Delineation of the Individual Effects of Vitamin E Isoforms on Early Life Incident Wheezing

Stone CA Jr, Cook-Mills J, Gebretsadik T, Rosas-Salazar C, Turi K, Brunwasser SM, Connolly A, Russell P, Liu Z, Costello K, Hartert TV

J Pediatr. 2018 Dec 5. pii: S0022-3476(18)31552-X. doi: 10.1016/j.jpeds.2018.10.045. [Epub ahead of print]

Abstract

OBJECTIVES:

To test the hypothesis that maternal plasma alpha-tocopherol levels are associated with protection from childhood wheeze and that this protection is modified by gamma-tocopherol.

STUDY DESIGN:

We conducted a prospective nested study in the Infant Susceptibility to Pulmonary Infections and Asthma Following Respiratory Syncytial Virus Exposure birth cohort of 652 children with postpartum maternal plasma vitamin E isoforms used as a surrogate for pregnancy concentrations. Our outcomes were wheezing and recurrent wheezing over a 2-year period, ascertained using validated questionnaires. We assessed the association of alpha- and gamma-tocopherol with wheezing outcomes using multivariable adjusted logistic regression, and tested for interaction between the isoforms with respect to the risk for wheezing outcomes.

RESULTS:

Children with wheezing (n = 547, n = 167; 31%) and recurrent wheezing (n = 545, n = 55; 10.1%) over a 2-year period were born to mothers with significantly lower postpartum maternal plasma concentrations of alpha-tocopherol, P = .016 and P = .007, respectively. In analyses of IQR increases, alpha-tocopherol was associated with decreased risk of wheezing (aOR 0.70 [95% CI 0.53,0.92]) and recurrent wheezing (aOR 0.63 [95% CI 0.42,0.95]). For gamma-tocopherol, the aOR for wheezing was 0.79 (95% CI 0.56-1.10) and the aOR for recurrent wheezing was 0.56 (95% CI 0.33-0.94, with nonmonotonic association). The association of alpha-tocopherol with wheezing was modified by gamma-tocopherol (P interaction = .05).

CONCLUSIONS:

Increases in postpartum maternal plasma alpha-tocopherol isoform concentrations were associated with decreased likelihood of wheezing over a 2-year period. Gamma-tocopherol modified this association.

Galmés S, Serra F, Palou A

Nutrients. 2018 Dec 4;10(12). pii: E1919. doi: 10.3390/nu10121919.

Abstract

Vitamin E (VE) has a recognized leading role as a contributor to the protection of cell constituents from oxidative damage. However, evidence suggests that the health benefits of VE go far beyond that of an antioxidant acting in lipophilic environments. In humans, VE is channeled toward pathways dealing with lipoproteins and cholesterol, underlining its relevance in lipid handling and metabolism. In this context, both VE intake and status may be relevant in physiopathological conditions associated with disturbances in lipid metabolism or concomitant with oxidative stress, such as obesity. However, dietary reference values for VE in obese populations have not yet been defined, and VE supplementation trials show contradictory results. Therefore, a better understanding of the role of genetic variants in genes involved in VE metabolism may be crucial to exert dietary recommendations with a higher degree of precision. In particular, genetic variability should be taken into account in targets concerning VE bioavailability per se or concomitant with impaired lipoprotein transport. Genetic variants associated with impaired VE liver balance, and the handling/resolution of oxidative stress might also be relevant, but the core information that exists at present is insufficient to deliver precise recommendations.

Goswami AR, Ghosh T

High Alt Med Biol. 2018 Dec 4. doi: 10.1089/ham.2018.0045. [Epub ahead of print]

Abstract

Vitamin E reduces hypobaric hypoxia-induced immune responses in male rats. High Alt Med Biol 00:000-000, 2018.-In hypobaric hypoxia (HH) at high altitude, the immune responses are changed probably due to oxidative stress-induced production of free radicals and nonradicals. Vitamin E is an antioxidant and protects the cells from oxidative damage. The present study was carried out to study the antioxidant role of vitamin E on the immune changes induced by oxidative stress in HH at high altitude. Select immune responses (phagocytic activity of white blood cell [WBC], cytotoxic activity of splenic mononuclear cells [MNCs], and delayed type of hypersensitivity [DTH]) and hematological changes (total count and differential count [DC] of WBC) were measured in male rats exposed to intermittent HH (at 5486.4 m in a simulated chamber for 8 hours/d for 6 consecutive days) and in normobaric condition with and without p.o. administration of vitamin E in three different doses (20, 40, and 60 mg/kg body weight). The increase of phagocytic activity of blood WBC, and reduction of cytotoxic activity of splenic MNC and DTH response were observed in rats exposed to HH. After the administration of vitamin E at different doses, the immune changes were blocked in a dose-dependent manner. Exposure to HH also led to the elevation of serum corticosterone (CORT), which was arrested after administration of vitamin E. The results indicate that the immune changes in HH at high altitude are probably mediated by the production of free radicals and nonradicals, and vitamin E can block these immune changes by its reactive oxygen species quenching effects.

Vilar-Gomez E, Vuppalanchi R, Gawrieh S, Ghabril M, Saxena R, Cummings OW, Chalasani N

Hepatology. 2018 Dec 1. doi: 10.1002/hep.30368. [Epub ahead of print]

Abstract

Vitamin E improves liver histology in non-diabetic adults with nonalcoholic steatohepatitis (NASH), but its impact on long-term patient outcomes is unknown. We evaluated whether vitamin E treatment improves clinical outcomes of NASH patients with bridging fibrosis or cirrhosis. Two hundred and thirty-six patients with biopsy-proven NASH and bridging fibrosis or cirrhosis seen at Indiana University Medical Center between October 2004, and January 2016 were included. Ninety of them took 800 IU/day of vitamin E for ≥ 2 years (vitamin E users) and were propensity matched to 90 adults who did not take vitamin E (controls) after adjusting for fibrosis severity, age, gender, body mass index, comorbidities and their treatment, LDL cholesterol, liver biochemistries and length of follow-up on vitamin E. Covariate-adjusted cox and competing risk regression models were assessed to evaluate association between vitamin E treatment and patient outcomes. The median follow-up was 5.62 (IQR: 4.3-7.5) and 5.6 (IQR: 4-6.9) years for vitamin E users and controls respectively. Vitamin E users had higher adjusted transplant-free survival (78% vs. 49%, P<.01) and lower rates of hepatic decompensation (37% vs. 62%, P=.04) than controls. After controlling for severity of fibrosis, calendar year of patient enrollment and other potential confounders, vitamin E treatment decreased the risk of death or transplant (adj. HR: 0.30, 95% CI: 0.12-0.74, P<.01) and hepatic decompensation (adj. sHR: 0.52, 95% CI: 0.28-0.96, P=.036). These benefits were evident in both diabetics as well as non-diabetics. Adjusted 10-year cumulative probability of HCC, vascular events and non-hepatic cancers were not different between vitamin E exposed and controls. CONCLUSION: vitamin E use was associated with improved clinical outcomes in patients with NASH and bridging fibrosis or cirrhosis.

Lewis ED, Meydani SN, Wu D

IUBMB Life. 2018 Nov 30. doi: 10.1002/iub.1976. [Epub ahead of print]

Abstract

Vitamin E, a potent lipid-soluble antioxidant, found in higher concentration in immune cells compared to other cells in blood, is one of the most effective nutrients known to modulate immune function. Vitamin E deficiency has been demonstrated to impair normal functions of the immune system in animals and humans, which can be corrected by vitamin E repletion. Although deficiency is rare, vitamin E supplementation above current dietary recommendations has been shown to enhance the function of the immune system and reduce risk of infection, particularly in older individuals. The mechanisms responsible for the effect of vitamin E on the immune system and inflammation have been explored in cell-based, pre-clinical and clinical intervention studies. Vitamin E modulates T cell function through directly impacting T cell membrane integrity, signal transduction, and cell division, and also indirectly by affecting inflammatory mediators generated from other immune cells. Modulation of immune function by vitamin E has clinical relevance as it affects host susceptibility to infectious diseases such as respiratory infections, in addition to allergic diseases such as asthma. Studies examining the role of vitamin E in the immune system have typically focused on α-tocopherol; however, emerging evidence suggests that other forms of vitamin E, including other tocopherols as well as tocotrienols, may also have potent immunomodulatory functions. Future research should continue to identify and confirm the optimal doses for individuals at different life stage, health condition, nutritional status, and genetic heterogeneity. Future research should also characterize the effects of non-α-alpha-tocopherol vitamin E on immune cell function as well as their potential clinical application.

Torquato P, Bartolini D, Giusepponi D, Piroddi M, Sebastiani B, Saluti G, Galarini R, Galli F

Free Radic Biol Med. 2018 Nov 30;131:115-125. doi: 10.1016/j.freeradbiomed.2018.11.036. [Epub ahead of print]

Abstract

Lipid peroxidation is one of the earliest pathogenic events of non-alcoholic fatty liver disease (NAFLD). In this context, an increased oxidation of the lipoperoxyl radical scavenger α-tocopherol (α-TOH) should occur already in the subclinical phases of the disease to compensate for the increase oxidation of the lipid excess of liver and possibly of other tissues. However, this assumption remains unsupported by direct analytical evidence. In this study, GC-MS/MS and LC-MS/MS procedures have been developed and applied for the first time to measure the vitamin Eoxidation metabolite α-tocopheryl quinone (α-TQ) in plasma of fatty liver (FL) subjects that were compared in a pilot cross-sectional study with healthy controls. The protein adducts of 4-hydroxynonenal (4-HNE) and the free form of polyunsaturated free fatty acids (PUFA) were measured as surrogate indicators of lipid peroxidation. α-TQ formation was also investigated in human liver cells after supplementation with α-TOH and/or fatty acids (to induce steatosis). Compared with controls, FL subjects showed increased (absolute and α-TOH-corrected) levels of plasma α-TQ and 4-HNE, and decreased concentrations of PUFA. α-TQ levels positively correlated with indices of liver damage and metabolic dysfunction, such as alanine aminotransferase, bilirubin and triglycerides, and negatively correlated with HDL cholesterol. Fatty acid supplementation in human hepatocytes stimulated the generation of cellular oxidants and α-TOH uptake leading to increased α-TQ formation and secretion in the extracellular medium – both were markedly stimulated by α-TOH supplementation. In conclusion, plasma α-TQ represents an early biomarker of the lipoperoxyl radical-induced oxidation of vitamin E and lipotoxicity of the fatty liver.

Razak AM, Khor SC, Jaafar F, Karim NA, Makpol S

Genes Nutr. 2018 Nov 29;13:31. doi: 10.1186/s12263-018-0618-2. eCollection 2018.

Abstract

BACKGROUND:

Several muscle-specific microRNAs (myomiRs) are differentially expressed during cellular senescence. However, the role of dietary compounds on myomiRs remains elusive. This study aimed to elucidate the modulatory role of tocotrienol-rich fraction (TRF) on myomiRs and myogenic genes during differentiation of human myoblasts. Young and senescent human skeletal muscle myoblasts (HSMM) were treated with 50 μg/mL TRF for 24 h before and after inducing differentiation.

RESULTS:

The fusion index and myotube surface area were higher (p < 0.05) on days 3 and 5 than that on day 1 of differentiation. Ageing reduced the differentiation rate, as observed by a decrease in both fusion index and myotube surface area in senescent cells (p < 0.05). Treatment with TRF significantly increased differentiation at days 1, 3 and 5 of young and senescent myoblasts. In senescent myoblasts, TRF increased the expression of miR-206 and miR-486 and decreased PTEN and PAX7 expression. However, the expression of IGF1R was upregulated during early differentiation and decreased at late differentiation when treated with TRF. In young myoblasts, TRF promoted differentiation by modulating the expression of miR-206, which resulted in the reduction of PAX7 expression and upregulation of IGF1R.

CONCLUSION:

TRF can potentially promote myoblast differentiation by modulating the expression of myomiRs, which regulate the expression of myogenic genes.

Dallak MA, Al-Ani B, El Karib AO, Abd Ellatif M, Eid RA, Al-Ani R, Mahmoud HM, Haidara MA

Arch Physiol Biochem. 2018 Nov 22:1-7. doi: 10.1080/13813455.2018.1538250. [Epub ahead of print]

Abstract

BACKGROUND:

We tested the hypothesis that vitamin E may protect against pre-diabetes-induced aortic injury (aortopathy), and exercise can augment the action of vitamin E.

MATERIAL AND METHODS:

Rats were either fed with a high fat and fructose diet (HFD) (model group) or a standard laboratory chow (control group) for 15 weeks before being sacrificed. The three protective groups were treated with vitamin E (HFD + Vit E), swimming exercises (HFD + Ex), and vitamin E plus swimming exercises (HFD + VitE + Ex), respectively.

RESULTS:

Aortopathy was developed in the model group as demonstrated by substantial tissue ultrastructural alterations, which were partially protected by vitamin E and effectively protected with vitamin E plus swim exercise. Also, swimming exercises significantly (p < .05) increased the modulatory effects of vitamin E on dyslipidemia, insulin resistance, blood pressure, oxidative stress, inflammation, leptin, and adiponectin, except coagulation and thrombosis.

CONCLUSIONS:

Swim exercise augments the protective effects of vitamin E in a pre-diabetic animal model.