Vitamin E as an Adjuvant Treatment for Non-alcoholic Fatty Liver Disease in Adults: A Systematic Review of Randomized Controlled Trials

Muhammad Usman, Nabiyah Bakhtawar

Cureus . 2020 Jul 6;12(7):e9018. doi: 10.7759/cureus.9018.

Abstract

Nonalcoholic fatty liver disease (NAFLD) is one of the most common causes of chronic liver disease. It is characterized by a variety of pathologies, ranging from benign fatty liver to extensive fibrosis and even hepatocellular cancer. Among the several potential risk factors, insulin resistance and increased oxidative stress are the most important. Vitamin E is an antioxidant with a potential to be used as a treatment for NAFLD. Therefore, we carried out a structured systematic review of all RCTs conducted between 2010 and January 2020. After screening, eight RCTs were included. Our systematic review showed that vitamin E has clinical utility in improving biochemical (ALT and AST levels) and histological abnormalities in NAFLD (hepatic steatosis and lobular inflammation). However, vitamin E does not seem to have significant effects on liver fibrosis. Still, vitamin E has the potential to be used as an adjuvant for the treatment of NAFLD, and its use in clinical practice should be advocated.

Ratnani H, Suprayogi T W, Sardjito T, Susilowati S, Azura S

Infect Dis Rep . 2020 Jul 6;12(Suppl 1):8721. doi: 10.4081/idr.2020.8721. eCollection 2020 Jul 7.

Abstract

Background: The effects of α-tocopherol on intracellular Ca²⁺ intensity in semen cryopreservation by regulate intracellular Ca²⁺ intensity have not been reported yet.

Objective: The research was conducted to evaluate the effect of supplementation α- tocopherol into egg yolk skim milk extender on sperm quality and intracellular Ca²⁺ intensity.

Methods: Semen samples were collected and supplemented with respectively 0mM (P0); 0.5mM (P1); 1mM (P2); 1.5mM (P3) and 2mM (P4) α-tocopherol in extender before cryopreservation processes. Post-thawing sperm was evaluated for motility, viability, and abnormality using Phase Contrast Microscope (200x) with eosin-nigrosine staining, and intracellular Ca²⁺ intensity of the best result dose was evaluated using Confocal Laser Scan Microscope (400x) with Fluo-3 Staining.

Results: The results showed there was a significant difference (P≤0.05) in sperm motility and viability between P0; P1 with P2; P3; P4. The Motility and viability between groups P0; P1 and P3; P4 showed no significant difference (P≥0.05), while P2 with P3; P4 showed significant difference (P≤0.05). There was a significant difference (P≤0.05) in sperm abnormality of P0; P1 with P2; P3; P4. The abnormality between P0; P1 and P2; P3 showed no significant difference (P≥0.05), while P2; P3 showed a significant difference with P4 (P≤0.05). The best result in sperm quality was supplementation with 1.5mM α-tocopherol. Ca²⁺ intracellular intensity: 142.76± 21.8 au (P0) and 176.06±61.43 au (P3).

Conclusions: It was concluded that 1.5mM α-tocopherol is the best dose to improve sperm quality by regulating intracellular Ca²⁺ intensity on Simmental bull cattle.

Ahmed Ali, Derar R Derar, Tamim M Alhassun, Tariq I Almundarij

Biol Trace Elem Res . 2020 Jul 6. doi: 10.1007/s12011-020-02276-8. Online ahead of print.

Abstract

This study aimed to investigate the effect of zinc (Zn), selenium (Se), and vitamin E (Vit E) administration on semen quality and fertility in male dromedary camels with impotentia generandi (IG, post-coital infertility). Factors that may affect response to treatment were investigated. Thirty-three IG-affected and five fertile camels were included. Case history was obtained, and breeding sound examination was performed. Semen was collected using electroejaculation. IG-camels were classified according to initial sperm count, body condition score, age, duration of infertility, IG-type, and testicular size. IG-camels were treated with a combination of intramuscular injections of Vit E (α-tocopherol acetate, 1 mg/kg bw) and Se (sodium selenite, 0.088 mg/kg bw) once every week for three successive weeks and by daily oral administration of 360 mg of zinc gluconate for 5 successive weeks. Semen quality was estimated before and after treatment. IG-treated camels were allowed to mate females in estrus, and conception rates were calculated. The results showed that sperm cell concentration, sperm motility, and viability significantly increased, while sperm abnormality significantly decreased after treatment (P < 0.01). Positive correlations were observed between initial sperm cell count and post-treated sperm count (P = 0.001), sperm motility (P = 0.01), and viability (P = 0.002). Other variables and their interactions did not affect response to treatment. Conception rates improved after treatment. In conclusion, Zn, Se, and Vit E administration improved semen quality and fertility in male dromedary camels with impotentia generandi. Initial sperm count can be used to predict the degree of camel response to treatment.

Mohammad Taghi Beigmohammadi, Sama Bitarafan, Azin Hoseindokht, Alireza Abdollahi, Laya Amoozadeh, Maedeh Mahmoodi Ali Abadi, Morteza Foroumandi

Trials . 2020 Jul 6;21(1):614. doi: 10.1186/s13063-020-04547-0.

Abstract

Objectives: This study will evaluate the main hypothesis that supplementation with vitamins A, B, C, D, and E significantly improves the severity and mortality rate in ICU patients with COVID-19.

Trial design: This study is a randomized, single-blinded, two-arm (1:1 ratio) parallel group clinical trial.

Participants: We are conducting this study in patients with COVID-19 admitted to intensive care units at the Imam Khomeini Hospital Complex in Tehran, Iran. The inclusion criteria are as follows: (1) aged between 20 and 60 years, (2) both male and female patients with COVID-19, (3) clinical or definitive diagnosis (using polymerase chain reaction (PCR) test), (4) patients have not participated in other clinical trials, and (5) no renal or hepatic abnormalities. The exclusion criteria are as follows: (1) patients with specific and rare viral diseases such as HIV and (2) patients who have been undergoing chemotherapy for the past month.

Intervention and comparator: Duration of intervention: 7 days from randomization Intervention in the treatment group: Vitamin A 25,000 IU daily Vitamin D 600,000 IU once during study Vitamin E 300 IU twice daily Vitamin C is taken four times per day B vitamins are taken as a daily Soluvit [which included thiamine nitrate 3.1 mg, sodium riboflavin phosphate 4.9 mg (corresponding to vitamin B₂ 3.6 mg), nicotinamide 40 mg, pyridoxine hydrochloride 4.9 mg (corresponding to vitamin B₆ 4.0 mg), sodium pantothenate 16.5 mg (corresponding to pantothenic acid 15 mg), sodium ascorbate 113 mg (corresponding to vitamin C 100 mg), biotin 60 μg, folic acid 400 μg, and cyanocobalamin 5 μg] The control group will not receive any supplements or placebo. All supplements are made in Iran except for Soluvit (from Fresenius Kabi, New Zealand).

Main outcomes: 1. Weight, height, and BMI 2. Severity of pulmonary involvement according to CT scan 3. Respiratory support (invasive or non-invasive) 4. Percentage of oxygen saturation (SpO2 level) 5. Serum levels of WBC, CRP, ESR, IL6, IFN-G, and TNF-α 6. The patient’s body temperature 7. The presence or absence of involvement of organs other than the lungs (e.g., heart, liver, kidneys) 8. Duration of hospitalization 9. Mortality rate RANDOMIZATION: At baseline, eligible patients were randomly assigned to a 1:1 ratio to one of two groups: intervention and control. Block randomization is used based on the gender of patients.

Blinding (masking): Patients are unaware of being placed in the intervention or control groups after signing consent. All treatment staff will be aware of which group each of the patients is in due to the specific conditions of the ICU and the absence of placebo for the control group.

Numbers to be randomized (sample size): The researchers plan to include 60 patients in total, with 30 patients in each group.

Trial status: This is the first version of the protocol which started on April 2, 2020. Recruitment began April 2, 2020, and is expected to be complete by July 4, 2020.

Shima Mehrabadi, Seyed Shahabeddin Sadr

Neurol Res . 2020 Jul 4;1-7. doi: 10.1080/01616412.2020.1787624. Online ahead of print.

Abstract

Alzheimer’s disease (AD) is the most common neurodegenerative disease across the world. The major cause of AD is extensive oxidative stress and inflammation in central nervous system (CNS). Vitamin D₃ and E are the most known vitamins that control oxidative stress and mitochondrial respiratory function. They may prevent neuronal loss in AD. Few studies have been conducted to assess the effect of vitamins on AD. Therefore, the aim of this study was to assess the effect of vitamin D₃ and E on AD. Methods: In this study, 60 rats were randomly divided into six groups (n = 10) namely the control group, sham group, AD group with intra-hippocampal Aβ1-40 injection, AD+vitamin D₃ group, AD+vitamin E group and AD+vitamin D₃ and E group. Memory and learning were measured by the Novel Object Recognition (NOR) test. Neuronal survival was assessed by H&E and cresyl violet staining, and oxidative stress was measured by malondialdehyde (MDA) level and superoxide dismutase (SOD) activity. In vitamin-treated groups, learning and memory, which were measured by NOR, improved significantly. Vitamin D₃ and E administration decreased neuronal loss in AD brain rats. Results: Results showed that MDA decreased and SOD increased in treatment groups; but, a combination of vitamin D₃ and E was more effective in decreasing oxidative stress in AD compared to other treatment groups. Conclusion: The present study indicated that vitamin D₃ and E and their combination can improve memory and learning deficit, and decrease neuronal loss and oxidative stress in Alzheimer’s model.

Yuefeng Gao, Wei Lu, Luyang Jian, Zoltan Machaty, Hailing Luo

Anim Biotechnol . 2020 Jul 2;1-9. doi: 10.1080/10495398.2020.1788044. Online ahead of print.

Abstract

The effect of Vitamin E on the proliferation of ovine Sertoli cells was investigated. Sertoli cells were isolated and treated with various amounts of Vitamin E (0 μM, 400 μM, 800 μM, 1000 μM, 1200 μM, 1400 μM and 1600 μM) for 24 h. We found that at the concentration of 1200 μM, Vitamin E promoted Sertoli cell proliferation very effectively. It also increased the proportion of cells in the G1 phase while reduced that in the S and G2/M phases, suggesting that its effect on Sertoli cell proliferation is achieved by enhancing progression through the cell cycle. In addition, Vitamin E significantly up-regulated the transcript level of the PDPN, BMP6, AMPKα, GSK3β, Myc, and CDK6 genes and down-regulated that of PPARγ, Cyclin B1 and CDK4 as determined by qRT-PCR. Western blot analysis revealed that the expression of BMP6 and PDPN was also upregulated at the protein level, in accordance with the results of the qRT-PCR. Taken together, Vitamin E promoted Sertoli cell proliferation by affecting the expression of genes that regulate cell division and the cell cycle; this indicates that it can have a positive effect on sheep reproductive performance.

Matthew J Kuchan, Katherine M Ranard, Priyankar Dey, Sookyoung Jeon, Geoff Y Sasaki, Karen J Schimpf, Richard S Bruno, Martha Neuringer, John W Erdman

J Nutr . 2020 Jul 2;nxaa174. doi: 10.1093/jn/nxaa174. Online ahead of print.

Abstract

Background: α-Tocopherol (αT) in its natural form [2’R, 4’R, 8’R αT (RRR-αT)] is more bioactive than synthetic α-tocopherol (all rac-αT). All rac-αT is widely used in infant formulas, but its accretion in formula-fed infant brain is unknown.

Objective: We sought to compare αT and stereoisomer status in infant rhesus macaques (Macaca mulatta) fed infant formula (RRR-αT or all rac-αT) with a reference group fed a mixed diet of breast milk and maternal diet.

Methods: From 1 d after birth until 6 mo of age, infants (n = 23) were either nursery reared and exclusively fed 1 of 2 formulas by staff personnel or were community housed with their mothers and consumed a mixed reference diet of breast milk (69 mL/d at 6 mo) transitioning to monkey diet at ∼2 mo (MF; n = 8). Formulas contained either 21 μmol RRR-αT/L (NAT-F; n = 8) or 30 μmol all rac-αT/L (SYN-F; n = 7). Total αT and αT stereoisomers were analyzed in breast milk at 2, 4, and 6 mo and in monkey plasma and liver and 6 brain regions at 6 mo of age. α-Tocopherol transfer protein (α-TTP), lipoprotein αT, and urinary α-carboxyethyl-hydroxychroman (α-CEHC) were measured. One-way ANOVA with Tukey’s post-hoc test was used for analysis.

Results: At study termination, plasma, liver, lipoprotein, and brain total αT did not differ between groups. However, the NAT-F-fed group had higher RRR-αT than the SYN-F-fed group (P < 0.01) and the MF group (P < 0.0001) in plasma (1.7- and 2.7-fold) and brain (1.5- and 2.5-fold). Synthetic αT 2R stereoisomers (SYNTH-2R) were generally 3- and 7-fold lower in brain regions of the NAT-F group compared with those of the SYN-F and MF groups (P < 0.05). SYNTH-2R stereoisomers were 2-fold higher in MF than SYN-F (P < 0.0001). The plasma percentage of SYNTH-2R was negatively correlated with the brain percentage of RRR-αT (r = -0.99, P < 0.0001). Brain αT profiles were not explained by α-TTP mRNA or protein expression. Urine α-CEHC was 3 times higher in the NAT-F than in the MF group (P < 0.01).

Conclusions: Consumption of infant formulas with natural (NAT-F) compared with synthetic (SYN-F) αT differentially impacted brain αT stereoisomer profiles in infant rhesus macaques. Future studies should assess the functional implications of αT stereoisomer profiles on brain health.

Maria Wallert, Lisa Börmel, Stefan Lorkowski

Mol Nutr Food Res . 2020 Jul 21;e2000097. doi: 10.1002/mnfr.202000097. Online ahead of print.

Abstract

Inflammation-driven diseases and related comorbidities, such as the metabolic syndrome, obesity, fatty liver disease and cardiovascular diseases cause significant global burden. There is a growing body of evidence that nutrients alter inflammatory responses and can therefore make a decisive contribution to the treatment of these diseases. Recently, the inflammasome, a cytosolic multiprotein complex, was identified as a key player in inflammation and the development of various inflammation-mediated disorders, with nucleotide-binding domain and leucine-rich repeat pyrin domain (NLRP) 3 being the inflammasome of interest. Here we provide an overview about the cellular signaling pathways underlying nuclear factor ‘kappa-light-chain-enhancer’ of activated B-cells (NF-κB)- and NLRP3-mediated inflammatory processes, the pathogenesis of the inflammatory diseases atherosclerosis and non-alcoholic fatty liver disease (NAFLD); next, we discuss the current state of knowledge for drug-based and dietary-based interventions for treating cardiovascular diseases and NAFLD. To date one of the most important antioxidant in the human diet is vitamin E. Various in vitro and in vivo studies suggest that the different forms of vitamin E and also their derivatives have anti-inflammatory activity. Recent publications suggest that vitamin E – and possibly metabolites of vitamin E – are a promising therapeutic approach for treating inflammatory diseases such as NAFLD.

Kok-Yong Chin, Benjamin Ka Seng Thong, Rhivaldy Faahim Kamalulloh, Nur Vaizura Mohamad, Sok Kuan Wong, Azlan Mohd Arlamsyah, Rahma Triliana, Ima Nirwana Soelaiman

Drug Des Devel Ther . 2020 Jul 2;14:2561-2572. doi: 10.2147/DDDT.S260565. eCollection 2020.

Abstract

Purpose: Prolonged use of proton pump inhibitors may cause bone loss, and limited therapeutic agents are available to prevent this skeletal side effect. The combination of annatto tocotrienol, a bone anabolic agent, with calcium presents a novel strategy to prevent bone loss caused by proton pump inhibitors. This study aims to compare the effects of calcium alone and in combination with annatto tocotrienol or vitamin D₃ (Caltrate Plus) in preventing bone loss caused by pantoprazole.

Methods: Three-month-old Sprague Dawley male rats (n=30) were randomised into five groups (n=6/group). Bone loss was induced by pantoprazole (3 mg/kg p.o.) in four groups, and they were treated concurrently with either calcium carbonate (77 mg p.o.), calcium carbonate (77 mg p.o.) plus annatto tocotrienol (60 mg/kg p.o.) or Caltrate Plus (31 mg p.o.) for 60 days. The rats were euthanised at the end of the experiment, and their femurs were harvested for X-ray micro-computed tomography, bone cellular histomorphometry and bone mechanical strength analysis.

Results: Pantoprazole caused significant deterioration of trabecular bone microstructures but did not affect other skeletal indices. Calcium supplementation with or without annatto tocotrienol prevented the deterioration of trabecular microstructures at the femur but did not improve other skeletal indices. Annatto tocotrienol did not enhance the skeletal actions of calcium, whereas Caltrate Plus did not affect the bone health indices in these rats.

Conclusion: Calcium supplementation per se can prevent the deterioration of bone trabecular microstructures in rats receiving long-term treatment of pantoprazole.

Elliot Rosen, Oluseyi O Fatanmi, Stephen Y Wise, V Ashutosh Rao, Vijay K Singh

Health Phys . 2020 Jul;119(1):12-20. doi: 10.1097/HP.0000000000001221.

Abstract

The aim of this study was to analyze the changes in mouse jejunum protein expression in response to prophylactic administration of two promising tocols, γ-tocotrienol (GT3) and α-tocopherol succinate (TS), as radiation countermeasures before irradiation to elucidate the molecular mechanism(s) of their radioprotective efficacy. Mice were administered GT3 or TS (200 mg kg) subcutaneously 24 h prior to exposure to 11 Gy Co γ-radiation, a supralethal dose for mice. Jejunum was harvested 24 h post-irradiation. Results of the two-dimensional differential in-gel electrophoresis (2D-DIGE), coupled with mass spectrometry, and advanced bioinformatics tools suggest that the tocols have a corresponding impact on expression of 13 proteins as identified by mass spectrometry. Ingenuity Pathway Analysis (IPA) reveals a network of associated proteins involved in inflammatory response, organismal injury and abnormalities, and cellular development. Relevant signaling pathways including actin cytoskeleton signaling, RhoA signaling, and Rho family GTPase were identified. This study reveals the major proteins, pathways, and networks involved in preventing the radiation-induced injury in gut that may be contributing to enhanced survival.