieszka Dobrowolska, Iwona Krela-Kaźmierczak

Clin Nutr . 2022 May 6;41(7):1557-1565. doi: 10.1016/j.clnu.2022.04.032. Online ahead of print.


Proper dietary habits are a vital element of cardiovascular (CV) treatment, and – according to the current guidelines – a diet rich in antioxidants is generally recommended. It remains, however, inconclusive whether antioxidant nutrients should be supplemented for CV health, and if so, in which form and dosage. Currently available data suggest that vitamin E may be essential in preventing CVD, especially in coronary heart disease and atherosclerosis – nevertheless, vitamin E supplementation may be questionable and may even be associated with adverse outcomes. Further, current studies highlight a strong need for identifying sex-specific strategies, which could improve guidelines for both the prevention and management of cardiovascular disease (CVD). It should also be emphasized that understanding the role of genetic variants in genes involved in VE metabolism may also be crucial for more precise nutritional recommendations for patients suffering from CVD. Therefore, we summarize the current knowledge regarding vitamin E antioxidant properties, which could be essential from CV perspective, and aim to assess whether vitamin E supplementation can be beneficial in CV prevention, especially in the high-risk group of women with obesity.

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Effect of vitamin E supplementation on cardiometabolic risk factors, inflammatory and oxidative markers and hormonal functions in PCOS (polycystic ovary syndrome): a systematic review and meta-analysis

Ghazale Tefagh, Moloud Payab, Mostafa Qorbani, Farshad Sharifi, Yasaman Sharifi, Mahbubeh Sadat Ebrahimnegad Shirvani, Farzad Pourghazi, Rasha Atlasi, Zhaleh Shadman, Nafiseh Rezaei, Erfan Mohammadi-Vajari, Bagher Larijani, Mahbube Ebrahimpur

Sci Rep . 2022 Apr 6;12(1):5770. doi: 10.1038/s41598-022-09082-3.


Polycystic ovary syndrome (PCOS) is a common endocrinopathy among reproductive-age women. Various therapeutical approaches are currently used to manage or control symptoms associated with PCOS. This systematic review intended to assess the effects of Vit E supplementation on cardiometabolic risk factors, inflammatory and oxidative markers, and hormonal functions in PCOS women based on the clinical trial’s results. The databases including PubMed, Scopus, Cochrane, Web of Science, and Embase were used to find all relevant studies. The authors reviewed all relevant clinical trials via systematic evaluation of abstracts and titles. Searches were conducted on August 1, 2020. After the initial search and reading of the article’s title and abstract, 353 articles were reviewed; finally, 12 articles met the inclusion criteria. Vitamin E supplementation improves lipid profile, decreases insulin and HOMA-IR levels. Furthermore, while Vitamin E supplementation decreases LH and testosterone concentrations, it increases FSH and progestrone concentrations. The following meta-analysis showed that vitamin E supplementation made statistically significant improvements in triglyceride (TG) and low-density lipoproteins (LDL) levels, meanwhile, pooled mean difference for waist circumference (WC) and HOMA-IR were also statistically significant. Supplementary regimens containing vitamin E can positively affect metabolic and hormonal parameters in women with PCOS.

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Vitamin E: Where Are We Now in Vascular Diseases?

Anahita Garg, Jetty Chung-Yung Lee

Life (Basel) . 2022 Feb 18;12(2):310. doi: 10.3390/life12020310.


Vitamin E is one of the most popular fat-soluble vitamins in pathological research and has been under scrutiny since the 1980s as a vital dietary component of food. The antioxidant effect of vitamin E has been widely studied due to its benefits in the prevention of various cardiovascular diseases. In recent years, alternative effects of vitamin E, in terms of anti-inflammatory pathways and gene regulation, have also been of interest to researchers. This review examines the role of dietary vitamin E (α-tocopherol) as an antioxidant and bioactive molecule in promoting vascular health. While the antioxidant effect of vitamin E is well established, knowledge about its capacity as a promising regulatory molecule in the control of the vascular system is limited. The aim of this review is to discuss some of these mechanisms and summarize their role in the prevention of cardiovascular diseases (CVD). Here, we also briefly discuss foods rich in vitamin E, and deliberate some potential toxicological effects of excessive supplemental vitamin E in the body.

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Mitigation of late cardiovascular effects of oxygen ion radiation by γ-tocotrienol in a mouse model

Ashley S Nemec-Bakk, Vijayalakshmi Sridharan, Reid D Landes, Preeti Singh, Maohua Cao, John W Seawright, Xingui Liu, Guangrong Zheng, Paari Dominic, Rupak Pathak, Marjan Boerma

Life Sci Space Res (Amst) . 2021 Nov;31:43-50. doi: 10.1016/j.lssr.2021.07.006. Epub 2021 Aug 3.


Purpose: While there is concern about degenerative tissue effects of exposure to space radiation during deep-space missions, there are no pharmacological countermeasures against these adverse effects. γ-Tocotrienol (GT3) is a natural form of vitamin E that has anti-oxidant properties, modifies cholesterol metabolism, and has anti-inflammatory and endothelial cell protective properties. The purpose of this study was to test whether GT3 could mitigate cardiovascular effects of oxygen ion (16O) irradiation in a mouse model.

Materials and methods: Male C57BL/6 J mice were exposed to whole-body 16O (600 MeV/n) irradiation (0.26-0.33 Gy/min) at doses of 0 or 0.25 Gy at 6 months of age and were followed up to 9 months after irradiation. Animals were administered GT3 (50 mg/kg/day s.c.) or vehicle, on Monday – Friday starting on day 3 after irradiation for a total of 16 administrations. Ultrasonography was used to measure in vivo cardiac function and blood flow parameters. Cardiac tissue remodeling and inflammatory infiltration were assessed with histology and immunoblot analysis at 2 weeks, 3 and 9 months after radiation.

Results: GT3 mitigated the effects of 16O radiation on cardiac function, the expression of a collagen type III peptide, and markers of mast cells, T-cells and monocytes/macrophages in the left ventricle.

Conclusions: GT3 may be a potential countermeasure against late degenerative tissue effects of high-linear energy transfer radiation in the heart.

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Interventional study with vitamin E in cardiovascular disease and meta-analysis

Francesco Violi, Cristina Nocella, Lorenzo Loffredo, Roberto Carnevale, Pasquale Pignatelli

Free Radic Biol Med . 2021 Nov 25;S0891-5849(21)00825-X. doi: 10.1016/j.freeradbiomed.2021.11.027. Online ahead of print.


Cardiovascular disease (CVD) is one of the major causes of morbidity and mortality and atherosclerosis is the common root to most of the CVD. Oxidative stress is one of the most important factors driving atherosclerosis and its complications. Thus, strategies for the prevention and treatment of cardiovascular events had oxidative changes as a potential target. Natural vitamin E consists of a family of eight different compounds, four tocopherols and four tocotrienols. All tocopherols and tocotrienols are potent antioxidants with lipoperoxyl radical-scavenging activities. In addition, α-tocopherol possesses also anti-inflammatory as well as anti-atherothrombotic effects by modulating platelet and clotting system. Experimental and in vitro studies described molecular and cellular signalling pathways regulated by vitamin E antithrombotic and antioxidant properties. While observational studies demonstrated an inverse association between vitamin E serum levels and CVD, interventional trials with vitamin supplements provided negative results. This review focus on the impact of vitamin E in the atherothrombotic process and describes the results of experimental and clinical studies with the caveats related to the interventional trials with vitamin E to prevent CVD.

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A double-blind randomised controlled trial on the effect of Tocovid, a tocotrienol-rich capsule on postoperative atrial fibrillation at the National Heart Institute, Kuala Lumpur: an interim blinded analysis

Ahmad Farouk Musa, Jeswant Dillon, Mohamed Ezani Md Taib, Alwi Mohamed Yunus, Abdul Rais Sanusi, Mohd Nazeri Nordin, Julian A Smith

J Cardiothorac Surg . 2021 Nov 24;16(1):340. doi: 10.1186/s13019-021-01721-6.


Introduction: Post-operative atrial fibrillation (POAF) is associated with poorer outcomes, increased resource utilisation, morbidity and mortality. Its pathogenesis is initiated by systemic inflammation and oxidative stress. It is hypothesised that a potent antioxidant and anti-inflammatory agent such as tocotrienol, an isomer of Vitamin E, could reduce or prevent POAF.

Aims: The aim of this study is to determine whether a potent antioxidative and anti-inflammatory agent, Tocovid, a tocotrienol-rich capsule, could reduce the incidence of POAF and affect the mortality and morbidity as well as the duration of ICU, HDU and hospital stay.

Methods: This study was planned as a prospective, randomised, controlled trial with parallel groups. The control group received placebo containing palm superolein while the treatment group received Tocovid capsules. We investigated the incidence of POAF, the length of hospital stay after surgery and the health-related quality of life.

Results: Recruitment commenced in January 2019 but the preliminary results were unblinded as the study is still ongoing. Two-hundred and two patients have been recruited out of a target sample size of 250 as of January 2021. About 75% have completed the study and 6.4% were either lost during follow-up or withdrew; 4% of participants died. The mean age group was 61.44 ± 7.30 years with no statistical difference between the groups, with males having a preponderance for AF. The incidence of POAF was 24.36% and the mean time for developing POAF was 55.38 ± 29.9 h post-CABG. Obesity was not a predictive factor. No statistically significant difference was observed when comparing left atrial size, NYHA class, ejection fraction and the premorbid history. The mean cross-clamp time was 71 ± 34 min and the mean bypass time was 95 ± 46 min, with no difference between groups. There was a threefold increase in death among patients with POAF (p = 0.008) and an increase in the duration of ICU stay (p = 0.01), the total duration of hospital stay (p = 0.04) and reintubation (p = 0.045).

Conclusion: A relatively low incidence rate of POAF was noted although the study is still ongoing. It remains to be seen if our prophylactic intervention using Tocovid would effectively reduce the incidence of POAF.

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Vitamins E and C do not effectively inhibit low density lipoprotein oxidation by ferritin at lysosomal pH

Oluwatosin O Ojo, David S Leake

Free Radic Res . 2021 Aug 16;1-10. doi: 10.1080/10715762.2021.1964494. Online ahead of print.


Low density lipoprotein (LDL) might be oxidized by iron in the lysosomes of macrophages in atherosclerotic lesions. We have shown previously that the iron-storage proteinferritin can oxidize LDL at lysosomal pH. We have now investigated the roles of the most important antioxidant contained in LDL, α-tocopherol (the main form of vitamin E) and of ascorbate (vitamin C), a major water-soluble antioxidant, on LDL oxidation by ferritin at lysosomal pH (pH 4.5). We incubated LDL with ferritin at pH 4.5 and 37 °C and measured its oxidation by monitoring the formation of conjugated dienes at 234 n min a spectrophotometer. α-Tocopherol is well known to inhibit LDL oxidation at pH 7.4, but enrichment of LDL with α-tocopherol was unable to inhibit LDL oxidation by ferritin at pH 4.5. Ascorbate had a complex effect on LDL oxidation by ferritin at lysosomal pH and exhibited both antioxidant and pro-oxidant effects. It had no antioxidant effect on partially oxidized LDL, only a pro-oxidant effect. Ascorbate completely inhibited LDL oxidation by copper at pH 7.4 for a long period, but in marked contrast did not inhibit LDL oxidation by copper at lysosomal pH. Dehydroascorbate, the oxidation product of ascorbate, had a pronounced pro-oxidant effect on LDL incubated with ferritin at pH 4.5. The inability of α-tocopherol and ascorbate to effectively inhibit LDL oxidation by ferritin at lysosomal pH might help to explain why the large clinical trials with these vitamins failed to show protection against cardiovascular diseases.

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Implications of advanced oxidation protein products and vitamin E in atherosclerosis progression

Leila Azouaou Toualbi, Adnane Mounir, Ballouti Wafa, Arab Medina, Khelfi Abderrezak, Toualbi Chahine, Chader Henni, Bennoui Abdelghani, Seba Atmane

Arch Med Sci Atheroscler Dis . 2021 Jun 30;6:e135-e144. doi: 10.5114/amsad.2021.107823. eCollection 2021.


Introduction: Advanced oxidation protein products (AOPP) are considered as markers of oxidative stress and inflammation, and highly predictive of atherosclerosis. Vitamin E (Vit-E) is a powerful antioxidant, but no consensus on its effectiveness at the level of AOPP or the process of atherosclerosis has been made. Hence this was the aim of the present study.

Material and methods: A longitudinal study was conducted on 205 patients with chronic kidney disease (CKD) and 40 controls. The correlations between AOPP and glomerular filtration rate (GFR) and different biological markers were analyzed. Supra-aortic trunk echo-Doppler was conducted to assess the correlation of AOPP with intima-media thickness. The effects of Vit-E treatment on AOPP levels and atherosclerosis progression were also investigated.

Results: AOPP levels increased in parallel to the alteration of renal functions in CKD patients, compared to the control group (p < 0.05). The mean value of AOPP increased concomitantly with the intima-media thickness (p < 0.05). Furthermore, AOPP mean value was higher in patients with atherosclerotic plaques (p < 0.05) compared to those without plaques. Vit-E treatment stabilized the levels of AOPP but had no effect on the atherosclerotic progression.

Conclusions: AOPP were proved to be effective markers of oxidative stress and their high levels help to predict the progression of atherosclerosis. As a powerful antioxidant, Vit-E stabilized the AOPP levels.

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A Systematic Review of Effects of Vitamin E on the Cardiovascular System

Sunil Shah, Yasir Shiekh, Jannel A Lawrence, Francis Ezekwueme, Mohammad Alam, Saru Kunwar, Domonick K Gordon

Cureus . 2021 Jun 12;13(6):e15616. doi: 10.7759/cureus.15616. eCollection 2021 Jun.


Vitamin E is a fat-soluble vitamin and an antioxidant that prevents the peroxidation of lipid in vitro. The antioxidant role of vitamin E in preventing adverse cardiovascular outcomes is controversial as some studies support it, while others reject it. Therefore, this review aims to determine whether there is an association between vitamin E and cardiovascular diseases (CVDs). An electronic search was done to find out relevant articles. Papers were shortlisted after the initial title and abstract screen. A full-text study was done, and inclusion and exclusion criteria were applied before the quality assessment of each paper was done. Only high-quality papers were selected for analysis. Full-text articles of the last ten years were included, while non-English articles, gray literature, and animal studies were excluded. The majority of the papers, including 75% of the total population in this review, suggested no role of vitamin E in preventing CVD and CVD mortality. Some studies also suggested that a high level of vitamin E can be associated with adverse cardiovascular outcomes. Thus, one should be prudent about taking vitamin E supplementation for cardiovascular risk prevention.

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The effects of tocotrienols intake on obesity, blood pressure, inflammation, liver and glucose biomarkers: a meta-analysis of randomized controlled trials

Fengxiang Li, Biao Xu, Samira Soltanieh, Fernando Zanghelini, Ahmed Abu-Zaid, Jian Sun

Crit Rev Food Sci Nutr . 2021 Apr 28;1-14. doi: 10.1080/10408398.2021.1911926. Online ahead of print.


The objective of this study is to accomplish a systematic review and meta-analysis of all randomized controlled trials that dissected the influence of tocotrienol supplementation on various anthropometric and cardiometabolic indices in all individuals, irrespective of health condition. This research was carried out in line with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement guidelines. 17 eligible articles were included in the final quantitative analysis. Current study revealed that tocotrienol consumption was not associated with CRP, WC, MDA, BMI, IL-6, HbA1C, ALT, AST, creatinine TNF-α, FPG, BW, DBP, and SBP. We did observe an overall increase in BW (SMD: 0.063 kg, 95% CI: -0.200, 0.327, p = 0.637) and DBP (SMD: 0.249 mmHg, 95% CI: 0.053, 0.446, p = 0.013). In addition, a significant reduction in SBP was observed (SMD: -0.616 mmHg, 95% CI: -1.123, -0.110, p = 0.017). In summary, our meta-analysis revealed that tocotrienol consumption was associated with increase in BW and DBP and decrease in SBP. Significant associations were not observed for other outcomes.

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