The Effects of Magnesium and Vitamin E Co-Supplementation on Hormonal Status and Biomarkers of Inflammation and Oxidative Stress in Women with Polycystic Ovary Syndrome

Shokrpour M, Asemi Z

Biol Trace Elem Res. 2018 Dec 18. doi: 10.1007/s12011-018-1602-9. [Epub ahead of print]

Abstract

Synergistic approach of magnesium and vitamin E may benefit clinical symptoms of patients with polycystic ovary syndrome (PCOS) through improving their metabolic profiles and reducing oxidative stress and inflammation. This study was designed to determine the effects of magnesium and vitamin E co-supplementation on hormonal status and biomarkers of inflammation and oxidative stress in women with PCOS. This randomized, double-blind, placebo-controlled trial was conducted among 60 women with PCOS, aged 18-40 years old. Participants were randomly divided into two groups to take 250 mg/day magnesium plus 400 mg/day vitamin E supplements or placebo (n = 30 each group) for 12 weeks. Fasting blood samples were taken at baseline and after the 12-week intervention to quantify related variables. Magnesium and vitamin E co-supplementation resulted in a significant reduction in hirsutism (β - 0.37; 95% CI, - 0.70, - 0.05; P = 0.02) and serum high-sensitivity C-reactive protein (hs-CRP) (β - 0.67 mg/L; 95% CI, - 1.20, - 0.14; P = 0.01), and a significant increase in plasma nitric oxide (NO) (β 3.40 μmol/L; 95% CI, 1.46, 5.35; P = 0.001) and total antioxidant capacity (TAC) levels (β 66.32 mmol/L; 95% CI, 43.80, 88.84; P < 0.001). Overall, magnesium and vitamin E co-supplementation for 12 weeks may benefit women with PCOS on hirsutism, serum hs-CRP, plasma NO, and TAC levels.

Zingg JM

IUBMB Life. 2018 Dec 17. doi: 10.1002/iub.1986. [Epub ahead of print]

Abstract

Vitamin E modulates signal transduction pathways by several molecular mechanisms. As a hydrophobic molecule located mainly in membranes it contributes together with other lipids to the physical and structural characteristics such as membrane stability, curvature, fluidity, and the organization into microdomains (lipid rafts). By acting as the main lipid-soluble antioxidant, it protects other lipids such as mono- and poly-unsaturated fatty acids (MUFA and PUFA, respectively) against chemical reactions with reactive oxygen and nitrogen species (ROS and RNS, respectively) and prevents membrane destabilization and cellular dysfunction. In cells, vitamin E affects signaling in redox-dependent and redox-independent molecular mechanisms by influencing the activity of enzymes and receptors involved in modulating specific signal transduction and gene expression pathways. By protecting and preventing depletion of MUFA and PUFA it indirectly enables regulatory effects that are mediated by the numerous lipid mediators derived from these lipids. In recent years, some vitamin E metabolites have been observed to affect signal transduction and gene expression and their relevance for the regulatory function of vitamin E is beginning to be elucidated. In particular, the modulation of the CD36/FAT scavenger receptor/fatty acids transporter by vitamin E may influence many cellular signaling pathways relevant for lipid homeostasis, inflammation, survival/apoptosis, angiogenesis, tumorigenesis, neurodegeneration, and senescence. Thus, vitamin E has an important role in modulating signal transduction and gene expression pathways relevant for its uptake, distribution, metabolism, and molecular action that when impaired affect physiological and patho-physiological cellular functions relevant for the prevention of a number of diseases.

Lee P, Ulatowski LM

IUBMB Life. 2018 Dec 17. doi: 10.1002/iub.1993. [Epub ahead of print]

Abstract

Although vitamin E has been recognized as a critical micronutrient to neuronal health for more than half a century, vitamin E transport and regulation in the brain remain a mystery. Currently, the majority of what is known about vitamin E transport has been delineated in the liver. However, clues from the pathogenesis of neurological-related vitamin E deficient diseases point to compromised neuronal integrity and function, underlining the critical need to understand vitamin E regulation in the CNS. Additionally, most of the same molecular players involved in vitamin E transport in the liver are also found in CNS, including sterol SRB1, TTP, and ABCA/ABCG, suggesting similar intracellular pathways between these organ systems. Finally, based on chemical similarities, intracellular CNS shuttling of vitamin E likely resembles cholesterol’s use of ApoE particles. Utilizing this information, this review will address what is currently known about trafficking vitamin E across the blood brain barrier in order to ensure an adequate supply of the essential nutrient to the brain. Although debatable, the health of the brain in relation to vitamin E levels has been demonstrated, most notably in oxidative stress-related conditions such as ataxias, Alzheimer’s disease, and Parkinson’s disease. Future vitamin E research is vital in understanding how the regulation of the vitamin can aid in the prevention, treatment, and curing of neurological diseases.

Khadangi F, Azzi A

IUBMB Life. 2018 Dec 14. doi: 10.1002/iub.1990. [Epub ahead of print]

Abstract

α-Tocopherol is the only tocopherol that has been shown to prevent the human deficiency disease Ataxia with Isolated Vitamin E Deficiency (AVED), and thus it is the only one that, for humans, can be called vitamin E. Vitamin E in addition to preventing AVED has documented immune boosting properties and an activity against nonalcoholic hepatosteatosis and low-grade inflammation. Epidemiological studies indicating that vitamin E could prevent cardiovascular events, neurodegenerative disease, macular degeneration, and cancer were in general not confirmed by clinical intervention studies. Vitamin E and some of its metabolites modulate cell signaling and gene transcription. Future research is needed to achieve a better understanding of the molecular events leading to gene regulation by vitamin E, especially in its phosphorylated form. Isolation and characterization of the vitamin E kinase and vitamin E phosphate phosphatase will help in the understanding of cell regulation processes modulated by vitamin E. A clarification of the pathogenesis of AVED remains an important goal to be achieved.

Naguib MM, Valvano MA

mSphere. 2018 Dec 12;3(6). pii: e00564-18. doi: 10.1128/mSphere.00564-18.

Abstract

Burkholderia cenocepacia is an opportunistic Gram-negative bacterium that causes serious respiratory infections in patients with cystic fibrosis. Recently, we discovered that B. cenocepacia produces the extracellular bacterial lipocalin protein BcnA upon exposure to sublethal concentrations of bactericidal antibiotics. BcnA captures a range of antibiotics outside bacterial cells, providing a global extracellular mechanism of antimicrobial resistance. In this study, we investigated water-soluble and liposoluble forms of vitamin E as inhibitors of antibiotic binding by BcnA. Our results demonstrate that in vitro, both vitamin E forms bind strongly to BcnA and contribute to reduce the MICs of norfloxacin (a fluoroquinolone) and ceftazidime (a β-lactam), both of them used as model molecules representing two different chemical classes of antibiotics. Expression of BcnA was required for the adjuvant effect of vitamin E. These results were replicated in vivousing the Galleria mellonella larva infection model whereby vitamin E treatment, in combination with norfloxacin, significantly increased larva survival upon infection in a BcnA-dependent manner. Together, our data suggest that vitamin E can be used to increase killing by bactericidal antibiotics through interference with lipocalin binding.

Jiang Q

IUBMB Life. 2018 Dec 11. doi: 10.1002/iub.1978. [Epub ahead of print]

Abstract

The disappointing results from large clinical studies of α-tocopherol (αT), the major form of vitamin E in tissues, for prevention of chronic diseases including cancer have cast doubt on not only αT but also other forms of vitamin E regarding their role in preventing carcinogenesis. However, basic research has shown that specific forms of vitamin E such as γ-tocopherol (γT), δ-tocopherol (δT), γ-tocotrienol (γTE) and δ-tocotrienol (δTE) can inhibit the growth and induce death of many types of cancer cells, and are capable of suppressing cancer development in preclinical cancer models. For these activities, these vitamin E forms are much stronger than αT. Further, recent research revealed novel anti-inflammatory and anticancer effects of vitamin E metabolites including 13′-carboxychromanols. This review focuses on anti-proliferation and induction of death in cancer cells by vitamin E forms and metabolites, and discuss mechanisms underlying these anticancer activities. The existing in vitro and in vivo evidence indicates that γT, δT, tocotrienols and 13′-carboxychromanols have anti-cancer activities via modulating key signaling or mediators that regulate cell death and tumor progression, such as eicosanoids, NF-κB, STAT3, PI3K, and sphingolipid metabolism. These results provide useful scientific rationales and mechanistic understanding for further translation of basic discoveries to the clinic with respect to potential use of these vitamin E forms and metabolites for cancer prevention and therapy.

Noguchi M, Yamawaki I, Takahashi S, Taguchi Y, Umeda M

J Oral Sci. 2018;60(4):579-587. doi: 10.2334/josnusd.17-0422.

Abstract

It is widely accepted that vitamin E (VE) acts as an antioxidant and is involved in various metabolic systems including the regulation of gene expression and inhibition of cell proliferation. The most predominant isoform of VE in the living body is α-tocopherol. However, the influence of α-tocopherol on bone marrow mesenchymal cells (BMMCs) in a background of type II diabetes mellitus (DM) has not been investigated. The focus of the present study was to clarify the effect of α-tocopherol on BMMCs derived from rats with type II DM and the underlying mechanisms involved. BMMCs were isolated from rats with type II DM. The BMMCs were either untreated or exposed to α-tocopherol at concentrations of 1.0, 10, and 100 μM, and the resulting effects of α-tocopherol on cell proliferation, H₂O₂ activity, and antioxidant and inflammatory cytokine production were examined. At 100 μM, α-tocopherol had no effect on cell proliferation, but H₂O₂ activity was significantly increased. At 10 μM, α-tocopherol increased the gene expression of IL-1β, and markedly promoted that of TNF-α. Expression of catalase in the presence of 100 μM α-tocopherol was lower than for the other concentrations. At a low concentration, α-tocopherol exerted good antioxidant and anti-inflammatory effects on BMMCs. The study suggests that maintaining α-tocopherol at a low concentration might promote the recovery of BMMCs from oxidative stress.

Desrumaux CM, Mansuy M, Lemaire S, Przybilski J, Le Guern N, Givalois L, Lagrost L

Front Behav Neurosci. 2018 Dec 11;12:310. doi: 10.3389/fnbeh.2018.00310. eCollection 2018.

Abstract

Vitamin E, the most important lipophilic radical scavenging antioxidant in vivo, has a pivotal role in brain. In an earlier study, we observed that adult mice with a defect in the gene encoding plasma phospholipid transfer protein (PLTP) display a moderate reduction in cerebral vitamin Elevels, and exacerbated anxiety despite normal locomotion and memory functions. Here we sought to determine whether dietary vitamin Esupplementation can modulate neurotransmitter levels and alleviate the increased anxiety phenotype of PLTP-deficient (PLTP ^-/-) mice. To address this question, a vitamin E-enriched diet was used, and two complementary approches were implemented: (i) “early supplementation”: neurotransmitter levels and anxiety were assessed in 6 months old PLTP ^-/- mice born from vitamin E-supplemented parents; and (ii) “late supplementation”: neurotransmitter levels and anxiety were assessed in 6 months old PLTP ^-/- mice fed a vitamin E-enriched diet from weaning. Our results show for the first time that an inadequate supply of vitamin E during development, due to moderate maternal vitamin E deficiency, is associated with reduced brain vitamin E levels at birth and irreversible alterations in brain glutamate levels. They also suggest this deficiency is associated with increased anxiety at adulthood. Thus, the present study leads to conclude on the importance of the micronutrient vitamin E during pregnancy.

Shvachko LP, Zavelevich MP, Gluzman DF, Kravchuk IV, Telegeev GD

Exp Oncol. 2018 Dec;40(4):328-331.

Abstract

BACKGROUND:

Chronic myeloid leukemia (CML) is a clonal hematopoietic stem cell disorder associated with the activity of BCR-ABL fusion oncogene. Tyrosine kinase inhibitors are the current treatment of CML, but secondary mutations finally contribute to therapy resistance and blast crisis of the disease. The search for the novel compounds for the effective control of CML is now in the spotlight. The progression of CML to blast crisis is correlated with down-modulation of C/EBP alpha. Therefore, C/EBP alpha may be considered as a putative target in differentiation therapies in myeloid leukemias. The aim of the study was to assess the potential of vitamin E as the possible inducer of C/EBP alpha expression in BCR-ABL-positive CML K562 cells.

MATERIALS AND METHODS:

RNA extracted from K562 cells cultured with valproic acid or vitamin E was converted to cDNA, RT-PCR reactions were carried out using HotStarTaq DNA polymerase with primers for C/EBP alpha and granulocyte colony-stimulating factor receptor (G-CSFR).

RESULTS:

We have not found detectable expression of C/EBP alpha in K562 cells. Upon 48-h culture with vitamin E at a dose of 100 µM, K562 cells expressed both C/EBP alpha and G-CSFR.

CONCLUSION:

Vitamin E restored the expression of C/EBP alpha mRNA in chronic myelogenous leukemia K562 cells. In this setting, G-CSFR expression in vitamin E treated K562 cells seems to suggest the activation to granulocytic differentiation. It should be further elucidated whether such effects of vitamin E on C/EBP alpha transcription factor are direct or mediated indirectly due to antioxidant properties of vitamin E.

Melčová M, Száková J, Mlejnek P, Zídek V, Fučíková A, Praus L, Zídková J, Mestek O, Kaňa A, Mikulík K, Tlustoš P

Pol J Vet Sci. 2018 Dec;21(4):731-740. doi: 10.24425/124312.

Abstract

The normotensive (Wistar) and spontaneously hypertensive (SHR) rats were examined to assess the response of the organism to selenium (Se) overdose. Moreover, the effect of zinc (Zn) and vitamin E, i.e. dietary components interacting in many biochemical processes with Se, on the Se uptake was evaluated. The control group was fed an untreated diet, and the diets of two other groups were overdosed with Se in the form of sodium selenite (9 mg/kg) and supplemented with Zn (13 mg/kg). Two experimental groups were fed a diet supplemented with Zn (13 mg/kg) and Se at an adequate level (0.009 mg/kg); a half of the animals was supplemented with vitamin E. The results showed significant differences in the Se contents between the rat strains in case of Se-overdosed groups, where in the liver and kidney tissue Se contents of SHR rats exceeded 3- and 7-fold the normotensive ones. The Se uptake was altered by the vitamin E; no effect of Zn was observed. Activities of antioxidant enzymes were determined in the animal tissues indicating different patterns according to rat strain, tissue analysed, and administered Se dose. Thus, Se overdose, for instance, via an incorrectly prepared dietary supplement, can result in serious imbalances of the biochemical status of the animals.