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Non-alcoholic fatty liver disease (NAFLD): a review of pathophysiology, clinical management and effects of weight loss.
Pouwels, S, Sakran, N, Graham, Y, Leal, A, Pintar, T, Yang, W, Kassir, R, Singhal, R, Mahawar, K, Ramnarain, D
BMC endocrine disorders. 2022;(1):63
Abstract
Given the increasing prevalence of diabetes and obesity worldwide, the deleterious effects of non-alcoholic fatty liver disease (NAFLD) are becoming a growing challenge for public health. NAFLD is the most common chronic liver disease in the Western world. NAFLD is closely associated with metabolic disorders, including central obesity, dyslipidaemia, hypertension, hyperglycaemia and persistent abnormalities of liver function tests.In general NAFLD is a common denominer for a broad spectrum of damage to the liver, which can be due to hepatocyte injury, inflammatory processes and fibrosis. This is normally seen on liver biopsy and can range from milder forms (steatosis) to the more severe forms (non-alcoholic steatohepatitis (NASH), advanced fibrosis, cirrhosis and liver failure). In these patients, advanced fibrosis is the major predictor of morbidity and liver-related mortality, and an accurate diagnosis of NASH and NAFLD is mandatory. Histologic evaluation with liver biopsy remains the gold standard to diagnose NAFLD. Diagnosis of NAFLD is defined as presence of hepatic steatosis, ballooning and lobular inflammation with or without fibrosis. Weight loss, dietary modification, and the treatment of underlying metabolic syndrome remain the mainstays of therapy once the diagnosis is established. Dietary recommendations and lifestyle interventions, weight loss, and the treatment of underlying metabolic syndrome remain the mainstays of therapy once the diagnosis is established with promising results but are difficult to maintain. Pioglitazone and vitamin E are recommended by guidelines in selected patients. This review gives an overview of NAFLD and its treatment options.
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Effects of vitamin E on stroke: a systematic review with meta-analysis and trial sequential analysis.
Loh, HC, Lim, R, Lee, KW, Ooi, CY, Chuan, DR, Looi, I, Kah Hay, Y, Abdul Karim Khan, N
Stroke and vascular neurology. 2021;(1):109-120
Abstract
There are several previous studies on the association of vitamin E with prevention of stroke but the findings remain controversial. We have conducted a systematic review, meta-analysis together with trial sequential analysis of randomised controlled trials to evaluate the effect of vitamin E supplementation versus placebo/no vitamin E on the risk reduction of total, fatal, non-fatal, haemorrhagic and ischaemic stroke. Relevant studies were identified by searching online databases through Medline, PubMed and Cochrane Central Register of Controlled Trials. A total of 18 studies with 148 016 participants were included in the analysis. There was no significant difference in the prevention of total stroke (RR (relative risk)=0.98, 95% CI 0.92-1.04, p=0.57), fatal stroke (RR=0.96, 95% CI 0.77-1.20, p=0.73) and non-fatal stroke (RR=0.96, 95% CI 0.88-1.05, p=0.35). Subgroup analyses were performed under each category (total stroke, fatal stroke and non-fatal stroke) and included the following subgroups (types of prevention, source and dosage of vitamin E and vitamin E alone vs control). The findings in all subgroup analyses were statistically insignificant. In stroke subtypes analysis, vitamin E showed significant risk reduction in ischaemic stroke (RR=0.92, 95% CI 0.85-0.99, p=0.04) but not in haemorrhagic stroke (RR=1.17, 95% CI 0.98-1.39, p=0.08). However, the trial sequential analysis demonstrated that more studies were needed to control random errors. Limitations of this study include the following: trials design may not have provided sufficient power to detect a change in stroke outcomes, participants may have had different lifestyles or health issues, there were a limited number of studies available for subgroup analysis, studies were mostly done in developed countries, and the total sample size for all included studies was insufficient to obtain a meaningful result from meta-analysis. In conclusion, there is still a lack of statistically significant evidence of the effects of vitamin E on the risk reduction of stroke. Nevertheless, vitamin E may offer some benefits in the prevention of ischaemic stroke and additional well-designed randomised controlled trials are needed to arrive at a definitive finding. PROSPERO registration number: CRD42020167827.
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Beneficial Effects of Vitamin E Supplementation on Endothelial Dysfunction, Inflammation, and Oxidative Stress Biomarkers in Patients Receiving Hemodialysis: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.
Nguyen, TTU, Yeom, JH, Kim, W
International journal of molecular sciences. 2021;(21)
Abstract
Inflammation and oxidative stress are closely related to cardiovascular complications and atherosclerosis, and have the potential to lead to an increase in death in patients receiving hemodialysis. Vitamin E has antioxidant and anti-inflammatory properties. We conducted a systematic review and meta-analysis to assess the effects of vitamin E supplementation on endothelial dysfunction, inflammation, and oxidative stress biomarkers in adult patients receiving hemodialysis. We searched the MEDLINE, EMBASE, Web of Science, and Cochrane Library databases and identified randomized controlled trials of adult patients receiving hemodialysis until 30 August 2021. A total of 11 trials with 491 randomized patients were included. The pooled data indicated that vitamin E supplementation significantly decreased intercellular adhesion molecule-1 [standardized mean difference (SMD): -1.35; 95% confidence interval (CI): -2.57, -0.13; p = 0.03, I2 = 89%], vascular cell adhesion molecule-1 (SMD: -1.08; 95% CI: -2.05, -0.11; p = 0.03, I2 = 81%), C-reactive protein (SMD: -0.41; 95% CI: -0.75, -0.07; p = 0.02, I2 = 64%), and malondialdehyde (SMD: -0.76; 95% CI: -1.26, -0.25; p = 0.003, I2 = 77%) levels, but not interleukin-6 levels compared to those in the control group. Our results suggest that vitamin E supplementation may help alleviate oxidative stress and both vascular and systemic inflammation in patients receiving hemodialysis.
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Fructose, Omega 3 Fatty Acids, and Vitamin E: Involvement in Pediatric Non-Alcoholic Fatty Liver Disease.
Alberti, G, Gana, JC, Santos, JL
Nutrients. 2020;(11)
Abstract
Non-alcoholic fatty liver disease (NAFLD) is currently the most common form of liver disease in both adults and children, becoming the leading cause for liver transplant in many countries. Its prevalence has increased considerably in recent years, mainly due to the explosive increase in pediatric obesity rates. NAFLD is strongly associated with central obesity, diabetes, dyslipidemia and insulin resistance, and it has been considered as the hepatic manifestation of the metabolic syndrome. Its complex pathophysiology involves a series of metabolic, inflammatory and oxidative stress processes, among others. Given the sharp increase in the prevalence of NAFLD and the lack of an appropriate pharmacological approach, it is crucial to consider the prevention/management of the disease based on lifestyle modifications such as the adoption of a healthy nutrition pattern. Herein, we review the literature and discuss the role of three key nutrients involved in pediatric NAFLD fructose and its participation in metabolism, Omega-3 fatty acids and its anti-inflammatory effects and vitamin E and its action on oxidative stress.
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Purified and specific cytoplasmic pollen extract: a non-hormonal alternative for the treatment of menopausal symptoms.
Genazzani, A, Panay, N, Simoncini, T, Depypere, H, Mueck, A, Egarter, C, Biglia, N, Fait, T, Birkhaeuser, M, Skouby, SO, et al
Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology. 2020;(3):190-196
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Abstract
Research into non-hormonal, alternative therapies is necessary for women for whom menopausal hormone therapy is contraindicated or for women who do not wish to take hormones. This review focuses on one such non-hormonal option, namely, purified and specific cytoplasmic pollen extract, or PureCyTonin®. This extract has been evaluated in several preclinical and clinical studies, where it demonstrated its value as a safe and non-estrogenic alternative for menopause. This review presents the beneficial effects of PureCyTonin® in the treatment of menopausal symptoms (e.g. hot flushes) in healthy women, as well as in premenstrual syndrome. We discuss the mechanism of action of PureCyTonin®, an SSRI-'like' therapy. The lack of estrogenic effect demonstrated in preclinical studies suggests that PureCyTonin® may also be a suitable option for the management of menopausal symptoms in women with breast cancer.
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Novel Antioxidative Activity of Astaxanthin and Its Synergistic Effect with Vitamin E.
Kogure, K
Journal of nutritional science and vitaminology. 2019;(Supplement):S109-S112
Abstract
Astaxanthin (Asx) is known to be a potent quencher of singlet oxygen and an efficient scavenger of superoxide anion. However, the scavenging activity of Asx toward the hydroxyl radical was currently unclear because the high lipophilicity of Asx prevents analysis of such activity in water. Liposomes containing Asx (Asx-lipo) were previously shown to be dispersed in water. Analysis of the hydroxyl radical scavenging activity of Asx-lipo demonstrated a dose-dependence in water, with the effect of Asx being more potent than the vitamin E α-tocopherol (α-T). Furthermore, liposomes co-encapsulating Asx and vitamin E derivatives, namely tocotrienols (T3), showed a synergistic elimination effect on singlet oxygen and hydroxyl radical, although the antioxidative activity of liposomes co-encapsulating Asx and α-T was lower than the calculated additive value of each independent activity. A calculation of the most stable structure of Asx in the presence of α-T or T3, suggested that only T3 was able to hydrogen bond with Asx, and the Asx polyene chain partially interacting with the α-T3 triene chain, which could explain the synergistic effect between Asx and T3, but not Asx and α-T. This review introduces the hydroxyl radical scavenging activity of Asx, and its synergistic effect with T3.
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Vitamin E and Alzheimer's disease: what do we know so far?
Browne, D, McGuinness, B, Woodside, JV, McKay, GJ
Clinical interventions in aging. 2019;:1303-1317
Abstract
Vitamin E has been proposed as a potential clinical intervention for Alzheimer's disease (AD) given the plausibility of its various biological functions in influencing the neurodegenerative processes associated with the condition. The tocopherol and tocotrienol isoforms of vitamin E have multiple properties including potent antioxidant and anti-inflammatory characteristics, in addition to influences on immune function, cellular signalling and lowering cholesterol. Several of these roles offer a theoretical rationale for providing benefit for the treatment of AD-associated pathology. Diminished circulating concentrations of vitamin E have been demonstrated in individuals with AD. Reduced plasma levels have furthermore been associated with an increased risk of AD development while intake, particularly from dietary sources, may limit or reduce the rate of disease progression. This benefit may be linked to synergistic actions between vitamin E isoforms and other micronutrients. Nevertheless, randomised trials have found limited and inconsistent evidence of vitamin E supplementation as an effective clinical intervention. Thus, despite a strong rationale in support of a beneficial role for vitamin E for the treatment of AD, the evidence remains inconclusive. Several factors may partly explain this discrepancy and represent the difficulties of translating complex laboratory evidence and dietary interactions into clinical interventions. Methodological design limitations of existing randomised trials and restrictions to supplementation with a single vitamin E isoform may also limit the influence of effect. Moreover, several factors influence individual responsiveness to vitamin E intake and recent findings suggest variation in the underlying genetic architecture attenuates vitamin E biological availability and activity which likely contributes to the variation in clinical responsiveness and the failure of randomised trials to date. Importantly, the clinical safety of vitamin E remains controversial and warrants further investigation.
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Update on Vitamin E and Its Potential Role in Preventing or Treating Bronchopulmonary Dysplasia.
Stone, CA, McEvoy, CT, Aschner, JL, Kirk, A, Rosas-Salazar, C, Cook-Mills, JM, Moore, PE, Walsh, WF, Hartert, TV
Neonatology. 2018;(4):366-378
Abstract
Vitamin E is obtained only through the diet and has a number of important biological activities, including functioning as an antioxidant. Evidence that free radicals may contribute to pathological processes such as bronchopulmonary dysplasia (BPD), a disease of prematurity associated with increased lung injury, inflammation and oxidative stress, led to trials of the antioxidant vitamin E (α-tocopherol) to prevent BPD with variable results. These trials were all conducted at supraphysiologic doses and 2 of these trials utilized a formulation containing a potentially harmful excipient. Since 1991, when the last of these trials was conducted, both neonatal management strategies for minimizing oxygen and ventilator-related lung injury and our understanding of vitamin E isoforms in respiratory health have advanced substantially. It is now known that there are differences between the effects of vitamin E isoforms α-tocopherol and γ-tocopherol on the development of respiratory morbidity and inflammation. What is not known is whether improvements in physiologic concentrations of individual or combinations of vitamin E isoforms during pregnancy or following preterm birth might prevent or reduce BPD development. The answers to these questions require adequately powered studies targeting pregnant women at risk of preterm birth or their premature infants immediately following birth, especially in certain subgroups that are at increased risk of vitamin E deficiency (e.g., smokers). The objective of this review is to compile, update, and interpret what is known about vitamin E isoforms and BPD since these first studies were conducted, and suggest future research directions.
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Vitamin E for Alzheimer's dementia and mild cognitive impairment.
Farina, N, Llewellyn, D, Isaac, MG, Tabet, N
The Cochrane database of systematic reviews. 2017;(1):CD002854
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Abstract
BACKGROUND Vitamin E occurs naturally in the diet. It has several biological activities, including functioning as an antioxidant to scavenge toxic free radicals. Evidence that free radicals may contribute to the pathological processes behind cognitive impairment has led to interest in the use of vitamin E supplements to treat mild cognitive impairment (MCI) and Alzheimer's disease (AD). This is an update of a Cochrane Review first published in 2000, and previously updated in 2006 and 2012. OBJECTIVES To assess the efficacy of vitamin E in the treatment of MCI and dementia due to AD. SEARCH METHODS We searched the Specialized Register of the Cochrane Dementia and Cognitive Improvement Group (ALOIS), the Cochrane Library, MEDLINE, Embase, PsycINFO, CINAHL, LILACS as well as many trials databases and grey literature sources on 22 April 2016 using the terms: "Vitamin E", vitamin-E, alpha-tocopherol. SELECTION CRITERIA We included all double-blind, randomised trials in which treatment with any dose of vitamin E was compared with placebo in people with AD or MCI. DATA COLLECTION AND ANALYSIS We used standard methodological procedures according to the Cochrane Handbook for Systematic Reviews of Interventions. We rated the quality of the evidence using the GRADE approach. Where appropriate we attempted to contact authors to obtain missing information. MAIN RESULTS Four trials met the inclusion criteria, but we could only extract outcome data in accordance with our protocol from two trials, one in an AD population (n = 304) and one in an MCI population (n = 516). Both trials had an overall low to unclear risk of bias. It was not possible to pool data across studies owing to a lack of comparable outcome measures.In people with AD, we found no evidence of any clinically important effect of vitamin E on cognition, measured with change from baseline in the Alzheimer's Disease Assessment Scale - Cognitive subscale (ADAS-Cog) over six to 48 months (mean difference (MD) -1.81, 95% confidence interval (CI) -3.75 to 0.13, P = 0.07, 1 study, n = 272; moderate quality evidence). There was no evidence of a difference between vitamin E and placebo groups in the risk of experiencing at least one serious adverse event over six to 48 months (risk ratio (RR) 0.86, 95% CI 0.71 to 1.05, P = 0.13, 1 study, n = 304; moderate quality evidence), or in the risk of death (RR 0.84, 95% CI 0.52 to 1.34, P = 0.46, 1 study, n = 304; moderate quality evidence). People with AD receiving vitamin E showed less functional decline on the Alzheimer's Disease Cooperative Study/Activities of Daily Living Inventory than people receiving placebo at six to 48 months (mean difference (MD) 3.15, 95% CI 0.07 to 6.23, P = 0.04, 1 study, n = 280; moderate quality evidence). There was no evidence of any clinically important effect on neuropsychiatric symptoms measured with the Neuropsychiatric Inventory (MD -1.47, 95% CI -4.26 to 1.32, P = 0.30, 1 study, n = 280; moderate quality evidence).We found no evidence that vitamin E affected the probability of progression from MCI to probable dementia due to AD over 36 months (RR 1.03, 95% CI 0.79 to 1.35, P = 0.81, 1 study, n = 516; moderate quality evidence). Five deaths occurred in each of the vitamin E and placebo groups over the 36 months (RR 1.01, 95% CI 0.30 to 3.44, P = 0.99, 1 study, n = 516; moderate quality evidence). We were unable to extract data in accordance with the review protocol for other outcomes. However, the study authors found no evidence that vitamin E differed from placebo in its effect on cognitive function, global severity or activities of daily living . There was also no evidence of a difference between groups in the more commonly reported adverse events. AUTHORS' CONCLUSIONS We found no evidence that the alpha-tocopherol form of vitamin E given to people with MCI prevents progression to dementia, or that it improves cognitive function in people with MCI or dementia due to AD. However, there is moderate quality evidence from a single study that it may slow functional decline in AD. Vitamin E was not associated with an increased risk of serious adverse events or mortality in the trials in this review. These conclusions have changed since the previous update, however they are still based on small numbers of trials and participants and further research is quite likely to affect the results.
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Effects of Vitamin E-Coated versus Conventional Membranes in Chronic Hemodialysis Patients: A Systematic Review and Meta-Analysis.
D'Arrigo, G, Baggetta, R, Tripepi, G, Galli, F, Bolignano, D
Blood purification. 2017;(1-3):101-122
Abstract
INTRODUCTION Accruing evidence suggests that vitamin E-coated membranes (ViE-m) might improve the clinical management of chronic hemodialysis (HD) patients. METHODS We conducted a systematic review and meta-analysis of RCTs comparing ViE-m to conventional HD. Endpoints of interest were a series of biomarkers pertaining to anemia status, inflammation, oxidative stress and dialysis efficacy/status. RESULTS Sixty studies were included. ViE-m significantly improved the Erythropoietin Resistance Index but had no impact on other anemia parameters. As for oxidative stress and inflammation, ViE-m produced a significant decrease in interleukin-6 levels, thiobarbituric acid reactive substances, plasma and red blood cell (RBC) malonylaldehyde and a significant increase in blood and RBC vitamin E. Conversely, ViE-m use had no impact on lipid profile, dialysis adequacy, blood pressure, albumin and uric acid. CONCLUSIONS ViE-m might ameliorate anemia management by reducing oxidative stress and inflammation. Benefits of these bio-membranes on harder clinical outcomes are uncertain and need to be investigated by future, targeted trials.