The Role of Vitamin E in the Treatment of NAFLD

Perumpail BJ, Li AA, John N, Sallam S, Shah ND, Kwong W, Cholankeril G, Kim D, Ahmed A

Diseases. 2018 Sep 24;6(4). pii: E86. doi: 10.3390/diseases6040086

Abstract

There has been a growing interest in the role of vitamin E supplementation in the treatment and/or prevention of nonalcoholic fatty liver (NAFLD). We performed a systematic review of the medical literature from inception through 15 June 2018 by utilizing PubMed and searching for key terms such as NAFLD, vitamin E, alpha-tocopherol, and nonalcoholic steatohepatitis (NASH). Data from studies and medical literature focusing on the role of vitamin E therapy in patients with NAFLD and nonalcoholic steatohepatitis (NASH) were reviewed. Most studies assessing the impact of vitamin E in NAFLD were designed to evaluate patients with NASH with documented biochemical and histological abnormalities. These studies demonstrated improvement in biochemical profiles, with a decline in or normalization of liver enzymes. Furthermore, histological assessment showed favorable outcomes in lobular inflammation and hepatic steatosis following treatment with vitamin E. Current guidelines regarding the use of vitamin E in the setting of NAFLD recommend that vitamin E-based treatment be restricted to biopsy-proven nondiabetic patients with NASH only. However, some concerns have been raised regarding the use of vitamin E in patients with NASH due to its adverse effects profile and lack of significant improvement in hepatic fibrosis. In conclusion, the antioxidant, anti-inflammatory, and anti-apoptotic properties of vitamin E accompanied by ease-of-use and exceptional tolerability have made vitamin E a pragmatic therapeutic choice in non-diabetic patients with histologic evidence of NASH. Future clinical trials with study design to assess vitamin E in combination with other anti-fibrotic agents may yield an additive or synergistic therapeutic effect.

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Antiglycation study of HMG-R inhibitors and tocotrienol against glycated BSA and LDL: A comparative study.

Nabi R, Alvi SS, Khan RH, Ahmad S, Ahmad S, Khan MS

Int J Biol Macromol. 2018 Sep;116:983-992. doi: 10.1016/j.ijbiomac.2018.05.115. Epub 2018 May 18.

Abstract

Non-enzymatic glycation mediated advanced glycation end products (AGEs) generation results in the pathogenesis of diabetic complications and atherosclerotic cardiovascular disease (ASCVD) which is greatly influenced by 3-hydroxy-3-methyl-glutaryl Co-A reductase (HMG-R) activity. HMG-R inhibitors, statins, are well known for reducing mortality and morbidity of ASCVD in patients with diabetes due to their pleiotropic effects independent of cholesterol lowering. Due to distinct chemical structures, various statins may play important role in the inhibition of AGEs mediated pathologies. Herein, we evaluated the anti-glycating potential of atorvastatin (AT), rosuvastatin (RT), pitavastatin (PT), fluvastatin (FT), simvastatin (ST) alone as well in combination with ezetimibe (EZ) and tocotrienol (TT) against d-ribose mediated BSA and LDL glycation by various physicochemical approaches. Our data suggested that AT, TT, RT, EZ, EZ-AT, and EZ-RT were able to substantially inhibit the AGEs formation via modulation of hyperchromicity, fluorogenic AGEs, % contribution of α-helix and β-sheets to protein secondary structure, amide-I band stretching, carbonyl and HMF content in Gly-BSA as well as Gly-LDL. On the basis of above findings, we concluded that HMG-R inhibitors and TT, alone or in combination with EZ, may be established as terrific therapeutic agents for the patients suffering from AGEs induced diabetic cum ASCVD complications.

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Role of dietary α- and γ-tocopherol from Rosa mosqueta oil in the prevention of alterations induced by high-fat diet in a murine model

Tapia G, Silva D, Romero N, Pettinelli P, Dossi CG, de Miguel M, González-Mañán D

Nutrition. 2018 Sep;53:1-8. doi: 10.1016/j.nut.2018.01.012. Epub 2018 Apr 3.

Abstract

OBJECTIVE:

The aim of this study was to evaluate the contribution of tocopherols present in Rosa mosqueta oil (RM) in the prevention of high-fat diet (HFD)-induced alterations.

METHODS:

Male C57 BL/6 J mice (n = 9/group) were fed for 12 wk and divided into four groups: control (CD; 10% kcal fat, 20% kcal protein, 70% kcal carbohydrates); HFD (60% as fat, 20% kcal protein, 20% kcal carbohydrates); HFD + RM (0.01 mL/g body weight/d); and HFD + RM without tocopherols (0.01 mL/g body weight/d). Parameters of obesity, liver steatosis (histology, triacylglycerols content), inflammation (adipose NLRP3 inflammasome, tumor necrosis factor-α and interleukin-1 β expression, hepatic nuclear factor-κB) and oxidative stress (hepatic Nrf2 activation, carbonylated proteins) were evaluated.

RESULTS:

Liver steatosis, inflammatory, and oxidative stress parameters were significantly (P < 0.05) increased in the HFD + RM compared with the HFD + RM, with no differences between HFD and HFD + RM.

CONCLUSION:

The present study suggests that α- and γ-tocopherols from RM may have an important role in the prevention of alterations induced by HFD.

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Endogenous metabolites of vitamin E limit inflammation by targeting 5-lipoxygenase

Pein H, Ville A, Pace S, Temml V, Garscha U, Raasch M, Alsabil K, Viault G, Dinh CP, Guilet D, Troisi F, Neukirch K, König S, Bilancia R, Waltenberger B, Stuppner H, Wallert M, Lorkowski S, Weinigel C, Rummler S, Birringer M, Roviezzo F, Sautebin L, Helesbeux JJ, Séraphin D, Mosig AS, Schuster D, Rossi A, Richomme P, Werz O, Koeberle A

Nat Commun. 2018 Sep 20;9(1):3834. doi: 10.1038/s41467-018-06158-5.

Abstract

Systemic vitamin E metabolites have been proposed as signaling molecules, but their physiological role is unknown. Here we show, by library screening of potential human vitamin E metabolites, that long-chain ω-carboxylates are potent allosteric inhibitors of 5-lipoxygenase, a key enzyme in the biosynthesis of chemoattractant and vasoactive leukotrienes. 13-((2R)-6-hydroxy-2,5,7,8-tetramethylchroman-2-yl)-2,6,10-trimethyltridecanoic acid (α-T-13′-COOH) can be synthesized from α-tocopherol in a human liver-on-chip, and is detected in human and mouse plasma at concentrations (8-49 nM) that inhibit 5-lipoxygenase in human leukocytes. α-T-13′-COOH accumulates in immune cells and inflamed murine exudates, selectively inhibits the biosynthesis of 5-lipoxygenase-derived lipid mediators in vitro and in vivo, and efficiently suppresses inflammation and bronchial hyper-reactivity in mouse models of peritonitis and asthma. Together, our data suggest that the immune regulatory and anti-inflammatory functions of α-tocopherol depend on its endogenous metabolite α-T-13′-COOH, potentially through inhibiting 5-lipoxygenase in immune cells.

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Tocotrienol-Rich Vitamin E from Palm Oil (Tocovid) and Its Effects in Diabetes and Diabetic Nephropathy: A Pilot Phase II Clinical Trial.

Tan SMQ, Chiew Y, Ahmad B, Kadir KA

Nutrients. 2018 Sep 17;10(9). pii: E1315. doi: 10.3390/nu10091315.

Abstract

Tocotrienol-rich vitamin E from palm oil (Tocovid) has been shown to ameliorate diabetes through its superior antioxidant, antihyperglycemic, and anti-inflammatory properties in diabetic rats. This study aimed to investigate the effects of Tocovid on diabetic nephropathy in patients with type 2 diabetes. Baseline parameters of potential subjects such as HbA1c, blood pressure, Advanced Glycation Endproduct (AGE), soluble receptor for AGE (sRAGE), Nε-Carboxymethyllysine (Nε-CML), and Cystatin C were assessed for possible correlation with diabetic nephropathy. Only subjects with diabetic nephropathy or urine microalbuminuria-positive defined as Urine Albumin to Creatinine Ratio (UACR) >10 mg/mmol were recruited into a prospective, randomized, double-blinded, placebo-controlled trial. The intervention group (n = 22) received Tocovid 200 mg twice a day while the control group (n = 23) received placebo twice a day for 8 weeks. Changes in Hemoglobin A1c (HbA1c), blood pressure, serum biomarkers and renal parameters such as UACR, serum creatinine, and estimated Glomerular Filtration Rate (eGFR) were compared between the two groups. It was found that serum Nε-CML significantly correlated to the severity of microalbuminuria. For every 1 ng/mL increase in serum Nε-CML, the odds of diabetic nephropathy increased by 1.476 times. Tocovid, compared to placebo, significantly reduced serum creatinine but not eGFR, UACR, HbA1c, blood pressure, and serum biomarkers. In conclusion, serum Nε-CML is a potential biomarker for diabetic nephropathy. Treatment with Tocovid significantly reduced serum creatinine; therefore Tocovid may be a useful addition to the current treatment for diabetic nephropathy.

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Exploring the effect of vitamin E in cancer chemotherapy-A biochemical and biophysical insight

Bhori M, Singh K, Marar T, Chilakapati MK

J Biophotonics. 2018 Sep;11(9):e201800104. doi: 10.1002/jbio.201800104. Epub 2018 Jun 8.

Abstract

Many oncologists contend that patient undergoing chemotherapy must avoid antioxidant supplementation as it may interfere with the activity of the drug. In the present investigation, we have explored the influence of vitamin E, a well-known antioxidant on Camptothecin (CPT), a potent anti-cancer drug induced cell apoptosis and death of cervical cancer cells. HeLa cells were treated with different concentrations of CPT in presence and absence of 100 μm vitamin E. Treated cells were subjected to cytotoxicity studies, catalase assay, DNA fragmentation assay, clonogenic assay and flow cytometry based apoptosis detection. Also, Raman spectroscopy a label free technique which provides global information, in conjunction with multivariate tools like PCA, PCLDA and FDA, was investigated to explore vitamin E supplementation induced alterations. Our data based on biochemical and biophysical experimental analysis reveals that CPT causes DNA damage along with protein and lipid alteration culminating in cell death. Importantly, Raman spectroscopic analysis could uniquely differentiate the cluster of control and vitamin E control from CPT and CPT + Vit E treated cells. We conclusively prove that presence of vitamin E at 100 μM concentration shows promising antioxidant activity and displays no modulatory role on CPT induced effect, thereby causing no possible hindrance with the efficacy of the drug. Vitamin E may prove beneficial to alleviate chemotherapy associated side effects in patients during clinical settings which may open the doors further for subsequent exploration in in vivo preclinical studies.

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Efficacy of two vitamin E formulations in patients with abetalipoproteinemia and chylomicron retention disease

Cuerq C, Henin E, Restier L, Blond E, Drai J, Marçais C, Di Filippo M, Laveille C, Michalski MC, Poinsot P, Caussy C, Sassolas A, Moulin P, Reboul E, Charriere S, Levy E, Lachaux A, Peretti N

J Lipid Res. 2018 Sep;59(9):1640-1648. doi: 10.1194/jlr.M085043. Epub 2018 Jul 18.

Abstract

Abetalipoproteinemia (ABL) and chylomicron retention disease (CMRD) are extremely rare recessive forms of hypobetalipoproteinemia characterized by intestinal lipid malabsorption and severe vitamin E deficiency. Vitamin E is often supplemented in the form of fat-soluble vitamin E acetate, but fat malabsorption considerably limits correction of the deficiency. In this crossover study, we administered two different forms of vitamin E, tocofersolan (a water-soluble derivative of RRR-α-tocopherol) and α-tocopherol acetate, to three patients with ABL and four patients with CMRD. The aims of this study were to evaluate the intestinal absorption characteristics of tocofersolan versus α-tocopherolacetate by measuring the plasma concentrations of α-tocopherol over time after a single oral load and to compare efficacy by evaluating the ability of each formulation to restore vitamin E storage after 4 months of treatment. In patients with ABL, tocofersolan and α-tocopherolacetate bioavailabilities were extremely low (2.8% and 3.1%, respectively). In contrast, bioavailabilities were higher in patients with CMRD (tocofersolan, 24.7%; α-tocopherol acetate, 11.4%). Plasma concentrations of α-tocopherol at 4 months were not significantly different by formulation type in ABL or CMRD. This study provides new insights about vitamin E status in ABL and CMRD and suggests the potential of different formulations as treatment options.

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Vitamin E status and its determinants in patients with cystic fibrosis

Sapiejka E, Krzyżanowska-Jankowska P, Wenska-Chyży E, Szczepanik M, Walkowiak D, Cofta S, Pogorzelski A, Skorupa W, Walkowiak J

Adv Med Sci. 2018 Sep;63(2):341-346. doi: 10.1016/j.advms.2018.04.001. Epub 2018 Aug 3.

Abstract

PURPOSE:

The risk of vitamin E deficiency is of primary concern in cystic fibrosis patients. However, early diagnosis and routine vitamin Esupplementation can lead to its normal or even high levels. In the present study, we assessed vitamin E status in a large group of cystic fibrosis patients. Moreover, we also aimed to establish determinants of its body resources in cystic fibrosis patients.

MATERIAL AND METHODS:

The study group comprised 211 cystic fibrosis patients aged from 1 month to 48 years. In all of them serum α-tocopherol concentration was analyzed using high-performance liquid chromatography.

RESULTS:

Median vitamin E concentration was 9.9 μg/ml (1st-3rd quartile: 7.5-13.5). Vitamin E deficiency was found in 17 (8.0%) and high levels were documented in 24 (11.4%) participants. Patients with and without vitamin E deficiency did not differ significantly with respect to age, standardized body weight and height, FEV1, albumin concentration and vitamin E supplementation dose. However, vitamin E deficiency appeared more frequently in participants without vitamin E supplementation. Moreover, in multiple linear regression analysis pancreatic insufficiency, severe CFTR gene mutation and vitamin E dose, were potentially defined as determinants of vitamin E concentration.

CONCLUSIONS:

Vitamin E deficiency in cystic fibrosis patients is rather rare nowadays. Excessive vitamin E levels seem to be more frequent. Vitamin E status wasn’t documented to be strictly related to clinical determinants. Beyond vitamin E supplementation, exocrine pancreatic function and CFTR gene mutations may have had an impact on the vitamin E body resources in cystic fibrosis patients.

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Synergistic effect of glucosamine and vitamin E against experimental rheumatoid arthritis in neonatal rats

Dai W, Qi C, Wang S

Biomed Pharmacother. 2018 Sep;105:835-840. doi: 10.1016/j.biopha.2018.05.136. Epub 2018 Jun 18.

Abstract

The effect of glucosamine and vitamin E against rheumatoid arthritis (RA) in a neonatal rat model was investigated. Lipid peroxidation, superoxide dismutase (SOD), catalase, reduced glutathione (GSH), glutathione peroxidase (Gpx), matrix metalloproteinase-3 (MMP-3), prostaglandin E2 (PGE2), ceruloplasmin, copper, zinc, nitric oxide (NO), uric acid, inducible nitric oxide synthase (iNOS), and nuclear factor-kappaB (NF-κB) levels were determined in control and rheumatoid arthritis neonatal rats. Glucosamine plus vitamin E supplementation reduced the MDA level by 61.9% and increased the SOD, catalase, GSH, Gpx, and zinc levels. MMP-3, PGE2, ceruloplasmin, copper, NO and uric acid levels were significantly reduced by supplementation of glucosamine plus vitamin E. NF-κB, and iNOS protein levels were decreased by 47.7% and 39.5%, respectively, by glucosamine plus vitamin E supplementation. Thus, supplementation with glucosamine plus vitamin E exerted a synergistic effect against RA.

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Optimizing microencapsulation of α-tocopherol with pectin and sodium alginate

Singh J, Kaur K, Kumar P

J Food Sci Technol. 2018 Sep;55(9):3625-3631. doi: 10.1007/s13197-018-3288-6. Epub 2018 Jul 11.

Abstract

αTocopherol is a well-known fat-soluble antioxidant and is widely used in the food industry for stabilizing free radicals. Incorporation and stability of it into food is another challenge as directly added αtocopherol is prone to inactivation by food constituents. This study was aimed at optimizing conditions for encapsulation of αtocopherol using combination of sodium alginate (0.5, 1.0, 1.5 and 2.0%) as primary wall material and pectin (2.0%) as filler. The optimum conditions were selected on the basis of encapsulation efficiency, shape, size, bulk density, yield and swelling index with syringe method. The encapsulation efficiency of αtocopherol in microencapsules produced under optimal conditions was 52.91% using sodium alginate 1.5% w/v and pectin 2.0% w/v. αTocopherol was encapsulated with encapsulator using standard conditions and was compared with syringe method. The encapsulation efficiency was found more (55.97%) in microencapsules prepared with encapsulator and 52.11% in microencapsules prepared with syringe.

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