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.

Abstract

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.

Erdem Danyer, Tanay Bilal, Ayşen Altiner, İsmail Aytekin, Hasan Atalay

J Anim Physiol Anim Nutr (Berl) . 2021 Jun 11. doi: 10.1111/jpn.13560. Online ahead of print.

Abstract

The study aimed to investigate the effects of vitamin E injection for the prevention of transport stress on ewes. Kivircik ewes (2-3 years old, n = 24) were randomly separated into three groups; G1 (Control) and G2 treated with 14 ml. saline as the placebo, G3 treated with 2100 IU/ind. DL-alpha-tocopherol acetate prior to transport. G2 and G3 were transported at 80 km/h for 4 h on a truck. Serum samples were obtained before (T0) and after (T1) transport. Serum cortisol, catalase, IgG, ceruloplasmin, C-reactive protein, complement component 4, interleukin-1 beta, tumour necrosis factor-alpha, glutathione peroxidase (GPx), superoxide dismutase, malondialdehyde analyses performed by ELISA, and serum alpha-tocopherol concentrations were evaluated by HPLC-UV. Wilcoxon and Kruskal-Wallis tests were used for statistical assessments (p < 0.05). Alpha-tocopherol concentrations were founded 1.22 ± 0.82, 0.27 ± 0.14 and 0.14 ± 0.07 µmol/L, respectively, in G1, G2 and G3 at T1. Alpha-tocopherol concentration decreased significantly in G2 between T0 and T1. GPx concentrations were increased twofold in G2 and G3 between T0 and T1 (p < 0.01). As a result, G2 alpha-tocopherol concentrations decreased but, the stress and oxidative parameters tested in this study were not affected by treating 2100 IU/ind. DL-alpha-tocopherol acetate before transport.

William S Blaner, Igor O Shmarakov, Maret G Traber

Annu Rev Nutr . 2021 Jun 11. doi: 10.1146/annurev-nutr-082018-124228. Online ahead of print.

Abstract

Vitamin A, acting through its metabolite, all-trans-retinoic acid, is a potent transcriptional regulator affecting expression levels of hundreds of genes through retinoic acid response elements present within these genes. However, the literature is replete with claims that consider vitamin A to be an antioxidant vitamin, like vitamins C and E. This apparent contradiction in the understanding of how vitamin A acts mechanistically within the body is a major focus of this review. Vitamin E, which is generally understood to act as a lipophilic antioxidant protecting polyunsaturated fatty acids present in membranes, is often proposed to be a transcriptional regulator. The evaluation of this claim is another focus of the review. We conclude that vitamin A is an indirect antioxidant, whose indirect function is to transcriptionally regulate a number of genes involved in mediating the body’s canonical antioxidant responses. Vitamin E, in addition to being a direct antioxidant, enables the increase of peroxidized lipids that alter both metabolic pathways and gene expression profiles within tissues and cells. However, there is little compelling evidence that vitamin E has a direct transcriptional mechanism like that of vitamin A. Thus, we propose that the term antioxidant not be applied to vitamin A, and we discourage the use of the term transcriptional mediator when discussing vitamin E.

Alexander T Watt, Brian Head, Scott W Leonard, Robyn L Tanguay, Maret G Traber

J Nutr Biochem . 2021 Jun 10;108801. doi: 10.1016/j.jnutbio.2021.108801. Online ahead of print.

Abstract

An evaluation of the impact of vitamin E deficiency on expression of the alpha-tocopherol transfer protein (α-TTP) and related CRAL_TRIO genes was undertaken using livers from adult zebrafish based on the hypothesis that increased lipid peroxidation would modulate gene expression. Zebrafish were fed either a vitamin E sufficient (E+) or deficient (E-) diet for 9 months, then fish were euthanized, and livers were harvested. Livers from the E+ relative to E- fish contained 40-times more α-tocopherol (P<0.0001) and one fourth the malondialdehyde (P = 0.0153). RNA was extracted from E+ and E- livers, then subject to evaluation of gene expression of ttpa and other genes of the CRAL_TRIO family, genes of antioxidant markers, and genes related to lipid metabolism. Ttpa expression was not altered by vitamin E status. However, one member of the CRAL_TRIO family, tyrosine-protein phosphatase non-receptor type 9 gene (ptpn9a), showed a 2.4-fold increase (P=0.029) in E- relative to E+ livers. Further, we identified that the gene for choline kinase alpha (chka) showed a 3.0-fold increase (P=0.010) in E- livers. These outcomes are consistent with our previous findings that show vitamin E deficiency increased lipid peroxidation causing increases in phospholipid turnover.

Kacper Szewczyk, Aleksandra Chojnacka, Magdalena Górnicka

Int J Mol Sci . 2021 Jun 9;22(12):6222. doi: 10.3390/ijms22126222.

Abstract

Tocopherols and tocotrienols are natural compounds of plant origin, available in the nature. They are supplied in various amounts in a diet, mainly from vegetable oils, some oilseeds, and nuts. The main forms in the diet are α- and γ-tocopherol, due to the highest content in food products. Nevertheless, α-tocopherol is the main form of vitamin E with the highest tissue concentration. The α- forms of both tocopherols and tocotrienols are considered as the most metabolically active. Currently, research results indicate also a greater antioxidant potential of tocotrienols than tocopherols. Moreover, the biological role of vitamin E metabolites have received increasing interest. The aim of this review is to update the knowledge of tocopherol and tocotrienol bioactivity, with a particular focus on their bioavailability, distribution, and metabolism determinants in humans. Almost one hundred years after the start of research on α-tocopherol, its biological properties are still under investigation. For several decades, researchers’ interest in the biological importance of other forms of vitamin E has also been growing. Some of the functions, for instance the antioxidant functions of α- and γ-tocopherols, have been confirmed in humans, while others, such as the relationship with metabolic disorders, are still under investigation. Some studies, which analyzed the biological role and mechanisms of tocopherols and tocotrienols over the past few years described new and even unexpected cellular and molecular properties that will be the subject of future research.

N C M Amorim, A G C L Silva, A S Rebouças, D S Bezerra, M S R Lima, J F Pires, L C P Liberalino, R Dimenstein, K D S Ribeiro

Br J Nutr . 2021 Jun 9;1-23. doi: 10.1017/S0007114521001963. Online ahead of print.

Abstract

Despite evidence showing that the intake of ultra-processed food has a negative impact on health, diet quality and dietary vitamin E, its impact on vitamin E nutritional status and breast milk remains unknown. This study aimed to assess the influence of the consumption of ultra-processed foods on vitamin E biomarkers of lactating women. A cross-sectional study was performed with 294 lactating women. Food consumption was obtained by 24-hour dietary recall and foods were grouped according to the NOVA classification. Levels of alpha-tocopherol were analyzed by High Performance Liquid Chromatography. Breast milk vitamin E (BMVE) adequacy was based on the quantity of the vitamin in the estimated intake volume. The Kruskal-Wallis test was used to compare the tertiles and linear regression to association between ultra-processed food consumption and biomarkers. Ultra-processed foods accounted for 16% of energy intake and vitamin E intakes by all women were considered low. Serum alpha-tocopherol was 26.55 (SD 7.98) µmol/L, 5% (n=11) showed inadequate vitamin E (<12µmol/L), and 78% had an inadequate BMVE content (< 4mg/780mL). The regression showed that a higher dietary share of ultra-processed foods was associated with lower concentrations of serum alpha-tocopherol (β=-0.168, CI=-0.047-0.010, p=0.003) and inadequate BMVE content (β=-0.144, CI=-0.505-0.063, p=0.012) (adjustment for income and maternal age). Thus, higher dietary shares of ultra-processed foods had an impact on vitamin E biomarkers, suggesting that inadequate dietary intake practices during lactation may reduce the supply of vitamin E to women and breast milk.

Huixian Yan, Xiyou Du, Rujuan Wang, Guangxi Zhai

Colloids Surf B Biointerfaces . 2021 Jun 8;205:111914.

Abstract

Currently, multidrug resistance (MDR) is one of the major reasons for failure in clinical cancer chemotherapy. Overexpression of the ATP binding cassette (ABC) transporter P-glycoprotein (P-gp), which significantly increases the efflux of anticancer drugs from tumor cells, enhances MDR. In the past few decades, four generations of P-gp inhibitors have appeared. However, they are limited in clinical application due to their severe toxic side effects. As a P-gp inhibitor and carrier for loading chemotherapy agents, TPGS has received increasing attention due to its advantages and unique properties of reversing MDR. TPGS is an amphipathic agent that increases the solubility of most chemotherapy drugs and decreases severe side effects. In addition, TPGS is an excellent carrier with P-gp-inhibiting ability. In this review, we summarize the latest articles on TPGS-based nanodelivery systems to prevent MDR.

Karl Michaëlsson, Susanna C Larsson

Nutrients . 2021 Jun 5;13(6):1940. doi: 10.3390/nu13061940.

Abstract

Recent cohort studies indicate a potential role of the antioxidant α-tocopherol in reducing bone loss and risk of fractures, especially hip fractures. We performed a Mendelian randomization investigation of the associations of circulating α-tocopherol with estimated bone mineral density (eBMD) using heel ultrasound and fractures, identified from hospital records or by self-reports and excluding minor fractures. Circulating α-tocopherol was instrumented by three genetic variants associated with α-tocopherol levels at p < 5 × 10^-8 in a genome-wide association meta-analysis of 7781 participants of European ancestry. Summary-level data for the genetic associations with eBMD in 426,824 individuals and with fracture (53,184 cases and 373,611 non-cases) were acquired from the UK Biobank. Two of the three genetic variants were strongly associated with eBMD. In inverse-variance weighted analysis, a genetically predicted one-standard-deviation increase of circulating α-tocopherol was associated with 0.07 (95% confidence interval, 0.05 to 0.09) g/cm² increase in BMD, which corresponds to a >10% higher BMD. Genetically predicted circulating α-tocopherol was not associated with odds of any fracture (odds ratio 0.97, 95% confidence interval, 0.91 to 1.05). In conclusion, our results strongly strengthen a causal link between increased circulating α-tocopherol and greater BMD. Both an intervention study in those with a low dietary intake of α-tocopherol is warranted and a Mendelian randomization study with fragility fractures as an outcome.

Quang Luu Quoc, Tra Cao Thi Bich, Seo-Hee Kim, Hae-Sim Park, Yoo Seob Shin

J Cell Mol Med . 2021 Jun 4. doi: 10.1111/jcmm.16675. Online ahead of print.

Abstract

Accumulating evidence reveals that ROS is one of the key mediators that contribute to the development of asthma. Studies on antioxidants have shown to have beneficial effects on asthma management. However, we still do not know the precise mechanism, and the effects depend on age. This study was conducted to assess the levels of ROS and the effect of antioxidants in younger and older mice using an eosinophilic asthma model. We analyzed airway hyperresponsiveness (AHR), cytokines in bronchoalveolar lavage fluid (BALF), inflammatory cell counts, and the expression levels of NFκB, Nrf2, EPx, and EDN in the lung tissue, as well as the level of ROS in the lung tissue and BALF. The degree of eosinophilia and the levels of IL-5, ROS, and NFκB were significantly increased, whereas the endogenous levels of vitamin E and Nrf2 were decreased in the lung and BALF in the older mice compared to younger mice. The administration of vitamin E attenuated AHR, airway inflammation, and the level of IL-13 and ROS and enhanced the Nrf2 level in the older mice compared to the younger mice. Taken together, vitamin E treatment may have the therapeutic potential through restoration of the Nrf2 level, especially in elderly asthma.

Fernanda Mateus Queiróz Schmidt, Carol V Serna González, Rodrigo Calixto Mattar, Luciana Biagini Lopes, Marinilce Fagundes Dos Santos, Vera L C de Gouveia Santos

J Wound Care . 2021 Jun 1;30(Sup6):S44-S50. doi: 10.12968/jowc.2021.30.Sup6.S44.

Abstract

Objective: Little is known about the efficacy of products aiming to prevent radiodermatitis, which affects between 90-95% of women with breast cancer. The use of antioxidants is promising, however, there is a lack of evidenceon their effectiveness. Here, the authors present a clinical trial protocol to evaluate the effects of applying a cream containing nanoparticles with vitamin E to prevent radiodermatitis in patients with breast cancer.

Method: The protocol recommends that 108 women with breast cancer, receiving radiotherapy, are included in this triple-blinded, randomized, controlled study at an oncology hospital. Patients will be divided in three groups of 36 individuals each: group A will receive a cream with lipid nanoparticles and vitamin E, group B will receive a cream without nanoparticles nor vitamin E, and group C will receive a cream with nanoparticles without vitamin E. The primary endpoints will evaluate the incidence, degree, and time of onset of radiodermatitis. The secondary endpoints will focus on the quality of life, symptoms, and local temperature. Patients will be assessed three times a week, from the start of their radiotherapy treatment to two weeks after the last session. This protocol was approved by the research ethics committee of the institutions involved and registered on an international trials database.